No abstract

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

Heart failure (HF) is a systemic illness with grave implications for bodily functions. The brain, among other vital organs, often suffers insults as a result of HF, and both anatomic and functional brain abnormalities were found in the HF population. This injury was demonstrated across a wide range of clinical conditions and cardiac functions and was shown to affect patients' outcomes. Although reduced cardiac output and high burden of cardiovascular risk factors are the prevailing explanations for these findings, there are data showing the involvement of neurohormonal, nutritional, and inflammatory mechanisms in this complex process. Here, the authors review the suggested pathophysiology behind brain injury in HF, describe its effect on patients' outcomes, offer a diagnostic approach, and discuss possible therapeutic options.

Analysis of carotid waveforms using intrinsic frequency methods can be used to document left ventricular ejection fraction with accuracy comparable with that of MRI. The measurements require no training to perform or interpret, no calibration, and can be repeated at the bedside to generate almost continuous analysis of left ventricular ejection fraction without arterial cannulation.