Fioretti, Francesco

Abstract Background and Aims Whether hemodynamic and symptomatic benefits of the APTURE left atrial-to-coronary sinus shunt translate into clinical outcome benefit in heart failure with left ventricular ejection fraction >40% remains unknown. Methods In this post hoc analysis of ALT-FLOW EFS patients undergoing APTURE implantation, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score-predicted 1-year all-cause mortality was compared with observed mortality by Kaplan-Meier analysis of adjudicated events. Heart failure hospitalization (HFH) rates were compared for the 12 months before vs after implantation. Additional analyses included stratification by baseline sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and N-terminal pro-B-type natriuretic peptide (NT-proBNP), recurrent HFH cumulative hazard estimation (Nelson-Aalen), and H2FPEF score calculation. Results Among 95 patients (mean age 70.9 ± 8.5 years; 50% women; 93% New York Heart Association Class III; 85.9% with H2FPEF score >3), MAGGIC-predicted 1-year mortality was 13.0%. Observed 1-year survival was significantly higher than predicted (94.7% vs 87.0%; P=0.04), consistent across SGLT2i subgroups (log-rank P=0.59). The proportion of patients with HFH declined from 37.9% pre implantation to 9.6% post implantation (P<0.0001), with event rates falling from 0.61 to 0.21 per patient-year (P<0.001) and a 1-year cumulative hazard of recurrent HFH of 0.19 (95% confidence interval, 0.12-0.31). HFHs were evenly distributed across NT-proBNP strata. Conclusions In ALT-FLOW EFS, observed 1-year mortality was lower than MAGGIC-predicted mortality, and post implantation HFH rates were lower than pre implantation rates. These hypothesis-generating findings will require confirmation in the randomized, sham-controlled ALT-FLOW II trial.

Abstract Introduction Left atrial-to-coronary sinus (LA-to-CS) shunting through the APTURE transcatheter shunt system aims to unload the LA while preserving the interatrial septum. This article aims to examine the 3-year health status, functional capacity, and clinical outcomes of the ALT-FLOW Early Feasibility Study (EFS). Methods Device safety, patency, and echocardiographic parameters, but also symptoms, health status, and exercise capacity were assessed in patients with left ventricular ejection fraction (LVEF) > 40% (n & 95). Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score predicted 3-year all-cause mortality was compared with observed mortality assessed by Kaplan–Meier analysis using adjudicated events. Predicted and observed HF hospitalization (HFH)-free survival rates were also compared. Results At 3 years, the safety profile remained stable with no new safety signals, and all implanted shunts remained patent. 76.3% of patients improved by at least one NYHA class, and mean KCCQ Overall Summary Scores increased by 25 points from baseline (P < .0001). The 6-min walk distance improved by an average of 39 m (P & .002). These benefits were consistent regardless of baseline pulmonary vascular resistance (PVR). Right heart echocardiographic parameters after 3 years were stable, though a reduction in TAPSE was observed, primarily in the high PVR subgroup. The observed 3-year survival was significantly higher than the MAGGIC-predicted survival (84.4% vs 70.2, respectively; P & .009), as well as the HFH-free survival (68.0% vs 24.0%, respectively; P < 0001). Conclusion In patients with HF and LVEF >40%, the APTURE LA-to-CS shunting confirmed an acceptable safety profile with stable right heart parameters and sustained improvements in symptoms, quality of life, and functional capacity at 3 years. Observed survival and HFH were superior to MAGGIC predictions.

Abstract Background and Aims In the VICTOR trial (NCT05093933), vericiguat was neutral for the primary composite endpoint of cardiovascular death or hospitalization for heart failure (HF). VICTOR was powered to independently assess cardiovascular death. This study reports detailed analysis on the effects of vericiguat on mortality. Methods VICTOR, a double-blind, placebo-controlled, randomized trial, enrolled 6105 ambulatory patients with HF and reduced ejection fraction (HFrEF) without recent worsening and randomized them to vericiguat or placebo. The main outcome for this analysis was the pre-specified secondary endpoint of cardiovascular death. All-cause death, sudden cardiac death, and death related to HF were also assessed. Results Over a median of 19.7 months (inter-quartile range 14.6–25.4), cardiovascular deaths occurred in 292 patients (5.7 deaths per 100 patient-years) and 346 patients (6.8 deaths per 100 patient-years) in the vericiguat and placebo groups, respectively (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71–0.97; P = .020). Risk of death from any cause was lower with vericiguat vs placebo (377 [7.3 deaths per 100 patient-years] vs 440 [8.6 deaths per 100 patient-years]; HR 0.84, 95% CI 0.74–0.97; P = .015). Sudden cardiac death and HF-related deaths were lower with vericiguat vs placebo (1.6 vs 2.2 events per 100 patient-years; HR 0.75, 95% CI 0.56–0.99; P = .042 and 1.7 vs 2.4 events per 100 patient-years; HR 0.71, 95% CI 0.54–0.94; P = .016, respectively). Lower mortality rates were consistent across subgroups including baseline therapy. Consistent cardiovascular and all-cause mortality benefit was seen across baseline N-terminal pro-B-type natriuretic peptide levels. Conclusions In ambulatory well-treated participants with HFrEF, vericiguat was associated with clinically meaningful reductions in the key secondary outcome of cardiovascular death, as well as all-cause mortality.

Abstract Heart failure with reduced or preserved ejection fraction is associated with elevated left atrial pressure at rest due to fluid overload or during exercise, leading to pulmonary venous congestion. Even with available treatments, heart failure hospitalizations remain high, and improvements in quality-of-life scores and functional capacity are modest. Thus, there is growing interest in non-pharmacological methods to decompress the left atrium and improve heart failure symptoms and outcomes. Left-to-right shunts have emerged as a potential therapeutic option to reduce left atrial hypertension, improve quality of life, and impact long-term outcomes. This nascent field carries both potential therapeutic promise and many unanswered questions. Recent data have questioned whether the effects of this therapy vary based on the left ventricular ejection fraction, pulmonary vascular resistance, and/or right ventricular structure and function. This review discusses the basis for left-to-right shunt therapies, synthesizes past and ongoing clinical trials, and offers future directions.