Circulation: Heart Failure最新文献

Background: People with HIV (PWH) may have a higher risk of heart failure (HF) due to traditional and HIV-related factors. Incidence and risk prediction of HF in PWH are not well characterized. We aimed to quantify the risk of HF events in a global population of PWH with low-to-moderate estimated atherosclerotic cardiovascular disease risk.

Methods: HF incidence (events/1000 person years) was described overall and by demographic, HIV-specific, and HF factors, including estimated Predicting Risk of Cardiovascular Disease Events 10-year risk of HF. Confirmed HF events included adjudicated HF hospitalization and adverse events identified via a standardized Medical Dictionary for Regulatory Archives HF query.

Results: We analyzed 7769 REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) participants from 5 global regions (median, 50 years; 31% female). Over a median follow-up of 5.6 years (interquartile range, 4.3-5.9), HF incidence was higher in women, among Black participants in high-income regions, participants in sub-Saharan Africa, and among those with preexisting hypertension and obesity compared with the absence of these factors. Current and nadir CD4+T-cell count, and HIV-1 RNA level were not related to the incidence of HF events. Median (Q1-Q3) Predicting Risk of Cardiovascular Disease Events HF score was 1.66% (1.01-2.62). HF incidence was 1.65/1000 person-years (95% CI, 1.30-2.09). Expected number of HF events by Predicting Risk of Cardiovascular Disease Events HF (n=73) was consistent with observed (n=67).

Conclusions: Select demographics, clinical factors, and global regions contribute to a higher incidence of HF events among PWH. In PWH, the observed overall number of HF events aligned with the estimated Predicting Risk of Cardiovascular Disease Events HF risk rates.

Background: In patients with right ventricular (RV) outflow tract stenosis and pulmonary regurgitation (PR), percutaneous pulmonary valve implantation (PPVI) aims to preserve RV and left ventricular (LV) integrity and function. Our study aimed to assess acute changes in biventricular intrinsic myocardial function occurring with PPVI.

Methods: Twenty patients with RV outflow tract dysfunction (mean±1 SD; age, 23.0±10.9 years; mean peak echocardiographic RV outflow tract gradient, 64±25 mm Hg) underwent PPVI with biventricular assessment of pressure-volume loops using the conductance catheter technique during the same cardiac catheterization. Load-independent parameters of ventricular contractility (ventricular elastance) and ventricular compliance function, as well as pulmonary/systemic arterial elastance and ventriculoarterial coupling, were assessed before and directly after PPVI. Cardiac magnetic resonance for quantification of biventricular volumes, function, and PR was also performed.

Results: After PPVI, both RV ventricular elastance (median [interquartile range], 0.26 [0.16-0.83]-0.19 [0.13-0.42] mm Hg/mL per m²; P=0.029) and pulmonary systemic arterial elastance (0.32±0.20-0.25±0.19 mm Hg/mL per m²; P<0.001) decreased significantly, while right ventriculoarterial coupling (1.14±0.61-1.10±0.59; P=0.76) did not change statistically significant. LV ventricular elastance (1.31±0.93-1.23±0.72 mm Hg/mL per m²; P=0.68) and left ventriculoarterial coupling (0.75 [0.51-1.23]-0.82 [0.53-1.10]; P=0.98) were not affected by PPVI although systemic arterial elastance increased significantly (0.83±0.26-0.90±0.34 mm Hg/mL per m²; P=0.032). Both RV (P=0.37) and LV (P=0.20) compliance showed no significant change after PPVI. Patients with relevant PR (≥25%; n=10) had lower RV ventricular elastance (P=0.043) before and higher LV compliance (P=0.010) after PPVI compared with patients with minor PR (<25%; n=10), whereas ventriculoarterial coupling was similar between the 2 groups.

Conclusions: Acute reduction of RV overload by PPVI is accompanied by an instantaneous decline in RV contractility with persistent and inefficient ventriculoarterial coupling. The LV adequately adapts to an increase in pre- and post-load with nonsignificant changes in LV intrinsic function and ventriculoarterial coupling. The relevance of these response patterns on long-term biventricular remodeling requires further investigation.

Background: Decompensated heart failure with reduced ejection fraction (HFrEF) is associated with systemic inflammation that predicts unfavorable outcomes. We aimed to determine whether anakinra, an IL-1 (interleukin-1) blocker, favors inflammation resolution (CRP [C-reactive protein]) and improves peak oxygen consumption (VO₂) in patients with recently decompensated HFrEF.

Methods: We randomized 102 adult patients recently hospitalized for HFrEF and CRP ≥2 mg/L (2:1) to receive anakinra 100 mg subcutaneously daily (n=68) or placebo for 24 weeks (n=34). The primary end point was the peak VO₂ change at 24 weeks. Data are presented as median (Q1, Q3) or number (%).

Results: Of the 102 patients, 84 had primary end point data available (57 treated with anakinra and 27 with placebo). Peak VO₂ increased from 13.0 (10.9, 17.0) to 14.9 (12.0, 18.0) mL·kg⁻¹·min⁻¹ (P<0.001) in the entire cohort, without significant differences between anakinra and placebo (+1.5 [-0.2, +3.4] and +1.2 [+0.5, +3.9] mL·kg⁻¹·min⁻¹, respectively; P=0.40; median difference +0.30 mL·kg⁻¹·min⁻¹ [95% CI from -1.70 to +0.90]). A significant reduction in CRP levels was seen, with a -76% (-87%, -36%) in anakinra-treated patients and -48% (-77%, +14%) in the placebo group (P=0.050 between groups). There were no unexpected treatment-related serious adverse events, and no differences in HFrEF events between groups. CRP<2 mg/L was achieved in 47% and 37% of the anakinra and placebo groups, respectively (P=0.48). Patients achieving CRP<2 mg/L had a significantly greater increase in peak VO₂ versus those with CRP≥2 mg/L (+2.6 [+0.7, +4.6] and +1.0 [-0.3, +1.9] mL·kg⁻¹·min⁻¹; P=0.007) and lower rates of HFrEF-related events (8% and 26%; P=0.045).

Conclusions: Patients with recently decompensated HFrEF treated with maximally tolerated medical therapy had a significant improvement in CRP and peak VO₂. The addition of anakinra had a modest effect on CRP levels and no significant effect on peak VO₂ or other clinically relevant secondary end points.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797001.

Inhibiting SGLT2 (sodium-glucose cotransporter 2) has recently transformed the medical care of patients with left heart disease. Right ventricular failure is a major predictor for patients suffering from pulmonary hypertension of various causes, including those with postcapillary pulmonary hypertension due to left heart disease. Similar to how SGLT2 inhibition benefits patients with left heart failure, recent studies have suggested utilizing these molecules to enhance right ventricular function in pulmonary hypertension. In this review, we summarize the current knowledge on the use of SGLT2is (SGLT2 inhibitors) in pulmonary hypertension. Further dedicated trials are necessary to establish their role in right ventricular pulmonary vascular disease.

Background: Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality in children, but treatment options are limited. Aficamten, a next-in-class cardiac myosin inhibitor, directly targets the hypercontractility underlying HCM. Aficamten improved exercise capacity, health status, and symptoms in adults with obstructive HCM in the pivotal, phase 3 SEQUOIA-HCM trial (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM; NCT05186818).

Methods: CEDAR-HCM (Clinical Evaluation of dosing With Aficamten to Reduce Obstruction in Pediatric Population With HCM) is an international, multicenter, randomized, double-blind, placebo-controlled trial followed by an open-label extension to evaluate the efficacy, safety, and pharmacokinetics of aficamten in pediatric participants with symptomatic obstructive HCM. The trial will enroll ≈55 adolescents (12 to <18 years) and subsequently expand to include at least 10 children (6 to <12 years) with nonsyndromic obstructive HCM, left ventricular ejection fraction ≥60%, Valsalva left ventricular outflow tract gradient ≥50 mm Hg, and New York Heart Association functional class ≥II. Participants will be randomized 2:1 to aficamten or placebo in addition to standard of care therapy or as monotherapy, with echocardiogram-guided dose adjustments targeting a Valsalva left ventricular outflow tract gradient <30 mm Hg while maintaining left ventricular ejection fraction ≥50%. The primary end point is the change in Valsalva left ventricular outflow tract gradient from baseline to week 12. Secondary end points include change in resting left ventricular outflow tract gradient, cardiac biomarkers, New York Heart Association functional class, and assessment of pharmacokinetics. After completing the 12-week randomized period, eligible participants will continue into a long-term open-label extension.

Results: The trial is currently enrolling.

Conclusions: Results of CEDAR-HCM will provide insight into the safety and efficacy of aficamten in adolescents and in children as young as 6 years of age.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06412666.

Background: Takotsubo cardiomyopathy is an acute cardiac emergency presenting with severe left ventricular dysfunction. Physical exercise training or cognitive behavioral therapy may enhance myocardial recovery after takotsubo cardiomyopathy.

Methods: In a prospective multicenter clinical trial conducted between February 2020 and August 2023, patients with acute takotsubo cardiomyopathy were randomized 1:1:1 to physical exercise training, cognitive behavioral therapy, or standard care for 12 weeks after index presentation. The primary end point was resting phosphocreatine/gamma-ATP ratio assessed by ³¹P-magnetic resonance spectroscopy. Secondary end points were the rate of oxygen consumption at peak exercise on cardiopulmonary exercise testing, 6-minute walk distance, left ventricular global longitudinal strain, and the Minnesota Living With Heart Failure Questionnaire. Twelve-week changes in outcome were compared between allocated trial interventions.

Results: Seventy-six participants were recruited: the median age was 66 years, and 91% were women. Compared with standard care, the primary end point of myocardial phosphocreatine/gamma-ATP ratio was improved by physical exercise training (0.4 [95% CI, 0.1-0.8]; P=0.016) and cognitive behavioral therapy (0.3 [0.01-0.7]; P=0.043). Both physical exercise training and cognitive behavioral therapy improved rate of oxygen consumption at peak exercise (4.7 [1.4-8.0] and 4.0 [1.5-6.4] mL/min per kg; P=0.001 and 0.004, respectively) and 6-minute walk distance (92.6 [24.7-160.6] and 73.3 [7.9-138.8] m; P=0.004 and 0.029, respectively) compared with standard care. There were no differences in global longitudinal strain or symptom burden.

Conclusions: In patients with acute takotsubo cardiomyopathy, a 12-week intervention with exercise training or cognitive behavioral therapy improved left ventricular myocardial energetics and exercise performance without demonstrable effects on symptoms of heart failure.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04425785.