Impact of percutaneous mitral valve repair using the MitraClip™ system on ventricular arrhythmias and ICD therapies

Transcatheter edge-to-edge repair (TEER) using the MitraClip™ device has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high or prohibitive surgical risk. Only limited information regarding the impact of TEER on ventricular arrhythmias (VA) has been reported. The aim of the present study was to assess the impact of TEER using the MitraClip(TM) device on the burden of VA and ICD (Implantable Cardioverter Defibrillator) therapies. Among 600 MitraClip(TM) implantations performed in our clinic between September 2009 and October 2018, we identified 86 patients with successful TEER and an active implantable cardiac device (pacemaker, ICD, CRT-P/D (Cardiac Resynchronization Therapy-Pacemaker/Defibrillator)) eligible for retrospective VA analyses. These patients presented with mainly functional MR (81.4%) and severely reduced left ventricular ejection fraction (mean LVEF 22.1% ± 10.3%). The observation period comprised 456 ± 313 days before and 424 ± 287 days after TEER. The burden of ventricular arrhythmias (sustained ventricular tachycardia (sVT) and ventricular fibrillation (VF)) was significantly reduced after TEER (0.85 ± 3.47 vs. 0.43 ± 2.03 events per patient per month, p = 0.01). Furthermore, the rate of ICD therapies (anti-tachycardia pacing (ATP) and ICD shock) decreased significantly after MitraClip(TM) implantation (1.0 ± 3.87 vs. 0.32 ± 1.41, p = 0.014). However, reduction of VA burden did not result in improved two-year survival in this patient cohort with severely reduced LVEF. Mitral valve TEER using the MitraClip™ device was associated with a significant reduction of ventricular arrhythmias and ICD therapies

Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study

Background: Angiotensin converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. Methods and results: 4,723 out-patients with stable HFrEF prescribed either enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21,939 patient-years, 360 (49.5%), 337 (52.4%), and 1,119 (33.4%) patients died amongst those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality as compared with ramipril treatment (HR 1.46, 95% CI 1.30-1.65, p < 0.001, and HR 1.38, CI 1.22-1.56, p < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, p = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, p = 0.40; HR 1.12, 95% CI 0.96-1.32, p = 0.16; and HR 1.08, HR 1.10, 95% CI 0.93-1.31, p = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HFrEF, rhythm, and systolic blood pressure. Conclusion: Our results suggest that enalapril, lisinopril and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses

Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D). The comparative efficacy of individual SGLT2i remains unclear. We searched PubMed, www.clinicaltrials.gov and the Cochrane Central Register of Controlled Trials for randomised controlled trials exploring the use of canagliflozin, dapagliflozin, empagliflozin or ertugliflozin in patients with T2D. Comparators included placebo or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality and worsening heart failure (HF). Evidence was synthesised using network meta-analysis (NMA). Sixty-four trials reporting on 74,874 patients were included. The overall quality of evidence was high. When compared with placebo, empagliflozin and canagliflozin improved all three endpoints, whereas dapagliflozin improved worsening HF. When compared with other SGLT2i, empagliflozin was superior for all-cause and cardiovascular mortality reduction. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Ertugliflozin had no effect on any of the three endpoints investigated. Sensitivity analyses including extension periods of trials or excluding studies with a treatment duration of < 52 weeks confirmed the main results. Similar results were obtained when restricting mortality analyses to patients included in cardiovascular outcome trials (n = 38,719). Empagliflozin and canagliflozin improved survival with empagliflozin being superior to the other SGLT2i. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Prospective head-to-head comparisons would be needed to confirm these results

Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe

Objective: To describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries. Methods: We identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995–2005 vs period 2: 2006–2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses. Results: Among 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33–105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics. Conclusion: Ambulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF

Statins attenuate but do not eliminate the reverse epidemiology of total serum cholesterol in patients with non-ischemic chronic heart failure

© 2017 Elsevier B.V. Background In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival – while statin usage is not. The impact of statin treatment on the “reverse epidemiology” of cholesterol is unclear. Methods 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. Results 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤ 3.6 mmol/L), moderate (3.7–4.9 mmol/L), high (4.8–6.2 mmol/L), and very high ( >  6.2 mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p  <  0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77–0.90, p  <  0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p  <  0.001). Conclusions Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF

Comparative effectiveness of loop diuretics on mortality in the treatment of patients with chronic heart failure – a multicenter propensity score matched analysis

Background: Loop diuretics are given to the majority of patients with chronic heart failure (HF). Whether the different pharmacological properties of the three guideline-recommended loop diuretics result in differential effects on survival is unknown. Methods: 6293 patients with chronic HF using either bumetanide, furosemide or torasemide were identified in three European HF registries. Patients were individually matched on both the respective propensity scores for receipt of the individual drug and dose-equivalents thereof. Results: During a follow-up of 35,038 patient-years, 652 (53.7%), 2179 (51.9%), and 268 (30.4%) patients died amongst those prescribed bumetanide, furosemide, and torasemide, respectively. In univariable analyses of the general sample, bumetanide and furosemide were both associated with higher mortality as compared with torasemide treatment (HR 1.50, 95% CI 1.31–1.73, p &lt; 0.001, and HR 1.34, CI 1.18–1.52, p &lt; 0.001, respectively). Mortality was higher in bumetanide users when compared to furosemide users (HR 1.11, 95% CI 1.02–1.20, p = 0.01). However, there was no significant association between loop diuretic choice and all-cause mortality in any of the matched samples (bumetanide vs. furosemide, HR 1.03, 95% CI 0.93–1.14, p = 0.53; bumetanide vs. torasemide, HR 0.98, 95% CI 0.78–1.24, p = 0.89; furosemide vs. torasemide, HR 1.02, 95% CI 0.84–1.24, p = 0.82). The results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HF, rhythm, and systolic blood pressure. Conclusions: In patients with HF, mortality is not affected by the choice of individual loop diuretics

Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure

© 2017, Springer-Verlag Berlin Heidelberg. Aims: Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. Methods and results: 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71–0.91, p  <  0.01, and HR 0.86, 95% CI 0.78–0.94, p  <  0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82–1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76–1.06; p = 0.20; HR 1.10, 95% CI 0.93–1.31, p = 0.24; and HR 1.08, 95% CI 0.95–1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. Conclusion: Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF

Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy?

Background: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. Methods and results: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > −5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p  −10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. Conclusion: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters