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Safety and feasibility of dobutamine-atropine stress echocardiography in patients with ischemic left ventricular dysfunction.

The aim of this study was to analyze whether left ventricular dysfunction affects the safety and feasibility of high-dose dobutamine-atropine stress echocardiography. We examined the results of the test in 318 consecutive patients who were referred for high-dose dobutamine-atropine stress echocardiography and also underwent diagnostic cardiac catheterization. Forty-four patients had a left ventricular ejection fraction of 25% or less (mean, 21%; range, 15% to 25%). In the entire group of 318 patients, no serious complications (death, myocardial infarction, or ventricular fibrillation) occurred. The overall feasibility of completing the test was excellent (97%). A trial fibrillation occurred in four patients, nonsustained ventricular tachycardia in 12, and sustained ventricular tachycardia in one. A decrease in systolic blood pressure of greater than 40 mm Hg or a peak systolic pressure of less than 80 mm Hg was present in eight cases. In the group with an ejection fraction of 25% or less, there was a higher rate of significant tachyarrhythmias (14% versus 5%; p = 0.03), whereas the feasibility of the test was slightly lower (89%; p < 0.01), but no difference for hypotension was found. By multivariate analysis, a history of tachyarrhythmias was the only predictor of stress-induced arrhythmias. Advanced left ventricular dysfunction does not represent a contraindication for dobutamine-atropine stress testing.

Adrenergic beta-Agonists↗

Mechanism and significance of a decrease in ejection fraction during exercise in patients with coronary artery disease and left ventricular dysfunction at rest.

The purpose of this study was to determine whether an exercise-induced decrease in ejection fraction in patients with coronary artery disease and left ventricular dysfunction at rest represents ischemia or the nonspecific response of a compromised left ventricle to exercise stress. Accordingly, radionuclide ejection fraction responses of 246 patients with coronary artery disease and an ejection fraction at rest of less than 0.50 were compared with those of a "nonischemic" control group of 48 patients with idiopathic dilated cardiomyopathy and a similar degree of ventricular dysfunction. The significance of the ejection fraction response in the group with coronary artery disease was further examined by relating it to the angiographic extent of coronary artery disease, severity of angina, incidence of chest pain and electrocardiographic ST segment depression during exercise and long-term prognosis. The ejection fraction decreased by greater than or equal to 0.01 and greater than or equal to 0.05 during exercise in 48 and 28%, respectively, of the patients with coronary artery disease compared with only 8 and 2%, respectively, of the patients with cardiomyopathy. When exercise was limited by fatigue at a submaximal heart rate, the ejection fraction decreased in 25% of the patients with coronary artery disease but in none of the patients with cardiomyopathy. Patients with coronary artery disease whose ejection fraction decreased during exercise had a significantly higher incidence of three vessel disease, exercise-induced chest pain or ST depression and late mortality than did patients whose ejection fraction did not decrease. These relations were confirmed equally in subgroups of patients with moderate (ejection fraction 0.30 to 0.49) and severe (ejection fraction less than 0.30) left ventricular dysfunction. Thus, in patients with coronary artery disease and left ventricular dysfunction at rest, a decrease in ejection fraction during exercise is more likely to indicate ischemia than a nonspecific left ventricular response to exercise stress. In the individual patient, a decrease of 0.05 or greater, or a decrease during submaximal exercise, appears to be highly specific for ischemia. A decrease in ejection fraction identifies a subgroup of patients with a high prevalence of multivessel coronary artery disease and a high risk of death during long-term follow-up on medical therapy.

Adult↗

Risk stratification of patients with coronary artery disease and left ventricular dysfunction by exercise radionuclide angiography and exercise electrocardiography.

