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The current guidelines advocate prophylactic implantable cardioverter-defibrillator (ICD) for all patients with symptomatic heart failure (HF) with low left ventricular ejection fraction. Because many patients will never use their device, a score delineating subgroups with differential ICD benefit is crucial. We aimed to evaluate the MADIT-II-based Risk Stratification Score (MRSS) feasibility to delineate the ICD survival benefit in a nationwide registry of patients with HF with prophylactic ICDs. Accordingly, all Israeli patients with HF with prophylactic ICD/cardiac resynchronization therapy defibrillators were categorized into MRSS-based risk subgroups. The study end points included overall mortality, sustained ventricular arrhythmia (VA), and a competing risk of VA (potential preventable arrhythmic death, where ICD could benefit survival) versus nonarrhythmic death. Potential ICD survival benefit was estimated by the area between these cumulative incidence curves. In 2,177 patients with HF implanted prophylactic device, 189 patients (8.7%) had VA and 316 (14.5%) died during a median follow-up of 2.9 years. The MRSS risk subgroups were significantly associated with overall mortality (p <0.001) and weakly with VA (p = 0.3). The competing risk analysis of VA versus nonarrhythmic death revealed a significantly shorter duration (p <0.001) and smaller magnitude of ICD survival benefit with increased risk subgroups, yielding an estimated 76, 60, 38, and 0 life days gained from prophylactic ICD implant during a 5-year follow-up for the MRSS low-, intermediate-, high-, and very high-risk subgroups, respectively (p for trend <0.05). In conclusion, MRSS use in a nationwide registry of patients with ischemic and nonischemic cardiomyopathy, revealed subgroups with differing ICD survival benefit, suggesting it could help evaluate prophylactic ICD survival benefit., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Multisite cardiac resynchronization therapy (MSCRT) with dual-vein left ventricular (LV) pacing has theoretical advantages over conventional CRT in faster and more physiological LV activation. We aimed to define indications, feasibility, safety, acute, and long-term results of MSCRT., Methods: All patients implanted with MSCRT during 2008-2014 in a single center were reviewed and analyzed., Results: Thirty-nine patients (90% CRT-defibrillators, 64 ± 9 years, 85% male, 74% ischemic etiology) were included. Four groups of indications were recognized: (1) significant tricuspid regurgitation (TR) in patients planned for device implantation without right ventricular lead (n = 3). Follow-up (f/u) of 4 ± 3 years showed major symptomatic improvement in all, with stable LV size and function and deferral of valve surgery; (2) severe heart failure with reduced ejection fraction (HFrEF) and refractory ventricular tachycardia (VT) (n = 4). Except for 1 early death for acute renal failure, all others showed no VT episodes and HF improvement (f/u 4.5 ± 0.5 years); (3) severe HFrEF and wide QRS (≥ 150 ms) or failure of biventricular pacing to narrow QRS during implantation (n = 5). One patient had periprocedural mortality. The others had major clinical improvement; (4) severe HF and narrow QRS/RBBB (n = 27). 23/24 patients with available f/u of 3 ± 1.7 years improved clinically and 57% had EF improvement. In 3 patients, LV1 was disabled and one had LV2 dislodgement., Conclusions: MSCRT is feasible, safe, and valuable in selected patients with a need to avoid RV lead during device implantation, refractory VT with no other solution, severe HFrEF with wide QRS or CRT non-responsiveness, and severe HF without LBBB. Randomized controlled studies are required.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF); however, a third of patients are non-responders. The development of quadripolar left ventricular (LV) lead was shown, mainly in single manufactures' registry, to improve LV remodeling and overall mortality. However, limited reports exist on the impact of quadripolar LV leads on HF hospitalization rates in real-life cohorts. We evaluated the clinical outcomes associated with quadripolar LV leads in a large nation-wide registry including all patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D)., Methods: Between July 2010 and October 2016, 2913 consecutive patients were implanted with a CRT-D and all were prospectively enrolled in the Israeli ICD Registry. Quadripolar LV leads were implanted in 973 (33.4%) patients during this period, and their clinical outcomes were compared to CRT-D recipients implanted with a bipolar LV lead. Primary endpoint was HF hospitalization rate., Results: Quadripolar leads were implanted more in patients with non-ischemic cardiomyopathy and for primary prevention indication and less in post-infarction patients and for secondary prevention of sudden death. Longer QRS duration was observed with quadripolar leads (147 ± 23 vs 143 ± 25; p < 0.001). Outcome event rate for 100 patient years revealed no difference in HF hospitalization rates between bipolar and quadripolar LV leads. Quadripolar lead implant led to lower cardiac mortality, with no influence on overall mortality. Multivariate analysis revealed no significant differences in study endpoints between bipolar and quadripolar LV leads., Conclusion: In a large real-life registry, implantation of quadripolar LV leads in patients with CRT-D did not influence HF hospitalization rates.

