enalapril and Arrhythmias--Cardiac

A variety of clinical syndromes can cause T-wave inversion (TWI), ranging from life-threatening events to benign conditions. One benign cause of TWI is cardiac memory, which is characterized by the transient inversion of T-waves following abnormal activation of the ventricles, commonly due to intermittent left bundle branch block (LBBB), tachydysrhythmias, electrical pacing, or ventricular pre-excitation.. A 72-year-old man presented to the emergency department with chest pain, nausea, vomiting, and headache. Upon arrival, his electrocardiogram (ECG) showed new-onset LBBB with appropriate secondary ST-T wave changes. A subsequent ECG showed disappearance of LBBB and newly inverted T-waves in precordial leads V1-V5, followed by a repeat ECG that again showed LBBB. Serial troponin testing was unremarkable. During hospitalization, echocardiogram and nuclear perfusion stress test were normal. The transient TWIs in this patient were believed to be due to cardiac memory. We performed a literature review and identified 39 published cases of cardiac memory. The most common etiology for cardiac memory was after cardiac pacemaker placement, followed by intermittent LBBB (as was seen in our patient), and post-tachydysrhythmia. Patient ages ranged from 21 to 88 years, with an equal number of cases reported in men and women. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cardiac memory is a poorly understood, rarely observed phenomenon that can occur in the setting of intermittent LBBB. Testing for acute cardiac ischemia and underlying coronary artery disease is still recommended, as the diagnosis of cardiac memory can only be made after negative workup.

Topics: Aged; Amlodipine; Arrhythmias, Cardiac; Aspirin; Bundle-Branch Block; Chest Pain; Electrocardiography; Emergency Service, Hospital; Enalapril; Headache; Heart Ventricles; Humans; Isosorbide Dinitrate; Male; Nausea; Nitroglycerin; Platelet Aggregation Inhibitors; Vasodilator Agents; Vomiting

The heart failure is one of the pathologies with major social and economic impact in the western world. The neurohormonal modulation is the only effective pharmacological approach. The increasing use of implantable devices apparently sets against the possibilities of implementing in the patient's treatment scheme. However, the anti-adrenergic therapy, once used at optimal dose, is highly effective on sudden death and on rates of implantable cardioverter defibrillators discharges. CIBIS-III proposes the beta-blocker use as primary approach, even prior to ACE inhibitors. This might be specifically true in the patient whit evidence of autonomic imbalance resulting in sympathetic hyperactivity. CIBIS-III shows that bisoprolol can be used in chronic heart failure patients also in absence of the concomitant enalapril therapy. Using bisoprolol as primary approach allows to reach optimal doses more effective on arrhythmic risk. CIBIS III results propose new strategies to the current international heart failure guidelines's recommendations.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Bisoprolol; Death, Sudden, Cardiac; Defibrillators, Implantable; Enalapril; Heart Failure; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Time Factors

The failure of encainide and flecainide to reduce mortality after infarction in the Cardiac Arrhythmia Suppression Trial and the failure of low-dose amiodarone to prevent sudden cardiac death in patients with a low left ventricular ejection fraction has shifted attention to other strategies, such as beta-adrenergic blocking agents, to prevent sudden cardiac death. Evidence suggesting that beta-adrenergic blocking agents might be useful, especially in patients with low left ventricular ejection fraction, is accumulating. Previous data from studies using beta-adrenergic blocking agents and the mechanisms by which beta-adrenergic blocking agents might be of value in preventing sudden cardiac death are reviewed. These considerations and the availability of new investigational beta-adrenergic blocking agents with vasodilator properties provide a new opportunity to test the hypothesis that beta-adrenergic blocking agents are useful in preventing sudden cardiac death, especially in patients with a low left ventricular ejection fraction.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiac Output, Low; Cardiomyopathy, Dilated; Catecholamines; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Diuretics; Enalapril; Heart Ventricles; Humans; Magnesium; Myocardial Infarction

The two major causes of death in congestive heart failure (CHF) are progressive heart failure (approximately 60% of cases) and sudden death (30%). Sudden death in CHF is caused primarily by malignant ventricular arrhythmias. The underlying mechanism has yet to be established, but myocardial metabolic factors are probably involved. Although there is a clear association between complex ventricular arrhythmias and left ventricular function, it has not been shown convincingly that antiarrhythmic agents can reduce sudden death in CHF. Progressive deterioration of myocardial function is associated with altered myocardial energy production. Notably, the physiological effects of neuroendocrine activation in chronic CHF may be deleterious to myocardial function. The CONSENSUS study was carried out to evaluate the association between neuroendocrine activation and deterioration of myocardial function using ACE inhibitors. A marked reduction in mortality rate occurred in the enalapril-treated group, where the one-year mortality was reduced by 31%. The reduction in mortality was solely among patients with progressive CHF (a reduction of 50%); there was no difference in the incidence of sudden death. Analysis of blood samples drawn at baseline in the placebo group showed a significant positive correlation between mortality and plasma angiotensin II (P less than 0.05), aldosterone (P = 0.003), noradrenaline (P less than 0.001), adrenal levels (P less than 0.001), and atrial natriuretic peptide (P = 0.003). This was not observed in enalapril-treated patients. The significant reduction in mortality in the enalapril group was found consistently among patients with baseline hormone levels above the median value. In CHF, the underlying disease may induce serious arrhythmias and/or progressive failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Enalapril; Heart Failure; Heart Ventricles; Hormones; Humans; Prognosis

