scholarly journals Sex Differences, Genetic and Environmental Influences on Dilated Cardiomyopathy

2021 ◽  
Vol 10 (11) ◽  
pp. 2289
Author(s):  
Angita Jain ◽  
Nadine Norton ◽  
Katelyn A. Bruno ◽  
Leslie T. Cooper ◽  
Paldeep S. Atwal ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Sex Ratio ◽  
Dilated Cardiomyopathy ◽  
Systolic Function ◽  
Pathogenic Variants ◽  
Research Findings ◽  
Reported Data ◽  
Chemotherapy Agents ◽  
Male To Female

Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle and impaired systolic function and is the second most common cause of heart failure after coronary heart disease. The etiology of DCM is diverse including genetic pathogenic variants, infection, inflammation, autoimmune diseases, exposure to chemicals/toxins as well as endocrine and neuromuscular causes. DCM is inherited in 20–50% of cases where more than 30 genes have been implicated in the development of DCM with pathogenic variants in TTN (Titin) most frequently associated with disease. Even though male sex is a risk factor for heart failure, few studies have examined sex differences in the pathogenesis of DCM. We searched the literature for studies examining idiopathic or familial/genetic DCM that reported data by sex in order to determine the sex ratio of disease. We found 31 studies that reported data by sex for non-genetic DCM with an average overall sex ratio of 2.5:1 male to female and 7 studies for familial/genetic DCM with an overall average sex ratio of 1.7:1 male to female. No manuscripts that we found had more females than males in their studies. We describe basic and clinical research findings that may explain the increase in DCM in males over females based on sex differences in basic physiology and the immune and fibrotic response to damage caused by mutations, infections, chemotherapy agents and autoimmune responses.

scholarly journals A reversible hypocalcemic dilated cardiomyopathy caused by primary hypoparathyroidism

2019 ◽  
Vol 10 (2) ◽  
pp. 65-68
Author(s):  
Zhenli Cheng ◽  
Shiv Kumar Yadav ◽  
Xiaoyan Liu ◽  
Qijian Yi
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Dilated Cardiomyopathy ◽  
Systolic Function ◽  
Myocardial Dysfunction ◽  
Case Presentation ◽  
Aggressive Management

Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of one or both ventricles. Affected patients have impaired systolic function and may or may not develop overt heart failure (HF). Prognosis is generally poor without heart transplantation. We experienced a case of a 10-year-old child with dilated cardiomyopathy (DCM) accompanied by undiagnosed primary hypoparathyroidism. In our case,aggressive management of hypoparathyroidism significantly improved the manifestations of DCM. The case presentation highlights the importance of considering hypoparathyroidism as a cause of reversible myocardial dysfunction.

scholarly journals Hyperthyroidism-induced dilated cardiomyopathy

2019 ◽  
Vol 7 (27) ◽  
pp. 64-66 ◽  
Author(s):  
Phumpattra Chariyawong ◽  
Angela Rao ◽  
Deepa Panikkath ◽  
Ragesh Panikkath
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Dilated Cardiomyopathy ◽  
Systolic Function ◽  
Cardiac Contractility ◽  
Contributing Factors ◽  
Endocrine Disorder ◽  
Hyperdynamic State ◽  
History Of ◽  
High Output

Hyperthyroidism is a common endocrine disorder with a prevalence of 1.3% in the generalpopulation, affecting more women than men. Prolonged hyperthyroidism without appropriatemanagement may lead to high output cardiac failure characterized by increases in heart rate,cardiac contractility, and cardiac output and by reductions in peripheral systemic vascularresistance. Dilated cardiomyopathy with impaired systolic function is rare and occurs in lessthan 1% of patients with thyrotoxicosis. The exact mechanism of hyperthyroidism-induceddilated cardiomyopathy is not well established. The combination of direct toxic effects of excessthyroid hormone along with prolonged tachycardia, arrhythmia, and a hyperdynamic state couldbe contributing factors. We present a case of a young woman with prolonged sinus tachycardiadue to a long history of medication non-compliance who developed dilated cardiomyopathywith low output heart failure. Early detection and management of hyperthyroidism are crucialto restore cardiac function.

scholarly journals Clinical and Genetic Investigations of 109 Index Patients With Dilated Cardiomyopathy and 445 of Their Relatives