BACKGROUND: The results of multicenter trials indicate that patients with left ventricular dysfunction and either three-vessel or left main coronary artery disease have improved prognosis when treated surgically. OBJECTIVE: As part of a larger evaluation and follow-up study of coronary artery disease, the objective of this investigation was to determine whether exercise radionuclide angiography can be used, in patients with mild symptoms of coronary artery disease and left ventricular dysfunction at rest, to identify patients with three-vessel or left main coronary artery disease. METHODS AND RESULTS: Eighty-four consecutive patients were studied with angiographically defined coronary artery disease in whom left ventricular ejection fraction at rest ranged from 20% to 40%. Patients underwent exercise electrocardiography, rest and exercise radionuclide angiography, and 24-hour electrocardiographic monitoring. There were 22 patients with one-vessel, 31 with two-vessel, 27 with three-vessel, and four with left main coronary artery disease. All but four patients had a documented history of myocardial infarction. By univariate analysis, the following parameters were related to the anatomic severity of coronary artery disease: magnitude of ST segment depression with exercise (p < 0.001), magnitude of change in ejection fraction with exercise (p < 0.005), and occurrence of angina during exercise (p < 0.005). However, because of the extensive overlap among anatomic subgroups, no single factor had both a satisfactory sensitivity and a satisfactory specificity in identifying patients with three-vessel and left main coronary artery disease. Multivariate stepwise regression analysis also failed to predict three-vessel or left main coronary artery disease satisfactorily (sensitivity 73% and specificity 73%; positive predictive accuracy 59% and negative predictive accuracy 83%). Nonetheless, this multivariate analysis provided important prognostic information. During medical therapy (mean follow-up 56 months), the patients with a high likelihood of three-vessel or left main coronary artery disease had a greater risk of death or reinfarction than had patients with a low likelihood (p < 0.05). These functional data were better than coronary anatomy alone in providing risk stratification. Four of six patients with two-vessel disease who died were classified incorrectly by the multivariate analysis in the high-likelihood group for three-vessel or left main coronary artery disease, but classified correctly as being at high risk; whereas none of the patients with three-vessel disease who were misclassified in the low-likelihood group died during medical therapy. CONCLUSION: Although exercise radionuclide angiography in patients with minimal symptoms of coronary artery disease and left ventricular dysfunction is not precise in predicting three-vessel or left main coronary artery disease, it provides important functional information regarding subsequent prognosis during medical therapy.

Adult↗

Selective activation of atrial natriuretic peptide in patients with myocardial infarction and mild left ventricular dysfunction.

The purpose of this study was to investigate whether neurohumoral activation occurs in asymptomatic patients with acute myocardial infarction (AMI) and without clinical signs of heart failure. During the early phase of AMI (mean 8 days), the neurohumoral profiles of 60 patients (mean age 59 range 37 to 70) were examined. Blood levels of the following humoral parameters were measured: atrial natriuretic peptide (ANP), plasma renin activity, aldosterone and vasopressin. All patients underwent cardiac catheterization during hospitalization. Baseline hemodynamic characteristics identified left ventricular dysfunction (ejection fraction < or = 45% and/or left ventricular end-diastolic pressure > or = 15 mmHg) in 32 patients; the remaining 28 patients had normal hemodynamic parameters. In patients with AMI, plasma ANP levels differed significantly from control subjects (111 +/- 74 pg/ml vs. 53 +/- 18 pg/ml; P < 0.001). In patients with AMI and mild left ventricular dysfunction ANP levels were significantly increased when compared to patients with AMI and normal left ventricular function (129 +/- 73 pg/ml vs. 82 +/- 69 pg/ml; P < 0.001). The hemodynamic data showed a significant correlation with ANP only in patients with AMI and left ventricular dysfunction (EF% r = 0.42; LVEDP r = 0.44; P < 0.001). These data show that in patients with myocardial infarction and without heart failure, the atrial natriuretic peptide is the only neurohumoral system activated out of all neurohumoral systems tested in this population and its circulating levels are strictly related to the degree of left ventricular dysfunction.

Adult↗

Predictors of right ventricular dysfunction in patients with coronary artery disease and reduced left ventricular ejection fraction.

