Vasodilator Therapy In Patients Research Articles

Effects of Stopping Long-term Vasodilator Therapy in Patients with Chronic Aortic Insufficiency

We studied the effects of stopping long-term vasodilator therapy in 17 patients with chronic stable aortic insufficiency. These patients received hydralazine for 37 +/- 15 months (mean +/- SD) and, as a result, had experienced a significant decrease in left ventricular volumes. All patients were followed clinically and ten of the patients underwent serial radionuclide evaluation at baseline, while receiving drug, and at 20 +/- 7 months after stopping drug therapy. No patient showed evidence of acute clinical deterioration when drug therapy was stopped. The rate of progression to valve replacement due to onset of symptoms or left ventricular dysfunction was not significantly different from that previously reported in a population with similar characteristics. Left ventricular size, however, returned to levels similar to baseline after drug therapy was stopped. We conclude that long-term vasodilator therapy may be discontinued in patients with chronic stable aortic insufficiency without causing clinical deterioration or significant alteration in rate of progression to valve replacement.

Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure.

Early development of nitrate tolerance has been shown in patients with chronic congestive heart failure (CHF) receiving continuous nitroglycerin therapy. The influence of dosing interval of oral isosorbide dinitrate (ISDN), the nitrate preparation most widely used for the treatment of CHF, has not been investigated. We performed a prospective, randomized study to evaluate the effect of various regimens of oral ISDN on the development of early tolerance to its effect on left ventricular filling pressure in patients with moderate to severe CHF. Forty-four responders (20% or greater reduction in mean pulmonary artery wedge pressure lasting 1 hour or longer) were divided into four groups of 11 patients each, and randomized to receive their effective ISDN dose (40-120 mg) Q 4 hours, Q 6 hours, Q 8 hours, or t.i.d. (drug given at 0, 6, 12, and 24 hours allowing 12 hours of ISDN washout interval between the third and fourth doses). All groups demonstrated a significant and comparable reduction in LV filling pressure following administration of the first ISDN dose. Early attenuation of hemodynamic response was demonstrated with frequent dosing (Q 4 hours and Q 6 hours) ISDN. Tolerance was with a Q 8-hour regimen as demonstrated by preserved hemodynamic response to each dose. The effect of each dose, however, was short-term, with return of pulmonary artery wedge pressure to baseline level at 2 to 4 hours, resulting in an intermittent effect totaling no longer than 12 hours of the 30-hour study period. The use of a t.i.d. regimen resulted in marked attenuation of response after the third dose with complete restoration of nitrate effect following a 12-hour washout period between the third and fourth doses. ISDN plasma concentration was measured in five patients in each of the Q 4- and Q 8-hour groups. In the Q 4-hour group, plasma levels were significantly higher after administration of the last dose than after the first dose (area under the curve, 242 +/- 216 versus 123 +/- 130 ng/ml, p less than 0.05), and trough levels before administration of the second and the fifth dose (15 +/- 17 and 27 +/- 27 ng/ml, respectively) were both markedly higher than the baseline value of 2 +/- 4 ng/ml. Our data demonstrate the development of tolerance and early attenuation of effect on left ventricular filling pressure with frequent oral dosing (Q 4 and Q 6 hours) with ISDN in patients with chronic CHF, which may be related to persistently elevated trough blood levels of ISDN. The development of tolerance can be reversed after a washout period of 12 hours and can be prevented with a Q 8-hour administration. These regimens, however, are limited by an inconsistent effect. Although long-term implications of these findings need further evaluation, the present study demonstrates the difficulty of maintaining a persistent ISDN-mediated reduction in left ventricular filling pressure in patients with chronic, moderate to severe CHF. These results suggest the need to use intermittent ISDN therapy allowing a daily nitrate washout interval and the rationale for combined vasodilator therapy in patients with CHF.

