The utility of troponin measurement to detect myocardial infarction: review of the current findings

Myocardial infarction (MI) is defined by the presence of myocardial necrosis in combination with clinical evidence of myocardial ischemia. Cardiac troponins are regulatory proteins within the myocardium that are released into the circulation when damage to the myocyte has occurred. Therefore, serum troponin is an exquisitely sensitive marker of myocardial injury and is necessary for establishing the diagnosis of MI. High-sensitivity troponin assays are improving the diagnostic accuracy and rapid detection of myocardial infarction. The early identification of MI is vital for the institution of anti-thrombotic therapy to limit myocardial damage and preserve cardiac function. Troponin has both diagnostic and prognostic significance in the setting of acute coronary syndrome (ACS). Increased troponin levels in the absence of ACS should prompt an evaluation for an alternative, non-thrombotic mechanism of troponin elevation and direct management at the underlying cause. This review describes the role of troponin in the evaluation of patients with suspected myocardial infarction

Differences in NT-proBNP Response and Prognosis in Men and Women With Heart Failure With Reduced Ejection Fraction.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a prognostic biomarker in heart failure (HF) with reduced ejection fraction. However, it is unclear whether there is a sex difference in NT-proBNP response and whether the therapeutic goal of NT-proBNP ≤1000 pg/mL has equivalent prognostic value in men and women with HF with reduced ejection fraction. Methods and Results In a secondary analysis of the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial we analyzed trends in NT-proBNP and goal attainment by sex. Differences in clinical characteristics, HF treatment, and time to all-cause death or HF hospitalization were compared. Landmark analysis at 3 months determined the prognostic value of early NT-proBNP goal achievement in men and women. Of the 286 (32%) women and 608 (68%) men in the GUIDE-IT trial, women were more likely to have a nonischemic cause and shorter duration of HF. Guideline-directed medical therapy was less intense over time in women. The absolute NT-proBNP values were consistently lower in women; however, the change in NT-proBNP and clinical outcomes were similar. After adjustment, women achieving the NT-proBNP goal had an 82% reduction in death or HF hospitalization compared with a 59% reduction in men. Conclusions Men and women with HF with reduced ejection fraction had a similar NT-proBNP response despite less intensive HF treatment among women. However, compared with men, the early NT-proBNP goal of ≤1000 pg/mL had greater prognostic value in women. Future efforts should be aimed at intensifying guideline-directed medical therapy in women, which may result in greater NT-proBNP reductions and improved outcomes in women with HF with reduced ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840

High-risk percutaneous coronary intervention is associated with reverse left ventricular remodeling and improved outcomes in patients with coronary artery disease and reduced ejection fraction

BACKGROUND: Therapies that reverse pathologic left ventricular (LV) remodeling are often associated with improved outcomes. The incidence and impact of reverse LV remodeling after high-risk percutaneous coronary intervention (PCI) are unknown. METHODS: The PROTECT II study was a multicenter trial in patients with complex, multivessel coronary artery disease and reduced ejection fraction (EF) that revealed an increase in visual EF after high-risk PCI. Among patients with quantitative echocardiography (LV volumes and biplane EF), we assessed the extent and predictors of reverse LV remodeling, defined as improved systolic function with an absolute increase in EF ≥5% and correlated these findings with clinical events. RESULTS: Quantitative echocardiography was performed in 184 patients at baseline and longest follow-up. Mean EF at baseline was 27.1%. Ninety-three patients (51%) demonstrated reverse LV remodeling with an absolute increase in EF of 13.2% (P \u3c .001). End-systolic volume decreased from 137.7 to 106.6 mL (P = .002). No significant change in EF or end-systolic volume was seen among non-remodelers. Reverse LV remodeling occurred more frequently in patients with more extensive revascularization (odds ratio, 7.52; 95% CI [1.31-43.25]) and was associated with significantly fewer major adverse events (composite of death/myocardial infarction/stroke/transient ischemic attack): 9.7% versus 24.2% (P = .009). There was also a greater reduction in New York Heart Association class III/IV heart failure among reverse LV remodelers (66.7% to 24.0%) than non-remodelers (56.3% to 34.4%), P = .045. CONCLUSIONS: Reverse LV remodeling can occur after high-risk PCI in patients with complex coronary artery disease and reduced EF and is associated with improved clinical outcomes

Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide

BACKGROUND: Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction. METHODS AND RESULTS: In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kg CONCLUSIONS: This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose-effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388464