Arterial hypertension is by definition a haemodynamic disorder. At least 3 different subsets of cardiovascular pathophysiological features can be identified in so-called essential hypertension: The young lean patient characterised by an elevated cardiac output and renal blood flow, elevated plasma renin activity and circulating catecholamine levels, as well as symptoms and signs of hyperadrenergic hypertension. The elderly patient characterised by a low cardiac output often with left ventricular hypertrophy, elevated total peripheral resistance, nephrosclerosis, and symptoms and signs of target organ disease. The obese patient (and to a lesser degree the black patient) characterised by expanded fluid volume state, elevated cardiac output, a normal to low total peripheral resistance, and symptoms and signs of volume overload. To initiate antihypertensive therapy, the drug of choice in the young patient is a beta-adrenergic receptor blocker; in the elderly it is a haemodynamic vasodilator (anti-adrenergic drug, slow channel calcium blocker, or converting enzyme (ACE) inhibitor), and in black or obese patients it remains a thiazide diuretic. Enalapril, a new ACE inhibitor is indicated as a first-step agent in the great majority of hypertensive patients in whom the elevated arterial pressure should be reduced by a decrease in total peripheral resistance, without compromising systemic or regional blood flow. In contrast to other antihypertensive agents, enalapril will lower preload and afterload to the left ventricle while improving systemic and regional flow in elderly patients with latent or manifest congestive heart failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Cardiomegaly; Coronary Disease; Enalapril; Heart; Hemodynamics; Humans; Hypertension; Obesity; Racial Groups

In the era of early reperfusion therapy, life-threatening ventricular arrhythmias (VA) remain common after recanalization of an occluded coronary artery. Experimental studies reported that angiotensin-converting (ACE) inhibitors suppress reperfusion-induced VA. However, whether ACE inhibitors lower the incidence of reperfusion clinical VA is unknown. We examined the effects of low doses of intracoronary (i.c.) enalaprilat (EN) as an adjunct to direct percutaneous coronary interventions (PCI) on reperfusion VA in the acute phase of myocardial infarction (MI).. We randomly assigned 22 patients with a first acute MI, who underwent successful direct PCI, to EN, 50 mug, i.c., or placebo (PL), administered immediately after reperfusion. VA were manually edited and counted from 24-hour Holter recordings begun upon hospital admission.. There were no significant between-groups differences in clinical characteristics. Mean RR interval before and after PCI, and the incidence of VA before PCI were similar in both groups. After PCI the incidence of reperfusion-induced VA was significantly lower in the EN-treated group (VPB/h: PL 29.9 +/- 12 vs EN 43.2 +/- 42, P < 0.05; couplets/h: EN 0.9 +/- 0.7 vs PL 4.1 +/- 5.0, P < 0.01; triplets/h: EN 0.3 +/- 0.2 vs PL 1.2 +/- 1.5, P < 0.05; ventricular tachycardia/h: EN 0.3 +/- 0.1 vs PL 0.8 +/- 0.5, P < 0.01).. Compared with PL, i.c. EN significantly lowered the incidence of reperfusion-associated VA. This previously unrecognized antiarrhythmic effect might be an important therapeutic benefit conferred by ACE inhibitors, beyond limitation of infarct size.

Topics: Aged; Angioplasty, Balloon, Coronary; Antihypertensive Agents; Arrhythmias, Cardiac; Coronary Artery Disease; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Prospective Studies

Left ventricular hypertrophy (LVH) in hypertensive subjects is associated with an increased prevalence of ventricular arrhythmias. To evaluate the effect of antihypertensive treatment on cardiac arrhythmias (CA) and transient episodes of myocardial ischemia (TEMI), we studied 46 hypertensive patients with LVH, divided into four groups randomly treated with enalapril, hydrochlorothiazide (HCTZ), atenolol, or verapamil (SR-V) for 6 months. Office blood pressure and office heart rate values were recorded, in basal conditions, after 1 and 6 months of treatment, and all patients underwent echocardiography, electrocardiographic Holter monitoring, and stress testing. All drugs significantly lowered blood pressure, whereas left ventricular mass index was reduced by atenolol, enalapril, and SR-V, but not by HCTZ. Treatment induced a significant reduction in the number of patients with supraventricular arrhythmias (35 v 15, P < .034, and 28 v 8, excluding patients treated with HCTZ, P < .008). The number of patients with ventricular arrhythmias was also reduced (32 v 16 considering all groups, P < .08, and 24 v 9, excluding patients treated with HCTZ, P < .04). The number of TEMI during Holter monitoring significantly decreased from 47 to 23 (P = .043) in all patients, and from 39 to 14 (P = .013) excluding patients treated with HCTZ. In all groups, irrespective of treatment, a reduction of blood pressure, heart rate, and systolic blood pressure/heart rate product measured by exercise stress test was observed. The present study shows that in hypertensive patients with LVH, antihypertensive treatment with atenolol, enalapril and SR-V reduces LVH and decreases the prevalence of CA and TEMI. Treatment with HCTZ during the 6-month study did not alter LVH and did not appear to reduce CA and TEMI.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Atenolol; Blood Pressure; Electrocardiography, Ambulatory; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome; Verapamil

