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Effects of the left ventricular assist device on right ventricular function.

Right ventricular failure is a leading cause of death in patients who require the left ventricular assist device. Previous reports suggested right ventricular functional deterioration during left ventricular assist but lacked a method by which right ventricular function could be quantified adequately. This study examined the effects of left ventricular volume unloading on right ventricular systolic function by means of the stroke work/end-diastolic volume relationship, a load-insensitive index of myocardial performance. In 12 anesthetized open-chested dogs, right ventricular and left ventricular pressures were measured with micromanometers while ultrasonic dimension transducers measured left and right ventricular orthogonal diameters. Left ventricular unloading was accomplished with left atrial-to-femoral artery bypass with a centrifugal pump. Data were recorded during transient vena caval occlusion in the control state and with maximal left ventricular unloading by full support by the left ventricular assist device. Modified ellipsoidal geometry was used to calculate simultaneous biventricular volumes, and linear regression analysis of right ventricular stroke work versus end-diastolic volume was used to quantify right ventricular systolic function. Average slope and x intercept of this relationship under control conditions were 2.2 +/- 0.3 X 10(4) erg/ml and 10.7 +/- 5.0 ml, respectively. During full support by the left ventricular assist device (mean flow rate, 2.4 +/- 0.3 L/min), left ventricular end-diastolic volume decreased by 31% (p less than 0.01), left ventricular septal-free wall diameter decreased by 7% (p less than 0.001), and rate of rise of right ventricular peak positive pressure declined by 13% (p less than 0.05). The corresponding slope and x intercept of the right ventricular stroke work/end-diastolic volume relationship during full unloading of left ventricular assist device were 2.3 +/- 0.3 X 0.3 X 10(4) erg/ml and 14.3 +/- 4.8 ml, respectively; these values were not significantly different from control values (p greater than 0.5). Additionally, analysis of right ventricular end-diastolic pressure-volume relationships suggested improved right ventricular chamber compliance, although the effects were small and did not reach statistical significance (p = 0.10). These data imply that marked alterations in biventricular geometry accompanying left ventricular volume unloading by the left ventricular assist device in a normal heart do not significantly alter right ventricular performance characteristics.

Animals

Left ventricular functional reserve in patients with syndrome X: evaluation by continuous ventricular function monitoring.

OBJECTIVES: The objective of this study was to evaluate cardiac functional reserve in patients with syndrome X. BACKGROUND: Syndrome X is characterized by stress-induced anginal pain and ST segment depression, normal findings on coronary angiography and normal left ventricular function at rest. Reduced coronary vasodilative reserve and abnormal myocardial lactate metabolism have been described in such patients. METHODS: To assess left ventricular functional reserve in patients with syndrome X, continuous radionuclide monitoring of left ventricular end-diastolic volume, end-systolic volume and ejection fraction was performed in 12 patients and 13 normal control subjects during supine bicycle ergometer exercise. RESULTS: In control subjects, end-diastolic volume increased at peak exercise from 100% to 106.5% (p < 0.01), end-systolic volume decreased from 39.1% to 22.6% (p < 0.01) and ejection fraction increased from 60.9% to 78.6% (p < 0.01). In patients with syndrome X, end-diastolic volume increased at peak exercise from 100% to 106% (p < 0.01), and end-systolic volume decreased at ST segment depression < or = 0.5 mm (the ST point) from 37% to 28.8% (p < 0.01) but increased at peak exercise to 44.7% (p < 0.01 vs. the ST point). Thus, ejection fraction increased at the ST point from 63% to 72.7% (p < 0.01) but decreased at peak exercise to 57.7% (p < 0.01 vs. the ST point and control subjects) in proportion to the degree of ST segment depression. In nine patients (75%), ejection fraction at peak exercise was lower than baseline values. All patients and control subjects showed a rapid ejection fraction increase just after exercise during the recovery period. The degree of ejection fraction "overshoot" in patients was similar to that in control subjects, but the interval from the end of exercise to the overshoot in patients was significantly longer than that in control subjects (118 vs. 65 s, p < 0.01). CONCLUSIONS: In patients with syndrome X subjected to exercise stress, left ventricular function remained normal before the onset of ST segment depression. Once ST segment depression appeared, left ventricular function deteriorated in proportion to the degree of depression, and reduced left ventricular function persisted into the recovery period. Continuous ventricular function monitoring is thus a useful predictor of reduced left ventricular functional reserve in patients with syndrome X.

