KEY POINTS/

STUDY GUIDE
©2019 American College of Cardiology. G19010
ACCSAP Study Guide and Key Points

Introduction • Overall mean systolic blood pressures are declining

globally, particularly in North America, but with
This study guide pulls together the key points from each notable increases in Africa and East Asia.
module in ACCSAP so that you have them all in one place.
Please use it to get an overview of the product, to review • Mean global total cholesterol values are also
key concepts, or to study for the Boards. This document declining, particularly driven by changes in Europe,
will be updated as Key Points are added/updated within North America, and Australasia. However, values are
ACCSAP. increasing in both east and south Asia.

• The prevalence of obesity and diabetes is increasing

General Information and Study Guide everywhere, particularly in Oceania. This trend
threatens to reduce the magnitude of the gains in
Chapter: How to Prepare for the Boards life-expectancy and CVD prevalence seen in recent
How to Prepare for the Boards decades.
• Visit the American Board of Internal Medicine • Three complementary types of interventions in high-
website (www.abim.org) to read the details of the income countries have resulted in large reductions in
examination. age-adjusted CVD mortality rates:
• Prepare well in advance. Targeting patients with acute or established CVD
• Know common cardiovascular conditions and ACC/ for secondary prevention
AHA guideline Class I and Class III recommendations. Identification of those at high risk before their first
CVD event (primary prevention)
• Practice multiple choice questions and identify
knowledge gaps for further learning and self-directed Mass education or policy interventions directed at
study. the entire population to reduce the overall level of
risk factors (primordial prevention)
• For the initial certification exam, prepare separately
• Primary prevention is paramount for the large number
for the electrocardiography and imaging portions of
of individuals who are at high risk for CVD. A cost-
the examination, using the coding sheet.
effective primary prevention strategy includes use
• Practice evidence-based medicine and use ACC/AHA of prediction rules or risk scores to identify those
guidelines, wherever applicable. at higher risk in order to effectively target specific
behavioral or drug interventions. Risk scores typically
include age, sex, hypertension, smoking status,
General Principles of Cardiovascular Medicine diabetes mellitus, and lipid values. Some also include
family history. Some risk scores do not require
Chapter: General Principles of Cardiovascular Medicine laboratory testing.
Global Burden of Cardiovascular Disease
• Cardiovascular disease (CVD) accounts for • Education and public policy interventions that have
approximately 30% of deaths worldwide. However, reduced smoking rates, lowered mean blood pressure
there is great variation in regional CVD mortality levels, and improved lipid profiles have contributed to
rates. the reduction in coronary heart disease rates.

• Countries have moved through phases of the Biostatistics

epidemiologic transition that are characterized by • Medical research studies can be observational (case
different life expectancies, different rates of CVD series, case-control studies, cross-sectional studies,
mortality, and different levels of CVD risk factors. and cohort studies) or interventional (clinical trials),
and provide varying levels of evidence depending on
• Global trends in risk factors are as follows: the design.

2 ACCSAP Study Guide and Key Points

 • A statistically significant difference between two the incremental gain in health benefit. It is critical
groups can be identified by either comparing the that the comparator in a cost-effectiveness analysis
p-value against the stated alpha (usually 0.05), or by is the next best treatment alternative, as excluding a
determining that the confidence intervals exclude no relevant alternative will yield misleading results.
difference.
• Optimally, health benefit is measured in terms of life
• Ability to calculate sensitivity, specificity, positive years or quality adjusted life years (QALYs) gained.
predictive value, and negative predictive value, QALYs acknowledge that not all years of life are
and an understanding of the concepts of Bayes’ equally desirable, and are obtained by multiplying
theorem of post-test probability are important for life expectancy in different health states by utility
interpretation of the literature. weights, which represent relative preferences for
different health states from the societal perspective,
• Receiver operating characteristic curves and the
and can be elicited or estimated in a variety of ways.
area under the curve are two ways to assess the
usefulness of a diagnostic test. • Cost-effectiveness analyses can be model-based,
trial-based, or a hybrid of the two. When originally
• The net reclassification index (NRI) is a method of
introduced, cost-effectiveness utilized decision
assessing the incremental prognostic impact of a new
analytic models based on estimates of cost and
test, by assessing how often and how accurately it
effectiveness outcomes obtained from nonsampled
reclassifies individuals from a lower-risk category to
secondary data. This approach employs sensitivity
a higher-risk category, and vice versa. The NRI <0 and
analysis to examine the variability in results as
the integrated discrimination index assess somewhat
uncertain model inputs are varied over reasonable
similar information, but calculate risk as a continuous
ranges. More recently, economic studies have
variable without predefined risk categories.
been incorporated into clinical trials, enabling cost-
• T-tests are used to compare means between two effectiveness to be evaluated directly, using primary
independent groups; chi-square is used to compare patient-level data on both clinical outcomes and
proportions between two groups. costs, with variability around results examined using
statistical approaches. A hybrid approach is used in
• The square of the correlation coefficient (r2) tells the setting in which short-term results from a clinical
what percentage of the variability in one measure trial (e.g., the reduction in nonfatal events) need to be
can be predicted by knowing the measurement of the projected over the lifetime of patients to arrive at an
other variable. estimate of life years or QALYs gained.

• Linear regression and logistic regression are used to • Cost-effectiveness analyses are used to provide
predict the value of a dependent variable (or outcome additional support for clinical practice guidelines, to
measure) from one or more independent variables (or inform reimbursement decisions, and in the design of
covariates). insurance benefit packages.

• Kaplan-Meier plots can be used to plot survival (or Quality of Care: Measurement and Improvement
time-dependent) data; Cox proportional hazards • Health care quality is highly relevant to patients,
models are used with survival data to adjust for clinicians, and society.
confounding variables.
• High-quality health care is effective, safe, timely,
Cost – and Comparative Effectiveness efficient, equitable, and patient-centered (the six
• The United States spends a larger proportion of Institute of Medicine domains).
its wealth on health care than any other developed
nation. Cardiovascular disease accounts for a • The major domains of quality assessment
substantial proportion of health care spending. are structure, process, and outcomes of care
Cost-effectiveness analysis aims to generate insight (Donabedian’s triad).
regarding the economic efficiency with which new
• Scientific evidence, data standards, clinical practice
interventions generate health benefit.
guidelines, quality metrics, performance measures,
• When a new treatment or management strategy and area under the curve are key tools for defining
is associated with both greater costs and greater and measuring quality of care.
effectiveness than the current standard of care, the
• Quality improvement requires a system infrastructure
index used to measure cost-effectiveness is the
that facilitates accurate data collection, risk
incremental cost-effectiveness ratio, which is the
adjustment and benchmarking, ongoing and iterative
incremental costs of the new treatment divided by
cycles of quality improvement, clinician champions,

3 ACCSAP Study Guide and Key Points

 and organizational support. National clinical • For elderly patients requiring aortic valve
registries, such as the National Cardiovascular Data replacement, but who have a high risk for
Registry, are designed to meet these needs. perioperative complications or who cannot undergo
surgery, transcatheter aortic valve replacement has
Special Populations: Gender, Age, and Race/Ethnicity emerged as an effective treatment, with functional
• The presentation of coronary heart disease (CHD) and mortality benefit sustained at 5 years.
differs in women compared with men. Women tend
to have less obstructive disease on angiography, • Nonsteroidal anti-inflammatory drugs are commonly
but they experience more frequent symptoms and used in the management of arthritis, but they can
myocardial ischemia. cause salt and water retention and worsen blood
pressure control.
• Women with diabetes women have a higher risk for
CHD, heart failure, and stroke compared with patients • The high prevalence of hypertension in African
without diabetes and with men. Americans is associated with rates of mortality that
are four- to fivefold those in whites. Overall, African
• Although women may present with classic clinical Americans have a risk of death from coronary heart
features of myocardial ischemia and infarction, disease (CHD) that is two- to threefold that of whites.
women report atypical symptoms more frequently
than men. • Asian Indian men and women and Filipino men had
a greater proportionate mortality burden from CHD.
• Microvascular disease owing to endothelial High-risk Asian American subgroups have not seen
dysfunction plays a significant role in the the decline in mortality from heart disease that has
pathophysiology of ischemia in women without been observed in non- Hispanic whites.
significant epicardial disease.
• Blacks, American Indians, Alaska Natives, and Asian/
• The CHA2DS2-VASc score is recommended to assess Pacific Islanders have younger mean ages at stroke
the risk of stroke in patients with atrial fibrillation. onset than whites, and the mean age at stroke
Female sex is an independent risk factor for stroke in death is younger in these groups and in Hispanics
atrial fibrillation. compared with non-Hispanics.
• In 2011, heart failure was the most common cause
of hospitalization in patients ages >85 years and the Arrhythmias
second most common cause in patients ages 65-84
years. Chapter: Sinus Node Dysfunction and
Atrioventricular Conduction Disease
• Decreased cardiovascular reserve in older adults
Sinus Node Dysfunction
can predispose to decompensation when they are
confronted with hemodynamic challenges, such as • The sinus node is located at the junction of the
more strenuous physical activity, fever, or triggering superior vena cava and lateral right atrium. A
illness. spontaneously depolarizing current, know as If or
“funny current,” drives spontaneous sinus node
• Older patients more often present with atypical activity.
symptoms and nonspecific electrocardiogram
findings. However, they derive the same or greater • SND is a common and often age-related cause of
benefit from medical and interventional treatment bradycardia although extrinsic causes such as drug
than younger patients, but less often receive therapy also may cause apparent SND. 
guideline-directed therapy. Older patients also benefit
• SND comprises a number of different manifestations
from cardiac rehabilitation.
including symptomatic bradycardia, sinus pauses
• Complications of blood pressure treatment are due to sinus arrest or sinoatrial exit block, and
more common in the elderly, in relation to their chronotropic incompetence. 
comorbidities, altered autonomic nervous system
• Age-related SND also may be associated with AF,
function, and polypharmacy. Blood pressure
the so-called “tachy-brady” syndrome. This may
measurements should be made carefully, with
be associated with prolonged pauses, which can
attention to postural changes and to the phenomenon
be symptomatic after termination of AF. A common
of pseudohypertension.
scenario would be an elderly patient with persistent
• Although the elderly may have the lowest rates AF who develops a prolonged pause one termination
of blood pressure control, elderly patients of AF. This can be exacerbated by drugs, especially
derive impressive benefit from the treatment of those that block sodium channels such as flecainide.
hypertension.

4 ACCSAP Study Guide and Key Points

AV Conduction Disease Supraventricular Tachycardia
• AV block occurs due to a failure of impulse • PSVT may be due to AVNRT, accessory pathway
propagation through the cardiac conduction system. mediated tachycardia (AVRT), or AT. AT is most
Several types of AV block are recognized; most commonly due to a single abnormally firing focus
commonly first-, second-, and third-degree block. in the atrium. Unlike AVNRT and AVRT, AT is not
Prognosis of AV block is related to the severity of dependent on conduction through the AV node.
block. AV block may be due to failure of impulse Adenosine is an effective acute treatment of both
propagation in the AV nodal tissues (narrow QRS AVNRT and AVRT, but is less effective against
complex) or within the His-Purkinje system (intra- or AT, although use of adenosine in this situation
infra-Hisian block). Failure of impulse propagation may produce transient AV block and unmask the
due to infra-Hisian block may be associated with a mechanism of the tachycardia.
wide QRS complex with bundle branch or fascicular
block. • SVT can be distinguished by the timing relationship
of the R wave to the P wave. They are categorized as
• AV block should be distinguished from AV short R-P and long R-P tachycardias.
dissociation, where the ventricular rate is faster that
the atrial rate. In AV block, the atrial rate is faster than • SVTs can be distinguished by the rate, regularity,
the ventricular rate. mode of initiation, and effect of AV block including
vagal maneuvers during tachycardia.
• The diagnosis and treatment of SND and AV block
includes a thorough history and symptom evaluation, • SVT with aberrant conduction can be distinguished
as well as examination of the electrocardiographic from VT by looking for fusion or capture beats, or
evidence correlating these symptoms with electrical using well-established electrocardiographic criteria.
abnormalities.  • In patients with a normal 12-lead ECG (no pre-
• Patients with symptomatic irreversible bradycardia excitation or delta wave), the most common
due to SND or AV block require permanent mechanism of narrow complex tachycardia is AVNRT
pacemaker implantation. followed by AVRT. AT is the least common form of
SVT, accounting for <10% of cases.
• When evaluating patients with lesser degrees
of bradycardia, symptom-rhythm correlation is • Typical AVNRT is a short R-P tachycardia (≤70 ms)
important. This can be achieved with ambulatory and involves conduction down a slow pathway and
monitoring (Holter or similar). More prolonged up a fast pathway.
monitoring with an implantable subcutaneous • Genesis of the delta wave is due to “fusion” of
monitor may be needed in some cases.  impulses activating the ventricles via both the AV
• Much less commonly, an electrophysiological node and activation via the accessory pathway.
study can be performed to assess AV nodal and In other words, a delta wave is only present if the
His-Purkinje function, although in most cases, this accessory pathway can conduct from the atria to the
invasive approach is reserved for patients with ventricles. Factors that enhance AV nodal conduction
worrisome syncope. (such as exercise) cause predominantly more of
the ventricles to be activated in a normal fashion
• In patients with block at the AV node level, only block such that the delta wave will diminish with exercise,
will improve with exercise, but with infra-Hisian block whereas factors that slow AV nodal conduction such
(i.e., below the AV node), block will get worse with as drugs will increase the degree of pre-excitation. In
exercise. An exercise test should be recommended if other words, the degree of pre-excitation can change
there is a question regarding whether the bradycardia and is not fixed.
is intrinsic (heart rate will not improve or may even
worsen with exercise). In contrast, in patients in • Accessory pathways may be involved with
whom bradycardia is due to high vagal tone (athletes, tachycardia in three circumstances: orthodromic
for example), there will be a normal and appropriate AVRT, antidromic AVRT, and pre-excited tachycardias.
increase in heart rate with exercise. • Orthodromic AVRT produces an R-P interval >70 ms.
• In patients suspected of chronotropic incompetence The development of a BBB ipsilateral to the accessory
(failure to achieve expected heart rate with exercise), pathway usually increases the R-P interval; this is
a treadmill exercise test also can be recommended. diagnostic for orthodromic AVRT and localizes the
pathway to one side.
• Implantation of a permanent pacemaker is
indicated for patients with irreversible symptomatic • In all cases of narrow complex tachycardia, adenosine
may be administered even in patients with WPW.
bradycardia due to SND or AV block.
However, adenosine administration could be

5 ACCSAP Study Guide and Key Points

 potentially life-threatening in patients with pre- • Distinction of ventricular tachycardia in patients
excited AF. In this situation, the atria are in fibrillation, with or without structural heart disease is important
and activation of the ventricles is both via the AV since therapeutic approaches are very different. In
node AND the accessory pathway. Administration patients with structural heart disease, an implantable
of adenosine in this situation may result in AV block cardioverter-defibrillator is generally recommended
and 1:1 conduction of AF over the accessory pathway, (secondary prevention); in patients without structural
leading to ventricular fibrillation. heart disease, drug therapy or catheter ablation may
be effective in reducing or eliminating the arrhythmia.
• Even in patients presenting with narrow complex
tachycardia, resuscitation equipment should be • In patients with sustained ventricular tachycardia in
available. This is because adenosine shortens the the presence of structural heart disease, implantable
atrial refractory period, which predisposes to AF. cardioverter-defibrillator therapy is generally required.
Thus, with successful termination of the narrow
complex tachycardia, adenosine may be followed by • Ventricular tachycardia may be treated with
the onset of pre-excited AF, which is more unstable. antiarrhythmic drugs or catheter ablation.

• Pre-excited AF is AF with antegrade conduction down • Catheter ablation of ventricular tachycardia in

an accessory pathway and the AV node. It may be a patients with structural heart disease is associated
life-threatening condition and can be associated with with improved outcomes.
sudden death, especially if the shortest R-R interval • Predictors or improved outcomes after catheter
during AF is <250 ms. ablation include noninducibility of ventricular
• Management of pre-excited AF includes IV ibutilide, tachycardia and ejection fraction >30%.
procainamide, and DC cardioversion; AV nodal agents • Predictors of worse ventricular tachycardia (VT)-
including verapamil and adenosine should NOT be free survival include ejection fraction <30% and
used. inducible VT.
• Catheter ablation is recommended for symptomatic • The important differential diagnosis in right
WPW and is highly successful with a low rate of ventricular outflow tract ventricular tachycardia (VT)
complications. Asymptomatic pre-excitation is usually is VT occurring in the situation of arrhythmogenic
managed conservatively unless the person has a right ventricular cardiomyopathy (ARVC). One
high-risk occupation (e.g., military, airline pilot, etc.). important difference is that the resting 12-lead
Otherwise, no treatment is necessary unless symptoms echocardiogram (ECG) shows marked T-wave
occur. Most data would suggest risk of sudden cardiac inversion in the right precordial leads (V1-V3/4) and
death is very low indeed, although estimates vary and there may be evidence of an epsilon wave. The 12-
there is some controversy in this regard. lead ECG in patients with normal heart VT is normal.
• Catheter ablation is the preferred treatment option for If ARVC is suspected, computed tomography or
recurrent symptomatic PSVT – success rates exceed magnetic resonance imaging should be performed to
95% in good centers. Drug therapy (prophylaxis or as rule out this condition, which is a genetic abnormality.
the occasion arises with drugs that block AV node or • If arrhythmogenic right ventricular cardiomyopathy is
antiarrhythmic drugs) is rarely effective or helpful. diagnosed in an index case, family screening should
be considered. Implantable cardioverter-defibrillator
Ventricular Arrhythmias in Structural Heart Disease
therapy may be warranted. Patients should avoid
• Ventricular arrhythmia may be either monomorphic vigorous exercise, as this can clearly accelerate
with a single QRS morphology or polymorphic with disease progression.
changing QRS morphology. The most common cause
of polymorphic ventricular tachycardia (PVT) is acute • In premature ventricular contraction (PVC) patients,
myocardial ischemia, which may quickly progress to it is important to assess the burden of PVC (24-
ventricular fibrillation (VF). Less commonly, PVT is hour Holter monitor for quantification generally
caused by circumstances that prolong the Q-T interval recommended) and to rule out any degree of
(drugs and ion-channel disorders). It is important to ventricular dysfunction. A 12-lead echocardiogram
recognize which common drugs are associated with is also useful if it shows the same PVC in most of the
Q-T prolongation and discontinue. leads for localization of the site of origin.

• Monomorphic ventricular tachycardia (MVT) is most • Right ventricular outflow tract ventricular tachycardia
commonly due to a re-entry mechanism around an (VT) is important to recognize, as this is a focal VT
infarcted scar tissue. Less commonly, MVT is due to a amenable to curative catheter ablation. This form
single focus in patients without structural heart disease. of VT has a very characteristic echocardiogram
signature (left bundle branch block with inferior axis

6 ACCSAP Study Guide and Key Points

 and late R-wave progression beyond V3). Catheter origin. A cardiac MRI should be considered in certain
ablation is highly successful in this condition. The VT situations to help exclude other underlying structural
is not ischemia driven and therefore ischemic workup disease such as ARVD or incidental scarring from
is not required or necessary unless there are other remote inflammation.
symptoms, such as exertional chest pain with risk
factors that make coronary artery disease likely. • Treatment for idiopathic ventricular arrhythmias
includes suppressive pharmacologic agents such
• In many cases, premature ventricular contractions are as beta-blockers, nondihydropyridine calcium
benign and do not require further treatment unless channel antagonists, or class Ic antiarrhythmic drugs
symptomatic. (flecainide, propafenone). Catheter ablation, which
confers a high curative success rate, is recommended
• In patients with symptomatic premature ventricular either in cases where antiarrhythmic medications
contractions (PVC) or in situations where there is a high are ineffective, not tolerated, or as a first-line therapy
burden and it is felt that the burden of PVC is contributing where such medications are not desired based on
to left ventricular dysfunction, drug suppression of the patient preference.
PVC or catheter ablation may be considered.
• In patients with symptomatic PVC or in situations
Ventricular Arrhythmias in Patients With Normal Hearts where there is a high burden and it is believed that
• Idiopathic ventricular arrhythmias, particularly PVCs, the burden of PVC is contributing to LV dysfunction,
are common and usually are not associated with drug suppression of the PVC or catheter ablation can
cardiac arrest or sudden death. be considered.

• The clinical manifestations of idiopathic ventricular • As the risk of subsequent sudden cardiac death is
arrhythmia are highly variable and range from low, ICDs are not indicated in these individuals except
benign, asymptomatic PVCs to sustained VT or even in the rare cases where concomitant polymorphic
VF (infrequent). VT or VF occurs due to reproducible PVC triggers,
or when LV dysfunction fails to normalize following
• RVOT VT is important to recognize, as this is a focal catheter ablation.
VT amenable to curative catheter ablation. This
form of VT has a very characteristic ECG signature • In patients with recurrent episodes of idiopathic VF
(LBBB with inferior axis and late R-wave progression, initiated by PVCs with a consistent QRS morphology,
beyond V3). Catheter ablation is highly successful catheter ablation is useful. Nevertheless, late
in this condition. The VT is NOT ischemia driven, recurrences are observed in approximately 10% of
and therefore, ischemic workup is not required or patients such that implantation of an ICD is prudent
necessary unless there are other symptoms such as even if ablation is acutely successful.
exertional chest pain with risk factors that make CAD
likely. Atrial Fibrillation: Rate and Rhythm Control
• AF is the most common arrhythmia encountered
• The second most common site of idiopathic VT in clinical practice; risk factors include age,
is LVVT involving the posterior fascicle of the left hypertension, valvular heart disease, thyroid disease,
bundle branch and is characterized by an RBBB/left and HF.
anterior descending QRS pattern on the 12-lead ECG.
• AF is currently classified as paroxysmal, persistent,
• The mechanism of idiopathic OT ventricular long-standing persistent, and permanent. Permanent
arrhythmias is triggered by activity caused by DADs is a circumstance where further attempts at
mediated by calcium overload. Idiopathic LVVT is less restoration of sinus rhythm are abandoned.
well understood, but may involve reentry into the His-
Purkinje system. • Anticoagulation management should be informed by
current guidelines, based on the individual patient’s
• In many cases, PVCs are benign and do not require thromboembolic risk, and not by the type of AF or
further treatment unless symptomatic. presence or absence of AF symptoms.
• In such patients, it is important to assess the • Wherever possible, reversible causes for AF should
burden of PVC (the best way to do this is with a be sought and corrected. These include: hyperthyroid
24-hour Holter monitor) and to rule out any degree state, pulmonary embolism, and pericarditis.
of ventricular dysfunction. A 12-lead ECG also is
useful if it shows the same PVC in most of the leads • Chronic contributors to AF, including hypertension,
because this can help to determine the site of the VT obstructive sleep apnea, and obesity, should be

7 ACCSAP Study Guide and Key Points

 addressed in all patients. Not infrequently, rate • A less aggressive or lenient rate control appears
control and correction of these comorbidities can equivalent to more aggressive rate control in terms of
resolve symptoms. symptom control and outcomes.

• The main goal in treating AF is to address symptoms • Catheter ablation of the AV junction for
thought to be related to AF. Rate or rhythm control nonpharmacologic rate control is highly effective,
seems to be equivalent in terms of mortality. but renders the patient pacemaker dependent and
Selection of a therapeutic strategy takes into account is irreversible. It is most suitable for elderly patients
factors that include age, symptoms, duration of AF, with associated bradycardia or intolerance/inefficacy
evidence of tachycardia-mediated cardiomyopathy, or of rate control agents.
difficulty in achieving adequate rate control.
Prevention of Arterial Embolism and Stroke in Patients With Atrial Fibrillation
• A rhythm control approach is of choice if symptoms • AF is associated with increased risk of stroke. It
are believed to be due to AF and are not resolved by accounts for >15% of stroke in the United States,
adequate rate control and risk factor modification. more than a third of strokes in patients aged >80
• Choice of antiarrhythmic drug for rhythm control years, and up to 20% of cryptogenic strokes where a
is guided by a patient’s comorbidities, presence clear vascular etiology is not present.
and type of structural heart disease, and patient • The CHA2DS2-VASc and HAS-BLED score decisions
preference. Class Ic drugs such as flecainide are used to balance the need for long-term
and propafenone should be avoided in patients anticoagulant therapy against the risk of bleeding,
with structural heart disease (CAD or HF). In this respectively. These scoring systems are best utilized
situation, the choices include amiodarone, sotalol, in patients with nonvalvular AF, and do not apply
dronedarone, and dofetilide. to other special populations, such as those with
• If acceptable rhythm control cannot be achieved hypertrophic cardiomyopathy.
with antiarrhythmic agents, catheter ablation is a • The ATRIA risk score is another validated prediction
reasonable therapy in appropriate patients with model for the risk of thromboembolism.
symptomatic AF, particularly paroxysmal AF patients
without structural heart disease. Outcomes of • Dabigatran is a direct thrombin inhibitor.
catheter ablation are less favorable in patients with
persistent AF. • Rivaroxaban, apixaban, and edoxaban are potent
factor Xa inhibitors.
• Surgical AF ablation should be considered in patients
with symptomatic AF undergoing open cardiac • Direct anticoagulants are replacing warfarin as first-
surgery for other indications. line therapy for stroke prevention in patients with AF.

• Anticoagulation should be maintained for at least 8 • New reversal agents for DOACs have recently been
weeks after ablation. After this period, continuation developed.
of anticoagulation should be based on the patient’s • Successful restoration of sinus rhythm with drugs or
thromboembolic risk profile (CHA2DS2-VASc score), ablation does not reduce the risk of future stroke in
even if the procedure is perceived successful. patients with AF.
• Potential complications of PVI include cardiac • Electrical or chemical cardioversion are effective
tamponade, TIA or stroke, phrenic nerve injury, PV means of restoring sinus rhythm, but are associated
stenosis, and atrioesophageal fistula.
with a potential risk of thromboembolism.
• Cardioversion is highly successful at restoring sinus
Atrial Flutter: Rhythm and Rate Control
rhythm. However, since the drivers of AF remain, the
likelihood of recurrence is high. • AFL is a macro–re-entrant circuit most commonly
within the RA and is sustained through a region
• Because of the risk of cardioembolic stroke of slow conduction along a channel or “isthmus”
associated with cardioversion, anticoagulation is between the IVC and the tricuspid valve, the so
recommended independent of the CHA2DS2-VASc called “cavotricuspid isthmus.” Due to the critical
score in patients in whom AF has lasted >48 hours or dependence of the arrhythmia on conduction through
if there is uncertainty regarding onset time. this region, the rhythm is classified a “cavotricuspid
isthmus-dependent” or CTI-dependent AFL.

8 ACCSAP Study Guide and Key Points

 • AFL is a closely related rhythm to AF and is the the action potential with multiple small amplitude
second most common rhythm disorder encountered inward currents (ICa-L, INaL), balanced by the outward
in clinical practice. movement of K+ in delayed rectifier K+ channels
(IKr, IKs). In phase 3, rapid repolarization is due to
• CTI-dependent AFL can be treated with drugs for increased IKr, IKs, and IK1 with inactivation of inward
rate slowing or catheter ablation along the region current (ICa-L, INaL). In phase 4, the resting membrane
between the tricuspid valve and the IVC with high potential is maintained by activation of IK1.
success (>95%).
• If (for “funny current”) is located in the SA node and
• Non–isthmus-dependent atrial flutter involves drives sinus rate.
macro–re-entrant circuits elsewhere in the RA or
LA and may occur in a variety of clinical settings, • It is the heterogeneity of cardiac action potentials
including congenital heart disease, after cardiac in different regions of the heart and across the
surgery, and after catheter ablation of AF. ventricular wall that generate the surface ECG.

• Risk of stroke in patients with AFL is identical to risk • Mechanisms for tachycardia include re-entry
in patients with AF and should be estimated based on (most common), triggered activity, and abnormal
the CHA2DS2-VASc score, as is the case with AF. automaticity.

Basic Mechanisms of Cardiac Electrophysiology • Re-entry involves abnormal conduction requiring

• Cardiac ion channels are transmembrane proteins both regions of slow conduction and unidirectional
selectively permeable to specific ions. Ion channels block. Common examples include AV nodal re-
cycle (gate) through open (conducting), inactivated entrant tachycardia, AV re-entrant tachycardia, and
and closed (nonconducting) states that are voltage- VT due to scar from prior myocardial infarction.
and time-dependent, as well as regulated by • Increased automaticity refers to abnormal phase
various signaling and metabolic pathways. Many 4 depolarization that initiates action potentials and
ion channels display rectification or a nonlinear can be provoked by a variety of conditions such as
relationship between the membrane voltage and the ischemia, catecholamines, or hypoxia. It is important
current amplitude they pass. to recognize that some myocyte types (SA node, AV
• Na+ channels are voltage gated and open in response node) exhibit intrinsic automaticity, which determines
to membrane depolarization. Inward Na + current the normal heart rate.
is responsible for phase 0 of the membrane action • Triggered activity is due to initiation of an action
potential. The fraction of Na+ channels that are potential by an afterdepolarization. Two distinct types
available (i.e., not inactivated) depends on the resting of afterdepolarization are recognized: EAD), which
membrane potential and the velocity of impulse arises BEFORE the action potential has returned to
conduction in the heart is determined by the number resting membrane potential ,and DAD, which arises
of available Na + channels. AFTER the action potential has returned to resting
• Calcium channels in the heart are L-type and T-type membrane potential.
Ca2+ channels. L-type Ca2+ channels are voltage gated. • EADs occur in the setting of a prolonged action
Ca2+ entry into the myocyte supports depolarization potential (prolonged QT interval on the ECG) and can
and triggers Ca2+ release from the SR necessary for result from drug exposure (e.g., class Ia and class
contraction. The T-type Ca2+ channel participates III antiarrhythmic drugs, many noncardiovascular
mainly for depolarization in SA and AV nodal tissue. drugs), gene mutations that cause LQTS, and
• There are many types of K+ channels that conduct K+ clinical conditions such as marked hypokalemia or
ions out of the heart to control the resting membrane acute ischemia. EADs can initiate monomorphic or
potential and action potential shape and duration. polymorphic VT/VF.
The delayed rectifier K+ currents (IKr and IKs) are key • DADs occur in the setting of intracellular Ca2+ overload,
components for action potential repolarization, and such as in digitalis intoxication and ischemia.
blockade can result in a prolonged QT interval. In
atrial, Purkinje, and ventricular myocytes, the resting • Inherited arrhythmia syndromes are caused by gene
membrane potential is maintained at around -75 mV to mutations in surface membrane ion channel (α1-
-90 mV principally by inward rectifier K+ current (IK1). subunit or accessory subunit) proteins or SR
regulatory proteins. 
• The action potential consists of five phases (0-4).
Phase 0 is carried by the rapid activation of inward • There are 17 genes associated with LQTS. The three
Na+ current. Phase 1, the “notch,” is due to transient most commonly encountered are KCNQ1, KCNH2,
outward K+ currents (Ito) giving a brief repolarization. and SCN5A.
Phase 2, the plateau, is the most complex part of

9 ACCSAP Study Guide and Key Points

 • Gene mutations in SR regulatory proteins (RyR2 and • Carriers of LQT2 and LQT3 have a 2.81 and 4.00
CASQ2) alter intracellular Ca2+ regulation to cause relative higher risk of an arrhythmic event with beta-
syndromes such as CPVT.  blockers than patients with LQT1.

• Several ion channel genes are involved in multiple • Independent predictors of failure of beta-blockers include:
clinical disorders. An example is Na+ channel gene
mutations in SCN5A that underlie Brugada syndrome QTc >500 msec
(loss of function), LQT3 (gain of function), idiopathic Early occurrence of life-threatening ventricular
VF, and sinus node dysfunction. arrhythmia (before age 7)
LQT2 and LQT3 genotype
Sudden Cardiac Death Syndromes in Structurally Normal Hearts
• A number of inheritable syndromes associated with • The preferred beta-blocker for LQTS is nadalol.
increased risk of sudden death are recognized. Propranolol is the least effective.

• Prolongation of the QT interval is associated • ICD therapy is indicated in all LQTS patients with
with morphological changes in the T waves previous cardiac arrest (Class I).
and susceptibility to life-threatening ventricular
• ICDs may be beneficial in patients who continue
arrhythmias. The specific rhythm associated with
to experience symptoms of syncope despite beta-
LQTS is PVT or torsades de pointes.
blocker therapy at the appropriate dosage, and who
• Syncope and fainting are often precipitated by are compliant. 
exercise or emotional distress. 
• ICDs may be considered in some LQTS patients with
• LQTS can be diagnosed clinically if a patient presents “higher risk” of SCD such as LQT2 and LQT3 (Class IIb).
with recurrent syncope and QTc interval >480 msec
• Newer therapies include:
in repeated ECGs in the absence of secondary causes
(e.g., drugs, electrolytes).  Use of potassium supplements in LQT2 (Class IIb)

• Borderline QT prolongation (QTc 440-470 msec) can Mexilitine in some patients with LQT3 (Class IIb)
be difficult to diagnose in an asymptomatic patient.
Review of the T-wave morphology and screening of Brugada Syndrome
first-degree relatives may be useful. 
• BrS is an arrhythmogenic condition in patients with
• The largest proportion (approximately 90%) of a structurally normal heart and a characteristic ECG
LQTS mutations are found in three genes: KCNQ1 appearance of incomplete/complete RBBB pattern.
(LQT1), encoding for the K current IKs, KCNH2 (LQT2), Familial transmission is autosomal dominant, but
encoding for the K current IKr, and SCN5A (LQT3), often there is incomplete penetrance. 
encoding for the alpha unit of the sodium channel INa.
• BrS can be diagnosed in the presence of a type
• The success of genetic testing in LQTS depends in I spontaneous ECG pattern, with ≥2 mm J-point
large part on the robustness of the clinical diagnosis elevation, which is diagnostic of types 2 and 3. 
with mutations identified in 70-80% of cases when
• Use of a sodium channel-blocking agent (flecainide
the diagnosis is certain (QTc >480 msec), but
or ajmaline) can “unmask” BrS and can assist in the
dropping significantly in borderline cases. 
diagnosis of borderline cases. Recording leads V1
• All genotype-positive/phenotype-negative subjects and V2 in second and third intercostal space can also
should avoid QT-prolonging drugs and correct any assist in the diagnosis.
electrolyte abnormalities immediately. 
• Clinical presentation of BrS includes male
• Avoidance of strenuous competitive sports is predominance (8:1) and typical age presentation at 40
important (Class I). years, but can present at a younger age.

• Beta-blockers are the mainstay of treatment and • For BrS, SCN5A is most frequently involved with
are indicated in all patients with a clinical diagnosis the loss of function mutation (the opposite of LQT3
(Class I), and suggested in patients with silent forms mutations).
(genotype-positive/phenotype-negative) – Class IIb. 
• Clinical and genetic testing of probands is
• Some differences in the effectiveness of beta- recommended for family screening along with clinical
blockers are apparent depending on the genotype. In and genetic testing of all first- and second-degree
general, patients with LQT1 respond better to beta- relatives, even if phenotype negative, to assist with
blockers than patients with LQT2 and LQT3. counseling. 

10 ACCSAP Study Guide and Key Points

 • Risk factors for arrhythmia in BrS include drugs that • In selected patients with recurrent VT despite beta-
block INa channels and tricyclic antidepressants, fever blocker therapy, flecainide may have an additive
since the SCN5A channel is temperature sensitive, benefit in addition to ICD therapy.
and heavy meals. 
Syncope
• Sudden death can be the first manifestation of BrS, • Syncope is a common phenomenon with multiple
although most patients have a history of recurrent etiologies. Most commonly, syncope in patients
syncope, particularly at rest.  without structural heart disease is neurally mediated
• Risk stratification is difficult in BrS patients. reflex syncope.

• ICDs are indicated in BrS patients with prior cardiac • Syncope is distinguished from other transient loss of
arrest (Class I) and those with spontaneous type I consciousness, such as seizures, head trauma, drug
pattern and recurrent syncope. or alcohol intoxication, or falls in the elderly.

• Asymptomatic BrS patients without a spontaneous • Cardiogenic syncope is characterized clinically with
type I pattern (or type 2 or 3 pattern) are at low risk, sudden loss of consciousness and rapid recovery.
and an ICD is NOT indicated, even if an Na channel- Most cardiogenic syncope is related to bradycardia or
blocking drug evokes a type I pattern. a ventricular arrhythmia.

• For BrS patients, avoid/treat fever aggressively. Avoid • The presence of any structural heart disease, history
drugs that block SCN5A (www.brugadadrugs.org).  of cardiac disease, or electrocardiogram abnormality
significantly increases the likelihood that syncope is
• Quinidine may be effective to prevent recurrent due to a cardiac etiology.
arrhythmias in BrS patients with an ICD. 
• Neurological causes (such as subarachnoid
hemorrhage, stroke, and generalized seizures) have
Catecholaminergic Polymorphic Ventricular Tachycardia
profound clinical presentations. Therefore, in the
•  Syncope triggered by exercise or emotion is the absence of head injury concerns, or neurological
most common clinical presentation in CPVT. Typical signs, brain imaging and electroencephalogram are
onset is age 12-15 years.  not indicated.

• Triggered activity due to delayed DADs is the • Syncope during exertion is worrisome for
common mechanism of the arrhythmia in CPVT. an obstructive etiology such as hypertrophic
These are magnified by adrenergic activity.  cardiomyopathy or aortic valve stenosis. However,
syncope after exertion is situational syncope, usually
• Autosomal dominant and recessive patterns of due to profound vasodilation, and is benign.
transmission have been recognized in CPVT and
linked to genes that control calcium release from the • An evaluation of syncope includes a thorough history,
sarcoplasmic reticulum. Autosomal dominant form physical examination, and 12-lead electrocardiogram
CPVT1 is by far the most prevalent form, accounting to guide further diagnostic and therapeutic measures.
for >70% of cases and due to mutations in the RyR2
• Patient history and examination consistent with
gene encoding the cardiac ryanodine receptor.
vasovagal syncope without structural heart disease
• The autosomal recessive form (CPVT2) is due to does not require further testing, such as tilt table testing.
mutations in the CASQ2gene. 
• Orthostatic intolerance is common, especially in the
• All patients should be established on a beta-blocker elderly, and is frequently related to dehydration and drugs.
(Class I).
• The use of carotid Doppler ultrasound, transcranial
• In patients with a genetic diagnosis of CPVT without Doppler ultrasonography, and coronary angiography
phenotype, beta-blocker should also be used (Class IIa). should not be routine in the evaluation of syncope.

• An ICD is indicated for CPVT patients with a prior • Ambulatory monitoring should be commensurate with
cardiac arrest (Class I). the frequency of occurrence of symptoms. Implantable
monitors may be necessary for infrequent or unclear
• An ICD is indicated for CPVT patients with frequency of recurrence when no obvious structural
documented VF arrest with RyR2 mutation. heart disease or other etiology is apparent.

• An ICD is indicated for CPVT patients with recurrent • Transthoracic echocardiogram is necessary only
syncope, PVT, or bidirectional VT (the classic when structural heart disease is suspected.
morphology associated with this condition) despite
compliance with beta-blocker therapy.

11 ACCSAP Study Guide and Key Points

 • Therapy for recurrent vasovagal syncope should should be aware when considering use of drugs like
center on education and recognition of prodromal propafenone or flecainide in patients with elevated
symptoms. Counterpressure maneuvers can be pacing thresholds, as use of these drugs may
helpful; salt and fluid liberalization may be helpful in precipitate loss of capture.
selected patients.
• Class I drugs may manifest Brugada pattern on ECG.
• Pacemaker therapy may be effective in selected One scenario may be a patient who has surgery
patients with recurrent vasovagal syncope with with use of multiple medications that block sodium
spontaneous symptomatic pauses ≥3 seconds or channels (lidocaine, propofol, etc.), who then has an
asymptomatic pauses ≥6 seconds. ECG that looks like type I or possibly type II Brugada
pattern. This is benign and will resolve. No further
Pharmacology of Antiarrhythmic Drugs testing is needed, but can be confused with acute
• Class I drugs block inward sodium channels and slow coronary syndrome.
conduction velocity in the myocardium. Class I drugs
exhibit a phenomenon called “use dependence” in Pacemakers
which the extent of channel block is increased at a • Pacemakers provide bradycardia support in
higher heart rate. These drugs therefore block the patients with symptomatic irreversible bradycardia.
sodium channels to a greater degree at faster heart Pacemaker therapy is contraindicated for reversible
rates. Proarrhythmic potential of class I drugs can be bradycardia (drug therapy, Lyme causes, etc.) (Class
assessed by performing treadmill exercise testing to III indication).
increase the heart rate.
• Pacemakers can be programmed in a variety of
• Class III drugs block outward potassium channel modes, which is described as the Pacemaker Code
activity (IKs) and prolong refractoriness. These agents consisting of three letters: Chamber paced, chamber
exhibit “reverse use-dependence” in which a greater sensed, and response. A pacemaker programmed
degree of channel block is seen at slower heart rates. to VVI mode would only pace the ventricle, only
sense in the ventricular, and would inhibit output if a
• Proarrhythmic effect of class III drugs is due to ventricular event was sensed. The fourth letter relates
excessive prolongation of the QT interval, leading to to rate responsiveness.
polymorphic VT (torsades de pointes). Proarrhythmic
effect of class III drugs is maximal at slower heart rates. • Dual-chamber pacemakers provide AV synchrony,
whereas single-chamber ventricular pacemakers
• Elimination of antiarrhythmic drugs is via kidneys do not. Recognition of pacemaker syndrome is
and hepatic P450 system. Important interactions important. This is characterized by nonspecific
include amiodarone and warfarin (increased INR), symptoms of fatigue, dyspnea, and palpitations in
and P-glycoprotein a renal transporter for drugs such a patient with sinus rhythm, but a single-chamber
as digoxin. ventricular device. The correct management is to
offer an “upgrade” to a dual-chamber device by
• Class I drugs are contraindicated in patients with
addition of an atrial lead.
coronary artery disease after the CAST trial showed
that mortality after MI was significantly higher • Pacemakers are generally reliable, but may fail due
after being treated with class I drugs flecainide and to “failure to capture” or “failure to sense intrinsic
encainide. cardiac activity. It is important to distinguish
between these. One scenario could be a patient
• Dronedarone is contraindicated in those with severe
implanted for complete heart block who does well
heart failure or permanent AF.
for a while and then presents with intermittent
• Antiarrhythmic drugs may alter DFT, which is failure to capture the ventricle with very high
important in situations when the DFT is marginal at electrical impedance, suggesting lead fracture with
implant. Addition of a drug that increases DFT may intermittent “make and break.”
render the defibrillation process less likely to be
• Prolonged RV apical pacing may in some cases cause
successful. In this situation, where amiodarone is
a deleterious effect on ventricular function: DAVID
added for rhythm control (VT or AF), consideration
trial. Ventricular pacing alone may also increase the
should be given to repeat DFT testing. On the
likelihood of AF.
contrary, sotalol decreases the DFT and might be a
better choice in this circumstance. • Pacemaker-mediated tachycardia can occur in
patients with a dual-chamber pacemaker when
• Class I drugs also may increase pacing thresholds.
retrograde conduction (V to A) occurs. This
This is not generally a clinical problem, but clinicians

12 ACCSAP Study Guide and Key Points

 retrograde atrial activity is sensed by the atrial patients with hypertrophic cardiomyopathy, those
channel of the pacemaker, which responds by with congenital heart disease, or those with repeated
pacing the ventricle. This presents on a surface endovascular infection requiring lead and device
electrocardiogram as AV pacing at the upper rate removal.
limit of the pacemaker. It is important to recognize.
Acutely magnet application will interrupt, but long- • ICD therapy includes antitachycardia pacing and
term prevention is to increase the PVARP to prevent high output shocks. Shocks may be necessary
sensing of the retrograde atrial activity soon after or appropriate if there is a ventricular arrhythmia
ventricular pacing. present. Unnecessary or inappropriate therapy is
most often due to AF with rapid ventricular response,
• Magnet application will have a different effect but can also be due to detected “noise” from lead
on pacemaker function than ICD function. This fracture or external electromagnetic fields. It is
distinction is important. Magnet application over a important to accurately determine the mechanism
pacemaker will result in asynchronous pacing that is leading to ICD therapy during an ICD interrogation.
manufacturer specific and can give information about
battery status. • VT/VF storm, defined as ≥3 appropriate ICD shocks
in <24 hours, is considered a medical emergency.
• Magnet application to an ICD has NO effect on pacing Secondary causes including ischemia (most common),
function, but will suspend tachyarrhythmia sensing. electrolyte imbalance, and thyroid crisis must
In other words, in patients with recurrent ICD shocks be excluded and treated if present. Therapy with
that are unnecessary (e.g., shocks due to rapid antiarrhythmic drugs, most commonly lidocaine and
AF), magnet application will suspend tachycardia amiodarone, must be instituted urgently. Ischemia
detection and stop inappropriate shocks. Another may cause polymorphic VT or VF, and cardiac
scenario could be ICD patients going to emergent catheterization should be considered. Catheter ablation
surgery where cautery may be used, which could be can be considered if monomorphic VT is present.
erroneously detected as an arrhythmia.
• When recurrent inappropriate therapy occurs, the
Implantable Cardioverter-Defibrillator (ICD) cause must be sought. Most common causes of
• ICD therapy is proven to be superior to antiarrhythmic inappropriate shocks are AF with rapid ventricular
drug therapy in patients with structural heart disease response and lead fracture noise. Magnet application
who present with resuscitated sudden cardiac arrest over the generator acutely will stop further
or hemodynamically unstable ventricular tachycardia, unnecessary shocks.
based on three major trials for secondary prevention
Cardiac Resynchronization Therapy
of sudden cardiac death.
• Numerous clinical trials have shown CRT can improve
• ICD therapy is superior to antiarrhythmic drug therapy mortality, reduce hospitalization, and stimulate
in patients without prior ventricular arrhythmias favorable LV remodeling. CRT also may benefit selected
(primary prevention), with an EF ≤35% from prior patients with a lesser degree of LV dysfunction.
MIs and NYHA class II or III symptoms, or with an EF
≤30% with NYHA class I, II, or III symptoms. • Major criteria for selection of patients for CRT are:
QRSd, NYHA class, and LV function.
• In patients with other cardiomyopathies, such as
hypertrophic cardiomyopathy, arrhythmogenic RV • The learner should know current indications for CRT
cardiomyopathy, and sarcoidosis, and inherited and patient selection, as follows:
channelopathies, such as long QT syndrome, Sinus rhythm (SR), NYHA class II or III or
catecholaminergic polymorphic VT, and Brugada ambulatory IV, LBBB, and QRSd >150 ms (Class I)
syndrome, ICD implantation is a Class I indication for
those patients who have survived a cardiac arrest due SR, NYHA class II or III and ambulatory IV LBBB
to VT/VF. An ICD may be considered to be beneficial and QRSd 120-149 (Class IIa)
(Class IIa indication) in subgroups of patients with SR, NYHA class II or III or ambulatory IV, non-LBBB
high risk factor profiles, for example, hypertrophic and QRSd >150 ms (Class IIa)
cardiomyopathy with unexplained syncope, LV wall
AF and one of the above with 100% or near
thickness≥30 mm, or sudden cardiac death in a first-
ventricular pacing anticipated (AV node ablation
degree relative.
patient, for example) – Class IIa
• The subcutaneous ICD is not capable of delivering New requirement for ventricular pacing when
pacing therapy, however. Thus, it is not appropriate >40% ventricular pacing anticipated (Class IIa)
for any patients who require a pacemaker, or in whom
• CRT may be appropriate in patients with milder
antitachycardia pacing may be required to treat VTs.
systolic HF and in selected patients who are likely to
Candidates for this form of therapy include younger
need significant RV pacing (BLOCK-HF trial).

