Right and left ventricular function after cardiac transplantation. Changes during and after rejection

BACKGROUND. Attempts to identify noninvasive markers of ventricular dysfunction accompanying acute rejection have been hampered by a lack of detailed simultaneous hemodynamic data. Therefore, we prospectively performed serial monitoring of detailed left and right heart hemodynamic parameters in cardiac transplant recipients at the time of routine endomyocardial biopsy to better define the physiology of the allograft heart during and after acute rejection. METHODS AND RESULTS. To better assess the pathophysiology of the rejection process, 18 cardiac transplant patients were prospectively studied by serial right heart micromanometer catheterization and digital image processing at the time of routine endomyocardial biopsy. Eleven patients had 18 episodes of rejection. Studies of baseline (negative biopsy preceding rejection), rejection (acute moderate rejection), and resolved (first negative biopsy after rejection) states were compared. Seven patients who did not experience an episode of rejection served as the control group. Right ventricular minimum and end-diastolic pressures increased from baseline values of 0.9 +/- 3.2 and 6.9 +/- 3.7 mm Hg, respectively, to 3.2 +/- 5.5 and 9.9 +/- 6.6 mm Hg, respectively, with rejection (both variables, p less than 0.05) and remained elevated despite histological resolution of rejection (4.3 +/- 5.5 and 10.0 +/- 7.1 mm Hg, respectively; p less than 0.05 for both variables compared with baseline values). Concurrently, right ventricular end-diastolic volumes (133 +/- 29, 119 +/- 27, and 114 +/- 30 ml; baseline, rejection, and resolved, respectively) and left ventricular end-diastolic volumes (133 +/- 24, 117 +/- 20, and 113 +/- 30 ml; baseline, rejection, and resolved, respectively) significantly decreased during rejection and remained decreased after resolution of rejection (rejection and resolved compared with baseline values, p less than 0.05). Right ventricular chamber stiffness (0.055 +/- 0.035, 0.085 +/- 0.057, and 0.092 +/- 0.076 mm Hg/ml; baseline, rejection, and resolution, respectively; rejection and resolved compared with baseline values, p less than 0.05) increased with rejection and remained elevated after resolution of rejection. Right ventricular peak filling rate also increased from a baseline value of 2.48 +/- 0.45 to 2.76 +/- 0.63 ml end-diastolic volumes per second with rejection (p less than 0.05). Elevation of right ventricular filling pressures, peak filling rate, and chamber stiffness with a concomitant decrease in end-diastolic volume is consistent with a restrictive/constrictive physiology. Mean arterial blood pressure and systemic vascular resistance were elevated after the resolution of rejection (compared with either rejection or baseline values, p less than 0.05) associated with a higher mean daily dose of prednisone (resolved compared with either baseline or rejection values, p less than 0.05). The control group experienced a time-dependent increase in mean and diastolic systemic arterial pressures (both comparisons, p less than 0.05) without detectable diastolic dysfunction. CONCLUSIONS. Persistence of biventricular diastolic dysfunction may be due to an irreversible effect of rejection, although multifactorial changes in left ventricular afterload occur that may complicate serial assessment of ventricular function.