Adult

[Left ventricular function during atrial fibrillation assessed by left ventricular function curve using ECG-gated blood pool scintigraphy].

Cardiac function is difficult to assess in patients with atrial fibrillation due to the widely fluctuating cycle lengths resulting in variable ventricular hemodynamics. With respect to ECG-gated blood pool scintigraphy, distortion of the time activity curve occurs due to a summation of irregular cycle lengths. Therefore, performing such a study has been regarded meaningless. To evaluate left ventricular function during atrial fibrillation using scintigraphic technique, a new processing algorithm was devised to make multiple gated images which are discriminated by the preceding R-R interval, and left ventricular filling and function curves were established. The left ventricular filling curve, obtained by plotting end-diastolic volume against the preceding R-R intervals demonstrated an impairment of blood filling in cases of mitral stenosis and constrictive pericarditis, which resolved after mitral commissurotomy in case of mitral stenosis. The left ventricular function curve, established by plotting stroke volume against end-diastolic volume, was analyzed according to indices such as "slope" and "position". Both of these indices were significantly reduced in relation to the severity of heart failure according to the NYHA's functional classification and cardiomegaly on chest radiography. On individual comparisons of underlying diseases, the indices decreased in the following order; lone atrial fibrillation, hyperthyroidism, aging, hypertension, mitral valve disease, ischemic heart disease, dilated cardiomyopathy and aortic regurgitation. The indices correlated closely with ejection fraction. In cases of mitral regurgitation, however, the function curves were situated to the right and above those of lone atrial fibrillation and decreased in slope despite the fairly well-maintained ejection fraction. After treatment with digitalis and/or diuretics, the function curves shifted to the left and upward. In conclusion, left ventricular filling and function curves based on a newly-devised algorithm of ECG-gated blood pool scintigraphy are of considerable clinical value in evaluating cardiac performance in patients with atrial fibrillation. They are widely applicable to the assessment of therapeutic and interventional effects.

Atrial Fibrillation

Body weight is more important than family history of hypertension for left ventricular function.

Left ventricular function was studied in young men with a positive family history of hypertension for two generations (n = 15). The findings were compared with three control groups: one age-, sex-, and weight-matched group with a negative family history of hypertension (n = 14); one normotensive control group unselected as regards family history of hypertension (n = 27); and one group also unselected regarding family history of hypertension but selected with blood pressure criteria to have mild blood pressure elevation (n = 59). The group with a positive family history of hypertension, in comparison with the normotensive control group, was heavier, had higher blood pressure, increased left ventricular wall thickness, increased left ventricular mass, and signs of changes in diastolic and systolic left ventricular function. There were no differences in these variables between the group with a positive family history and the other two control groups. Data clearly indicated that subjects with a positive family history of hypertension, as well as subjects with mild blood pressure elevation, were heavier than the normotensive control group. It is not possible to judge, with available data, if the changes in left ventricular morphology and function in the two groups with a different family history of hypertension and in the group with mild blood pressure elevation occurred as a physiological response to the increase in afterload or if the neurohormonal and metabolic disturbances leading to the condition of slight overweight also affected left ventricular function.

Body Mass Index

[Intraoperative assessment of left ventricular function with left ventricular pressure-volume relationships in patients with open heart surgery].

There are few reports on the assessment of the left ventricular function from left pressure-volume relationships intraoperatively in open heart surgery. LV Emax, Ea/Ees and EW/PVA efficiency were assessed intraoperatively by using a left ventricular conductance catheter in patients with aortocoronary bypass. After dobutamine administration (DOB, 10 micrograms/kg/min), LV Emax was increased by 33 +/- 23% during cardiopulmonary bypass (CPB) and 60 +/- 38% after weaning from CPB. Ea/Ees changed from 2.14 +/- 1.36 to 1.08 +/- 0.47 after weaning from CPB with dobutamine administration. EW/PVA efficiency changed from 52 +/- 12% to 66 +/- 10%. The change of LV Emax after dobutamine administration was correlated with the change of LV Emax after weaning from CPB and was correlated with Ea/Ees and EW/PVA efficiency after weaning from CPB. We concluded that measuring LV Emax before and after dobutamine administration during CPB is useful to assess left ventricular contraction clinically.

Aged

Do symptoms reflect a change in left ventricular function after aortocoronary bypass grafting in patients with depressed left ventricular function?