BACKGROUND: The frequency and determinants of right ventricular (RV) dysfunction in patients with coronary artery disease (CAD) and reduced left ventricular (LV) function have not been thoroughly investigated. METHODS: The study population consists of 80 consecutive patients, invasively evaluated at our centre. Entry criteria were: LV ejection fraction < 45%; angiographic evidence of obstructive CAD; disease history of more than 3 months' duration. Exclusion criteria were: recent myocardial infarction and unstable angina. All patients underwent cardiac catheterization with coronary, LV and RV angiography. RV dysfunction was defined as a RV ejection fraction < 35%, which corresponds to the mean-three standard deviations of controls. RESULTS: Sixty-five patients (81%) had multi-vessel disease and 57 (71%) had a previous myocardial infarction. Mean LV ejection fraction was 31 +/- 8%. Mean RV ejection fraction was 46 +/- 11%. Right ventricular dysfunction was present in 14 patients (18%). An occluded proximal right coronary artery was associated with significantly lower RV ejection fraction (38 +/- 12% versus 47 +/- 10%; P = 0.009) but not LV ejection fraction (30 +/- 8% versus 32 +/- 9%; P = 0.444). However, at multivariate analysis, only pulmonary hypertension was an independent significant predictor of RV dysfunction (P < 0.001; OR: 1.13; CI: 1.06 -1.22). CONCLUSION: Right ventricular dysfunction in patients with chronic ischaemic LV dysfunction is detected in less than 20% of cases. Proximal right coronary artery occlusion is associated with a reduced RV ejection fraction. However, the role of right coronary artery disease is overwhelmed by the haemodynamic burden of pulmonary hypertension, which represents the only independent predictor of RV dysfunction in our population.

Aged↗

Abnormal coronary microvascular endothelial function in humans with asymptomatic left ventricular dysfunction.

BACKGROUND: Coronary endothelial dysfunction may potentially lead to myocardial ischemia and to the progression of heart failure. Though endothelial dysfunction is associated with advanced heart failure in humans, relatively little is known regarding their temporal relationship. Thus, the current study was designed to test the hypothesis that coronary endothelial dysfunction is present in patients with asymptomatic left ventricular dysfunction. METHODS AND RESULTS: Three hundred patients without symptoms of heart failure, with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine (ACH) and nitroglycerin. Patients were divided into 2 groups based on the left ventricular ejection fraction (EF): patients with asymptomatic left ventricular dysfunction (ALVD), EF <45% (n = 11); and patients with EF > or =45% (n = 289, controls). Except for a lower high-density lipoprotein level in patients with ALVD, there were no significant differences between the groups in regards to conventional cardiovascular risk factors. There was no difference in the change (mean +/- SE) in epicardial diameter in response to ACH (-21.7% +/- 7.2% vs -13.8% +/- 1.5%, P =.3). The change in coronary blood flow in response to ACH was significantly attenuated in the patients with ALVD when compared to the controls (-18.5% +/- 14.9% vs 74.0% +/- 7.2%, P <.013). By multivariate analysis, EF was an independent predictor of coronary microvascular dilation with ACH (P <.001). CONCLUSION: The current study demonstrates that coronary microvascular endothelial dysfunction is present in ALVD. Thus, coronary endothelial dysfunction may be an early event in the pathophysiology of heart failure.

Adult↗

Prediction of contractile reserve by cyclic variation of integrated backscatter of the myocardium in patients with chronic left ventricular dysfunction.

OBJECTIVE: To clarify whether assessment of the acoustic properties of the myocardium at rest can predict contractile reserve in patients with chronic left ventricular dysfunction. METHODS: 23 patients (mean (SD) age 63 (12) years) with chronic left ventricular dysfunction were studied. The magnitude of cardiac cycle dependent variation of integrated backscatter (CVIB) of the myocardium was measured at rest in the basal and mid segment of the septum and posterior wall of the left ventricle, using a real time two dimensional integrated backscatter imaging system. The results were compared with the percentage wall thickening and the wall motion at rest and during low dose dobutamine infusion. The wall motion was graded as normal, hypokinetic, or akinetic and contractile reserve was considered present when an akinetic or hypokinetic segment improved during dobutamine infusion. RESULTS: The CVIB at rest correlated with per cent wall thickening at rest and during dobutamine infusion (at rest, r = 0.61, p < 0.0001, during dobutamine, r = 0.76, p < 0.0001). Of the 76 segments examined, 27 showed contractile reserve. The mean CVIB at rest was significantly greater in segments with contractile reserve than in those without (p < 0.0001). CVIB above 3 dB at rest predicted segments with contractile reserve with a sensitivity and specificity of 81% and 60%, respectively (p < 0.0001). CONCLUSIONS: CVIB reflected not only myocardial contractility but also the functional capacity of the myocardium. It predicted segmental contractile reserve in patients with chronic left ventricular dysfunction.

Adult↗

A prospective clinical, scintigraphic, angiographic and functional evaluation of patients after inferior myocardial infarction with and without right ventricular dysfunction.

To elucidate the functional and prognostic significance of right ventricular dysfunction after acute inferior wall myocardial infarction, 74 consecutive patients with inferior infarction were prospectively evaluated with gated equilibrium blood pool imaging at rest, submaximal exercise thallium-201 scintigraphy and coronary angiography before hospital discharge. In addition, symptom-limited stress thallium-201 scintigraphy was performed in 61 patients at 3 months, and all patients were followed up clinically for 23 +/- 15 months. Utilizing predetermined radionuclide angiographic criteria, 47 patients (Group I) had normal right ventricular function, 12 patients (Group II) had mild to moderate dysfunction and 15 patients (Group III) had severe right ventricular dysfunction. There were no significant differences among the groups with regard to age, history of prior myocardial infarction, peak creatine kinase values, maximal Killip functional class, number or type of in-hospital complications, left ventricular ejection fraction, prevalence of multivessel disease or the distribution and severity of disease affecting the infarct-related vessel. Exercise tolerance as assessed by treadmill time, blood pressure-heart rate product and peak work load in METS was comparable among the three groups, both before hospital discharge and at 3 month follow-up. No differences in indicators of exercise-induced ischemia were noted among the groups, including the prevalence of redistribution thallium-201 defects, ST segment depression or symptoms of chest pain. Finally, cardiac mortality, reinfarction rate and the incidence of medically refractory angina pectoris were similar in the three groups. Thus, right ventricular dysfunction after acute inferior wall myocardial infarction does not appear to limit exercise tolerance or identify a subgroup of patients at higher risk for recurrent cardiac events.

Adult↗

Enalaprilat decreases plasma endothelin and atrial natriuretic peptide levels and preload in patients with left ventricular dysfunction after cardiac surgery.