Aims: Cardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) has downsides of high cost and inappropriate shocks compared to CRT without a defibrillator (CRT-P). Recent data suggest that the survival benefit of implantable cardioverter defibrillator (ICD) therapy is attenuated in the older age group. We hypothesized that, among octogenarians eligible for cardiac resynchronization therapy, CRT-P confers similar morbidity and mortality benefits as CRT-D., Methods and Results: We compared morbidity and mortality outcomes between consecutive octogenarian patients eligible for CRT therapy who underwent CRT-P implantation at Barzilai MC (n = 142) vs. those implanted with CRT-D for primary prevention indication who were prospectively enrolled in the Israeli ICD Registry (n = 104). Among the 246 study patients, mean age was 84 ± 3 years, 74% were males, and 66% had ischaemic cardiomyopathy. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rate of all-cause mortality was 43% in CRT-P vs. 57% in the CRT-D group [log-rank P = 0.13; adjusted hazard ratio (HR) = 0.79, 95% CI 0.46-1.35, P = 0.37]. Kaplan-Meier analysis also showed no significant difference in the rates of the combined endpoint of heart failure or death (46 vs. 60%, respectively, log-rank P = 0.36; adjusted HR was 0.85, 95% CI 0.51-1.44, P = 0.55). A Cox proportional hazard with competing risk model showed that re-hospitalizations for cardiac cause were not different for the two groups (adjusted HR 1.35, 95% CI 0.7-2.6, P = 0.37)., Conclusion: Our data suggest that, in octogenarians with systolic heart failure, CRT-P therapy is associated with similar morbidity and mortality outcomes as CRT-D therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Elevated level of antibodies to oxidized low-density lipoproteins (OxLDL-Ab) was shown to reliably predict morbidity and mortality in patients with heart failure (HF). Two hundred and eleven patients aged ≥65 years treated at the Heart Failure Unit, Tel Aviv-Sourasky Medical Center, were included in this retrospective study. The end points were time to the first hospitalization (morbidity), all-cause mortality, and a combination of the two (composite outcome). HF duration ranged from 8 to 10.5 years. Mean follow-up was 5.2 ± 1.9 years. The mean number of clinical visits was 18.3 ± 2.4. Participants were divided according to OxLDL-Ab level. Group 1 had Ox LDL-Ab level <200 arbitrary U/ml. Group 2 had OxLDL-Ab level ≥200 arbitrary U/ml. The mean time to the first hospitalization was 25.8 ± 17.0 months. The mortality rate was 44.1%. Combined mortality and hospitalization rate was 58.8%. Adjusted hazard ratios of OxLDL-Ab for hospitalization were 3.16, p <0.001, 95% confidence interval 1.740 to 5.736 and for composite outcome 2.67, p <0.001, 95% confidence interval 1.580 to 4.518. In conclusion, OxLDL-Ab level was the best predictor for both hospitalization and composite outcome. It may, thus, serve as a useful clue for early and more accurate detection of poorly controlled HF and as a marker for imminent exacerbations of thereof., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress., Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure., Methods: Baseline serum MPO levels were measured in 285 consecutive CHF patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality., Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 +/- 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values., Conclusions: MPO levels are elevated in CHF and correlate with disease severity. MPO has an additive predictive value on mortality in patients with intermediate NT-proBNP levels.

Background: Circulating endothelial progenitor cells (EPCs) are increased in conditions associated with ischaemia and can potentially support angiogenesis and vasculogenesis. EPC levels were also shown to predict outcome in patients with atherosclerotic vascular disease. We tested the hypothesis that circulating EPC can predict outcome in patients with congestive heart failure (CHF)., Methods: EPC-colony-forming units were measured in the peripheral blood of 107 consecutive patients with CHF with New York Heart Association (NYHA) functional class II-IV. Serum levels of vascular endothelial growth factor (VEGF), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitivity C-reactive protein (hsCRP) were also measured. End points were defined as CHF-related hospital admissions and all-cause mortality., Results: Age (p = 0.01), diabetes mellitus (p = 0.002) and EPC levels (p = 0.02) were found to be independent predictors of all-cause mortality. EPC levels did not predict CHF-related hospitalisations. EPC levels correlated positively with NYHA (p = 0.05, r = 0.19), but did not correlate with VEGF, NT-pro-BNP or hsCRP. EPC levels did not differ by the aetiology of CHF., Conclusions: EPC levels are independent predictors of all-cause mortality among patients with CHF.

Background: Cardiac resynchronization therapy is a modality with proven morbidity and mortality benefit in advanced systolic heart failure. Nevertheless, not all patients respond favorably to CRT. Natriuretic peptides and inflammatory markers are elevated in congestive heart failure and reflect disease severity., Objectives: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT., Methods: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus, Post-implantation levels were determined 2 weeks post-procedure in the PVB. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure., Results: At baseline, coronary sinus levels of BNP but not hsCRP were significantly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 +/- 102.5 pg/ml, 95% confidence interval 24.2-434, P< 0.0001; hsCRP mean difference 5.2 +/- 2.4 mg/dl, 95% CI 0.3-10.1, P= 0.001). During a mean follow-up of 17.7 +/- 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF. Baseline New York Heart Association and CSBNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations., Conclusions: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict clinical response and may guide patient management.