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Thomas M. Hey ◽  
Torsten B. Rasmussen ◽  
Trine Madsen ◽  
Mads Malik Aagaard ◽  
Maria Harbo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Family History ◽  
Dilated Cardiomyopathy ◽  
Prognostic Information ◽  
Tertiary Referral Center ◽  
Pathogenic Variants ◽  
Clinical Investigations ◽  
History Of ◽  
Sporadic Cases ◽  
Firm Basis

Background: It was the aim to investigate the frequency and genetic basis of dilated cardiomyopathy (DCM) among relatives of index patients with unexplained heart failure at a tertiary referral center. Methods: Clinical investigations were performed in 109 DCM index patients and 445 of their relatives. All index patients underwent genetic investigations of 76 disease-associated DCM genes. A family history of DCM occurred in 11% (n=12) while clinical investigations identified familial DCM in a total of 32% (n=35). One-fifth of all relatives (n=95) had DCM of whom 60% (n=57) had symptoms of heart failure at diagnosis, whereas 40% (n=38) were asymptomatic. Symptomatic relatives had a shorter event-free survival than asymptomatic DCM relatives ( P <0.001). Results: Genetic investigations identified 43 pathogenic (n=27) or likely pathogenic (n=16) variants according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Forty-four percent (n=48/109) of index patients carried a pathogenic/likely pathogenic variant of whom 36% (n=27/74) had sporadic DCM, whereas 60% (21/35) were familial cases. Thirteen of the pathogenic/likely pathogenic variants were also present in ≥7 affected individuals and thereby considered to be of sufficient high confidence for use in predictive genetic testing. Conclusions: A family history of DCM identified only 34% (n=12/35) of hereditary DCM, whereas systematic clinical screening identified the remaining 66% (n=23) of DCM families. This emphasized the importance of clinical investigations to identify familial DCM. The high number of pathogenic/likely pathogenic variants identified in familial DCM provides a firm basis for offering genetic investigations in affected families. This should also be considered in sporadic cases since adequate family evaluation may not always be possible and the results of the genetic investigations may carry prognostic information with an impact on individual management.

scholarly journals Electrocardiographic and Echocardiographic Profile of Dilated Cardiomyopathy Patients

2020 ◽  
Vol 12 (2) ◽  
pp. 109-112
Author(s):  
Rabindra Nath Barman ◽  
Shakil Ghafur ◽  
Haripada Sarkar ◽  
Md Abu Zahid ◽  
Md Abdullah Al Mahmud ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Sinus Tachycardia ◽  
Female Ratio ◽  
High Prevalence ◽  
Primary Disorder ◽  
Ecg Abnormalities ◽  
Male To Female ◽  
Diagnostic Centre ◽  
Standard Techniques

Background: Cardiomyopathy is a primary disorder of heart muscle with abnormal myocardial performance. It is an important cause of heart failure and accounts for upto 25% of causes of heart failure. In view of the high prevalence of chronic heart failure due to underlying dilated cardiomyopathy and the lack of data on DCM, the study was undertaken. Methods: A total of 100 patients (71 males and 29 females) of dilated cardiomyopathy were taken who was undergone Echocardiography at popular Diagnostic centre, Rangpur. ECG and echocardiography was done among all these patients using standard techniques. Results: Majority of the patient was above the age 50 years with male to female ratio is 2.4 :1. Sinus tachycardia, non specific ST-T change, LVH, non progression of R in v1-v5 were common ECG abnormalities. Conclusion: ECG may be normal in patients with DCM though sinus tachycardia and non specific ST-T abnormalities were common. Cardiovasc. j. 2020; 12(2): 109-112

scholarly journals Development of a Cardiac Sarcomere Functional Genomics Platform to Enable Scalable Interrogation of Human TNNT2 Variants

Circulation ◽  
2020 ◽  
Vol 142 (23) ◽  
pp. 2262-2275
Author(s):  
Anthony M. Pettinato ◽  
Feria A. Ladha ◽  
David J. Mellert ◽  
Nicholas Legere ◽  
Rachel Cohn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cell ◽  
Hypertrophic Cardiomyopathy ◽  
Dilated Cardiomyopathy ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Pathogenic Variants ◽  
Calcium Affinity ◽  
Uncertain Significance ◽  
Induced Pluripotent

