scholarly journals Effect of angiotensin/neprilysin inhibition on ventricular repolarization and clinical arrhythmogenesis

Cardio-IT ◽  
2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Sefa Gul ◽  
Osman Can Yontar ◽  
Mustafa Yenercag ◽  
Onur Osman Seker ◽  
Guney Erdogan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Sudden Cardiac Death ◽  
Stroke Volume ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Heart Failure Clinic ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor ◽  
The Impact

Background: The most common reason for sudden cardiac death in heart failure is malign ventricular arrhythmias. LCZ 696 improves hospitalization and sudden cardiac death outcomes in heart failure, however mechanisms in preventing sudden cardiac death are still unknown. There is little information available assessing effect of LCZ 696 on Tp-e interval and related calculations. In this study, we aimed to investigate the impact of Sacubitril/valsartan therapy on Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in heart failure patients and its reflections on clinical arrhythmogenesis. Methods: The study was designed as a prospective observational fashion. 265 patients with implantable cardioverter-defibrillator (ICD), who were on regular follow up at Samsun Training and Research Hospital Outpatient Heart Failure Clinic, were validated for the study. Clinical, echocardiographic, electrocardiogram and device data before initiation and six months after dose optimizing were obtained. Results: Stroke volume, cardiac output and ejection fraction significantly improved after LCZ 696 treatment. T wave related parameters, QT and QTC intervals significantly diminished. Furthermore, there was a negative correlation between baseline Tp-e interval duration and the absolute percentile increase of stroke volume(r:-0.234, p: 0.042) and cardiac output (r: -0.240, p: 0.037). Conclusion: In our study, switching Renin-Angiotensin-Aldosterone-System inhibitor with Angiotensin receptor/neprilysin inhibitor was associated with increase in left ventricle performance and decrease of sustained ventricular arrhythmias that required ICD shocks. These positive findings were accompanied by improvements in surface electrocaridogram changes such as Tp-e and related indices.

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

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.

Abstract 2415: Long-Term Baroreflex Activation Therapy Increases the Threshold for the Induction of Lethal Ventricular Arrhythmias in Dogs with Chronic Advanced Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mengjun Wang ◽  
Valerio Zaca ◽  
Alice Jiang ◽  
Itamar Ilsar ◽  
Matthew Ebinger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Lv Function ◽  
Baroreflex Activation Therapy ◽  
Increased Risk ◽  
Lv Remodeling ◽  
Activation Therapy

Heart failure (HF) is associated with a high incidence of ventricular tachycardia (VT) and fibrillation (VF). Patients with HF in whom these lethal arrhythmias can be induced by electrophysiological (EP) testing carry a high risk of sudden cardiac death. We showed that chronic electrical carotid baroreflex activation therapy (BAT) with the Rheos® System (CVRx, Inc.) improves LV function, attenuates LV remodeling and restores autonomic sympathetic-parasympathetic balance in dogs with HF. This study examined the effects of long-term therapy with BAT on the induction of VT or VF in dogs with coronary microembolization-induced HF (LV ejection fraction ~20%). Eleven dogs with HF underwent EP testing at baseline prior to therapy and after 3 and 6 months of therapy with BAT and again 6 weeks after withdrawal of BAT therapy (n = 7) or no therapy at all (Control, n = 4). Programmed ventricular stimulation was performed from the right ventricular apex and included delivery of up to 4 extrastimuli at progressively shorter coupling intervals (in steps of 10 msec). The extrastimuli were delivered following 8 ventricular paced beats with a drive cycle length between 600 and 200 msec. If a sustained monomorphic VT or VF could not be induced, isoproterenol infusion was initiated to increase the sinus rate by ~30% and the EP stimulation protocol was repeated. At baseline, a sustained VT or VF was induced in all 11 dogs (100%). After 3 and 6 months of follow-up, all Control dogs (100%) were induced into sustained VT or VF. After 3 months of BAT, only 3 of 7 dogs (43%) were induced into sustained VT or VF. After 6 months of BAT, only 2 of 7 dogs (29%) were induced into sustained VT or VF. Finally after withdrawal of BAT therapy, all dogs (100%) were again induced into systained VT or VF. In addition to improving LV function and attenuating LV remodeling, long-term monotherapy with BAT markedly increases the threshold for lethal ventricular arrhythmias in dogs with chronic HF. This is a marked improvement over inducibility of lethal arrhythmias seen in historical untreated controls. This benefit of BAT supports the continued exploration of this device as a therapeutic modality for treating patients with chronic HF and increased risk of sudden cardiac death.

scholarly journals Initiation of Angiotensin Receptor-Neprilysin Inhibitor in Heart Failure With Low Cardiac Output

2019 ◽  
Vol 74 (18) ◽  
pp. 2326-2327 ◽  
Author(s):  
Trejeeve Martyn ◽  
Kathleen D. Faulkenberg ◽  
Dmitry M. Yaranov ◽  
Chonyang L. Albert ◽  
Colleen Hutchinson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Angiotensin Receptor ◽  
Low Cardiac Output ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor

Common RyR2 variants associate with ventricular arrhythmias and sudden cardiac death in chronic heart failure

2010 ◽  
Vol 119 (5) ◽  
pp. 215-226 ◽  
Author(s):  
Yuqin Ran ◽  
Jingzhou Chen ◽  
Ning Li ◽  
Weili Zhang ◽  
Li Feng ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Chronic Heart Failure ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Protective Factor ◽  
Critical Role ◽  
Functional Variants ◽  
Increased Risk ◽  
Genes Encoding