Early Intervention in Heart Failure

Treatment for patients with congestive heart failure is primarily directed at reducing symptoms and improving functional capacity. In patients with moderate to severe heart failure, therapeutic interventions incorporating diuretics, digoxin and selected vasodilators, specifically angiotensin-converting enzyme (ACE) inhibitors, are designed to correct pathophysiological mechanisms such as left ventricular dysfunction, excessive vasoconstriction and renal reabsorption of sodium and water. Physician-investigators are turning their attention to identifying and treating patients early in the course of their disease. Vasodilator therapy in patients with mild symptoms of heart failure may not only improve exercise performance, but also reduce mortality. In addition, recent studies have suggested that ACE inhibitors may prevent progression of disease in patients with asymptomatic left ventricular dysfunction. It is hoped that ongoing research will demonstrate that early identification and treatment of these patients may prevent development of symptoms and improve survival.

Calcium Antagonists and Heart Failure

The systemic vasodilatory actions of the calcium antagonists make them potentially attractive for use as afterload reducing agents in patients with left ventricular failure. However, unlike other vasodilator drugs, these drugs also exert a direct negative inotropic effect on the myocardium. Clinical data suggest a limited role for the calcium antagonists as vasodilator therapy in patients with heart failure.

Hemodynamic studies-their uses and limitations

Hemodynamic studies are useful in the diagnosis of the pathophysiologic mechanisms of pump failure and low output state in patients with acute heart failure. Hemodynamic monitoring is extremely useful for the appropriate manipulation of the vasoactive drugs to optimize hemodynamic and clinical improvement of patients with acute heart failure and to stablize patients with severe refractory or unstable chronic heart failure. Determinations of the hemodynamic indexes of left ventricular function during hemodynamic studies also provide information regarding prognosis of patients with acute or chronic heart failure. In patients with stable chronic heart failure, correlations between the changes in hemodynamics after initiation of vasodilator therapy and subsequent changes in the clinical status and exercise tolerance are poor; thus, the value of hemodynamic studies for vasodilator therapy in patients with stable chronic heart failure is limited.

Oxygen therapy and vasodilator therapy in patients with chronic lung disease: the effects of episodic pulmonary hypertension during sleep and exercise performance.

In patients with chronic lung disease, we estimated the effectiveness of nocturnal oxygen therapy in eliminating episodes of sleep hypoxemia and concomitant elevations in the pulmonary arterial pressure. We also assessed the effect of vasodilators (ISDN, nifedipine) in improving exercise tolerance. Our results support the efficacy of nocturnal oxygen therapy. Vasodilators examined were not confirmed as effective or safe for wide use.

Comparison of Acute Hemodynamic Responses to Prostacyclin with Standard Vasodilators in Patients with Primary Pulmonary Hypertension

Although the benefit of long-term vasodilator therapy in patients with primary pulmonary hypertension (PPH) is still unsettled, efforts have been made to assess the role of evaluations of acute pulmonary vascular reactivity as a guide to long-term pharmacologic therapy.1 Because of problems inherent in these studies and the lack of a specific pulmonary arterial vasodilator, many potential pulmonary vasodilator agents from different pharmacologic classes have been tried in these acute studies.2 These acute drug studies can be lengthy and carry risk of substantial morbidity and even potential mortality.

Vasodilator therapy in chronic congestive heart failure

Benefits from vasodilator therapy in patients with chronic heart failure are partly related to the severity of functional derangements. Agents with an arteriolar-dilating effect are more likely to be effective in patients with higher left ventricular outflow resistance. Vasodilators with primary venodilating properties are more likely to be effective in the presence of an increased ventricular preload. The mechanisms by which preload and left ventricular outflow resistance increase in patients with cardiac insufficiency are not well understood and may not be similar in all patients. Vasodilators also have the capacity to ameliorate myocardial metabolic functional abnormalities by influencing myocardial energetics, but the effects of different agents on coronary hemodynamics may not be uniform. Effects on renal hemodynamics may also vary, as may neurohumoral changes after therapy. Angiotensin-converting enzyme inhibitors have been shown to exert beneficial effects on both coronary and renal hemodynamics in patients with chronic heart failure, while producing favorable neurohumoral changes. These agents provide some advantages over direct-acting vasodilators in that myocardial oxygen consumption is decreased, myocardial metabolic function is improved, and norepinephrine and aldosterone levels are reduced. Further controlled studies are needed to assess the efficacy of angiotensin-converting enzyme inhibitors in relation to other vasodilators for the long-term management of these patients.

