Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure?

BACKGROUND: The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. METHODS AND RESULTS: We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. CONCLUSIONS: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure.

BACKGROUND: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. METHODS AND RESULTS: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6+/-0.7, -5.4+/-0.7, and -4.6+/-0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0+/-0.4, -3.7+/-0.4, and -3.5+/-0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11+/-17, 68+/-17, 152+/-19, and 176+/-18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. CONCLUSIONS: In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.

Effect of mibefradil, a T-type calcium channel blocker, on morbidity and mortality in moderate to severe congestive heart failure: the MACH-1 study. Mortality Assessment in Congestive Heart Failure Trial.

BACKGROUND: Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. METHODS AND RESULTS: This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction <35%). The initial 50-mg daily dose of mibefradil was uptitrated to 100 mg after 1 month and continued up to 3 years. Patients were monitored at 1 week; 1, 2, and 3 months; and every 3 months thereafter. All-cause mortality, cardiovascular mortality, and cardiovascular morbidity/mortality were analyzed by use of the log-rank test (alpha=0.05). Substudies included exercise tolerance, plasma hormone and cytokines, echocardiography, and quality of life. Total mortality was similar between mibefradil- and placebo-treated patients (P=0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant (P=0.093). Treatment groups had similar cardiovascular mortality (P=0.246), cardiovascular morbidity/mortality (P=0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. CONCLUSIONS: When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.

Influence of left ventricular geometric patterns on prognosis in patients with or without coronary artery disease.

OBJECTIVES: We sought to examine patterns of left ventricular (LV) geometry as determined by echocardiography and their association with mortality in patients with or without coronary artery disease (CAD). BACKGROUND: The independent prognostic role of LV geometry remains uncertain. METHODS: We performed a cohort study based on 988 consecutive patients who underwent both coronary arteriography for presumed CAD and echocardiography and were followed up for a mean of 9 years (range 5 to 13). Patients were classified into four LV geometry patterns: normal, concentric remodeling, eccentric LV hypertrophy (LVH) and concentric LVH. RESULTS: Patients with concentric LVH consistently showed the largest increase in LV posterior wall and septal thickness and LV mass index, as well as relative wall thickness (RWT), regardless of status of the coronary arteries. This pattern conferred the highest risk of both all-cause and cardiac mortality. Eccentric LVH moderately increased the risk of death compared with normal geometry; no substantial increase in mortality was noted in patients with concentric remodeling. When LV index and RWT were analyzed as continuous measures and considered in the same Cox proportional hazards model, increases in LV mass were independently associated with risk, but this outcome was less clear for RWT. CONCLUSIONS: In this series of patients referred to coronary angiography for suspected CAD, LVH conferred most of the predictive information from echocardiography. Patients with both LVH and abnormal RWT--concentric LVH--represent a group with the greatest mortality risk. Concentric remodeling may not be associated with increased risk of death because the predictive value of RWT is not as strong as for LV mass.

Impact of left ventricular hypertrophy on ventricular arrhythmias in the absence of coronary artery disease.

Left ventricular hypertrophy has a grave prognosis. Ventricular arrhythmias may account for a large portion of this poor prognosis, but the contribution of coronary artery disease has not been excluded. The occurrence of ventricular arrhythmias was investigated by 24 h ambulatory electrocardiographic (ECG) monitoring in 49 hypertensive patients who had normal findings on coronary arteriography. The presence of left ventricular hypertrophy was assessed by both ECG and echocardiography. The frequency and complexity of ventricular arrhythmias were significantly related to the presence of left ventricular hypertrophy whether it was defined by wall thickness (interventricular septum or posterior wall greater than or equal to 1.2 cm) or by left ventricular mass indexed to height (left ventricular mass/height greater than or equal to 163 g/m in men and greater than or equal to 121 g/m in women). The relation between left ventricular mass or wall thickness to ventricular arrhythmia was graded and continuous; for every 1 mm increase in the thickness of interventricular septum or posterior wall there was an associated two- to threefold increase, respectively, in the occurrence and complexity of ventricular arrhythmias. In conclusion, left ventricular hypertrophy is associated with an increase in the frequency and complexity of ventricular arrhythmias in the absence of coronary artery disease, and the relation is graded and continuous.