Aims: Cardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) has downsides of high cost and inappropriate shocks compared to CRT without a defibrillator (CRT-P). Recent data suggest that the survival benefit of implantable cardioverter defibrillator (ICD) therapy is attenuated in the older age group. We hypothesized that, among octogenarians eligible for cardiac resynchronization therapy, CRT-P confers similar morbidity and mortality benefits as CRT-D.Methods and Results: We compared morbidity and mortality outcomes between consecutive octogenarian patients eligible for CRT therapy who underwent CRT-P implantation at Barzilai MC (n = 142) vs. those implanted with CRT-D for primary prevention indication who were prospectively enrolled in the Israeli ICD Registry (n = 104). Among the 246 study patients, mean age was 84 ± 3 years, 74% were males, and 66% had ischaemic cardiomyopathy. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rate of all-cause mortality was 43% in CRT-P vs. 57% in the CRT-D group [log-rank P = 0.13; adjusted hazard ratio (HR) = 0.79, 95% CI 0.46-1.35, P = 0.37]. Kaplan-Meier analysis also showed no significant difference in the rates of the combined endpoint of heart failure or death (46 vs. 60%, respectively, log-rank P = 0.36; adjusted HR was 0.85, 95% CI 0.51-1.44, P = 0.55). A Cox proportional hazard with competing risk model showed that re-hospitalizations for cardiac cause were not different for the two groups (adjusted HR 1.35, 95% CI 0.7-2.6, P = 0.37).Conclusion: Our data suggest that, in octogenarians with systolic heart failure, CRT-P therapy is associated with similar morbidity and mortality outcomes as CRT-D therapy. [ABSTRACT FROM AUTHOR]

Clinical Outcome of Single- versus Dual-Chamber ICDs Objective To compare the clinical outcomes of a single- versus dual-chamber ICD for primary prevention of sudden cardiac death in a large, national ICD registry. Methods Data were collected from the prospective Israeli ICD Registry. Baseline characteristics and clinical outcomes including mortality, admissions for heart failure (HF), and ICD therapy were compared between the two groups. Results A total of 1,125 subjects, 37% with a single-chamber and 63% with a dual-chamber ICD, constructed the baseline cohort. Approximately 80% had ischemic heart disease (IHD). Mean follow-up was 22 months, mean ejection fraction was 30%, and mean QRS width was 103 milliseconds in both groups. During follow-up, there were no significant differences in the rate of mortality, admissions for HF, appropriate or inappropriate therapy, or in time to any of the clinical outcomes. Using multivariate analysis, single-chamber ICD was not associated with increased risk of death or admission for HF. In a subgroup of patients with IHD, single-chamber ICD was associated with a higher rate of inappropriate therapy. Conclusions In this large retrospective population-based cohort, dual-chamber ICD showed no benefit in reducing the incidence of death or HF admissions, whereas in a subgroup of patients with IHD, single-chamber ICD was associated with increased inappropriate therapy. Further prospective studies are necessary to assess the benefit of dual-chamber ICD in reducing the rate of inappropriate therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF. Methods: HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population (n =7701) and associated with the HF admissions and mortality of the patients. Results: Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters (p <0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) (r =0.31 p =0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF (p =0.047). Conclusion: HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated. [Copyright &y& Elsevier]

Aim: Evaluate prevalence of heart failure (HF) medications and their association with ventricular arrhythmia (VA) and survival among patients implanted with primary prevention implantable cardiac defibrillator (ICD)/cardiac resynchronization therapy + defibrillator (CRTD) devices. Methods: Association of treatment and dose (% guideline recommended target) of beta-adrenergic receptor antagonist (BB), angiotensin-antagonists (AngA), and mineralocorticoid-antagonists (MRA), after ICD/CRTD implant with VA and mortality was retrospectively analyzed. Results: Study included 186 HF patients; 42.5% and 57.5% implanted with ICD and CRTD, respectively. During 3.8 (2.1;6.7) years; 52 (28%) had VA and 77 (41.4%) died. Treatment (% of patients) included: BB (83%), AngA (87%), and MRA (59%). Median doses were 25(12.5;50)% of target for all medications. BB treatment >25% target dose was associated with reduced VA incidence. In the multivariable model including age, gender, diabetes, heart rate, and medication doses, increased BB dose was associated with reduced VA (hazard ratio (HR) 0.443 95% CI 0.222–0.885; p = 0.021). In the multivariable model for overall mortality including age, gender, renal disease, VA, and medical treatment, VA was associated with increased mortality (HR 2.672; 95% CI 1.429–4.999; p = 0.002) and AngA treatment was associated with reduced mortality (HR 0.515; 95% CI 0.285–0.929; p = 0.028). Conclusions: In this cohort of real-life HF patients discharged after ICD/CRTD implant, prevalence of guideline-based HF medications was high, albeit with low doses. Higher BB dose was associated with reduced VA, while AngA was associated with improved survival. [ABSTRACT FROM AUTHOR]