Heart Failure in Patients with Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiomyopathy characterized as fibro-fatty replacement, and a common cause for sudden cardiac death in young athletes. Development of heart failure (HF) has been an under-recognized complication of ACM for a long time. The current clinical management guidelines for HF in ACM progression have nowadays been updated. Thus, a comprehensive review for this great achievement in our understanding of HF in ACM is necessary. In this review, we aim to describe the research progress on epidemiology, clinical characteristics, risk stratification and therapeutics of HF in ACM.

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Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium

Netherlands Heart Journal ◽

10.1007/s12471-021-01542-1 ◽

2021 ◽

Author(s):

R. W. Roudijk ◽

K. Taha ◽

M. Bourfiss ◽

P. Loh ◽

L. van den Heuvel ◽

...

Keyword(s):

Heart Failure ◽

Sudden Cardiac Death ◽

Early Detection ◽

Risk Stratification ◽

Dilated Cardiomyopathy ◽

Cardiac Death ◽

Diagnostic Techniques ◽

Arrhythmogenic Cardiomyopathy ◽

Early Detection Of Disease ◽

Non Invasive

AbstractIn relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy.

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State of the Art Review on Genetics and Precision Medicine in Arrhythmogenic Cardiomyopathy

International Journal of Molecular Sciences ◽

10.3390/ijms21186615 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6615

Author(s):

Viraj Patel ◽

Babken Asatryan ◽

Bhurint Siripanthong ◽

Patricia B. Munroe ◽

Anjali Tiku-Owens ◽

...

Keyword(s):

Precision Medicine ◽

Cardiac Death ◽

Genetic Basis ◽

State Of The Art ◽

Incomplete Penetrance ◽

Genetic Determinants ◽

Arrhythmogenic Cardiomyopathy ◽

Clinical Challenge ◽

Inherited Cardiomyopathy ◽

Increased Risk

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterised by ventricular arrhythmia and an increased risk of sudden cardiac death (SCD). Numerous genetic determinants and phenotypic manifestations have been discovered in ACM, posing a significant clinical challenge. Further to this, wider evaluation of family members has revealed incomplete penetrance and variable expressivity in ACM, suggesting a complex genotype-phenotype relationship. This review details the genetic basis of ACM with specific genotype-phenotype associations, providing the reader with a nuanced perspective of this condition; whilst also proposing a future roadmap to delivering precision medicine-based management in ACM.

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Cadherin 2-Related Arrhythmogenic Cardiomyopathy: Prevalence and Clinical Features

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003097 ◽

2021 ◽

Author(s):

Alice Ghidoni ◽

Perry M. Elliott ◽

Petros Syrris ◽

Hugh Calkins ◽

Cynthia A. James ◽

...

Keyword(s):

Heart Failure ◽

Clinical Features ◽

Genetic Screening ◽

Rare Variants ◽

Family Members ◽

Arrhythmogenic Cardiomyopathy ◽

Cascade Screening ◽

Pathogenic Variants ◽

Fatty Replacement ◽

The Right

Background - Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibro-fatty replacement of the right and/or left ventricle, often causing ventricular dysfunction and life-threatening arrhythmias. Variants in desmosomal genes account for up to 60% of cases. Our objective was to establish the prevalence and clinical features of ACM stemming from pathogenic variants, in the non-desmosomal cadherin 2 ( CDH2 ), a novel genetic substrate of ACM. Methods - A cohort of 500 unrelated patients with a definite diagnosis of ACM and no disease-causing variants in the main ACM genes was assembled. Genetic screening of CDH2 was performed through next-generation or Sanger sequencing. Whenever possible, cascade screening was initiated in the families of CDH2 -positive probands, and clinical evaluation was assessed. Results - Genetic screening of CDH2 led to the identification of 7 rare variants: five, identified in 6 probands, were classified as pathogenic or likely pathogenic. The previously established p.D407N pathogenic variant was detected in 2 additional probands. Probands and family members with pathogenic/likely pathogenic variants in CDH2 were clinically evaluated, and along with previously published cases, altogether contributed to the identification of gene-specific features (13 cases from this cohort and 11 previously published, for a total of 9 probands and 15 family members). Ventricular arrhythmic events occurred in most CDH2 -positive subjects (20/24, 83%), while the occurrence of heart failure was rare (2/24, 8.3%). Among probands, sustained ventricular tachycardia and/or sudden cardiac death occurred in 5/9 (56%). Conclusions - In this worldwide cohort of previously genotype-negative ACM patients, the prevalence of probands with CDH2 pathogenic/likely pathogenic variants was 1.2% (6/500). Our data show that this cohort of CDH2 -ACM patients has a high incidence of ventricular arrhythmias, while evolution toward heart failure is rare.

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450 How to assess the risk of sudden cardiac death in patients with postinfarction heart failure?