Prediction of mortality risk by different methods of indexation for left ventricular mass.

OBJECTIVES: We sought to compare the predictive value of echocardiographically determined left ventricular hypertrophy on death from all causes and cardiac mortality using various methods of indexation for left ventricular mass. BACKGROUND: Considerable controversy exists regarding the optimal method for indexing left ventricular mass to body size in the clinical setting. METHODS: The study included 988 consecutive patients who had both coronary angiograms and echocardiographic examinations in an inner-city public hospital in Chicago, Illinois. Patients were followed up for a mean of 7 years (range 2 to 11). RESULTS: Various left ventricular mass indexes (e.g., mass indexed for height, height2, height2.13, height2.7, body surface area and body surface area1.5 were highly correlated (r = 0.90 to 0.99). Used as a continuous measure, an increase in any left ventricular mass index was associated with similar risk of death from all causes and cardiac diseases. Although left ventricular hypertrophy assessed by mass indexed for body surface area using the published conventional partition values provided somewhat better prediction, the adjusted relative risk was in general not significantly different from hypertrophy based on other indexes. Patients with left ventricular hypertrophy defined concordantly by indexes based on both body surface area and height (or height2.7) had, by definition, the highest average mass indexes among all groups and experienced as much as a threefold greater risk of death than those without hypertrophy. A small proportion of patients (12%) who were classified into the hypertrophy group by height-based indexes alone, but not by body surface area, had a moderate increase in mass and showed no increase in risk, even though being overweight was extremely prevalent in this group. CONCLUSIONS: Because of the high correlation among various body size indexes, left ventricular hypertrophy, defined by different indexes for left ventricular mass, similarly confers increased risk of mortality in patients with or without coronary artery disease.

Natural history and patterns of current practice in heart failure. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators.

A total of 6,273 consecutive relatively unselected patients with heart failure or left ventricular dysfunction, or both (mean age 62 +/- 12 years, mean ejection fraction 31 +/- 9%), were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry over a period of 14 months. All patients were followed up for vital status and hospital admissions at 1 year. Ischemic heart disease was the underlying cause of failure or dysfunction in approximately 70% of patients, whereas hypertensive heart disease was considered to be primarily involved in only 7%. There were striking differences in the etiology of heart failure among blacks and whites: 73% of whites had an ischemic etiology of failure versus only 36% of blacks; 32% of blacks had a hypertensive condition versus only 4% of whites. The total 1-year mortality rate was 18%; 19% of patients had hospital admissions for heart failure and 27% either died or had a hospital admission for congestive heart failure during the 1st year of follow-up. Factors related to 1-year mortality or hospital admission for congestive heart failure included age, ejection fraction, diabetes mellitus, atrial fibrillation and female gender. There was no difference in mortality associated with congestive heart failure among blacks and whites, but hospital admissions for heart failure were more frequent in blacks. Digitalis and diuretic agents were the drugs most often used in these patients, who were often taking many medications in relation to severity of congestive heart failure symptoms and ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative neurohormonal responses in patients with preserved and impaired left ventricular ejection fraction: results of the Studies of Left Ventricular Dysfunction (SOLVD) Registry. The SOLVD Investigators.

OBJECTIVES: The aim of this study was to determine the differences in neurohumoral responses between patients with pulmonary congestion with and without impaired left ventricular ejection fraction. BACKGROUND: Previous studies have established the presence of neurohumoral activation in patients with congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to the impairment in systolic contractility. METHODS: The 898 patients recruited into the Studies of Left Ventricular Dysfunction (SOLVD) Registry substudy were examined to identify those patients with pulmonary congestion on chest X-ray film who had either impaired (< or = 45%, group I) or preserved (> 45%, group II) left ventricular ejection fraction. Plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were measured in these two groups of patients and compared with values in matched control subjects. RESULTS: Distribution of the New York Heart Association symptom classification was the same in the two groups of patients. Compared with control subjects, patients in group II with pulmonary congestion and preserved ejection fraction had no activation of the neurohumoral mechanisms, except for a small but statistically significant increase in arginine vasopressin and plasma renin activity. Compared with patients in group II, those in group I with pulmonary congestion and impaired ejection fraction had significant increases in plasma norepinephrine (p < 0.002), plasma renin activity (p < 0.02) and atrial natriuretic peptide levels (p < 0.0007). When we controlled for baseline differences between groups I and II, the between-group differences in plasma norepinephrine (p < 0.02) and atrial natriuretic peptide (p < 0.002) remained significant. However, plasma renin activity was not significantly different between groups I and II. When the effects of diuretic agents and angiotensin-converting enzyme inhibitors were adjusted, patients with lower ejection fraction were found to have significantly higher plasma norepinephrine and atrial natriuretic peptide levels. CONCLUSIONS: The results point to the importance of the decrease in left ventricular ejection fraction as one of the mechanisms for activation of neurohormones in patients with heart failure.

Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.

OBJECTIVES: We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). BACKGROUND: The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. RESULTS: The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels. CONCLUSIONS: Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.

Trends in hospitalization rates for heart failure in the United States, 1973-1986. Evidence for increasing population prevalence.

Discharge data from a representative sample of short-stay US hospitals were examined to obtain information regarding trends in the prevalence of congestive heart failure from 1973 through 1986. During this 14-year period, the number of discharges more than doubled and the age-adjusted rates increased from 53% to 88% among the four major sex-race groups. On average, nonwhite men experienced annual hospitalization rates 33% higher than white men, while for women the corresponding nonwhite rates were 50% higher. Hospitalization rates during this period remained constant for persons younger than 55 years but rose sharply in the elderly. Concurrently, a slight decline in case fatality rates for an individual hospitalization was seen. The two factors accounting for the growing prevalence of congestive heart failure seem to be the increasing average age of the population and the longer survival of persons with chronic heart disease. The role of improved medical therapy during the period of this study remains uncertain. Increasing demands to provide care for the congestive heart failure syndrome are likely to continue in the coming years, and medical facilities should develop new intervention strategies to treat or prevent the underlying conditions leading to heart failure as well as decrease the need for hospitalization in this common disorder.

Precipitating factors leading to decompensation of heart failure. Traits among urban blacks.

Potential precipitating factors that led to cardiac decompensation and subsequent hospital admission for heart failure were examined in 101 patients in a large public hospital serving a predominantly working-class minority population. Ninety-seven percent of patients were black; their age was 59 +/- 14 years (mean +/- SD); on average, they were hospitalized three times in the preceding year for problems related to their heart failure. Potential precipitating factors for decompensated heart failure were identified in 93% of patients. Lack of adherence to the prescribed medical regimen was the most commonly identified causative factor and was noted in 64% of the cases; noncompliance with diet amounted to 22%, with drugs to 6%, and with the combination of drugs and diet to 37%. Other factors also related to hospitalization were cardiac arrhythmias (29%), emotional/environmental issues (26%), inadequately conceived drug therapy (17%), pulmonary infections (12%), and thyrotoxicosis (1%). Thus, the key preventive measure necessary in at least two thirds of patients centered around better adherence to drug and/or diet regimen, highlighting the precept that better patient education is mandatory if we are to minimize the number of hospital admissions for decompensated heart failure.

Sex differences in the impact of coexistent diabetes on survival in patients with coronary heart disease.

OBJECTIVE: To evaluate the sex difference in the impact of diabetes on survival in patients with coronary heart disease. RESEARCH DESIGN AND METHODS: Cohort study based on a sample from a hospital registry in Chicago, IL. A total of 974 consecutive patients (585 men and 389 women) with angiographically confirmed coronary artery disease were followed for 4.6 yr. RESULTS: At baseline, 160 men and 155 women had diabetes. The age-adjusted relative risk of death from all causes for patients with diabetes versus patients without diabetes was 0.93 (95% confidence interval 0.65-1.34) in men and 1.99 (95% CI 1.30-3.05) in women. For cardiac death, the corresponding relative risk was 1.00 (95% CI 0.64-1.56) and 1.96 (95% CI 1.19-3.24) in men and women, respectively. Baseline differences in age, hypertension, body mass index, number of diseased vessels, and ejection fraction did not fully explain the excess mortality risk in diabetic women. Excess risk was apparent in both cardiac and noncardiovascular categories. Among nondiabetic patients, the risk of death was significantly lower in women compared with men (multivariate-adjusted relative risk = 0.61, 95% CI 0.41-0.89). However, the mortality risk of diabetic women became similar to men as a whole (relative risk = 1.13, 95% CI 0.80-1.60). CONCLUSIONS: Diabetes confers a substantially higher risk of mortality in women than in men when it occurs in the presence of coronary heart disease.

A new interference in some digoxin assays: anti-murine heterophilic antibodies.

BACKGROUND: We describe a patient with cirrhotic liver disease and atrial fibrillation who was treated with spironolactone and digoxin. He was hospitalized because of an incidental finding of a high serum digoxin level (4.2 micrograms/L), but he remained asymptomatic without emerging arrhythmias. Despite discontinuation of both drugs, his serum digoxin level persisted at or above 3.0 micrograms/L for approximately 5 weeks, drawing into question the accuracy of the digoxin assay. METHODS: Additional digoxin methods gave lower, discrepant results, providing evidence of an assay interference, and several possible sources of digoxin false positivity were evaluated. This included assessment of the contribution of digoxin-like immunoreactive factor (DLIF), digoxin metabolites, and spironolactone. Because the routine digoxin assay used a monoclonal antibody, we also tested for another hypothetical interference: human heterophilic ("anti-mouse") antibodies. RESULTS: We found no contribution from DLIF, digoxin antibodies, or spironolactone to the apparent digoxin results. However, the use of protein A to complex and selectively remove immunoglobulin G molecules markedly lowered the apparent digoxin value, as did the less specific process of ultrafiltration. CONCLUSIONS: These results suggest a previously unreported cause of digoxin false positivity: heterophilic antibodies, which have been reported to bind murine monoclonal antibodies in other assays. Because newer digoxin assays now use murine monoclonal antibodies, the possible presence of heterophilic, anti-mouse antibodies should now be considered in the interpretation of a high digoxin level.

Changes in pulmonary hemodynamics with aging in a predominantly hypertensive population.

The impact of aging on pulmonary hemodynamics was investigated in 322 patients who underwent right- and left-sided cardiac catheterization and echocardiographic examination, and were free of coronary disease, impaired left ventricular systolic function and left ventricular dilatation. Most of the patients were black (83%) and hypertensive (78%). Mean pulmonary artery pressures increased progressively with age: 16.7 +/- 4.6, 17.9 +/- 6.4 and 20.6 +/- 8.0 mm Hg for those aged less than 45 (n = 50), 45 to 64 (n = 238) and greater than or equal to 65 years (n = 34), respectively (p = 0.020). Pulmonary vascular resistance was 99 +/- 42, 116 +/- 62 and 160 +/- 68 dynes s cm-5, and the ratio of pulmonary to systemic vascular resistance was 78, 80 and 105%, respectively, for the 3 age groups (p less than 0.001). Along with these changes, a decrease in cardiac output and an increase in systolic blood pressure and systemic vascular resistance with age were noted. The effect of age on mean pulmonary artery pressure and pulmonary vascular resistance was statistically significant after adjustment for gender, smoking status, body weight, left ventricular hypertrophy, systolic blood pressure and systemic vascular resistance. Consideration should be given to age-related changes in the pulmonary circulation when defining physiologically normal values.

Bedside diagnosis of preserved versus impaired left ventricular systolic function in heart failure.

The importance of recognizing symptomatic heart failure with preserved left ventricular (LV) systolic function has only recently been appreciated. To determine its frequency and identify clinical features that make the bedside diagnosis likely, 82 patients admitted for decompensated heart failure were classified into 2 groups based on their LV systolic performance, as defined by fractional shortening (FS): group I (n = 59), with impaired systolic function (fractional shortening less than 24%), and group II (n = 23) with preserved systolic function (fractional shortening greater than or equal to 24%). Mean fractional shortening was 15 +/- 5% and 39 +/- 1% for groups I and II, respectively. Female gender (p less than 0.05), obesity (p less than 0.01) and diastolic blood pressure greater than or equal to 105 mm Hg (p less than 0.05) predominated in group II. Jugular venous distention was identified more frequently in group I (p less than 0.05). No statistically significant difference between the 2 groups was noted among various demographic variables (age, duration of symptoms, history of hypertension, ischemic heart disease and heavy alcohol drinking) or physical findings (S3 gallop, edema, cardiomegaly, pulmonary congestion and pulmonary edema). Echocardiographic mean left ventricular dimension measured 6.6 +/- 1 versus 5.0 +/- 1 cm (p less than 0.01) and mean posterior wall thickness 1.1 +/- 0.3 versus 1.4 +/- 0.4 cm (p less than 0.01) in group I and II, respectively. The combination of diastolic blood pressure greater than or equal to 105 mm Hg and an absence of jugular venous distention had a high specificity and positive predictive value (100%) for identifying group II patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies of Left Ventricular Dysfunction (SOLVD) Registry: rationale, design, methods and description of baseline characteristics.

