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Low systolic blood pressure (SBP) was previously suggested to be a marker for heart failure and mortality in patients with low left ventricular ejection fraction. We aimed to explore the association of SBP on risk of ventricular tachyarrhythmias (VTA) and atrial arrhythmias as well as appropriate and inappropriate Implantable Cardioverter Defibrillator (ICD) therapy. The study population comprised 1,481 of 1,500 (99%) patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy trial. Multivariate Cox proportional hazards regression modeling was used to identify the association of baseline SBP (recorded prior to ICD implantation) with the risk of VTA > 170 beats/min during follow-up (primary end point) and atrial arrhythmia, appropriate and inappropriate ICD therapy, hospitalization and death (secondary end points). SBP was dichotomized at 120 mm Hg (approximate mean and median) and was also assessed as a continuous measure. Multivariate analysis showed that each 10 mm Hg decrement in SBP was associated with corresponding 11% increased risk for VTA (p = 0.008). Low SBP (≤120 mm Hg) was associated with a significant 58% (p = 0.002) increased risk for VTA ≥170 beats/min; 53% (p = 0.019) increased risk for VTA ≥200 beats/min; and 65% (p = 0.001) increased risk for appropriate ICD therapy, as compared with SBP >120 mm Hg. Low SBP was not associated with increased risk of atrial arrhythmias, and inappropriate ICD therapy. In conclusion, in MADIT-RIT, SBP (≤120 mm Hg) predicted higher rates of VTA. These findings suggest that SBP may be utilized for VTA risk stratification in candidates for primary ICD therapy., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The clinical benefit of primary prevention implantable cardioverter-defibrillator (ICD) therapy in asymptomatic patients (New York Heart Association [NYHA] functional class I) with ischemic cardiomyopathy and left ventricular dysfunction is continually disputed., Objective: The purpose of this study was to evaluate the incidence of ventricular arrhythmias, mortality rates, and appropriate device therapies by NYHA class in a prospective national ICD registry., Methods: The study comprised 1670 consecutive patients with ischemic cardiomyopathy who were implanted with a primary prevention ICD and enrolled in the prospective national Israeli ICD Registry from 2010. The risk for clinical and arrhythmic events was assessed by NYHA class., Results: Asymptomatic patients (NYHA I) composed 19% of the study cohort. Comparison according to NYHA class showed that the highest mortality rate was in the NYHA III-IV group vs NYHA I and NYHA II (10.5% vs 5.4% and 5.8%, respectively; log rank P = .003). Conversely, cumulative incidence of appropriate ICD therapies, corrected for death as a competing risk, were higher among patients with NYHA I (11% vs 7%; P = .021). In a multivariate model, NYHA I vs ≥II remained independently associated with a significant 2-fold risk for appropriate ICD therapy (hazard ratio 2.03; 95% confidence interval 1.28-3.24)., Conclusion: Our findings indicate that patients with ischemic cardiomyopathy without heart failure symptoms have a higher risk of appropriate ICD therapy compared with symptomatic patients after adjustment for the competing risk of death, suggesting possible incremental benefit of primary ICD implantation in this population., (Copyright © 2019. Published by Elsevier Inc.)

