Cardiomyopathy

Mitochondria are the power factories of the cells and produce ATP by oxidizing reducing equivalents via the respiratory chain.

These reducing equivalents originate mainly from the citric acid cycle that also occurs within the mitochondria. Human mitochondria contain their own genetic material in the form of circular DNA that encodes for only a fraction of the mitochondrial components. The other mitochondrial components are nuclear encoded.

Furthermore, the respiratory chain and mitochondrionassociated monoamine oxidase are major producers of reactive oxygen radicals. As a result, mutations in mtDNA can deregulate multiple processes within cells and the balance of this deregulation may contribute to the clinical phenotype  Mitochondrial diabetes affects up to 1% of patients with diabetes and is often unrecognized by the physicians.

Diabetes and deafness (DAD) or maternally inherited diabetes and deafness (MIDD) or mitochondrial diabetes is a subtype of diabetes which is caused from a point mutation at position 3243 in human mitochondrial DNA, which consists of a circular genome. This affects the gene encoding tRNALeu. Diabetes mellitus is a common feature of mitochondrial disease, but rarely occurs in isolation; other clinical features depend largely on the underlying mtDNA or nuclear DNA mutation.

Because mitochondrial DNA is contributed to the embryo by the oocyte and not by spermatozoa, this disease is inherited from maternal family members only. As indicated by the name, MIDD is characterized by diabetes and sensori neural hearing loss. As suggested by the name, patients with MIDD are subject to sensorineural hearing loss. MIDD has also been associated with a number of other issues including kidney dysfunction, gastrointestinal problems, and cardiomyopathy

Diabetes mellitus is one of the most common chronic diseases worldwide. Diabetic cardiomyopathy (DM) is the deterioration of the myocardial function and morphology produced by the altered glucose metabolism imposed in diabetes. This process of cardiac deterioration involves the generation of oxidative species. In the diabetic heart, several sources contribute to the observed oxidative stress, such as xanthine oxidore‐ ductase (XOR), nicotinamide adenine dinucleotide phosphate (NADPH), nitrogen oxidases (NOX), mitochondria, and uncoupled nitric oxide synthases (NOS). A direct consequence of the increased production of reactive oxygen species (ROS) is NOS uncoupling. This is the aftermath of the oxidation of tetrahydrobioterin (BH4), an essential cofactor for NOS activity. When NOS is uncoupled, its activity is redirected toward the production of superoxide, instead of nitric oxide (NO), further contributing to the oxidative process. This nitroso‐redox disarrangement has a direct impact on the excitation‐contraction‐coupling machinery of the myocyte, in the mitochondrial stability impairing energy production and favoring apoptosis, myocardial fibrosis, ultimately reducing cardiac function. This review focuses on the impact of superoxide sources in the diabetic heart and the pharmacological approaches that are currently under investigation as possible therapeutic tools.

The second part of the review of peripartum cardiomyopathy includes contemporary
views of a specifics of disease onset. Detailed specifics of the disease onset is
provided according to their specificity and diagnostical value. The approaches to
diagnostics described beginning from physical examination to instrumental
methods. Taking into account of the microparticles role on the disease onset, the
importance ov their measurement is highlighted in peripartum cardiomyopathy,
especially peripheral vasodilators, diuretics, ACE inhibitors, antiarrhythmic drugs,
anticoagulants, pentoxyphilline, bromocryptine, cabergoline. The methods selected
of artificial circulation in severe disease course and the data provided on
plasmapheresis usage and implantable cardioverter-defibrillator. In general the
points of delivery problems discussed.
[In Russian]

Network Biology
ISSN 2220-8879
CODEN NBEICS

Volume 11, Number 2, 1 June 2021

http://www.iaees.org/publications/journals/nb/articles/2021-11(2)/2021-11(2).asp

Articles

Network pharmacology and component analysis of four herbs decoction molecular mechanism in hypertension treatment
Network Biology, 2021, 11(2): 54-67
Fui Fui Lem, Fernandes Opook, Fahcina P. Lawson, Wilson Thau Lym Yong, Fong Tyng Chee
[Abstract] [XML] [EndNote] [RefManager] [BibTex] [DOAJ] [PubMed]
[ Full PDF (1729K)][Supplementary Material (33K)]
[Email Article] [Comment/Review Article]