13 ACCSAP Study Guide and Key Points

 • MADIT-CRT: CRT-D reduced rates of hospitalization • Autonomic failure syndromes tend to cause
compared with ICD alone in patients with LVEF <30%, neurogenic orthostatic hypotension.
QRSd >130 ms, and NYHA class I-II. There was no
difference in mortality. • Inappropriate sinus tachycardia may be explainable by a
dysautonomic condition or a direct sinus node problem.
• CRT is NOT indicated in patients with NYHA class I-II
and non-LBBB native conduction and QRSd <150 ms • The goal with therapy is to improve many often
(Class III). nonspecific symptoms. Most therapies have not been
well tested, and the conditions themselves may or may
• About two thirds of patients respond to CRT with not respond to more conservative measures to start.
symptomatic improvement. Pre-implant causes
of CRT non-response include non-LBBB native
conduction, or a relatively narrow native QRS.
Coronary Artery Disease

• CRT non-response can also be due to loss of LV lead Chapter: Patient Assessment
capture or poor LV lead position. History and Physical Exam
• Obtaining a detailed family history is important, since
• CRT response is dependent on >90% biventricular
many cardiovascular disorders are heritable.
pacing. Causes of nonresponse to CRT through
diminished pacing include atrial fibrillation with rapid • In the evaluation of the patient with suspected
conduction, inappropriate device programming, and congestion, a symptom or sign in isolation has limited
frequent ventricular ectopy. diagnostic sensitivity, specificity, and predictive value.

Autonomic Disorders • In patients with symptomatic heart failure or

• Dysautonomic syndromes can present in a variety asymptomatic left ventricular dysfunction, the
of different ways but are linked by orthostatic presence of an elevated jugular venous pressure or S3
intolerance (i.e., failure of blood pressure reflexes to predicts heart failure hospitalizations and death from
maintain adequate cerebral perfusion in the upright pump failure.
position). Subtypes include postural orthostatic
• Assessment of the heart failure patient based on their
tachycardia syndrome (POTS), vasovagal syncope
hemodynamics—perfusion status (warm or cold) and
(transient and often situational), inappropriate sinus
volume status (dry or wet)—is useful in assessing
tachycardia, and chronic fatigue.
prognosis and guiding therapy.
• Nonspecific symptoms include positional
• The harsh murmur of aortic stenosis may sound like
palpitations, dizziness, “brain-fog,” weakness, and
a blowing murmur of mitral regurgitation at the apex
blurred vision. Orthostatic blood pressure drop is
(Gallavardin effect).
not a feature of postural orthostatic tachycardia
syndrome (POTS). POTS should not be diagnosed • Diastolic murmurs are always pathologic.
based on symptoms alone.
• Angina pain may be atypical in certain populations.
• The definition of postural orthostatic tachycardia
syndrome (POTS) is >30 bpm heart rate increase within 10 • Cardiac dyspnea can be caused by an elevated
mins of standing or >40 in individuals 12-19 years of age. pulmonary capillary wedge, low cardiac output, or
right-to-left shunting.
• Emphasize simple nondrug treatment plans such as
a structured exercise program, tilt training, or drug • The best measure of an elevated jugular venous
therapy with midodrine in refractory cases. pressure is if it is seen above the clavicle in the seated
position.
• Inappropriate sinus tachycardia is marked by
presentation of palpitations, dyspnea, and often • Early diastolic heart sounds that may be present that
decreased exercise tolerance. include an opening snap, pericardial knock, and an S3
in that order.
• Dysautonomic syndromes are generally related to
orthostatic intolerance and have been explained by a • The Valsalva maneuver consists of 4 components,
variety of different potential disturbances. a rise in aortic pressure, a fall in pressure with
tachycardia, a further initial fall in blood pressure with
• Postural orthostatic tachycardia syndrome (POTS) is release of the Valsalva, and then a recovery period
a heterogeneous group of disorders that has similar with bradycardia.
clinical characteristics.

14 ACCSAP Study Guide and Key Points

 • An abnormal response to the Valsalva maneuver • Stress echocardiography in combination with
might be seen in patients with heart failure. contrast enhanced endocardial borders is highly
sensitive and specific and can be safely performed
Exercise Testing in most patients. Myocardial contrast perfusion may
• The two most potentially serious contraindications to further improve stress echocardiography detection of
exercise tolerance testing (ETT) that can sometimes ischemia.
be overlooked are aortic dissection and pulmonary
embolus. • Global longitudinal strain measured by speckle-
tracking echocardiography improves prognostication
• For exercise test diagnostic accuracy, the major in various cardiomyopathies; further improvement in
variable analyzed is ST-segment depression. Ischemic standardizing strain measurements is needed prior to
response is conventionally defined as ≥1.0 mm routine use.
horizontal or downsloping ST-segment depression
measured 0.08 seconds after the J point. Nuclear Cardiology
• There is a misconception that magnetic resonance
• The major impact of verification bias (i.e., post-test imaging, echocardiogram, and computed
referral) on exercise test accuracy is an artifactual tomography are superior to nuclear cardiology
increase in test sensitivity and a decrease in test imaging because of their superior spatial resolution.
specificity. Yet, it is this superior contrast resolution that allows
• Bayes’ Theorem states that the post-test probability us to differentiate between normal and abnormal
that a patient has coronary artery disease (CAD) myocardial perfusion, metabolism, and function.
depends not only on the test results, but also on the • Positron emission tomography (PET) is more
patient’s pretest probability of CAD. sensitive than single photon emission computed
• The strongest prognostic exercise test variable is tomography (SPECT) (higher count rate) and provides
exercise duration. a more robust soft tissue attenuation correction.
The consequence of these advantages with PET
• Several exercise test scores have been developed for is the possibility for a quantitation of the tracer
risk stratification, and the most commonly applied concentration in absolute units.
score is the Duke treadmill score.
• Gated PET is rapidly gaining recognition as a
• The two most common applications of valuable adjunct to interpretation of PET myocardial
cardiopulmonary exercise testing are: 1) identification perfusion. Its unique advantage over SPECT is that
of underlying cardiac or pulmonary disease in a the stress ejection fraction (EF) is obtained at peak
patient with unexplained dyspnea and prognostic pharmacologic stress rather than in a poststress
assessment, and 2) assessment of candidacy for cardiac situation, as with SPECT. The disadvantage of PET EF
transplantation in a patient with congestive heart failure. is that it is limited to pharmacologic stress only with
current PET isotopes.
• The standard ETT is the initial procedure of
choice, rather than stress imaging, for noninvasive • Patients with electrocardiographic (ECG)-defined
assessment of CAD in a patient at intermediate left bundle branch block have a high false-positive
pretest probability of CAD who is capable of adequate rate with exercise or dobutamine stress testing
exercise and who has a normal or near normal resting due to abnormal patterns of septal perfusion and
electrocardiogram. contraction.

Echocardiography • The transient 2.5- to 3-fold increase above baseline

• Doppler measurements of velocity should coronary blood flow produced by intravenous
align as parallel as possible to flow to prevent vasodilator drugs is a proven, clinically useful
underestimation. alternative to maximal exercise stress.

• Transesophageal imaging is preferred for evaluation • Exercise and pharmacologic SPECT are well-validated
of left atrial thrombus, high suspicion of endocarditis, methods for diagnosis of coronary artery disease
and left-sided prosthetic valve dysfunction. (CAD).

• When technically feasible, three-dimensional • The scintigraphic hallmark of myocardial ischemia is

echocardiography is recommended for measurement a reversible perfusion defect.
of left ventricular volumes and ejection fraction,
• The scintigraphic hallmark of myocardial infarction
evaluation of mitral valve stenosis, and guidance in
(MI) is a fixed or irreversible perfusion defect.
transcatheter procedures.
However, in the absence of prior MI or ECG Q-waves,
particularly in patients with new-onset heart failure,

15 ACCSAP Study Guide and Key Points

 hibernating but viable myocardium should be • SPECT assessment of LV function is an integral and
considered and assessed with additional myocardial recommended part of the assessment of myocardial
viability study. perfusion. It provides a wealth of nonperfusion
variables, which help in the diagnosis and prognosis
• Nuclear tests, which in general are expected to be of CAD.
positive only in the presence of hemodynamically
significant stenosis, are associated with a very low • When the oxygen supply is decreased, the heart
risk of either cardiac death or nonfatal myocardial protects itself from an oxygen-deficient state
infarction when normal. by switching its energy source to glycolysis,
downregulating mitochondrial oxidative metabolism,
• A patient with severe perfusion abnormalities on and reducing contractile function.
their stress imaging may have a five- to tenfold higher
likelihood of cardiac death compared with a patient • A metabolic switch from fatty acids to glucose
with a normal myocardial perfusion study. seems pivotal in preserving myocardial viability and
likely represents the earliest adaptive response to
• A combination of perfusion and function information myocardial ischemia.
provides robust prognostic value and serves to guide
medical and revascularization strategies. • The most common definition of myocardial viability
has been the temporal improvement in contractile
• The most important and useful clinical application function of a dysfunctional region after the restoration
of SPECT myocardial perfusion imaging is to stratify of blood flow. Requirements for cellular viability
patients into low- and high-risk categories, and thus include sufficient myocardial blood flow, intact
contribute to the management of patients. sarcolemmal and mitochondrial membrane function,
• One of the strongest features of stress myocardial and preserved metabolic activity.
perfusion SPECT imaging is its ability to identify • Available data regarding detection and intervention
low-risk patients. Patients with unequivocal normal for hibernating myocardium have largely been based
exercise or pharmacologic stress myocardial on meta-analysis and observational studies. These
perfusion SPECT images exhibit less than a 1% future suggest that the presence of substantial hibernating
cardiac event rate, which is the same as the general myocardium in patients with ischemic heart failure is
population. associated with improvement of LV function and better
• SPECT is widely used in numerous patient populations survival when revascularized compared with medical
for risk stratification such as women, diabetics, chronic therapy.
kidney disease, and preoperative assessment. • Nuclear imaging techniques, such as rest-
• Stress perfusion and gated EF components provide redistribution and stress-4-hour redistribution-
incremental information to the other, even after reinjection thallium imaging have higher sensitivity,
considering premyocardial perfusion study data. whereas contractile techniques (such as dobutamine
echo) have higher specificity for predicting LV function
• Use of optimal medical therapy and SPECT in improvement post-revascularization.
accordance with published appropriate use criteria
could help guide effective management of CAD. • Radiolabeled [123I]-mIBG is a norepinephrine
analogue, which shares the reuptake mechanism
• Patients undergoing revascularization have an and endogenous storage with norepinephrine, but is
increasing survival benefit over patients who are neither metabolized nor interacts with postsynaptic
undergoing medical therapy when moderate to severe receptors.
ischemia (>10% of the total myocardium ischemic) is
detected by myocardial perfusion study. • [123]-mIBG has received Food and Drug
Administration approval for imaging cardiac
• Radionuclide angiography (first-pass and equilibrium) sympathetic innervation of the heart in the United
is an excellent, reproducible nuclear technique for States to help identify patients with lower levels of
evaluation of left ventricular (LV) and right ventricular 1- and 2-year mortality risk as indicated by a heart-to-
function. mediastinal ratio ≥1.6.

• Radionuclide angiography (multigated acquisition) is • The feasibility of molecular imaging has been
the most widely accepted method for serial evaluation demonstrated for the assessment of inflammation
of cardiac function in patients undergoing doxorubicin and microcalcification in the carotid and coronary
therapy. vasculature and is associated with the high-risk carotid
and coronary plaques.

16 ACCSAP Study Guide and Key Points

Cardiac Computed Tomography Technology • CMR is a highly sensitive and specific imaging test for
• Scanner temporal and spatial resolution has led to the diagnosis of cardiac amyloidosis.
high accuracy and clinical applicability of cardiac
• CMR can accurately quantitate myocardial iron
computed tomography (CT) in general cardiology
noninvasively, and can be used to guide chelation
practice.
therapy.
• Cardiac CT can be accomplished using low levels of
• Many more cases of cardiac sarcoidosis are detected
radiation exposure, particularly when utilizing a scan
using CMR than by using common clinical criteria,
protocol including an axial scan mode with the X-ray
and abnormal DE-CMR portends a significantly
tube potential optimized to body size.
increased risk of adverse cardiac events and death.
• Considerations in the selection of patients for cardiac
• MR imaging is often useful for the evaluation of
CT include renal function because of the need for
patients suspected of having arrhythmogenic right
iodinated contrast, body size because of the impact
ventricular cardiomyopathy, but can supply only one
on image quality, and a controlled heart rate (typically
major or minor criterion.
<60-65 bpm) during normal sinus rhythm.
• CMR is the most sensitive and specific imaging test
• Calcium scanning is appropriate for coronary
for the detection of ventricular thrombi, being at least
heart disease (CHD) risk prediction in those with
twice as sensitive as echocardiography.
intermediate pretest CHD risk or a family history of
CHD. • CMR provides a multifaceted approach to diagnosis
of various cardiac pathophysiologic conditions by
• Calcium scanning detects subclinical atherosclerosis
enabling the assessment of morphology, function,
that may be quantitated using the age/sex/ethnicity-
perfusion, viability, tissue characterization, and blood
dependent calcium score, which independently and
flow during a single comprehensive examination.
strongly predicts future CHD outcomes.
Hemodynamic Evaluation in the Cardiac Catheterization Laboratory
• Cardiac CT angiography is most appropriately
performed in symptomatic patients with low or • Invasive hemodynamic evaluation is indicated
intermediate pretest probability for coronary artery to determine the severity of disease if there are
disease (CAD). discrepant findings between the clinical history,
physical examination, and imaging findings, or if
• Cardiac CT angiography is highly accurate for the noninvasive imaging is not conclusive.
detection of obstructive CAD in native coronary
arteries and bypass grafts. • Pitfalls in the interpretation of various hemodynamic
findings will influence the accurate determination of
• Cardiac CT can accurately assess right and left valve function studies.
ventricular systolic function, and provides a novel
method of assessment of cardiac valve structure that • The appreciation of pathophysiologic wave forms
is increasingly relevant in the transcutaneous valve during assessment and treatment of structural heart
intervention era. disease provides real time information about the
status of the procedure and potential complications.
Cardiac MR
• Constrictive physiology has characteristic
• Using accelerated imaging and single-shot
hemodynamic findings related to dynamic respiratory
techniques, cardiac magnetic resonance (CMR)
variation between ventricular pressures.
exams can now be performed even in cases of
arrhythmia or limited patient cooperation. • Invasive hemodynamic findings will assist in the
accurate determination of the etiology of congestive
• Delayed enhancement (DE)-CMR is the most
heart failure.
sensitive imaging technique for the detection of
myocardial infarction, and picks up significantly more • Mixed aortic stenosis and regurgitation
subendocardial infarctions than does single photon hemodynamic findings will influence the accurate
emission computed tomography (SPECT) imaging. determination of valve area.

• Stress CMR perfusion imaging has been shown to be • Specific examination of arterial pressures assist in the
more sensitive than SPECT imaging for the detection accurate determination of valve function and great
of coronary artery disease. vessel obstruction (coarctation) studies.

• Myocardial scarring as detected by DE-CMR Coronary Angiography

imaging is often found in patients with hypertrophic • Coronary arteriography provides the most specific
cardiomyopathy, and the extent of scar may be a risk information about the presence or absence of coronary
factor for malignant ventricular tachyarrhythmias.

17 ACCSAP Study Guide and Key Points

 artery narrowing and continues to guide decisions determine the functional/hemodynamic significance
regarding medical therapy and revascularization in of a coronary stenosis.
patients with coronary artery disease.
• Stenting of coronary lesions that are not significant
• The most frequent complication of catheterization is by FFR (>0.8) can be safely deferred and treated with
related to the vascular access site. These complications maximal medical therapy.
occur in 1-3% of patients and include local bleeding
and hematoma, femoral arterial pseudoaneurysm, • A strategy of multivessel stenting that incorporates
retroperitoneal bleeding, femoral arteriovenous fistula, FFR results in superior outcomes, fewer stents per
the need for blood transfusion or required surgical patient, and less cost compared to angiographically-
repair, and prolonged discomfort and length of stay. driven percutaneous coronary intervention.

• Major complications are uncommon (<1%) after Aortic and Pulmonary Computed Tomography and
coronary arteriography but include death (0.10- Magnetic Resonance Angiography
0.14%), myocardial infarction (0.06-0.07%), and stroke • Both computed tomography angiography (CTA) and
(0.07-0.14%). magnetic resonance angiography (MRA) can be used
to assess the aortic and pulmonary vasculature.
• Coronary diagnostic catheters are shaped to
selectively engage coronary and bypass graft • Iodinated and gadolinium contrast agents
ostia and are designed to allow advancement and are relatively and absolutely contraindicated,
directional control without kinking. respectively, in patients with chronic kidney disease
(stages 4 and 5).
• Due to the orientation of the heart within the chest
cavity, the coronary circulation is best visualized • Alternate contrast agents can be used for MRA in
using angulated right anterior oblique and left those with chronic kidney disease (stages 4 and 5).
anterior oblique projections with cranial or caudal
• By using the as low as reasonably achievable
angulation.
(ALARA) principle for limiting radiation exposure
• Coronary arteriography is regarded as appropriate in during CTA, diagnostic studies can ideally be
symptomatic patients with a high pretest probability obtained at doses of 1–6 mSv.
of disease, with suspected ACS, or with intermediate-
• Decisions about which specific test to use are
or high-risk findings on noninvasive diagnostic
dependent on several factors, including test
testing.
accessibility, test indication, patient age, gender,
Intravascular Imaging Techniques renal function, other comorbidities, or presence of
• Intravascular ultrasound (IVUS) is a safe and accurate implanted ferromagnetic metal.
method of characterizing vessel wall composition. Radiation Safety During Cardiac Imaging Procedures
• IVUS is able to define the mechanism of vessel wall • Patient radiation exposure in the United States has
changes contributing to lumen renarrowing after increased threefold since the 1980s from all medical
percutaneous coronary intervention (PCI). sources, with current cardiovascular imaging and
intervention accounting for almost 20% of the total.
• IVUS is useful in optimizing PCI results, particularly in The initial step in radiation safety is procedure
complex lesions. justification.
• Other functional modalities, rather than IVUS, should • Adverse effects from radiation are classified as
be primarily used to determine the physiologic either deterministic or stochastic. Stochastic effects
significance of atherosclerotic lesions. are caused by radiation-induced damage to a cell’s
biochemistry. This does not disrupt cell viability, but
• Optical coherence tomography is a new intravascular
it does increase the probability of genetic defects
imaging technique that has a 10-fold higher resolution
and cancer. Deterministic effects result in injury to
than IVUS.
the structure and function of the cells. Cell death
Physiologic Assessment of Coronary Stenosis can occur and is most commonly seen as skin injury
• There is a poor correlation between a physiologically presenting weeks after the event.
significant stenosis and angiographic percent • Radiation dose varies considerably among the various
diameter stenosis. cardiovascular procedures. Using the latest techniques,
• Intracoronary pressure measurements and the exposure from computed tomography (CT)
measurement of fractional flow reserve (FFR) angiography, diagnostic cardiac catheterization, and
during drug-induced hyperemia provide a means to TC-99m studies are all about the same (approximately
7-9 mSv). Percutaneous coronary intervention studies

18 ACCSAP Study Guide and Key Points

 approximately double the dose in general. Thallium • ABI <0.9 is diagnostic of peripheral arterial disease.
has the highest exposure because of its mode of
excretion and long half-life. • The angle of insonation for Doppler imaging is 60
degrees.
• A radiation safety program should be incorporated
into the catheterization laboratory quality • Abdominal aortic aneurysms are diagnosed when
improvement program. Best practices for patient ≥3.0 cm and treated when 5.0 cm.
dose reduction benefit the operator and staff, and • Internal carotid artery stenosis is considered severe
vice versa with pre-, during, and postprocedure when systolic velocities are >230 cm/sec and diastolic
dose management required. Intraprocedural dose velocities are >100 cm/sec.
management includes optimal shielding, time on
pedal, distance from source, and proper equipment • Routine carotid screening is not indicated in
specifications and use. asymptomatic patients.

• CT delivers radiation more uniformly around the Chapter: Prevention

patient than fluoroscopy. In CT, consideration for tube Atherosclerotic Risk Assessment
current, voltage, filters, and acquisition mode may
• A fundamental tenet of preventive cardiology is
potentially impact image contrast, but will clearly
matching treatment intensity to underlying risk
reduce the overall radiation dose when properly
in order to increase the likelihood that treated
understood and implemented.
individuals will benefit. Consequently, risk
• Time, distance, and shielding are the keys to reducing assessment is critical to guiding therapeutic decision
operator and patient exposure. making.

Contrast Media Complications • Novel clinical risk equations derived from four US
• Acute hypotension, overt shock, laryngospasm, cohorts incorporate race/ethnicity, in addition to
bronchospasm, rash, and gastrointestinal symptoms traditional risk factors, as an input (black, white),
after intravascular iodinated contrast administration and provide 10-year risk estimates for the combined
should be immediately recognized and require endpoint of coronary death, nonfatal myocardial
prompt and timely therapy. infarction (MI), and fatal or nonfatal stroke.

• Delayed hypersensitivity reactions can occur in • The 2013 ACC/AHA risk assessment guideline
approximately 1.5% of patients who receive nonionic provides Class IIb indications for assessment
dimers and are manifested by a self-limited pruritic of lifetime risk, family history, coronary artery
rash, nausea, and vomiting. calcium (CAC) score, ankle-brachial index (ABI), and
C-reactive protein (CRP) as potential adjuncts that
• Other side effects may include depressed ventricular “may be considered” to supplement clinical risk
contractility, arrhythmias, and general discomfort. scoring.