Seventy-nine patients with moderate to severe left ventricular dysfunction who underwent aortocoronary bypass grafting between 1971 and 1977 had follow-up heart catheterization at a mean interval of 3 years. Thirty-three patients (42%) had angiographic improvement in left ventricular function at follow-up and 18 (25%) had a decrease in left ventricular end-diastolic pressure. Fifty-eight patients (73%) had improvement in angina of at least one New York Heart Association class at follow-up. There was no correlation between late improvement in left ventricular function and improvement in angina. Improvement in left ventricular function did not correlate with preoperative indices of severity of coronary disease or with indices of completeness of surgical repair.

Adult

Left ventricular function in diabetes mellitus. II: Relation between clinical features and left ventricular function.

We have shown a close relation between clinical microvascular complications and abnormalities of left ventricular function in 185 established diabetics without clinical heart disease. In 50 insulin-dependent diabetics who presented at under 20 years of age there was a correlation between the duration of diabetes and the isovolumic relaxation time, minimal dimension to mitral valve opening, and ratio of pre-ejection period to left ventricular ejection time. Diabetics with mild microvascular complications were similar to diabetics with no complications except for minor prolongation of the diastolic time intervals. Those with severe complications were significantly different from diabetes with milder complications and normal controls in all variables of left ventricular function. A close relation between left ventricular function and the microvascular complications index (code 0 when no complications to code 7 when all present and severe) was found for the following variables: isovolumic relaxation time, the interval from minimal dimension to mitral valve opening, ratio of pre-ejection period to left ventricular ejection time, and pre-ejection period index. It is concluded that in diabetes abnormalities of left ventricular function are related to duration of disease and complications; and that a diabetic specific heart muscle disorder occurs frequently in patients with severe microvascular complications.

Adult

[Right ventricular function in patients with poor left ventricular function: studies in patients undergoing coronary artery bypass surgery].

In many patients, right ventricular (RV) dysfunction is due to RV infarction. In some patients, however, RV dysfunction may be secondary to the left ventricular (LV) dysfunction. In order to clarify the influence of poor LV function on RV function, RV ejection fraction (EF) was evaluated serially by thermodilution techniques (REF-1, Edwards Laboratories) in patients with LVEF less than 40% who underwent aorto-coronary bypass surgery with uneventful postoperative course. The patients were divided into four groups depending on the site of LV infarction; anterior (n = 13), inferior (n = 8), anterior + inferior (n = 16), and no infarction (n = 4). Control (n = 11) consisted of the patients with LVEF more than 60% and with no significant stenosis of the right coronary artery. Cardiac index, intracardiac pressures and amount of catecholamine used during postoperative course showed no significant differences among the groups including control. However, the groups except for the group of anterior infarction showed significantly low pre- and postoperative RVEF compared with control. Only the group of anterior infarction had almost normal RVEF. These results mean that RV dysfunction associated with inferior infarction remain long afterwards and that low LVEF due to anterior infarction caused little effect on RV function.

Aged

Influence of resting left ventricular function on the left ventricular response to exercise in patients with coronary artery disease.

First-pass radionuclide angiocardiography was used to access the left ventricular response to submaximal exercise in 150 patients with coronary artery disease (CAD). To test the hypothesis that resting systolic left ventricular function as determined by left ventricular ejection fraction (LVEF) was a predictor of the hemodynamic response to exercise, the study group included patients with a wide range of resting LVEF (0.12-0.82). The influences of resting LVEF, resting end-diastolic volume, the number of diseased vessels, exercise end point and exercise double product on the change in LVEF (delta LVEF) during exercise were tested using multiple linear regression analyses. Resting LVEF was a highly significant predictor of the delta LVEF (p = 0.0001). Exercise duration was not related to either the resting LVEF or the delta LVEF. For the 112 patients in whom coronary anatomy was known, resting LVEF retained its significance as a predictor of delta LVEF (p = 0.002) even after adjustment for the significance of the extent of CAD (p = 0.0007) and the exercise end point (p = 0.06). Patients with normal resting LVEF showed the most profound decreases in LVEF, the highest frequency of new regional dysfunction and the largest relative increase in end-diastolic volume during exercise. As rest LVEF decreased, the magnitude of the delta LVEF and the frequency of new regional dysfunction decreased. Therefore, left ventricular function at rest is an important determinant of the direction and magnitude of change in left ventricular function during exercise.

Adult

Electrophysiologic testing in patients at high risk for sudden cardiac death. I. Nonsustained ventricular tachycardia and abnormal ventricular function.