Predicting lung cancer survivability: A machine learning regression model
Network Biology, 2021, 11(2): 68-81
Iffat Jabin, Mohammad Motiur Rahman
[Abstract] [XML] [EndNote] [RefManager] [BibTex] [DOAJ] [PubMed]
[ Full PDF (959K)]
[Email Article] [Comment/Review Article]


A bit-capacity scaling algorithm for the constrained minimal cost network flow problem
Network Biology, 2021, 11(2): 82-96
Muhammad Tlas
[Abstract] [XML] [EndNote] [RefManager] [BibTex] [DOAJ] [PubMed]
[ Full PDF (152K)]
[Email Article] [Comment/Review Article]


Analyzing capacitated networks via Boolean-based coherent pseudo-Boolean functions
Network Biology, 2021, 11(2): 97-124
Ali Muhammad Ali Rushdi, Omar Mutab Alsalami
[Abstract] [XML] [EndNote] [RefManager] [BibTex] [DOAJ] [PubMed]
[ Full PDF (919K)]
[Email Article] [Comment/Review Article]

Primary cardiomyopathy is one of the most common inherited cardiac diseases and harbors significant phenotypic and genetic heterogeneity. Because of this, genetic testing has become standard in treatment of this disease group. Indeed, in recent years, next-generation DNA sequencing has found broad applications in medicine, both as a routine diagnostic tool for genetic disorders and also as a high-throughput discovery tool for identifying novel disease causing genes. We describe a male infant with primary dilated cardiomyopathy that was diagnosed using intrauterine echocardiography, and found to progress to hypertrophic cardiomyopathy after birth. This proband was born to a non-consanguineous family with a past history of a male fetus that died due to cardiac abnormalities at 30 weeks of gestation. Using whole-exome sequencing, a novel homozygous frameshift mutation (c.2018delC; p.Gln675SerfsX30) in ALPK3 was identified and confirmed with Sanger sequencing. Heterozygous family members were normal with echocardiographic examination. To date, only two studies have reported homozygous pathogenic variants of ALPK3, with a total of seven affected individuals with cardiomyopathy from four unrelated consanguineous families. We include a discussion of the patient's phenotypic features and a review of relevant literature findings.

The role of personal computer (PC) and its associated accessories in this present knowledge-based global economy cannot be overemphasized. Its application is highly significant being a tool for the transfer of information worldwide, this consequently resulted in an increase in the rate at which the public interact with it. Computer system has been identified as formites which could serve as a portal through which pathogens can be transmitted among user. An essential part of a PC is the keyboard; certain microbes have been isolated from the surface of computer keyboard (CK) which had been linked with many infections and disease conditions. The need to identify the possibilities of CK to act as a reservoir host for the transmission of this pathogenic organism to ambient users led to this study. This study aimed to review the role CKs play in the transfer of pathogens in Nigeria and to sensitize Nigerian on the possibilities of contacting infectious diseases through CKs. This paper also provides policy recommendations on the necessary measures that could be adopted to minimize such infections.