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(05)80291-7 ◽

2005 ◽

Vol 4 (1) ◽

pp. 105-105

Keyword(s):

Heart Failure ◽

Sudden Cardiac Death ◽

Cardiac Death

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Faculty Opinions recommendation of Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726155351.793515453 ◽

2016 ◽

Author(s):

Luis Ruilope ◽

Enrique Morales

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Systematic Review ◽

Sudden Cardiac Death ◽

Randomized Controlled Trials ◽

Cardiac Death ◽

Meta Analysis ◽

Controlled Trials ◽

Aldosterone Antagonists ◽

Randomized Controlled

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Prognostic implications of troponin T variations in inherited cardiomyopathies using systems biology

npj Genomic Medicine ◽

10.1038/s41525-021-00204-w ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Rameen Shakur ◽

Juan Pablo Ochoa ◽

Alan J. Robinson ◽

Abhishek Niroula ◽

Aneesh Chandran ◽

...

Keyword(s):

Heart Failure ◽

Systems Biology ◽

Sudden Cardiac Death ◽

Risk Stratification ◽

Clinical Data ◽

Cardiac Death ◽

Troponin T ◽

Management Options ◽

Familial Cardiomyopathy ◽

The Impact

AbstractThe cardiac troponin T variations have often been used as an example of the application of clinical genotyping for prognostication and risk stratification measures for the management of patients with a family history of sudden cardiac death or familial cardiomyopathy. Given the disparity in patient outcomes and therapy options, we investigated the impact of variations on the intermolecular interactions across the thin filament complex as an example of an unbiased systems biology method to better define clinical prognosis to aid future management options. We present a novel unbiased dynamic model to define and analyse the functional, structural and physico-chemical consequences of genetic variations among the troponins. This was subsequently integrated with clinical data from accessible global multi-centre systematic reviews of familial cardiomyopathy cases from 106 articles of the literature: 136 disease-causing variations pertaining to 981 global clinical cases. Troponin T variations showed distinct pathogenic hotspots for dilated and hypertrophic cardiomyopathies; considering the causes of cardiovascular death separately, there was a worse survival in terms of sudden cardiac death for patients with a variation at regions 90–129 and 130–179 when compared to amino acids 1–89 and 200–288. Our data support variations among 90–130 as being a hotspot for sudden cardiac death and the region 131–179 for heart failure death/transplantation outcomes wherein the most common phenotype was dilated cardiomyopathy. Survival analysis into regions of high risk (regions 90–129 and 130–180) and low risk (regions 1–89 and 200–288) was significant for sudden cardiac death (p = 0.011) and for heart failure death/transplant (p = 0.028). Our integrative genomic, structural, model from genotype to clinical data integration has implications for enhancing clinical genomics methodologies to improve risk stratification.

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Unusual Presentation of Kratom Overdose With Rhabdomyolysis, Transient Hearing Loss, and Heart Failure

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/23247096211005069 ◽

2021 ◽

Vol 9 ◽

pp. 232470962110050

Author(s):

Vikram Sangani ◽

Naseem Sunnoqrot ◽

Kurdistan Gargis ◽

Akshay Ranabhotu ◽

Abbas Mubasher ◽

...

Keyword(s):

Heart Failure ◽

Hearing Loss ◽

Cardiac Death ◽

Multidisciplinary Approach ◽

Kidney Injury ◽

Lethal Effect ◽

Limited Information ◽

Emergency Physicians ◽

Behavioral Impairment ◽

Elevated Creatinine

Kratom mainly grows in Southeast Asia. It is widely used for pain management and opioid withdrawal, which is available online for cheaper prices. Alkaloids extracted from kratom such as mitragynine and 7-hydroxy mitragynine exhibit analgesic properties by acting through µ receptors. Commonly reported side effects of kratom include hypertension, tachycardia, agitation, dry mouth, hallucinations, cognitive and behavioral impairment, cardiotoxicity, renal failure, cholestasis, seizures, respiratory depression, coma, and sudden cardiac death from cardiac arrest. Rhabdomyolysis is a less commonly reported lethal effect of kratom. Limited information is available in the literature. In this article, we present a case of a 45-year-old female who is overdosed with kratom and presented with lethargy, confusion, transient hearing loss, and right lower extremity swelling and pain associated with weakness who was found to have elevated creatinine phosphokinase. She was diagnosed with rhabdomyolysis, compartment syndrome, multiorgan dysfunction including acute kidney injury, liver dysfunction, and cardiomyopathy. She underwent emergent fasciotomy and required hemodialysis. Her renal and liver function subsequently improved. We described the case and discussed pharmacology and adverse effects of kratom toxicity with a proposed mechanism and management. We conclude that it is essential for emergency physicians, internists, intensivists, cardiologists, and nephrologists to be aware of these rare manifestations of kratom and consider a multidisciplinary approach.

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