OBJECTIVE: To study the acute effects of angiotensin-converting enzyme inhibition by intravenous enalaprilat infusion in patients with left ventricular dysfunction after cardiac surgery. DESIGN: Prospective, consecutive sample, before-after trial. SETTING: Surgical intensive care unit in a tertiary care university hospital. PARTICIPANTS: Eight patients with left ventricular dysfunction after cardiac surgery. Patients were defined as having left ventricular dysfunction if the pulmonary capillary wedge pressure persisted above 18 mmHg in spite of conventional vasoactive medication (inotropic or vasodilating and diuretic drugs) and intermittent mandatory ventilation during the first postoperative week. INTERVENTIONS: Enalaprilat was infused initially at 1 mg/ hour. The rate was doubled every 30 minutes until pulmonary capillary wedge pressure decreased at least 20% or until a maximum total dose of 10 mg was achieved. MEASUREMENTS AND RESULTS: Central hemodynamics, systemic oxygenation, and hormonal regulation of circulation (plasma renin activity, plasma endothelin, atrial natriuretic peptide, norepinephrine, epinephrine, and vasopressin concentrations, serum angiotensin-converting enzyme activity, and serum levels of aldosterone) were assessed at baseline before enalaprilat infusion, and repeatedly over 2 hours after the infusion. Enalaprilat infusion (median dose, 2.0 mg; infusion time, 48 minutes) caused a significant decrease in pulmonary capillary wedge pressure (p = 0.004), lasting until the end of the 2 hours' follow-up. This coincided with inhibition of serum angiotensin-converting enzyme activity (p < 0.001), an increase in plasma renin activity (p = 0.022), and decreases in plasma endothelin (p = 0.035), atrial natriuretic peptide (p = 0.005), and serum aldosterone (p = 0.001) concentrations. Cardiac output, venous admixture, and oxygen delivery and consumption remained unchanged. CONCLUSIONS: Adding enalaprilat to conventional therapy makes it possible to unload the left ventricle and to relieve overt neurohormonal activation temporarily while maintaining cardiac function and systemic oxygenation.

Adult↗

[Effect of chronic therapy with low dose of angiotensin converting enzyme inhibitors on mortality in patients with left ventricular dysfunction after acute myocardial infarction].

UNLABELLED: Angiotensin converting enzyme inhibitors (ACE-I) used in patients with postinfarction left ventricular dysfunction reduce the risk of death. Some patients do not tolerate high dose of medications which benefit was well documented in multicentre trials. THE AIM OF THIS STUDY: was to evaluate the effect of low doses of ACE-I on mortality rate in patients with ejection fraction (EF) below < or = 35% after acute myocardial infarction (MI) in long-term observation. MATERIAL AND METHODS: Study population consisted of 84 patients (pts) (67 men and 17 women) aged 38-79 (mean age 61 +/- 11) years with post-MI left ventricular dysfunction (EF < or = 35%). Patients were divided into 2 groups according to applied treatment: the group ACE-I (+) - 50 pts who received captopril, enalapril, trandolapril, perindopril or quinapril at doses not exceeding half of target dose in chronic heart failure and the group ACE-I (-) - 34 pts not treated with ACE-I. The end point of this observation was total mortality during 48 month follow-up. RESULTS: During long-term observation 33 from 84 patients died (39%). Mortality from all causes in the group ACE-I (+) was non significantly reduced as compared with the group ACE-I (-) (36% vs. 44%). CONCLUSION: In patients with left ventricular dysfunction (EF < or = 35%) after acute myocardial infarction chronic treatment with low doses of ACE-I do not reduce total mortality rate.

Angiotensin-Converting Enzyme Inhibitors↗

High-sensitivity C-reactive protein and parameters of left ventricular dysfunction.

BACKGROUND: Elevated levels of high-sensitivity C-reactive protein (CRP), an inflammatory marker, have been associated with heart failure. However, it is not known which parameters of left ventricular dysfunction correlate with elevated levels of CRP. METHODS AND RESULTS: In this cross-sectional study of 98 patients referred for cardiac catheterization, we investigated whether commonly used clinical indices of left ventricular dysfunction correlated with CRP levels. CRP levels were elevated to a greater degree in participants with diabetes mellitus (P =.006) and heart failure (P =.003). Increased CRP levels were associated with increased plasma levels of B-type natriuretic peptide (BNP; P =.0001), decreased left ventricular ejection fraction (LVEF; P =.02), and increased left-ventricular end-diastolic pressure (LVEDP; P =.0005). After multivariable adjustment, LVEDP and CRP were independently associated (P =.046). CONCLUSION: CRP is increased in patients with heart failure. Of the clinical parameters of left ventricular dysfunction, direct measurement of left ventricular end-diastolic pressure is most closely associated with CRP.

Aged↗

Exercise-induced left ventricular dysfunction in symptomatic and asymptomatic patients with aortic regurgitation: assessment with radionuclide cineangiography.