Background: Pathogenic TNNT2 variants are a cause of hypertrophic and dilated cardiomyopathies, which promote heart failure by incompletely understood mechanisms. The precise functional significance for 87% of TNNT2 variants remains undetermined, in part, because of a lack of functional genomics studies. The knowledge of which and how TNNT2 variants cause hypertrophic and dilated cardiomyopathies could improve heart failure risk determination, treatment efficacy, and therapeutic discovery, and provide new insights into cardiomyopathy pathogenesis, as well. Methods: We created a toolkit of human induced pluripotent stem cell models and functional assays using CRISPR/Cas9 to study TNNT2 variant pathogenicity and pathophysiology. Using human induced pluripotent stem cell–derived cardiomyocytes in cardiac microtissue and single-cell assays, we functionally interrogated 51 TNNT2 variants, including 30 pathogenic/likely pathogenic variants and 21 variants of uncertain significance. We used RNA sequencing to determine the transcriptomic consequences of pathogenic TNNT2 variants and adapted CRISPR/Cas9 to engineer a transcriptional reporter assay to assist prediction of TNNT2 variant pathogenicity. We also studied variant-specific pathophysiology using a thin filament–directed calcium reporter to monitor changes in myofilament calcium affinity. Results: Hypertrophic cardiomyopathy–associated TNNT2 variants caused increased cardiac microtissue contraction, whereas dilated cardiomyopathy–associated variants decreased contraction. TNNT2 variant–dependent changes in sarcomere contractile function induced graded regulation of 101 gene transcripts, including MAPK (mitogen-activated protein kinase) signaling targets, HOPX , and NPPB . We distinguished pathogenic TNNT2 variants from wildtype controls using a sarcomere functional reporter engineered by inserting tdTomato into the endogenous NPPB locus. On the basis of a combination of NPPB reporter activity and cardiac microtissue contraction, our study provides experimental support for the reclassification of 2 pathogenic/likely pathogenic variants and 2 variants of uncertain significance. Conclusions: Our study found that hypertrophic cardiomyopathy–associated TNNT2 variants increased cardiac microtissue contraction, whereas dilated cardiomyopathy–associated variants decreased contraction, both of which paralleled changes in myofilament calcium affinity. Transcriptomic changes, including NPPB levels, directly correlated with sarcomere function and can be used to predict TNNT2 variant pathogenicity.

scholarly journals The Failing Heart in Pediatric Dilated Cardiomyopathy Caused by Excessive Water Drinking: A Case Report and Brief Review

2021 ◽  
Vol 03 ◽  
Author(s):  
Aditya Doni Pradana ◽  
Jarot Widodo
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Acute Heart Failure ◽  
Systolic Function ◽  
Pediatric Population ◽  
Left Ventricular ◽  
Initial Assessment ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Cardiothoracic Ratio

: Acute heart failure in dilated cardiomyopathy (DCM) is a rare cardiac disease in the pediatric population. A 15- year-old boy admitted to the emergency department of Kendal Islamic Hospital, Kendal, Indonesia on June 26th, 2020 with shortness of breath, tachycardia, and oxygen desaturation. The chest X-ray showed significant cardiomegaly with a cardiothoracic ratio was 70% and signs of pulmonary congestion. Transthoracic echocardiography revealed dilation of the left atrium and left ventricle (LV), decreased global LV systolic function with reduced left ventricular ejection fraction of 22%. Subsequently, he was diagnosed with acute heart failure in dilated cardiomyopathy and discharged on day sixth of hospitalization. Focus initial assessment and time-to-therapy in acute heart failure settings needs to be understood by all clinicians especially emergency care physicians.

scholarly journals Pathogenic Variants Associated with Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis

2021 ◽  
Author(s):  
Franziska Seidel ◽  
Manuel Holtgrewe ◽  
Nadya Al-Wakeel-Marquard ◽  
Bernd Opgen-Rhein ◽  
Josephine Dartsch ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Enrichment Analysis ◽  
Event Free Survival ◽  
Genetic Characteristics ◽  
Free Survival ◽  
Coronary Syndrome ◽  
Pathogenic Variants ◽  
Common Causes ◽  
Significant Enrichment

Background - Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. Methods - A cohort of 42 patients (MYCPEDIG) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. MYCPEDIG patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (MYC-NonDCM) and 20 patients with DCM (MYC-DCM). Results - MYC-DCM patients (median age 1.4 years) were younger than MYC-NonDCM patients (median age 16.1 years; p<0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one likely pathogenic/pathogenic (LP/P) variant was identified in 9/42 patients (22%), 8 of them were heterozygous, and 7/9 were in MYC-DCM. LP/P variants were found in genes validated for primary DCM ( BAG3 , DSP , LMNA , MYH7 , TNNI3 , TNNT2 , and TTN ). Rare variant enrichment analysis revealed significant accumulation of high impact disease variants in MYC-DCM versus healthy individuals (p=0.0003). Event-free survival was lower (p=0.008) in MYC-DCM patients compared to MYC-NonDCM and primary DCM. Conclusions - We report heterozygous LP/P variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of LP/P variants, and poor outcome. These phenotype- and age-group specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.