Keywords: Computer, Mouse, Keyboard, Nosocomial, Formites, Microorganism

mitochondrial respiratory chain dysfunction (1–4). It results from loss-of-function mutations of the tafazzin (TAZ) gene (5). The major consequence of this loss-of-function is the defi cient remodeling of the mitochondrial phospho-lipid cardiolipin (CL), a process that normally leads to the mature acyl composition (6, 7). CL is the signature lipid of mitochondria, where it is an important constituent of the inner membrane, essential for supercomplex formation, oxidative phosphorylation (i.e., mitochondrial energy metabolism), and protein import, and is capable of triggering mitophagy and mitochondria-mediated apoptosis (8–16). Because the remodeling of CL is deficient in BTHS, biochemical abnormalities in patients include a decreased level of mature CL (CLm), an increased level of monolysocardiolipin (MLCL), and altered CL acyl composition [i.e., the presence of immature CL (CLi) species]. Historically, the diagnosis of BTHS has relied on identi-fi cation of the clinical symptoms accompanied by neutro-penia and 3-MGCA and has then been confi rmed by the fi nding of TAZ mutations. More recently, assays of CL alone or of the ratio of CL to MLCL have been used in Europe. However, each of these diagnostic approaches has problems. There are multiple reports of false-negative disease detection by urinary organic acid screening (4). TAZ sequencing is relatively slow and expensive, and CL analysis involves many steps including extraction of lipids and isolation of CL molecular species by complex chromato-graphic techniques. Consequently, although measurement of CL/MLCL ratio has 100% diagnostic sensitivity and specifi city, it is only available in a few clinical laboratories Abstract Barth syndrome (BTHS), an X-linked disease associated with cardioskeletal myopathy, neutropenia, and organic aciduria, is characterized by abnormalities of card iolipin (CL) species in mitochondria. Diagnosis of the disease is often compromised by lack of rapid and widely available diagnostic laboratory tests. The present study describes a new method for BTHS screening based on MALDI-TOF/MS analysis of leukocyte lipids. This generates a " CL fi nger-print " and allows quick and simple assay of the relative levels of CL and monolysocardiolipin species in leukocyte total lipid profi les. To validate the method, we used vector algebra to analyze the difference in lipid composition between controls (24 healthy donors) and patients (8 boys affected by BTHS) in the high-mass phospholipid range. The method of lipid analysis described represents an important additional tool for the diagnosis of BTHS and potentially enables therapeutic monitoring of drug targets, which have been shown to ameliorate abnormal CL profi les in cells. —Angelini, R., S. Lobasso, R. Gorgoglione, A. Bowron, C. G. Steward, and A. Corcelli. Cardiolipin fi ngerprinting of leukocytes by MALDI-TOF/MS as a screening tool for Barth syndrome. J. Lipid Res. 2015. 56: 1787–1794. Supplementary key words cardiomyopathy • lysophospholipids • mass spectrometry • matrix-assisted laser desorption/ionization • mito-chondria • phospholipids • phospholipids/metabolism • tafazzin • time-of-fl ight

This work reports another episode in the life of one dog, Happy, who was previously followed during heartworm recovery. It may describe a trivial coincidence but the response seemed compelling suggesting a link between riboflavin intake, against an already plentiful list of nutrients, and a possible heart problem. Putative diet related DCM is still an area of interest at the FDA and at least one paper found reduced riboflavin content in foods associated with DCM reports [62]. This result may also be a clue about prior coincidence of coughing with aromatic amino acid intake that seems peculiar to her. Although her kibble had changed during a similar time frame suggesting that as a possible contributor too. It also introduces a combination of ingredients that may form an "anti-pathogen energy drink" for a class of dogs. At least one other dog has shown a health improvement on this and waiting for 16s rRNA to determine if any potential pathogens have been removed. This is a draft and has not been peer reviewed or completely proof read but released in some state where it seems worthwhile given time or other constraints. Typographical errors are quite likely particularly in manually entered numbers. This work may include output from software which has not been fully debugged. For information only, not for use for any particular purpose see fuller disclaimers in the text. Caveat Emptor. Note that any item given to a non-human must be checked for safety alone and in combination with other ingredients or medicines for that animal. Animals including dogs and cats have decreased tolerance for many common ingredients in things meant for human consumption. I am not a veterinarian or a doctor or health care professional and this is not particular advice for any given situation. Read the disclaimers and take prudent steps to evaluate this information.

Background: The antisynthetase syndrome (ASS) is a rare chronic autoimmune disorder associated with a various manifestation including myositis, interstitial lung disease, fever, Raynaud’s phenomenon, “mechanic’s hands, polyarthritis and antibody specificity. Cardiac involvement is relatively rare but possible. We report a case of ASS anti PL12 positive with cardiac manifestations.

Case report: A 36 year old woman was admitted to the Department of Cardiology in our hospital for presyncope episodes, and exertional dyspnea. Physical examination revealed signs of congestive heart failure. Her heart rate was 40 bpm with a second-degree AV block Mobitz I on the electrocardiography. Transthoracic echocardiography showed cardiomyopathy with severe biventricular dysfunction and pulmonary hypertension. Further investigations were done to identify the cause of this cardiomyopathy especially as the patient presented arthralgias for last 2 years and history suggestive of Raynaud’s phenomenon and weakness of limbs. They revealed ASS syndrome with anti PL12 antibodies, diffuse interstitial lung involvement and cardiac involvement. The patient was treated with diuretic and corticosteroid therapy (methylprednisolone 1g pulse). On 4th day of admission, patient developed a complete AV block. Permanent dual chamber pacemaker implantation was performed. The patient was initiated on Cyclophosphamide and oral prednisolone which resulted in improved muscle strength and exercise tolerance.

