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Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study.

OBJECTIVE: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. METHODS: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment. RESULTS: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ. CONCLUSION: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

Adult↗

Left atrial volume provides independent and incremental information compared with exercise tolerance parameters in patients with heart failure and left ventricular systolic dysfunction.

OBJECTIVE: Left atrial volume (LAV) is a powerful predictor of outcome in patients with chronic heart failure (CHF) independently of symptomatic status, age and left ventricular (LV) function. It is unknown whether LAV provides independent and incremental information compared with exercise tolerance parameters. METHODS: 273 patients with CHF (mean (SD) 62 (9) years; 13% female) prospectively underwent echocardiography and exercise testing with maximal oxygen consumption (Vo(2)). The primary end point was composite and included cardiac death, hospitalisation for worsening heart failure or cardiac transplantation. RESULTS: At Cox proportional hazard analysis, LAV normalised for body surface area (LAV/BSA) was strongly associated with mortality (hazard ratio (HR) = 1.027 (95% CI 1.018 to 1.04), p<0.001). The predictive value of LAV/BSA was independent of Vo(2) and LV ejection fraction (EF) (HR = 1.014 (1.002 to 1.025), p = 0.02; HR = 0.95 (0.91 to 0.99), p = 0.02; HR = 0.89 (0.82 to 0.98), p = 0.02 for LAV/BSA, EF and Vo(2), respectively). Receiver operator characteristic (ROC) curve analysis identified the best cut-off values for prediction of the end point. LAV/BSA >63 ml, EF <30% and Vo(2) <16 ml/kg/min were considered to be risk factors. Patients with three risk factors had an HR of 38 (95% CI 11 to 129) compared with patients with no risk factors. CONCLUSION: LAV provides powerful prognostic information incrementally and independently of Vo(2). LAV, EF and Vo(2 )can be used to build a risk prediction model, which can be used clinically.

Adult↗

Agreement between community echocardiography and hospital echocardiography in patients suspected of having left ventricular systolic dysfunction.

BACKGROUND: Smaller echocardiography machines, when used in hospitals, are accurate for detecting left ventricular dysfunction and valvular disease. This paper assessed the detection of left ventricular dysfunction and of valvular disease in the community setting by a smaller machine. AIMS: To measure the agreement in patients with suspected heart failure between community echocardiography and traditional echocardiography in the hospital in detecting left ventricular dysfunction and significant valve disease. METHODS: Suspected heart failure patients were referred to one of the authors (SJ) for community echocardiography using a Siemens Cypress machine. The patients had a second echocardiogram in the hospital by another sonographer who was blinded to the results of the first echocardiogram. The reports of the two sonographers were assessed for agreement using kappa statistics. RESULTS: 458 patients had a community echocardiogram and 136 agreed to a second echocardiogram in the hospital. There was excellent agreement, kappa = 0.87 (0.06 SE), for the detection of left ventricular dysfunction between community echocardiography and the hospital machine. The detection of significant valvular disease was good, kappa = 0.75 (0.06) between the community echocardiogram and hospital machines. CONCLUSIONS: In suspected heart failure patients, community echocardiography gives comparable results to traditional hospital echocardiography for left ventricular dysfunction detection and for significant valvular disease detection.

Aged↗

Left ventricular hypertrophy and impaired diastolic filling in essential hypertension. Diastolic mechanisms for systolic dysfunction during exercise.

Left ventricular ejection fraction is normal at rest but may respond abnormally to exercise in many patients with essential hypertension. To assess the determinants of the abnormal ejection fraction response to exercise, we performed radionuclide angiography at rest and during exercise in 41 hypertensive patients without coronary artery disease. In 22 patients (group 1), the ejection fraction increased more than 5% during exercise; in the other 19 patients (group 2), the ejection fraction either increased by less than 5% or decreased with exercise. Left ventricular diastolic filling was impaired at rest in patients in group 2 compared with group 1, with reduced peak filling rate (2.5 +/- 0.4 vs. 3.1 +/- 0.7 end-diastolic volume/sec; p less than 0.01) and prolonged time to peak filling rate (175 +/- 28 vs. 153 +/- 22 msec; p less than 0.01). Impaired diastolic filling in group 2 was associated with less augmentation in end-diastolic volume during exercise compared with group 1 (p less than 0.01). These observations were not dependent on the threshold value that was arbitrarily chosen to define an abnormal ejection fraction response, as there were significant correlations for the entire group between the magnitude of change in ejection fraction with exercise and both the resting peak filling rate (r = 0.46) and the change in end-diastolic volume with exercise (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly↗

A case of dilated cardiomyopathy with abnormal atrioventricular conduction 5 years before the appearance of left ventricular systolic dysfunction.

The first manifestation of dilated cardiomyopathy is usually dyspnea as a result of left heart failure. In this report we describe an unusual patient with third-degree atrioventricular (AV) block unaccompanied by left ventricular dysfunction. Severe left ventricular dysfunction occurred 5 years after the implantation of a permanent pacemaker. We conclude that AV block should not be overlooked as an initial clinical manifestation of dilated cardiomyopathy.

Adult↗

Coronary microvascular abnormality in the reversible systolic dysfunction observed after noncardiac disease.

Acute reversible left ventricular wall motion abnormalities mimicking myocardial stunning have been reported with noncardiac disease and their coronary angiograms did not demonstrate organic stenosis or vasospasm in the epicardial coronary arteries. Thus, this mechanism has not yet been fully clarified. Two patients are reported as demonstrating acute reversible wall motion abnormalities after noncardiac disease. The electrocardiographic and echocardiographic findings mimicked myocardial stunning and confirmed the previous reports. The coronary angiograms did not show any corresponding coronary stenosis or vasospasm, but did show a reduced coronary flow reserve. Cardiac metaiodobenzylguanidine scintigraphy demonstrated regional defects involving the apex, a decreased heart/mediastinum ratio and an enhanced washout rate, which partially returned to normal after 3 months. Microvascular dysfunction and sympathetic nervous abnormalities might be responsible for the reversible contractile impairment.

3-Iodobenzylguanidine↗

Increase in creatinine and cardiovascular risk in patients with systolic dysfunction after myocardial infarction.

Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Cardiovascular Diseases↗