Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ß-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy (HCM) is a primary cardiac disease characterized by unexplained cardiac hypertrophy and a relatively high incidence of sudden cardiac death, especially in young people.1,2 The extent of left ventricular hypertrophy is one of the major determinants of symptoms and prognosis. 3,4 Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. 5,6 Inhibition of angiotensin-converting enzyme (ACE) or the angiotensin II type 1 receptor (AT1-R) induced regression of myocardial hypertrophy in patients with hypertension or after myocardial infarction. [7][8][9] In HCM, ACE and AT1-R gene polymorphisms have been shown to be associated with severity of hypertrophy, a high incidence of atrial fibrillation and the risk of sudden cardiac death. -17Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter study to test the safety and effects of AT1-R antagonist candesartan in patients with nonobstructive HCM. We hypothesized that long-term use of candesartan would be associated with regression of left ventricular (LV) hypertrophy and improvement of LV function. Materials and Methods PatientsThis was a double-blind, placebo-controlled, randomized multicenter study. The study population consisted of 24 consecutive, genetically independent, adult (Ն18 years) patients (age 43 Ϯ 13 yrs; 46% males) with nonobstructive HCM, and normal ejection fraction (Ն60%) and sinus rhythm, who visited the participating in...

Background In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods and results CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure. Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. ClinicalTrials identifier ISRCTN43070564

Interhospital transfer for coronary angioplasty of patients with AMI complicated by an early onset of AHF is feasible and safe. Transport for angioplasty may even reduce the risk of heart failure progression and improve clinical outcome compared to immediate thrombolysis in the nearest community hospital.

SUMMARYThe main aim of the present study was to investigate whether long distance interhospital transport for primary angioplasty (delayed mechanical reperfusion) influences the resulting left ventricular function after myocardial infarction as compared with thrombolysis at the nearest hospital (immediate pharmacological reperfusion).Primary coronary angioplasty is more effective than thrombolysis in restoring coronary flow in patients with acute myocardial infarction. It is not known whether a delay in reperfusion due to transport to an angioplasty centre compromises left ventricular function, and whether combination therapy (ie, thrombolysis during transport to an angioplasty centre) would help preserve ejection fraction.The "PRAGUE-1" Study randomised 300 patients with myocardial infarction admitted to community hospitals without a cath-lab into 3 groups: group A (thrombolysis, no transport, n = 99), group B (thrombolysis during transport to an angioplasty centre, n = 100), and group C (transport for primary angioplasty, n = 101). Transport distances were below 75 kilometres, and mean transport time was 38 minutes. This paper presents for the first time the echocardiographic data from the early (discharge, day 30) and mid-term (6 months) follow-up. Only patients who survived until discharge (A: 85, B: 88, C: 94) could be analysed.Ejection fraction improved between discharge and 6 months (P < 0.01) in all three groups: from 47% to 51% in group A, from 47% to 52% in group B, and from 48% to 52% in group C. The differences between the groups were not significant. The same differences were found for the wall motion score index. Left ventricular end-diastolic diameter did not differ between the groups/examinations. Greater improvement was documented in the period between hospital discharge and day 30, compared to the period between day 30 and 6 months.The time delay associated with an inter-hospital transport strategy for primary angioplasty did not compromise left ventricular function. The strategy of thrombolysis during transport did not further improve left ventricular function compared to transport for priFrom

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