Charité Research Organisation, Universitätsmedizin Berlin, Charité, Berlin, Germany
[Applied Cardiopulmonary Pathophysiology 15: 220-229, 2011]
In cardiac transplantation postoperative right ventricular dysfunction is a major cause of morbidity and mortality. Recipients with pulmonary hypertension due to end-stage heart failure and a donor heart, fragile because of ischemia-reperfusion injury, and not previously adapted to an elevated pulmonary resistance are the causes of right ventricular dysfunction, that unless aggressively treated may progress to overt right ventricular failure. Dysfunctional pulmonary vascular endothelium with diminished release of NO and increased expression of endothelin-1 is considered to be the primary pathophysiology that induces pulmonary hypertension. New therapeutic approaches are aimed at ameliorating endothelial dysfunction. How extensively pulmonary hypertension has to be treated depends on the degree of functional impairment of the right ventricle resulting from the acute increase of right ventricular afterload at heart transplantation. Mainstays in the treatment of pulmonary hypertension are optimizing right ventricular preload, increasing contractility, lowering right ventricular afterload, improving coronary perfusion and failing these therapeutic interventions mechanical circulatory support. Judicious use of volume therapy is mandatory to avoid volume overload in the postoperative setting. As a general rule to explore right ventricular preload reserve volume should only be carefully administered by observing filling pressures up to a maximum of a central venous pressure of 10 mm Hg. Volume administration is not indicated if it only increases right atrial filling pressure without subsequently increasing cardiac output. In most cases relative volume overload is the clinical problem and not hypovolemia. In this situation aggressive diuretic therapy and in cases of acute renal failure renal replacement therapy is mandatory.
Positive inotropic therapy is indicated to treat consecutive right ventricular dysfunction. Dobutamine may be a choice in the presence of a low cardiac index but preserved systemic pressures and epinephrine in cases of low cardiac output syndrome and systemic hypotension. A useful adjunct to catecholamine therapy is phosphodiesterase-III-inhibitors in the absence of arterial hypotension. Most importantly, pulmonary arterial pressures and right ventricular afterload have to be lowered in pulmonary hypertension compromising right ventricular function. Systemic vasodilators to treat pulmonary hypertension are non-selective and may induce arterial hypotension. This also applies to intravenously administered prostanoids. Inhaled NO in therapeutic doses selectively dilates the pulmonary vasculature without inducing systemic hypotension. To prevent a rebound phenomenon, inhaled NO therapy has to be slowly weaned. To account for the individually different response to inhaled NO, dose titration is recommended with doses of 10–50 ppm NO to lower pulmonary arterial pressures. Inhaled NO has been successfully used for all indications in the treatment of pulmonary hypertension in cardiac surgery. It has proved to be especially effective after implantation of left ventricular assist devices and following heart transplantations. As an alternative therapy, inhalation of aerosolized prostanoids similar to inhaled NO selectively decreases pulmonary arterial pressures.
In recent years there has been growing evidence that the orally available phosphodiesterase 5 inhibitor sildenafil may be a useful adjunct to therapy in right ventricular failure. Inhibition of posphodiesterase 5 by sildenafil selectively induces pulmonary vasodilatation without deleterious effects on the systemic circulation. It can also be employed to facilitate weaning heart transplant recipients of inhaled NO, catecholamines and mechanical ventilator support. It has also been reported to have synergistic effects with inhaled NO and may be a treatment option in refractory cases. Potential drug interactions with immunosuppressive drugs have to be accounted for.
Although clinical data are still limited administration of the calcium sensitizer levosimendan with reported inotropic effects and at the same time decreasing pulmonary pressures may be an attractive treatment option in patients after heart transplantation presenting with right ventricular dysfunction.
Endothelin antagonists are effective in the treatment of moderate to severe pulmonary hypertension, but their future role still has to be determined in further studies.
Supportive therapeutic measures in acute pulmonary hypertension are the use of 100% oxygen, moderate hyperventilation and correction of acidosis.
If right ventricular failure progresses to a low cardiac output syndrome, implantation of an intraaortic balloon pump has to be considered to improve coronary perfusion. In refractive pulmonary hypertension and frank right ventricular failure implantation of a right ventricular assist device remains the last resort for treatment.
Key words: right ventricular function, heart transplantation, donor heart
Frank Wagner, MD, PhD
Charité Research Organisation
Universitätsmedizin Berlin, Charité