Abstract 2911: T-182C Polymorphism in the Norepinephrine Transporter Gene (SLC6A2) and Risk of Cardiovascular Events in Patients with Dilated Cardiomyopathy: Association of the T allele with a Reduced Risk for Cardiovascular Events

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
TAKAYUKI NAGAI ◽  
Akiyoshi Ogimoto ◽  
Kazuhisa Nishimura ◽  
Akira Kurata ◽  
Jun Suzuki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Cardiovascular Event ◽  
Cardiac Death ◽  
Cardiovascular Events ◽  
Protective Factor ◽  
Systolic Function ◽  
Norepinephrine Transporter ◽  
Left Ventricular ◽  
Adverse Cardiovascular Event

Backgrounds: The increase in sympathetic activity is one of the hallmarks of the chronic heart failure and has been shown to have an important impact on survival in patients with dilated cardiomyopathy (DCM). Norepinephrine transporter (NET) recaptures as much as 90% of released norepinephrine in the heart, making it a critical mediator of norepinephrine inactivation and presynaptic catecholamine homeostasis. Recently, the polymorphism of NET T-182C was reported to be associated with the improvement of left ventricular systolic function by beta-blockers in patients with DCM. However, the association between the incidence of cardiovascular events and the NET polymorphism in patients DCM has not been understood. The purpose of this study was to evaluate the effect of this polymorphism on the incidence of cardiovascular events in patients with DCM. Methods: Eighty-three genetically unrelated patients with nonfamilial DCM (64 males, mean age at initial clinical evaluation 59 ± 14 years) were enrolled in this study. An adverse cardiovascular event was defined as cardiac death or hospitalization for cardiac reasons. The time to the first adverse cardiovascular event was analyzed by the Kaplan-Meier method. The TaqMan polymerase chain reaction method was used for the determination of genotypes of the NET T-182C gene (SLC6A2) (rs#2242446). Results: The distribution of the NET T-182C genotypes (T/T, T/C, and C/C) was 43%, 45%, and 12%, respectively. The NET T-182C T allele frequency was 0.63. During a mean follow-up period of 45 months, 20 cardiovascular events had occurred. Eight patients died from cardiac cause (1 from pump failure and 7 from sudden cardiac death) and there were 12 hospitalizations for new onset or worsening of heart failure symptoms. The cardiovascular event rate of the patients carrying the T allele (T/T and T/C genotype, n = 73) was significantly lower than that of the patients not carrying the T allele (C/C genotype, n = 10) (p = 0.03). Conclusion: Our data suggested that the T allele of the NET T-182C gene may be a protective factor against cardiovascular events in patients with DCM.

Serelaxin for infant heart failure in congenital dilated cardiomyopathy

2018 ◽  
Vol 28 (5) ◽  
pp. 734-736 ◽  
Author(s):  
Patrick O. Myers ◽  
Alice Bordessoule ◽  
Cécile Tissot
Keyword(s):  
Heart Failure ◽  
Extracorporeal Membrane Oxygenation ◽  
Dilated Cardiomyopathy ◽  
Marked Improvement ◽  
Systolic Function ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Compassionate Use ◽  
Ventricular Systolic Function ◽  
Membrane Oxygenation

AbstractSerelaxin has been studied in trials in adults with acute heart failure, but not in children. We report the first compassionate use of serelaxin in an infant. A 6-month-old girl with dilated cardiomyopathy was placed on extracorporeal membrane oxygenation following cardiac arrest unresponsive to medical treatment. Extracorporeal membrane oxygenation weaning failed despite maximal ino-dilator therapy. During the 48-hour infusion of serelaxin, we observed marked improvement in brain natriuretic peptide, left ventricular systolic function, and dilatation. The patient was successfully weaned from extracorporeal membrane oxygenation 24 hours later. The child died after a second extracorporeal membrane oxygenation run owing to sepsis.

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