• Chronic kidney failure, diabetes mellitus, age, • Among established methods to refine cardiovascular
periprocedural hypotension, congestive heart (CV) risk, CAC scoring remains the most predictive
failure, and anemia are well-established risk factors of (i.e., exhibits the highest discriminatory value for)
for contrast induced acute kidney injury (CI-AKI) future CV events and mortality.
development.
• Additional established and emerging risk markers (or
• CI-AKI is associated with increased rates of causal mediators) of atherosclerotic cardiovascular
major adverse cardiovascular events and long- disease (ASCVD) include low-density lipoprotein
term mortality; however, causality has not been particle (LDL-P) burden [Apo(b), LDL-P number],
established. lipoprotein(a), carotid intima-media thickness and
plaque, and 9p21.3, among other genetic markers.
• Proper pre- and postprocedural intravenous
hydration is the most important step in CI-AKI • Novel tools designed to simplify risk communication
prevention. N-acetylcystein, statins, ascorbic acid, may promote shared decision making with patients,
and sodium bicarbonate have not proved their particularly in primary prevention settings.
efficacy in reducing CI-AKI.
• Global CV risk assessment, the cornerstone of
Noninvasive Vascular Evaluation (Ultrasound-Arterial/Venous) preventive care, serves to guide the intensity of
• Ankle-brachial index (ABI) is calculated by using the medical management.
highest blood pressure per limb over the highest arm
• The 2013 ACC/AHA guideline put forward 10-year
pressure.
Pooled Cohort ASCVD risk equations that overcome

19 ACCSAP Study Guide and Key Points

 several limitations of the previous Framingham risk • Sodium intake should be <2,400 mg/day for all
score, incorporating more diverse cohorts in its individuals, and <1,500 mg/day will result in even
derivation, including African Americans, as well as a greater blood pressure reduction.
broader composite endpoint inclusive of death from
coronary heart disease, MI, and fatal/nonfatal stroke. • All adults should consume two servings of oily fish per
week that are rich in long-chain omega-3 fatty acids
• Acknowledging the limitation of current risk models (eicosapentaenoic acid and docosahexaenoic acid).
for certain clinical scenarios, the 2013 ACC/AHA
guideline allows for consideration of the following to • Antioxidant vitamin supplements (i.e., vitamins
inform decision making: family history, lifetime risk, C and E) and folic acid supplementation have
evidence of inherited dyslipidemia, CAC scoring, CRP, not been shown to reduce CV events and are not
or ABI. recommended for CV risk reduction.

Lipid Management • Obesity is defined as a body mass index (BMI) >30

kg/m2, while overweight is defined as 25-29.9 kg/m2,
• Patients are no longer categorized by Adult Treatment
and normal weight is defined as18.5-24.9 kg/m2.
Panel III into three risk categories. The ACC, AHA,
and the National Heart, Lung, and Blood Institute • A waist circumference >102 cm for men and >88
released updated blood cholesterol guidelines that cm for women is associated with a higher risk of
now recognize four statin benefit groups including: adverse metabolic consequences of adiposity, even
1) individuals with known clinical atherosclerotic in those who are not obese.
cardiovascular disease (ASCVD), defined as coronary
heart disease, stroke, and peripheral arterial disease; 2) • The 2013 AHA/ACC/TOS Guideline for the
primary elevations of low-density lipoprotein (LDL)-C Management of Overweight and Obesity in Adults
≥190 mg/dl (i.e., familial hypercholesterolemia); 3) suggests an initial prescription of 1,200-1,500 kcal/
individuals with diabetes ages 40-75 years with LDL-C day for women and 1,500-1,800 kcal/day for men for
70-189 mg/dl and without clinical ASCVD; and 4) weight loss, or a 500-700 kcal/day energy deficit.
individuals ages 40-75 years without known clinical
• Even modest, sustained weight loss of 3-5% will
ASCVD or diabetes with LDL-C 70-189 mg/dl and
result in clinically meaningful improvements in lipids
estimated 10-year ASCVD risk >7.5%. To lower ASCVD
and blood glucose.
risk, the new guidelines emphasize high- or moderate-
intensity statin therapy. LDL-C should be reduced • Pharmacologic therapy may be appropriate for those
≥50% from baseline for those requiring high-intensity with a BMI >27 kg/m2 with comorbidity or those with
therapy and 30-49% for those requiring moderate- a BMI >30 kg/m2.
intensity statin therapy.
• Bariatric surgery is considered an appropriate
• Statin therapy is recommended for all diabetic option for patients with a BMI >40 kg/m2 or >35 kg/
patients, as well as primary prevention patients m2 with serious comorbid conditions, including
whose 10-year ASCVD risk is ≥7.5%. hypertension, diabetes, sleep apnea, and coronary
artery disease.
• Therapeutic lifestyle changes, including exercise,
dietary modification, smoking cessation, and healthy • Bariatric surgery can lead to significant
weight, can lead to substantial improvements in lipids improvements in body weight, lipids, and
and lowering of ASCVD risk. particularly in diabetes, with possible improvements
in mortality and CV events.
• All patients should be routinely counseled regarding
a healthy lifestyle and medication adherence. Smoking Cessation
Nutrition and Obesity • Tobacco use is a leading preventable cause of
morbidity and mortality and contributes to >480,000
• The 2013 AHA/ACC Guideline on Lifestyle
deaths annually in the United States.
Management to Reduce Cardiovascular (CV) Risk
emphasizes an overall healthy eating pattern, rather • Cigarette smoking is associated with increased
than focusing on a specific nutrient or food. inflammation, endothelial dysfunction, unfavorable
changes in the lipid profile, and increased
• Specific dietary recommendations consist of a
thrombotic factors.
balanced diet with limitations of saturated fat intake
to <7% of daily calories and trans fat to <1% of daily • Identification of tobacco users is the first step in
calories. Recommendations also include increased improving rates of abstinence.
emphasis on vegetables, fruits, and whole grains;
consumption of oily fish, poultry, legumes, and
nontropical vegetable oils and nuts.

20 ACCSAP Study Guide and Key Points

 • The “5 A’s” (ask, advise, assess, assist, and arrange diuretics, angiotensin-converting enzyme inhibitors,
follow-up) is an effective tool to systematically beta-blockers, and calcium channel blockers are
identify and promote smoking cessation. acceptable therapies, depending on individual
patient characteristics.
• Nicotine replacement therapy can double abstinence
rates. • Management of dyslipidemia in diabetic patients
includes medium-intensity statin therapy for the
• Combination therapy with nicotine patches and average risk individuals between 40 and 75 years of
supplemental nicotine or bupropion and nicotine age; high-intensity therapy is recommended if risk of
replacement therapy significantly increase quit rates. CV disease is ≥7.5% in 10 years.
• There is not enough data to support the use of Metabolic Syndrome
electronic nicotine delivery systems as a smoking
• The metabolic syndrome (MetS) is a clustering of risk
cessation aid.
factors associated with insulin resistance, known to
Diabetes promote or increase the risk for developing diabetes
• Diabetes is growing in prevalence and is currently the and cardiovascular disease (CVD).
seventh leading cause of death in the United States. • The prevalence of MetS continues to comprise
• Nearly 70% of patients with diabetes die of a significant proportion of the population;
cardiovascular (CV) causes, and the risk of a approximately one-third of the adult population of
myocardial infarction in a diabetic patient without developed countries can be characterized as having
existing heart disease is nearly equal to that of a MetS using different definitions.
nondiabetic patient with existing disease. • MetS, even in the absence of diabetes, is associated
• Metabolic syndrome is a clustering of three or more with an increased risk of coronary heart disease and
risk factors associated with an increased risk of CVD mortality.
developing diabetes. • An evaluation for the MetS should be performed
• General prevention strategies for diabetes consist of routinely, including measurement of blood glucose,
lifestyle management, including caloric, carbohydrate, triglycerides, high-density lipoprotein (HDL)-C, waist
and fat reductions to reach ideal body weight, circumference, and blood pressure.
increased physical activity, and smoking avoidance. • Optional screening for subclinical atherosclerosis can
• Lifestyle intervention and/or metformin are indicated further complement CV risk assessment.
as the first-line therapy in newly diagnosed patients • Lifestyle management is the foundation of managing
with diabetes. Acarbose and metformin may be able to the MetS and can improve atherogenic dyslipidemia,
delay the onset of diabetes in prediabetic individuals. elevated blood pressure, elevated glucose, abdominal
• Hyperglycemia is associated with an excess risk of CV obesity, and a prothrombotic state.
events. Although the association between intensive • A multidisciplinary team of health care providers,
glucose control and a reduction in microvascular including physicians, nurses/nurse practitioners,
complications has been established in randomized dietitians, and exercise specialists, is crucial for
trials, intensive glucose control has not been achieving success in the management of MetS.
consistently linked to improved macrovascular
outcomes. Newer agents, such as dipeptidyl peptidase Cardiovascular Disease Prevention: Considerations for Women
(DPP)-4 inhibitors and glucagon-like peptide-1 (GLP-1) • Cardiovascular disease (CVD) is the leading cause
agonists, and analogs appear to be safe and also result of mortality in women, and CVD prevalence and
in some weight loss. Hypoglycemia appears to identify mortality are higher in women than men, particularly
poor overall prognosis and should be avoided. in younger women.
• Low-dose aspirin can be considered in diabetic • The atherosclerotic cardiovascular disease (ASCVD)
patients at elevated coronary heart disease risk who Risk Score is a useful tool that is validated in
do not have a history of vascular events. women and can predict term (10-year) and lifetime
population risk.
• The target blood pressure for diabetic patients
is systolic blood pressure BP <140 mm Hg and
diastolic blood pressure <90 mm Hg. Thiazide

21 ACCSAP Study Guide and Key Points

 • There are a number of risk factors for CVD that are activity (e.g., parking the car farther away from stores
unique to women. when shopping, avoiding elevators/escalators, walk
breaks at work).
• Postmenopausal hormone therapy should not be
used for the prevention of CVD. • The absolute risk of exercise-related cardiovascular
events during outpatient cardiac exercise therapy is
• Women are more likely to be undertreated and extremely low. The risk of cardiac arrest and death
receive fewer preventive recommendations, such as are approximately 1 in 115,000, and 1 in 750,000
lipid-lowering therapy, aspirin, and lifestyle advice, patient-hours of participation, respectively.
than do men with similar risk scores.
• The fervor of the physician’s recommendation
Exercise Rehabilitation and Exercise for Prevention appears to be the single most powerful predictor of
• Exercise-based cardiac rehabilitation (CR) includes exercise-based CR participation.
outcomes (e.g., regular physical activity, improved
cardiorespiratory fitness) that have been shown to Chapter: Acute Coronary Syndromes
reduce the risk of recurrent cardiovascular events. UA/NSTEMI: Myocardial Infarction: Pathophysiology
• Among coronary patients, each 1 MET increase • Most acute coronary syndromes (ACS) result from
in exercise capacity is associated with an 8-35% disruption of a vulnerable atherosclerotic plaque
reduction in mortality. The reported reductions in often marked by thin-capped fibroatheroma (TCFA).
mortality are comparable to or greater than those • Factors that determine risk for plaque rupture include
observed for many cardioprotective medications location of the plaque, the degree of inflammation
(e.g., aspirin, statins, beta-blockers). within the plaque, and the integrity of the plaque’s
• There are four phases of CR: Phase I (inpatient phase) fibrous cap.
involves physical therapy and patient education after • Novel work with optical coherence spectrometry has
a cardiac event. Phase II (outpatient phase) consists demonstrated that although the absolute number of
of individualized exercise prescription and risk factor TCFA lesions is greater in nonsevere stenoses than
reduction under supervision of a medical team. severe stenoses, the plaque within a severe stenosis
Phases III and IV (maintenance phase) emphasize is twice as likely to be TCFA.
long-term lifestyle changes to maintain healthy
behavior via independent continuation of the exercise • In the initial phases of coronary lesion formation,
program and cardiovascular risk reduction learned vascular remodeling occurs wherein the plaque area
during phase II. typically expands outward, away from the lumen, as
a compensatory mechanism to prevent narrowing of
• Referral to outpatient CR is indicated for patients with the coronary vessel.
chronic stable angina, systolic heart failure, non–ST-
elevation or ST-elevation myocardial infarction in • Fibroatheroma forms and progresses as the lipid-
the last 12 months, and those who have undergone rich core encapsulated by fibrous tissue is invaded
cardiac surgery (coronary artery bypass grafting, by macrophages, a necrotic core forms, collagen is
valve replacement/repair, or heart/heart-lung actively digested, and the rim of fibrous tissue that
transplant) or percutaneous coronary intervention. separates the core from the vascular lumen thins.

• The minimum or threshold intensity for improving • When the fibrous cap ruptures, intensely
cardiorespiratory fitness in cardiac patients procoagulant substances are exposed to the blood
approximates 45% of the oxygen uptake reserve, pool, leading to platelet adhesion, activation, and
which corresponds to approximately 70% of the aggregation.
highest heart rate achieved during peak or symptom-
limited exercise testing. • Platelet aggregation occurs via the glycoprotein IIb/
IIIa receptor and allows for the coagulation cascade
• Walking on level ground at 2 and 3 mph approximates to proceed with the fixation of the prothrombinase
2 and 3 METs, respectively. At a 2 mph walking complex and thrombin generation.
speed, each 3.5% increase in treadmill grade adds
approximately 1 MET to the gross energy cost. For • When intracoronary thrombus forms, it may obstruct
patients who can negotiate a 3 mph walking speed, the coronary lumen entirely, leading to ST-elevation
recognize that each 2.5% increase in treadmill grade myocardial infarction or sudden cardiac death; less
adds 1 additional MET to the gross energy expenditure. severe obstruction may result in no symptoms,
unstable angina, or non–ST-elevation myocardial
• Structured exercise should be complemented by infarction.
resistance training and increased lifestyle physical

22 ACCSAP Study Guide and Key Points

 • Myocardial necrosis and resultant biomarker discharge or on an outpatient basis in a timely fashion
positivity due to a nonobstructive intracoronary (within 72 hours).
thrombus most often results from platelet-rich
microaggregates that embolize to the myocardial • Early risk stratification should be conducted in all
resistance vessels downstream to the epicardial patients with suspected non–ST-elevation ACS
plaque rupture. (NSTE-ACS). Early risk assessment should focus on
the clinical exam (history and physical examination),
• Other causes of ACS include supply-demand inequity, ECG findings, and cardiac markers. Such assessment
coronary emboli or vasospasm, and plaque erosion. may help guide clinical decision making, including
the site of care (observation, inpatient, intensive
UA/NSTEMI: Initial Management, Risk Assessment, and Risk Stratification care unit), optimal medical therapy, and decisions
• Patients with ongoing symptoms suggestive regarding coronary angiography.
of acute coronary syndromes (ACS) should be
instructed to call 911 and referred to a facility • Optimal risk stratification requires a multivariable
(such as an emergency department) that allows approach that accounts for multiple prognostic
evaluation by a physician and the recording of a 12- factors. Clinically validated risk-stratification models,
lead electrocardiogram (ECG) and cardiac markers such as the TIMI or GRACE risk scores, are useful to
determination. Transportation by an ambulance is assist with decision making regarding management
favored over friends or relatives. strategy and timing of invasive assessments in
patients with suspected NSTE-ACS.
• The initial assessment of patients with suspected
ACS should prioritize two questions: Are the • The Universal Definition of MI requires elevation in
symptoms indicative of an ongoing ACS? If so, what cardiac troponins, with a rise and/or fall in levels over
is the short-term risk of adverse events? serial measurement, together with symptoms or
signs of cardiac ischemia. Many conditions other than
• A patient’s symptom description is a critical cardiac ischemia may lead to elevation in troponins.
diagnostic step, and typical symptoms such as Moreover, MI may be due either to plaque rupture
retrosternal pressure or heaviness are the hallmarks (type 1 MI) or due to supply demand mismatch, with
of angina. However, some patients, like women or without underlying coronary artery disease (type
and the elderly, may be more likely to present with 2 MI).
atypical symptoms such as nausea, dyspnea, and
diaphoresis as “anginal equivalents.” Antiplatelet Therapy for Non-ST-Segment Elevation Acute Coronary Syndromes
• Non–ST-elevation acute coronary syndromes (NSTE-
• In all patients with symptoms suggestive of ACS, a ACS) is a platelet-centric disease; greater platelet
12-lead ECG should be performed in a timely manner inhibition is associated with reduced ischemic event
after arrival at the emergency department (with occurrence.
a goal of within 10 minutes) and reviewed by an
experienced emergency clinician. • Because NSTE-ACS patients are at high risk for both
acute and long-term ischemic event occurrences, a
• ECGs should be reviewed for ST-segment deviation great clinical challenge exists to balance the risks of
(elevation or depression), which are the most specific stent thrombosis and ischemic complications versus
signs of ischemia, or T-wave changes. Patients with bleeding.
a nondiagnostic ECG at presentation and a high
suspicion of ACS should have posterior ECG leads • Aspirin remains the bedrock oral antiplatelet agent
(V7-V9) reviewed to disclose possible true posterior in patients with NSTE-ACS. The efficacy of new oral
ST-elevation myocardial infarction (MI) to avoid antiplatelet agents has been studied on top of aspirin
delays in lifesaving reperfusion. in clinical trials. These agents are always prescribed
in addition to aspirin in common clinical practice.
• Troponin is the preferred biomarker to diagnose
myocardial necrosis and should be measured in all • Dual antiplatelet therapy is standard of care in
patients with suspected ACS. Patients with negative patients with NSTE-ACS.
cardiac markers within 6 hours of symptom onset
should have biomarkers remeasured in the time • The optimal pretreatment antiplatelet strategy for
frame of 3-6 hours after symptom onset. NSTE-ACS patients undergoing an invasive treatment
strategy remains controversial.
• If the patient remains asymptomatic and repeated
ECG/cardiac markers are negative, a stress test to • The optimal duration of dual antiplatelet therapy in
provoke ischemia should be performed either before NSTE-ACS patients beyond 1 year is controversial.

23 ACCSAP Study Guide and Key Points

 • The DAPT (Dual Antiplatelet Therapy) and PEGASUS- • Vorapaxar is a first-in-class, selective, reversibly
TIMI 54 (Prevention of Cardiovascular Events in binding, orally administered protease-activated
Patients with Prior Attack Using Ticagrelor Compared receptor-1 inhibitor. Based on the favorable net
to Placebo on a Background of Aspirin-Thrombolysis clinical benefit observed in patients with a previous
in Myocardial Infarction 54) trials compared the myocardial infarction (MI) in the TRA 2°P-TIMI
efficacy of long-term (>12 months) P2Y12 inhibitor 50 (Thrombin Receptor Antagonist in Secondary
therapy on top of aspirin. Both trials demonstrated Prevention of Atherothrombotic Ischemic Events)
enhanced efficacy of long-term dual antiplatelet trial, the FDA approved the use of vorapaxar added
therapy at the expense of greater bleeding. to aspirin and/or clopidogrel to reduce the risk of MI,
stroke, cardiovascular death, and revascularization in
• Both of the new P2Y12 inhibitors, prasugrel (an patients with a previous MI without a history of stroke
irreversible, third-generation thienopyridine) and or transischemic attack.
ticagrelor (a reversibly binding, direct-acting agent),
are associated with a faster onset of action, greater • Bleeding is associated with worse clinical outcomes,
platelet inhibition, and lower on-treatment platelet and strategies to minimize its occurrence are
reactivity than clopidogrel. Improved clinical mandatory in the care of the NSTE-ACS patient.
outcomes, including less stent thrombosis compared
with clopidogrel, have been demonstrated in two UA/NSTEMI: Anticoagulant Therapy
large ACS clinical trials comparing these agents with • Current guidelines have simplified the choices
clopidogrel. However, increased coronary artery of anticoagulant therapies irrespective of the
bypass grafting (CABG) and non−CABG-related major management strategy (early invasive vs. ischemia-
bleeding were associated with prasugrel therapy, and guided). In the most updated version, irrespective
increased CABG-related bleeding was associated of the management strategy, administration of
with ticagrelor. parenteral anticoagulant agents to all patients with
non–ST-elevation acute coronary artery syndrome
• The pharmacologic agents that directly block the (NSTE-ACS) is recommended as soon as possible
binding of fibrinogen to glycoprotein (GP) IIb/IIIa after presentation (Class I).
receptors are more effective in inhibiting platelet
aggregation than any oral antiplatelet strategy. • Four different agents are recommended as Class
I options for initial anticoagulation in NSTE-ACS
• The initial antiplatelet strategy for patients with patients: unfractionated heparin (UFH), enoxaparin,
definite or likely NSTE-ACS undergoing ischemia- bivalirudin, or fondaparinux.
guided therapy includes aspirin and either clopidogrel
or ticagrelor (Class I recommendations). A Class IIa • For NSTE-ACS patients undergoing percutaneous
recommendation is given for preference of ticagrelor coronary intervention (PCI), acceptable regimens
over clopidogrel. include enoxaparin, bivalirudin, or UFH (Class I).