In patients with aortic regurgitation,, left ventricular dysfunction at rest, which is associated with a poor long-term prognosis, often develops before severe symptoms. To determine whether evidence of left ventricular dysfunction could be detected before it appeared at rest, 43 patients with severe aortic regurgitation were studied using radionuclide cineangiography during exercise. In 30 normal subjects, left ventricular ejection fraction increased during exercise (57 +/- 1 percent [mean +/- standard error] at rest, 71 +/- 2 percent during exercise, P less than 0.001). In contrast, among 21 symptomatic patients, ejection fraction was normal at rest in 14 patients (average 47 +/- 2 percent) but normal during exercise in only one patient (average 38 +/- 2 percent, P less than 0.001). Ejection fraction was normal at rest in 21 of 22 asymptomatic patients (average 62 +/- 2 percent) but was normal during exercise in only 13 (average 57 +/- 3 percent, P less than 0.001). Thus, exericse-induced left ventricular dysfunction can precede symptoms and dysfunction at rest. Radionuclide assessment of left ventricular function during exercise may prove valuable in sequentially following the state of left ventricular function in patients before the onset of symptoms or of irreversible left ventricular failure.

Adolescent↗

Early- and long-term comparison of the on- and off-pump bypass surgery in patients with left ventricular dysfunction.

OBJECTIVE: The adverse effects of extracorporeal circulation increase the morbidity and mortality risk of coronary bypass surgery, especially in patients with left ventricular dysfunction. The purpose of this study was to provide a comparison of the early and long-term outcome between patient groups with left ventricular dysfunction (LVEF<40% or LVPS>or=15) operated with or without using cardiopulmonary bypass. METHODS: Fifty-one patients with left ventricular dysfunction, who were operated on between October 1992 and March 1994, were investigated retrospectively. They were divided into two groups: BH-group included 26 patients and cardiopulmonary bypass group had 25 patients. Mean age and risk factors were identical. All patients received one vessel bypass left internal mammary artery to left descending artery. RESULTS: There was no early mortality and perioperative myocardial infarction in either group. In the early postoperative period the need of cardiac support therapy was significantly higher in the cardiopulmonary-bypass group than in the beating heart-group: 32% versus 7.7% (p<0.05). The need for blood products (for fresh frozen plasma 3.63 +/- 2.15u versus 2.5 +/- 1.34u; p = 0.023; for packed red blood cells 1.8 +/- 0.75u versus 1.25 +/- 0.46u; p = 0.048), the extubation time (18.2 +/- 5.5 hours versus 15.3 +/- 3.8 hours; p = 0.03) and the hospital stay (10.64 +/- 3.2 days versus 7.92 +/- 2.25 days; p = 0.001) were higher in the cardiopulmonary bypass -group than in the beating heart-group. Actuarial survival for the beating heart-group was 92.3 +/- 5.2% at 6 years, and for the cardiopulmonary bypass group was 92 +/- 5.4% at 6 years (p = 0.67). CONCLUSIONS: In spite of more than four times as many patients in the cardiopulmonary bypass group requiring inotropic support after surgery, survival and cardiac death rates were similar for both groups. Off-pump bypass surgery conserves the blood constituents. The benefits of both techniques to improve the left ventricular performance score and ejection fraction were similar, but postoperative extubation time, length of intensive care unit and hospital stay were reduced significantly in the beating heart group. With these good results of the beating heart coronary bypass surgery and considering its cost effectiveness, we concluded that coronary bypass on a beating heart can be an alternative to cardiopulmonary bypass technique in selective patient groups.

Adult↗

Experience with nifekalant hydrochloride in a patient with ischemic cardiomyopathy and severe ventricular dysfunction after dor operation.