Potentially Deleterious Effects of Long-term Vasodilator Therapy in Patients with Heart Failure

SUMMARY It is clear that we clinicians have accepted a philosophy of treating heart failure with vasodilator compounds, and we are fortunate to have a variety of pharmacotherapeutic agents from which we can choose. Each group has certain advantages and potentially deleterious effects, and as a general class of compounds, it is critical to remember the hemodynamic effects of these drugs. The advantages of the angiotensin-converting enzyme inhibitors include well-documented long-term efficacy with significant reduction in symptoms, improved exercise tolerance, and amelioration of detrimental hemodynamics. There is a large clinical experience with both captopril and enalarpril, with one agent, captopril, currently having the blessing of the Food and Drug Administration for use in congestive heart failure. Enalapril may have fewer side effects than captopril because of the absent sulfhydryl group and is suitable for once or twice daily dosing because of prolonged activity. The major disadvantages of the angiotensin-converting enzyme inhibitors include hypotension and pre-renal azotemia, but other potentially serious side effects such as neutropenia and proteinuria seem, fortunately, to be rare. Other vasodilators, such as hydralazine, prazosin, and nitrates, have some potential advantages, including the long-term demonstrated efficacy of nitrates in terms of hemodynamic and symptomatic improvement and relative freedom from serious side effects. Of additional importance are the recently published data from the VA cooperative study of vasodilators in heart failure, which demonstrated an attentuation of mortality in patients receiving the combination of oral isosorbide dinitrate and hydralazine (Apresoline). 8 This reduction in mortality was seen despite a complicated regimen of drug administration (300 mg of hydralazine per day and 160 mg of isosorbide dinitrate per day) and a 22 percent discontinuation of treatment in this group (usually because of deleterious effects). The major disadvantage of prazosin, which did not have the same effect on mortality as the combination of hydralazine and isosorbide dinitrate, seems to be the lack of demonstrated long-term efficacy. Still, the possibility of serious side effects from hydralazine (lupus syndrome), the requirement for frequent dosing (at least thrice daily), and the necessity of combining the agent with other vasodilators to achieve concomitant reduction in preload, remain disadvantages for hydralazine. Calcium-channel blocking agents have several physiologic properties, including peripheral and coronary vasodilation, electrophysiologic and antiarrhythmic effects, and the tendency to increase diastolic compliance, which, theoretically, make them beneficial drugs in certain patients with heart failure. The potential cardiodepressant effects and the limited clinical experience with calcium-channel blockers in congestive heart failure make for difficult titration, but, clearly, patients with ischemic heart disease and moderately depressed left ventricular function might benefit from them without developing serious deleterious consequences during long-term therapy. Also, patients who have heart failure with diastolic dysfunction such as hypertrophic cardiomyopathies would probably improve more predictably with these vasodilators than others. The use of combined vasodilator drugs may offer distinct advantages to the patient with heart failure, and the best example of this is the combination of nitrate therapy with hydralazine (Apresoline). Theoretically, nitrates and nifedipine or any of the other calcium-channel blockers would also be beneficial because the primary preload-reducing effects of nitrates would ameliorate one aspect of hemodynamic abnormality not affected by the relatively pure after-load-reducing advantage of the other. Results of combining two vasodilators effecting similar hemodynamic responses in patients with heart failure is unknown. Thus, combinations of angiotensin-converting enzyme inhibitors and prazosin or of hydralazine and nifedipine should not routinely be designed. It is possible that no additive vasodilator effects would be evident, but the patient might be exposed to an additional burden of toxic effects, particularly with respect to idiosyncratic reactions. It certainly might be appropriate to combine vasodilator drugs if the patient's condition was refractory to manipulation with one compound, but precise hemodynamic characterization of the clinical state would be mandatory. Should a decision be made to combine two or more vasodilators, choosing agents from disparate classes seems most logical. The choice of which single vasodilator agent to use clinically in patients with left ventricular dysfunction is one that must be individualized, juxtaposing the pharmacologic properties of agents with the hemodynamic, neurohumoral, and clinical characteristics of particular patients, always weighing the possibility of deleterious effects in the decision-making matrix. This demands beng cognizant of whether the patient is relatively well compensated and asymptomatic or whether symptoms are present that relate to low-output syndrome or the congestive state of heart failure.