This study was designed to evaluate in 45 hypertensive patients with left ventricular hypertrophy (LVH) the effects of a 6-month course with one of three different antihypertensive regimens (the calcium channel blocker isradipine, the angiotensin converting enzyme inhibitor spirapril in monotherapy, or a combination of the two drugs, n = 15 per group) on blood pressure, LVH regression, and various functional correlates of LVH. All three treatment modalities decreased significantly LV mass index by an average of 10%, although the combination had the greatest blood pressure-lowering effect and spirapril had the least, as assessed by office resting pressures, ambulatory monitoring, and isometric grip testing. There was no correlation between magnitude of blood pressure lowering and degree of LVH regression. The effects of treatment on pressor hormone profiles differed among groups, as spirapril tended to suppress angiotensin II and norepinephrine, whereas isradipine had opposite effects. Exercise tolerance was prolonged by all three regimens, but significantly more by the combination. All three regimens decreased significantly the double product by 10% to 15%. Indices of electrophysiologic stability calculated from analysis of ambulatory electrocardiogram exhibited significant improvement in several parameters such as QRS duration, presence of late potentials, and measures of heart rate variability, resulting in fewer episodes of simple or complex ventricular arrhythmia. We conclude that all three regimens produce significant LVH regression associated with improved functional capacity and electrical stability. These results reflect the sum of the differential hemodynamic and hormonal effects exerted by each treatment modality.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male

Angiotensin convertase inhibitor (Enalapril) was used in 51 children aged 4 days up to 18 years (mean 4.3 +/- 5.5, years). As many as 27 subjects were newborns (4) and infants (23). The patients suffered from circulatory insufficiency due to congestive cardiomyopathy (13 cases). 6 treated subjects suffered from circulatory insufficiency due to congenital heart malformations before cardiac surgery and 22 after it (including complex malformations operated according to Fontan method). 10 children were treated because of arterial hypertension. 4 subjects suffered form life-threatening arrhythmias coexisting with circulatory insufficiency. (These subjects were already mentioned among the patients suffering from circulatory insufficiency). Enalapril (mainly as a drug named Benalapril) was used in the mean dose of 0.21 mg/kg of body mass daily. 4 patients (8%) died during treatment but their deaths can not be related to angiotensin convertase inhibitor therapy. In the other children (82%) the beneficial influence of angiotensin convertase inhibitor use was found (improvement in comparison with the state before convertase inhibitor introduction). In 10% of subjects enalapril did not show any significant therapeutic effect. According to authors' opinion enalapril use is exceptionally profitable in the subjects surgically treated for complex heart malformations (Fontan operation). The beneficial effect was also found in majority of children suffering from congestive cardiomyopathy. Convertase inhibitor was always successfully used as the unique antihypertensive drug in children suffering from arterial hypertension. In the other cases treatment was combined (mainly with digitalis). This combination seems to be exceptionally useful in children suffering from congestive cardiomyopathy. Only in 1 case unserious side effect was found (persistent cough).

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiac Output, Low; Child; Child, Preschool; Enalapril; Heart Defects, Congenital; Heart Failure; Humans; Hypertension; Infant; Infant, Newborn; Postoperative Care; Premedication; Survival Rate; Treatment Outcome

Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mostly small and of short duration. We prospectively studied 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction < or = 35%). Five hundred fifty-three patients from the prevention trial and 181 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months of double-blind therapy with either placebo or enalapril (2.5 to 10 mg twice daily). The prospectively defined primary analysis was by intent-to-treat and revealed no significant differences in ventricular premature complexes between the placebo and enalapril groups at baseline (87 +/- 13 vs 84 +/- 13/hour), 4 months (100 +/- 15 vs 85 +/- 12/hour), or 12 months (80 +/- 12 vs 90 +/- 14/hour). Likewise, there was no difference between the placebo and enalapril groups in runs of nonsustained ventricular tachycardia: baseline (8.3 +/- 4.1 vs 1.9 +/- 0.4 runs/day), 4 months (16 +/- 12 vs 7.2 +/- 4.1 runs/day), or after 12 months of blinded therapy (11 +/- 7.0 vs 6.1 +/- 4.4 runs/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Female; Heart Ventricles; Humans; Male; Middle Aged; Prospective Studies; Ventricular Dysfunction, Left

