Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans.

BACKGROUND: Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction. There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the very-early-release kinetics of cTns after an ischemic event. Copeptin may have a supplementary role in ruling out myocardial infarction early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans. METHODS: Thirty-four patients (median age, 60 years [interquartile range, 51-64]; 15 men, 43%) with angiographically normal coronary arteries were randomly assigned into 4 groups with different durations of induced myocardial ischemia (0, 30, 60, 90 s). Ischemia was induced by inflating a balloon in the left anterior descending artery between the first and second diagonal branch. Blood was collected before balloon inflation (baseline) every 15 minutes for the first 3 hours, and every 30 minutes for the next 3 hours. The cTns were analyzed by 3 high-sensitivity (hs) cTn assays: hs-cTnT (Roche), hs-cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay. RESULTS: None of the patients had any complications. Increased cTn concentrations were detected by all 3 assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 minutes after 90-s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 and 180 minutes, 1 (11%), 0, and 0 patients from the 60-s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90-s ischemia group, respectively, fulfilled criteria for a biochemical myocardial infarction. CONCLUSIONS: This study is the first to report the early-release kinetics of cTn concentrations after different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 s of ischemia. hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not change significantly. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03203057.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

BACKGROUND: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

Association of warfarin therapy duration after bioprosthetic aortic valve replacement with risk of mortality, thromboembolic complications, and bleeding.

CONTEXT: The need for anticoagulation after surgical aortic valve replacement (AVR) with biological prostheses is not well examined. OBJECTIVE: To perform a nationwide study of the association of warfarin treatment with the risk of thromboembolic complications, bleeding incidents, and cardiovascular deaths after bioprosthetic AVR surgery. DESIGN, SETTING, AND PARTICIPANTS: Through a search in the Danish National Patient Registry, 4075 patients were identified who had bioprosthetic AVR surgery performed between January 1, 1997, and December 31, 2009. Concomitant comorbidity and medication were retrieved. Poisson regression models were used to determine risk. MAIN OUTCOME MEASURES: Incidence rate ratios (IRRs) of strokes, thromboembolic events, cardiovascular deaths, and bleeding incidents by discontinuing warfarin as opposed to continued treatment 30 to 89 days, 90 to 179 days, 180 to 364 days, 365 to 729 days, and at least 730 days after surgery. RESULTS: The median duration of follow-up was 6.57 person-years. Estimated rates of events per 100 person-years in patients not treated with warfarin compared with those treated with warfarin with comparative absolute risk were 7.00 (95% CI, 4.07-12.06) vs 2.69 (95% CI, 1.49-4.87; adjusted IRR, 2.46; 95% CI, 1.09-5.55) for strokes; 13.07 (95% CI, 8.76-19.50) vs 3.97 (95% CI, 2.43-6.48; adjusted IRR, 2.93; 95% CI, 1.54-5.55) for thromboembolic events; 11.86 (95% CI, 7.81-18.01) vs 5.37 (95% CI, 3.54-8.16; adjusted IRR, 2.32; 95% CI, 1.28-4.22) for bleeding incidents; and 31.74 (95% CI, 24.69-40.79) vs 3.83 (95% CI, 2.35-6.25; adjusted IRR, 7.61; 95% CI, 4.37-13.26) for cardiovascular deaths within 30 to 89 days after surgery; and 6.50 (95% CI, 4.67-9.06) vs 2.08 (95% CI, 0.99-4.36; adjusted IRR, 3.51; 95% CI, 1.54-8.03) for cardiovascular deaths within 90 to 179 days after surgery. CONCLUSION: Discontinuation of warfarin treatment within 6 months after bioprosthetic AVR surgery was associated with increased cardiovascular death.

Echocardiographic Predictors of Mortality in Women With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Previous studies found that global longitudinal strain is a superior predictor of mortality in male patients with heart failure with reduced ejection fraction (EF). This does not apply to women. Our aim was to investigate sex-specific differences in cardiac function and identify echocardiographic predictors of mortality in women with heart failure with reduced EF. METHODS AND RESULTS: Echocardiographic examinations were retrieved from 968 patients with heart failure with reduced EF (26.7% women). Images were analyzed offline, and the end point was all-cause mortality. During follow-up (median: 41 months) 163 patients (16.8 %) died. Women had significantly higher left ventricular (LV) EF (27.1% versus 25.4%, P=0.004), global longitudinal strain (-9.9% versus -8.9%, P<0.001), and global circumferential strain (-10.9% versus -9.7%, P<0.001). Moreover, women displayed higher E/e' (14.4 versus 13.0, P=0.004), LV diastolic elastance (1.16 versus 0.75, P<0.001), and lower e' (6.2 cm/s versus 6.9 cm/s, P<0.001). In women, tricuspid annular plane systolic excursion and LV isovolumetric relaxation time were significant predictors of outcome after multivariable adjustment (tricuspid annular plane systolic excursion: hazard ratio, 1.11; 95% CI, 1.04-1.18; P=0.003 per 1 mm decrease; isovolumetric relaxation time: hazard ratio, 1.07; 95% CI, 1.03-1.10; P=0.001 per 5 ms decrease). LVEF and global longitudinal strain were significant predictors in men (LVEF: hazard ratio, 0.94; 95% CI, 0.90-0.99; P=0.014 per 1% increase; global longitudinal strain: hazard ratio, 1.20; 95% CI, 1.04-1.38; P=0.013 per 1% decrease). CONCLUSIONS: Tricuspid annular plane systolic excursion and LV isovolumetric relaxation time provide prognostic information in women but not in men. Hence, in women with heart failure with reduced EF, right ventricular function, and LV diastolic function seem paramount in predicting mortality, whereas LV systolic function is more important in men.

Plasma high-mobility group box 1 levels predict mortality after ST-segment elevation myocardial infarction.

OBJECTIVES: We evaluated the potential association between plasma high-mobility group box 1 (HMGB1) levels and outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. BACKGROUND: The positive effect of reperfusion after STEMI may be compromised by ischemic/reperfusion injury. HMGB1 is released by necrotic cells and, in pre-clinical studies, has been implicated to play a role in myocardial ischemic/reperfusion injury. METHODS: The study included 141 STEMI patients, with acute occlusion of the left anterior descending coronary artery successfully treated with percutaneous coronary intervention. Plasma HMGB1 levels were measured by enzyme-linked immunoadsorbent assay at admission. Forty-two healthy individuals served as control subjects. RESULTS: After a median of 10 months of follow-up, 13 STEMI patients died. There were no significant differences with regard to baseline variables between the group of patients who survived and those who died. Baseline HMGB1 levels were increased in STEMI patients when compared with control subjects. Furthermore, the STEMI patients who died had higher HMGB1 levels than those who survived. After adjusting for age, sex, troponin I, and creatine kinase-myocardial band, we found that a doubling of HMGB1 concentrations increased the risk of mortality by 75% (hazard ratio: 1.75; 95% confidence interval: 1.1 to 2.8). CONCLUSIONS: Plasma HMGB1 levels are elevated in STEMI patients compared with healthy control subjects. Furthermore, after a follow-up period of 10 months, plasma HMGB1 levels are shown to be independently associated with increased mortality in STEMI patients treated with PCI. These data suggest that plasma HMGB1 may be used as a new prognostic biomarker in STEMI patients.