Biomarker profiles associated with reverse ventricular remodelling in patients with heart failure and a reduced ejection fraction: Insights from the echocardiographic substudy of the VICTORIA trial.

AIMS: Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. METHODS AND RESULTS: We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a >5% LVEF increase or >15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57-74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow-up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77-0.88), growth differentiation factor-15 (ratio 0.74, 95% CI 0.66-0.84), and insulin-like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73-0.88). CONCLUSIONS: Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism.

Individual and Joint Associations of High-Sensitivity Troponin I and High-Sensitivity Troponin T with Cardiac Phenotypes and Outcomes in the General Population: An Analysis From the Dallas Heart Study.

BACKGROUND: High-sensitivity troponin I (hs-cTnI) and T (hs-cTnT) provide complementary information regarding cardiovascular disease risk. The explanation for their distinct risk profiles is incompletely understood. METHODS AND RESULTS: hs-cTnI and hs-cTnT were measured in Dallas Heart Study participants. Associations of hs-cTnI and hs-cTnT with demographics and phenotypes were assessed using linear regression. Associations with incident heart failure, atherosclerotic cardiovascular disease, global cardiovascular disease, and cardiovascular and all-cause mortality were assessed using Cox models. Among 3276 participants (56% women, 50% Black persons, median age 43 years), the correlation between hs-cTnI and hs-cTnT was modest (Spearman rho=0.35). Variables associated with hs-cTnI but not hs-cTnT included hypertension, higher body mass index and total cholesterol, and lower high-density lipoprotein and cholesterol efflux capacity. Older age, male sex, and diabetes were positively associated, and smoking was negatively associated, with hs-cTnT but not hs-cTnI. Hs-cTnI and hs-cTnT were associated with heart failure (hazard ratio [HR] per SD log hs-cTnI 1.53 [95% CI, 1.30-1.81] and HR per SD log hs-cTnT 1.65 [95% CI, 1.40-1.95]), global cardiovascular disease (HR, 1.22 [95% CI, 1.10-1.34] and HR, 1.27 [95% CI, 1.15-1.32]), and all-cause mortality (HR, 1.12 [95% CI, 1.01-1.25], and HR, 1.17 [95% CI, 1.06-1.29]). After adjustment for N-terminal pro-B-type natriuretic peptide and the alternative troponin, both remained associated with heart failure (HR per SD log hs-cTnI 1.32 [95% CI, 1.1-1.58] and HR per log hs-cTnT 1.27 [95% CI, 1.06-1.51]). CONCLUSIONS: Hs-cTnI and hs-cTnT are modestly correlated, demonstrate differential associations with cardiac and metabolic phenotypes, and provide complementary information regarding heart failure risk.

Predictors and outcomes of heart failure with mid-range ejection fraction.

AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community. METHODS AND RESULTS: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78). CONCLUSIONS: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.

The Use of Very Low Concentrations of High-sensitivity Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test.

BACKGROUND: Recent single-center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high-sensitivity cardiac troponin T (hs-cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia. OBJECTIVE: We aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries. METHODS: TRAPID-AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs-cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4-14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days. RESULTS: We included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs-cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs-cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%). CONCLUSIONS: In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.

Echocardiography in the cardiac transplant recipient.

Despite the widespread use of echocardiography in the cardiac allograft recipient, the clinical usefulness of this practice is not well defined. In this article, the authors review the spectrum of echocardiographic findings in the adult heart transplant patient. Appreciation of typical alterations from "normal" allows the transplant physician to identify clinically significant changes and to avoid unnecessary invasive procedures based on misinterpretation of these differences. Though abnormalities of systolic and diastolic function correlate with episodes of acute rejection, the primary diagnostic usefulness of echocardiography in acute rejection is guiding the endomyocardial biopsy. Additionally, echocardiography has found a role as a supplement to invasive angiography in the diagnosis of cardiac allograft vasculopathy.