Sundaram, Varun

Objective To evaluate the clinical effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in reducing the risk of hospital admission for heart failure and mortality in a contemporary nationwide cohort of patients with heart failure with preserved ejection fraction (HFpEF). Design Nationwide cohort study (REFINE-HFpEF). Setting 170 veteran health medical centres across the US, 1 January 2014 to 31 December 2021. Participants 2177 patients with type 2 diabetes and HFpEF; 1129 patients were newly prescribed SGLT2 inhibitors and 1048 were newly prescribed dipeptidyl peptidase 4 (DPP4) inhibitors or sulfonylureas. Main outcome measures The primary outcome was a composite of all cause mortality and hospital admission for heart failure. Secondary outcomes included all cause mortality only and serial changes in body weight. Hazard ratios were derived from Cox proportional hazards models, incorporating inverse probability of treatment weighting based on propensity scores to account for confounding. Results From a validated cohort of 179 288 patients with type 2 diabetes and HFpEF, the study included 1129 new users of SGLT2 inhibitors (active treatment) and 1048 new users of DPP4 inhibitors or sulfonylureas (comparators). After a median follow-up of 2.63 years, 46.4% of the study population had at least one hospital admission for heart failure (n=1011) and the overall mortality rate was 45.9% (n=1000). Use of SGLT2 inhibitors was associated with a relative risk reduction in the primary composite outcome of 18% compared with the use of DPP4 inhibitors or sulfonylureas (hazard ratio 0.82, 95% confidence interval 0.70 to 0.96; P=0.01). The adjusted hazard ratio for all cause mortality only was 0.73 (0.60 to 0.89; P=0.002). Weight loss was similar in the two groups. Conclusions In this large, contemporary, nationwide cohort of patients with HFpEF, type 2 diabetes, and high event rates, starting SGLT2 inhibitors was associated with a significantly lower risk of hospital admission for heart failure and all cause mortality compared with starting treatment with DPP4 inhibitors or sulfonylureas.

BACKGROUND: With evolving therapy for heart failure with reduced ejection fraction, the benefits of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT) remain unclear, particularly for nonischemic cardiomyopathy (NICM). This study evaluates long-term survival among patients with NICM treated with CRT defibrillator (CRT-D) versus CRT pacemaker (CRT-P). METHODS: DECIDE-CRT (Cardiac Resynchronization With or Without Defibrillator in Non-Ischemic Cardiomyopathy) is a multicenter cohort study across 170 US Veterans Affairs hospitals. We identified patients with NICM receiving primary-prevention CRT-P or CRT-D between January 1, 2006, and December 31, 2020. Using a propensity score approach, we applied inverse probability of treatment weighting to balance baseline characteristics between the CRT-P and CRT-D groups. An inverse probability of treatment weighting–weighted Cox model estimated hazards for all-cause mortality. Secondary outcomes included generator replacement, device-related infections, hospitalization for heart failure, and ventricular arrhythmias. RESULTS: Of 16 609 CRT recipients, 3965 met NICM primary-prevention criteria (CRT-D=3158; CRT- P =807). At baseline, patients with NICM receiving CRT-P were much older, with more cardiovascular and noncardiovascular comorbidities compared with the CRT-D group. During the median follow-up of 5.2 years, the mortality rate for CRT-P versus CRT-D was 9.46 versus 9.21 per 100 person-years (RR, 0.97 [95% CI, 0.71–1.13]; P =0.66). The adjusted hazard ratio for all-cause mortality using the inverse probability of treatment weighting-Cox model was 0.90 (95% CI, 0.71–1.13; P =0.34). There was no difference in adjusted hazard for heart failure hospitalization (hazard ratio, 1.27 [95% CI, 0.86–1.87]), while the CRT-D group had higher rates of generator replacement and device-related infections. CONCLUSIONS: This nationwide observational study from the Veterans Affairs Health system did not demonstrate a clear survival advantage with the addition of a defibrillator among patients with NICM receiving CRT although residual confounding cannot be excluded. Given the uncertainty surrounding the incremental benefit of the defibrillator in this setting, a randomized trial is needed to test the incremental value of CRT-D over CRT-P in NICM.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised to be strongly associated with obesity and abnormalities in fat distribution. Epicardial fat has been associated with abnormal haemodynamics in HFpEF, with potential for direct mechanical effects on the heart causing constriction-like physiology and local myocardial remodelling effects from secretion of inflammatory and profibrotic mediators. However, patients with epicardial fat generally have more systemic and visceral adipose tissue making determination of causality between epicardial fat and HFpEF complex. In this review, we will summarise the evidence for epicardial fat being either directly causal in HFpEF pathogenesis or merely being a correlate of worse systemic inflammatory and generalised adiposity. We will also discuss therapies that directly target epicardial fat and may have potential for treating HFpEF and elucidating the independent role of epicardial fat in its pathogenesis.