In this study 24-h Holter electrocardiographic recordings were used to measure the effects of an angiotensin converting enzyme inhibitor, enalapril given for 4 weeks, on the frequency of cardiac arrhythmias in 24 patients (14 patients had enalapril, 30 patients had placebo) with congestive heart failure (New York Heart Association Functional Class 3) receiving maintenance therapy with digoxin and furosemide. Although the placebo group had no change in the frequence of arrhythmias, enalapril-treated patients showed significant decrease in the frequency of premature ventricular complexes couplet, bigemine VPS and ventricular tachycardia. Moreover, it was observed that six cases of atrial fibrillation returned to sinus rhythm. During enalapril treatment, some patients experienced increased serum potassium levels, but there was no change in serum digoxin levels. We also observed echocardiographic improvement in left ventricular function as well as clinical symptoms of congestive heart failure. Finally we observed that there was an antiarrhythmic effect of enalapril in congestive heart failure. We thought that the antiarrhythmic effect of enalapril in congestive heart failure was probably due to hemodynamic improvement.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Placebos; Potassium; Tachycardia, Ventricular; Ventricular Function, Left

The present study shows that enalapril prevents the excessive remodeling of the left ventricle after acute myocardial infarction. This randomized and double blind clinical study analysed 50 patients with an inferior myocardial infarction. The effect of enalapril was evaluated through cardiac volumes, ejection fraction, neurohormonal levels and incidence of the left ventricle disfunction after acute myocardial infarction. The patients treated with enalapril showed a significant reduction on the values of nor-epinefrine, angiotensine II, natriuretic hormone and vasopressine, four weeks after initiation of treatment. The ejection fraction and the level of the wall movement was more favourable, four weeks after infarction, in the group treated with enalapril. The incidence of congestive heart failure and arrhythmias was lower in the group treated with enalapril. So, we conclude that enalapril is a drug that prevents the excessive remodelling of the left ventricle after an acute myocardial infarction.

Topics: Aged; Arrhythmias, Cardiac; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged; Myocardial Infarction; Ventricular Function, Left

Recognition of the complex pathophysiology of heart failure and its high mortality has emphasized the need for prognostic markers that can be used in clinical assessment as well as in the design of mortality trials. Data from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT I, 642 patients; V-HeFT II, 804 patients) were therefore examined to determine the influence of prerandomization measurements on subsequent mortality.. Patients entered into these trials were men with cardiac dysfunction and reduced peak exercise capacity. Measurements included in this analysis were left ventricular ejection fraction (EF) measured by radionuclide angiography, peak bicycle exercise oxygen consumption (VO2), cardiothoracic ratio (CTR) measured on a chest x-ray, ventricular arrhythmias assessed in a core laboratory by short-term Holter monitoring, plasma norepinephrine and plasma renin activity measured in a core laboratory only in V-HeFT II, and a variety of diagnostic and demographic data. The variables related only weakly to each other. EF, VO2, and CTR were powerful independent predictors of all-cause mortality in both studies. Ventricular arrhythmia was a significant independent predictor in V-HeFT II but not in V-HeFT I. Plasma norepinephrine but not plasma renin activity measured in V-HeFT II also had independent prognostic value. Other variables did not exert an independent effect on mortality.. Optimal assessment of the mortality risk in an individual or a group of individuals with heart failure uses measurement of EF, peak VO2, CTR, plasma norepinephrine, and the presence of ventricular arrhythmias.

Topics: Arrhythmias, Cardiac; Cardiomegaly; Drug Therapy, Combination; Enalapril; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Prazosin; Prognosis; Stroke Volume; Ventricular Function, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Dipeptides; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Exercise Test; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Stroke Volume; Tachycardia, Ventricular; Ventricular Function, Left

The effect of lisinopril 5-20 mg once daily or enalapril 5-20 mg once daily on exercise capacity, ventricular ectopic activity, and signs and symptoms of heart failure have been studied in 278 patients with mild-to-moderate (New York Heart Association [NYHA] classes II and III) heart failure in a randomized, double-blind, parallel-group study of 12 weeks' duration. Exercise duration was significantly increased by both angiotensin-converting enzyme (ACE) inhibitors after 6 and 12 weeks of treatment compared with their respective baseline values. There was a trend toward a greater increase in exercise duration on lisinopril after 12 weeks, although this did not reach statistical significance (p = 0.0748). There were no significant treatment differences with respect to the effect of the 2 drugs on ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Both drugs were equally effective in improving NYHA grading and symptoms. Neither treatment had any significant effect on mean heart rate or mean blood pressures. Both treatments were equally well tolerated. The most commonly reported adverse events on both drugs were cough, dizziness, fall in blood pressure, vertigo, and myocardial infarction. The results of this study indicate that lisinopril 5-20 mg once daily is at least as effective and well tolerated as enalapril 5-20 mg once daily.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Blood Pressure; Dipeptides; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Exercise Test; Female; Heart Failure; Heart Rate; Humans; Lisinopril; Male; Middle Aged; Physical Exertion; Placebos; Potassium

The two major causes of death in congestive heart failure (CHF) are progressive heart failure (approximately 60% of cases) and sudden death (30%). Sudden death in CHF is caused primarily by malignant ventricular arrhythmias. The underlying mechanism has yet to be established, but myocardial metabolic factors are probably involved. Although there is a clear association between complex ventricular arrhythmias and left ventricular function, it has not been shown convincingly that antiarrhythmic agents can reduce sudden death in CHF. Progressive deterioration of myocardial function is associated with altered myocardial energy production. Notably, the physiological effects of neuroendocrine activation in chronic CHF may be deleterious to myocardial function. The CONSENSUS study was carried out to evaluate the association between neuroendocrine activation and deterioration of myocardial function using ACE inhibitors. A marked reduction in mortality rate occurred in the enalapril-treated group, where the one-year mortality was reduced by 31%. The reduction in mortality was solely among patients with progressive CHF (a reduction of 50%); there was no difference in the incidence of sudden death. Analysis of blood samples drawn at baseline in the placebo group showed a significant positive correlation between mortality and plasma angiotensin II (P less than 0.05), aldosterone (P = 0.003), noradrenaline (P less than 0.001), adrenal levels (P less than 0.001), and atrial natriuretic peptide (P = 0.003). This was not observed in enalapril-treated patients. The significant reduction in mortality in the enalapril group was found consistently among patients with baseline hormone levels above the median value. In CHF, the underlying disease may induce serious arrhythmias and/or progressive failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Enalapril; Heart Failure; Heart Ventricles; Hormones; Humans; Prognosis

Twenty-four-hour Holter electrocardiographic recordings were used to measure the effects of a converting-enzyme inhibitor, enalapril, given for 12 weeks, on the frequency of cardiac arrhythmias in 10 patients with congestive heart failure (New York Heart Association functional class II to III) receiving maintenance therapy with digoxin and furosemide. Nine patients were given placebo, and both study groups were conducted in a double-blind, parallel manner. The placebo group had no change in the frequency of arrhythmias, whereas enalapril-treated patients showed a significant decrease in the frequency of premature ventricular complexes, ventricular couplets and ventricular tachycardia. A minor, nonsignificant reduction in atrial premature complexes was seen in patients who received enalapril. Compared with placebo patients, those who received enalapril had an increase in plasma potassium levels of 0.33 mmol/liter, a decrease in plasma digoxin, and decreases in pulmonary artery wedge, mean pulmonary artery and right atrial pressures. However, none of these indexes were correlated with the concomitant decline in cardiac arrhythmias. It is concluded that enalapril reduces the frequency of ventricular arrhythmias in congestive heart failure, although the underlying mechanisms are not known.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dipeptides; Electrocardiography; Enalapril; Female; Furosemide; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Wedge Pressure

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arrhythmias, Cardiac; Benzothiadiazines; Blood Pressure; Clinical Trials as Topic; Death, Sudden; Diastole; Dipeptides; Diuretics; Double-Blind Method; Enalapril; Follow-Up Studies; Humans; Hypertension; Myocardial Infarction; Risk; Sodium Chloride Symporter Inhibitors

Topics: Angioedema; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Aspirin; Drug Hypersensitivity; Enalapril; Female; Humans; Hypertension; Middle Aged; Propafenone; Urticaria

Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels increase after acute myocardial infarction (AMI) in humans. Experimental data suggest that these cytokines regulate the initiation of scar formation after AMI. We investigated the interrelationships of IL-6 and TNF-alpha, tissue injury, infarct size, cardiac function, and collagen formation in humans.. Serum and plasma samples were taken on 93 patients receiving thrombolytic treatment for their first AMI. Collagen formation was evaluated by measuring concentrations of serum aminoterminal propeptide of type III procollagen (PIIINP).. IL-6 levels increased by 44% (P<.001) and peaked at 24 hours. Peak IL-6 levels correlated positively with area under the curve of creatine kinase MB mass (r=.31, P<.01), peak troponin T level (r=.34, P<.005), and PIIINP measured at discharge (r=.46, P<.001). There were no changes in TNF-alpha levels, and patients with left ventricular dysfunction (EF<40%) had similar TNF-alpha levels as those with preserved left ventricular function.. IL-6 may regulate collagen formation and thus remodeling of the left ventricle after AMI. In addition, TNF-alpha measurement is useless in the assessment of infarct size or left ventricular function during the immediate post-infarction period.

Topics: Angiotensin-Converting Enzyme Inhibitors; Area Under Curve; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Collagen; Creatine Kinase; Creatine Kinase, MB Form; Electrocardiography; Enalapril; Female; Finland; Humans; Interleukin-6; Isoenzymes; Male; Myocardial Infarction; Peptide Fragments; Procollagen; Quinapril; Severity of Illness Index; Statistics as Topic; Stroke Volume; Tetrahydroisoquinolines; Time Factors; Treatment Outcome; Trinitrotoluene; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

A domestic shorthaired cat was presented with a 1-month history of cardiomegaly and recurrent chylothorax. The heart rate was 130 beats/min and no P waves were present on a surface electrocardiogram. Thoracic radiographs and an echocardiogram demonstrated severe biatrial dilatation, pleural effusion and restrictive pleural disease. Permanent atrial standstill was suspected. Pleurocentesis was performed and therapy was started with enalapril, frusemide and aspirin. Intracardiac electrograms revealed no atrial activity, and atrial pacing failed to elicit atrial or ventricular depolarisations. The patient was euthanased. Necropsy showed severe atrial wall thinning with marked cardiocyte loss. Persistent atrial standstill is a rare disease in the cat. Clinical signs may have been due to loss of atrial function, ventricular diastolic dysfunction, bradycardia, neurohormonal activation and reduced atrial natriuretic peptide plasma concentrations.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Arrhythmias, Cardiac; Aspirin; Cardiomegaly; Cat Diseases; Cats; Chylothorax; Diuretics; Echocardiography, Doppler, Color; Electrocardiography; Electrophysiology; Enalapril; Fatal Outcome; Female; Furosemide; Heart Atria; Lameness, Animal; Myocardium; Radiography, Thoracic; Recurrence

Recent investigations have shown that antihypertensive drug treatment leads to enhanced myocardial beta-adrenoceptor sensitivity. This study was therefore conducted to establish whether or not such hypersensitivity might trigger myocardial arrhythmia subsequent to adrenaline exposure. Adult male Wistar rats (n = 6 per group) were treated with either placebo (vehicle), metoprolol (2.40 mg.kg-1.day-1), timolol (0.075 mg.kg-1.day-1), verapamil (5.50 mg.kg-1.day-1) or enalapril (0.50 mg.kg-1.day-1) for 20 consecutive days. Hearts were excised and perfused ad modum Langendorff in the presence of an adrenaline gradient (0-300 nM) for 20 min with either 3.0 mM or 5.9 mM of potassium in the perfusion buffer. Adrenaline threshold concentration (ATC, nanomolar) at myocardial fibrillation was recorded, as well as tissue cAMP contents, beta-adrenoceptor number, G-protein levels and signalling effector enzyme activities. The main findings were: (1) ATC and cAMP levels were affected in hearts perfused with low-concentration potassium buffer only. In terms of ATC, the beneficial effect of each drug regimen appeared to be in the rank order of: placebo = enalapril > verapamil > timolol > metoprolol. There was an inverse correlation between ATC and myocardial cAMP contents at the start of fibrillation; (2) Subsequent to fibrillation, beta-adrenoceptor number, hormone-elicited adenylate cyclase activities and Gs alpha:Gi2 alpha-ratio were no different from preperfusion values; (3) Significant inverse correlations between beta 1-adrenoceptor numbers and ATC were observed. We conclude that alterations in beta-adrenoceptor number, G proteins and cAMP induced by antihypertensive drugs are predictive of the myocardial sensitivity to adrenaline in terms of time to continuous and irrevocable fibrillation.

Topics: Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Cyclic AMP; Enalapril; Epinephrine; GTP-Binding Proteins; In Vitro Techniques; Male; Metoprolol; Perfusion; Potassium; Rats; Rats, Wistar; Receptors, Adrenergic, beta; Signal Transduction; Timolol; Verapamil

The effect of angiotensin-converting enzyme (ACE) inhibitors on ischemia-induced spatial dispersion of ventricular repolarization was investigated in 12 pentobarbitone-anesthetized sheep. The obtuse marginal coronary artery was occluded in the pretreated animals (enalapril maleate, 0.4 mg/kg, i.v., n = 6) and controls (normal saline, i.v., n = 6). The activation-recovery intervals were determined from the unipolar ECGs acquired from the ischemic region. There was a significant increase in the pooled activation-recovery interval dispersion in both groups at 30 min of coronary occlusion (p < 0.01), however, the increase in the treatment group was smaller than that of the controls (15.9 +/- 9.7 vs. 43.6 +/- 19.9 ms, p < 0. 01). Ventricular ectopic beats were observed in the 6 controls and in only 1 pretreated animal.. ACE inhibitors suppress the spatial dispersion of ventricular repolarization and this may be attributed to, at least in part, its antiarrhythmic effect.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Coronary Disease; Electrocardiography; Enalapril; Female; Male; Myocardial Ischemia; Sheep; Ventricular Function; Ventricular Premature Complexes

