enalapril and Cardiac-Output--Low

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

Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown.. We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema.. Of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001). The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups.. Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890 .).

Topics: Acute Disease; Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiac Output, Low; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neprilysin; Peptide Fragments; Stroke Volume; Tetrazoles; Valsartan

The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF.. Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF.. PIONEER-HF is a 12-week, prospective, multicenter, double-blind, randomized controlled trial enrolling a planned 882 patients at more than 100 participating sites in the United States. Medically stable patients >18 years of age with an EF <40% and an amino terminal-pro b-type natriuretic peptide >1600 pg/mL or b-type natriuretic peptide >400 pg/mL are eligible for participation no earlier than 24 hours and up to 10 days from initial presentation while still hospitalized. Patients are randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan titrated to 97/103 mg by mouth twice daily versus enalapril titrated to 10 mg by mouth twice daily for 8 weeks. All patients receive open-label treatment with sacubitril/valsartan for the remaining 4 weeks of the study. The primary efficacy end point is the time-averaged proportional change in amino terminal-pro b-type natriuretic peptide from baseline through weeks 4 and 8. Secondary and exploratory end points include serum and urinary biomarkers as well as clinical outcomes. Safety end points include the incidence of angioedema, hypotension, renal insufficiency, and hyperkalemia.. The PIONEER-HF trial will inform clinical practice by providing evidence on the safety, tolerability, and efficacy of in-hospital initiation of sacubitril/valsartan among patients who have been stabilized following an admission for acute decompensated HF with a reduced EF.

Topics: Administration, Oral; Aged; Aminobutyrates; Biphenyl Compounds; Cardiac Output, Low; Cause of Death; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Delivery Systems; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Survival Rate; Tetrazoles; Treatment Outcome; Valsartan

Chronic kidney disease (CKD), anemia, and declining kidney function are recognized as risk factors for adverse outcomes in patients with heart failure. This analysis was conducted to evaluate whether anemia is a risk factor for kidney function decrease in patients with heart failure. Data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized trial of enalapril versus placebo in patients with ejection fractions or=6 ml/min/1.73 m(2)/year. Anemia was defined as baseline hematocrit <36%. Multivariate logistic regression weighted by the number of GFR assessments was used to test the relation between anemia and rapid decrease. We also evaluated whether CKD (baseline GFR

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Chronic Disease; Cohort Studies; Creatinine; Diabetes Complications; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematocrit; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Placebos; Risk Factors; Stroke Volume

Day-activity rhythms of heart rate and blood pressure are thought to be mediated mainly through the sympathetic nervous system and may have greater amplitudes in patients with hypertension owing to increased daytime and largely normal nighttime values. Drug-induced nighttime hypotension in patients with chronic hypertension has been associated with the precipitation of cardiac failure and a fall in cerebral flow. The authors examined the effects of a single dose and of a 4-week treatment with different classes of antihypertensive drugs on ambulatory blood pressure (ABP) in 10 patients with mild hypertension. Data were assessed by polynomial analysis (Harvard Graphics 3). A single oral dose of enalapril 10 mg, amlodipine 5 mg, carvedilol 25 mg, and celiprolol 200 mg produced a mean reduction of 24-hour ABP compared to placebo of, respectively, 24/11, 11/5, 13/6, and 12/5 mm Hg (p values between <0.02 and <0.001). With enalapril, amlodipine, and carvedilol, between-subject variability contributed significantly to the overall variability in the measurements (p values between 0.05 and 0.01 versus zero), whereas with celiprolol this was not so. Although the beta blockers reduced daytime blood pressures similarly to the ACE inhibitor or the calcium channel blocker, they did not reduce nighttime blood pressures. These results were confirmed by an 8-week crossover trial comparing enalapril 10 mg daily with celiprolol 200 mg daily in the same group of patients. The authors conclude (1) that beta blockers produce a more stable reduction of blood pressure in patients with mild hypertension less affected by pressor effects through the sympathetic nervous system; (2) that beta blockers, unlike ACE inhibitors and calcium channel blockers, do not give rise to nighttime hypotension in this category of patients; and (3) that the selective beta blocker celiprolol may even perform better in these respects than the nonselective beta blocker carvedilol.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Carbazoles; Cardiac Output, Low; Carvedilol; Celiprolol; Cerebrovascular Circulation; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Enalapril; Female; Heart Rate; Humans; Hypertension; Hypotension; Male; Middle Aged; Placebos; Propanolamines; Sympathetic Nervous System

This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction.. APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown.. We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome.. APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users.. In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiac Output, Low; Cause of Death; Cohort Studies; Confidence Intervals; Coronary Disease; Death, Sudden, Cardiac; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Humans; Male; Middle Aged; Odds Ratio; Patient Admission; Placebos; Platelet Aggregation Inhibitors; Regression Analysis; Risk Factors; Sex Factors; Stroke Volume; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Output, Low; Enalapril; Exercise Test; Female; Heart Rate; Humans; Longitudinal Studies; Male; Middle Aged; Norepinephrine; Physical Exertion; Placebos; Renin-Angiotensin System; Rest; Stroke Volume; Sympathetic Nervous System; Sympathomimetics; Systole; Time Factors; Ventricular Dysfunction, Left

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

To investigate the actions of beta-blocker (atenolol) and ACE inhibitor (enalapril) for the secondary prevention of the main cardiac complications after acute myocardial infarction (AMI).. 1106 cases of AMI from 7 hospitals in the Beijing area were collected and were divided randomly into three groups: control (group C), atenolol (group A), and enalapril (group E). Drugs for investigation were administered 2-4 weeks after the onset of AMI, and the subjects were followed up for a median period of 19 months. All patients were given aspirin 50 mg/day. The end points of observation were cardiac events and non-cardiac events. Cardiac events included sudden cardiac death (SCD), heart failure death, total cardiac deaths, and myocardial re-infarction.. The clinical conditions of the three groups were compatible. Sixty-six cardiac events (6.0%) occurred. Comparing with group C, the rate of SCD decreased significantly by 68% in group A after atenolol treatment for 28 months. Both atenolol and enalapril significantly increased left ventricular ejection fraction (LVEF), whereas in group C the LVEF did not change during the follow-up period. There was obvious decreasing tendency of the survival curve in group C, compared with the other two groups. Totally drugs decrease one cardiac death 0/00/month. But the rate of myocardial re-infarction was the same in the three groups. No serious side effects on blood pressure or heart rate were observed.. Both atenolol and enalapril (domestic products) are beneficial to the secondary prevention of SCD and heart failure death after AMI, but not to re-infarction. Both drugs should be continued for a prolonged period to be effective. Drugs given 2-4 weeks after acute stage are also effective, with no serious side effects.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Atenolol; Cardiac Output, Low; Death, Sudden, Cardiac; Enalapril; Follow-Up Studies; Humans; Myocardial Infarction

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitors; Cardiac Output, Low; Circadian Rhythm; Dipeptides; Double-Blind Method; Enalapril; Heart Failure; Humans; Lisinopril; Middle Aged; Posture; Time Factors

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output, Low; Cause of Death; Double-Blind Method; Enalapril; Female; Heart Failure; Humans; Male; Middle Aged; Placebos; Survival Rate; Ventricular Function, Left

Fifty-six patients with a mean age of 58 years, 14 females and 42 males, all with dominant systolic heart failure (33 in functional class 3 and 4) were randomised to receive either added placebo or added enalapril to their heart failure medication. There were 13 patients in this group who had their trial drug switched after a certain period to allow direct but blind comparison between placebo and enalapril. Cardiac mortality with enalapril was 32 per cent compared to 48 per cent with placebo at intervals after initiating therapy of 20.0 +/- 19.4 versus 14.3 +/- 11.5 months respectively. When compared to a preceding control period, 80 per cent of the enalapril patients improved in contrast to 21 per cent of the placebo. However, when a comparison was made directly between enalapril and placebo, enalapril was better in 31 per cent and placebo was better in 8 per cent of the patients. It is concluded that in certain patients with systolic heart failure from non-valvular and non-hypertensive causes, enalapril is beneficial when added to the conventional treatment. An argument is also presented that to cost-effectively identify the group who will benefit, a short term ACE-I trial after the conventional antifailure therapy can be considered in all patients with systolic heart failure.

