International

Journal of
Preventive Medicine
Int J Prev Med. 5(Suppl 1): S10-S16

Management of Hypertension in Children with

Cardiovascular Disease and Heart Failure
Elaheh Malakan Rad, Farahnak Assadi12
Department of Pediatics, Division of Pediatric Cardiology, Children’s Medical Center (Pediatrics Center of
Excellence), Tehran University of Medical Sciences, Tehran, Iran
1. Department of Pediatrics Section of Nephrology Rush University Medical College Chicago, Illinois, USA
2. Department of Pediatrics, Child Growth and Development Research Center, Isfahan University of Medical
Sciences, Isfahan, Iran
Correspondence to: Dr. Elaheh Malakan Rad, Department of Pediatics, Division of Pediatric Cardiology,
Children’s Medical Center, Tehran University of Medical Sciences, Tehran 1419733151, Iran. E-mail:
[email protected]
Copyright: © International Journal of Preventive Medicine
Published in print: March 2014

Abstract
Although primary chronic hypertension (HTN) is increasingly common in
adolescence, secondary forms of HTN are more common among children.
Primary HTN is associated with being overweight and/or a positive family
history of HTN. Carotid intima-media thickness, a known risk factor for
atherosclerosis is frequent in both adults and children with HTN and other
associated cardiovascular (CV) risk factors including obesity, dyslipidemia,
diabetes and chronic kidney disease. Left ventricular (LV) hypertrophy is
also a common finding in children and adolescents with newly diagnosed
HTN. Children with certain medical conditions such as congenital heart
disease and Kawasaki disease can develop premature atherosclerosis
heart disease that may lead to coronary heart disease and heart failure.
Life-style interventions are recommended for all children with HTN, with
pharmacologic therapy added for symptomatic children based on the
presence of co-morbidities. As an example, beta-blockers, angiotensin-
converting enzyme (ACE) inhibitors, angiotensin receptor blocker and/or
calcium channel blockers would be best for children with CV risk factors
such as diabetes or renal disease, whereas an ACE inhibitor in
combination with a beta-blocker and diuretics including spironolactone are
recommended for patients with heart failure and reduced LV ejection
 fraction. This report will summarize new developments in the management
of pediatric HTN complicated with CV disease and heart failure and will
address the appropriate antihypertensive therapy that could potentially
reduce the future burden of adult CV disease.

INTRODUCTION
As in adults, children with hypertension (HTN) are at increased risk of cardiovascular
(CV) events including left ventricular (LV) hypertrophy, increased carotid intima-media
thickness, atherosclerosis, reduced arterial compliance and diastolic dysfunction.[123456]
Children and adolescents with certain medical conditions such as diabetes,
microalbuminuria and elevated C-reactive protein,[6] familial hypercholestromia,[7]
Kawasaki disease,[8] congenital heart disease,[9] chronic kidney disease (estimated
glomerular filtration rate <60 mL/min)[10] experience accelerated arteriosclerosis that
may lead to very early CV events and coronary heart disease, heart failure, cor pulmonale,
pericardial effusions and arrhythmias. Early arteriosclerosis is seen in the majority of these
diseases, with diabetes mellitus, chronic kidney disease and chronic inflammatory
illnesses of particular note.[124] However, most prevalent of all the cardiac morbidities is
systemic HTN. The reported prevalence of systemic HTN in children ranges from 1% to
4% with increasing prevalence of HTN paralleling the rise in childhood obesity.[11] Other
major risk factors for CV events include cigarette smoking, obesity (body mass index ≥30
kg/m2), physical inactivity, dyslipidemia and family history of premature, CV disease and
components of the metabolic syndrome.[123456]

For children with diagnoses like these, intensive CV risk reduction is of critical
importance.[12] Presence of metabolic syndrome can increase a person’s risk quickly.
[1112] As an example, when Stage 1 HTN added to borderline high total cholesterol
nearly triples a patient’s 10 year CV disease risk compared with total cholesterol of 200
mg/dL alone.[13] Diabetes plus low-high-density lipoprotein cholesterol increases a
patient’s 10 year CV disease risk 5 times higher than it would be with only one risk factor.
The Framingham risk score (age, total cholesterol, systolic blood pressure [BP], tobacco
smoking) is the cornerstone for risk stratification of asymptomatic individuals and helps
determine the intensity of therapy.