Ca2+ cycling plays a critical role in heart failure and lethal arrhythmias. As susceptibility to sudden cardiac death is considered to be a heritable trait in general population, we have therefore investigated whether potentially functional variants of genes encoding RyR2 (ryanodine receptor 2) and the L-type Ca2+ channel are related to the risk of ventricular arrhythmias and sudden cardiac death in CHF (chronic heart failure) in a case-control study. We found that the A allele of rs3766871 in RYR2 was associated with an increased risk of ventricular arrhythmias in patients with CHF {odds ratio, 1.66 [95% CI (confidence interval), 1.21–2.26]; P=0.002}. During a median follow-up period of 32 months in 1058 (85.0%) patients, 296 (28.0%) patients died from heart failure, of whom 141 (47.6%) had sudden cardiac death. After adjustment for age, gender and suspected risk factors, patients carrying the A allele of rs3766871 had an increased risk of cardiac death {HR (hazard ratio), 1.53 [95% CI, 1.11–2.12]; P=0.010} and sudden cardiac death [HR, 1.92 (95% CI, 1.25–2.94); P=0.003]. Patients carrying the A allele of rs790896 in RYR2 had a reduced risk of sudden cardiac death [HR, 0.65 (95% CI, 0.45–0.92); P=0.015]. In conclusion, the A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias, but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with CHF.

P6596S100A8/A9 and sRAGE peripheral blood levels in patients with heart failure and an implanted cardioverter/defibrillator: relation with sustained, fast ventricular arrhythmias

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Flevari ◽  
D Leftheriotis ◽  
C Kroupis ◽  
V Kitsinelis ◽  
V Stasinos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Nyha Class ◽  
Blood Levels ◽  
Ventricular Tachyarrhythmias ◽  
Group I ◽  
Group Ii ◽  
Sudden Cardiac Death Risk

Abstract Background Prediction of sudden cardiac death in heart failure (HF) remains suboptimal. Blood levels of the S100A8/A9 heterodimer protein complex and the soluble receptor of advanced glucation end product (sRAGE) are promising biomarkers in HF, reflecting inflammatory/fibrotic and apoptotic pathways, possibly involved in ventricular arrhythmogenesis. The relation of S100A8/A9 and sRAGE with ventricular arrhythmias and sudden cardiac death risk has not been previously assessed. Purpose Purpose of the study was to investigate whether S100A8/A9 and sRAGE serum blood levels of patients (pts) with systolic heart failure are related to the occurrence of life-threatening ventricular tachyarrhythmias. Patients and methods We studied 60 pts with clinically stable heart failure due to coronary artery disease (n=37) and dilated cardiomyopathy (n=23), all with a chronically implanted ICD for primary (n=43) or secondary (n=16) sudden death prevention, all in sinus rhythm. Their mean age (±1 SE) was 62±2 years, NYHA class I-II, mean LVEF 28±1%, Nt-pro-BNP 893±85 pg/dl. Blood was drawn at study initiation for S100A8/A9 and sRAGE assessment (ELISA, R&D Systems). They all were systematically followed-up for 4 years regarding the occurrence of fast ventricular tachyarrhythmias (>180 bpm) necessitating antiarrhythmic intervention through the ICD. Results S100A8/A9 and sRAGE levels were 16±1.6 ng/ml and 1076±99 pg/ml respectively. S100A8/A9 levels were lower than in normal controls, while sRAGE levels were within normal limits. During the 4-year follow-up period, 39 pts had an uneventful course (Group I), while 16 pts exhibited fast ventricular tachyarrhythmic episodes necessitating ICD activation (anti-tachycardia pacing or shock, Group II). Three pts died of pump failure and 2 pts of non-cardiac causes. No differences were observed between Group I and Group II pts regarding mean NYHA class, Nt-pro-BNP levels. Group II patients had significantly lower LVEF as well as S100A8/A9 serum levels relative to pts without ventricular arrhythmias (LVEF: 30±1.2 vs, 25±1.3%, p<0.05, S1OOA8/A9: 18.9±2.2 vs 11.8±1.5 ng/ml, p<0.05), while no difference was observed between Groups regarding sRAGE levels 1097±101 1105±239 pg/ml, p:NS). S100A8/A9 levels were not related significantly to LVEF (r:-21, p=0.13). Conclusion S100A8/A9 protein levels are reduced in pts with stable HF and an implanted ICD. They are even lower among pts with rapid ventricular tachyarrhythmias occurring during follow-up. This finding implies that S100A8/A9 may constitute a biomarker of increased sudden cardiac death risk in HF, in addition to reduced LVEF.

scholarly journals Hypertrophic Cardiomyopathy: A Review

2014 ◽  
Vol 8s1 ◽  
pp. CMC.S15717 ◽  
Author(s):  
Brian A. Houston ◽  
Gerin R. Stevens
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Clinical Syndrome ◽  
Monogenic Disease ◽  
Sarcomeric Genes ◽  
Ethnic Origins

Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both genders and of various racial and ethnic origins. Widely accepted as a monogenic disease caused by a mutation in 1 of 13 or more sarcomeric genes, HCM can present catastrophically with sudden cardiac death (SCD) or ventricular arrhythmias or insidiously with symptoms of heart failure. Given the velocity of progress in both the fields of heart failure and HCM, we present a review of the approach to patients with HCM, with particular attention to those with HCM and the clinical syndrome of heart failure.

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