Clinical presentation at first heart failure hospitalization does not predict recurrent heart failure admission

Abstract Aims There are limited data on whether clinical presentation at first heart failure (HF) hospitalization predicts recurrent HF events. We aimed to assess predictors of recurrent HF hospitalizations in mild HF patients with an implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Methods and results Data on HF hospitalizations were prospectively collected for patients enrolled in MADIT‐CRT. Predictors of recurrent HF hospitalization (HF2) after the first HF hospitalization were assessed using Cox proportional hazards regression models including baseline covariates and clinical presentation or management at first HF hospitalization. There were 193 patients with first HF hospitalization, and 156 patients with recurrent HF events. Recurrent HF rate after the first HF hospitalization was 43% at 1 year, 52% at 2 years, and 55% at 2.5 years. Clinical signs and symptoms, medical treatment, or clinical management of HF at first HF admission was not predictive for HF2. Baseline covariates predicting recurrent HF hospitalization included prior HF hospitalization (HR = 1.59, 95% CI: 1.15–2.20, P = 0.005), digitalis therapy (HR = 1.58, 95% CI: 1.13–2.20, P = 0.008), and left ventricular end‐diastolic volume >240 mL (HR = 1.62, 95% CI: 1.17–2.25, P = 0.004). Conclusions: Recurrent HF events are frequent following the first HF hospitalization in patients with implanted implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Neither clinical presentation nor clinical management during first HF admission was predictive of recurrent HF. Prior HF hospitalization, digitalis therapy, and left ventricular end‐diastolic volume at enrolment predicted recurrent HF hospitalization, and these covariates could be used as surrogate markers for identifying a high‐risk cohort

Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF

Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. URL: https://clinicaltrials.gov Unique Identifier: NCT01920711

De novo implantation vs. upgrade cardiac resynchronization therapy: a systematic review and meta-analysis

Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy (CRT). Our aim was to summarize the available evidences regarding the clinical benefits of upgrade procedures. A systematic literature search was performed from studies published between 2006 and 2017 in order to compare the outcome of CRT upgrade vs. de novo implantations. Outcome data on all-cause mortality, heart failure events, New York Heart Association (NYHA) Class, QRS narrowing and echocardiographic parameters were analysed. A total of 16 reports were analysed comprising 489,568 CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade procedures. All-cause mortality was similar after CRT upgrade compared to de novo implantations (RR 1.19, 95% CI 0.88-1.60, p = 0.27). The risk of heart failure was also similar in both groups (RR 0.96, 95% CI 0.70-1.32, p = 0.81). There was no significant difference in clinical response after CRT upgrade compared to de novo implantations in terms of improvement in left ventricular ejection fraction (DeltaEF de novo - 6.85% vs. upgrade - 9.35%; p = 0.235), NYHA class (DeltaNYHA de novo - 0.74 vs. upgrade - 0.70; p = 0.737) and QRS narrowing (DeltaQRS de novo - 9.6 ms vs. upgrade - 29.5 ms; p = 0.485). Our systematic review and meta-analysis of currently available studies reports that CRT upgrade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy. Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT upgrade may be safely and effectively offered in routine practice. CLINICAL TRIAL REGISTRATION: Prospero Database-CRD42016043747

Cardiac resynchronisation therapy: current benefits and pitfalls

Cardiac resynchronisation therapy (CRT) has been shown to reduce all-cause mortality, heart failure events, and symptoms while improving exercise capacity and quality of life. Nevertheless, despite a large number of multicentre randomised trials and clear evidence confirming the above, there is still a higher number of patients who fail to develop reverse remodelling. In order to select the optimal patient population, the current European Society of Cardiology guidelines recommend a simultaneous evaluation of QRS morphology and width. However, based on recent data, QRS width itself is a less accurate parameter in the prediction of the outcome, as compared to QRS morphology. Furthermore, the baseline left ventricular (LV) ejection fraction (LVEF), which is also an known criterion for selecting CRT candidates (partly applied due to cost-benefit reasons), can be misleading. Data showed that patients with LVEF > 35% might also benefit from this type of treatment. Thus, LVEF should be evaluated less rigorously when screening patients for resynchronisation therapy. While the subsequent beneficial response to CRT is multifactorial, procedure-related parameters, such as LV lead position, are also crucial. The first data released recently confirmed the previous empiric clinical experience indicating that the LV lead should be implanted into the lateral or posterior coronary sinus side branch. This location was associated with a better long-term clinical outcome in terms of death and heart failure events. Some issues related to CRT are awaiting further clarification, such as the choice of the type of the implanted device (pacemaker or defibrillator) or the decision about CRT device upgrade. This review discusses the current evidence regarding the above, focusing on the questions that should be handled with caution or require clarification

Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left bundle branch block patients

Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline

Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left bundle branch block patients

AIMS: Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro–B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline. METHODS AND RESULTS: Heart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23–0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23–1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28–36%; P<0.001), NT-proBNP (2771–1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11–0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16–0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients. CONCLUSION: Left bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome