Summary
Over the past 25 years, the concept of circulation in heart failure has evolved from that of a simple circuit with a weak pump and high pressures to a complex integrated system of cellular modification, cardiac compensation and systemic neurohumoral responses. The original model of cardiac afterload as the systemic vascular resistance has been refined to reflect the interdependence of preload and afterload and the central role of atrioventricular valve regurgitation.
It is becoming increasingly apparent that the impact of vasodilator therapy far exceeds the direct haemodynamic effects on preload and afterload, and depends on the mechanism by which vasodilation is achieved, with increasing emphasis on those agents which oppose neurohumoral activation. The potential goals of therapy have broadened to include not only haemodynamic stabilisation through tailored therapy for patients referred with advanced heart failure, but also the prevention of disease progression for patients with asymptomatic ventricular dilation. As the different profiles of heart failure have come to be recognised, the purpose and design of vasodilator treatment must now be considered individually for each patient.
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References
Ader R, Chatterjee K, Ports T, Brudage B, Hiramtsu B, et al. Immediate and sustained hemodynamic and clinical improvements in chronic heart failure by oral angiotensin-converting enzyme inhibitor. Circulation 61: 931 -937, 1980
Ahmed SS, Levenson GE, Weisse AB, Regan TL. The effect of angiotensin on myocardial contractility. Journal of Clinical Pharmacology 15: 276, 1975
Asmar RG, Pannier B, Santoni SL, London GM, Levy BI, et al. Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension. Circulation 78: 941–950, 1988
Awan NA, Evenson MK, Needham KE, Evans TO, Hermanovich J, et al. Hemodynamic effects of oral pirbuterol in chronic severe congestive heart failure. Circulation 63: 96–101, 1981
Beutler B, Cerami A. The common mediator of shock, cachexia, and tumor necrosis. Advanced Immunology 42: 213–231, 1988
Blythe WB. Captopril and renal autoregulation. New England Journal of Medicine 308: 390–391, 1983
Brown JJ, Davies DL, Johnson VW, et al. Renin relationship in congestive cardiac failure, treated and untreated. American Heart Journal 80: 329–342, 1970
Cambridge D, Davey MJ, Massingham R. Prazosin a selected antagonist of postsynaptic alpha adenoreceptors. British Journal of Pharmacology 59: 514p–515p, 1977
Captopril Multicenter Research Group. A cooperative multicenter study of captopril in congestive heart failure: hemodynamic effects and long-term response. American Heart Journal 110: 439–447, 1985
Carr JS, Stevenson LW, Heber D, Walden JA. Malnutrition in severe heart failure: prevalence and hemodynamic factors. American Journal of Cardiology 63: 709–713, 1989
Cernacek P, Stewart DJ. Immunoreactive endothelin in human plasma: marked elevations in patients in cardiogenic shock. Biochemistry and Biophysics Research Communications 162: 562–567, 1989
Chatterjee K, Ports TA, Brundge BH, Massie BM, Holly AN, et al. Sustained beneficial effects of oral hydralazine in chronic heart failure. Annals of Internal Medicine 92: 600–604, 1980
Chelimsky-Fallick C, Stevenson LW, Luu M, Hamilton MA, Moriguchi J, et al. Hydralazine rescue in advanced heart failure patients with hyponatremia. Circulation 82: III–387, 1990
Cohn JN. Vasodilator therapy for heart failure. Circulation 48: 5–8, 1973
Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. New England Journal of Medicine 314: 1547–1552, 1986
Cohn JN, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. New England Journal of Medicine 325: 303–310, 1991
Colucci WS, Alexander RW, Williams GH, et al. Decreased lymphocyte beta-adreriergic receptor density in patients with heart failure and tolerance to the beta adrenergic agonist pirbuterol. New England Journal of Medicine 305: 185–190, 1981
Colucci WS, Wright RF, Braunwald E. New positive inotropic agents in the treatment of congestive heart failure. New England Journal of Medicine 314: 290–299, 1986
Colucci WS, Wynne J, Holman BL, Braunwald Z. Long-term therapy of heart failure with prazosin: a randomized double-blind trial. American Journal of Cardiology 45: 337–344, 1980
CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. New England Journal of Medicine 316: 1429–1435, 1987
Cowley AJ, Wyne RD, Hamptom JR. The effects of BT5 49465 on blood pressure and peripheral arteriolar and venous tone in normal volunteers. Journal of Hypertension 6: 547–549, 1984
Creager MA, Faxon DP, Halperin JL, Melidossian CD, McCabe CH, et al. Determinants of clinical response and survival in patients with congestive heart failure treated with captopril. American Heart Journal 104: 1147–1154, 1982
Creager MA, Faxon DP, Cutler SS, Kohlmann O, Ryan TJ, et al. Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system. Journal of the American College of Cardiology 7: 758–765, 1986
Cushman DW, Hang FL, Furgu C, Harvey CM, DeForrest JM. Differentiation of angiotensin converting enzyme inhibitors by their selective inhibition of ACE in physiologically important target organs. American Journal of Hypertension 2: 294–306, 1989
Desch CE, Magorien RD, Triffon DW, Blanford MF, Unverferth DV, et al. Development of pharmacodynamic tolerance to prazosin in congestive heart failure. American Journal of Cardiology 44: 1178–1182, 1979
DiBianco R, Shabetai R, Silverman BD, Leier CV, Benotti JR and Amrinone Multicenter Investigators. Oral amrinone for the treatment of chronic congestive heart failure. Journal of the American College of Cardiology 4: 855–866, 1984
Dzau VJ. Significance of vascular renin angiotensin pathway. Hypertension 8: 553–559, 1986
Dzau VJ. Implications of local angiotensin production in cardiovascular physiology and pharmacology. American Journal of Cardiology 59: 59A–65A, 1987
Falotico R, Haertlein BJ, Lakas-Weiss CS, Salasa JJ, Tobia AJ. Positive inotropic and hemodynamic properties of flosequinan, a new vasodilator, and a sulfone metabolite. Journal of Cardiovascular Pharmacology 14:412–418, 1989
Feldman AM, Cates AE, Baumgartner W, Baugham KL, Van Dop C. Alterations of the Mr 40,000 pertussis toxin substrate in human heart failure. Circulation 76: IV–432, 1987
Feldman MD, Copelas L, Gwathmey JK, Phillips P, Warren SE, et al. Deficient production of cyclic AMP; pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 7: 331–339, 1987
Figulla HR, Rechenberg JV, Wiegand V, Soballa R, Kreuzer H. Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy. Journal of the American College of Cardiology 13: 653–658, 1989
Flaherty JT. Nitrate tolerance: a review of the evidence. Drugs 37: 523–550, 1989
Fonarow G, Chelimsky-Fallick C, Stevenson LW, Luu M, Hamilton MA, et al. Survival with angiotensin-converting-erizyme inhibition vs. direct vasodilation for the same hemodynamic goals in advanced heart failure: 106 randomized patients. Journal of the American College of Cardiology, in press, 1992
Fonarow G, Chelimsky-Fallick C, Stevenson LW, Stevenson WG, Luu M, et al. Impact of vasodilator regimen on sudden death in advanced heart failure: a randomized trial of angiotensin-converting-enzyme inhibition and direct vasodilation. Journal American College of Cardiology 17: 92A, 1991
Fowler MB, Laser JA, Hopkins GL, Minobe W, Bristow MR. Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation 74: 1290–1302, 1986
Franciosa JA, Nordstrom LA, Cohn JN. Nitrate therapy for congestive heart failure/Journal of the American Medical Association 240: 443–336, 1978
Franciosa JA, Weber KT, Levine B, et al. Hydralazine in the long-term treatment of chronic heart failure: lack of difference from placebo. American Heart Journal 104: 587–594, 1982
Franciosa JA, Jordan RA, Wilen MM, Leddy CL. Minoxidil in patients with chronic left heart failure: contrasting hemodynamic and clinical effects in a controlled trial. Circulation 70: 63–68, 1984
Greenberg TT, Richmond WH, Stocking RA, Gupta PD, Meehan JP, et al. Impaired atrial receptor responses in dogs with heart failure due to tricuspid insufficiency and pulmonary artery stenosis. Circulation Research 32: 424–433, 1973
Greenberg S, Touhey B, Paul J. Effect of flosequinan (BT5 49465) on myocardial oxygen consumption. American Heart Journal 119: 1355–1366, 1990
Hamilton MA, Luu M, Brunken RC, Child JS. Right ventricular function does not depend on etiology of advanced heart failure. (Abstract). Circulation 82: III–117, 1990a
Hamilton MA, Stevenson LW, Child JS, Moriguchi JD, Walden J, et al. Sustained reduction in valvular regurgitation and atrial volumes with tailored vasodilator therapy in advanced congestive heart failure secondary to dilated (ischemic or idiopathic) cardiomyopathy. American Journal of Cardiology 67: 259–263, 1990b
Hasenfuss G, Holubarsch C, Heiss W, Meinterz T, et al. Myocardial energetics in patients with dilated cardiomyopathy. Circulation 80: 51–64, 1989
Haskings GJ, Esler MD, Jennings GL, Burton D, Johns JA, et al. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardio-renal sympathetic nervous activity. Circulation 73: 615–621, 1986
Hermiller JB, Magorien RD, Leithe ME, Unverferth DV, Leier CV. Clonidine in congestive heart failure: a vasodilator with negative inotropic effects. American Journal of Cardiology 51: 791–795, 1983
Ignarro L. Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circulation Research 65: 1–20, 1989
Jamieson SW, Oyer PE, Reitz BA, Baumgartner WA, Bieber CP, et al. Cardiac transplantation at Stanford. Journal of Heart Transplantation 1: 86–91, 1981
Jordan RA, Seth L, Casebolt P, Hayes MJ, Wilen MM, et al. Rapidly developing tolerance to transdermal nitroglycerin in congestive heart failure. Annals of Internal Medicine 104: 295–298, 1986
Kaiser L, Spickard RC, Olivier NB. Heart failure depressed endothelium-dependent responses in canine femoral artery. American Journal of Physiology 256: H962–967, 1989
Kessler PD, Packer M. Hemodynamic effects of BT5 49465, a new long-acting systemic vasodilator drug in patients with congestive heart failure. American Heart Journal 113: 137–143, 1987
Kovick RB, Tillisch JH, Berens SC, Bramowitz AD, Shine KI. Vasodilator therapy for chronic left ventricular failure. Circulation 53: 322–328, 1976
Kramer BL, Massie BM, Topic N. Controlled trial of captopril in chronic heart failure. Circulation 67: 807–816, 1983
Kruszyna H, Kruszyna R, Smith RP, Wilcox DE. Red blood cells generate nitric oxide from directly acting, nitrogenous vasodilators. Toxicology and Applied Pharmacology 91: 429–438, 1987
Leier CV, Huss P, Magorien RD, Unverferth DV. Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation 67: 817–822, 1983
Luderer JR, Lookingbill DP, Schneck DW, et al. Captopril induced skin eruptions. Clinical Pharmacology 22: 151–159, 1982
Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J. Diverse mechanisms of unexpected sudden cardiac arrest in advanced heart failure. Circulation 80: 1675–1680, 1989
Mancini DM, Rein R, Mull R, Eisen H, Kussmal W, et al. Value of peak oxygen consumption to risk-stratify cardiac transplantation candidates. Circulation 83: 778–783, 1991
Massie BM, Conway M, Yonge R, Frostick S, Sleight P, et al. 31-P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure. American Journal of Cardiology 60: 309–315, 1987
Massie BM, Kramer BL, Topic N. Lack of relationship between the short-term hemodynamic effects of captopril and subsequent clinical responses. Circulation 69: 1135–1141, 1984
Matsumoto S, Iti T, Sada T, et al. Hemodynamic effects of nifedipine in congestive heart failure. American Journal of Cardiology 46: 476–480, 1980
May DC, Popma JJ, Black WH, Schaefer S, Lee HR, et al. In vivo induction and reversal of nitroglycerin tolerance in human coronary arteries. New England Journal of Medicine 317: 805–809, 1987
McEwan JR, Fuller RW. Angiotensin converting enzyme inhibitors and cough. Journal of Cardiovascular Pharmacology 13 (Suppl. 3): S67–S69, 1989
Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. New England Journal of Medicine 391: 385–392, 1988
Packer M. Sudden unexpected death in patients with congestive heart failure: a second frontier. Circulation 72: 681–685, 1985
Packer M, Lee WH, Medina N, Yushak M, Bernstein JL, et al. Prognostic importance of the immediate hemodynamic response to nifedipine in patients with severe left ventricular dysfunction. Journal of the American College of Cardiology 10: 1303–1311, 1987
Packer M, Medina N, Yushak M. Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure. Circulation 70: 1038–1047, 1984b
Packer M, Medina Y, Yushak M. Relationship between serum sodium concentration and the hemodynamic and clinical responses to converting enzyme inhibition with captopril in severe heart failure. Journal of the American College of Cardiology 3: 1035–1043, 1984a
Packer M, Meller J, Medina N, Gorlin R, Herman MV. Rebound hemodynamic events after the abrupt withdrawal of nitroprusside in patients with severe chronic heart failure. New England Journal of Medicine 301: 1193–1197, 1979
Packer M, Meller J, Medina N, Gorlin R, Herman MV. Dose requirements of hydralazine in patients with severe chronic congestive heart failure. American Journal of Cardiology 45: 655–660, 1980
Packer M, Meller J, Medina N, Yushak M. Sustained effectiveness of minoxidil in heart failure after development of tolerance to other vasodilator drugs. American Journal of Cardiology 48: 375–379, 1981
Parker JO, Farrell B, Lahey KA, Moe G. Effect of intervals between doses on the development of tolerance to isosorbide dinitrate. New England Journal of Medicine 316: 1440–1444, 1987
Perry HM. Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. American Journal of Medicine 54: 58–72, 1973
Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. New England Journal of Medicine 319: 80–86, 1988
Pierpont GL, Cohn JN, Franciosa JA. Combined oral hydralazine-nitrate therapy in left ventricular failure: hemodynamic equivalency to sodium nitroprusside. Chest 73: 8–13, 1978
Pierpont GL, Francis GS, Cohn JN. Effect of captopril on renal function in patients with congestive heart failure. British Heart Journal 46: 522–527, 1981
Pinsky DJ, Wilson PB, Ahern D, Kukin ML, Gottlieb SS, Packer M. Flosequinan improves symptoms and exercise tolerance in heart failure: results of a placebo-controlled trial. Abstract. Circulation 82: III–322, 1990
Reicher-Reiss H, Barasch E. Calcium antagonists in patients with heart failure: a review. Drugs 42: in press, 1991
Rosenthal J, Thurnreiter M, Plaschke M, Geyer M, Reiter W, et al. Renin-like enzymes in human vasculature. Hypertension 15: 848–853, 1990
Sharma B, Goodwin JF. Beneficial effect of salbutamol on cardiac function in severe congestive cardiomyopathy. Circulation 58: 449–460, 1978
Sharpe DN, Murphy J, Conon R, et al. Enalapril in patients with chronic heart failure: a placebo-controlled randomized, double-blind study. Circulation 70: 271–278, 1984
Sharpe N, Murphy J, Smith F, et al. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet 1: 255–259, 1988
Spokas EG, Foko G, Quilley J, Cander P, McGiff JC. Endothelial mechanism in the vascular action of hydralazine. Hypertension 5: I107–I111, 1983
Stevenson LW, Belil D, Grover-McKay M, Brunken RC, Schwaiger M, Tillisch JH, et al. Effects of afterload reduction on left ventricular volume and mitral regurgitation in severe congestive heart failure. American Journal of Cardiology 60: 654–658, 1987
Stevenson LW, Brunken RC, Belil D, Grover-McKay M, Schwaiger M, et al. Afterload reduction decreases mitral valve regurgitation during upright exercise in advanced heart failure. Journal of American College of Cardiology 15: 174–180, 1990a
Stevenson LW, Dracup KA, Tillisch JH. Efficacy of medical therapy for severe congestive heart failure in patients referred for urgent cardiac transplantation. American Journal of Cardiology 63: 461–464, 1989
Stevenson LW, Perloff JK. The limited reliability of physical signs for the estimation of hemodynamics in chronic heart failure. Journal of the American Medical Association 261: 884–888, 1989
Stevenson LW, Sietsema K, Tillisch JH, et al. Exercise capacity for survivors of cardiac transplantation or sustained medical therapy for stable heart failure. Circulation 81: 78–85, 1990b
Stevenson LW, Tillisch JH. Maintenance of cardiac output with normal filling pressures in dilated heart failure. Circulation 74: 1303–1308, 1986
Stevenson LW, Tillisch JH, Hamilton M, Luu M, Chelimsky-Fallick C, et al. Importance of hemodynamic response to therapy in predicting survival with ejection fraction < 20% secondary to ischemic or non-ischemic dilated cardiomyopathy. American Journal of Cardiology 66: 1348–1354, 1990c
Strauss RH, Stevenson LW, Dadourian BJ, Child JS. The predictability of mitral regurgitation detected by Doppler echocardiography in patients referred for cardiac transplantation. American Journal of Cardiology 59: 892–894, 1987
Swartz SL, Williams GH, Hollenberg NK, et al. Captopril-induced changes in prostaglandin production. Journal of Clinical Investigation 65: 1257–1264, 1980
Walden JA, Stevenson LW, Dracup K, Wilmarth J, Kobashigawa J. et al. Heart transplantation may not improve quality of life for patients with stable heart failure. Heart Lung 18: 497–506, 1989
Walsh WF, Greenberg BH. Results of long-term vasodilator therapy in patients with refractory congestive heart failure. Circulation 64: 499–505, 1981
Wang W, Jwo-Sheng C, Zucker IH: Carotid sinus baroreceptor sensitivity in experimental heart failure. Circulation 81: 1959–1966, 1990
Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. Journal of the American College of Cardiology 13: 1637–1652, 1989
Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Circulation 83: 1849–1965, 1991
Weiner DH, Fink LI, Maris J, Jones RA, Chance B, Wilson JR. Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow. Circulation 73: 1127–1136, 1986
Weisman HF, Weisfeldt ML. Toward an understanding of the molecular basis of cardiomyopathies. Journal of the American College of Cardiology 11: 1135–1138, 1987
Wilkins MR, Stott RAW, Lewis HM. Atrial natriuretic factor. Annals of Clinical Medicine 26: 115–118, 1989
Yang HYT, Erdo EG, Levin Y. A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochemica et Biophysica Acta 214: 374–376, 1970
Yusuf S, SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. New England Journal of Medicine 325: 293–302, 1991
Zelis R, Mason DT, Braunwald E. A comparison of the effects of vasodilator stimuli on peripheral resistence vessels in normal subjects and in patients with congestive heart failure. Journal of Clinical Investigation 59: 1092–1097, 1979
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Stevenson, L.W., Fonarow, G. Vasodilators. Drugs 43, 15–36 (1992). https://doi.org/10.2165/00003495-199243010-00003
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DOI: https://doi.org/10.2165/00003495-199243010-00003