Right Ventricular Failure: Pathophysiology and Treatment

Symposium on the Latest Advances in Cardiac Surgery

Right Ventricular Failure Pathophysiology and Treatment

Paul A. Spence, M.D.,* Richard D..:_Weisel, M.D.,t and Tomas A. Salerno, M .D .:f:

RIGHT VENTRICULAR ASSISTANCE Right ventricular (RV) failure may precipitate cardiogenic shock following cardiac surgery, despite a technically adequate procedure. 26 · 29--3° Rightsided heart failure is usually manifested by low cardiac output and a higher right atrial pressure than left atrial pressure. Although more marked when pulmonary hypertension is present, RV failure may also occur with normal pulmonary artery pressures if RV dysfunction is accompanied by left ventricular and septal dysfunction. In most cases, correction of hypoxia and acidosis, physiologic pacing, and volume loading produce an adequate cardiac output. Pharmacologic support (with inotropic and pulmonary vasodilator agents) and intra-aortic balloon counterpulsation also have been successful in restoring cardiac output. However, if RV failure persists despite these measures, mechanical assistance may be required. Both pulmonary arterial balloon counterpulsation 9 · 24 • 26 and RV bypass 29--32 have been successful under these conditions. This article discusses the pathophysiology of RV failure and the methods of support for the right ventricle that have been used both experimentally and clinically.

PATHOPHYSIOLOGY OF RIGHT VENTRICULAR FAILURE Early canine experiments promoted the view that the right ventricle was dispensable for normal cardiac function. Coagulation of the entire RV Supported by the Canadian and Ontario Heart Foundation and the Medical Research Council of Canada *Cardiovascular Research Fellow, St. Michael's Hospital, Toronto, Ontario, Canada tAssociate Professor of Surgery, Toronto General Hospital, Toronto, Ontario, Canada +Associate Professor of Surgery, St. Michael's Hospital, Toronto, Ontario, Canada

Surgical Clinics of North America-Yo!. 65, No. 3, June 1985

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free wall produced no significant hemodynamic alteration: the systemic blood pressure, 42 right atrial pressure, 1• 42 and the ability of the right ventricle to pump against increased afterload remained the same. 19 The success of the Fontan operation also supported the view that the right ventricle was not necessary for the maintenance of the circulation. 3• 7• 12• 33• 38 In both animal experiments8 • 15• 16 and in patients, 25 the circulation has been maintained during ventricular fibrillation with left-sided cardiac bypass alone (left atrium to aorta) by establishing passive flow through the lungs. Thus, if pulmonary vascular resistance is low, RV function is not required for an adequate cardiac output and the pulmonary circulation may act as a portal circulation. However, if pulmonary vascular resistance is elevated, the right ventricle must act as a pump to maintain the circulation. Probably the most common cause of acute RV failure is increased pulmonary vascular resistance. After massive pulmonary embolization, RV failure may occur even when the right ventricle is normal. Both clinical and experimental studies have demonstrated RV decompensation under these circumstances. 21 • 26• 28 The RV dysfunction is usually reversible; a brief period of circulatory support (which also corrects hypoxia and acidosis) and pulmonary embolectomy have been successful in restoring RV function. 2• 43 However, some patients treated with these measures have required prolonged circulatory support with an extracorporeal membrane oxygenator. 5• 17 When RV failure follows cardiac surgical procedures, the function of both ventricles is usually compromised. Patients with congenital, valvular, or coronary arterial disease frequently have limited ventricular reserve from the effects of the cardiac defect or inadequate perioperative preservation. In this circumstance, milder degrees of pulmonary hypertension may result in RV failure. Pulmonary hypertension is common following prolonged cardiopulmonary bypass and is exacerbated by measures to treat cardiogenic shock. RV failure occurs most frequently with concomitant left ventricular (LV) compromise, particularly LV septal dysfunction. RV function is critically dependent on LV septal motion. The arrangement of muscle fibers ensures that changes in LV contractility will be transferred to the right ventricle. 1 When septal function is normal, RV output frequently can be maintained, despite extensive injury to the RV free wall. 1• 19• 42 However, Guiha and colleagues observed that the RV response to volume loading was markedly depressed by injury to the RV free wall. 14 Following cardiac surgical procedures employing cardiopulmonary bypass, the interventricular septum moves abnormally in 70 per cent to 92 per cent of patients. 35 The abnormality may represent either perioperative injury to the septum or an abnormal anterior motion with normal contractility. 10• 20• 34• 45 Under each circumstance, the release of the pericardia! restraint may interfere with LV septal support of right ventricular output. Therefore, in the early postoperative period, patients may be at greater risk of developing right ventricular failure because of diminished septal support for the right ventricle. RV failure may also occur with normal pulmonary vascular resistance if moderate LV and septal dysfunction accompany RV dysfunction. The syndrome of RV failure during acute myocardial infarction, first reported in 1974, is an example. 4 In these patients cardiac output is low, and both right

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and left ventricular filling pressures are increased because of biventricular dysfunction. However, right-sided pressures are increased in excess of those on the left. The right atrial pressure approaches the pulmonary artery pressure (the pressure generated by the right ventricle is negligible). 4 Because the right ventricle develops little pressure, blood flow in this situation depends on the passive pressure gradient between the right and left atria. In this situation, LV dysfunction plays an important role. LV dysfunction reduces RV contractility by septal interaction and also reduces the hydrostatic gradient across the lungs by increasing left atrial pressure. RV failure may then occur with normal pulmonary vascular resistance when biventricular dysfunction is present. The most common cause of postoperative cardiogenic shock is LV decompensation. When pharmacologic support and intra-aortic balloon counterpulsation are effective in maintaining an adequate cardiac output, the increased left atrial pressure and progressive pulmonary edema, frequently induced by volume loading, may produce severe afterload stress that induces RV decompensation. Pulmonary arterial counterpulsation or rightsided cardiac bypass may be required under these circumstances to support the progressively failing right ventricle. 9• 24• 26• 29-32 If LV failure is severe, a left-sided cardiac bypass may be necessary to support the failing left-sided circulation. 3
Postoperative RV failure is treated by RV preload, pharmacologic measures to improve RV contractility and reduce pulmonary vascular resistance, balloon counterpulsation, and right-sided cardiac bypass.

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Right Ventricular Preload Volume loading remains the first treatment for restoring systemic perfusion when RV failure limits cardiac output. The benefits, however, may be limited. Although volume loading successfully increases cardiac output with RV infarction, pulmonary embolus, and experimental RV failure, it will be unsuccessful if the RV dysfunction is not rapidly reversible or minimal. Massive fluid infusions invariably lead to cardiac edema and distention, which may lead to progressive ventricular dysfunction. Prolonged volume loading will also induce pulmonary edema, and the increased pulmonary vascular resistance will restrict RV output. Pharmacologic Measures Adjustment of pH and improvement of oxygenation are the most important factors in the pharmacologic maintenance of pulmonary vascular resistance. Sade has demonstrated quantitatively the importance of modifications in pH and oxygenation on pulmonary flow in dogs subjected to anastomosis of a right atrial artery to the pulmonary artery. 38 Inotropic agents have been used to treat RV failure. These agents may induce further ischemic injury if the increased oxygen demands of the right ventricle cannot be met by increased coronary blood flow because of coronary artery disease, ventricular hypertrophy, cardiac edema, or reperfusion injury. 22• 44 Many inotropic medications may also induce pulmonary vasoconstriction and limit right ventricular output. Isoproterenol (Isuprel) is an exception. Although a potent inotrope, it has been shown to reduce pulmonary vascular resistance. 23 Isoproterenol has the disadvantage, however, of potentially producing ischemic injury. The use of inotropes is thus limited by the potential to produce ischemic damage to the heart and increase pulmonary vascular resistance. The benefit of pulmonary vasodilator agents is not certain. Patients with chronic pulmonary hypertension have improved after taking long-term hydralazine and nifedipine. 6• 37 Nitroglycerin and nitroprusside have been used to treat acute postoperative RV failure, but their therapeutic efficacy has never been confirmed. Unfortunately, potent pulmonary vasodilators are limited by their systemic effects. Profound hypotension will diminish biventricular perfusion. Attempts to reduce systemic hypotension by infusion of vasodilators directly into the pulmonary artery have not been successful.13 Balloon Counterpulsation

Intra-aortic BaUoon Counterpulsation. Balloon counterpulsation in the aorta should be considered in all cases of RV failure. Because LV dysfunction invariably coexists with RV failure, aortic counterpulsation may improve overall cardiac performance. Intra-aortic balloon counterpulsation has been shown to improve coronary perfusion and reduce the afterload of the left ventricle. Improved perfusion may enhance LV function and augment the septal contribution to RV contraction. It may also lead to a decrease in left atrial pressure and thus increase the hydrostatic gradient across the pulmonary circulation.

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Pulmonary Arterial Balloon Counterpulsation. Pulmonary arterial balloon counterpulsation (PABC) has been reported recently in four patients with postoperative RV failure; one of these patients survived. 9• 24 • 26 In our communications with other surgeons in North America, it appears that PABC has been used more widely than these limited reports indicate. Currently, PABC is performed by anastomosis of a preclotted graft (20 to 22 mm) to the pulmonary artery during full cardiopulmonary bypass. 9• 24• 26 A standard intra-aortic (40 ml) balloon is placed within the graft, and the end of the graft is tied with a heavy tie or umbilical tape. Counterpulsation is produced with the aortic balloon console. Our experimental results suggest that the onset of balloon inflation should be later than that used for intra-aortic counterpulsation. This technique requires regperation for removal of the balloon and graft. Currently, efforts are under way to develop a balloon that could be inserted percutaneously into the pulmonary artery.38 This device would also be useful for RV failure in other clinical situations, such as following acute myocardial infarction. PABC has proved effective in supporting the right ventricle in experimental RV failure caused by pulmonary hypertension. 21 • 28• 41 In 1969, Kralios first studied a small pulmonary artery balloon in a model of pulmonary hypertension produced by embolization of the pulmonary artery. He observed that PABC could increase the cardiac output. Jett later confirmed these results by using a much larger balloon in a graft anastomosed to the pulmonary artery. 18 He produced RV failure by applying a constriction to the main pulmonary artery, and a right ventriculotomy was then performed to damage the right ventricle. In our laboratory, RV failure was studied during left-sided cardiac assist in pigs. 39• 40 Global cardiac failure was produced by an infusion of propranolol, and the left side of the heart was fully supported by a left-sided cardiac bypass (left atrium to aorta). Two types of pulmonary balloons were studied: an intrapulmonary (22 ml) balloon39 and a larger (40 ml) one40 within a graft anastomosed to the pulmonary artery. Both balloons significantly increased RV output, but the improvement was more substantial with the larger balloon (Fig. lB) than the smaller balloon (Fig. lA). However, neither balloon could restore systemic perfusion to normal levels. A study of the mechanism of action of PABC in the animals with the 40-ml balloon provided an explanation for these findings. PABC was found to cause blood to flow through the pulmonary circulation during diastole as the balloon inflated (Fig. 2A). In systole the balloon deflated, and the right ,...,

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Figure 1. Improvement in right ventricular output (RVO) with pulmonary balloons. A, Small (22-ml) balloon. B, Large (40-ml) balloon.

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ventricle ejected blood into the space vacated by the balloon within the graft (Fig. 2B). Although the work of the right ventricle was reduced to filling a graft several centimeters above the right ventricle, the severely damaged right ventricle could not eject an adequate stroke volume to maintain the cardiac output. Thus, in severe RV depression, PABC will not restore the RV output and a mechanical pump should be considered. Right Ventricular Bypass RV bypass has been used to treat isolated RV failure as well as to treat patients who develop RV failure during left-sided cardiac assist. 29 • 3()...,3 2 The right atrium is cannulated for venous drainage. Return to the pulmonary artery can be performed by direct cannulation of the pulmonary artery or by anastomosis of a graft to the pulmonary artery, allowing a cannula to be placed inside the graft. 29 • 30-3 2 Among the variety of pumps used, the vortex (Biomedicus) and the pneumatic ventricle (Pierce Donaghy) have met with the greatest clinical approval. When an RV assist pump is used to treat isolated RV failure, most patients survive. 29-32 However, when RV assist pumping is necessary in addition to left-sided cardiac bypass, the results have been very poor. 30 • 32 Only one long-term survivor has been reported. 3°Following several days of right-sided cardiac assist pumping, the pulmonary artery pressures typically decrease and the right ventricle begins to eject blood. When weaning is possible, the patient is returned to the operating room for removal of the assist device. 29-3 1 The experimental evaluation of RV support by Gaines has been exceedingly useful. 11 He demonstrated that in the face of profound RV depression (ventricular fibrillation) during left-sided cardiac bypass, only mechanical assistance of the right ventricle with a pump device can provide adequate blood flow through the pulmonary circulation. In his experi-

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Figure 2. The mechanism of action of pulmonary artery balloon counterpulsation is demonstrated. A, In diastole, balloon inflation ejects blood from the graft through the pulmonary circulation. B, During systole, the right ventricle fills the graft after the balloon deflates. There is almost no flow through the pulmonary circulation in systole.

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ments, passive flow through the pulmonary circulation produced a flow of only 31.1 ml per minute per kg. Pulsation with a 40-ml balloon in a graft anastomosed to the pulmonary artery increased flow to only 44.4 ml per minute per kg, providing inadequate systemic perfusion. A 65-ml pulsatile assist device in the pulmonary artery provided marginally adequate pulmonary artery flow (64.3 ml per minute per kg), but a pneumatic pump increased right ventricular output to 70.9 ml per minute per kg. The pump was the only device capable of restoring systemic perfusion in the severely depressed right ventricle. It must be pointed out that mechanical pumping of the right ventricle is not without risk. Fortunately, when a right-sided cardiac assist is used alone, complications have been limited and clinical results have been good. However, when a right-sided cardiac assist pump is used together with a left-sided cardiac assist pump, massive hemorrhage is the rule.

SUMMARY The cardiac surgeon is faced with RV failure in two main situations: in isolation or in patients with left-sided cardiac assist. Adequate volume loading, correction of acidosis and oxygenation, cardiac pacing, pharmacologic agents, and systemic intra-aortic balloon pumping allow stabilization in most of these patients. When these measures fail, some form of mechanical assistance of the right ventricle becomes necessary. Balloon counterpulsation in the pulmonary artery improves RV output but does not restore the systemic perfusion if the right ventricle is profoundly depressed. When the right ventricle is profoundly depressed, a mechanical assist pump is the only device capable of restoring systemic perfusion. Like the left ventricle, the right ventricle, given time and support, can recover enough function to allow weaning from the assist device and survival.

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33. Puga, F. J., and McGoon, D. G.: Exclusion of the right ventricle from the circulation: Hemodynamic observations. Surgery, 73:607-613, 1973. 34. Rakowski, H., Gilbert, B. W., Phaneuf, D. C., et al.: Late movement in septal and left ventricular wall motion following aortocoronary bypass surgery.· Am. J. Cardiol. (Abstract.), 75:114, 1983. 35. Righetti, A., Crawford, M. H., O'Rourke, R. A., eta!.: Interventricular septal motion and left ventricular function after coronary bypass surgery: Evaluation with echocardiography and radionuclide angiography. Am. J. Cardiol., 39:372-377, 1977. 36. Rodbard, S., and Wagner, D.: Bypassing the right ventricle. Proc. Soc. Exp. Bioi. Med., 71:6!}-70, 1949. 37. Rubin, L., and Pater, R. H.: Oral hydralazine for primary pulmonary hypertension. N. Engl. J. Med., 302:6!}-73, 1980. 38. Sade, R. M., and Dearing, J. P.: Augmentation of pulmonary blood flow after right ventricular bypass. J. Thorac. Cardiovasc. Surg., 81:928-933, 1981. 39. Spence, P. A., Weisel, R. D., Easdown, J., et a!.: Pulmonary artery balloon counterpulsation in the management of right ventricular failure during left heart bypass. J. Thorac. Cardiovasc. Surg., 89:264--268, 1985. 40. Spence, P. A., Weisel, R. D., Easdown, J., eta!.: The hemodynamic effects and mechanism of action of pulmonary artery balloon counterpulsation in the treatment of right ventricular failure during left heart bypass. Ann. Thorac. Surg., 39:32!}-335, 1985. 41. Spotnitz, H. M., Berman, M. A., Reis, R. L., eta!.: The effects of synchronized counterpulsation of the pulmonary artery on right ventricular hemodynamics. J. Thorac. Cardiovasc. Surg., 61:167.::.174, 1971. 42. Starr, I., Jeffers, W. A., and Meade, R. H.: The absence of conspicuous increments of venous pressure after severe damage to the right ventricle of the dog, with a discussion of the relation between clinical congestive failure and heart disease. Am. Heart J., 26:291-301, 1943. 43. Tschinkov, A., Kranse, E., Elert, 0., et al.: Surgical management of massive pulmonary embolism. J. Thorac. Cardiovasc. Surg., 75:730-733, 1978. 44. Willerson, J. T., Hutton, I., Watson, J. T., et al.: Influence of dopamine on regional myocardial blood flow and ventricular performance during acute and chronic myocardial ischemia in dogs. Circulation, 53:828-837, 1976. 45. Vignola, P. A., Boucher, L. A., Curfman, G. D., et a!.: Abnormal interventricular septal motion following cardiac surgery. Am. Heart. J., 104:263-268, 1982. Tomas A. Salerno, M.D. St. Michael's Hospital Division of Cardiovascular Surgery 30 Bond Street Toronto, Ontario Canada M5B 1W8