enalapril and Ventricular-Dysfunction

Nowadays angiotensin-converting enzyme inhibitors (ACE-Is) are considered to be a cornerstone in the treatment of congestive heart failure (CHF). These agents have been shown to improve survival and functional status of patients with CHF. It is logical to start therapy with ACE-Is in the first hours or days of acute myocardial infarction (MI) to further improve survival and prevent CHF after MI. The several randomized placebo-controlled trials were performed to assess the effects of early therapy with ACE-Is on the outcomes of MI. Mortality after MI was significantly reduced only in these trials in which therapy with ACE-Is was introduced 3-16 days after MI in patients with clinical evidence of CHF or left ventricular systolic dysfunction as well as in patients with noneffective thrombolysis (or without thrombolysis) or diabetes mellitus.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Diabetes Complications; Enalapril; Heart Failure; Humans; Indoles; Middle Aged; Myocardial Infarction; Ramipril; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Ventricular Dysfunction

Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment of cardiovascular disease since they improve blood pressure control in patients with hypertension and prolong survival in patients with acute myocardial infarction, asymptomatic left ventricular dysfunction and congestive heart failure. Most of the information about the therapeutic role of ACE-inhibitors has been achieved during the last 20 years since the publication of some pivotal trials mostly involving the use of ACE-inhibitors like captopril and enalapril. In particular the treatment with enalapril has considerably improved the clinical outcome of patients with either mild-to-moderate (SOLVD studies) or severe (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in patients with congestive heart failure has also involved a remarkable reduction in the rate of hospitalization, thus contributing to improve the pharmaco-economic approach to the disease. Most of the beneficial effect of ACE-inhibitors in clinical practice is dependent on their capacity of inhibiting the renin-angiotensin system, although some recent trials have supported a primary role for such drugs (in particular enalapril) in the prevention of atrial fibrillation. After more than 25 years from their discovery, ACE-inhibitors must be again considered among the first-line treatment in many patients with cardiovascular disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Captopril; Cardiovascular Diseases; Enalapril; Heart Failure; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Renin-Angiotensin System; Ventricular Dysfunction

Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Child; Echocardiography; Enalapril; Exercise Test; Exercise Tolerance; Female; Fontan Procedure; Humans; Hypotension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Systole; Treatment Outcome; Vascular Stiffness; Ventricular Dysfunction

The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensin-converting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Down-Regulation; Enalapril; Hemodynamics; Male; Myocardial Infarction; Peptide Fragments; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction; Ventricular Function, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiology; Enalapril; Humans; Terminology as Topic; Ventricular Dysfunction

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cyanosis; Enalapril; Female; Heart Defects, Congenital; Heart Diseases; Humans; Male; Treatment Outcome; Ventricular Dysfunction

Heart failure is today one of the most serious health problems of modern industrialized societies. The increase in the mean age of the population is an additional factor which favours a high incidence of episodes of heart failure. Age is also a relevant factor in mortality linked with heart failure. On this basis more emphasis has been given by researchers and physicians to improve a preventive and therapeutic approach to heart failure. For many years the pharmacological treatment of heart failure patients was based on the increase in inotropism through the digitalis and on the reduction in sodium-water retention through diuretics, while less importance was given to the improvement of the afterload. We have had knowledge of vasodilatory drugs in chronic heart failure for at least 20 years but only 10 years ago with the Vasodilator-Heart Failure Trial (V-HeFTI), it was proved that the combination of hydralazine and nitrates in addition to the conventional treatment, improved the survival of patients affected by moderate-severe heart failure. With the advent of the ACE-inhibitors, in the '80s, the first studies concerning the role of such drugs in heart failure were carried out. In the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS I) it was proved for the first time that an ACE-inhibitor (enalapril), added to the conventional heart failure therapy, improved the survival of patients with severe congestive heart failure (NYHA class IV). The result was so extraordinary that the study was interrupted for ethical reasons. However, it has raised a considerable interest in the study of the ACE-inhibitors in heart failure and now it has been proved that such drugs are a milestone in a correct pharmacological approach to heart failure.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Digoxin; Drug Therapy, Combination; Enalapril; Felodipine; Follow-Up Studies; Heart Failure; Humans; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Randomized Controlled Trials as Topic; Time Factors; Vasodilator Agents; Ventricular Dysfunction