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; 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: 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: Circulating microRNAs are promising biomarkers of acute cellular rejection (ACR) and antibody-mediated rejection (AMR) in heart transplantation. The study objective was to assess the characteristics and diagnostic performance of previously identified microRNAs and clinical rejection scores (CRS) in distinct blood samples obtained at the time of an endomyocardial biopsy (EMB).

Methods: In the 5-center, prospective, longitudinal cohort study, GRAfT (Genomic Research Alliance for Transplantation), microRNA sequencing was performed on blood samples. The previously identified microRNAs associated with ACR (n=12) and AMR (n=17) were used to fit a logistic regression model to the current cohort, and the scores were scaled from 0 to 100. Diagnostic performance of ACR and AMR microRNA panels was assessed by the area under the receiver-operating characteristic curve. An adjusted Cox proportional hazard model evaluated the effect of CRS on long-term outcomes.

Results: In 173 heart transplant recipients (29% female sex, 41% Black race, median follow-up 374 days after transplant), 922 blood samples were sequenced, 720 paired with EMB. Among 14 episodes of ACR, the median ACR CRS was 78 compared with 42 without ACR, P<0.001. Among 25 episodes of AMR, median AMR CRS was 75 compared with 53 without AMR, P<0.001. The area under the receiver-operating characteristics curve for the CRS was 0.93 for ACR and 0.92 for AMR. Using a CRS threshold of 65, the ACR CRS had 79% sensitivity, 97% specificity, and 100% negative predictive value; the AMR CRS had 84% sensitivity, 86% specificity, and 99% negative predictive value. The ACR and AMR CRS were both <65 in 589 (82%) of the tests. After adjustment, a 10-point increase in CRS was associated with ≥42% increase in hazard of the composite outcome: subsequent ACR or AMR by EMB, allograft dysfunction, or death (ACR hazard ratio, 1.42 [95% CI, 1.20-1.69]; P<0.001; AMR hazard ratio, 1.45 [95% CI, 1.14-1.86]; P=0.003).

Conclusions: Circulating microRNAs reliably identified ACR and AMR on EMB. An elevated microRNA CRS was associated with an increased risk of subsequent rejection, allograft dysfunction, or death. This biomarker, with further validation, can serve as a noninvasive test to screen and diagnose ACR and AMR without the need for an EMB.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.

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: Up-titration of guideline-directed medical therapy (GDMT) is known to enhance left ventricular function in heart failure (HF) with reduced ejection fraction. However, data regarding its effect on right ventricular (RV) function remain sparse. We aimed to assess the impact of GDMT up-titration on the RV, especially RV to pulmonary artery coupling, and its prognostic value in these patients.

Methods: All consecutive patients (n=291) with left ventricular ejection fraction <50% followed for GDMT up-titration in a dedicated HF clinic in a tertiary center from January 2019 to June 2022 with an echocardiography at baseline (before up-titration) and at follow-up (end of up-titration) were included.

Results: The median age is 65 (55-74) years; 24% are female. Ischemic cardiomyopathy was the main cause of HF (47%), and left ventricular ejection fraction was 30% (22%-34%). After 2 years, 49 patients (17%) reached the primary end point (all-cause death or hospitalization for acute HF). RV size and function significantly improved after GDMT up-titration (all, P<0.001), including RV to pulmonary artery coupling assessed by tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (0.62 versus 0.81 mm/mm Hg; P<0.001). Tricuspid annular plane systolic excursion/systolic pulmonary artery pressure <0.65 mm/mm Hg at follow-up remained associated with the primary end point after adjustment with comorbidities (hazard ratio, 5.9 [95% CI, 2.8-12.1]; P<0.001), clinical and biological severity (hazard ratio, 6.4 [95% CI, 2.4-17.8]; P<0.001), and echocardiography (hazard ratio, 3.6 [95% CI, 1.6-8.4]; P=0.002). In addition, tricuspid annular plane systolic excursion/systolic pulmonary artery pressure was associated with an incremental prognostic value (C-index improvement, P<0.01), over and above prognostic factors, including left ventricular ejection fraction.

Conclusions: This study highlights the independent and incremental prognostic value of tricuspid annular plane systolic excursion/systolic pulmonary artery pressure in HF with reduced ejection fraction during GDMT up-titration, suggesting to also consider RV to pulmonary artery coupling with echocardiography as a treatment goal.

Background: Biomarkers in heart failure (HF) provide mechanistic and prognostic insights, but their role in predicting treatment response is less understood. We evaluated whether multiple baseline biomarker profiles from the REHAB-HF trial (Rehabilitation Therapy in Older Acute Heart Failure Patients) could stratify functional improvement following a 12-week physical rehabilitation intervention (RI).

Methods: Participants ≥60 years hospitalized with heart failure were randomized to a 12-week outpatient RI or attention control. Functional outcomes included changes in the short physical performance battery and 6-minute walk distance. Blood collected at baseline and 12 weeks was analyzed for cardiac (cTnI and cTnT, NT-proBNP [N-terminal pro-brain natriuretic peptide]), renal (creatinine), and inflammatory (CRP [C-reactive protein]) biomarkers. Associations between baseline biomarker levels and 12-week functional gains by treatment group were evaluated using adjusted linear regression models and machine learning-based decision trees.

Results: Baseline biomarker data were available for 242 of 349 participants (69%). Using linear regression, higher cTnI and T were associated with greater 12-week gains in the short physical performance battery and 6-minute walk distance, respectively, among RI participants versus attention control (interaction P=0.040 and 0.032). In the decision tree, analyses combining all biomarkers, CRP emerged as the primary biomarker for both outcomes. Among participants with CRP ≥9.9 mg/L, RI was associated with a +2.4 point (95% CI, 1.8-3.1) greater increase in the short physical performance battery and a +79 m (95% CI, 50-109) greater increase in 6-minute walk distance compared with attention control. In contrast, for those with CRP <9.9 mg/L, the differential benefit of the RI was limited (+0.8 in short physical performance battery [95% CI, 0.1-1.6]; +30 m in 6-minute walk distance [95% CI, -1.0 to 61]). The biomarker levels (except for creatinine) decreased by 12 weeks posthospitalization, but with no differences based on treatment assignment.

Conclusions: Higher inflammation, measured by CRP, may identify older adults recently hospitalized for heart failure with the greatest functional benefit from a physical RI. Biomarker profiling may predict the benefits of this treatment.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02196038.