Effects of combination therapy with captopril and nifedipine in severe or resistant hypertension.

To assess the effect of potent vasodilator therapy in patients with severe or resistant hypertension, 10 patients underwent therapy with captopril and nifedipine alone and in combination. Blood pressure (BP), heart rate, and blood chemistry values were monitored for 4 weeks during captopril monotherapy and after 8 weeks during combination therapy with captopril and nifedipine. Compared with baseline, the BP decreased during captopril monotherapy (180 +/- 11/98 +/- 7 vs. 209 +/- 16/118 +/- 12 mm Hg; P less than 0.005). After the addition of nifedipine, the BP was further reduced (148 +/- 23/85 +/- 16 mm Hg), but there was no change in heart rate. In three patients not achieving the diastolic BP goal during combination therapy with dosing every 8 hours, automatic 24-hour ambulatory BP monitoring demonstrated lack of antihypertensive control for only the last 2 to 3 hours of the dosing interval. These data demonstrate that combination therapy with captopril and nifedipine is effective in patients with severe hypertension, but frequent dosing intervals are necessary for adequate antihypertensive control.

Assessment of vasodilator therapy in patients with severe congestive heart failure: Limitations of measurements of left ventricular ejection fraction and volumes

Although noninvasive techniques are often used to assess the effect of vasodilator therapy in patients with congestive heart failure, it is unknown whether changes in noninvasively determined left ventricular ejection fraction, volume, or dimension reliably reflect alterations in intracardiac pressure and flow. Accordingly, we compared the acute effect of sodium nitroprusside on left ventricular volume and ejection fraction (determined scintigraphically) with its effect on intracardiac pressure and forward cardiac index (determined by thermodilution) in 12 patients with severe, chronic congestive heart failure and a markedly dilated left ventricle. Nitroprusside (infused at 1.3 ± 1.1 [mean ± standard deviation] μg/kg/min) caused a decrease in mean systemic arterial, mean pulmonary arterial and mean pulmonary capillary wedge pressure as well as a concomitant increase in forward cardiac index. Simultaneously, left ventricular end-diastolic and end-systolic volume indexes decreased, but the scintigraphically determined cardiac index did not change significantly. Left ventricular ejection fraction averaged 0.19 ± 0.05 before nitroprusside administration and increased by less than 0.05 units in response to nitroprusside in 11 of 12 patients. The only significant correlation between scintigraphically and invasively determined variables was that between the percent change in end-diastolic volume index and the percent change in pulmonary capillary wedge pressure (r = 0.68, p = 0.01). Although nitroprusside produced changes in scintigraphically determined left ventricular ejection fraction end-systolic volume index and cardiac index, these alterations bore no predictable relation to changes in intracardiac pressure, forward cardiac index, or vascular resistance. Furthermore, nitroprusside produced a considerably greater percent change in the invasively measured variables than in the scintigraphically determined ones.

