Circulation: Heart Failure最新文献

Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events.

Methods: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no HF, normal biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide] <125 pg/mL; high sensitivity cardiac troponin T [hs-cTnT] <14 ng/L), and normal cardiac structure/function. Stage B (pre-HF): no HF but elevated NT-proBNP, hs-cTnT, or abnormal cardiac structure/function. Stage C/D: symptomatic HF. End points include the primary composite (cardiovascular death and HF-related events), major adverse cardiovascular events, and kidney-related composites (≥50% decline in estimated glomerular filtration rate, kidney failure, or kidney death). Using competing-risk proportional hazards models, we examined the association between HF stage and these end points, and the effect of sotagliflozin versus placebo by HF stage.

Results: There were 741 patients (7%) in stage A, 6560 (62%) in stage B (pre-HF), and 3283 (31%) in stage C/D (established HF). The median NT-proBNP and hs-cTnT increased with HF stage. Increasing HF stage was associated with a 2- to 4-fold increase in the primary outcome/major adverse cardiovascular events in the placebo group. The kidney-specific composite was 5-fold higher in stage B (pre-HF) versus stage A but similar in stages B and C/D. The effect of sotagliflozin versus placebo was similar, irrespective of HF stage (primary outcome: hazard ratio, 0.74 [95% CI, 0.63-0.88]; P_interaction=1.00), with higher absolute benefit in each HF stage (P-trend_IRR=0.002). The absolute benefit for the kidney-specific end point was comparable for stages B and C/D.

Conclusions: Increasing HF stage is associated with a higher risk of HF, major adverse cardiovascular events, and kidney events. Asymptomatic stage B (pre-HF) increased cardiovascular and renal events by >2- and 5-fold, respectively. The benefits of sotagliflozin are consistent, irrespective of HF stage.

Background: Mitral regurgitation (MR) is a frequent comorbidity in patients with hypertrophic cardiomyopathy (HCM), which includes distinct subtypes with various characteristics. However, data on the long-term prognostic impact of MR and its progression or regression over time remain limited, particularly across individual HCM subtypes.

Methods: Patients with HCM were retrospectively included from a Japanese multicenter registry and compared by MR severity (moderate or greater versus mild or less) within each subtype: hypertrophic obstructive cardiomyopathy (HOCM), end-stage HCM (ES-HCM), and other HCM (including nonobstructive, midventricular obstruction, and apical HCM).

Results: Among 3602 patients (HOCM: n=837; ES-HCM: n=275; other HCM: n=2490), the prevalence of moderate or greater MR was highest in HOCM (36.3%), followed by ES-HCM (21.5%) and other HCM (8.5%). During a median follow-up of 5.3 (interquartile range, 2.1-9.3) years, the cumulative 5-year incidence of all-cause death or heart failure hospitalization was not significantly different between the moderate or greater MR and mild or less MR groups in HOCM (14.6% versus 12.4%; P=0.35) or ES-HCM (60.7% versus 54.7%; P=0.84). After adjustment for clinical covariates, no significant association was observed in either subtype (HOCM: hazard ratio, 1.13 [95% CI, 0.79-1.60], P=0.51; ES-HCM: hazard ratio, 0.84 [95% CI, 0.55-1.28], P=0.42). In contrast, in other HCM, moderate or greater MR was significantly associated with the higher 5-year cumulative incidence of all-cause death or heart failure hospitalization (34.2% versus 13.9%, P<0.001), which remained significant after adjustment, with a significant interaction (hazard ratio, 1.45 [95% CI, 1.09-1.91], P=0.01; P_interaction=0.02). MR severity improved over time in HOCM, showed no clear change in ES-HCM, and worsened in other HCM (P<0.001, 0.46, and <0.001, respectively; P_interaction <0.001).

Conclusions: In patients with HCM, moderate or greater MR was not associated with worse outcomes in HOCM or ES-HCM, but had significant prognostic implications in other HCM subtypes, suggesting the need for HCM subtype-specific MR management.

Background: To investigate the proteomic signatures of heart failure (HF) in diabetes. The underlying mechanisms of the elevated risk of HF in diabetes are unknown.

Methods: In 10 189 ARIC study (Atherosclerosis Risk in Communities) participants free of HF (mean age 57±7 years, 56% women, 22% Black adults, 14% with diabetes), we conducted discovery and internal validation for the associations of 4955 plasma proteins with HF by diabetes status. We performed (1) Cox regression to identify proteins associated with HF by diabetes status, (2) external validation in the MESA study (Multi-Ethnic Study of Atherosclerosis, n=5233, 633 with diabetes), and (3) pathway analyses for identified proteins.

