Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a PARADIGM‐HF analysis

2021 ◽  
Author(s):  
Luis E. Rohde ◽  
Muthiah Vaduganathan ◽  
Brian L. Claggett ◽  
Carisi A. Polanczyk ◽  
Pranav Dorbala ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Ejection Fraction ◽  
Cardiac Death ◽  
Dynamic Changes ◽  
Reduced Ejection Fraction

scholarly journals Electroanatomic Ratios and Mortality in Patients With Heart Failure: Insights from the ASIAN‐HF Registry

2021 ◽  
Author(s):  
Janice Y. Chyou ◽  
Wan Ting Tay ◽  
Inder S. Anand ◽  
Tiew‐Hwa Katherine Teng ◽  
Jonathan J. L. Yap ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Ejection Fraction ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Size ◽  
Reduced Ejection Fraction ◽  
Left Ventricular Size ◽  
All Cause Mortality

Background QRS duration (QRSd) is a marker of electrical remodeling in heart failure. Anthropometrics and left ventricular size may influence QRSd and, in turn, may influence the association between QRSd and heart failure outcomes. Methods and Results Using the prospective, multicenter, multinational ASIAN‐HF (Asian Sudden Cardiac Death in Heart Failure) registry, this study evaluated whether electroanatomic ratios (QRSd indexed for height or left ventricular end‐diastole volume) are associated with 1‐year mortality in individuals with heart failure with reduced ejection fraction. The study included 4899 individuals (aged 60±19 years, 78% male, mean left ventricular ejection fraction: 27.3±7.1%). In the overall cohort, QRSd was not associated with all‐cause mortality (hazard ratio [HR], 1.003; 95% CI, 0.999–1.006, P =0.142) or sudden cardiac death (HR, 1.006; 95% CI, 1.000–1.013, P =0.059). QRS/height was associated with all‐cause mortality (HR, 1.165; 95% CI, 1.046–1.296, P =0.005 with interaction by sex p interaction =0.020) and sudden cardiac death (HR, 1.270; 95% CI, 1.021–1.580, P =0.032). QRS/left ventricular end‐diastole volume was associated with all‐cause mortality (HR, 1.22; 95% CI, 1.05–1.43, P =0.011) and sudden cardiac death (HR, 1.461; 95% CI, 1.090–1.957, P =0.011) in patients with nonischemic cardiomyopathy but not in patients with ischemic cardiomyopathy (all‐cause mortality: HR, 0.94; 95% CI, 0.79–1.11, P =0.467; sudden cardiac death: HR, 0.734; 95% CI, 0.477–1.132, P =0.162). Conclusions Electroanatomic ratios of QRSd indexed for body size or left ventricular size are associated with mortality in individuals with heart failure with reduced ejection fraction. In particular, increased QRS/height may be a marker of high risk in individuals with heart failure with reduced ejection fraction, and QRS/left ventricular end‐diastole volume may further risk stratify individuals with nonischemic heart failure with reduced ejection fraction. Registration URL: https://Clinicaltrials.gov . Unique identifier: NCT01633398.

Abstract 395: A Synonymous Coding SNP Alters SCN5A Regulation by miR-24 and Associates With Non-Arrhythmic Death in Heart Failure

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Xiaoming Zhang ◽  
Jin-Young Yoon ◽  
Michael Morley ◽  
Patrick Breheny ◽  
Heather Bloom ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Clinical Signs ◽  
Heart Rhythm ◽  
Coding Sequence ◽  
Reduced Ejection Fraction ◽  
Arrhythmic Death ◽  
And Function ◽  
Myocardial Gene Expression

Mutations disrupting SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and SNPs linked to SCN5A splicing, localization and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. Recently, we generated a transcriptome-wide map of microRNA (miR) binding sites in human heart and evaluated their interface with polymorphisms. Among >500 common SNPs residing within miR target regions, we identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within SCN5A coding sequence. This SNP is known to reproducibly associate with heart rhythm measurements, but is not considered to be “causal”. Here, we show that miR-24 potently suppresses SCN5A and that rs1805126 modulates this regulation. In further exploring the clinical significance of this, we found that rs1805126 minor allele homozygosity associates with decreased cardiac SCN5A expression and increased mortality in heart failure patients. Unexpectedly, this risk was not linked with arrhythmic sudden cardiac death, but rather, with clinical signs of worsening heart failure (e.g. reduced ejection fraction) and myocardial gene expression changes related to bioenergetics, inflammation and extracellular remodeling. Together, these data attribute a molecular mechanism to this firmly-established GWAS SNP and highlight a novel and surprising link between common variations in SCN5A expression and non-arrhythmic death in heart failure.

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