Accuracy of cardiac output, oxygen uptake and arteriovenous oxygen difference at rest, during exercise and after vasodilator therapy in patients with severe, chronic heart failure

Measurement of cardiac output, arteriovenous oxygen difference and oxygen uptake in patients with heart failure may be subject to technical and biologic inaccuracies. We measured these 3 variables in 16 patients with chronic heart failure at rest and during exercise. When cardiac output was measured by thermodilution and compared with values calculated by the Pick principle, there was a significant correlation at rest ( r = 0.91, p < 0.001) and at exercise ( r = 0.93, p < 0.001). When the arteriovenous oxygen difference was measured by spectrophotometry of arterial and mixed venous samples and compared with values calculated by the Pick principle, there was a significant correlation at rest (r = 0.80, p < 0.01) and at exercise (r = 0.76, p < 0.01). When oxygen uptake was measured from expired gas analysis and compared with values calculated by the Pick principle, there was a significant correlation at rest ( r = 0.84, p < 0.01) and at exercise (r = 0.94, p < 0.001). In addition, 10 patients received vasodilator treatment which increased cardiac output and decreased the arteriovenous oxygen difference at rest and exercise. There was no significant difference between measured and calculated values for the 3 variables under those additional conditions. It is concluded that despite technical and biologic difficulties, cardiac output, arteriovenous oxygen difference and oxygen uptake, when calculated from Pick's principle, yield results equivalent to direct measurement.

The Effect of Vasodilator Therapy on Systolic and Diastolic Time Intervals in Congestive Heart Failure

To determine the effects of vasodilator drugs on systolic and diastolic time intervals in patients with congestive heart failure, these noninvasive measurements were made in 50 patients with moderately severe disease before and after vasodilator therapy. These data were compared with direct hemodynamic measurements obtained simultaneously from a flow-directed triple-lumen pulmonary artery catheter placed in each patient. Oral vasodilators included isosorbide dinitrate 20 mg (n-8), hydralazine 75 mg (n-8), and 100 mg (n-8), and first-dose prazosin 2 mg (n-8) and 5 mg (n-8). Ten additional patients received intravenous dose-response infusions of isosorbide dinitrate, nitroglycerin, and nitroprusside. Increases in cardiac output and stroke volume effected a decrease (improvement) in the systolic time interval parameter of ventricular performance, PEP/LVET. The correlation coefficient for vasodilator-induced changes in cardiac output vs changes in PEP/LVET was -0.82 (P less than 0.05) and for changes in stroke volume and PEP/LVET was -0.75 (P less than 0.05). In general, the diastolic time period was not significantly affected by these drugs. The systolic time intervals are a simple and useful method for evaluation of vasodilator therapy in patients with congestive heart failure.

Acute and chronic effects of captopril therapy in patients with refractory heart failure.

British Journal of Clinical PharmacologyVolume 14, Issue S2 p. 153S-159S Free Access Acute and chronic effects of captopril therapy in patients with refractory heart failure. WF Walsh, WF WalshSearch for more papers by this authorCL Lee, CL LeeSearch for more papers by this author WF Walsh, WF WalshSearch for more papers by this authorCL Lee, CL LeeSearch for more papers by this author First published: April 1982 https://doi.org/10.1111/j.1365-2125.1982.tb02072.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References ADER, R., CHATTERJEE, K., PORTS, T., BRUNDAGE, B., HIRAMATSU, B. & PARMLEY, W. (1980). Immediate and sustained haemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation, 61, 931– 937. COHN, J.N. (1973). Vasodilator therapy for heart failure: the influence of impedance on left ventricular performance. Circulation, 48, 5. DAVIS, R., RIBNER, H.S., KEUNG, E., SONNENBLICK, E.H. & LeJEMTEL, T.H. (1979). Treatment of congestive heart failure with captopril, an oral inhibitor of angiotensin converting enzyme. N. Engl. J. Med., 301, 117– 121. DZAU, V.J., COLUCCI, W.S., WILLIAMS, G.H., CURFMAN, G., MEGGS, L. & HOLLENBERG, N. (1980). Sustained effectiveness of converting enzyme inhibitor in patients with severe congestive heart failure. N. Engl. J. Med., 302, 1373– 1379. FRANCIOSA, J. (1982). Effectiveness of long term vasodilator administration in treatment of chronic left ventricular failure. Prog. Cardiovasc. Dis., 1A, 319– 330. MASSIE, B., PORTS, T., CHATTERJEE, K. PARMLEY, W., OSTLAND, J., O'YOUNG, J. & HAUGHOM, F. (1981). Long term vasodilator therapy for heart failure: Clinical response and its relation to haemodynamic measurements. Circulation, 63, 269. PACKER, M., MELLER, J., GORLIN, R. & HERMAN, M.V. (1979). Haemodynamic and clinical tachyphylaxis to prazosin mediated afterload reduction in patients with severe chronic congestive heart failure. Circulation, 59, 531– 539. PACKER, M., MELLER, J., MEDINA, N., YUSHAK, M. & GORLIN, R. (1982). Haemodynamic characterisation of tolerance to long term hydralazine therapy in severe chronic heart failure. N. Engl. J. Med., 306, 57– 62. PACKER, M. & LeJEMTEL, T.H. (1982). Physiologic and pharmacologic determinants of vasodilator response: A conceptual framework for rational drug therapy for chronic heart failure. Prog. Cardiovas. Dis., 24, 275– 292. WALSH, W.F. & GREENBERG, B.H. (1981). Results of long term vasodilator therapy in patients with refractory congestive heart failure. Circulation, 64, 499– 505. Volume14, IssueS2April 1982Pages 153S-159S ReferencesRelatedInformation

