Circulation: Heart Failure最新文献

Background: The mechanism of cardiac reverse remodeling (CRR) mediated by the left ventricular assist device remains unclear. This study aims to identify the specific cell type responsible for CRR and develop the therapeutic target that promotes CRR.

Methods: The nuclei were extracted from the left ventricular tissue of 4 normal controls, 4 CRR patients, and 4 no cardiac reverse remodeling patients and then subjected to single-nucleus RNA sequencing for identifying key cell types responsible for CRR. Gene overexpression in transverse aortic constriction and dilated cardiomyopathy heart failure mouse model (C57BL/6J background) and pathological staining were performed to validate the results of single-nucleus RNA sequencing.

Results: Ten cell types were identified among 126 156 nuclei. Cardiomyocytes in CRR patients expressed higher levels of ATP5F1A than the other 2 groups. The macrophages in CRR patients expressed more anti-inflammatory genes and functioned in angiogenesis. Endothelial cells that elevated in no cardiac reverse remodeling patients were involved in the inflammatory response. Echocardiography showed that overexpressing ATP5F1A through cardiomyocyte-specific adeno-associated virus 9 demonstrated an ability to improve heart function and morphology. Pathological staining showed that overexpressing ATP5F1A could reduce fibrosis and cardiomyocyte size in the heart failure mouse model.

Conclusions: The present results of single-nucleus RNA sequencing and heart failure mouse model indicated that ATP5F1A could mediate CRR and supported the development of therapeutics for overexpressing ATP5F1A in promoting CRR.

Background: Caregivers of patients with advanced heart failure may experience burden in providing care, but whether changes in patient health status are associated with caregiver burden is unknown.

Methods: This observational study included older patients (60-80 years old) receiving advanced surgical heart failure therapies and their caregivers at 13 US sites. Patient health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (range, 0-100; higher scores are better). Caregiver burden was assessed using the Oberst Caregiving Burden Scale, which measures time on task (OCBS-time) and task difficulty (OCBS-difficulty; range, 1-5; lower scores are better). Measurements occurred before surgery and 12 months after in 3 advanced heart failure cohorts: patients receiving long-term left ventricular assist device support; heart transplantation with pretransplant left ventricular assist device support; and heart transplantation without pretransplant left ventricular assist device support. Multivariable linear regression was used to identify predictors of change in OCBS-time and OCBS-difficulty at 12 months.

Results: Of 162 caregivers, the mean age was 61.0±9.4 years, 139 (86%) were female, and 140 (86%) were the patient's spouse. At 12 months, 99 (61.1%) caregivers experienced improved OCBS-time, and 61 (37.7%) experienced improved OCBS-difficulty (versus no change or worse OCBS). A 10-point higher baseline 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (β=-0.09 [95% CI, -0.14 to -0.03]; P<0.001) and OCBS-difficulty (β=-0.08 [95% CI, -0.12 to -0.05]; P<0.001). Each 10-point improvement in the 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (β=-0.07 [95% CI, -0.12 to -0.03]; P=0.002) and OCBS-difficulty (β=-0.09 [95% CI, -0.12 to -0.06]; P<0.001).

Conclusions: Among survivors at 12 months, baseline and change in patient health status were associated with subsequent caregiver time on task and task difficulty in dyads receiving advanced heart failure surgical therapies, highlighting the potential for serial 12-item Kansas City Cardiomyopathy Questionnaire assessments to identify caregivers at risk of increased burden.

Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT02568930.

Background: Caring for someone with heart failure takes an emotional and physical toll. Engaging in self-care may decrease stress and improve the health of informal caregivers. We conducted a randomized controlled trial testing the efficacy of a virtual health coaching intervention, compared with health information alone, on the self-care, stress, coping, and health status of heart failure caregivers.

Methods: We enrolled 250 caregivers providing care at least 8 hours/week, reporting poor self-care, and able to use technology. All received a tablet device programmed with websites providing vetted information on heart failure and caregiving. Half were randomized to also receive 10 synchronous support sessions virtually with a health coach over 6 months. Data on self-care, stress, coping, and health status were collected at baseline and 3 and 6 months. Linear mixed-effects models were used to assess the interaction between time and treatment group.