Conclusion: Antisynthetase syndrome is a rare inflammatory myopathy. The cardiac involvement is even rarer and it is associated with worse outcome. The cardiovascular manifestations are various. This is the first report of ASS associated with complete heart block, cardiomyopathy and pulmonary hypertension in the same patient. Given the possible severe consequences, the cardiac involvement should be considered in patients with antisynthetase syndrome and clinicians should be familiar with this entity.

Objective. To investigate the ability of two-dimensional longitudinal strain echocardiography (2DST), to detect the early doxorubicin cardiotoxicity. Patients and Methods. The study included 25 children with newly diagnosed acute lymphoblastic leukemia (ALL) aged 5–15 years and 30 healthy control children. They had echocardiographic examination with conventional 2-dimensional (2D), pulsed tissue Doppler (PTD), and 2DST echocardiography before and within 1 week after doxorubicin treatment. Results. There was no significant difference in left ventricle (LV) systolic and diastolic functions measured by conventional 2-D and PTD echocardiography between patients and controls. However, there was significant decrease in LV global and peak systolic strain detected by 2-DST echocardiography in study group than control. After doxorubicin treatment, there was no significant difference in LV systolic and diastolic functions measured by conventional 2-D and PTD echocardiography than before treatment except for prolonged IVCT and IVRT, but LV global and peak systolic strain was significantly lower after treatment. Conclusion. 2-D longitudinal strain echocardiography was more sensitive than conventional 2-D and PTD in detecting the early LV doxorubicin-induced cardiotoxicity in children with ALL.

A 38-year-old man of Indian origin, who migrated to Greece 13 years prior to presentation, was admitted to our hospital with a 2-month history of nonprogressive, intermittent (mostly evening), low-grade (up to 38.5°C) fever, accompanied by night sweats, dry cough, mild dyspnea on exertion (modified Medical Research Council Dyspnea Scale grade 1), anorexia, fatigue, and weight loss of 10 kg. He also experienced continuous palpitations, which were regular, not associated with chest pain or dizziness, and aggravated on exertion. He had not taken any medication for his condition, except for antipyretic agents, nor had he sought medical advice. He was a nonsmoker, had a history of past alcohol dependence, and had been hospitalized twice for acute pancreatitis due to hypertriglyceridemia. He had also been diagnosed with diabetes mellitus, presumably poorly controlled because he mentioned not taking any medication or having regular follow-up.

Dilatative Cardiomyopathy (DC) with low Ejection Fraction % (EF %>35%), Spontaneous Echo-Contrast (DEC) in the Left Ventricle (LV) seen at echocardiography and in sinus rhythm predisposes to the intraventricular thrombus formation and subsequently embolization, resulting in stroke. Current guidelines recommend oral vitamin K antagonists (VKAs) to prevent brain’s cardio-embolic events deriving from SEC present in LV, as previously evidenced in several trials (HELAS, WASH, WACH, WARCEF). This treatment to prevent embolic stroke is effective both for ischemic and non-ischemic DC with SEC in LVN and in sinus rhythm. But, in the future, could be timely to treat with new oral anticoagulants (NOACs) non-ischemic DC alone, whereas this prophylactic treatment adopted in ischemic DC (already treated with antiplatelet drugs) could raise the risk of minor or major bleedings.
Keywords: Dilatative Cardiomyopathy in sinus rhythm and low ejection fraction; spontaneous echocontrast ; echocardiography.

T-Wave alternans (TWA) testing using 12-lead electrocardiogram/Frank leads is emerging as an important non-invasive biomarker to identify patients at high risk of Sudden Cardiac Death (SCD). Cardiac scarring is very common among cardiomyopathy patients; however, its influence on the body surface distribution of TWA has not yet been defined. Our objective was to perform a simulation study in order to determine whether cardiac scarring affects the distribution of TWA on thorax such that the standard leads fail to detect TWA in some of cardiomyopathy patients; thereby producing a false-negative test. Developing such a novel lead configuration could improve TWA quantification and potentially optimize electrocardiogram (ECG) lead configuration and risk stratification of SCD in cardiomyopathy patients. The simulation was performed in a 1500-node heart model using ECGSIM. TWA was mimicked by simulating action potential duration alternans in the ventricles. Cardiac scarring with different sizes were simulated by manipulating the apparent velocity, transmembrane potential and transition zone at varied locations along the left ventricular posterior wall. Our simulation study showed that the location of maximum TWA depends on the location and size of the myocardium scarring in patients with cardiomyopathy, which can give rise to false-negative TWA signal detection using standard clinical leads. The TWA amplitude generally increased with the increment of scar size (P<0.00001). We found one specific location (a non-standard lead) that consistently appeared as the top five maximum TWA leads and could be considered as an additional lead to improve the outcome of the TWA testing in cardiomyopathy patients.