MANAGEMENT OF HYPERTENSIVE PATIENTS WITH CV

DISEASE
Current guidelines for the management of HTN in children and adolescents following CV
events recommend pharmacological therapy should be initiated with stage 2 HTN[2]
Antihypertensive medications should begin with the recommended initial dose of desired
medication and should be titrated upward until the BP target is reached. Consider adding a
second medication with a complementary mechanism of action if BP control is not
achieved. A combination of a beta-blocker and an angiotensin-converting enzyme (ACE)
inhibitor or an angiotensin receptor blocker (ARB) in low doses is the preferred choice.
Add a third antihypertensive drug of a different class if the target BP is not reached.[2]
Younger children may require higher doses as mg/kg basis than older children.[14]

Many of the options are available for the treatment of high BP, but shortly after the
occurrence of an acute CV event, guidelines suggest ACE inhibitor therapy that is titrated
upward at short intervals, every 1-2 weeks, until the target BP has been reached [Table 1].
[14] For patients who have previously discontinued ACE inhibitor therapy due to
intolerance or allergy, an ARB should be substituted.[3] Combined ACE inhibitor/ARB
therapy is not recommended, as the combination was associated with an increase in
serious adverse effects, but no greater benefit.[15] The combination of a beta-blocker and
a thiazide diuretic is less effective than the combination of a CCB and an ACE inhibitor
for controlling elevated BP and preventing stroke and CV disease.[16]

See full table

Table 1. Antihypertensive drugs commonly used in hypertensive
patients with cardiovascular disease and heart failure

HTN is also a strong predictor of stroke and treating HTN is a well-documented means of
primary stroke prevention. There is a strong evidence that antihypertensive therapy is
effective for the prevention of recurrent stroke.[17] Another strong predictor of stroke in
patients is visit-to-visit variability in systolic BP.[18] This fluctuation in BP differs from
“white-coat” HTN and reflects actual changes in BP that escalate with age and are more
common among women.

Based on 2010 American Heart Association/American Stroke Association guidelines, in

patients with a history of stroke or transient ischemic attack.[19]

Studies suggest benefits from an average BP reduction of approximately 10/5 mm

 Hg; Joint National Committee seven has defined target BP levels as <120/80 mm Hg
Comprehensive antihypertensive therapy should include salt restriction; weight loss;
consumption of a diet rich in fruits, vegetables and low-fat dairy products; regular
aerobic physical activity and limited alcohol consumption
Individualize drug therapy according to pharmacologic properties, mechanisms of
action and indications based on patient characteristics (e.g., renal impairment, CV
disease and diabetes).

TREATMENT OF HYPERTENSIVE PATIENTS WITH

HEART FAILURE
Although high BP is a common cause of congestive heart failure (CHF), it also is a
predictor of better survival in patients with CHF. This is probably because more severe
cardiac dysfunction causes a decline in systemic BP, making low BP a marker for more
advanced CHF and the bigger issue in terms of survival. Consequently, HTN remains an
important target in patients with CHF since HTN imposes an increased hemodynamic load
on the failing ventricle. Several classes of drugs have been shown to prolong survival in
patients with CHF, including ACE inhibitors, ARBs, beta-blockers and aldosterone
antagonists.[202122]

The stage of CHF is an important consideration for therapy, based on the 2009 American
College of Cardiology Foundation/American Heart Association guideline update.[21] For
patients with HTN, CV disease or diabetes, staging is as follows:

Stage A: No impaired LV function, hypertrophy

Stage B: Asymptomatic patients with evidence of LV hypertrophy and/or impaired
LV function
Stage C: Patients with current or past symptoms of CHF associated with underlying
structural heart disease (the bulk of patients with CHF)
Stage D: Patients with truly refractory CHF who might be eligible for mechanical
circulatory support.

Recommended therapy
Of all the available therapies for these patients, ACE-inhibitor therapy is the one
recommended for all patients with current or prior symptoms of CHF and reduced LV
ejection fraction (LVEF). In addition, one of the 3 beta-blockers proven to reduce
mortality (bisoprolol, carvedilol and sustained- release metoprolol succinate) is
recommended for all stable patients with current or prior symptoms of CHF and reduced
LVEF.