Treatment of sleep-disordered breathing in heart failure impacts cardiac remodeling: Insights from the CAT-HF Trial

Background: Sleep-disordered breathing (SDB), including central and obstructive sleep apnea, is a marker of poor prognosis in heart failure (HF) and may worsen cardiac dysfunction over time. Treatment of SDB with adaptive servoventilation (ASV) may reverse pathologic cardiac remodeling in HF patients. Methods: The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Servo-Ventilation Therapy in Heart Failure (CAT-HF) trial randomized patients with acute decompensated HF and confirmed SDB to either optimal medical therapy (OMT) or treatment with ASV and OMT. Patients with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) were included. Echocardiograms, performed at baseline and 6 months, assessed cardiac size and function and evaluated cardiac remodeling over time. The CAT-HF trial was stopped early in response to the SERVE-HF trial, which found increased mortality among HFrEF patients with central sleep apnea treated with ASV. Results: Of the 126 patients enrolled prior to trial cessation, 95 had both baseline and 6-month echocardiograms (77 HFrEF and 18 HFpEF). Among HFrEF patients, both treatment arms demonstrated a significant increase in EF: + 4.3% in the ASV group (. 0004) and+ 4.6% in OMT alone (P=. 007) and a significant decrease in LV end-systolic volume index:-9.4mL/m(2) in the ASV group (P =.01) and-8.6mL/m(2) in OMT alone (P=. 003). Reductions in left atrial (LA) volume and E/e' were greater in the ASV arm, whereas patients receiving OMT alone demonstrated more improvement in right ventricular function. HFpEF patients treated with ASV also had a decrease in LA size that was greater than those receiving OMT alone. Although there were significant intragroup changes within the ASV + OMT and OMT-alone groups, there were no significant intergroup differences at 6 months. Conclusions: Significant reverse LV remodeling was seen among HFrEF patients with SDB regardless of treatment allocation. Substantial reductions in LA volume among HFrEF and HFpEF patients receiving ASV suggest that ASV treatment may also improve diastolic function and warrant further investigation. (C) 2018 Elsevier Inc. All rights reserved

Left ventricular hypertrophy and clinical outcomes over 5 years after TAVR : an analysis of the PARTNER Trials and registries

OBJECTIVES: This study sought to evaluate the association between severity of left ventricular hypertrophy (LVH) before transcatheter aortic valve replacement (TAVR) and outcomes out to 5 years. BACKGROUND: Prior studies assessing the association between baseline LVH and outcomes after surgical or TAVR for aortic stenosis (AS) have yielded conflicting results. METHODS Patients with severe symptomatic AS at intermediate or high risk in the PARTNER (Placement of Aortic Transcatheter Valve) 1, 2, and S3 trials and registries who received TAVR and had baseline measurements for left ventricular mass index (LVMi) were analyzed. The presence and severity of LVH was determined by LVMi using American Society of Echocardiography sex-specific cutoffs. RESULTS: Among 4,280 patients, those with no (n ¼ 1,325), mild (n ¼ 777), moderate (n ¼ 628), and severe (n ¼ 1,550) LVH had 5-year rates of death of 32.8%, 37.3%, 37.2%, and 44.8%, respectively (p < 0.001), and 5-year rates of cardiovascular (CV) death or rehospitalization of 33.6%, 39.2%, 42.4%, and 49.2%, respectively (p < 0.001). After adjustment, severe LVH (compared with no LVH) was associated with increased all-cause death (adjusted hazard ratio: 1.16; 95% confidence interval: 1.00 to 1.34; p ¼ 0.04) and CV death or rehospitalization (adjusted hazard ratio: 1.34; 95% confidence interval: 1.16 to 1.54; p < 0.001), but no increased hazard was observed for mild or moderate LVH. In spline analyses performed in males and females separately, there was a consistent linear association between increased LVMi and an increased adjusted hazard of CV mortality or rehospitalization. A similar relationship was observed for all-cause death in females, but not males. CONCLUSIONS: Severe baseline LVH is associated with higher 5-year death and rehospitalization rates after TAVR. These findings may have implications for the optimal timing of valve replacement and the potential role for medical therapy to slow or prevent LVH as AS progresses before valve replacement, but further studies are needed. (J Am Coll Cardiol Intv 2020;13:1329–39) © 2020 by the American College of Cardiology Foundation