Topics: Adult; Aged; Cardiac Output, Low; Double-Blind Method; Enalapril; Female; Humans; Male; Middle Aged

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Pressure; Cardiac Output, Low; Cardiac Volume; Enalapril; Exercise Test; Female; Gated Blood-Pool Imaging; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Norepinephrine; Placebos; Radionuclide Ventriculography; Renin; Stroke Volume; Time Factors; Ventricular Function, Left

Ten hypertensive patients with symptoms of heart failure and normal systolic function but with diastolic dysfunction were treated with 10 mg enalapril twice a day for 9 +/- 3 months to evaluate the effects of this agent alone on heart failure induced by diastolic dysfunction. After therapy, all patients improved and echocardiographic parameters of diastolic dysfunction became normalized. It is concluded that enalapril appears to be useful in the treatment of heart failure in hypertensive patients with normal systolic function and diastolic dysfunction.

Topics: Adult; Cardiac Output, Low; Diastole; Echocardiography; Enalapril; Female; Heart; Hemodynamics; Humans; Hypertension; Male; Middle Aged

A total of 12 patients (mean age +/- SEM 63 +/- 2.6 years) with moderate to severe heart failure (ejection fraction = 23 +/- 3.2%) were included in a placebo-controlled crossover trial. Patients were randomly allocated to 4 periods of 6 weeks each: placebo, placebo and physical training, lisinopril 10 mg daily, and lisinopril and physical training. The exercise time increased from 13.6 +/- 0.9 min with placebo to 15 +/- 1 min with training alone, and to 16.1 +/- 0.7 min with lisinopril and training. With lisinopril alone there was a non-significant increase in exercise time, to 14.5 +/- 0.6 min. Improvements in exercise time were accompanied by a similar increase in peak oxygen consumption. Overall, the most significant improvements in symptoms and indices of cardiorespiratory fitness were achieved with a combination of lisinopril and training. Thus physical training is not only a useful adjunct to the existing medical therapy for heart failure, but it may also provide symptomatic benefits in its own right.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Combined Modality Therapy; Double-Blind Method; Enalapril; Exercise Therapy; Female; Humans; Lisinopril; Male; Middle Aged; Physical Exertion

Autologous cell transplantation may restore viable muscle after a myocardial infarction. We compared the effect of three cell types or an angiotensin-converting enzyme (ACE) inhibitor on preservation of ventricular function after cardiac injury.. A uniform transmural myocardial scar was created in adult rats by cryoinjury. Three weeks later the rats were randomly assigned to one of four blinded treatments: transplantation with 5 x 10(6) aortic smooth muscle cells (SMC, n = 12), ventricular heart cells (VHC, n = 13), skeletal muscle cells (SKC, n = 13) or culture medium alone (control, n = 11). The ACE inhibitor group (n = 8) received enalapril (1.0 mg/kg per day), also beginning 3 weeks after cryoinjury. Five and 12 weeks after transplantation, left ventricle (LV) function was assessed in a Langendorff apparatus, and histologic and immunohistological evaluation of the LV scars was performed.. At 5 weeks, greater scar elastin content and better LV function was noted with cell transplantation or ACE inhibitor therapy compared with control rats (p < 0.05). Twelve weeks after transplantation, cell-transplanted rats still had greater elastin content and better LV function than control rats, although elastin content and LV function had declined in ACE inhibitor-treated animals to levels below those observed in control rats (p < 0.05).. Transplantation of SMC, VHC, and SKC preserved ventricular function equivalent to the effects of an ACE inhibitor. Muscle cell transplantation, but not ACE inhibitor therapy, continues to be effective later after cryoinjury. No differences were detected between the muscle cells.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Cardiac Output, Low; Cell Transplantation; Cells, Cultured; Cicatrix; Cryopreservation; Elastin; Enalapril; Heart Injuries; Heart Ventricles; Immunohistochemistry; Muscle, Skeletal; Muscle, Smooth, Vascular; Myocardial Infarction; Myocardium; Rats; Rats, Inbred Lew; Ventricular Function, Left