Aims: Heart failure patients with advanced chronic kidney disease (CKD) may experience an increased rate of non-arrhythmic mortality due to associated comorbidities. We aimed to evaluate the risk of mortality without appropriate implantable cardioverter-defibrillator (ICD) shocks in this high-risk population., Methods and Results: The study population comprised 3542 patients who received an ICD, were enrolled, and prospectively followed-up in the Israeli ICD registry. Study patients were categorized into two groups: those with advanced CKD [defined by a glomerular filtration rate of <30 mL/min/1.73 m2 or being on dialysis at time of implantation (n = 197)], and those without advanced CKD (n = 3344). The primary endpoint was the risk of death without receiving appropriate ICD shock. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rates of death without prior ICD shock were significantly higher in the advanced kidney disease group (46%) compared with the non-advanced CKD group (19%; log-rank P-value <0.001). Consistently, multivariate analysis showed that the risk of death without receiving appropriate ICD shock therapy at 5 years was 2.5-fold (P < 0.001) higher among advanced CKD patients. In contrast, the rate of appropriate ICD shock therapy at 5 years among advanced CKD patients was only 9%, with a very high mortality rate (63%) within 3.5 years subsequent to shock therapy., Conclusion: Nearly one-half of ICD with advanced CKD die within 5 years without receiving an appropriate ICD shock. These findings stress the importance of appropriate patient selection for primary ICD implantation in this high-risk population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Renal dysfunction is associated with increased mortality in heart failure (HF) patients. However, there are limited data regarding clinical and arrhythmic outcomes associated with implantable cardioverter defibrillator (ICD) therapy in this population., Methods: We evaluated outcomes associated with the severity of renal dysfunction with or without dialysis among 2,289 patients who were enrolled and prospectively followed up in the Israeli ICD Registry. The primary endpoint of the study was all-cause mortality. Secondary endpoints included cardiac mortality, HF hospitalization, non-cardiac hospitalization, and appropriate and inappropriate ICD therapy., Results: Severe renal dysfunction patients (estimated glomerular filtration rate<30 ml/min/1.73 m2; n=144 patients; 6%) were older, with higher comorbidities prevalence, and more likely to suffer from advanced HF. Among severe renal dysfunction patients, those on dialysis had a lower prevalence of wide QRS and complete left bundle branch morphology, resulting in lower cardiac resynchronization therapy defibrillator (CRTD) implantation rates. Dialysis was associated with an overall increased risk for all-cause mortality (hazard ratio (HR) 3.22; 95% CI 1.69-6.13; p<0.01) and for noncardiac hospitalizations (HR 2.80; p<0.001) compared to all other study patients. However, within the subgroup of patients with severe renal dysfunction, the presence of dialysis was not an independent risk factor for all-cause mortality (HR 0.99; p=0.97) as compared to non-dialysis. The rate of appropriate ICD therapy for ventricular tachyarrhythmias increased with declining renal function, with the highest rate observed among those undergoing dialysis., Conclusions: The present findings suggest that dialysis does not significantly modify the adverse outcomes associated with severe renal dysfunction following ICD/CRTD implantation., (© 2015 S. Karger AG, Basel.)

Background: Identification of infants at risk for sudden arrhythmic death remains one of the leading challenges of modern medicine. We present a family in which a common polymorphism (single nucleotide polymorphism) inherited from the father, combined with a stop codon mutation inherited from the mother (both asymptomatic), led to 2 cases of sudden infant death., Methods and Results: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, CACNA1c, CACNB2b, and KCNJ2 genes were amplified and analyzed by direct sequencing. Functional electrophysiological studies were performed with the single nucleotide polymorphism and mutation expressed singly and in combination in Chinese ovary (CHO-K1) and COS-1 cells. An asymptomatic woman presenting after the death of her 2-day-old infant and spontaneous abortion of a second baby in the first trimester was referred for genetic analysis. The newborn infant had nearly incessant ventricular tachycardia while in utero and a prolonged QTc (560 ms). The mother was asymptomatic but displayed a prolonged QTc. Genetic screening of the mother revealed a heterozygous nonsense mutation (P926AfsX14) in KCNH2, predicting a stop codon. The father was asymptomatic with a normal QTc but had a heterozygous polymorphism (K897T) in KCNH2. The baby who died at 2 days of age and the aborted fetus inherited both K897T and P926AfsX14. Heterologous coexpression of K897T and P926AfsX14 led to loss of function of HERG current much greater than expression of K897T or P926AfsX14 alone., Conclusions: Our data suggest that a common polymorphism (K897T) can markedly accentuate the loss of function of mildly defective HERG channels, leading to long-QT syndrome-mediated arrhythmias and sudden infant death.