Results: The sample was majority female (85.2%), White (62.2%), spouses (59.8%), and aged 55±13.6 years. Many were employed full time (41.8%). They had been caring for the patient 8 hours/day for a median of 3.25 years. In the intention-to-treat analysis, caregivers who received the health coach intervention had statistically and clinically greater improvement across 6 months compared with the control group in the primary outcome of self-care maintenance (5.05±1.99; P=0.01) and stress (-4.50±1.00; P<0.0001). Self-care neglect declined significantly (-0.65±0.32; P=0.04), but the difference between the treatment arms disappeared when the results were adjusted for multiple comparisons. Mental health status improved statistically but not clinically (3.35±1.61; P=0.04). Active coping improved in both groups but not significantly more in the intervention group (P=0.10). Physical health status was unchanged (P=0.27).

Conclusions: This virtual health coaching intervention was effective in improving self-care and stress in heart failure caregivers.

Background: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity.

Methods: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters.

Results: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure (P=0.043), hepatic injury (P=0.049), and suspected/definite infection (P=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P=0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; P_adj=0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; P_adj<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; P_adj=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; P_adj=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; P_adj=0.008).

Conclusions: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.

Background: LMNA (lamin A/C)-related dilated cardiomyopathy is a rare genetic cause of heart failure. In a phase 2 trial and long-term extension, the selective p38α MAPK (mitogen-activated protein kinase) inhibitor, ARRY-371797 (PF-07265803), was associated with an improved 6-minute walk test at 12 weeks, which was preserved over 144 weeks.

Methods: REALM-DCM (NCT03439514) was a phase 3, randomized, double-blind, placebo-controlled trial in patients with symptomatic LMNA-related dilated cardiomyopathy. Patients with confirmed LMNA variants, New York Heart Association class II/III symptoms, left ventricular ejection fraction ≤50%, implanted cardioverter-defibrillator, and reduced 6-minute walk test distance were randomized to ARRY-371797 400 mg twice daily or placebo. The primary outcome was a change from baseline at week 24 in the 6-minute walk test distance using stratified Hodges-Lehmann estimation and the van Elteren test. Secondary outcomes using similar methodology included change from baseline at week 24 in the Kansas City Cardiomyopathy Questionnaire-physical limitation and total symptom scores, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration. Time to a composite outcome of worsening heart failure or all-cause mortality and overall survival were evaluated using Kaplan-Meier and Cox proportional hazards analyses.

Results: REALM-DCM was terminated after a planned interim analysis suggested futility. Between April 2018 and October 2022, 77 patients (aged 23-72 years) received ARRY-371797 (n=40) or placebo (n=37). No significant differences (P>0.05) between groups were observed in the change from baseline at week 24 for all outcomes: 6-minute walk test distance (median difference, 4.9 m [95% CI, -24.2 to 34.1]; P=0.82); Kansas City Cardiomyopathy Questionnaire-physical limitation score (2.4 [95% CI, -6.4 to 11.2]; P=0.54); Kansas City Cardiomyopathy Questionnaire-total symptom score (5.3 [95% CI, -4.3 to 14.9]; P=0.48); and NT-proBNP concentration (-339.4 pg/mL [95% CI, -1131.6 to 452.7]; P=0.17). The composite outcome of worsening heart failure or all-cause mortality (hazard ratio, 0.43 [95% CI, 0.11-1.74]; P=0.23) and overall survival (hazard ratio, 1.19 [95% CI, 0.23-6.02]; P=0.84) were similar between groups. No new safety findings were observed.

Conclusions: Findings from REALM-DCM demonstrated futility without safety concerns. An unmet treatment need remains among patients with LMNA-related dilated cardiomyopathy.

Registration: URL: https://classic.clinicaltrials.gov; Unique Identifiers: NCT03439514, NCT02057341, and NCT02351856.

Background: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support.

Methods: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality.

Results: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times (P<0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P=0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P=0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P<0.001).

Conclusions: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered.