Vasodilator Therapy In Heart Failure Research Articles

Guiding heart failure care by invasive hemodynamic measurements: Possible or useful?

The quest to discover effective methodologies to monitor the course of disease and response to therapeutic agents in patients with chronic heart failure continues. The relentless progression of underlying left ventricular dysfunction and periodic, severe symptomatic decompensation often requiring hospitalization remain essential features of the heart failure syndrome despite significant therapeutic advances. Clinical trials of specific therapeutic agents have shown efficacy in large groups of patients. But outcome, even with the most effective agents, is recognized to be heterogeneous for largely unexplained reasons. The idea that treatment of individual patients with heart failure could be guided by serial measurements of surrogate end points for mortality and morbidity remains attractive to clinicians. Several assumptions underlie the concept that sequential physiologic measurements such as hemodynamics can be used to guide therapy: (1) measurements indicative of clinical response during heart failure can be ascertained, albeit with varying degrees of difficulty; (2) serial determinations of these measurements, such as left ventricular dysfunction, neurohormonal activation, and central hemodynamics, will predict clinical responses to general measures and pharmacologic therapy; (3) these measurements are not sufficiently risky, expensive, or cumbersome to preclude their being obtained as a part of routine clinical practice; (4) these measurements are sufficiently reproducible to provide the basis for making therapeutic changes in individual patients; (5) continuous measurements rather than serial snapshots of, for example, hemodynamics are likely best; (6) adjustment of currently available treatment strategies will favorably effect the measures that are monitored; (7) the frequency of therapeutic adjustments and subsequent follow-up study prompted by serial measurements is feasible for most patients; and (8) monitoring physiologic aspects of the disease process will provide more benefit than expending similar resources on changes in the process of delivery of care, ie, measurements of right heart hemodynamics with medication adjustment versus patient management via a heart failure program. Magalski et al in this issue of Journal of Cardiac Failure describe one strategy for monitoring the course of chronic heart failure that begins early work to address some of these issues.

Ambulatory vasodilator therapy in heart failure: systematic review of the literature and personal observational experience.

Ambulatory vasodilator therapy in heart failure: systematic review of the literature and personal observational experience.

Mathematical model of cardiovascular mechanics for diagnostic analysis and treatment of heart failure: Part 2 analysis of vasodilator therapy and planning of optimal drug therapy

Using a mathematical model of cardiovascular mechanics, various complicated responses to vasodilator therapy for heart failure have been well accounted for through common logic: (i) the differential effects of various vasodilators on cardiac output; (ii) the opposite response of cardiac output to sodium nitroprusside in a normal state and heart failure state; (iii) the different responses of cardiac index, arterial pressure and left ventricular end-diastolic pressure to hydralazine in different types of heart failure. The response to combined vasodilator-inotropic agent therapy was simulated well by the model. The optimal therapeutic regimen was then formulated to simultaneously control the cardiac output, systemic and pulmonary arterial and venous pressures, and the degree of coronary ischaemia by multiple drug delivery, and the problem was solved using the model. We conclude that the model provides a useful basis for obtaining a guidance for more appropriate therapeutic regimen in heart failure.

Prostaglandin E2 in dogs with heart failure: hemodynamic, hormonal, and renal effects.

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the hemodynamic, hormonal, and renal effects of prostaglandin E2 (1.5-150 ng/kg/min) in six conscious dogs before and after induction of heart failure by right ventricular pacing (250 beats/min, 10 days). In healthy dogs, PGE2 decreased the mean arterial pressure (MAP) by a reduction in total peripheral resistance (TPR), increased cardiac output (CO), stroke volume (SV), and heart rate with no effect on right atrial pressure (RAP). Plasma levels of renin (PRC) and norepinephrine (NE) were increased at the highest dosage. Renal plasma flow (RPF) and sodium excretion (UNaV) were augmented without a change in the glomerular filtration rate (GFR) and urine flow (UF). In dogs with heart failure, PGE2 lowered the MAP and TPR and elevated the CO and SV without an effect on the RAP, PRC, and NE. The RPF and GFR were not changed, but the increase in UNaV was preserved and UF significantly augmented. In experimental heart failure, PGE2 increases the CO due to arteriolar dilation and afterload reduction without inducing further neurohumoral activation and exerts potent natriuretic and diuretic action. Therefore, PGE2 may have beneficial effects in heart failure therapy.