Vasodilator therapy: Implications in acute myocardial infarction and congestive heart failure

The physiologic effects of systemic vasoconstriction on left ventricular performance and the salutary hemodynamic effect of acute administration of vasodilator drugs to patients with heart failure provide a rational basis for vasodilator therapy in acute myocardial infarction and chronic congestive heart failure. Use of vasodilators during the acute phase of myocardial infarction may reduce mortality when left ventricular filling pressure remains markedly elevated for at least 8 hours after the onset of clinical syndrome. Use of chronic vasodilator therapy in patients with congestive heart failure appears to have been effective in some patients in prolonging exercise tolerance; however, the likelihood of a beneficial effect and the impact of this therapy on the natural history of the disease remain unclear. A Veterans Administration Cooperative Study to address these questions is currently in progress. The new effort directed to studying the effects of vasodilator drugs in these syndromes has appropriately focused attention on their pathophysiology and natural history.

Physiologic and pharmacologic determinants of vasodilator response: A conceptual framework for rational drug therapy for chronic heart failure

This article has attempted to summarize the increasing number of pharmacologic and physiologic variables that are being recognized as important determinants in the response to vasodilator therapy in patients with severe chronic heart failure. It is apparent that a careful consideration of many factors is necessary before proper selection of a specific drug can be made for a specific patient, since not all patients with refractory heart failure demonstrate beneficial hemodynamic and clinical responses to all agents. Each patient presents us with a unique set of physiologic variables; each drug has its own advantages and limitations. Identification of those subgroups of patients most likely to benefit from a specific agent or combination of agents is a major goal for future research. Although a number of hemodynamic variables can be made to improve acutely with a wide variety of vasodilator drugs, well tolerated sustained meaningful clinical benefits are probably observed in relatively few patients. Rational and successful vasodilator therapy is possible only through a highly individualized approach.

Value of the tricuspid valve echogram for estimating right ventricular end-diastolic pressure during vasodilator therapy