Nonsustained ventricular tachycardia, although usually asymptomatic, is associated with a high risk of sudden cardiac death in patients with depressed left ventricular function. To test the vulnerability of such patients to symptomatic and potentially life-threatening arrhythmias, complete electrophysiologic studies were performed in 58 patients with clinically documented nonsustained ventricular tachycardia (greater than or equal to three complexes but less than 15 seconds of self-terminating ventricular tachycardia by 24 hour ambulatory electrocardiographic [Holter] or telemetric monitoring) and abnormal left ventricular function (ejection fraction less than 50% by radionuclide angiography). All patients had nonsustained ventricular tachycardia in the absence of antiarrhythmic drugs, acute ischemia, long QT syndrome, recent infarction or electrolyte abnormalities. The stimulation protocol for each patient included the introduction of single, double and triple ventricular extrastimuli at three cycle lengths (sinus, 600 and 450 ms) and two right ventricular sites (apex and outflow tract). A sustained ventricular tachyarrhythmia was induced in 23 patients (40%) and a nonsustained ventricular tachycardia in 14 patients (24%). Induction of sustained tachycardia correlated with the presence of akinesia or aneurysm, or both, by radionuclide angiography, but not with ejection fraction or presence or absence of coronary artery disease. These results indicate that: 1) patients with clinical nonsustained ventricular tachycardia and chronic left ventricular dysfunction have a high incidence of inducible sustained ventricular tachycardia or ventricular fibrillation; and 2) electrophysiologic testing may allow further substratification of risk of sudden cardiac death in high risk patients with nonsustained ventricular tachycardia.

Adult

Left ventricular functional reserve in nonobstructive hypertrophic cardiomyopathy: evaluation by continuous left ventricular function monitoring.

UNLABELLED: The cardiac functional response to exercise in patients with nonobstructive hypertrophic cardiomyopathy (HCM) was evaluated using a continuous ventricular function monitor with a cadmium telluride detector (CdTe-VEST). METHODS: Supine ergometric exercise was performed under CdTe-VEST monitoring in 41 patients with nonobstructive HCM (34 men and 7 women, age 18-72 yr, mean 51 yr) and 15 patients without cardiac disease (9 men and 6 women, age 36-56 yr, mean 49 yr). RESULTS: Although 20 of 41 patients with HCM maintained a LVEF above baseline at peak exercise (Group A), 21 did not show an EF increase at peak exercise (Group B). Exercise duration and work load in Group A were longer and higher, respectively, than in Group B. Resting EF in Group B (72 +/- 7.7%) was significantly higher than that in Group A (65 +/- 8.2%) and the control group (62 +/- 5.9%). The EF increase from baseline to EF overshoot during recovery and the time to EF overshoot were lower and longer, respectively, in Group B than in Group A and the control group. Septal wall thickness and the septum-to-posterior-wall-thickness ratio between Groups A and B were not different. ST-segment depression was observed in all 21 Group B patients and in 8 of the Group A patients. CONCLUSION: In patients with nonobstructive HCM, left ventricular dysfunction during exercise and during recovery was frequently observed but was not related to the degree of septal wall hypertrophy. The CdTe-VEST is a useful means to evaluate left ventricular functional reserve to exercise in patients with HCM.

Adolescent

[Surgical results in mitral insufficiency: prognostic value of the indices of left ventricular function].

Left ventricular function is a major prognostic factor in patients with mitral regurgitation, but the ability of echocardiographic and hemodynamic parameters to predict the surgical result is controversial. We investigated the prognostic role of various pre-operative indices of left ventricular function in 23 consecutive patients who underwent successful surgical correction of chronic mitral regurgitation. At a mean follow-up of 20 +/- 16 months, patients underwent echocardiography and radio-nuclide angiography and were grouped according to the post-operative left ventricular ejection fraction. Group A was made up of 16 patients with a left ventricular ejection fraction greater than or equal to .45: they showed post-operative reduction of the left ventricular end-diastolic diameter (from 36.3 +/- 3.2 to 30.5 +/- 4.5 mm/m2; p less than .001) and of the radius/thickness ratio (from 3.5 +/- 0.6 to 2.9 +/- 0.6; p less than .01). In 7 patients (group B), post-operative left ventricular ejection fraction was less than .45 and no significant changes in the left ventricular end-diastolic diameter (from 41.5 +/- 2.7 to 36.9 +/- 6.1 mm/m2; NS) or the radius/thickness ratio (from 3.9 +/- 0.9 to 3.4 +/- 1.0; NS) were observed. During the follow-up all group A patients remained asymptomatic or minimally symptomatic, whereas 2 group B patients died of refractory left ventricular failure. Pre-operative left ventricular volumes and diameters, both at end-diastole and end-systole, were significantly greater in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of left heart bypass on right ventricular function.