• In patients undergoing percutaneous coronary • Patients treated initially with fondaparinux who
intervention (PCI), a Class I recommendation is require PCI should be treated with UFH at the time of
given for a loading dose of clopidogrel, prasugrel, or the PCI to avoid catheter-related thrombus.
ticagrelor. A Class IIa recommendation is given for
• The duration of anticoagulation for patients
preference of ticagrelor or prasugrel over clopidogrel.
undergoing PCI is up until (but not after) the PCI is
• In patients with NSTE-ACS and high-risk features performed.
(e.g., elevated troponin) and not adequately
• The duration of anticoagulation for patients
pretreated with clopidogrel or ticagrelor at the time of
undergoing coronary artery bypass grafting (CABG)
PCI, a Class I recommendation is given for GP IIb/IIIa
is up to CABG for patients treated with UFH; up to 3
inhibitors (abciximab, double-bolus eptifibatide, or
hours prior to CABG for bivalirudin (with continuance
high-dose bolus tirofiban).
of UFH); up to 12-24 hours prior to CABG for low
• Cangrelor directly, reversibly, and competitively molecular weight heparin (LMWH); and up to 24
inhibits binding of adenosine diphosphate to hours prior to CABG for fondaparinux.
the P2Y12 receptor. Cangrelor is a parenterally
• For medically managed patients (either
administered drug with a short half-life (3-6 minutes)
conservatively managed patients who do not
and rapid onset/offset of action. These features are
undergo angiography or invasively managed patients
desirable in high-risk patients undergoing urgent PCI
who do not undergo PCI or CABG), the recommended
or surgery. Cangrelor is still awaiting Food and Drug
duration of anticoagulation is typically for a minimum
Administration (FDA) approval as an adjunct to PCI.
of 48 hours (for patients treated with UFH) or the
length of hospital stay (up to 8 days) for patients

24 ACCSAP Study Guide and Key Points

 treated with LMWH or fondaparinux. Patients who • Risk stratification after the initial reperfusion
have been treated with bivalirudin and are medically strategy should include assessment of the success of
managed following diagnostic angiography can have reperfusion (epicardial and microvascular), detection
the bivalirudin stopped or continued for up to 72 of heart failure or mechanical complications,
hours at the physician’s discretion. evaluation of left ventricular function, and selective
assessment for provokable ischemia.
• Protamine is indicated for life-threating or serious
bleeding with UFH and LMWH. It binds to both UFH • The presence of frequent ventricular ectopy, low
and LMWH to form a stable ion pair that does not heart rate variability, reduced baroreflex sensitivity,
possess anticoagulant properties. It has, however, and T-wave alternans are all associated with a higher
a more complete effect on UFH over LMWH, likely risk of sudden death after STEMI. However, to date,
due to greater binding to UFH. Adverse reactions neither these noninvasive approaches, nor invasive
to protamine can be seen among patients who are electrophysiological testing has proved sufficiently
allergic to fish or who have received porcine insulin useful to recommend their routine use in practice.
(such as NPH insulin). Cryoprecipitate and fresh Left ventricular dysfunction and the occurrence of
frozen plasma do not reverse the effects of indirect (late) sustained ventricular arrhythmias are the most
thrombin inhibitors such as heparins. important indicators of a higher risk of sudden death
and are linked to specific therapeutic recommendations.
• The benefits and risks of triple antithrombotic therapy
with aspirin, P2Y12 receptor inhibitor, and warfarin STEMI: Reperfusion Therapy for STEMI
have not been clearly established, which leaves this • Immediate recognition of ST-elevation myocardial
recommendation at Class IIb. Such therapy should be infarction (STEMI) with timely initiation of reperfusion
selected for clear indications for extended duration therapies significantly decreases cardiovascular
of oral anticoagulation, and given for the shortest morbidity and mortality.
duration of time, at the minimally effective doses
necessary to achieve protection (i.e., aspirin 81 mg, • The selection of reperfusion strategy in STEMI
and warfarin titrated to INR 2.0-2.5). Clopidogrel is the (pharmacologic vs. invasive vs. pharmacoinvasive)
P2Y12 receptor inhibitor of choice when triple therapy is dependent on the time from onset of symptoms,
is necessary. mortality risk of STEMI, bleeding risk, and time
for transport to a skilled percutaneous coronary
STEMI: Initial Assessment and Risk Stratification intervention (PCI) facility.
• The initial evaluation and management of patients
with possible ST-elevation myocardial infarction • Primary PCI (PPCI) is associated with a superior rate
(STEMI) are focused on: of TIMI 3 flow restoration, a lower rate of reinfarction
and mortality, and less intracranial bleeding,
Rapid diagnosis. compared with fibrinolytic therapy.
Expedited assessment of risks for reperfusion • Bleeding is an important outcome measure in PCI and
therapy. is significantly associated with mortality. Strategies to
Timely initiation of a reperfusion strategy. reduce bleeding include transradial access and careful
selection of antithrombotic/antiplatelet strategies.
Continuous reassessment of the risk for and
presence of complications. • Routine aspiration thrombectomy is no longer
• Diagnosis of STEMI is dependent on recognition of recommended in PPCI. Distal protection device
ST-segment elevation along with clinical symptoms utilization and routine rheolytic thrombectomy are
of ischemia. Because ST-segment changes not recommended in PPCI.
precede the release of detectable concentrations of
• The use of drug-eluting stents in PPCI is a reasonable
biomarkers of necrosis by hours, treatment, including
alternative to bare-metal stents and decreases target
reperfusion therapy, should not be delayed awaiting
vessel revascularization.
biomarker results in patients with diagnostic ST
elevation. • Nonculprit PCI, during either the index procedure or
a staged procedure, may be reasonable even in the
• Symptoms, signs, and biomarkers of heart failure
absence of cardiogenic shock.
are the strongest predictors of mortality in patients
presenting with STEMI. Early electrocardiographic • Fibrinolytic agents have significant differences in fibrin
indicators of high risk are those that reflect specificity, pharmacokinetics, efficacy, and safety.
particularly large territory at risk (e.g., extreme
magnitude of ST elevation, posterior extension, • While combination therapy and facilitated therapy
involvement of the conduction system). can no longer be recommended, a pharmacoinvasive
strategy for reperfusion with fibrinolytics and early
directed angiography is a preferred strategy.

25 ACCSAP Study Guide and Key Points

 • Delayed PCI of a totally occluded artery >24 hours • STEMI patients presenting to facilities without
after STEMI in asymptomatic patients with one or two interventional capabilities who receive thrombolysis
vessel coronary artery disease is not recommended if should be transferred immediately to a referral center
patients are hemodynamically and electrically stable, with a cardiac catheterization laboratory.
and do not demonstrate evidence of severe ischemia.
STEMI: Ancillary Therapy II: Secondary Prevention After STEMI
STEMI: Ancillary Therapy I: Antithrombin and Antiplatelet Therapy • Early administration of beta-blockers, especially
• Unfractionated heparin (UFH) is recommended in intravenously in ST-elevation myocardial infarction
association with fibrinolysis. Recommended duration (STEMI) patients with high-risk characteristics (older
of infusion should not exceed 48 hours in the absence age, hemodynamic instability, increased heart rate,
of an ongoing indication for anticoagulation given lower blood pressure, and signs of chronic heart
the risk of heparin-induced thrombocytopenia; failure [CHF]) may increase the risk of cardiogenic
when longer infusions will be required, other shock and shock-related death.
antithrombotic agents should be considered.
• Long-term treatment with beta-blockers is beneficial
• Utility of low molecular weight heparin in the setting after STEMI for reduction of death and recurrent
of thrombolysis is limited by excess bleeding with adverse events.
these agents.
• Beta-blockers should be avoided in patients with
• Bivalirudin is associated with lower cardiovascular STEMI associated with cocaine use.
mortality and bleeding events in ST-elevation
myocardial infarction (STEMI) patients, relative to • Among patients with STEMI with and without left
UFH with glycoprotein inhibitors, but may carry an ventricular (LV) systolic dysfunction, early initiation
increased risk of stent thrombosis. (within 24 hours) of oral angiotensin-converting
enzyme inhibitors (ACEIs) and continued long-term
• Fondaparinux requires ancillary antithrombotic treatment significantly reduce mortality and recurrent
therapy during cardiac catheterization given cardiovascular (CV) events.
the increased risk of catheter thrombosis with
fondaparinux alone. • All patients following STEMI should be considered
for ACEI therapy. The groups that are least likely to
• All STEMI patients should receive aspirin and a benefit include those with preserved LV function in
P2Y12 receptor inhibitor. Prasugrel is contraindicated the setting of adequate revascularization.
in patients with prior stroke or transient ischemic
attack. Ticagrelor is contraindicated in patients with • Patients who are intolerant of ACEIs may be treated
severe liver impairment or a history of intracranial with angiotensin-receptor blockers (ARBs).
hemorrhage. • The aldosterone blocker eplerenone has been shown
• Genetic polymorphisms influence response to to reduce mortality for post-STEMI patients with an
clopidogrel, but the role of pharmacogenomic and/or LV ejection fraction (EF) ≤40% and without significant
platelet function testing has yet to be defined. renal dysfunction or hyperkalemia who are already
receiving therapeutic doses of an ACEI and have
• Fondaparinux is an anti-thrombotic agent. It binds either symptomatic CHF or diabetes.
to antithrombin III, leading to inhibition of factor
Xa inhibitor. Fondaparinux monotherapy has been • Nitrates may be useful in the convalescent phase
associated with catheter-associated thrombosis after STEMI for the treatment of recurrent angina,
during percutaneous coronary intervention (PCI) but randomized trial data suggest that they do not
and is not recommended. Guidelines recommend significantly reduce mortality; nitrate use should not
additional intravenous antithrombotic agent preclude use of beta-blockers or ACEIs.
administration for STEMI patients who received • Calcium channel blockers may be hazardous and
fondaparinux prior to PCI. increase adverse events in certain patients after
• There is increased risk of bleeding with combination STEMI. Verapamil and diltiazem should be avoided in
of warfarin and aspirin. If aspirin is to be used in STEMI patients with LV systolic dysfunction and CHF.
combination with warfarin, the aspirin dose should be Short-acting nifedipine is generally contraindicated in
low (75-162 mg) and the international normalized ratio the treatment of STEMI.
(INR) goal of 2.0-3.0. If triple therapy is warranted, i.e., • Certain calcium channel blockers may be useful
warfarin combined with aspirin and clopidogrel after for treatment of angina, hypertension, and atrial
PCI, such patients should receive low-dose aspirin tachyarrhythmias in select patients after STEMI when
(75-81 mg), no more than 75 mg/d of clopidogrel, and beta-blockers (or nitrates) are ineffective, not tolerated,
maintain an INR of 2.0-2.5.

26 ACCSAP Study Guide and Key Points

 or contraindicated, and in whom there are no signs of Right-heart catheterization shows an increase, or
CHF, LV dysfunction, or atrioventricular block. “step up” in oxygen saturation at the level of the
right ventricular.
• The goal of intensive glucose control with IV insulin in
the setting of an acute MI should be to maintain blood Emergent surgical repair is the treatment of
glucose levels <180 mg/dl and to avoid hypoglycemia. choice, even if the patient is hemodynamically
stable. Patients who survive surgery have good
• Long-term intensive glucose control with an HbA1c prognosis.
goal <6 is associated with increased rates of
• Papillary Muscle Rupture
hypoglycemia and detrimental clinical outcomes.
Papillary muscle rupture usually involves the
• A fasting lipid profile should be assessed in all
posteromedial papillary muscle that receives
patients and within 24 hours of hospitalization for
perfusion from the right coronary artery,
those with an acute CV or coronary event.
whereas the anterolateral papillary muscle has
• Starting dietary therapy is recommended for all dual blood supply.
patients. Reduce intake of saturated fats (to <7% of Papillary muscle rupture usually presents with
total calories), trans fatty acids, and cholesterol (<200 acute pulmonary edema and cardiogenic shock.
mg/day).
Patients may have a soft or absent systolic
• Managing warfarin to an international normalized murmur due to rapid equalization of pressures in
ratio equal to 2.0-3.0 for paroxysmal or chronic atrial the left ventricle and the left atrium during systole.
fibrillation or flutter is recommended, and in post- Echocardiography can confirm the diagnosis and
MI patients when clinically indicated (e.g., atrial demonstrate the site of rupture.
fibrillation, LV thrombus).
Emergent surgical repair is the treatment of
• Labetalol and carvedilol have both alpha- and beta- choice. Afterload reduction with intra-aortic
blocker properties. Either of these drugs can be balloon pump and nitroprusside administration
used in the setting of cocaine-induced myocardial may serve as bridge to surgery. Percutaneous
infarction to reduce systemic blood pressure without mitral valve repair can be of clinical benefit in
increasing coronary vasospasm. Beta-blockers inoperable patients.
such as metoprolol should be avoided in the setting • Right Ventricular Infarction
of cocaine-induced myocardial infarction due to
coronary vasospasm. The classic triad of hypotension, elevated jugular
venous pressure, and clear lungs is strongly
• Verapamil and diltiazem are nondihydropyridine suggestive of right ventricular infarction in
calcium channel blockers and should not be used in patients with inferior acute myocardial infarction.
patients with LV systolic dysfunction or CHF.
Administration of nitroglycerin or other preload-
STEMI: Mechanical Complications of Myocardial Infarction reducing agents can cause profound hypotension
• Free Wall Rupture in right ventricular infarction patients.
Volume loading, inotropic support, and early
Free wall rupture usually manifests as tamponade,
reperfusion are the mainstays of right ventricular
pulseless electrical activity, and death.
infarction treatment.
Reperfusion therapy decreases the risk of free wall
rupture. Chapter: Stable Ischemic Heart Disease
Risk Stratification
Echocardiography shows hyperechoic pericardial
effusion with signs of tamponade. • Stable ischemic heart disease (SIHD), also termed
chronic coronary artery disease, encompasses
Emergent surgical repair of the rupture offers the a heterogeneous population that varies in terms
best chance for survival. of comorbidities, symptoms, and risk of future
• Ventricular Septal Rupture cardiovascular events.

Ventricular septal rupture usually presents as • Categorization of patients into low-, intermediate-,
chest pain and cardiogenic shock. and high-risk categories should be a primary goal in
the evaluation of patients with SIHD. Patients with an
Usually patients have a loud, holosystolic murmur.
annual mortality rate of <1% are considered low risk,
1-3% are considered intermediate risk, and >3% are
considered high risk.

27 ACCSAP Study Guide and Key Points

 • Risk stratification in patients with SIHD should left ventricular ejection fraction <40% with heart
proceed in a stepwise and logical progression. failure or prior MI.

• There are four broad categories of risk stratification • SIHD patients receiving intensive medical therapy who
that should be considered: 1) clinical evaluation and are at low risk for a cardiovascular (CV) event do not
assessment of comorbidities, 2) functional capacity/ benefit from angiotensin-converting enzyme inhibitor
stress test results, 3) ventricular function, and 4) (ACEIs) therapy. Conversely, ACEIs reduce CV mortality
coronary anatomy. Most patients will not need all and morbidity in “high-risk” patients with vascular
four domains tested. disease (i.e., those with poorly controlled risk factors,
diabetes, and other CV risk factors).
• Based on the strength of evidence, cost, and ease,
stress testing should be, in most cases, the first-line • If SIHD patients are statin intolerant or have
test for functional capacity among patients who can inadequate responses to high- or moderate-intensity
exercise and have an interpretable electrocardiogram. statin therapy, nonstatin agents may be used or
Some patients may have an indication for additional added, including proprotein convertase subtilisin
imaging, but even when imaging is obtained, exercise kexin 9 (PCSK9) inhibitors, ezetimibe, bile acid
stress, rather than pharmacologic stress, is preferred sequestrants, nicotinic acid, fibrates, and probucol.
whenever possible to obtain functional information.
Indications for Revascularization
• Regardless of the clinical situation, left ventricular • Medical therapy with antiplatelet agents, lipid-
function is not only one of the most powerful lowering therapy, and antianginal agents is the
predictors of short- and long-term outcomes, but mainstay of treatment in patients with stable
it also carries therapeutic implications regarding ischemic heart disease.
appropriate medical, revascularization, and device-
based therapies. Left ventricular function, therefore, • The goals of revascularization are to improve survival
should be assessed in all patients with SIHD, even and provide relief of ischemic symptoms.
without any signs or symptoms of heart failure.
• Revascularization is indicated in patients with
• Coronary angiography should be performed significant left main stenosis and in patients
based on the results of clinical history and with multivessel disease involving the proximal
noninvasive risk-stratification tools. Many low- to left anterior descending artery, particularly with
intermediate-risk patients with SIHD may not require subnormal left ventricular systolic function.
coronary angiography, whereas in other patients,
• Factors influencing the decision to perform coronary
catheterization may be the first diagnostic test after
revascularization include the anatomical degree of
the initial clinical evaluation. Defining the coronary
coronary artery burden, the amount of inducible
anatomy should be considered an important tool for
ischemia on noninvasive testing, the severity of
risk stratification, and not simply as a diagnostic tool
symptoms, the intensity of medical therapy, and
to identify potential lesions for revascularization.
associated comorbidities.
Medical Therapy
• With improvements in both surgical and
• Unless contraindicated, all patients with evidence of percutaneous revascularization techniques, the risks
SIHD should receive aspirin to prevent myocardial of revascularization procedures in elderly patients
infarction (MI). are declining, and data from more recent studies
• Patients with a history of MI may derive greater indicate that selected elderly patients derive similar,
benefit from prolonged dual antiplatelet therapy if not more relative benefit from revascularization
(DAPT), but decision-making regarding prolonged compared with younger patients.
DAPT requires a personalized consideration of each Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting
individual’s future thrombotic versus bleeding risk.
• Revascularization with coronary artery bypass
• Vorapaxar is contraindicated in patients with stroke or grafting (CABG) to improve survival is indicated in
transischemic attack. patients with significant left main coronary artery
disease (CAD) or severe three-vessel CAD involving
• Beta-blockers are the only antianginal drugs proven the proximal left anterior descending coronary artery.
to prevent reinfarction and improve survival in
patients who have had an MI. • In patients with single-vessel CAD, long-term
outcomes following successful percutaneous
• Beta-blockers should be used for at least 3 years coronary intervention (PCI) and CABG are similar.
following an MI, and appropriate beta-blocker therapy
should be continued indefinitely for all patients with • In patients with multivessel CAD without a high level
of complexity (e.g., low-to-intermediate SYNTAX

28 ACCSAP Study Guide and Key Points

 score), successful revascularization with CABG or PCI reversible with lifestyle modification and treatment of
results in similar long-term outcomes. risk factors.

• In patients with complex multivessel CAD (high • Coronary microvascular dysfunction may lead to
SYNTAX score), revascularization with CABG symptoms and signs of myocardial ischemia, as seen
results in fewer repeat revascularization procedures in patients with microvascular angina in the absence
and improved long-term survival compared with of obstructive coronary artery disease.
multivessel PCI.
• Assessment of the coronary microcirculation
• In diabetic patients with multivessel CAD, CABG depends on evaluation of its functional aspects. Both
results in improved survival compared with PCI. invasive and noninvasive methods are available to
assess coronary microvascular function.
• Patients with significant left main or complex
multivessel CAD ideally should be evaluated by a • Most available methods do not assess coronary
multidisciplinary heart team to determine the most microvascular function in isolation. They assess the
appropriate method of revascularization. total impact of both epicardial coronary disease and
microvascular dysfunction on myocardial perfusion.
Hibernation, Stunning/Viability
• The term “myocardial stunning” describes the • A coronary flow reserve (CFR) <2.5 is generally
state of postischemic myocardial dysfunction in the considered abnormal. Decreased CFR in the setting of
presence of relatively normal blood flow. normal epicardial vessels is representative of coronary
microvascular dysfunction.
• The term “myocardial hibernation” describes the
state of chronic myocardial dysfunction at rest that • Assessment of coronary microvascular function
can be partially or completely restored to normal may allow early identification of at-risk patients,
either by improving blood flow and/or by reducing monitoring of treatment, or perhaps open new
demand. options for therapeutic intervention.

• In the STICH trial, the assessment of myocardial • Management includes traditional antianginal drugs
viability with dobutamine stress echocardiography and novel therapies, including potassium-channel
and/or single photon emission computed openers, metabolic agents, rho-kinase inhibitors,
tomography did not identify patients with a angiotensin-converting enzyme inhibitors, late
differential survival benefit from coronary artery sodium-channel modifiers, and statins.
bypass grafting, compared with medical therapy
Assessment of Asymptomatic Coronary Artery Disease
alone, in contrast with the prior literature.
• It cannot be automatically assumed that diagnosing
• Several noninvasive imaging methods are available disease in an early, asymptomatic state prevents
that assess myocardial viability either indirectly clinical disease or improves health.
(by measuring morphology or contractile reserve)
or directly (by measuring metabolic activity or cell • It cannot be automatically assumed that if a test
membrane integrity). predicts clinical events, its routine use will prevent
events.
• Understanding the underlying assumptions in current
viability assessment methods is important. • Although a test may “independently” predict events
by standard statistical criteria, it may fail to improve
Microvascular Angina clinicians’ ability to discriminate patients who will
• Chronic stable angina, even among patients develop disease from those who will not, and to
with “completely” normal appearing coronary properly reclassify patients’ risk.
angiography, carries a significant burden in terms of
• More importantly, although a test may predict
morbidity and overall adverse outcome.
events, it may not predict response to preventive
• Coronary microvascular function is an important interventions.
prognostic factor in a wide range of disorders and
• All asymptomatic adults should be checked for global
diseases.
risk based on standard cardiovascular risk factors,
• Coronary microvascular dysfunction may be present and for family history of premature coronary artery
in the absence of overt disease in conduit arteries. disease.

• Coronary microvascular dysfunction can be detected • Physicians may refer intermediate-risk patients for a
in the presence of vascular risk factors and may be number of tests, but they should inform their patients

29 ACCSAP Study Guide and Key Points

 that it is not known whether obtaining information myocardial contraction. Myocardial relaxation is an
from additional tests will lead to better health. These ATP-dependent process, unlike myocardial contraction.
tests include high-sensitivity C-reactive protein (for
those meeting JUPITER [Justification for the Use of • Pressure-volume loops depict instantaneous
Statins in Prevention: an Intervention Trial Evaluating recordings of ventricular pressure against ventricular
Rosuvastatin] criteria), urine analysis, and resting volume during a single cardiac cycle. The loop area,
electrocardiography (in people with hypertension which represents stroke work, changes based on
or diabetes), carotid intima-media thickness, ankle- varying preload and afterload and also in response to
brachial index, and coronary calcium scores. changes in the intrinsic properties of the myocardium.

• Randomized trials are needed to improve physicians’ • Persistent activation of the sympathetic nervous
ability to work with patients and make informed system and renin-angiotensin-aldosterone system
evidence-based decisions about screening for after myocardial injury has a proremodeling effect.
coronary artery disease in asymptomatic adults. Other neurohormones also may be implicated,
including arginine-vasopressin and endothelin-1.
Nitric oxide, atrial natriuretic peptide, and B-type
Heart Failure and Cardiomyopathy natriuretic peptide have antiremodeling properties.

Chapter: Heart Failure and Cardiomyopathy • Patients with heart failure with preserved ejection
Epidemiology, Risk Factors, and Comorbidities fraction (HFpEF) are older and more often women,
when compared with heart failure with reduced
• Heart failure (HF) is a worldwide pandemic, with both
ejection fraction (HFrEF) patients. Comorbidities are
increasing prevalence and incidence, particularly in
common in this population.
the elderly population.
• Patients with HFpEF have true HF, defined as
• Despite the decreasing mortality with symptomatic
increased cardiac and pulmonary filling pressures
HF, approximately 50% of patients with HF will die
and vasoconstriction of the systemic and
within 5 years.
pulmonary circulations. The disease appears to
• HF represents America’s largest diagnosis-related be pathophysiologically distinct and not merely a
group, and the 90-day readmission rate after an index continuum with HFrEF.
hospitalization for HF is as high as 47% of discharges,
• A number of pathophysiologic processes contribute
leading to the fact that more Medicare dollars are
to this syndrome, and not all patients have the same
spent on HF than on any other diagnosis.
contributors, leading to significant phenotypic
• Among the numerous risk factors for HF, the common heterogeneity. Therapy is currently focused on
ones include coronary artery disease, hypertension, identification and treatment of underlying processes.
renal dysfunction, older age, diabetes mellitus, and
Clinical Assessment (Prognosis, Functional Capacity, Quality of Life)
obesity, which represent important targets for HF
prevention initiatives. • Given the ability of the lung lymphatics to adapt to
chronic left ventricular pressure elevations, many
• The identification of asymptomatic patients with patients presenting with decompensated heart failure
left ventricular ejection fraction ≤40% is important (HF) have clear lungs on exam and on chest X-ray
because effective therapy (i.e., angiotensin- (sensitivity of rales is only 15%).
converting enzyme inhibitors or angiotensin-
receptor blockers) can be initiated that can slow the • Several basic laboratory findings can identify patients
progression of the HF syndrome and prolong life. with heart failure who are at risk for poor outcomes,
including hyponatremia, renal insufficiency, anemia,
Basic Mechanisms and Pathophysiology of Heart Failure elevated natriuretic peptides, and elevated troponins.
• Myosin, actin, tropomyosin, and the troponins are
• Most clinical scores (Framingham, Boston) used
sarcomeric proteins that interact with calcium and
to diagnose HF have poor sensitivity, but excellent
adenosine triphosphate (ATP) to produce myocardial
specificity.
contraction and relaxation.
• The diagnosis of HF with preserved ejection fraction
• Excitation-contraction coupling is the mechanism by
(HFpEF) can be challenging, but is aided by signs and
which small amounts of extracellular calcium enter
symptoms of HF, normal ejection fraction, evidence
the myocyte during the action potential to initiate

30 ACCSAP Study Guide and Key Points

 of diastolic dysfunction on echocardiography, and • Composite scores for quantifying the degree of
elevated natriuretic peptide levels. congestion are emerging.

• When considering a diagnosis of a familial • Patients should be classified based on the presence
cardiomyopathy, a family history of at least three or absence of congestion and adequacy or
generations should be recorded; when genetic testing inadequacy of perfusion.
is considered, it should be performed in the individual
with the most obvious phenotypic features of the • Invasively measured hemodynamics via right-heart
disease. catheterization (RHC) allows direct measure of the
PCWP and cardiac output, but careful attention to
• Current data suggest that according to the ACC and detail when performing this procedure is necessary
AHA staging system, of all individuals who can be to obtain reliable information.
classified as Stage A-D heart failure, approximately
22% ages >45 years have risk factors (Stage A), while • Estimation, rather than measurement of VO2, can lead
34% have evidence of structural heart disease (Stage to important errors when measuring cardiac output
B) in the absence of symptoms. by the Fick method.

• The New York Heart Association classification is a • The ESCAPE (Evaluation Study of Congestive
subjective measure of functional capacity, and may Heart Failure and Pulmonary Artery Catheterization
be affected by symptoms due to noncardiovascular Effectiveness) trial demonstrated no significant
disease. benefit of routine RHC in patients with advanced
heart failure.
• Several surveys of quality of life of HF patients
have been developed. The Minnesota Living with • Currently, invasive RHC would be indicated for
Heart Failure Questionnaire and the Kansas City patients with decompensated heart failure who
Cardiomyopathy Questionnaire are validated, reliable, are not responding as expected when decision
and reproducible surveys that are often used as making is based on noninvasive methods (persistent
endpoints in outcome studies. symptoms, hypotension, renal failure despite apparent
volume overload) and in patients in whom therapies
• The Heart Failure Survival Score can help estimate with significant risks (inotropes, LV assist devices,
1-year survival and the need for heart transplantation; transplant) are being considered.
however, it requires peak exercise oxygen
consumption data as part of its scoring system, which • An implantable sensor, which wirelessly transmits
may not be readily available to all clinicians. pulmonary arterial pressures, has gained Food
and Drug Administration approval for New York
• The Seattle Heart Failure Model is a more recent Heart Association class III patients who have
validated scoring system that predicts 1-, 2-, and been hospitalized in the prior year. Benefit was
5-year survival based on a number of readily available demonstrated both in those with a reduced or
variables. preserved LV ejection fraction.

Hemodynamic Assessment Cardiomyopathies

• Hemodynamic disturbances are central to the • Dilated cardiomyopathy (DCM) reflects the common
symptoms of patients with heart failure, and there are phenotypic expression of a wide variety of primary
both noninvasive and invasive assessment methods and secondary processes affecting the myocardium.
available to clinicians.
• A large proportion of DCM is likely related to a genetic
• The history and physical examination remain the cause; however, routine genetic testing is likely low
foundation of noninvasive assessments, with yield in the absence of a strong family history of
congestion being assessed best by the jugular cardiomyopathy or typical presentation.
venous pressure (JVP) and presence of orthopnea.
• Postpartum cardiomyopathy, tachycardia-
• A novel symptom of heart failure, dyspnea when related cardiomyopathy, and stress (takotsubo)
bending forward (bendopnea), is associated with cardiomyopathy represent important DCM
elevated pulmonary capillary wedge pressure syndromes that may be reversible with appropriate
(PCWP), often in the setting of a low cardiac index. medical treatment.

• Although the JVP, as a reflection of the right atrial • Restrictive cardiomyopathies (RCMs) are less
pressure, often is concordant with left ventricular common than DCM and may be related to a
(LV) filling pressures, it is not a direct measure. Thus, broad range of infiltrative, inflammatory, and
when the clinical course is unexpected based on JVP endomyocardial processes. The prevalence of
estimates, alternative methods of assessing LV filling specific etiologies varies by region and the population
pressures would be warranted. under study.

31 ACCSAP Study Guide and Key Points

Completed Trials of Renin Angiotensin Aldosterone Antagonists
in Heart Failure with Preserved Ejection Fraction
Trial Drug HR
N Inclusion Criteria Endpoint
(Target Dose) (95% CI)

CHARM- Candesartan 3023 NYHA II-IV HF, EF >40% CV death/HF 0.89

Preserved (32 mg) hospitalization (0.77-1.03)

PEP-CHF Perindopril 850 Ages ≥70 years, All-cause death/ 0.92

(4 mg) NYHA II-IV HF, HF hospitalization (0.70-1.21)
Diastolic dysfunction
on echocardiography

I-Preserve Irbesartan 4128 Ages ≥60 years, NYHA All-cause death/ 0.95
(300 mg) II-IV HF, EF ≥45%, HF CV hospitalization (0.86-1.05)
hospitalization or Table 1
substrate for HF
Completed Trials of Renin Angiotensin
TOPCAT Spironolactone 3445 Age ≥50 years, NYHA CV death/aborted 0.89
(45 mg) II-IV HF, EF ≥45%, HF cardiac arrest/HF (0.77-1.04)
Aldosterone Antagonists in Heart Failure
hospitalization or hospitalization With Preserved Ejection Fraction
elevated BNP

• Endomyocardial biopsy may be useful in identifying be candidates for therapeutic interventions such as
a specific cardiomyopathy etiology. The yield is likely implantable cardioverter-defibrillator (ICD).
highest in those with RCM and those with DCM and
rapidly progressive heart failure. • HCM remains the most common cause of sudden
death in young patients (including athletes). Patients
• Arrhythmogenic right ventricular cardiomyopathy with one or more of the five primary sudden death
is an important contributor to sudden death in the risk factors may be considered at increased risk and
young and represents an inherited disease of the considered for ICD therapy for primary prevention. In
desmosome. addition, the extent of late gadolinium enhancement
(i.e., myocardial fibrosis) by contrast-enhanced CMR
• Patients with arrhythmogenic right ventricular may help identify high-risk patients who have none of
cardiomyopathy should be instructed to avoid the traditional risk markers, and help resolve complex
strenuous exercise in order to minimize the ICD decision-making in patients whose high-risk
progression of disease. status remains uncertain after assessment with the
Hypertrophic Cardiomyopathy traditional risk markers.

• Hypertrophic cardiomyopathy (HCM) is a genetic • LV outflow tract obstruction due to systolic anterior
cardiomyopathy caused by mutations of the cardiac motion with ventricular-septal contact and associated
sarcomere resulting in heterogeneous phenotypic mitral regurgitation is present in the majority of HCM
expression with respect to the extent, location, and patients at rest or with exercise, and is a strong and
distribution of left ventricular (LV) wall thickening, as independent promoter of heart failure symptoms
well as a diverse clinical course, including sudden and death in this disease. Exercise echocardiography
death, heart failure, and stroke. should be used to identify provokable gradients in
patients without rest obstruction. The presence of
• Two-dimensional echocardiography can be used
central or anteriorly directed mitral regurgitation jets
to reliably diagnose patients with HCM when an
suggests the presence of intrinsic mitral valve disease.
area of increased LV wall thickness is imaged in the
absence of another cause, as well as to determine • HCM patients with obstruction and heart failure
the presence and magnitude of LV outflow tract symptoms can be initially treated with beta-blockers
obstruction and associated mitral regurgitation. and calcium channel blockers or disopyramide.
In addition, cardiac magnetic resonance (CMR) Patients with New York Heart Association class III/
can be used to clarify a diagnosis of HCM or the IV symptoms and LV outflow tract gradients ≥50 mm
extent of wall thickness in patients in whom LV wall Hg who fail medical therapy become candidates for
thickness measurements remain uncertain with two- invasive septal reduction therapy.
dimensional echocardiography.
• Surgical myectomy remains the gold standard
• Genetic testing is now available for clinical use, and for treatment of obstructive HCM, with aspirin an
can be used to identify family members who may be important alternative treatment option. The decision
at risk of developing HCM or identify patients who of which procedure may be best for an individual
may have a disease that appears phenotypically patient should be arrived at in the context of the
similar to sarcomere HCM, such as Fabry disease or current literature and clinical experience of the
a lysosomal/glycogen storage disease. Results of respective institutions, through physician and patient
genetic testing do not impact management strategies, discussions and ultimately a fully informed patient.
such as identifying patients at high risk who would

32 ACCSAP Study Guide and Key Points

 Noninvasive Markers of Diseases Commonly Confused With Heart Failure
Elevated Left Ventricular (LV) Filling Pressures With Preserved Ejection Fraction

Modality Findings Indicative of Elevated LV Filling Pressures Cardiovascular Noncardiovascular

Physical exam Jugular distention or abdominojugular reflux, gallop sounds,
peripheral edema, ascites, hepatomegaly, pleural effusion
• Hypertrophic cardiomyopathy • Pulmonary disease
• Infiltrative or restrictive cardiomyopathy • Anemia
Chest radiography Cardiomegaly, pulmonary venous hypertension or edema,
• Pulmonary arterial hypertension • Obesity
pulmonary artery enlargement, pleural effusion
• Constrictive pericarditis • Deconditioning
Echocardiography Abnormal transmitral or pulmonary vein Doppler (high E/A • High output heart failure • Renal artery stenosis
ratio, short E wave deceleration time), high tissue Doppler
E/e’ ratio, left atrial enlargement, elevated pulmonary artery • Valvular heart disease • Thyroid disease
pressure estimates, dilation, and/or failure of collapse in the • Coronary artery disease • Neuromuscular disease
inferior vena cava
• Pulmonary embolism
Blood testing Elevated B-type natriuretic peptide or N-terminal proBNP levels • Right ventricular myopathies

Table 2 Table 3
Nonivasive Markers of Elevated Left Ventricular (LV) Diseases Commonly Confused With Heart Failure With
Filling Pressures Preserved Ejection Fraction

• End-stage HCM occurs in approximately 5% of • Surgical revascularization offers the potential for
patients, and is associated with significant LV improved survival and quality of life, particularly in
remodeling causing systolic dysfunction (ejection patients with more extensive multivessel disease
fraction <50%) as well as wall thinning and cavity and the greatest degree of left ventricular systolic
dilation. Patients in the end-stage remain at increased dysfunction and remodeling.
risk of sudden death and advanced heart failure
Medical Therapy for Chronic Heart Failure
symptoms, and should be considered for ICD therapy
• In general, all patients with heart failure (HF) and
and early consideration for heart transplantation.
reduced left ventricular ejection fraction (LVEF)
• Atrial fibrillation (AF) is common in HCM and when should have angiotensin-converting enzyme
present is often responsible for significant worsening inhibitors (ACEIs) and beta-blockers instituted and
in symptom limitation and an increased risk for titrated to the target doses used in clinical trials.
thromboembolic event. The CHADS2 score has not
• Angiotensin-receptor blockers (ARBs) should be
been specifically validated in HCM, but in general a
prescribed in the event of ACEI intolerance due to
low threshold for initiating anticoagulation should
cough or angioedema. ARBs do not provide any
be considered for all patients with symptomatic AF
particular benefit over ACEIs if cardiorenal limitations
episodes. The majority of patients with symptomatic
(e.g., hypotension, renal insufficiency, hyperkalemia)
AF who fail antiarrhythmic therapy can be considered
are the reason for ACEI intolerance.
for pulmonary vein catheter-based ablation, with a
significant reduction in the burden of AF. • Aldosterone antagonists should be considered in
patients with symptomatic HF, as long as serum
Coronary Artery Disease and Heart Failure
creatinine is <2.5 mg/dl and potassium levels are <5.0
• Coronary artery disease (CAD) now surpasses
mmol/L.
hypertension as the major etiologic factor in heart
failure (HF) in the developed world. • Hydralazine and isosorbide dinitrate in combination
should be considered, particularly in African-
• A baseline coronary angiogram is indicated in most
American populations, if advanced symptoms (e.g.,
patients with HF and CAD, especially if they have
HF of New York Heart Association class III-IV) persist.
frank angina or chest pain, unless patients are not
candidates for revascularization. • Digoxin may have symptomatic benefits in patients
with HF, but effective serum levels rarely require
• Viability testing may be considered in patients with
doses >0.125 mg daily.
HF and reduced ejection fraction. However, it is
unclear whether it has added utility when combined • Diuretics should be used at the lowest doses tolerated
with other traditional clinical risk factors and in the to maintain a stable compensated volume status.
presence of guideline-directed medical therapy However, high-dose diuretics can be administered
(GDMT) in predicting survival after coronary artery safely in patients with acute decompensated HF.
bypass grafting.
• Anticoagulation with warfarin or a novel oral
• GDMT remains the cornerstone of treatment for all anticoagulant is warranted when HF is complicated
patients with HF regardless of the presence of CAD. by a history of a prior thromboembolic event (e.g.,
stroke), atrial fibrillation, or presence of LV thrombus.
33 ACCSAP Study Guide and Key Points
 • Statins are not recommended solely to improve and follow-up care. For patients at high risk of
outcomes in patients with HF. readmission, referral to an HF disease management
program can help to maintain clinical stability.
• LCZ696 (sacubitril plus valsartan) has been shown to
be superior to enalapril in patients with symptomatic Heart Failure With Preserved Ejection Fraction
HF and reduced LVEF, and can be considered instead • One-half of patients with heart failure (HF) have
of ACEIs and ARBs to reduce cardiovascular mortality preserved ejection fraction (EF), and the prevalence
and HF hospitalizations. of HFpEF relative to HF with reduced EF is growing
with the aging US population. Outcomes are similarly
• Ivabradine can be considered to decrease HF
poor in HFpEF relative to HFrEF. The dominant risk
hospitalizations in symptomatic HF with reduced EF
factors for HFpEF are age, hypertension, and female
and normal sinus rhythm with a resting heart rate
sex.
≥70 bpm despite optimal beta-blockade or in those
intolerant of beta-blockers. • The pathophysiology of HFpEF is complex and is
related to left ventricular (LV) diastolic dysfunction,
• To avoid complications of polypharmacy, close,
causing elevated filling pressures and venous
frequent surveillance of symptoms, clinical status,
congestion, ventricular-arterial stiffening promoting
and laboratory tests is required.
blood pressure lability, and limitations in systolic,
• Neurohormonal antagonists have not been proven diastolic, and chronotropic reserve responses with
beneficial in HF with preserved EF (Table 8). The stress, leading to exertional dyspnea and fatigue.
guidelines recommend adequate blood pressure and
• Diagnosis of HFpEF is clinical and relies on
heart rate control with judicious use of diuretics for
establishing symptoms of HF (e.g., dyspnea, fatigue)
symptom palliation.
with objective signs of congestion (Table 2) and/or
Acute Decompensated Heart Failure and Cardiorenal Syndrome inadequate cardiac output at rest or stress. Typical
• At the time of admission for acute decompensated echocardiographic findings include concentric LV
heart failure (ADHF), several routine clinical and remodeling, left atrial dilatation, diastolic dysfunction,
laboratory variables can be used to stratify the risk of and pulmonary hypertension. Invasive assessment
in-hospital mortality in patients with HF. Likewise, a and cardiopulmonary exercise testing are useful
number of predischarge variables can help to predict diagnostic tests in equivocal cases.
the likelihood of HF readmission and to prioritize the • Many cardiovascular and noncardiovascular diseases
timing and intensity of postdischarge care. produce findings that mimic HFpEF (Table 1). Most of
• Bedside assessment of hemodynamic status should these entities have their own specific treatments and,
include evaluation for systemic venous or pulmonary thus, must be distinguished from “garden variety”
congestion and systemic hypoperfusion. Most HFpEF through appropriate evaluation.
patients admitted with ADHF present with congestion • There is no proven treatment for HFpEF. Trials
and normal perfusion and will respond to treatment examining angiotensin-converting enzyme inhibitors,
with IV loop diuretics. angiotensin-receptor blockers, and digoxin have
• If patients do not respond to initial diuretic therapy, been negative, whereas beta-blockers, devices, and
consideration should be given to the administration of aldosterone antagonists have not been adequately
parenteral vasodilator or inotropic therapy. Vasodilators studied to date. Guidelines recommend control of
are preferred unless limited by hypotension. Positive volume overload with diuretics, control of blood
inotropes may contribute to proarrhythmia and are pressure, and control of ventricular rate in atrial
associated with adverse outcomes. fibrillation. Evaluation for ischemia and consideration
of cardioversion for atrial fibrillation should be
• An acute HF admission offers an important considered in appropriate patients.
opportunity to adjust or add guideline-directed
medical therapy, to address problems associated with Advanced Therapies: Transplantation, Ventricular
reduced ejection fraction, such as arrhythmia and Assist Devices, and Surgical Management
thromboembolic risk, and to manage comorbidities, • Survival following heart transplantation is >85% at 1
including diabetes, anemia, and chronic kidney year, 70% at 5 years, and 50% at 10 years.
disease regardless of ejection fraction.
• Advanced heart failure (HF) therapies should be
• Discharge planning should include patient and considered when either HF symptoms become
family education on activity level, sodium and fluid refractory to conventional medical, surgical, and
restriction, medication adherence, weight monitoring,

34 ACCSAP Study Guide and Key Points

 device interventions or when end-organ dysfunction therapy can be used, but requires significant
becomes apparent. caregiver support.

• The primary indication for heart transplantation is • Inotropes may improve the patient’s symptoms
based on objective measures of functional capacity, and overall quality of life, but also may accelerate
but is integrated into a comprehensive assessment of mortality. The goals of therapy should be discussed
patient risk and prognosis. in detail with the patient and caregivers.

• Complications following transplantation include • It is reasonable to forgo generator change in a patient

rejection, infection, renal insufficiency, malignancy, whose device has reached the end of battery life, but
and cardiac allograft vasculopathy. this decision requires review with the patient and
family.
• Heart transplantation is the treatment of choice for
end-stage HF, but remains limited by donor organs • Selective deactivation of an implantable cardioverter-
and comorbidities in potential candidates. defibrillator (ICD) should be discussed with the
patient and family members when the patient enters
• The continuous flow left ventricular assist device the terminal phase of HF in order to prevent shocks in
(LVAD) is now an established therapeutic option as the dying patient.
a permanent solution for advanced HF, as well as a
“bridge” to transplantation, myocardial recovery, • Unlike ICDs, cardiac resynchronization (CRT) has
and/or further consideration of long-term options been shown to improve quality of life. Therefore, it
(e.g., “bridge to decision”). may be appropriate to continue biventricular pacing
for patients even when the decision has been made to
• Bleeding, stroke, driveline infection, right ventricular turn off ICDs.
dysfunction, and device failure/thrombosis are
potential complications following VAD placement. • In patients who are being considered for left
ventricular assist device (LVAD) implantation, it is
• Myocardial recovery after VAD support remains critical that the patient establishes advance directives
uncommon, but will likely evolve over time as before implantation and has a preparedness plan that
VAD support will be used as a platform for direct outlines the conditions under which he or she desires
myocardial therapies. the device to be turned off.
• Revascularization in severe ischemic LV dysfunction • In LVAD patients who have a catastrophic and life-
should generally be individualized on the basis of the changing complication without a meaningful recovery,
STICH trial. it is important to have an open and honest discussion
• Current evidence does not support surgical with the family regarding device deactivation.
ventricular remodeling or mitral valve repair for most • Judicious use of oxygen, opioids, and diuretics
patients with severe systolic HF. should be used to control symptoms of anxiety,
Palliative Care in End-Stage Heart Disease dyspnea, and pain.

• Patients with ACCF/AHA stage D heart failure (HF) • Hospice care is a specialized form of palliative care
have progressed to the point that their options in which the patient has decided to forgo all life-
include heart transplant, mechanical support, home prolonging treatment. Hospice patients usually have
inotropes, experimental protocols, or palliative care/ a life expectancy of less than 6 months.
hospice.
Disease Management in Heart Failure
• The focus of palliative care is symptom relief, but • Despite recent advances in heart failure (HF) care, HF
does not preclude reasonable active treatment, admission and readmission rates remain high, with
unless the patient has transitioned to hospice. 30-day post discharge readmission rates of 20-25%
• Patient preferences are a key component to decision and 6-month readmission rates of up to 50%.
making, and a multidisciplinary care approach (e.g., • Financial penalties attached to excess readmission of
delivered by a palliative care team) is important and Medicare beneficiaries following HF hospitalization
fully supportable. have prompted HF disease management (HFDM)
• Medical therapy for HF should be continued unless it activities that may be favorably affecting
is not tolerated or upon patient/family request. readmissions.

• For patients who are not candidates for cardiac • Patient factors (e.g., nonadherence to medications,
transplant or ventricular assist device therapy, diet, and fluid restrictions), physician factors (e.g.,
chronic, continuous outpatient intravenous inotropic inadequate patient education and implementation
of guideline recommendations), and health system

35 ACCSAP Study Guide and Key Points

 factors (e.g., inadequate discharge planning, care • Immunosuppression has no known benefit in acute
transitions, and follow-up) all contribute to high viral myocarditis, but may have a role in chronic
readmission rates and poor health outcomes in HF inflammatory cardiomyopathy that persists despite
patients. optimal medical treatment.

• Multidisciplinary HFDM programs reduce all-cause

readmission rates by 20-30% and HF readmission Valvular Disease
rates by approximately 50%; favorable effects on
mortality, quality of life, and cost of care have also Chapter: Valvular Disease
been demonstrated in some but not all studies. Epidemiology of Valvular Heart Disease
• There has been a major shift in the etiology of valve
• Data on the utility of structured telephone support
disease from a rheumatic etiology to a degenerative
and telemonitoring services in the management of HF
one, except in poorer developing countries.
patients are conflicting, and additional study of these
Approximately 60% of all valvular diseases in
interventions is needed.
industrialized countries are caused by a degenerative
• Current guidelines state that “Effective systems of care etiology that includes mitral valve prolapse and aortic
coordination with special attention to care transitions stenosis as the main causes.
should be deployed for every patient with chronic HF
• In industrialized countries, approximately 2.5% of the
that facilitate and ensure effective care that is designed
population has evidence for valvular heart disease,
to achieve guideline-directed medical therapy and
with the prevalence of mitral versus aortic disease
prevent hospitalization” (Class I, Level of Evidence B).
varying according to study design.
Myocarditis
• Valvular heart disease increases in prevalence with
• Myocarditis has a variable presentation and can be age, impacting survival.
caused by a wide range of pathogens.
• Rheumatic fever (RF) and rheumatic heart disease
• The most frequently identified pathogens are viral (RHD) remain a serious problem in developing
and the spectrum of identified viruses has changed countries, especially in Asia and Africa. There are
with time; currently, parvovirus B19 and human at least a half million new cases of RF each year.
herpes virus-6 (HHV-6) are the most common viruses Approximately 15 million people worldwide have
in the United States and Europe. RHD, and over a quarter of a million patients with
RHD die each year. New guidelines for the diagnosis
• The pathogenesis of myocarditis is a three-stage
of acute RF with carditis have been published in 2015
process: injury and activation of innate immunity,
that include use of echocardiography and allow for
acute myocardial inflammation, and progression to
the diagnosis of subclinical acute RF.
dilated cardiomyopathy.
• Degenerative aortic valve disease increases in
• One should suspect giant cell myocarditis (GCM),
prevalence with age. One-third of patients >75 years
sarcoidosis, or Lyme or Chagas disease when the
of age have aortic sclerosis and 2.6% have aortic
cardiomyopathy is associated with high-grade heart
stenosis. The risk factors for these disorders are
block.
similar to those related to atherosclerosis.
• GCM is a fulminant and rapidly progressive disease
• Bicuspid aortic valve (BAV) patients typically
that affects young, healthy individuals; it is a
predominate in younger patients with aortic valve
pathologic diagnosis with high biopsy sensitivity.
stenosis or regurgitation, whereas degenerative
• Endomyocardial biopsy (EMB) is the “gold standard” valve disease of congenitally tricuspid aortic valves
for diagnosing myocarditis; Cardiac magnetic predominates in older patients. Half of the patients
resonance has a synergistic role with EMB and with a BAV also have an abnormally dilated aortic
improves diagnostic accuracy. root caused by inherent defects in the aortic root
structure. At least 9% of patients with a BAV will have
• Myocarditis primarily affects the left ventricular (LV) a first-degree relative with the same process. More
and is more frequently diagnosed by LV biopsy, which men than women have a bicuspid valve.
has a low rate of complications in experienced centers.
• Aortic regurgitation is rare (0.8%) in the general
• The primary treatment strategy for myocarditis population and is more common in men.
consists of guideline-based heart failure treatment
regimens.

