AstraZeneca, Biosensors, and The Medicines Company.

Background-Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. Methods and Results-In a substudy of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (Pϭ0.039) and 3.03 (Pϭ0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months. Conclusions-Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post-acute myocardial infarction collagen turnover changes.

Background-Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. Methods and Results-This nationwide registry in France included 223 centers and 1714 patients over a 1-month periodat the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (Pϭ0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. Conclusions-When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI. (Circulation. 2008;118: 268-276.)

The evaluation of clopidogrel responsiveness by platelet function tests is largely influenced by the choice of blood preservative and functional tests. Measures of aggregation stabilization, and of consequent secretion and activation, identified most patients as responders, contrasting with measures of peak aggregation, by likely reflecting better the interactions clopidogrel and the P2Y12 receptor.

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AimsTo test the hypothesis that an earlier post-acute myocardial infarction (AMI) eplerenone initiation in patients with left ventricular systolic dysfunction (LVSD) and heart failure (HF) is associated with better long-term outcomes. Methods and resultsThe 6632 patients of the EPHESUS study were randomized from day 3 to 14 after the index AMI (median ¼ 7 days), of these 3319 were assigned to eplerenone. We analysed the differential effects of time-to-eplerenone initiation vs. placebo, based on the median time to initiation of treatment (,7 days-'earlier', 7days-'later'). Effects on outcomes were evaluated over a mean 16-month follow-up, using Cox proportional hazards regression analysis. The earlier eplerenone initiation (,7 days) reduced the risk of all-cause mortality by 31% (P ¼ 0.001) when compared with the 'earlier' placebo' and also reduced the risks of cardiovascular (CV) hospitalization/CV mortality by 24% (P , 0.0001) and sudden cardiac death (SCD) by 34% (P , 0.0001). In contrast, later eplerenone initiation (7 days) had no significant effect on outcomes. Interactions between time-to-randomization and treatment were significant. These associations remained substantially unchanged after risk adjustment in multivariable models. ConclusionAn earlier eplerenone administration (3-7days) post-AMI improved outcomes in patients with LVSD and HF. This benefit was not observed when eplerenone was initiated later (7days).--

The results of this large registry of real-world practice indicate no survival benefit for patients treated with primary angioplasty compared with those who received thrombolytic therapy.

Purpose:To prospectively assess the use of cardiac MRI with delayed contrast enhancement (DCE) for identifying patients with active myocarditis among those presenting with acute coronary syndrome (ACS) but no coronary stenosis. Materials and Methods:A total of 27 consecutive patients (age ϭ 45 Ϯ 17 years; 14 male) presenting with ACS (chest pain, positive troponin-I) and no coronary stenosis, underwent cardiac MRI 9 Ϯ 7 days after pain onset and 8 Ϯ 5 months later (N ϭ 19). Steady-state free-precession pulse (SSFP) sequence was applied for the assessment of myocardial function and both inversion-recovery (IR) and SSFP sequences were used for analyzing the topography and extent of DCE areas. Rest sestamibi-gated-single photon emission CT (SPECT) was also systematically performed.Results: Subepicardial DCE pattern typical of acute myocarditis was documented in 12 patients (44%). Ischemic DCE pattern (transmural or subendocardial focal DCE) was documented in 12 of the 15 remaining patients (44%). Patients with subepicardial DCE had: higher C-reactive protein (CRP) levels (38 Ϯ 32 vs. 14 Ϯ 24 mg/mL; P ϭ 0.04), lower Framingham cardiovascular risk (3 Ϯ 3% vs. 9 Ϯ 5%; P Ͻ 0.001), lower incidence of perfusion SPECT defects (17% vs. 73%; P ϭ 0.01), higher left ventricular (LV) enddiastolic volume (77 Ϯ 16 vs. 64 Ϯ 10 mL/m 2 ; P ϭ 0.02), and higher regression of DCE areas at follow-up (-65 Ϯ 17% vs. -18 Ϯ 23%; P ϭ 0.002).Conclusion: DCE pattern of active myocarditis can be seen in patients presenting with ACS but no coronary stenosis.