Usha Raval

Beneficial Effects of Intravenous and Oral Carvedilol Treatment in Acute Myocardial Infarction A Placebo-Controlled, Randomized Trial

BACKGROUND Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.

Prognostic value of stress dobutamine technetium-99m sestamibi single-photon emission computed tomography (SPECT) in patients with suspected coronary artery disease

Inotropic stress using graded dobutamine infusion has evolved as an alternative form of pharmacologic stress in conjunction with perfusion and functional imaging for evaluation of coronary heart disease. However, the prognostic value of technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in patients undergoing dobutamine stress testing for the detection of coronary artery disease is unclear. Accordingly, 61 patients undergoing coronary arteriography for the evaluation of chest pain on the basis of symptoms and treadmill exercise electrocardiography underwent SPECT imaging at rest and during stress. Patients were followed up for 19 +/- 11 months (2 to 33) during which 2 died, 2 had acute myocardial infarction, 13 developed unstable angina, and 3 had congestive heart failure. Univariate Cox regression analysis revealed that those with reversible defects (95%) and defects in multiple vascular territories (80%) on SPECT had a greater number of cardiac events compared to those without (59% [p = 0.02] and 34% [p = 0.002], respectively). The number of reversible (3.9 +/- 2.1) and fixed (2.3 +/- 2.0) segments (12-segment model) were greater in patients with cardiac events compared to those without, (2.3 +/- 2.5, p = 0.009 and 1.1 +/- 2.0, p = 0.02) respectively. When multivariate analysis was performed using clinical, exercise testing, and SPECT variables, the independent predictors of cardiac events were a history of myocardial infarction (p <0.001), number of reversible segments (p = 0.001), and presence of defects in multiple vascular territories (p = 0.01). In summary, dobutamine stress Tc-99m sestamibi SPECT is a powerful predictor of future cardiac events in patients undergoing coronary arteriography for evaluation of chest pain and may be used to stratify patients for further intervention.

Prognostic value of predischarge exercise testing, ejection fraction, and ventricular ectopic activity in acute myocardial infarction treated with streptokinase☆

The relative importance of prognostic parameters that delineate left ventricular function, myocardial ischemia, and arrhythmogenic potential after thrombolytic therapy is not clear. This study investigated 112 patients with acute myocardial infarction who were treated with thrombolysis to determine the relative prognostic value of predischarge treadmill exercise testing, radionuclide ventriculography, and ambulatory electrocardiographic monitoring for ventricular ectopic activity. During a mean follow-up period of 18 months (range 6 to 30), 42 first cardiac events were recorded, consisting of 3 deaths, 6 reinfarctions, 16 bouts of unstable angina, 16 episodes of heart failure, and 1 arrhythmic event. Univariate analysis revealed ejection fraction, exercise time, and ventricular ectopic count of > or = 10/hour to be predictive of future cardiac events. Subsequent multivariate analysis showed ejection fraction (p <0.001) and exercise time (p=0.002 to have independent prognostic value, but ventricular ectopic activity did not provide additional information. Ventricular ectopic count > or = 10/hour was additionally predictive only when combined with either ejection fraction (R2=5.4%) or exercise time (R2=2.9%). Event-free survival analysis revealed hazard ratios for ejection fraction <40% and exercise time <7 minutes of 3.63 (p=0.001) and 2.16 (p=0.01), respectively. Although ejection fraction and exercise time were able to predict future episodes of heart failure, neither could adequately identify patients at risk of recurrent ischemic events.

Technetium 99m-labeled sestamibi imaging reliably identifies retained contractile reserve in dyssynergic myocardial segments

BackgroundRecently there has been considerable controversy regarding the use of 99mTc-labeled sestamibi as an agent for the detection of viable myocardium. In this study we have used dobutamine-induced left ventricular wall thickening by echocardiography in regions with evidence of resting dyssynergy of the left ventricle as an indicator of retained contractile reserve and compared this with 99m Tc-labeled sestamibi uptake in the same regions.Methods and ResultsTwenty-seven patients with documented coronary artery disease and severe regional wall motion abnormalities underwent low-dose (5 to 15 μg/kg/min) dobutamine echocardiography and maximal (15 to 40 μg/kg/min) stress dobutamine 99mTc-labeled sestamibi single-photon emission computed tomographic imaging. Separate-day rest 99mTc-labeled sestamibi scanning was also performed. 99mTc-labeled sestamibi uptake was assessed semiquantitatively from grades from 1 to 4, from normal to absent perfusion. Regions with grade 3 or less uptake were considered viable by 99mTc-labeled sestamibi. Of the 34 regions with severe wall motion abnormalities by echocardiography, 32 showed improved wall thickening with low-dose dobutamine. Rest 99mTc-labeled sestamibi detected retained myocardial viability in 29 of these regions (91%) that were deemed to have contractile reserve by echocardiography (concordance: 91% [K=0.53; p<0.001]). Furthermore, stress-rest 99mTc-labeled sestamibi revealed completely reversible defects in five regions (16%), partially reversible defects in 24 regions (75%), and grade 4 uptake and fixed (nonviable) defects in three (9%) of these 32 regions with retained contractile reserve.ConclusionUptake of 99mTc-labeled sestamibi at rest accurately identifies regions of segmental dyssynergy in which recovery of function may be provoked by inotropic stimulation. Addition of stress dobutamine 99mTc-labeled sestamibi provides further proof of retained myocardial viability in these dysfunctional segments.