Although angiotensin-converting enzyme (ACE) inhibitors are known to influence favorably the structural remodeling of the heart after myocardial infarction, the mechanisms by which ACE inhibitors improve survival are not well understood. The hypothesis that ACE inhibitors may possess antiarrhythmic activity has been studied in various isolated tissue preparations. However, the electrophysiologic effects of ACE inhibitors in the intact heart are not well understood. The effect of the ACE inhibitor enalaprilat on intact heart electrophysiology was studied by using multisite optical action-potential recordings with voltage-sensitive dyes. Action potentials were recorded simultaneously from 128 left ventricular epicardial sites in 15 Langendorff perfused hearts subjected to an endocardial cryoablation procedure, which was used to restrict propagation to a thin viable rim of epicardium. Action-potential duration (APD) was significantly prolonged in 67% of preparations perfused with 5 mg/L enalaprilat. Higher concentration of enalaprilat (50 mg/L) prolonged APD in all preparations tested. This APD-prolonging effect persisted over a broad range of stimulus rates, indicating the absence of reverse use-dependent properties. Enalaprilat did not modify conduction velocity, nor did it affect spatial dispersion of repolarization times. In addition, enalaprilat had no effect on ventricular fibrillation threshold and failed to suppress the initiation of ventricular tachycardia using an anatomically defined reentrant circuit. These findings indicate that in the intact heart, enalaprilat does indeed have electrophysiologic effects that cause APD prolongation, particularly at high drug concentrations. However, this effect was not of sufficient magnitude in the guinea pig to suppress the initiation of ventricular fibrillation or reentrant ventricular tachycardia.

Topics: Action Potentials; Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Electrophysiology; Enalapril; Guinea Pigs; Heart; Male

Cardiac transplantation is a proven, effective therapy for selected patients with end-stage congestive heart failure. Recipient selection is performed by a multidisciplinary team consisting of transplant physicians and surgeons. Clinicians responsible for patient assessment must establish the severity of cardiac dysfunction, formulate a prognosis, and stratify patients according to risk for mortality. Patients whose survival and quality of life are most limited without cardiac transplantation are candidates for therapy. The scarcity of organ donors makes careful screening of potential recipients necessary to identify those individuals most likely to obtain a long-term benefit. Recipient selection criteria and management strategies are evolving because of extended waiting times and high mortality caused by the lack of sufficient numbers of donors. Alternative therapies should be applied wherever possible.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Case Management; Cause of Death; Communicable Diseases; Enalapril; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hemodynamics; Humans; Hypertension, Pulmonary; Life Expectancy; Patient Selection; Prognosis; Risk Factors; Waiting Lists

To verify the effect of enalapril on ventricular function and on the incidence of ventricular arrhythmias in patients with Chagas' disease with congestive heart failure.. We studied 20 patients with Chagas' disease, aged between 24 to 64 (mean 44) years. There were 17 male. All patients have positive serologic blood tests for Chagas' disease (immunofluorescence and Machado-Guerreiro test), left ventricular diastolic diameter superior to 55mm and ejection fraction less than 0.60. The patients were divided aleatory in two groups: control group (CG) with 9 patients receiving conventional treatment (digital and diuretics) and enalapril group (EG), with 11 patients where enalapril was added to conventional treatment. The treatment was maintained during two months and the patients were evaluated at the beginning and at the end, when they were submitted to clinical examination, echo-doppler-cardiogram, stress test and 24h Holter monitoring. At two dimensional echocardiographic study we evaluate left ventricular and left atrial diameters, at doppler study the E/A relations, the systolic volume and cardiac index. At the stress test and Holter monitoring we evaluate the incidence of ventricular arrhythmias.. The comparison between initial and final evaluations, showed that there was a significant improvement of diastolic function (p = 0.04) and a trend to improvement of systolic function (great systolic volume and cardiac index) at EG. The incidence of non sustained ventricular tachycardia was the same in the two groups.. In Chagas' disease enalapril improves significantly diastolic dysfunction in patients with heart failure. After two months of treatment we observed tendency to improvement of systolic dysfunction and the incidence of arrhythmias induced by stress test.

Topics: Adult; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Echocardiography; Enalapril; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Ventricular Function

In a longitudinal study comprising a total of 18 patients, the paradoxical time course of hANP plasma levels, i.e. the reproducibility of the low levels previously reported in cases of extreme cardiac insufficiency after administration of amiodarone, was investigated over a period of 9 months. At the same time, the effect of the degree of cardiac insufficiency and arrhythmia on the secretion of hANP was observed. The patients had been admitted to hospital because of the diagnoses "cardiac insufficiency secondary to cardiomyopathy" or "Grade IVb arrhythmia according to Lown's classification". During in-patient treatment, antiarrhythmic therapy was commenced in all patients. Clinical examinations and determinations of humoral parameters during therapy showed a substantial number of patients, who exhibited no increase in hANP levels despite massive cardiac decompensation. As far as drug therapy of patients with severe arrhythmias secondary to congestive (dilated) cardiomyopathy is concerned, amiodarone has proved to be the drug of choice in combination with digitalis, ACE inhibitors and diuretics. There is a close correlation between the degree of cardiac insufficiency and plasma hANP levels.

Topics: Aged; Aldosterone; Amiodarone; Arginine Vasopressin; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Captopril; Cardiomyopathy, Dilated; Drug Therapy, Combination; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Longitudinal Studies; Male; Middle Aged

Topics: Aging; Animals; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Enalapril; Fibrosis; Hypertension; In Vitro Techniques; Incidence; Myocardial Reperfusion; Myocardium; Oxygen; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Reference Values

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.