Dilated cardiomyopathy (DCM) is a common cardiac disease which leads to the deterioration in cardiac performance. A computational fluid dynamics (CFD) approach can be used to enhance our understanding of the disease, by providing us with a detailed map of the intraventricular flow and pressure distributions. In the present work, effect of ventricular size on the intraventricular flow dynamics and intraventricular pressure gradients (IVPGs) was studied using two different implementation methods, i.e. the geometry-prescribed and the fluid structure interaction (FSI) methods. Results showed that vortex strength and IVPGs are significantly reduced in a dilated heart, leading to an increased risk of thrombus formation and impaired ventricular filling. We suggest FSI method as the ultimate method in studying ventricular dysfunction as it provides additional cardiac disease prognostic factors and more realistic model implementation.

dures. We totally agree with the fact that the incidence of this complication is certainly underestimated because of delayed occurrence and lack of systematic diagnostic screening. It is likely that a proportion of the sudden deaths occurring after discharge from the hospital could be attributed to ascending aortic dissection. Finally, as the population of patients undergoing coronary artery bypass grafting is steadily aging and carrying more comorbid illness, this complication will likely be seen more often. In this context, prevention with avoidance of aortic manipulation in the presence of an atherosclerotic, dystrophic aortic wall is paramount. When aortic side clamping is necessary, the systemic arterial pressure must be lowered with transient clamping of the inferior vena cava if necessary [2]. Total arterial revascularization with a no-touch technique using pedicled or composite grafts is an elegant solution to this problem. We also agree with their comment about new devices that allow performance of proximal anastomosis without clamping the aorta. We also thank Dr Meharwal and Dr Trehan for their judicious comments about screening the aorta for atherosclerotic plaque and disease. Digital palpation of the aorta under low pressure during transient clamping may be an option to increase the sensitivity of this technique. However, epiaortic ultrasound is increasingly acknowledged as the gold standard for assessing the ascending aorta and probably will be used more extensively in the future to guide the operative strategy during off-pump coronary artery bypass grafting [3].

Mutations in the A-type lamin (LMNA) gene are associated with
age-associated degenerative disorders of mesenchymal tissues,
such as dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and limb-girdle muscular dystrophy. The molecular mechanisms that connect mutations inLMNAwith different human diseases are poorly understood. Here, we report the identification
of a Muscle-enriched A-type Lamin-interacting Protein, MLIP
(C6orf142and2310046A06rik), a unique single copy gene that is an
innovation of amniotes (reptiles, birds, and mammals). MLIP
encodes alternatively spliced variants (23–57 kDa) and possesses
several novel structural motifs not found in other proteins.MLIPis
expressed ubiquitously and most abundantly in heart, skeletal, and smooth muscle. MLIP interacts directly and co-localizes with
laminAandCin the nuclear envelope. MLIP also co-localizes with
promyelocytic leukemia (PML) bodies within the nucleus. PML,
like MLIP, is only found in amniotes, suggesting that a functional
link between the nuclear envelope and PML bodies may exist
through MLIP. Down-regulation of lamin A/C expression by
shRNA results in the up-regulation and mislocalization of MLIP.
Given that MLIP is expressed most highly in striated and smooth
muscle, it is likely to contribute to the mesenchymal phenotypes of laminopathies.