A 52-year-old male with ischemic cardiomyopathy and severe ventricular dysfunction underwent coronary artery bypass grafting and left ventricular reconstruction (Dor operation). The patient developed acute onset of incessant ventricular tachycardia in the early postoperative period that was refractory to therapy with class I antiarrhythmic agents, and multiple attempts at electrical cardioversion were required. A combination of intravenous nifekalant hydrochloride and enteral amiodarone was elected as treatment for this recurrent incessant ventricular tachycardia. Nifekalant hydrochloride was administered as a loading dose (0.3 mg/kg/5 min), followed by an intravenous infusion (0.4 mg/kg/hr). Several days after initiating therapy, the patient no longer experienced episodes of ventricular tachycardia, and there was no compromise in hemodynamics. We conclude that nifekalant hydrochloride is a useful agent for suppression of ventricular tachycardia in patients with severe left ventricular dysfunction, especially during the early postoperative period.

Anti-Arrhythmia Agents↗

[Symptomatic left ventricular dysfunction and Behçet disease. Report of 2 cases].

Behçet's disease is associated with cardiac complications which may affect all three cardiac layers in 1 to 6% of cases. Although pericardial and coronary disease are the most common, the myocardium may also be affected. The clinical presentation may be left ventricular dysfunction with signs of dilated cardiomyopathy. The cause of the left ventricular dysfunction is usually coronary artery disease but it can also be inflammatory, resulting in a myocarditis with normal coronary arteries. The authors report two cases of Behçet's disease with symptomatic left ventricular dysfunction presenting as dilated cardiomyopathy with normal coronary arteries in one of the cases. Recent echocardiographic studies suggest that the incidence of myocardial disease is underestimated in this pathology: 20 to 35% of patients with Behçet's disease but no cardiac symptoms had left ventricular diastolic dysfunction. A more attentive investigation of left ventricular diastolic function in these patients should enable earlier diagnosis of this complication.

Adult↗

Adverse effects of ACE inhibitors in patients with chronic heart failure and/or ventricular dysfunction : meta-analysis of randomised clinical trials.

BACKGROUND: The evidence-based benefit/risk evaluation of therapeutic interventions in randomised clinical trials should include both the assessment of the benefits and of the adverse outcomes. There is ample evidence that ACE inhibitors improve the symptoms and prognosis of chronic heart failure (CHF) and ventricular dysfunction. However, there is little systematic information on the tolerability and adverse effects associated with their use in these conditions. OBJECTIVE: To estimate the adverse events related to ACE inhibitor use in the treatment of CHF and ventricular dysfunction. DESIGN AND METHODS: Description of adverse events in reports of randomised clinical trials of ACE inhibitors in CHF or ventricular dysfunction was examined, and a meta-analysis was performed. Trials were included if they were placebo- or standard treatment-controlled, and if the treatment duration was at least 8 weeks. Relative risks and their 95% CIs were estimated with a random effects model. RESULTS: Only 22 (43%) of 51 original reports contained information on the number of withdrawals and their causes. Missing information from the remaining 29 trials was obtained from the authors. The weighted mean duration of treatment was 100.2 weeks. After excluding administrative reasons, heart failure, myocardial infarction and hypertension, the withdrawal rates attributed to adverse events were 13.8% and 9.4% for the ACE inhibitor and control groups, respectively (RR = 1.54 [95% CI 1.30-1.83]; weighted difference = 3.1 per 100 treated patients [95% CI 1.8-4.4]). Cough, hypotension, renal dysfunction, dizziness, hyperkalaemia, and impotence were all significantly more prevalent among patients treated with ACE inhibitors than among those in the control groups. CONCLUSIONS: Among patients with CHF or ventricular dysfunction enrolled in randomised clinical trials, treatment with an ACE inhibitor for an average of 2 years leads to an additional 3% of treatment withdrawals. In a significant proportion of the reports on these randomised clinical trials, information on adverse events leading to treatment withdrawal was inadequate. Proper evidence-based evaluation of the benefit/risk of therapeutic interventions needs a more systematic approach to reporting of adverse events experiences recorded in clinical trials.