Right ventricular function has been studied in a canine ejecting heart model in-situ with intact sympathetic innervation and constant cardiac output, during varying degrees of left heart bypass ratio ranging from nil to total left ventricular decompression. The right ventricular function deteriorates as the left heart bypass ratio increases, reaching the maximal degree of RV depression when the LV is maximally decompressed. Some practical implications for the conduction of left heart bypass are discussed.

Animals

Importance of left ventricular function and systolic ventricular interaction to right ventricular performance during acute right heart ischemia.

To determine whether modulation of systolic ventricular interaction influences right ventricular performance during right heart ischemia, the effects of septal ischemia and inotropic stimulation were studied in 15 dogs in an open chest preparation. Right coronary branch occlusions led to right ventricular dilation and free wall dyskinesia, reversed septal curvature and reduced left ventricular diastolic volume. In systole, the septum thickened but bulged paradoxically into the right ventricle generating an active but depressed right ventricular systolic pressure (28.9 +/- 5.5 to 22.1 +/- 4.5 mm Hg), with associated decreases in right ventricular stroke work (5.66 +/- 0.94 to 1.92 +/- 0.53 g.m/m2) and left ventricular systolic pressure (123 +/- 11 to 80 +/- 10 mm Hg). Septal ischemia induced systolic septal thinning, left ventricular dilation and decreased left ventricular systolic pressure (80 +/- 10 to 55 +/- 10 mm Hg) and stroke work. Although the extent of paradoxic septal displacement increased, there were further decrements in right ventricular systolic pressure (22.1 +/- 4.5 to 18.7 +/- 4.3 mm Hg) and stroke work (1.92 +/- 0.53 to 0.7 +/- 0.2 g.m/m2). Dopamine infusion augmented left ventricular free wall contraction and increased left ventricular systolic pressure (55 +/- 10 to 172 +/- 17 mm Hg) and stroke work. Although systolic septal thinning persisted, the extent of paradoxic septal displacement increased strikingly and, despite continued right ventricular free wall dyskinesia, right ventricular systolic pressure increased (18.7 +/- 4.3 to 39.6 +/- 6.2 mm Hg) as did right ventricular stroke work (0.7 +/- 0.2 to 7 +/- 1.6 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Effects of nicorandil on regional perfusion and left ventricular function.

Left ventricular function and regional perfusion were evaluated by two study designs in patient groups with stable ischemic coronary artery disease (CAD): (1) using conventional left ventricular angiographies and (2) applying myocardial contrast echocardiography. The aim of the studies was to establish the effects of sublingually or orally applied nicorandil (N) on pacing-induced myocardial ischemia (MIS). In the first angiographic study, in nine patients with ischemic CAD and with pacing-inducible MIS, the effect of N, 20 mg sublingually, on hemodynamics and regional wall motion (RWM) were studied. There were no parameter changes without MIS being induced when comparing measurements at the 7th and 14th minute after N application to control values (p > 0.05). In the 15th and 16th minutes after N, pacing-induced MIS could no longer be elicited but left ventricular pump function improved; comparing MIS with N versus MIS without N: ejection fraction improved by 21%, cardiac index by 37%, and RWM by 21%, while filling pressure fell by 41% and systemic vascular resistance fell by 29%. Thus, N-mediated "protection from ischemia" with rather improved hemodynamics and RWM corresponds with alterations that theoretically could have been expected after nitroglycerin given under the above conditions. In the second echocardiographic study, regional perfusion was assessed in 10 patients by intracoronary injection of a newly developed echo contrast medium (ECM) and measurement of ECM washout halftime (t1/2) over opacified myocardial regions of interest, which displayed wall motion abnormalities already at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Left ventricular function during stable sustained ventricular tachycardia. Hemodynamic and echo-Doppler analysis.

To assess the left ventricular function during sustained stable ventricular tachycardia (VT), ten patients, aged 58 to 74, underwent simultaneous echo-Doppler and hemodynamic studies during sinus rhythm and induced sustained stable monomorphic VT. The VT cycle length was 447 +/- 92 ms (mean +/- SD). During VT, cardiac index fell from 2.32 +/- 0.54 to 1.62 +/- 0.63 L/min/m2 (p less than 0.001), and systemic systolic blood pressure fell from 129 +/- 18 to 107 +/- 18 mm Hg (p less than 0.001), while left ventricular end-diastolic pressure showed a rising trend from 9 +/- 7 to 15 +/- 12 mm Hg, and pulmonary artery wedge pressure rose from 10.2 +/- 1.6 to 24.2 +/- 2.3 mm Hg (p less than 0.005). By echo-Doppler the ejection fraction and the presence and degree of valvular regurgitation were not significantly changed during VT. The mean maximal left ventricular inflow tract velocities, mean time velocity integrals, and the mean time velocity integrals normalized for heart rate (measures of left ventricular diastolic filling) decreased from 0.59 +/- 0.074 to 0.40 +/- 0.053 m/s (p less than 0.05), from 0.12 +/- 0.029 to 0.021 +/- 0.012 m (p less than 0.001), and from 7.43 +/- 1.20 to 3.21 +/- 1.49 m x beats/min (p less than 0.001) during VT, respectively. We conclude that hemodynamic changes during stable sustained VT are neither associated with significant changes in systolic left ventricular function nor related to valvular regurgitation and are likely caused by impaired left ventricular diastolic filling.

Aged

[Correlation of stimulus-induced ventricular echo beats and left ventricular function in patients without ventricular tachycardia].

110 patients (105 male, 5 female, mean age +/- S.D.: 52.9 +/- 5.9 years) with and without coronary artery disease were prospectively studied by programmed right ventricular stimulation (single and double premature stimuli during sinus rhythm and a paced ventricular drive of rates of 120, 140, 160 and 180 b.p.m.). The incidence of ventricular echobeats (VE) was correlated with angiographic and electrocardiographic findings. The end of the stimulation protocol was reached as soon as four or more ventricular echobeats were initiated. 0 to 3 VE occurred in 61/110 patients, 4-9 VE in 31 patients (28%), and greater than or equal to 10 VE were induced in 16 patients. Four or more VE were initiated in 68% of cases up to a paced ventricular rhythm of 120 b.p.m. after one or two premature stimuli. Patients with abnormal results of stimulation showed a tendency to an increase in the frequency of ventricular extrasystoles and couplets during long-term ECG recording. 86% of the patients with normal angiographic findings had 0-3 VE and 14% greater than or equal to 4 VE. In 49% of the patients with abnormal left ventricular function, 0-3 VE and in 51%, greater than or equal to 4 VE could be induced. The type of left ventricular contraction abnormality was significantly correlated to the results of programmed ventricular stimulation. greater than or equal to 4 VE were observed in 74% of patients with anterior wall myocardial infarction. Patients with inferior wall myocardial infarction had greater than or equal to 4 VE in 54% of cases. Ventricular tachycardia was induced in 30% of patients with anterior and in only 12% of patients with inferior wall myocardial infarction (n.s.). To conclude, this prospective study has shown a correlation between the incidence of inducible ventricular echobeats in response to programmed ventricular stimulation and left ventricular function. The prognostic significance of these findings has to be assessed.

Electric Stimulation

Amrinone therapy in patients with heart failure. Lack of improvement in functional capacity and left ventricular function at rest and during exercise.

Short-term amrinone therapy has been shown to exert beneficial hemodynamic effects in patients with heart failure. To determine whether this improvement persists longer, the effects of maximally tolerated doses of amrinone on exercise duration, oxygen consumption, and left ventricular function and volumes were examined during maintenance therapy. After four weeks of amrinone therapy, 75 to 150 mg three times a day (mean 292 +/- 70 mg daily), treadmill exercise duration, maximal oxygen consumption, and functional class were unchanged from control values. Radionuclide-derived ejection fraction and end-diastolic and end-systolic volumes were not altered at rest or during maximal supine exercise. Similarly, significant changes in echocardiographic end-systolic and end-diastolic dimensions did not occur. This lack of clinical benefit on functional capacity and left ventricular function, together with frequent adverse reactions, will limit the application of amrinone in the treatment of heart failure. These findings are relevant to the investigation of amrinone-like derivations presently being studied for the treatment of heart failure. Before their release, these agents will require careful evaluation and demonstration of a therapeutic action during maintenance therapy, together with a low incidence of adverse reactions.

Administration, Oral