The Studies of Left Ventricular Dysfunction (SOLVD) comprises 2 double-blind, randomized clinical trials to test improved survival by angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction, with or without congestive heart failure. Patients entering the trials may be a highly selected subset of the population of such patients; those with the worst and best prognosis are likely to be excluded. To obtain the clinical history of a broader group, a registry of 6,273 patients included a relatively unselected cohort of patients with heart failure or left ventricular dysfunction, or both, from SOLVD hospitals. Registry data were obtained from hospital records. Because data collection from medical records may lead to incomplete data and more investigations in "sicker" patients, 898 randomly chosen subjects from different disease strata were seen in clinic where neurohumoral measures, echocardiograms, x-rays and electrocardiograms were obtained, and a 6-minute walking test was performed. The design and methodologic features, and the baseline characteristics of the participants in this 2-tiered registry are described, and its use in complementing the results and interpretation of the SOLVD trials is discussed.

Initial blood pressure response to enalapril in hospitalized patients (Studies of Left Ventricular Dysfunction [SOLVD]).

Studies of Left Ventricular Dysfunction (SOLVD) is a randomized trial of enalapril versus placebo in reducing mortality in patients with cardiac dysfunction (defined as left ventricular ejection fraction less than or equal to 35%). Before randomization, patients at risk for hypotension were hospitalized for a test dose of 2.5 mg of enalapril administered orally at baseline and again 12 hours later. As of February 1989, 89 of 7,539 (1.2%) patients had been studied during hospitalization. Baseline systolic and diastolic blood pressures were 115 +/- 18 and 73 +/- 10 mm Hg, respectively. After enalapril, systolic blood pressure decreased slightly but significantly 8 to 20 hours after the initial dose (mean reduction 8 to 11 mm Hg). In this highly selected group of 89 patients, symptoms relating to decrease in blood pressure were noted in 13 (15%). It is emphasized that most patients with cardiac dysfunction readily tolerate enalapril. However, the agent should be administered with caution to patients with advanced congestive failure and diminished baseline blood pressure, owing to a significant incidence of symptomatic hypotension.

Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry.

Diabetes is an independent predictor of morbidity and mortality in patients with symptomatic heart failure, patients with asymptomatic left ventricular dysfunction (defined as an ejection fraction of 35% or less), and in a broader registry population with less stringent entry criteria. Although the SOLVD Trials made a major clinical contribution by proving the value of enalapril, diabetes remains a significant predictor of outcome even after adjusting for treatment with enalapril.

Chronic therapy for congestive heart failure with benazepril HCl, a new angiotensin converting enzyme inhibitor.

Benazepril HCl is an orally effective angiotensin converting enzyme (ACE) inhibitor previously shown to have significant acute hemodynamic benefits in patients with congestive heart failure. In this study, 21 patients with New York Heart Association Class III or IV congestive heart failure were treated with 2 to 15 mg of benazepril HCl as a single daily oral dose for 28 days to determine the clinical and hemodynamic value of chronic therapy. Each patient underwent clinical evaluation during the 28-day period, as well as invasive hemodynamic studies on the first two and last two days of the trial. Plasma ACE activity and aldosterone levels fell significantly and renin levels rose after therapy. Benazepril HCl produced significant (p less than 0.01) reductions in arterial pressure and systemic vascular resistance, with corresponding increases in cardiac output and decreases in pulmonary artery wedge pressure. Responses after 28 days of therapy were equivalent to those after the initial doses. Clinical effects included reduced rest, exertional and paroxysmal nocturnal dyspnea, as well as reduced peripheral edema. Only one patient developed symptomatic orthostatic hypotension. Thus, benazepril HCl, given once daily, is an effective and well tolerated oral agent for the chronic treatment of advanced congestive heart failure.