Currently, limited guideline-directed medical therapies are available for heart failure (HF) with preserved and mildly reduced ejection fraction (EF). Both are associated with an increased risk of hospitalization and death, especially in overweight, obese, or diabetic individuals. We searched Cochrane, Embase, and MEDLINE from inception to November 2024. Trials with HF patients randomized for GLP-1RA (glucagon-like peptide-1 receptor agonists) and reported adverse cardiovascular and mortality outcomes were included. Statistical analysis was performed using Cochrane Review Manager 5.4.1. 4474 patients with HF (preserved and mildly reduced EF) were included in the study. 2278 (50.91 %) received a GLP-1RA [either semaglutide (1914, 84 %) or Tirzepatide (364, 16 %)], and 2196 (49.01 %) received a placebo. GLP-1RA reduced the composite event of cardiovascular mortality and worsening HF exacerbation [139 vs. 194, RR: 0.64 (95 % CI: 0.45-0.92)]. However, on subgroup analysis, there was no significant difference in cardiovascular (CV) deaths [67 vs. 71, RR 0.89 (95 % CI: 0.65-1.24)]. The HF exacerbations were significantly reduced in the GLP-1RA group [83 vs. 138, RR 0.59 (95 % CI: 0.45-0.76)]. Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) was favorable for GLP-1RA [Std Mean Difference (SMD): 7.38 (95 % CI: 5.51-9.26)], reflected by an increase in 6-min walk distance in GLP-1RA groups [SMD: 17.69 (95 % CI: 11.87-23.34)] and contributed by a decrease in body weight in GLP-1RA groups [SMD -9.56 (95 % CI -12.74 to -6.39)]. GLP-1RA reduce HF exacerbations and can play a role in reducing hospitalizations, improving patient's functional status, and significantly impacting the global healthcare burden of HF. However, the current data does not indicate any overall mortality benefit.

Cardiac pacing has undergone a significant transformation in the last decade. Leadless pacing (LP), once only a conceptual idea stemming from the early interest in eliminating lead-related complications of transvenous pacemakers, has now become a reality in clinical practice. Since the introduction of the first human single-chamber asynchronous leadless ventricular pacing in 2012, atrioventricular-synchronized single- or dual-chamber leadless pacing systems have been approved for clinical use since 2020. Leadless cardiac resynchronization therapy (CRT) has shown optimistic results in case series and awaits its full utility in real-world clinical practice. With the successful feasibility study of leadless conduction system pacing, we are eagerly awaiting long-term safety and efficacy data on a large scale. Another important frontier is the development of self-rechargeable LP, which may be an ideal pacemaker for the future and may reduce the burden of multiple device replacements as batteries near the end-of-service. Totally extravascular percutaneous leadless pericardial micro-pacemaker system implantation is under development. In this state-of-the-art review, we examine the evolution of cardiac pacing, emphasizing the development and utility of LP to meet maximum physiological pacing needs, optimize atrioventricular synchrony and cardiac resynchronization, and broaden its indications.