"Aritmojenik sağ ventriküler kardiyomyopati (ARVC), sağ ventrikül duvarındaki myokardiyal liflerin yağ ve bağ dokusuna dönüştüğü, daha çok Akdeniz ülkelerinde görülen bir patolojidir. Bu patolojide, sağ ventrikül lifleri arasında, myokard liflerini adalar ya da yamalar halinde bırakan yaygın fibroadipö doku infiltrasyonu görülür. Klinikte, ileti sistemi patolojilerine bağlı bulgular (senkop, taşiaritmi, aritmi gibi) izlenebilir. Ondokuz yaşında kadın olgumuz, banyoda arkadaşları tarafından baygın halde bulunmuş ve hastaneye götürüldükten bir saat sonra ölmüştür. Otopside sağ ventrikül duvarında, aritmojenik sağ ventriküler kardiyomyopatinin makroskopisi ile uyumlu değişiklikler görülmüştür. Bu bulgular, mikroskobik olarak da doğrulanmıştır. ARVC genç populasyonda ani ölümlerin önemli bir nedenidir. Olgu, ani genç ölümlerinde özellikle aritmojenik sağ ventriküler kardiyomyopatinin akıllarda tutulmasını sağlamak amacıyla literatür bilgileri ışığında tartışılarak sunulmuştur.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a pathology in which myocardial fibers of right ventricular wall transform into fat and connective tissue and observed more in Mediterranean countries. In this pathology, there is common fibroadipose tissue infiltration which leaves myocardial fibers in islands or patches between the fibers of the right ventricle. In the clinic, findings related to conduction system pathology (syncope, tachycardia, arrhythmia, etc.) can be monitored. The patient was a 19 year old female and her friends found her unconscious in bath. She was taken to hospital where she died one hour after. At autopsy, macroscopic changes in the wall of the right ventricle compatible with arrhythmogenic right ventricular cardiomyopathy. These findings were confirmed microscopically. ARVC is an important cause of sudden death in the young population. The case is presented and discussed in the light of literature aiming to bear in mind arrhythmogenic right ventricular cardiomyopathy especially cases of sudden death of young people."

Sudden cardiac death (SCD) in young athletes represents a challenging issue in forensic practice. The pathologist is frequently asked to establish the cause of death basing upon anatomical findings and to evaluate the role of the physician in preparticipation evaluation (PPE) and eligibility decision. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of SCD during sport activity. However, in the last few years, forms with predominant or even isolated involvement of the left ventricle (LV) have progressively been correlated with a high risk of SCD. We present a case of SCD in an apparently healthy 19-year-old semi-professional football player. Annual PPEs performed in accordance with international and Italian recommendations, were unremarkable. At autopsy, a 1-cm area of subepicardial fibro-fatty replacement was observed at the postero-lateral wall of the LV. The finding was diagnostic of arrhythmogenic left ventricular cardiomyopathy (ALVC). A review of this ...

A type of viral pneumonia that broke out in Wuhan, China in December 2019, and new strains of it are spreading rapidly around the world, is called coronavirus disease 2019 (COVID-19). The incidence of cardiovascular complications has increased both in the general population and in patients diagnosed with the disease during the COVID-19 epidemic. One of the conditions is stress cardiomyopathy, which may be related to COVID-19. During the COVID-19 epidemic, stress cardiomyopathy may be present as a complication of acute infection or as an indirect consequence of quarantine. These conditions have created complications in patient care that have led to increased adverse outcomes, hospitalization, and medical costs. Stress cardiomyopathy is caused by various emotional and physical stressors such as anger, sadness, happiness, surgery, multiple medications, general anesthesia, and infectious diseases. The outbreak of the new coronavirus has posed an ongoing challenge for these patients with several medical and economic consequences. Providing useful information on stress and COVID-19 to people with heart disease and their families can be very important, and also, education and psychotherapy of heart patients can reduce the number of hospitalization and their complications.

Trypanosoma cruzi causes Chagas disease in the Americas. Outcome of infection ranges from lifelong asymptomatic status to severe disease. Understanding how history of T. cruzi lineage (TcI-TcVI) infection relates to clinical prognosis is challenging. We previously described peptide-based lineage-specific ELISA with Trypomastigote Small Surface Antigen (TSSA). A novel rapid diagnostic test (Chagas Sero K-SeT) incorporating a peptide corresponding to the TSSA-II/V/VI common epitope was developed, and validated by comparison with ELISA. Patients from Bolivia and Peru were then tested by Chagas Sero K-SeT, including individuals with varying cardiac pathology, and matched mothers and neonates. Chagas Sero K-SeT and ELISAs, with a Bolivian subset of cardiac patients, mothers and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) against classes B (ECG suggestive of Chagas cardiomyopathy) and C/D (moderate/...

Cardiomyopathies are present in many forms and are the result of numerous etiologies with one well-established etiology being chronic kidney disease (CKD). With recent discoveries linking early stages of CKD to profound cardiovascular disease (ischemic or non-ischemic cardiomyopathy), our focus has shifted to a seemingly inexplicable link between focal segmental glomerulosclerosis (FSGS) and non-ischemic cardiomyopathy. The cardiovascular and renal organ systems possess a unique relationship which we presume to be a bi-directional association of cause-and-effect. We present two cases in which our patients, with underlying FSGS, present with signs and symptoms of systolic heart failure.