Starting therapy with an ACE inhibitor is recommended before beta-blockade is

implemented. Begin with low doses (e.g., enalapril 0.08 mg/kg/day or captopril 0.3
mg/kg/dose twice or trice daily) to reduce the likelihood of hypotension and azotemia
[Table 1]. If initial therapy is tolerated, increase the dose gradually to maximum doses of
0.6 mg/kg/day of enalapril (up to 40 mg/day), 6 mg/kg/dose 3 times daily of captopril (up
to 450 mg/day), unless side-effects occur.[1314]

Systolic dysfunction

About half of CHF patients have systolic dysfunction or low cardiac output. They develop
the classical symptoms of CHF, including edema. Systolic dysfunction is best treated with
beta-blockers, ACE inhibitors ARB and spironolactone [Table 1] plus a low-sodium diet.
[1314]

Diastolic dysfunction

These patients have a normal systolic ejection fraction with a stiff or LV hypertrophy
(LVH) that can’t take in adequate blood, leading to diastolic dysfunction.
Echocardiography is usually necessary to make the distinction between those patients with
systolic dysfunction and those with a normal systolic ejection fraction.

The major causes of diastolic heart failure are chronic HTN with LVH, hypertrophic
cardiomyopathy, aortic stenosis with a normal LVEF and coronary heart disease.

Asymptomatic diastolic dysfunction is more prevalent than symptomatic disease.

Symptomatic dysfunction may be associated with typical CHF symptoms, such as reduced
exercise capacity and neurohumoral activation, although these are generally less severe
than in patients with systolic dysfunction. They are also subject to flash pulmonary edema.

For diastolic dysfunction, drugs that slow heart rate may diminish the stiffness, but
otherwise there is no firm set of therapeutic strategies. Regression of LVH is an important
therapeutic goal, since it may improve diastolic function. ARB, calcium channel blockers
and ACE inhibitors tend to produce significantly more regression than beta-blockers and
may be the preferred choices for management of HTN in these patients.
CHF and refractory volume overload
Volume overload is typically addressed with loop diuretics, but a challenging subset of
CHF patients exhibits fluid overload despite significant doses of loop diuretics.

In a landmark study, investigators reported that, use of any of several thiazide-type

diuretics in combination with a loop diuretic can be more effective than loop diuretic
monotherapy in CHF patients with refractory fluid overload [Table 1].[1318] They
showed greater weight loss. The synergistic effects on diuresis appear to be a class effect
seen with all thiazide-type diuretics studied.

However, combination therapy comes with a risk of inducing severe hypokalemia,

hyponatremia, hypotension and worsening renal function, all warranting close laboratory
monitoring.

To avoid the adverse effects of combined diuretic therapy, the study makes the following
recommendations:[19]

Combination therapy is only appropriate for patients with gross fluid overload
refractory to optimized doses of intravenous (IV) loop diuretics, especially patients
with chronic decompensated systolic CHF and impaired renal function
Adequate doses of loop diuretic can be defined as furosemide 160 to 320 mg/d IV in
divided doses or by continuous infusion
Carefully selected patients with advanced, refractory, or end-stage (Stage D) systolic
CHF may be candidates for outpatient combination diuretic therapy as a means to
prevent the recurrent hospitalization for fluid overload, although this approach is not
well studied and requires close follow-up.

MANAGEMENT CONSIDERATION IN SPECIAL

CONTEXTS AORTIC COARCTATION
Systemic HTN is the main presentation of aortic coarcation that includes 5-10% of all
congenital heart defects. The stenosis causing the coractation and HTN is best treated
either by transcatheter stent implanatation or surgical correction.[2324] If severe
symptoms are present, labetolol or esmolol is recommended in children with coarctation
before definitive surgical or tarnscatheter procedure.[25] However, this disorder, even if
primarily treated at an early age with no residual coarctation, can still produce late
systemic HTN in approximately 75% of cases 20 to 30 years following the surgical
correction.[2526]