Aims Despite the common occurrence of coronary artery disease (CAD) and heart failure (HF) with preserved ejection fraction (HFpEF), there is limited evidence to guide revascularization. Methods and Results We investigated the long‐term outcomes of coronary artery bypass grafting (CABG) in patients with HF and significant CAD across the spectrum of ejection fraction, using a large national cohort of patients from the Veteran Affairs (VA) Medical Centers in the US. Patients with HF were stratified into groups, HFpEF, HF with mid‐range ejection fraction (HFmrEF), and HF with reduced ejection fraction (HFrEF) and compared to patients with no preoperative HF. We analysed 10 396 patients. Despite an increased hazard in the first year following revascularization, the long‐term survival (median follow‐up 6.6 years; interquartile range 3.7–10.1) of HFpEF post‐CABG was similar to controls (hazard ratio 0.85, 95% confidence interval 0.68‐1.06), but survival progressively declined with HFmrEF and HFrEF. Similar trends were seen with recurrent HF hospitalization with lower risk with baseline HFpEF (43.9 ± 6.9/100 patient‐years) compared to HFmrEF (65.9 ± 3.8/100 patient‐years) and HFrEF (93.4 ± 4.8/100 patient‐years). Although HFpEF patients had lower mortality and HF hospitalization post‐CABG compared to patients with a lower ejection fraction, they experienced the highest rates of future myocardial infarction. Conclusion Although HFpEF patients with CAD have greater short‐term risk post‐CABG, their long‐term survival is comparable to controls. However, they are at increased risk for HF hospitalizations and myocardial infarction. These data support the safety of CABG in HFpEF patients and suggest continuum of mortality risk for ischaemic HF when stratified by baseline ejection fraction before revascularization.

Objective Bioprosthetic valves are being used with increased frequency for valve replacement, with controversy regarding risk:benefit ratio compared with mechanical valves in younger patients. However, prior studies have been too small to provide comparative estimates of less common but serious adverse events such as infective endocarditis. We aimed to compare the incidence of infective endocarditis between bioprosthetic valves and mechanical valves. Methods We searched PubMed, Cochrane, EMBASE, Scopus and Web of Science from inception to April 2018 for studies comparing left-sided aortic and mitral bioprosthetic to mechanical valves for randomised trials or observational studies with propensity matching. We used random-effects model for our meta-analysis. Our primary outcome of interest was the rate of infective endocarditis at follow-up. Results 13 comparison groups with 43 941 patients were included. Mean age was 59±7 years with a mean follow-up of 10.4±5.0 years. Patients with bioprosthetic valves had a higher risk of infective endocarditis compared with patients receiving mechanical valves (OR 1.59, 95% CI 1.35 to 1.88, p<0.001) with an absolute risk reduction of 9 per 1000 (95% CI 6 to 14). Heterogeneity within the included studies was low (I2=0%). Exclusion of the study with maximum weight did not change the results of the analysis (OR 1.57, 95% CI 1.14 to 2.17, p=0.006). A meta-regression of follow-up time on incidence of infective endocarditis was not statistically significant (p=0.788) indicating difference in follow-up times did not alter the pooled risk of infective endocarditis. Conclusions Bioprosthetic valves may be associated with a higher risk of infective endocarditis. These data should help guide the discussion when deciding between bioprosthetic and mechanical valves in individual patients.

A 33-year-old male with systemic lupus erythematosus (SLE) presented with acute abdominal pain and was found to have lupus mesenteric vasculitis on imaging and during exploratory laparotomy. Post laparotomy he continued to have persistent nausea and dyspepsia and an electrocardiogram showed evidence of an inferior ST elevation myocardial infarction (STEMI). Emergency cardiac catheterization showed evidence of thrombotic right coronary artery occlusion. His coronaries were otherwise normal with no evidence of underlying coronary artery disease. Extensive workup with trans-esophageal echo, serologies for antiphospholipid antibody syndrome (APS) and bubble study was negative. This effectively ruled out Libman–Sacks endocarditis, APS-induced arterial thrombus and paradoxical emboli as potential causes of his STEMI. By exclusion of other causes, the etiology of his STEMI was felt to be secondary to in-situ coronary artery thrombosis in the setting of active SLE. To the best of our knowledge, this is the first report of a patient with SLE presenting with both lupus mesenteric vasculitis and in-situ coronary arterial thrombosis in the absence of APS.