Topics: Analysis of Variance; Animals; Arrhythmias, Cardiac; Blood Flow Velocity; Blood Pressure; Electrocardiography; Enalapril; Endomyocardial Fibrosis; Heart Rate; Heart Ventricles; Hypertension; Male; Rats; Rats, Inbred SHR; Ventricular Fibrillation

We studied, by 48-hour Holter monitoring, 33 patients with chronic stable heart failure (radionuclide ejection fraction less than 35%), complex ventricular arrhythmias and no electrolyte abnormalities, after a period during which they were treated with digoxin and diuretics. Before Holter monitoring blood samples were analyzed for serum concentration of sodium, potassium, magnesium, urea, creatinine, digoxin, aldosterone and for plasmatic renin activity in addition to urinary aldosterone and catecholamines determination. After these investigations in 23 patients, 5-20 mg of enalapril were progressively added to the conventional therapy, while 10 patients continued the previous therapy. After 8 weeks 30 patients were subjected to a second 48-hour Holter monitoring and to the same biochemical and hormonal tests. One patient died and 2 were lost to follow up. Only the enalapril group showed a significant decrease in the number of premature ventricular complexes (PVC) (p less than 0.01), and the frequency of couplets and episodes of ventricular tachycardia (VT) declined significantly (P less than 0.01). In the two groups there were no significant changes in digoxin, sodium, or magnesium, while potassium concentration increased in both groups (p less than 0.01). In the enalapril group heart rate and systolic and diastolic pressure declined significantly (p less than 0.01), and New York Heart Association class (NYHA) improved (p less than 0.001). In the other group there were no significant changes in these parameters. Enalapril caused a significant increase in the plasmatic renin activity (p less than 0.01) and a significant fall of plasma and urinary aldosterone (p less than 0.01; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Chronic Disease; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged

To investigate the determinants of mortality in patients with chronic congestive heart failure, we prospectively evaluated 84 patients with this disorder who underwent detailed biochemical, clinical, and functional tests at the time of initial evaluation and were then followed for 12 to 52 months (mean 31). During this period of follow-up, 58% of the patients died, of whom 71% died suddenly. The most important pretreatment predictor of mortality in these patients was the frequency of ventricular extrasystoles, followed by echocardiographic fractional shortening, a diagnosis of coronary artery disease, and duration of treadmill exercise. The finding of hypokalemia and hyponatremia in these patients at the time of entry into the study was associated with a poor prognosis by univariate analytical methods, but these electrolyte abnormalities did not provide independent prognostic information. The presence of ventricular arrhythmias was related to the severity of left ventricular dysfunction, exercise intolerance, and neurohormonal activation, suggesting that such arrhythmias are multifactorial in origin and may not simply be related to electrolyte abnormalities.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Captopril; Enalapril; Exercise Test; Female; Heart Failure; Heart Ventricles; Humans; Hypokalemia; Hyponatremia; Male; Middle Aged; Prognosis; Prospective Studies

The renin-angiotensin system has a range of physiological actions concerned with the control of the circulation. Angiotensin II has both an immediate and a delayed pressor effect; it stimulates the secretion of aldosterone and antidiuretic hormone, promotes thirst, stimulates the sympathetic nervous system at various sites while inhibiting vagal tone, and has a range of direct effects on the kidney. Several aspects of this range of actions can become deranged in a number of forms of hypertension as well as in congestive cardiac failure. Hence much effort has been directed in recent years to the development of agents designed to interfere with the renin-angiotensin system and to apply these clinically in the treatment of hypertension and congestive cardiac failure. Orally active converting enzyme inhibitors are of proven benefit not only in renovascular hypertension, but also, when combined with loop diuretics, in the treatment of intractable hypertension as well as, both alone and in combination with thiazide diuretics, in the treatment of essential hypertension. In congestive cardiac failure controlled trials have shown that converting enzyme inhibitors can improve exercise tolerance while diminishing lassitude, correct potassium deficiency, and limit ventricular arrhythmias. Energetic efforts are being made to develop orally active inhibitors of the enzyme renin itself, since these should be more specific in action than the presently available and very successful converting enzyme inhibitors.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Benzothiadiazines; Blood Pressure; Diuretics; Dogs; Enalapril; Enzyme Inhibitors; Heart Failure; Humans; Hypertension; Hypertension, Renovascular; Kidney; Oligopeptides; Rats; Renal Circulation; Renin-Angiotensin System; Sodium Chloride Symporter Inhibitors; Teprotide

Topics: Adrenergic alpha-Antagonists; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Captopril; Coronary Disease; Diazoxide; Drug Tolerance; Enalapril; Hemodynamics; Humans; Hydralazine; Hypertension; Minoxidil; Muscle, Smooth; Nitroglycerin; Vasodilator Agents