After cardiac transplantation

Majority of patients after cardiac transplantation (96%) develop systemic HTN. ACE
inhibitors or diuretics are suggested as probably the first-line treatments in these patients.
Beta blockers are allowed to be used in those with refractory HTN despite optimal therapy
with aforementioned drugs.[27]

Systemic HTN and aortic dissection

Although a minority of patients with HTN experience aortic dissection, it is still both a
risk factor of aortic dissection and a consequent of aortic dissection as a result of renal
ischemia or renovascular HTN. Refractory HTN in patients with aortic dissection may be
caused by dissection flap. In the context of congenital heart disease, it should be
remembered that Marfan syndrome, Loeys-Dietz aneurysm syndrome, bicuspid aortic
valve and Turner syndrome all can be associated with aortic aneurysm and dissection.[28]

Co-existence of cardiac and renal abnormalities

Congenital heart diseases are often associated with congenital renal structural anomalies.
[29] This coexistence may occur as a recognized pattern such as existence of coarctation
and renal anomalies in Turner syndrome.[30] Therefore on dealing with systemic HTN in
children with CV disease (CVD), particularly those with congenital heart disease, we
should always bear in mind that renal anomalies may coexist with various congenital heart
diseases [Figures 1 and 2].

View larger version

Figure 1. Left panel: Shows the aortogram in lateral view in a 1-year-old
male infant after surgical correction for interrupted aortic arch and large
ventricular septal defect at the age of 6 months. The abdominal fluoroscopy
at the end of the procedure showed lack of any functioning left kidney. Right panel: Renal
ultrsonography shows left non-functioning multicystic cystic kidney disease. This patient had normal
blood urea nitrogen and creatinine both before and 24 h after the cardiac catheterization and
angiography
 View larger version
Figure 2. Radiographic imaging of an 18-month-old female infant
with Holt-Oram syndrome, very large secundum type atrial septal
defect extending to vicinity of superior vena cava. (a) Absent radius of
the right hand. (b) Abnormally dilated esophagus on anteroposterior view during cardiac catheterization.
(c) Fluoroscopy of abdomen during cardiac catheterization showed no evidence of a functioning right
kidney. Abdominal ultrasonography revealed unilateral right-sided renal agenesis

Transcatheter options for treatment of systemic HTN

Until date, there are mainly two transcatheter modalities for treatment of HTN. The first is
endovascular stenting for patients with coarcation, middle aortic syndrome, renal artery
stenosis and aortic dissection and the second is catheter ablation of renal sympathetic
nerves in adults with resistant HTN. However, catheter ablation of renal sympathetic
nerves has not yet been reported in the pediatric population.[31]

In summary, treatment of systemic HTN in children is tailored, depending on the

pathophysiology mechanism/s, status of systolic or diastolic function of the heart, severity
of HTN, presence of end-organ damage and coexisting renal abnormalities.[32]

CONCLUSIONS
Treatment of systemic HTN in children is tailored, depending on the pathophysiology
mechanism/s, status of systolic or diastolic function of the heart, severity of HTN,
presence of end-organ damage and coexisting renal abnormalities.

Footnotes
Source of Support: Nil

Conflict of Interest: None declared

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[Back]

Table 1.
Antihypertensive drugs commonly used in hypertensive patients with cardiovascular disease and heart failure
[Back]
[Back]

Figure 1.
Left panel: Shows the aortogram in lateral view in a 1-year-old male infant after surgical correction for
interrupted aortic arch and large ventricular septal defect at the age of 6 months. The abdominal
fluoroscopy at the end of the procedure showed lack of any functioning left kidney. Right panel: Renal
ultrsonography shows left non-functioning multicystic cystic kidney disease. This patient had normal
blood urea nitrogen and creatinine both before and 24 h after the cardiac catheterization and
angiography

[Back]
[Back]

Figure 2.
Radiographic imaging of an 18-month-old female infant with Holt-Oram syndrome, very large
secundum type atrial septal defect extending to vicinity of superior vena cava. (a) Absent radius of the
right hand. (b) Abnormally dilated esophagus on anteroposterior view during cardiac catheterization. (c)
Fluoroscopy of abdomen during cardiac catheterization showed no evidence of a functioning right
kidney. Abdominal ultrasonography revealed unilateral right-sided renal agenesis

[Back]