Hemodynamic, Hormonal, and Renal Effects of the Prostacyclin Analogue Iloprost in Conscious Dogs With and Without Heart Failure

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the effects of the prostacyclin-derivative iloprost (1.5-150 ng/kg/min) in seven conscious dogs before and after induction of heart failure by right ventricular pacing (250/min. 10 days). In healthy dogs, iloprost (150 ng/kg/min) decreased mean arterial blood pressure (MAP) (-45%) by a decrease in total peripheral resistance (TPR) (-55%), and increased cardiac output (CO) (+24%) and heart rate (HR) (+20%) with no effect on right atrial and pulmonary arterial pressures (RAP, PAP). Plasma norepinephrine (NE) (+47%), renin (+351%), and aldosterone (+126%) were increased. Urine flow (-70%) and Na excretion (-53%) were decreased. Iloprost (15 ng/kg/min) increased renal blood flow (RBF) (+29%), but did not change glomerular filtration rate (GFR). In dogs with heart failure, iloprost decreased arterial BP (-31%), TPR (-42%) and pulmonary vascular resistance (-28%) and increased CO (+29%), with no change in RAP and PAP. Plasma NE (+34%), renin (+385%), and aldosterone (+146%) were increased. RBF was unchanged. GFR (-24%) and filtration fraction (FF) (-30%) were decreased, as was urine flow (-65%). In experimental heart failure, iloprost is a potent arteriolar dilator, increasing CO with no preload effect. These beneficial effects are limited, however, by further neurohumoral activation and deterioration of renal function.

Vasodilator therapy for heart failure: what have we learned from controlled clinical trials?

Vasodilator therapy for heart failure: what have we learned from controlled clinical trials?

Vasodilator Therapy for Heart Failure: What Have We Learned From Controlled Clinical Trials?

Vasodilator therapy has now gained wide acceptance as appropriate adjuvant drug treatment for congestive heart failure. Although this therapy previously was reserved for relief of persistent symptoms in patients who were already taking digitalis and diuretics, recent data have provided support for the concept that use of these drugs may prolong life in addition to relieving symptoms. 1,2 The evidence that systemic

Determinants of cardiac augmentation by elevations in intrathoracic pressure.

We studied the cardiovascular effects of phasic increases in intrathoracic pressure (ITP) by high-frequency jet ventilation in an acute pentobarbital-anesthetized intact canine model both before and after the induction of acute ventricular failure by large doses of propranolol. Chest and abdominal pneumatic binders were used to further increase ITP. Respiratory frequency, percent inspiratory time, mean ITP, and swings in ITP throughout the respiratory cycle were independently varied at a constant-circulating blood volume. We found that pertubations in mean ITP induced by ventilator adjustments accounted for all observable steady-state hemodynamic changes independent of respiratory frequency, inspiratory time, or phasic respiratory swings in ITP. Changes in ITP were associated with reciprocal changes in both intrathoracic vascular pressures (P less than 0.01) and blood volume (P less than 0.01). When cardiac function was normal, left ventricular (LV) stroke volume decreased, whereas in acute ventricular failure, LV stroke volume increased in response to increasing ITP when apneic LV filling pressure was high (greater than or equal to 17 Torr) and did not change if apneic LV filling pressure was low (less than or equal to 12 Torr). However, in all animals in acute ventricular failure, LV stroke work increased with increasing ITP. Our study demonstrates that the improved cardiac function seen with increasing ITP in acute ventricular failure is dependent upon adequate LV filling and decreased LV afterload in a manner analogous to that seen with arterial vasodilator therapy in heart failure.

Assessment of Dynamic Cardiac Reserve for the Prediction of the Ventricular Response to Vasodilator Therapy in Heart Failure

Assessment of Dynamic Cardiac Reserve for the Prediction of the Ventricular Response to Vasodilator Therapy in Heart Failure

Hemodynamic effects of vasodilators and long-term response in heart failure

Hemodynamic responses to vasodilators are commonly assessed when starting long-term vasodilator treatment in patients with chronic left ventricular failure, although the relation between short- and long-term responses is not established. Thus, short- and long-term hemodynamic responses to placebo and vasodilators (isosorbide dinitrate, minoxidil and enalapril or captopril) were measured and long-term clinical efficacy was assessed by changes in exercise capacity after 1 to 5 months of vasodilator administration (plus digitalis and diuretic agents) in 46 patients with New York Heart Association functional class II to IV heart failure caused by cardiomyopathy. There were no significant changes in hemodynamics or exercise capacity during placebo treatment. After initial doses and during long-term administration of vasodilator drugs, hemodynamics were significantly improved. After long-term vasodilator treatment, maximal oxygen uptake during exercise increased by 2.9 +/- 5.7 ml/min per kg from a control value of 14.1 +/- 5.6 ml/min per kg (p less than 0.01), and exercise duration also increased by 1.8 +/- 3.5 minutes (p less than 0.01). Changes in maximal oxygen uptake, however, did not correlate with short-term changes in pulmonary wedge pressure (correlation coefficient [r] = -0.14), cardiac index (r = -0.01) or systemic vascular resistance (r = -0.20). Long-term hemodynamic changes also failed to correlate with changes in exercise capacity. Baseline hemodynamics, cardiac dimensions and left ventricular ejection fraction before vasodilator administration all failed to correlate with baseline exercise capacity or with long-term changes in exercise capacity. Thus, hemodynamic measurements at initiation or during follow-up of vasodilator therapy do not relate to long-term clinical efficacy assessed by exercise capacity in patients with chronic left ventricular failure. Therefore, the rationale for making invasive hemodynamic measurements before initiating long-term vasodilator therapy for heart failure is questioned.

Lack of relationship between the short-term hemodynamic effects of captopril and subsequent clinical responses.

The role of hemodynamic monitoring during the initiation of vasodilator therapy for heart failure remains to be defined, despite the tremendous potential socioeconomic and clinical ramifications. We therefore performed resting and exercise hemodynamic studies before and during the initial 48 hr of captopril therapy in 14 stable patients with New York Heart Association Class II or III chronic congestive heart failure. Their clinical response to therapy was determined by evaluating changes in clinical status and the measured changes in exercise tolerance, heart size, and ejection fraction after 3 months. Significant improvement in each of these indexes was found for the group as a whole, but the baseline hemodynamics and the hemodynamic responses to captopril differed little between the patients showing marked improvement and those exhibiting little or no change. Correlations between the hemodynamic measurements and the changes in clinical class, exercise tolerance, heart size, and ejection fraction were generally poor. Even when they achieved significance, these correlations were too loose to allow prediction of the clinical efficacy of captopril in individual subjects. These findings indicate that the routine use of invasive hemodynamic monitoring during the initiation of captopril is unnecessary and potentially misleading, although such measurements remain valuable for diagnosis, the management of patients with complex conditions, and for investigation. The response to captopril may be best evaluated by serial measurements of exercise tolerance and heart size in addition to clinical assessment.

Acute Hemodynamic Effects of Nitrendipine in Chronic Congestive Heart Failure

The acute hemodynamic response to a single oral dose of nitrendipine (10-20 mg) was evaluated in eight subjects with severe chronic congestive heart failure during right heart catheterization. A hemodynamic effect began within 1 h. At peak effect (1-2 h after drug administration), mean arterial pressure fell from 84.0 +/- 9.2 to 76.0 +/- 9.2 mm Hg (mean +/- SD), right arterial pressure from 10.6 +/- 5.9 to 8.0 +/- 7.1 mm Hg, mean pulmonary arterial pressure from 35.5 +/- 9.2 to 30.1 +/- 9.4 mm Hg, pulmonary wedge pressure from 23.6 +/- 6.7 to 17.7 +/- 6.3 mm Hg, and cardiac index rose from 1.91 +/- 0.38 to 2.45 +/- 0.34 L/min/m2. Heart rate did not change (85 +/- 18 to 82 +/- 18 beats/min) despite the significant fall in arterial pressure. Systemic and pulmonary vascular resistances fell significantly. Whereas forearm blood flow increased from 1.44 +/- 0.52 to 2.06 +/- 0.41 ml/min/100 g (p less than 0.05), hepatic and renal blood flows were unchanged. This study demonstrates the acute effectiveness of nitrendipine in reducing ventricular preload and impedance in heart failure and in increasing cardiac output that appears to be preferentially directed to the skeletal bed. The left-upward shift of the Frank-Starling curve suggests the absence of any clinically important negative inotropic effect of nitrendipine. Nitrendipine therefore may be a useful agent for vasodilator therapy of heart failure.