The extent to which age plays a role in the underutilization of angiotensin-converting enzyme (ACE) inhibitors in heart failure patients has not been well studied.. We studied age-related variation in the use of ACE inhibitors in older Medicare beneficiaries discharged alive in Alabama with a diagnosis of heart failure with left ventricular systolic dysfunction.. A total of 285 patients had a mean age +/- SD of 78 +/- 6.9 years; 59% were female and 21% were African American. Of the 285 patients, 181 (63%) were prescribed ACE inhibitors at discharge. Therapy with ACE inhibitors was initiated in 47% of the patients. Compared with patients 65 to 74 years, those 85 years and older had lower odds of receiving ACE inhibitors at discharge. Among patients not admitted on an ACE inhibitor, those 85 years and older also had lower odds of ACE inhibitor therapy being initiated.. The overall rate of ACE inhibitor use was low, and age of 85 years and older was independently associated with lower use and initiation of ACE inhibitors. Opportunities remain to increase the use of ACE inhibitors in older patients with heart failure.

Topics: Age Factors; Aged; Aged, 80 and over; Alabama; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiac Output, Low; Cardiology; Drug Utilization; Enalapril; Female; Hospitalization; Humans; Logistic Models; Male; Odds Ratio; Referral and Consultation; Retrospective Studies; Ventricular Dysfunction, Left

Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats.

Topics: Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Cardiomegaly; Cardiovascular System; Chronic Disease; Enalapril; Losartan; Male; Mesenteric Arteries; Myocardial Infarction; Rats; Rats, Wistar

We evaluated the effects of chronic oral administration of an angiotensin II type 1 (AT1)-receptor antagonist YM358 and an angiotensin converting enzyme inhibitor enalapril on hemodynamics and cardiac hypertrophy in rats with volume overload-induced heart failure. We assessed changes of cardiac hemodynamics and cardiac hypertrophy at 2 and 4 weeks after administration of YM358 (3, 30 mg/kg per day) or enalapril (30 mg/kg per day) in abdominal aortocaval shunt rats. YM358 (30 mg/kg) attenuated increases of left ventricle (LV)/body weight (BW), left atrium (LA)/BW, right ventricle (RV)/BW and heart/BW ratios, but did not affect cardiac hemodynamics in shunt rats. Enalapril also reduced the increased LV/BW and heart/BW ratios together with significant reductions of systolic blood pressure, left ventricular systolic pressure and the first derivative of left ventricular pressure. These data suggest that the effects on attenuation of the development of cardiac hypertrophy are not different for YM358 and enalapril, although the effects on cardiac hemodynamics are different for the same dosages. The attenuating action of YM358 on cardiac hypertrophy was independent of the action on hemodynamics and indicated the direct action of the AT1 receptor on the heart.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Aorta, Abdominal; Azoles; Biphenyl Compounds; Body Weight; Cardiac Output, Low; Cardiomegaly; Coronary Circulation; Enalapril; Heart; Male; Organ Size; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Time Factors

Knowledge of the electrophysiologic abnormalities in the failing heart is meager. In this work morphologic and electrophysiologic changes were investigated in the cardiomyopathic hamster (BIO TO-2) at 11 months of age. The results were compared with control hamsters (F1B) of the same age.. Conventional KCl microelectrodes were used to measure membrane potential, conduction velocity, and refractoriness. Histologic studies consisted of Harris' hematoxylin and eosin, Masson trichrome, and von Kossa's calcium stain. The resting potential of myopathic fibers (-67.8 mV; SEM 1 0.83) in the cardiomyopathic hamsters was less negative than the control subjects' potential (-78.5 V; SEM + 1), and the action potential duration measured at 50% of repolarization was increased by 213%. The conduction velocity (36.9 cm/s) was 15.7% lower than that of the control subjects. Enalapril (50 micrograms/mL) caused a hyperpolarization of 6.8 mV, it increased the action potential duration at 90% of repolarization by 110%, and the conduction velocity of the myopathic fibers was appreciably increased compared to the control hamsters'. The refractoriness of myopathic and normal ventricular fibers was also increased by enalapril. Histologic studies performed on the right and left ventricular wall indicated interstitial fibrosis, necrotic foci, and extensive calcification.. The results indicate severe morphologic and electrophysiologic abnormalities in the failing ventricular muscle. The effect of enalapril on membrane potential and conduction velocity might indicate that the activation of the cardiac renin-angiotensin system during the process of heart failure is, in part, responsible for the abnormalities described here. The improvement of impulse propagation and the increase in refractoriness seem to represent important factors involved in the antiarrhythmic action of enalapril.