Results: Over 24 years in ARIC, there were 2417 HF events (605 among individuals with diabetes). In 993 individuals with diabetes in the discovery sample, 19 proteins were associated with HF (P<10^-5), 12 proteins replicated in the internal validation sample (P<0.05/19). Six of the internally validated proteins replicated in MESA (false discovery rate, q<0.05). Five proteins were specifically associated with HF in those with diabetes: 4 are novel (inactive tyrosine-protein kinase 7, chondroadherin, leucine-rich repeat, and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 and fibulin-5) and 1 is the previously known (cartilage intermediate layer protein 2). NPPB (N-terminal pro-BNP) was associated with HF in those with and without diabetes. Pathways over-represented among proteins associated with diabetes-related HF were lipid metabolism, inflammation, and brown adipose tissue (false discovery rate, q<0.05).

Conclusions: We identified 5 proteomic markers (4 novel) uniquely related to HF risk among individuals with diabetes and not among those without diabetes.

Background: While the immediate goal of cardiopulmonary resuscitation is to achieve return of spontaneous circulation, the patient-centered goal is to minimize neurological injury. Several medications used during cardiac arrest have been associated with poor neurological outcomes. For patients cannulated for veno-arterial extracorporeal membrane oxygenation during cardiac arrest, termed extracorporeal cardiopulmonary resuscitation, the patient-centered impact of these medications has not yet been described.

Methods: We conducted a retrospective Extracorporeal Life Support Organization registry-based analysis. The primary outcome was cerebral performance category (CPC) score at hospital discharge. Cumulative odds models assessed the association between either (1) binary receipt of a medication or (2) the number of epinephrine milligrams given, and CPC score. The model reports the probability of having a score lower than each CPC level. To minimize bias in the receipt of advanced cardiovascular life support drugs, we used inverse probability treatment weights.

Results: Antiarrhythmics were associated with better neurological outcomes (amiodarone: CPC ≤ 1 [odds ratio [OR], 1.28 [95% CI, 1.00-1.65]; P=0.048] and CPC ≤ 2 [OR, 1.38 [95% CI, 1.06-1.78]; P=0.015]; lidocaine: CPC ≤ 1 [OR, 1.69 [95% CI, 1.32-2.17]; P<0.001], CPC ≤ 2 [OR, 1.82 [95% CI, 1.39-2.38]; P<0.001], CPC ≤ 3 [OR, 1.76 [95% CI, 1.30-2.40]; P<0.001]). Intraarrest sodium bicarbonate administration resulted in a lower likelihood of a CPC < 2 to 3 (CPC ≤ 2 [OR, 0.63 [95% CI, 0.49-0.81]; P<0.001], CPC ≤ 3 [OR, 0.65 [95% CI, 0.49-0.86]; P=0.003]). There was no significant difference in CPC score among adults who received intraarrest calcium. The unweighted cumulative effects model demonstrated a dose-dependent increasing relationship between epinephrine doses and harm for all CPC levels (OR, 0.89-0.94; P<0.001 for all).

Conclusions: Our data support that increasing doses of epinephrine and nonantiarrhythmic advanced cardiovascular life support medications both worsen the probability of neurologically intact survival for patients who undergo extracorporeal cardiopulmonary resuscitation.

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.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome affecting ≈32 million individuals worldwide. It accounts for at least half of all heart failure cases and is associated with substantial morbidity and mortality. Although the prevalence of HFpEF increases with age, a substantial proportion of the HFpEF subjects present with cardiometabolic alterations, marking a specific phenogroup of HFpEF. Obesity, diabetes, and hypertension are considered central features in the pathophysiology of HFpEF, driving its development and disease progression by a complex interplay of metabolic-, hemodynamic-, and neurohormonal impairments, resulting in systemic inflammation and immune system dysregulation. Cellular and systemic immunometabolic stress induces vascular endothelial microvascular dysfunction, infiltration of immune cells in the myocardium, and activation of innate and adaptive immune cells in cardiac tissue. The resulting bidirectional crosstalk between systemic and cardiac metabolism influences immune cell reprogramming, sustaining a vicious cycle of cardiac chronic inflammatory response, ultimately leading to adverse structural and functional cardiac remodeling. In this review, we discuss the role of cellular interactions and immunometabolic mechanisms of immune system dysregulation resulting in cardiometabolic HFpEF and elaborate on therapeutic strategies targeting cardiometabolic risk.