To evaluate the potential usefulness of the tricuspid valve echogram for assessing right ventricular end-diastolic pressure, 9 patients with right heart failure and 10 normal subjects were studied. In the nine patients, the initial P-R interval of 184 ± 26 (±1 standard deviation) ms did not differ significantly from the normal subjects' value of 170 ± 17 ms; however, the A-C Interval of 162 ± 23 ms was significantly longer (p < 0.001) and the PR-AC interval of 21 ± 16 ms was shorter (p < 0.001) when compared with corresponding control measurements. Nitroprusside infusion significantly decreased the right ventricular end-diastolic pressure from 15 ± 4 to 8 ± 4 mm Hg in the nine patients (p < 0.001). Additionally, it decreased the average A-C interval to 137 ± 25 ms (p < 0.001) and the mean PR-AC interval to 46 ± 18 ms (p < 0.05). However, the PR-AC interval did not correlate closely with the right ventricular end-diastolic pressure. Furthermore, it did not separate elevated right ventricular end-diastolic pressures from normal pressures. However, a qualitative assessment of the morphologic appearance of tricuspid valve closure motion during the A-C segment was predictive of right ventricular enddiastolic pressure over the wide range produced by nitroprusside infusion. In addition, it reliably identified patients with elevated end-diastolic pressures. All nine patients had a B plateau or hump in the initial resting tricuspid valve echogram when the right ventricular end-diastolic pressure was 9 mm Hg or greater. Therefore, an analysis of morphologic changes in the tricuspid valve closure motion provides a valuable noninvasive tool for assessing right ventricular end-diastolic pressure at rest and during acute vasodilator therapy in patients with right heart failure.

VASODILATOR THERAPY FOR CHRONIC LEFT VENTRICULAR FAILURE

KOVICK, R. B.; TILLISCH, J. H.; BERENS, S. C.; BRAMOWITZ, A. D.; SHINE, K. I. Author Information

Effects of vasodilator therapy for severe pump failure in acute myocardial infarction on short-term and late prognosis.

Forty-three patients with severe pump failure complicating acute myocardial infarction were treated with vasodilators (nitroprusside (40) and phentolamine (3)) for four hours to 27 days. Cardiac index, stroke volume index, and stroke work index (SWI) increased while the left ventricular filling pressure (LVFP) decreased during vasodilator therapy. Twenty-four of the 43 patients (56%) survived. Of patients with initial SWI between 11-20 gm-m/m2 and LVFP less than 15 mm Hg, 68% survived. In contrast only 18% of patients with SWI of 10 gm-m/m2 or less and LVFP greater than 15 mm Hg survived. Of the 17 patients with clinical shock, 8 (47%) survived. All 24 patients discharged from the hospital were followed for at least 12 months. Fourteen patients died one to 25 months (average 9.2 months) after discharge and the cause of death was pump failure in ten of them (71%). The ten survivors at last follow-up had been followed for 15 to 32 months (average 24 months). The cumulative survival at 24 months was 28%. Thus, despite improvement in short-term prognosis with vasodilator therapy in patients with severe pump failure complicating acute myocardial infarction, the prognosis for long term survival remains unfavorable, possibly due to severe intrinsic cardiac damage.

Vasodilator therapy for chronic left ventricular failure.

The effects of chronic oral vasodilator therapy were studied in a group of patients with refractory congestive heart failure. Fifteen patients were treated acutely with intravenous sodium nitroprusside and sublingual isosorbide dinitrate. After continuous therapy with nitroprusside and isosorbide dinitrate for up to 72 hours the patients were then placed on isosorbide dinitrate and oral phenoxybenzamine. Hemodynamic responses to nitroprusside, isosorbide dinitrate, and phenoxybenzamine with isosorbide dinitrate were determined. After a mean follow-up of seven months, nine patients who were receiving isosorbide dinitrate and phenoxybenzamine underwent repeat hemodynamic studies. Beneficial effects of acute vasodilator therapy included a significant reduction in pulmonary capillary wedge pressure and systemic vascular resistance, and significant increases in cardiac index and stroke work index. Mean arterial blood pressure and heart rate were unchanged. During the period of chronic vasodilator administration, no other change in basic therapy with isosorbide dinitrate and phenoxybenzamine (3-21 months), the favorable effects observed acutely were maintained. All patients demonstrated symptomatic improvement with minimal side effects. The beneficial hemodynamic responses that are noted with acute vasodilator therapy in patients in advanced congestive heart failure are maintained with oral therapy on a chronic basis.