Angiotensin-Converting Enzyme Inhibitors↗

Efficacy and safety of calcium channel blockers in hypertensive patients with concomitant left ventricular dysfunction.

The use of calcium channel blockers (CCBs) in the treatment of hypertension and concomitant left ventricular dysfunction is reviewed. Some CCBs, particularly second-generation dihydropyridine agents such as felodipine, isradipine, nicardipine, nimodipine, and nitrendipine, have properties that enhance their usefulness in these patients. All CCBs have a similar mechanism of action. Differences in their selective action at various tissue sites determine which are most appropriate for patients with concomitant hypertension and left ventricular dysfunction. Most CCBs do not produce reflex stimulation of the heart or induce intravascular expansion. While all CCBs produce arteriolar dilation, all local beds and regional circulations in target organs are not affected equally. Most CCBs can decrease cardiac mass, and second-generation CCBs tend to have little or no negative inotropic effects at therapeutic dosages. In addition, they increase blood flow and reduce myocardial oxygen requirements. Because of differences in functional and electrophysiologic effects, specific CCBs may not be appropriate for all patients. Since second-generation dihydropyridine CCBs lack clinically relevant negative inotropic effects, and have been shown to improve exercise tolerance and coronary artery perfusion, they are appropriate for hypertensive patients with left ventricular dysfunction, angina, and coronary heart disease. Second-generation CCBs tend to lack cardiodepressant side effects and are less likely to react with digoxin than are first-generation CCBs.

Antihypertensive Agents↗

Prognostic value of myocardial viability in medically treated patients with global left ventricular dysfunction early after an acute uncomplicated myocardial infarction: a dobutamine stress echocardiographic study.

BACKGROUND: Residual viable myocardium identified by dobutamine stress after myocardial infarction may act as an unstable substrate for further events such as subsequent angina and reinfarction. However, in patients with severe global left ventricular dysfunction, viability might be protective rather than detrimental. The aim of this study was to assess the impact on survival of echocardiographically detected viability in medically treated patients with global left ventricular dysfunction evaluated after acute uncomplicated myocardial infarction. METHODS AND RESULTS: The data bank of the large-scale, prospective, multicenter, observational Echo Dobutamine International Cooperative (EDIC) study was interrogated to select 314 medically treated patients (271 men; age, 58+/-9 years) who underwent low-dose (</=10 microg x kg-1 x min-1) dobutamine for the detection of myocardial viability and high-dose dobutamine for the detection of myocardial ischemia (</=40 microg x kg-1 x min-1 with atropine </=1 mg) performed 12+/-6 days after an acute uncomplicated myocardial infarction and showing a moderate to severe resting left ventricular dysfunction (wall motion score index [WMSI] >1.6). Patients were followed up for 9+/-7 months. Low-dose dobutamine stress echocardiography identified myocardial viability in 130 patients (52%). Dobutamine-atropine stress echocardiography was positive for ischemia in 148 patients (47%) and negative in 166 patients (53%). During the follow-up, there were 12 cardiac deaths (3.8% of the total population). With the use of Cox proportional hazards model, delta low-dose WMSI (the variation between rest WMSI and low-dose WMSI) was shown to exert a protective effect by reducing cardiac death by 0.8 for each decrease in WMSI at low-dose dobutamine (coefficient, -0.2; hazard ratio, 0.8; P<0.03); WMSI at peak stress was the best predictor of cardiac death in this set of patients (hazard ratio, 14.9; P<0.0018). CONCLUSIONS: In medically treated patients with severe global left ventricular dysfunction early after acute uncomplicated myocardial infarction, the presence of myocardial viability identified as inotropic reserve after low-dose dobutamine is associated with a higher probability of survival. The higher the number of segments showing improvement of function, the better the impact is of myocardial viability on survival. The presence of inducible ischemia in this set of patients is the best predictor of cardiac death.

Aged↗