36 ACCSAP Study Guide and Key Points

 • Over 2% of the general population exhibit mitral valve quantitative criteria beyond color jet dimensions,
disease. Women are more likely to suffer this than particularly if jets are nonholosystolic or eccentric.
men.
• Cardiac magnetic resonance imaging complements
• Mitral annular calcium is common, with 45% of the echocardiographic assessment of mitral
patients >65 years of age exhibiting evidence for this. regurgitation.
It can occasionally lead to both mitral regurgitation
and mitral stenosis. • For chronic, primary mitral regurgitation, no
pharmacologic agent has been shown to slow
• With the increase in the number of patients progression toward surgical intervention.
with systolic heart failure and both ischemic
and nonischemic mitral regurgitation (MR), the • For primary mitral regurgitation, surgical mitral valve
prevalence of functional MR is now greater than that (MV) repair is recommended over MV replacement
of primary mitral valve disease. because of preserved left ventricular (LV) function,
lower operative mortality rate, and lower rate of
• Mitral stenosis caused by rheumatic heart disease is complications associated with prosthetic valves in the
very rare in industrialized countries (0.1%). Women long term.
predominate, and it is a major cause of pregnancy
complications in endemic areas. • For severe, chronic, secondary mitral regurgitation,
medications and interventions (including
• Minor degrees of tricuspid and pulmonary revascularization and/or cardiac resynchronization
regurgitation are extremely common. therapy) to treat left ventricular systolic dysfunction
should be optimized before mitral valve intervention.
1. Endocarditis remains a serious disease, and there has
been a shift to older patients, more device infections, • For severe, secondary mitral regurgitation, surgical
and a change in the most common organism from mitral valve repair or replacement may improve left
streptococci to staphylococci. ventricular function and clinical symptoms, but has
not been shown to improve survival.
Mitral Regurgitation
• Anatomic or functional abnormalities of the mitral • Surgical repair rates and operative mortality
annulus, leaflets, subvalvular apparatus, or left rates are strongly influenced by operator and
ventricle may result in mitral regurgitation. center experience.

• Causes of mitral regurgitation may be broadly • For chronic, severe secondary ischemic mitral
differentiated as primary (predominantly regurgitation, valve replacement may be preferable
degenerative) or secondary (functional), a to valve repair to lower the risk of recurrent mitral
classification that has significant impact on prognosis regurgitation. But for chronic, moderate ischemic
and management. mitral regurgitation undergoing coronary artery
bypass grafting, the role of concomitant mitral repair
• Secondary mitral regurgitation is generally due to is uncertain.
left ventricular systolic dysfunction and remodeling,
which restricts mitral leaflet mobility and impairs • Although additional indications are being evaluated,
their coaptation. transcatheter mitral valve repair with the MitraClip
device is currently indicated for patients with severe,
• Chronic, severe primary mitral regurgitation symptomatic, primary mitral regurgitation who
may be clinically tolerated for several years have prohibitive risk for cardiac surgery.
before progressive changes result in dyspnea,
pulmonary hypertension, atrial fibrillation, or Mitral Valve Stenosis
left ventricular systolic dysfunction, which may • Mitral stenosis occurs in most cases as a
indicate need for intervention. consequence of rheumatic fever and accounts for
10% of mitral valve disease.
• Acute, severe mitral regurgitation is poorly
tolerated clinically due to lack of ventricular • The elevated left atrial pressure due to the valve
adaptation and reduced forward stroke volume; stenosis causes dyspnea, pulmonary edema, and
it should be treated by urgent surgery. hemoptysis; the low output causes fatigue.

• Echocardiography is the most useful diagnostic • Without intervention, the survival rate of patients
test to inform the etiology and severity of mitral with symptomatic mitral is <50%.
regurgitation. Echocardiographic grading of more-
than-trivial mitral regurgitation should include • The echocardiogram is the diagnostic mainstay
and is used to assess the etiology, morphology, and

37 ACCSAP Study Guide and Key Points

 severity of the mitral stenosis. The analysis of the • With low-flow, low-gradient aortic stenosis (AS) and a
morphology of the mitral valve apparatus (including normal left ventricular ejection fraction, the diagnosis
leaflet thickness and mobility, leaflet calcification, of severe AS is based on multiple clinical and imaging
subvalvular thickening, and chordal fusion) and the parameters.
appearance of the commissures are key features
for the diagnosis of rheumatic MS. They also have • Careful monitoring with periodic clinical evaluation
important implications for the choice of the most for symptoms and serial echocardiogram for disease
appropriate intervention. severity is essential to determine appropriate timing
for intervention.
• Percutaneous mitral balloon commissurotomy is
indicated in symptomatic patients or asymptomatic • With low-flow, low-gradient aortic stenosis (AS) and
patients with pulmonary hypertension, moderate or a reduced left ventricular ejection fraction (<50%),
severe stenosis, and favorable valve morphology in severe AS is defined as a velocity of 4 m/sec and a
the absence of left atrial thrombus or moderate to valve area of ≤1.0 cm2, at any flow rate, on low-dose
severe mitral regurgitation. dobutamine stress echocardiogram.

• Prophylaxis for endocarditis should be given only • Valvular aortic stenosis is a progressive disease with
to high-risk patients prior to dental procedures. inevitable hemodynamic progression once even mild
Prophylaxis is no longer recommended for stenosis is present.
procedures involving the respiratory tract and • The primary indication for aortic valve replacement
gastrointestinal or genitourinary procedures, unless (AVR) is symptoms due to severe aortic stenosis (AS).
there is active infection. AVR is also recommended in asymptomatic patients
• Anticoagulation with warfarin is indicated in patients with severe AS and a reduction in ejection fraction
with mitral stenosis and atrial fibrillation, in patients (<50%), and may be considered with very severe AS,
with a prior embolic event, and in patients in whom rapid AS progression, or at the time of other cardiac
left atrial thrombus is detected. Aspirin, other surgery.
antiplatelet drugs, or the novel anticoagulants are not • The choice of surgical versus transcatheter aortic
valid alternatives. valve replacement is based on several factors,
Aortic Stenosis including procedural risk, comorbidities, age, and
patient preferences.
• Aortic stenosis is a disease of the elderly affecting
approximately 2.6% of those >75 years of age. Aortic Regurgitation
• The most common cause of aortic stenosis is • Significant aortic regurgitation is more common in
calcification of a congenitally bicuspid or normal males than females.
trileaflet aortic valve.
• Aortic regurgitation may be due to abnormalities of
• The initial symptoms of severe aortic stenosis the aortic valve and/or aorta.
(AS) are exertional dyspnea or reduced exercise
• Patients with aortic regurgitation on the basis of
capacity. Heart failure, angina, and syncope are late
a bicuspid aortic valve should be evaluated and
manifestations seen in patients who had not been
followed for abnormalities of the aorta.
diagnosed previously or when mild symptoms had
not been correctly attributed to AS. • Chronic severe aortic regurgitation can be
asymptomatic for many years. With time, however,
• Key measures of severe aortic stenosis include a peak
there is progressive left ventricular (LV) dilatation and
aortic valve velocity ≥4.0 m/sec and a mean aortic
eventual LV dysfunction.
valve gradient ≥40 mm Hg when flow is normal.
Valve area typically is ≤1.0 cm2 but may be larger with • Left ventricular dysfunction and dilatation can be
mixed stenosis and regurgitation or in patients with a reversible if valve replacement is performed in a
large body size. timely fashion. Therefore, serial follow-up with
clinical examinations and echocardiography is
• Severe aortic stenosis (AS) may be present with a
recommended to identify patients who require
lower velocity and gradient when transaortic stroke
intervention before symptoms develop.
volume is <35 mL/m2. With low-flow, low-gradient
severe AS, valve area is ≤1.0 cm2 or ≤0.6 cm2/m2 when • Acute aortic regurgitation can be catastrophic; urgent
indexed to body surface area. surgical intervention can be lifesaving.

• Aortic stenosis severity should only be measured • Individuals with or at risk for aortic regurgitation (AR)
when the patient is normotensive. are categorized into stages A-D (where A is at risk, B

38 ACCSAP Study Guide and Key Points

 is progressive AR, C is asymptomatic severe AR, and • Tricuspid stenosis is due to rheumatic heart disease
D is symptomatic severe AR). in 90% of cases and is almost always associated with
mitral stenosis.
• Surgery remains the mainstay of therapy. Medical
therapy is limited to individuals with chronic aortic • The characteristic clinical features are low cardiac
regurgitation and hypertension, and it is limited in output and right-sided congestion, including fatigue,
those who are not surgical candidates because of pedal edema, hepatomegaly, and ascites out of
comorbidities. proportion to the degree of dyspnea.

Tricuspid Valve Disorders • Severe tricuspid stenosis is diagnosed when there is

• The main cause of tricuspid regurgitation (TR) is a mean diastolic gradient ≥7 mm Hg or the valve area
secondary or secondary TR due to annulus dilation. is ≥1.0 cm2.

• Echocardiography is the standard test of choice • Medical therapy is not beneficial in most cases.
for the diagnosis and assessment of tricuspid Tricuspid valvuloplasty is rarely an option and, when
regurgitation. the valve is too abnormal, surgical replacement
should be considered.
• In addition to Doppler color jet area, quantitative
measures should be integrated to determine tricuspid Pulmonary Valve Disorders
regurgitation (TR) severity, including Doppler • Pulmonic stenosis is most commonly a congenital
characteristics of the TR jet, jet density, contour anomaly that may be seen in isolation or in
by continuous wave, width of the vena contracta, combination with other congenital anomalies.
systolic hepatic vein flow, proximal isovelocity
surface area (PISA)–derived regurgitant fraction and • Physical examination may be notable for systolic
effective regurgitant orifice area (EROA), as well as ejection click that decreases with inspiration with
right atrium and ventricle size and function. Systolic or without a harsh peaking crescendo-decrescendo
hepatic vein flow reversal is the strongest correlate systolic murmur over the upper left sternal border;
for severe TR. among patients with severe pulmonic stenosis, right
heart gallops may be heard and a prominent A wave
• The severity of tricuspid regurgitation is inversely may be present.
correlated with long-term survival.
• Congenital pulmonic stenosis may be associated
• Operative and longer-term outcomes are poorer with pulmonary artery dilation due to associated
for tricuspid valve repair or replacement surgery in arteriopathy.
comparison with other valve surgeries, due to the
increased comorbidities and prior cardiac surgery in • In the absence of significant pulmonic regurgitation,
patients with tricuspid regurgitation. percutaneous pulmonic valvuloplasty is
recommended for symptomatic patients (unexplained
• Tricuspid valve annuloplasty repair of tricuspid right heart failure, cyanosis from interatrial right-
regurgitation (TR) is indicated for patients with to-left shunting, and/or exercise intolerance) with
severe, secondary TR undergoing mitral valve moderate to severe valvular stenosis via balloon
surgery (Class I indication). valvuloplasty.

• A diameter cut-off of 4 cm is used to identify patients • Pulmonic regurgitation may be iatrogenic following
who should have tricuspid repair at the time of left- surgical or percutaneous pulmonic valvuloplasty or
sided surgery even in the absence of severe tricuspid as a short- or long-term complication of intervention
regurgitation. for right ventricular outflow tract obstruction, such as
in tetralogy of Fallot.
• Tricuspid valve repair or replacement surgery is
indicated for severe tricuspid regurgitation (TR) • Symptoms of severe pulmonic regurgitation are
associated with symptoms of right ventricular insidious, typically progressive fatigue with later
dysfunction despite medical therapy. The outcome development of right heart failure (elevated neck
in secondary TR is dependent on the severity of right veins, right heart gallops, ascites, edema) requiring
ventricular dysfunction. diuretic therapy.

• Percutaneous technologies represent a potential tool • On physical examination, the murmur of severe
to treat patients with tricuspid regurgitation at high pulmonic regurgitation is very short decrescendo
risk for open-heart surgery. diastolic murmur.

• Severe pulmonic regurgitation may be missed

on echocardiography since color jets may be

39 ACCSAP Study Guide and Key Points

 monochromatic and of low velocities; continuous- • Management of infective endocarditis requires a
wave Doppler interrogation is important. multidisciplinary approach among health providers
from a variety of backgrounds and should include
• Management of pulmonic valve disorders demands cardiologists, infectious disease specialists, and
the ability to accurately assess right ventricular size cardiovascular surgeons.
and function.
• Surgical treatment is used in approximately half of
• Patients with severe pulmonary regurgitation and infective endocarditis patients because of severe
increased right ventricular volumes as measured complications. Congestive heart failure is the primary
by magnetic resonance imaging are less likely to reason for surgical intervention. Other indications
favorably remodel right ventricular size and function for surgery are extensive valvular destruction,
after pulmonic valve replacement. large vegetations, paravalvular abscess, ineffective
Infective Endocarditis antimicrobial therapy, recurrent emboli on antibiotic
therapy, or the presence of a highly resistant
• Infective endocarditis continues to have a very high
organism.
mortality, with death in one of four patients despite
advances in antimicrobial therapy. • Surgical management of infective endocarditis
has the following objectives: completely excise all
• Several factors have changed the clinical presentation
infected and necrotic tissue, remove and/or replace
of infective endocarditis over the last several decades,
all infected prosthetic material, and reconstruct
including: significant reduction of the incidence
cardiac structures to restore proper physiology.
of rheumatic valve disease, increased old age life
expectancy, increased use of intracardiac devices, Prosthetic Heart Valves
increased prevalence of immune-compromised
• Selection of valve procedure (repair vs. replacement,
patients (e.g., organ transplantation), ubiquitous
surgical vs. transcatheter) and prosthetic valve
availability of echocardiography, and earlier
type (mechanical vs. bioprosthetic) has to
diagnosis.
be individualized according to the patient’s
• Only three-quarters of patients with infective characteristics, including age, surgical risk, and
endocarditis have known underlying heart disease. personal preferences.

• Streptococcus bovis endocarditis is often associated • Aspirin alone or direct anticoagulants are not an
with malignancy of the gastrointestinal track. alternative to warfarin for patients with mechanical
prosthetic valves.
• Endocarditis is a great mimic and patients may
present with a wide variety of symptoms or findings • Doppler echocardiography (transthoracic
that may involve noncardiac organ systems. echocardiography and transesophageal
echocardiography) is the method of choice for the
• The diagnosis of infective endocarditis is based diagnosis of prosthetic valve dysfunction (stenosis
on a constellation of history, clinical findings, and regurgitation).
laboratory studies (particularly blood cultures), and
echocardiography. Use of an imaging algorithm • Periodic clinical and echocardiographic evaluation of
reduces unnecessary use of echocardiography. patients with a prosthetic valve is essential for early
detection of prosthetic valve dysfunction. Careful
• Transesophageal echocardiography is indicated for medical management of patients with prosthetic
diagnosis and evaluation of vegetation size, abscess valves includes careful control of antithrombotic
formation, fistula formation, leaflet perforation, or therapy and prescription of infective endocarditis
prosthetic valve dehiscence. prophylaxis.

• The sensitivity of Duke Criteria can be improved • Patient prosthesis mismatch (PPM) is the most
by new imaging modalities (computed frequent cause of high transprosthetic gradients
tomography [CT], positron emission tomography/ following aortic valve replacement or mitral valve
computed tomography [PET/CT]) when replacement. The differential diagnosis between PPM
transthoracic echocardiography/transesophageal and acquired prosthetic valve stenosis can be made
echocardiography (TTE/TEE) are negative or by: 1) assessing leaflet morphology and mobility; 2)
doubtful. comparing measured echocardiographic parameters
of prosthetic valve function to normal reference
• Negative blood cultures are seen in approximately
values; and 3) assessing serial changes in the
10% of infective endocarditis cases. Of those,
echocardiographic parameters during follow-up.
approximately 50% had prior therapy with antibiotics.
• Prosthetic valve endocarditis is a life-threatening
complication that needs early detection by

40 ACCSAP Study Guide and Key Points

 echocardiography and positron emission the left atrium pressure rises and approaches that of
tomography/computed tomography (PET/CT), as well the aortic early diastolic pressure.
as rapid initiation of treatment.
• In acute rheumatic mitral valvulitis, a mitral stenosis
Cardiac Auscultation rumble may occur transiently, the so-called Carey
• The splitting of the second heart sound is a function Coombs murmur.
of the lower resistance in the pulmonary circuit
• In severe chronic mitral regurgitation, there may be
compared with the systemic circulation. This results
an accompanying S3.
in the right ventricular ejection time being longer than
the left ventricular ejection time. • The murmur of acute mitral regurgitation (MR) differs
from that of chronic MR because of the rapid rise in
• The only right-sided auscultatory event that
left atrium pressures in the acute setting. The acute
diminishes with inspiration is the pulmonary ejection
MR murmur may be short.
click associated with pulmonary valve stenosis.
• The timing of the click and murmur in mitral valve
• The midsystolic click in Ebstein’s anomaly is referred
prolapse occur earlier in systole with any maneuver
to as the “sail sound.”
that reduces the left ventricular volume (e.g., sitting,
• A single S2 may be present in severe pulmonary standing) and later in systole with squatting.
stenosis or aortic stenosis, transposition of the great
• The murmur of pulmonary regurgitation differs
arteries, or pulmonary hypertension.
greatly, depending on whether the pulmonary
• Fixed splitting of the second heart sound is classic pressure is low or high. In low-pressure pulmonary
for a patient with an atrial septal defect and is due regurgitation, there may be little diastolic gradient
to a fixed right ventricular stroke volume because of between the pulmonary artery and right ventricle,
reduced shunting that occurs with inspiration and and the murmur may be terminating early and
increased shunting with expiration. be quite soft, despite severe regurgitation. The
murmur is higher pitched and often holodiastolic
• Examples of early diastolic sounds include the mitral in severe pulmonary regurgitation with pulmonary
stenosis opening snap, tricuspid stenosis opening hypertension. Secondary acute pulmonary
snap, a pericardial knock, an S3, and an atrial myxoma regurgitation due to pulmonary hypertension
plop. is occasionally referred to as the Graham Steell
murmur.
• The murmur of aortic stenosis can often be
distinguished from mitral regurgitation by noting a • The murmurs of tricuspid stenosis and regurgitation
gap between the murmur and S1 and S2. are often soft, and the jugular venous pulse contour
should be examined closely for the diagnosis. Both
• As the murmur of aortic stenosis (AS) worsens,
murmurs increase with inspiration. The increase
the ejection sound and the intensity of A2 diminish;
in systolic murmur in tricuspid regurgitation is
the murmur peaks later in systole. The AS murmur
sometimes called Carvallo’s sign.
increases after a premature ventricular contraction.

• The murmur in aortic regurgitation (AR) differs

Transcatheter Aortic Valve Replacement
depending on whether it is acute or chronic in nature. • Aortic stenosis is the most prevalent form of valvular
Due to the rapid rise in left ventricular diastolic disease and many high-risk patients are not referred
pressures in acute AR, the diastolic murmur may for surgical aortic valve replacement.
be short, the mitral valve might close prematurely
• The two Food and Drug Administration (FDA)–
(S1 softens), and a mid-diastolic rumble of relative
approved transcatheter aortic valve replacement
mitral stenosis (the Austin-Flint murmur) may occur.
systems in the United States are the balloon-
In chronic AR, the murmur tends to be throughout
expandable valve and the self-expanding valve.
diastole.
• Risk assessment for surgical aortic valve replacement
• A Duroziez sign is elicited by compressing the femoral
is aided by scoring systems, such as the Society of
artery with the diaphragm of the stethoscope,
Thoracic Surgeons Predicted Risk of Mortality (STS-
creating a systolic murmur. If severe aortic
PROM) and European System for Cardiac Operative
regurgitation is present, a diastolic murmur from
Risk Evaluation (EuroSCORE). However, other factors
retrograde flow will also then be heard.
such as frailty, major organ system function, and
• With worsening of the stenosis in mitral stenosis obstacles to surgery must be considered.
(MS), the A2-opening snap interval in MS shortens as

41 ACCSAP Study Guide and Key Points

 • In the United States, transcatheter aortic valve • The most common type of PH observed by
replacement (TAVR) is approved for prohibitive-, cardiologists is Group 2, or that owing to left heart
high-, and intermediate-risk patients, as assessed disease. Treatment of the underlying disorder is the
by a multidisciplinary heart team. Ongoing studies mainstay of therapy.
are assessing TAVR safety and efficacy in low-risk
patients. • Pulmonary arterial hypertension (PAH) is defined
as a mean pulmonary artery pressure ≥25 mm Hg,
• Assessment for transcatheter aortic valve a left heart filling pressure (wedge, left ventricular
replacement includes transthoracic echocardiography end-diastolic pressure) ≤15 mm Hg, and a pulmonary
and computed tomography, which allow for vascular resistance ≥3 Wood units.
quantifying the degree of stenosis, the size of the
annulus, and vascular access issues. • Group 1 pulmonary arterial hypertension may be
idiopathic, inheritable, or associated with other
• Transfemoral access is preferred for transcatheter disorders such as connective tissue disease,
aortic valve replacement, although alternative access congenital heart disease, portal hypertension, or
routes exist for patients who do not have suitable human immunodeficiency virus.
iliofemoral anatomy.
• The concern for PAH often starts with the
• Transcatheter aortic valve replacement is superior echocardiogram. In addition to an elevated estimated
to medical therapy for the treatment of symptomatic pulmonary artery systolic pressure, right heart
aortic stenosis in prohibitive-risk surgical patients. enlargement, and dysfunction serve as clues to the
diagnosis of PAH. However, the diagnosis requires
• For patients with high surgical risk, transcatheter confirmation with a right-heart catheterization (RHC).
aortic valve replacement was noninferior to surgery
in the PARTNER IA (Placement of Aortic Transcatheter • The diagnostic algorithm for PAH is thorough and
Valves [Cohort A]: TAVR vs. Surgical AVR) trial methodical. Evaluation for chronic thromboembolic
and superior to surgery in the CoreValve High Risk pulmonary hypertension (CTEPH) should not be
(A Randomized Comparison of Self-Expanding forgotten as this disorder can be treated surgically.
Transcatheter and Surgical Aortic Valve Replacement
in Patients With Severe Aortic Stenosis Deemed High- • The RHC is the culmination of the diagnostic
Risk for Surgery) trial. evaluation and must meticulously measure key
hemodynamic parameters.
• For intermediate-risk patients, transcatheter aortic
valve replacement using either a balloon-expandable • A small proportion of patients (those who meet
or self-expanding valve was noninferior to surgical certain criteria at the time of acute vasodilator testing)
aortic valve replacement in terms of mortality, stroke, respond to calcium-channel blockers.
and paravalvular leak. • Background therapy for PAH may include
• Periprocedural rates of stroke are declining with anticoagulants, diuretics, and oxygen.
newer-generation valves. However, stroke after • Multiple therapies are now Food and Drug
transcatheter aortic valve replacement almost Administration-approved for the treatment of
doubles the mortality risk. PAH. They fall into three broad categories: the
• Paravalvular leak and the need for a permanent prostacyclins, the endothelin receptor antagonists,
pacemaker have declined over time but remain and agents that target the nitric oxide pathway
significant issues in the transcatheter aortic valve (phosphodiesterase type 5 inhibitors and soluble
replacement population. guanylate cyclase stimulators).

