The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study.

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.

Correlation between ECG and myocardial perfusion after mechanical reperfusion of acute myocardial infarction.

UNLABELLED: The identification of viable myocardium after myocardial infarction (MI) carries major prognostic impact. Due to myocardial stunning early after successful mechanical reperfusion of acute myocardial infarction, analysis of myocardial perfusion but not of contractile function can be used to differentiate between necrotic and viable myocardium. Although being widely regarded as an indicator of infarct transmurality, the relation between post-infarct Q-wave formation and the amount of viable myocardium has not been studied. We hypothesized that there was a correlation between the extent of Q-wave formation and the extent of perfusion abnormalities on myocardial contrast echocardiography early after successful mechanical reperfusion of first acute myocardial infarction and that the extent of post-infarct Q-wave formation might therefore be used as a simple estimate of the amount of viable myocardium. METHODS AND RESULTS: 47 patients with first MI and treated by direct PCI were enrolled. Patients were divided into 3 groups according the presence and number of abnormal Q waves (group A-no abnormal Q wave; group B-< or =2 abnormal Q waves, group C-> or =3 abnormal Q waves). Left ventricular pump function was defined by ejection fraction (EF) on ventriculography and wall motion score index (WMSI) on echocardiography. Myocardial perfusion was defined by perfusion score index (PSI) on myocardial contrast echocardiography. Patients in group A had significantly better LV function than patients in other groups [EF 57+/-5 vs. 48+/-11% (group B) and 47+/-10% (group C); p<0.05], also WMSI was the best in this group [1.34+/-0.22 vs. 1.67+/-0.39 (group B) and 1.68+/-0.31 (group C); p<0.01]. Myocardial perfusion assessed by PSI was best in group A (1.2+/-0.3, p<0.05). With respect to PSI, there was a significant difference between group B and C (1.41+/-0.21 vs. 1.56+/-0.29; p<0.05), even though EF and WMSI did not differ in these groups. The amount of perfused segments with severe wall motion abnormality was higher in group B compared to group C (47% vs. 25%; p<0.05). CONCLUSION: In patients after successful mechanical reperfusion of first MI, the extent of Q-wave formation on ECG may be regarded as a corollary of the amount of myocardial microvascular damage and may, therefore, be used to estimate the amount of viable myocardium post-infarct.

Interhospital transport for primary angioplasty improves the long-term outcome of acute myocardial infarction compared with immediate thrombolysis in the nearest hospital (one-year follow-up of the PRAGUE-1 study).

OBJECTIVE: Comparison of the long-term outcomes of three reperfusion strategies in patients with acute ST elevation myocardial infarction presenting to community hospitals. METHODS: One-year clinical outcomes were compared for 300 patients randomized in the PRimary Angioplasty in patients transferred from General community hospitals to specialized percutaneous coronary intervention Units with or without Emergency thrombolysis (PRAGUE-1) study to one of three treatment strategies: thrombolysis in a community hospital (group A, n=99); thrombolysis during immediate transportation for coronary angioplasty (group B, n=100); and immediate transportation for coronary angioplasty without thrombolysis (group C, n=101). RESULTS: Total mortality rates in group A, B and C patients were 18%, 12% and 13%, respectively (not significant). Nonfatal reinfarction occurred in 12%, 6% and 3% of patients, respectively (P<0.05). The combined endpoint (total mortality and nonfatal reinfarction rate) was reported in 30%, 18% and 16% of patients, respectively (P<0.05). In patients randomized within 2 h of the onset of symptoms, mortality rates were 18%, 3% and 8%, respectively (P<0.05). Additional revascularization procedures (percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery) were performed in 35%, 14% and 15% of patients, respectively (P<0.001). CONCLUSIONS: Primary angioplasty (even if delayed due to patient transportation to an interventional centre) is associated with better short- and long-term clinical outcomes than thrombolysis. The combination of the two strategies did not prove superior to coronary angioplasty alone. However, it may be superior in a subset of patients with early admission. The coronary angioplasty strategy decreases the need for revascularization procedures during the subsequent one-year follow-up.

Acute myocardial infarction complicated by early onset of heart failure: safety and feasibility of interhospital transfer for coronary angioplasty. Subanalysis of Killip II-IV patients from the PRAGUE-1 study.

OBJECTIVE: The objective of this study is to assess the feasibility and safety of interhospital transfer (within up to 60 minutes) for primary/rescue coronary angioplasty of patients with myocardial infarction (AMI) complicated by an early onset of acute heart failure (AHF) admitted to a community hospital without PCI facilities. DESIGN AND PATIENTS: From the multicenter randomized PRAGUE-1 study, a subgroup of 66 patients with AMI complicated by AHF on the first presentation to the community hospital were retrospectively analyzed. Group A patients (n = 21) were treated on site in community hospitals using thrombolysis (streptokinase), group B patients (n = 20) were transported with thrombolytic infusion to a PCI center for coronary angioplasty, and group C patients (n = 25) were immediately transported to a PCI center for primary angioplasty without thrombolysis. RESULTS: No patient died during transportation. One group B patient developed ventricular fibrillation during transfer. The time delay from the onset of chest pain to reperfusion was > 142 minutes, and 253 and 251 minutes in groups A, B, and C, respectively. Hospital stay (16 vs 11 vs 10 days, P = NS) was shorter in the angioplasty groups. Transported patients (groups B, C) displayed a significant decrease in heart failure progression within the first 24 hours after treatment (48% vs 15% vs 8%, P < 0.05). The combined end point, i.e., mortality + nonfatal reinfarction (43% vs 25% vs 8%, P < 0.05), was significantly less frequent in the coronary angioplasty group. CONCLUSIONS: 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.

Inter-hospital transport for primary angioplasty does not compromise left ventricular function: six-month echocardiographic follow-up of the PRAGUE 1 Study.

The 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 primary angioplasty alone.