Topics: Action Potentials; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Cricetinae; Electrophysiology; Enalapril; Heart; Heart Conduction System; Heart Ventricles; Male; Neural Conduction; Ventricular Function

Administration of angiotensin converting enzyme (ACE) inhibitors to patients with congestive heart failure (CHF) is associated to a decrease in the abnormal vasoconstrictor neurohormonal activity. This contributes to the sustained benefits of these drugs on symptoms and survival of patients with CHF. There is little information, however, regarding the effects of ACE inhibition on vasodilator and natriuretic hormones.. To evaluate the chronic effects of enalapril, in addition to digitalis and diuretics in patients with chronic cardiac failure.. Nine patients with an idiopathic dilated cardiomyopathy (8 male, aged 48 to 76 years old) under treatment with digitalis and diuretics, received enalapril 20 mg bid during eight weeks. Before and after this treatment period resting left ventricular ejection fraction, functional class, plasma levels of atrial natriuretic factor and bradykinins (BK) and urinary excretion of kalikreins (BK) and prostaglandin E2 (PGE2) were measured.. After enalapril therapy, there was a significant increase in maximal O2 consumption (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min, p < 0.05) and radionuclide LV ejection fraction (27.4 +/- 1.1 to 31.4 +/- 0.9% p < 0.05). This was associated with a significant decrease in plasma ANP levels (559 +/- 158 to 178 +/- 54.8 pg/ml) and UK (391 +/- 112 to 243 +/- 92 Cu/24 h).. The decrease in ANP levels, which is a well known marker of prognosis in CHF, could contribute to explain the sustained clinical benefits observed with ACE inhibitors in patients with CHF.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Bradykinin; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Dinoprostone; Enalapril; Female; Humans; Kallikreins; Male; Middle Aged; Oxygen Consumption; Stroke Volume; Vasodilator Agents

The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). In untreated dogs, the proportion of type I fibers was 27 +/- 1% before randomization and decreased to 23 +/- 1% (P < 0.05) at the end of 3 mo of follow up. In dogs treated with enalapril or metoprolol, the proportion of type I fibers was 30 +/- 4 and 28 +/- 2% before randomization and 33 +/- 4 and 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Dogs; Enalapril; Female; Forelimb; Male; Metoprolol; Muscle Fibers, Skeletal; Muscle, Skeletal; Physical Endurance; Physical Exertion

Topics: Cardiac Output, Low; Enalapril; Fatigue; Humans; Ventricular Dysfunction, Left

Topics: Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cardiac Output, Low; Drug Therapy, Combination; Enalapril; Humans; Imidazoles; Losartan; Male; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Cardiac Output, Low; Cardiology; Carvedilol; Enalapril; Exercise Test; Humans; Mortality; Propanolamines

This study examined the effects of early long-term monotherapy with enalapril on the severity of functional mitral regurgitation in dogs with moderate heart failure.. Functional mitral regurgitation often develops in patients with heart failure and, depending on its severity, can have a marked adverse impact on the stroke output of the failing left ventricle and contribute to progressive deterioration of the heart failure state.. Left ventricular dysfunction (ejection fraction 30% to 40%) was produced in 14 dogs by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months of therapy with enalapril (10 mg twice daily, n = 7) or no therapy at all (control, n = 7). The severity of functional mitral regurgitation was quantified by Doppler color flow mapping in seven control and six enalapril-treated dogs. Mitral annular diameter was assessed by echocardiography and left ventricular volumes and shape by ventriculography. Measurements were made before initiation and after completion of therapy.. In control dogs, the severity of mitral regurgitation increased during the follow-up period ([mean +/- SEM] 14 +/- 4 vs. 23 +/- 4%, p < 0.001) and was associated with increased left ventricular end-systolic and end-diastolic volumes. In contrast, the severity of regurgitation was not significantly changed in dogs treated with enalapril (18 +/- 3 vs. 16 +/- 6%, p < 0.59) and was associated with preservation of left ventricular volumes.. In dogs with moderate heart failure, early long-term therapy with enalapril prevents progressive worsening of functional mitral regurgitation. This beneficial effect is most likely achieved by prevention of progressive left ventricular dilation.