Hemodynamic and metabolic effects of vasodilator therapy for heart failure in acute myocardial infarction.

Hemodynamic effects of vasodilator agents (molsidomine, nitroglycerin, isosorbide dinitrate or prostaglandin I2) were studied in 53 patients with acute myocardial infarction. In 20 of these patients, effect on cardiac metabolism were also studied. Patients were divided into four groups according to the Forrester subset and hemodynamic effects of these agents were evaluated by the cardiac index (CI)-preload (PAEDP) relationship. In patients of Forrester subset II and IV, vasodilators were capable of producing a considerable reduction in preload without a significant decrease in cardiac output. However, in patients of Forrester subset IV, five of six patients had only a minimal improvement in cardiac performance with vasodilator therapy because of a severe pump failure. In these patients, a combination therapy with dopamine was necessary to maintain the cardiac output. In patients with Forrester subset III, vasodilator therapy decreased cardiac index and preload was also reduced. Thus, for these patients vasodilators could not be indicated but volume infusion may be indicated. In patients with Forrester subset I, although vasodilator therapy decreased cardiac output, coronary sinus flow and myocardial oxygen consumption were also decreased, indicating that the vasodilator therapy is also beneficial for patients even without heart failure because of the protective effect of unloading on ischemic myocardium. Three nitrate agents, i.e., molsidomine, nitroglycerin and isosorbide dinitrate, demonstrated the similar effect on hemodynamics; mean blood pressure and PAEDP decreased by 7-10% and 20-29%, respectively, while systemic vascular resistance was not significantly decreased. In contrast to nitrates, PGI2 decreased mean blood pressure and systemic vascular resistance significantly, whereas a decrease in PAEDP was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Captopril in congestive heart failure.

British Journal of Clinical PharmacologyVolume 14, Issue S2 p. 193S-199S Free Access Captopril in congestive heart failure. G Liebau, G LiebauSearch for more papers by this authorAJ Riegger, AJ RieggerSearch for more papers by this authorP Schanzenbacher, P SchanzenbacherSearch for more papers by this authorH Steilner, H SteilnerSearch for more papers by this authorS Oehrlein, S OehrleinSearch for more papers by this author G Liebau, G LiebauSearch for more papers by this authorAJ Riegger, AJ RieggerSearch for more papers by this authorP Schanzenbacher, P SchanzenbacherSearch for more papers by this authorH Steilner, H SteilnerSearch for more papers by this authorS Oehrlein, S OehrleinSearch for more papers by this author First published: April 1982 https://doi.org/10.1111/j.1365-2125.1982.tb02077.xCitations: 7AboutPDF 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 COHN, J.N. (1981). Physiological basis of vasodilator therapy for heart failure. Am. J. Med., 71, 135– 139. COLUCCI, W.S., WILLIAMS, G.H., ALEXANDER, R.W. & BRAUNWALD, E. (1981). Mechanisms and implications of vasodilator tolerance in the treatment of congestive heart failure. Am. J. Med., 71, 89– 99. GREENBERG, B.H., DeMOTS, H., MURPHY, E. & RAHIMTOOLA, S.H. (1982). Arterial dilators in mitral regurgitation: Effects on rest and exercise haemodynamics and long-term clinical follow up. Circulation, 65, 181– 187. FORD, L.E. (1980). Effect of afterload reduction on myocardial energetics. Circ. Res., 46, 161– 166. HOCKINGS, B.E., COPE, G.D., CLARKE, G.M. & TAYLOR, R.R. (1980). Comparison of vasodilator drug prazosin with digoxin in aortic regurgitation. Br. Heart J., 43, 550– 555. IKRAM, H., MASLOWSKI, A.H. & NICHOLLS, G.M. (1981). Haemodynamic effects of dobutamine in patients with congestive heart failure receiving captopril. Br. Heart J., 46, 528– 530. LIEBAU, G. (1982). Captopril in congestive heart failure. Klin. Wschr., 60, 107– 113. LIEBAU, G., RIEGGER, A.J.G. & STEILNER, H. (1981). Haemodynamic effects of captopril in patients with congestive heart failure and hypertension. In: Recent advances in hypertension therapy: captopril. pp. 76– 86, Amsterdam, Excerpta Medica. Citing Literature Volume14, IssueS2April 1982Pages 193S-199S ReferencesRelatedInformation