RATIONALE:
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenges accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues.

OBJECTIVE:
We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate.

METHODS AND RESULTS:
We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length (SL), and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large datasets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C (MYBPC3) gene, which causes hypertrophic cardiomyopathy (HCM), recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment.

CONCLUSIONS:
SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants.

Takotsubo Cardiomyopathy is a condition characterized by transient LV hypokinesis without evidence of obstructive coronary
disease that is typically triggered by a stressful event. We describe a 34-year-old woman with anorexia nervosa presenting
with hypotension, hypoglycemia, and tachycardia and found to have Takotsubo Cardiomyopathy. On admission, EKG
showed ST depression with T wave inversion in the inferolateral leads and Q waves in the anteroseptal leads (V1-V3). The
initial troponin was elevated at 1.2 ng/ml and increased to 1.94 ng/ml 4 hours later. Initial TTE showed global hypokinesisexcept
for a hyperkinetic basal segment suggestive of takostsubo cardiomyopathy and an EF of 15-20%. During
the course of management, subsequent TTEs revealed improved EF with resolution of the cardiomyopathy, but also the
presence of an LV thrombus. The pathophysiology of Takotsubo Cardiomyopathy is not fully understood, and the impact
of the hypoestrogenic state and the nutritional deficiencies on the development Takotsubo Cardiomyopathy in anorexia
nervosa patients remains to be a myth.

Patients under evaluation for cardiac transplant surgery were seen for routine psychiatric diagnosis and treatment. Of 35 patients with idiopathic cardiomyopathy, 83% (N = 29) had definite or probable panic disorder. Of 25 patients with postinfarction cardiac failure, rheumatic heart disease, or congenital heart disease, only 16% (N = 4) had definite or probable panic disorder. The authors suggest that autonomic mechanisms may underlie the association of cardiomyopathy and panic disorder and that increased cardiac sympathetic tone or circulating catecholamines may cause myocarditis and cardiomyopathy.

A segmental two-parameter empirical deformable model is proposed for evaluating regional motion abnormality of the left ventricle. Short-axis tagged MRI scans were acquired from 10 healthy subjects and 10 postinfarct patients. Two motion parameters, contraction and rotation, were quantified for each cardiac segment by fitting the proposed model using a non-rigid registration algorithm. The accuracy in motion estimation was compared to a global model approach. Motion parameters extracted from patients were correlated to infarct transmurality assessed with delayed-contrast-enhanced MRI. The proposed segmental model allows markedly improved accuracy in regional motion analysis as compared to the global model for both subject groups (1.22-1.40 mm versus 2.31-2.55 mm error). By end-systole, all healthy segments experienced radial displacement by similar to 25-35% of the epicardial radius, whereas the 3 short-axis planes rotated differently (basal: 3.3 degrees; mid: -1 degrees and apical: -4.6 degrees) to create a twisting motion. While systolic contraction showed clear correspondence to infarct transmurality, rotation was nonspecific to either infarct location or transmurality but could indicate the presence of functional abnormality. Regional contraction and rotation derived using this model could potentially aid in the assessment of severity of regional dysfunction of infarcted myocardium.

Link to full text articles :
http://www.ncbi.nlm.nih.gov/pubmed/25919317
http://iopscience.iop.org/0031-9155/60/10/4015/pdf/0031-9155_60_10_4015.pdf

First described in Japan, Takotsubo cardiomyopathy (TTC) is increasingly
becoming recognized worldwide as a cause of sudden and reversible diminished
left ventricular function characterized by left apical ballooning and hyperkinesis of
the basal segments, often with symptoms mimicking acute coronary syndrome.
Associated with physical or emotional stress, its exact pathogenesis has not
been established, though evidence suppor ts a neurohumoral etiology. Seizures
have been repor ted as triggers of Takotsubo cardiomyopathy. It is unknown if
seizure associated TTC differs from TTC associated with other triggers. In this
repor t, we present a rare case of Takotsubo cardiomyopathy in a young female
who presented with chest pain having a history of transient attacks of seizures.
Key Words: Broken Hear t Syndrome, Stress Cardiomyopathy, Apical Ballooning