Topics: Animals; Cardiac Output, Low; Dilatation, Pathologic; Disease Progression; Dogs; Echocardiography, Doppler; Enalapril; Mitral Valve Insufficiency; Myocardium; Treatment Outcome; Ventricular Function, Left

Topics: Cardiac Output, Low; Cardiotonic Agents; Enalapril; Humans; Placebos; Pyridazines; Research Design

In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation.

Topics: Angiotensin II; Animals; Cardiac Output, Low; Cardiac Pacing, Artificial; Dogs; Enalapril; Heart Ventricles; Iodine Radioisotopes; Iodocyanopindolol; Kinetics; Male; Membranes; Myocardium; Norepinephrine; Pindolol; Radioligand Assay; Receptors, Adrenergic, beta; Renin

Topics: Captopril; Cardiac Output, Low; Enalapril; Humans; Myocardial Infarction

As a rule, left ventricular relaxation is impaired in patients with coronary artery disease and congestive heart failure. In addition, the passive elastic properties in early and late diastole change when the ventricle dilates. Diastolic properties of the left ventricle were studied in 11 patients with congestive heart failure class II-IV (NYHA) before and 3 months after 10-20 mg enalapril was added to their regimen of salt restriction, a diuretic and occasionally digitalis. Haemodynamic studies were performed using radionuclide angiography and simultaneous pressure-volume measurements. Systemic vascular resistance decreased from 1479 to 1182 dynes.s.-1 cm-5 (P < 0.05) and left ventricular end-diastolic pressure from 19.2 to 15.9 mmHg (P < 0.05). Left ventricular end-diastolic volume index decreased from 130 +/- 22 to 81 +/- 22 ml (P < 0.01). Indices of early diastolic relaxation, such as peak filling rate (1.43 +/- 0.46 to 1.49 +/- 0.84 EDV/s), time to peak filling rate (460 +/- 70 to 490 +/- 70 ms), peak negative dP/dt (-903 +/- 190 to -891 +/- 190 mmHg/s) and tau, the time constant of isovolumic pressure decay (58.7 +/- 14.4 to 48.4 +/- 15.2 ms) did not change significantly. In nine patients pressure-volume loops shifted to the left in all patients but one due to reduction in end-systolic and end-diastolic volume. The steepness of the diastolic part of the pressure-volume relationship increased, indicating an increase in chamber stiffness. The stiffness constant increased about 25% towards a more normal value. The alteration in stiffness seemed to be mainly due to the change of the geometry of the ventricle and not to a major change in the visco-elastic properties of the ventricular wall. In conclusion, regression of remodelling induced by enalapril does not change diastolic function parameters in patients with chronic congestive heart failure beyond the changes caused by regression of ventricular dilation.

Topics: Blood Pressure; Cardiac Catheterization; Cardiac Output; Cardiac Output, Low; Cardiac Volume; Coronary Disease; Diastole; Enalapril; Gated Blood-Pool Imaging; Heart Failure; Humans; Long-Term Care; Myocardial Contraction; Stroke Volume; Systole; Ventricular Function, Left

The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output, Low; Chronic Disease; Diuresis; Enalapril; Furosemide; Humans; Male; Middle Aged; Natriuresis; Posture; Renin-Angiotensin System