Vasodilator therapy for heart failure. Concepts, applications, and challenges

Vasodilator therapy for heart failure. Concepts, applications, and challenges

Long-term vasodilator therapy for heart failure: clinical response and its relationship to hemodynamic measurements.

To assess the clinical efficacy of chronic vasodilator therapy for refractory congestive heart failure, the long-term follow-up (mean 13 months, range 3-30 months) was evaluated in 56 patients treated with hydralazine, usually in combination with nitrates. In the first 6 months, 73% improved subjectively and 59% improved by one or two New York Heart Association classifications; early improvement was usually sustained. Mortality was high, 22% at 6 months and 37% at 12 months, but was significantly lower in patients who had a clinical response to vasodilators (21% in responders vs 55% in nonresponders at 1 year). The only clinical indicator that differentiated responders from nonresponders was the presence or absence of symptomatic progression before initiation of vasodilator therapy. Pulmonary artery pressure, pulmonary capillary wedge (PCW) pressure and stroke work index (SWI) before and during vasodilator therapy correlated with clinical response and survival. Fifteen of 20 patients with PCW < 20 mm Hg and SWI greater than or equal to 30 g-m/m2 improved and survived, compared with two of 19 with PCS greater than or equal to 20 mm Hg and SWI < 30 g-m/m2. Patients who did not have acute hemodynamic improvement generally did not improve clinically, but neither the percentage change nor the absolute change in any hemodynamic variable predicted outcome in the remaining patients. The findings of this study indicate that vasodilators produce clinical improvement in many patients with refractory heart failure and that hemodynamic measurements are helpful in predicting the outcome of therapy.

Cardiovascular Diseases: An Annotated Bibliography of Recent Literature

Cardiovascular Diseases: An Annotated Bibliography of Recent Literature

Comparative hemodynamic effects of intravenous nitroprusside and oral prazosin in refractory heart failure

Beneficial effects of vasodilator therapy in heart failure have been amply described. Afterload reduction with intravenous nitroprusside improves hemodynamic values in patients with left ventricular dysfunction. The oral vasodilator prazosin was given to 10 patients with refractory heart failure, and its hemodynamic effects were compared with those of intravenous nitroprusside in the same patients. With prazosin, heart rate remained unchanged, mean arterial pressure decreased 13 percent ( P < 0.01), left ventricular filling and mean pulmonary arterial pressures decreased 31 and 24 percent, respectively (both P < 0.01) and cardiac index and left ventricular stroke work increased by 31 and 30 percent, respectively (both P < 0.01). Resistance levels in the systemic and pulmonary vascular beds declined by 29 and 27 percent, respectively (both P < 0.01). The hemodynamic changes appeared 1 hour after administration of a single dose of oral prazosin and persisted for 6 hours. Intravenous infusion of nitroprusside resulted in similar changes in heart rate and arterial pressure but greater reduction in left ventricular filling and mean pulmonary arterial pressures ( P < 0.05). Left ventricular stroke work index increased more with nitroprusside ( P < 0.01); however, changes in cardiac index and systemic and pulmonary vascular resistance levels were identical. Further, systolic pressure-heart rate product (index of myocardial oxygen demand) decreased significantly with oral prazosin as well as nitroprusside. These results suggest that prazosin has salutary effects on cardiovascular hemodynamics in heart failure, probably because of its vasodilator properties. These effects are qualitatively similar to those observed with intravenous infusion of nitroprusside. However, quantitatively, intravenous nitroprusside is slightly more potent.

Vasodilator therapy in heart failure due to congestive cardiomyopathy — A caveat

Vasodilator therapy in heart failure due to congestive cardiomyopathy — A caveat