• Choice of therapy depends upon many factors, and

Pulmonary Circulation Disorders most importantly, the severity of illness. There is
emerging data with upfront combination therapy.
Chapter: Pulmonary Hypertension
• Longitudinal assessment is critical to ensure
Pulmonary Hypertension
that patients meet treatment goals that improve
• Pulmonary hypertension (PH) is a common disorder, prognosis.
with many potential etiologies.

42 ACCSAP Study Guide and Key Points

 • Assessing severity of illness (i.e., risk stratification) • LQTS is typically autosomal dominant, but with
integrates clinical, echocardiographic, and variable penetrance, and is subdivided into 15 types
hemodynamic criteria. based on the underlying causative gene. Genetic
testing will identify a known LQTS mutation in
• Response to therapy should be assessed using approximately 75% of cases, and thus, can help with
specific clinically available criteria. diagnosis and guiding screening in at-risk family
members.
Miscellaneous • Factor V Leiden is a genetic variant that causes
activated protein C resistance and is the most common
Chapter: Cardiovascular Genetics
genetic cause of venous thromboembolism (VTE),
Cardiovascular Genetics
causing up to 50% of cases. It is transmitted in an
• Mendelian cardiovascular (CV) diseases include autosomal dominant fashion, and genetic testing for
hypertrophic cardiomyopathy (HCM), long QT this variant is indicated in certain patients with a VTE.
syndrome (LQTS), Marfan syndrome, and familial
dilated cardiomyopathy (DCM). These diseases are • Warfarin metabolism is determined partially by
characterized by a clear mode of inheritance, with genetic variants in two genes, the hepatic cytochrome
mutations within the genes showing strong association P450 enzyme CYP2C9 and VKORC1, which explain 30-
with the disease and marked phenotypic effects. 40% of the total variation in final warfarin dose. The
role of genetic testing for these variants is unclear
• Genetic testing of the affected individual (proband) as clinical trials have shown discordant results
is often indicated in these Mendelian CV genetic with respect to improvement in outcomes using a
diseases, not for diagnostic purposes (diagnosis is genotype-guided approach.
often a clinical diagnosis), but for facilitating genetic
testing and screening in at-risk family members. • Clopidogrel activation is mediated partially through
a hepatic cytochrome P450 enzyme coded by the
• When performing genetic testing in most Mendelian gene CYP2C19, and variants in this gene have been
CV genetic diseases, the best approach is usually to associated with reduced platelet inhibition and
perform a full screen of all available genetic variants worse clinical outcomes in patients treated with
in the index case (proband), and then perform clopidogrel. Routine genetic testing for clopidogrel
focused testing of only that genetic variant in at-risk metabolism is not recommended, but can be
family members. considered for moderate- or high-risk patients
when other P2Y12 inhibitors are not available or
• Marfan syndrome is a connective tissue disorder
contraindicated.
inherited in an autosomal dominant fashion, with
95% of cases caused by mutations in the fibrillin-1 • Common CV diseases, such as coronary artery
extracellular matrix protein gene. disease, myocardial infarction, and atrial fibrillation,
demonstrate a more complex model of genetic risk.
• Familial DCM is a heterogeneous genetic disease,
Thus, genetic testing is not currently indicated in
with variable presentation, reduced penetrance,
these diseases.
and different modes of inheritance. It is caused by
mutations in more than 33 known genes, but these • A single genetic mutation has not been found to
account for only 40-50% of cases. Thus, the role of explain most cases of bicuspid aortic valve (BAV)
genetic testing is unclear, but can be considered if risk disease. Clinical screening of first-degree relatives
stratification in family members is desired. with BAV disease is controversial.
• Familial HCM is a relatively common genetic • Novel genomic technologies, including epigenetics,
disease showing an autosomal dominant mode copy number variation testing, and DNA resequencing,
of inheritance, and is caused by mutations in 1 of may help refine the genetic architecture of several
18 genes encoding components of the sarcomere. common CV disease and facilitate development of
Genetic testing identifies one of these mutations more robust risk-prediction models.
in 50-75% of cases, and can be useful in helping to
confirm a diagnosis and for guiding screening in at- • Familial HCM needs to be differentiated from left
risk family members. ventricular hypertrophy resulting from other genetic
disorders such as Fabry disease, amyloidosis, or
• The phenotypic expression of familial HCM is other metabolic cardiomyopathies, especially in
variable, even amongst family members with the younger individuals.
same genotype.

43 ACCSAP Study Guide and Key Points

Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics • Interruptions in chest compressions should be avoided,
• Pharmacokinetics refers to all aspects of drug and even brief pauses of 10-15 seconds decrease the
absorption, transport, metabolism, and excretion, likelihood of achieving an ROSC.
which can greatly impact optimal dosing and drug-
• The “cardiac pump” and “thoracic pump” models
drug interactions.
describe the mechanism for blood flow during chest
• Hepatic cytochrome protein enzymes metabolize compressions. In the cardiac pump model, blood flow
a large proportion of medications and are a very is due to direct compression of the heart, whereas in the
common reason for cardiovascular drug interactions. thoracic pump model, blood flow is due to increases in
intrathoracic pressure with the heart functioning as a
• The actions of a medication in the body are known as passive conduit.
pharmacodynamic effects, and knowledge of these
can aid in avoiding toxicities and anticipating drug • CPR for bystanders emphasizes chest compressions
interactions. only and omits rescue breathing.

• Pharmacogenetics seeks to use knowledge of genetic • Other devices that may improve the delivery of CPR
variation and how it affects drug response to improve include an impedance threshold valve and active
dosing or targeting of medications. compression-decompression device, but the usefulness
of these therapies is unclear.
• Examples of the impact of pharmacogenetics on
cardiovascular medication prescribing include • The placement of automated external defibrillators
clopidogrel and warfarin. in public locations (“public access defibrillation”)
doubles the number of neurologically intact out-
Chapter: CPR, Emergency Care of-hospital cardiac arrest survivors when utilized
Cardiopulmonary Resuscitation by trained laypersons, compared to delaying
defibrillation for EMS arrival.
• The survival for out-of-hospital cardiac arrest with any
first recorded rhythm is 10.6%. However, since only 50- • Current AHA guidelines prioritize minimally
60% of cases are treated by emergency medical services interrupted chest compressions, and favor initial
(EMS) personnel, the overall survival rate is about 5.6%. ventilation with a bag-valve mask or other alternative
device over early intubation. A supraglottic airway
• When cardiac arrest is due to a ventricular
is a popular alternative to intubation because it is
tachyarrhythmia, the single most important determinant
relatively easy to place.
of survival is the time interval from initiation of the
cardiac arrest until defibrillation can be provided. • Resuscitation can be further guided by invasive and
noninvasive means. Invasive means include the use
• In-hospital cardiac arrest affects over 200,000 people
of an arterial line to maintain a minimum systolic
each year, with an overall survival to hospital discharge
pressure and diastolic pressure, the latter of which
of about 25%.
is a critical determinant of CPR. Noninvasive means
• Diagnostic testing lacks sufficient sensitivity or to guide resuscitation can employ the use of echo
specificity to identify patients at high risk for out-of- to identify potentially treatable causes and end-tidal
hospital cardiac arrest. carbon dioxide monitoring to guide the quality of
chest compressions.
• An effective community system of care includes early
recognition, initiation of cardiopulmonary resuscitation • Extracorporeal membrane oxygenation may have
(CPR), and activation of EMS services by bystanders. It a role to improve survival, but further studies are
also includes the provision of early defibrillation when needed to identify the appropriate patient for this
indicated, early advanced cardiac life support, and therapy.
expert post-resuscitation care as part of the elements of
the Chain of Survival concept.
Post-Resuscitation Care
• Post-resuscitation syndrome is common and should
• If the initial cardiac arrest rhythm is ventricular be aggressively treated to improve long-term,
tachycardia or ventricular fibrillation, survival is higher neurologically intact survival.
compared to nonshockable rhythms, but survival
diminishes by 7-10% for every minute delay from • Post-resuscitation myocardial dysfunction is common
collapse to defibrillation. due to a stunning phenomenon. Patients need to be
provided hemodynamic support for hypotension and
let ventricular dysfunction.

44 ACCSAP Study Guide and Key Points

 • Hyperventilation should be avoided in the post- unsuccessful defibrillation in randomized trials that
cardiac arrest period, and mechanical ventilation compared amiodarone with placebo or lidocaine.
should be adjusted to avoid hyperoxia or hypoxia, as
well as to maintain normocarbia. Critical Care for the Cardiologist
• With increasing age and comorbidities, along with
• Strict glucose control should be avoided in the post- the burgeoning use of invasive therapies, patients
cardiac arrest period. with cardiovascular disease now have greater
susceptibility to critical illness.
• Therapeutic hypothermia is a Class I
recommendation for comatose adult survivors from • Shock is a physiologic state characterized by a
out-of-hospital ventricular fibrillation cardiac arrest. It severe reduction in tissue perfusion, resulting in
may be considered in other patient groups, including decreased oxygen delivery, cellular injury, and
following an initial nonshockable rhythm or in- death. Types of shock including hypovolemic,
hospital arrest of any rhythm. distributive, and cardiogenic.
• With a targeted temperature management, the • Early and aggressive resuscitation is paramount
patient is cooled to 33°C as a target. There is some in all shock patients, although the methods by
evidence to suggest that a 36°C target provides which such resuscitation is achieved depend on the
similar outcomes. etiology of the shock.
• Adopt an aggressive approach to applying early • The choice of vasoactive medications should be
(upon arrival to the hospital) coronary angiography guided by the underlying physiology of shock (e.g.,
and percutaneous coronary intervention in vasopressors and volume support for distributive
appropriate post-resuscitation survivors with a likely shock, inotropes for cardiogenic shock).
cardiac etiology for their cardiac arrest. Nonetheless,
certain factors decrease the likelihood of benefit • Multiple temporary mechanical circulatory support
from post-resuscitation coronary angiography and (MCS) options exist, which provide varying levels of
intervention, including unwitnessed arrest and no hemodynamic support. The choice of MCS should
bystander cardiopulmonary resuscitation. be tailored to the individual patient (e.g., need for
right ventricular or pulmonary support) and the
• It is a “call to action” to recognize and optimally treat institutional capabilities (e.g., availability of an
post-cardiac arrest syndrome to improve long-term extracorporeal membrane oxygenation team).
survival. Designated “Resuscitation Centers” can
provide comprehensive post-resuscitation care that • Noninvasive positive pressure ventilation is a
includes therapeutic hypothermia and capability of valuable tool for treating respiratory insufficiency
24/7 emergent cardiac catheterization and intervention. associated with decompensated heart failure; it can
improve oxygenation and ventilation, and decrease
Pharmacologic Therapy in Cardiac Arrest the need for intubation and invasive mechanical
• Epinephrine stimulates both α- and ß-adrenergic ventilation.
receptors, giving a positive inotropic and chronotropic
response, and elevating coronary and cerebral Chapter: Miscellaneous Topics
perfusion pressures. Cardiac Trauma
• All patients presenting with polytrauma or at
• Vasopressin is an alternative to epinephrine that is
risk for blunt cardiac trauma should have an
no longer routinely recommended by resuscitation
electrocardiogram during their initial evaluation.
guidelines. It is unclear whether it may prevent
recurrences of ventricular arrhythmias by avoiding • Acute hemodynamic compromise at presentation,
ß-receptor stimulation. particularly when associated with a negative
focused assessment with sonography for trauma
• Advanced cardiac life support drugs must be
evaluation, should be considered a consequence of
administered quickly and without interruption of
hemorrhagic shock and/or tension pneumothorax
chest compressions to establish intravenous (IV)
rather than acute systolic dysfunction from blunt
access. Intraosseous (IO) administration is an
cardiac trauma.
important alternative route to achieve these goals.
• vFor those patients who have persistent
• Epinephrine is administered as 1 mg IV or IO every
hemodynamic instability without alternative
3-5 minutes. High-dose epinephrine regimens are not
explanations, an echocardiographic study should be
recommended, nor is endotracheal administration.
performed to evaluate for structural cardiovascular
• Amiodarone improved survival to hospital admission injuries, such as septal or free wall rupture, aortic
in ventricular fibrillation cardiac arrest after dissection, or acute valvular regurgitation.

45 ACCSAP Study Guide and Key Points

 • Cardiac biomarkers have limited utility and should agents are also associated with an increased risk of
be considered in patients who present with findings vascular events.
consistent with an acute coronary syndrome or
myocardial infarction, or those patients who present • Certain Bcr-Abl TKIs are associated with an increased
with a presumed cardiac etiology for underlying risk of arterial thrombotic events.
trauma (e.g., a fall in the wake of cardiac symptoms). • Immune modulatory agents such as thalidomide and
Cardiovascular Manifestations in HIV lenalidomide are associated with an increased risk of
ventricular thrombotic events.
• Human immunodeficiency virus (HIV)-infected
patients have a high rate of traditional risk factors • Platinum therapy is associated with an increased risk
that contribute to their increased cardiovascular of long-term adverse cardiac outcomes, including
disease (CVD) risk, most importantly lipoprotein hypertension, hyperlipidemia, atherosclerotic
profile abnormalities, cigarette smoking, obesity, coronary disease, and diabetes, compared with the
and insulin resistance. normal population.

• Increased inflammation and immune activation play a • Patients receiving androgen deprivation therapy
role in HIV-related CVD risk, especially when viremia is (ADT) should be evaluated periodically for blood
not controlled with antiretroviral therapy (ART). pressure, lipids, and fasting glucose. In general,
patients should be seen by their primary care
• The Framingham risk score is a reasonable measure
physicians within 3-6 months of initiating therapy,
of an HIV-infected individual’s CVD risk, but may
because the adverse effects of ADT typically occur in
underestimate actual risk because it does not take HIV-
this time frame.
specific factors into account.
• Mediastinal radiation is associated with long-
• Minimizing CVD risk is largely targeted at modifying
term cardiovascular toxicity, including premature
traditional risk factors and maintaining virologic
atherosclerosis, valvular heart disease, myocardial
suppression with combination ART.
fibrosis, conduction system abnormalities, and
• Initiating medications, like statins and fish oil, which pericardial disease.
are designed to improve lipids and triglycerides, are
• Screening for cancer therapy-induced cardiac
likely better options for decreasing CVD risk than
dysfunction is most commonly performed via serial
changing antiretrovirals.
evaluation of LVEF, with lack of clear consensus
• Statins not only improve dyslipidemia, but also regarding the optimal criteria to define cardiac
possess anti-inflammatory and immunomodulatory dysfunction. Strain by echocardiography, myocardial
properties that may help to improve CVD risk in the tissue characterization by cardiac magnetic resonance
HIV-infected population. imaging, and biomarkers are areas of active
investigation.
Cardio-Oncology
• Current cardioprotective strategies for anthracycline-
• Exposure to potentially cardiotoxic cancer therapy
induced cardiotoxicity include use of liposomal
agents is classified as Stage A heart failure.
doxorubicin, dexrazoxane, and early initiation of
• Cardiac dysfunction and heart failure can be observed angiotensin-converting enzyme inhibitors and beta-
with anthracyclines, human epidermal growth factor blockers.
receptor 2 (HER2) antagonists, and tyrosine kinase
inhibitor (TKI) therapy.
Sleep Disordered Breathing
• Obstructive sleep apnea (OSA) is a prevalent disease
• Risk factors for anthracycline-induced with important associations with most cardiovascular
cardiomyopathy include cumulative dose, extremes diseases.
of age (children and elderly), female sex, prior history
of cardiac disease or cardiovascular risk factors, prior • Two-thirds of patients with chronic heart failure (CHF)
mediastinal radiation, exposure to other cardiotoxic will have some form of sleep-disordered breathing
agents, and a prechemotherapy left ventricular (SDB).
ejection fraction (LVEF) of <50%.
• Cheyne-Stokes respirations is a form of SDB best
• Early detection of anthracycline and HER2 antagonist- treated by optimizing (CHF) medications.
mediated cardiomyopathy can lead to recovery of
• OSA may play an important role in the pathogenesis
ventricular function in a majority of patients.
of atrial fibrillation and sudden cardiac death.
• Hypertension is a common side effect of vascular
endothelial growth factors (VEGF) inhibitors. These

46 ACCSAP Study Guide and Key Points

 • Epidemiological, animal, and clinical studies also permits the implementation of risk-reduction
all suggest that OSA can cause or contribute to therapies in the preoperative and perioperative
hypertension. periods.

• Treatment of OSA with continuous positive airway • A thorough history and physical examination is the
pressure can improve blood pressure, although the most important component of the preoperative
effect may be modest. evaluation. Functional capacity is the single most
important factor for determining cardiovascular risk
• Patients with hypertension should be screened perioperatively.
for signs and symptom of OSA and referred for
evaluation and management if necessary. • High-risk cardiovascular conditions that warrant
surgical delay to facilitate treatment include unstable
Preparticipation Screening for Athletes coronary artery disease, decompensated heart
• The goal of preparticipation cardiovascular (CV) failure, significant cardiac arrhythmia, and severe
screening in athletes is to detect underlying, valvular heart disease.
potentially lethal heart disease.
• Several risk indices are available for estimating
• The sensitivity of the preparticipation evaluation perioperative risk. These include the Revised Cardiac
(PPE) alone appears to be increasing. Risk Index (RCRI), the American College of Surgeons
National Surgical Quality Improvement Program
• Although well-controlled prospective trials are lacking,
(ACS-NSQIP) universal surgical risk calculator, and
studies in small cohorts of athletes indicate that the
the Vascular Study Group of New England (VSGNE)
electrocardiogram (ECG) appears to increase the
risk index.
sensitivity of the PPE alone to detect underlying cardiac
disease, especially hypertrophic cardiomyopathy. • Noninvasive cardiac testing should be reserved
for patients in whom functional status is poor
• Because many of the conditions that cause sudden
or cannot be assessed, and in whom testing will
cardiac death in athletes demonstrate similar ECG
impact decision making or perioperative care.
findings compared with what is seen in normal
Revascularization prior to surgery is indicated only if
athletic adaptation, clinicians should follow some
it should be performed independent of the surgery.
simple rules for ECG interpretation in athletes and
need to be prepared for the consequences of both Pregnancy and Cardiac Disease
overinterpretation and underinterpretation of the ECG • Pregnancy is a time of significant hemodynamic
in athletes. changes, including an almost 50% increase in
• Although ECG-based screening has gained wide cardiac output, which may not be well tolerated in
acceptance in Europe, ECG-based CV screening of women with pre-existing heart disease.
young athletes is currently not recommended on a • Hypertension (HTN) during pregnancy is a
wide-spread basis in the United States. However, common complication, occurring in almost 20%
future studies designed specifically for the American of pregnancies. Women with pregnancy-induced
athlete at all levels may assist in evolving this field in HTN should be treated and watched closely for
the United States. proteinuria and other manifestations of pre-
• Whether PPE is performed with or without cardiac eclampsia.
testing, cardiologists are called to utilize published • Urgent delivery/induction is recommended in
guidelines to make prudent participation and/or women with gestational HTN and proteinuria in
return-to-play decisions in athletes with symptoms or the setting of other adverse conditions such as
underlying cardiac conditions. pulmonary edema, coagulopathy, or fetal distress.
• Cardiologists ought to develop a working knowledge of • In women with chronic HTN who become pregnant,
basic sports cardiology. goal blood pressure remains <140/90 mm Hg.
Preoperative Risk for Noncardiac Surgery • Women with a history of gestational HTN or
• Patients undergoing noncardiac surgery may be at pre-eclampsia are at a 2 fold increased risk of
risk for a perioperative cardiovascular event. A given cardiovascular disease (HTN, stroke, coronary
patient’s level of risk is determined by both patient artery disease) later in life and should therefore be
characteristics and surgery-specific characteristics. aggressively screened for risk factors as they age.

• Estimation of perioperative cardiovascular risk • Acute myocardial infarction is an increasingly common

allows for the understanding of the benefit-to-risk complication as women are having babies later in life.
balance of a procedure for a given patient and

47 ACCSAP Study Guide and Key Points

 Etiologies include coronary dissection, atherosclerosis, • Women with dilated aortic roots secondary to Marfan
and thromboembolic disease. syndrome or other congenital anomalies are at
increased risk of aortic dissection secondary to the
• Studies indicate that women with mitral stenosis changes in collagen that occur during pregnancy. In
face a cardiac event rate of at least 30%, and that this Marfan syndrome, women with aortic root diameters
event rate is higher in women with smaller valve areas ≥4.0 cm should be considered for aortic root
and women with symptoms prior to pregnancy. The replacement prior to pregnancy.
presence of pulmonary hypertension increases the risk
of cardiac complications. • In women of childbearing age who undergo valve
replacements, the choice of valve prosthesis must be
• For women with severe mitral stenosis and pregnancy thoroughly discussed with the patient. Bioprosthetic
who remain symptomatic despite optimal medical valves allow the patient to avoid anticoagulation
therapy, balloon mitral valvuloplasty has been shown to during pregnancy but may degenerate more quickly.
be a safe and effective option. The Ross procedure is also an option.
• Pregnant women with aortic stenosis have limited • Because of the difficulties with managing
therapeutic options, and although recent studies anticoagulation during pregnancy, women with
indicate improved outcomes for these women and their mechanical heart valves are at high risk for
babies, they should be counseled to avoid pregnancy thromboembolic events.
until their valvular disease can be treated.

• Pregnancy is well tolerated in patients with regurgitant

lesions (mitral regurgitation, aortic insufficiency)
secondary to the reduction in afterload that occurs.
However, these patients will need to be watched
closely after delivery for pulmonary edema since they
may not tolerate the rapid shifts in volume that occur
postpartum.

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48 ACCSAP Study Guide and Key Points