Increased activity of the renin-angiotensin system is thought to play a major role in the pathogenesis of salt retention and edema formation in congestive heart failure. The present study evaluates the effects of chronic inhibition of angiotensin-converting enzyme on the response to infusion of exogenous atrial natriuretic factor (ANF) in salt-retaining rats with chronic arteriovenous (a-v) fistula, an experimental model of high-output congestive heart failure. Administration of ANF in incremental doses (5-50 micrograms.kg-1.h-1) to Inactin-anesthetized, sham-operated control rats resulted in dose-dependent increases in urine flow, sodium excretion, and glomerular filtration rate, and significant decreases in mean arterial blood pressure. These effects of atrial peptide were markedly attenuated in salt-retaining rats with a-v fistula. However, chronic oral treatment with the angiotensin-converting-enzyme inhibitor enalapril restored the natriuretic response of sodium-retaining rats with a-v fistula to high doses of ANF. At a dose of 50 micrograms.kg-1.h-1, fractional excretion of Na (FENa) in a-v fistula rats given enalapril was 4.0 +/- 0.5%, which was significantly greater than that in a-v fistula rats without enalapril (0.5 +/- 0.4%, P less than 0.05) and not different from the response in sham-control rats (4.9 +/- 0.7%). The improvement in the natriuretic response after enalapril was not associated with a significant increase in GFR and occurred despite a decrease in mean arterial pressure. Moreover, chronic enalapril treatment did not significantly alter the plasma levels of immunoreactive ANF in either the sham controls or in the rats with a-v fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Disease Models, Animal; Enalapril; Kidney; Rats; Rats, Inbred Strains; Renin-Angiotensin System

We analyzed the effect of enalapril (0.1 mg/kg p.o. twice daily) on plasma electrolytes, urea, and creatinine in low cardiac output failure. In 14 male dogs implanted with chronic instrumentation, tachycardia was induced by ventricular pacing (265 impulses/min., 10-14 days). In 7 untreated dogs, pacing progressively lowered aortic flow by 44% and induced hyponatremia and elevations of plasma urea, creatinine, and potassium. Treatment with enalapril (n = 7) during pacing reduced the decrease in aortic flow by 33% and prevented changes in plasma urea, potassium, and sodium. We conclude that this is due to enalapril-induced retardation of heart failure progression.

Topics: Administration, Oral; Animals; Cardiac Output, Low; Cardiac Pacing, Artificial; Creatinine; Dogs; Enalapril; Hyponatremia; Male; Models, Biological; Potassium; Sodium; Tachycardia; Urea

There are several indications that the oxygen supply to the myocardium is inadequate in chronic heart failure. This is due to an increased intramyocardial vascular resistance, elevated filling pressures, and a shortened diastolic perfusion time. In parallel, the myocardial oxygen demand is heightened due to elevated wall stress, heart rate and contractility. This imbalance between myocardial oxygen supply and demand might be the cause of the adaptive metabolic changes seen in severe chronic heart failure. We showed increased LDH 5, decreased LDH 1 and increased ADP/ATP-carrier concentration in the myocardium from patients with chronic heart failure. After ACE-inhibitor treatment in 33 patients with chronic heart failure, LDH 1 increased from 38.7 +/- 6.7% to 42.3 +/- 5.5% (P less than 0.005) paralleled by a decrease in LDH 5 from 20.8 +/- 7.0% to 15.8 +/- 4.7% (P less than 0.001). The ADP/ATP-carrier concentration also decreased significantly within the normal range. This shift in the LDH isoenzyme pattern and decrease in the ADP/ATP-concentration can be interpreted as an indication for an improvement of myocardial energy balance in chronic heart failure under ACE-inhibitor therapy. This might help interrupt the self-perpetuation of chronic heart failure which is partially caused by a progressive subendocardial perfusion deficit.

Topics: Cardiac Output, Low; Chronic Disease; Enalapril; Glucose; Hemodynamics; Humans; Isoelectric Focusing; Isoenzymes; L-Lactate Dehydrogenase; Mitochondrial ADP, ATP Translocases; Myocardium

We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia. Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages. Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Cardiac Output, Low; Digoxin; Drug Therapy, Combination; Electrocardiography; Enalapril; Exercise Test; Female; Furosemide; Humans; Male; Patient Compliance; Peptidyl-Dipeptidase A; Time Factors

Regional cerebral blood flow (rCBF) was studied in anesthetized dogs subjected to acute left ventricular failure and its treatment with enalaprilat (MK-422). When failure was induced a reduction in rCBF paralleling the reduction in systemic blood pressure was observed. After treatment rCBF did not change in spite of further blood pressure reduction. The results are explained by changes in vascular resistance of larger cerebral arteries. Vasoconstriction in these vessels during failure was counteracted by enalaprilat through reduction in circulating angiotensin II.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Cerebrovascular Circulation; Dogs; Enalapril; Enalaprilat; Heart Ventricles; Hemodynamics; Vascular Resistance