Deficient acceleration of left ventricular relaxation during exercise after heart transplantation.
Authors: Paulus W J , Bronzwaer J G , Felice H , Kishan N , Wellens F 
Published: June 2012

BACKGROUND
The exercise-induced rise in left ventricular filling pressures after cardiac transplantation is considered to be the result of a blunted heart rate response, of elevated venous return, and of unfavorable passive late-diastolic properties of the cardiac allograft. In contrast to passive late-diastolic left ventricular properties, the effect of left ventricular relaxation on the exercise-induced rise in left ventricular filling pressures of the cardiac allograft has not yet been studied. In the present study, the response of left ventricular relaxation to exercise was investigated in transplant recipients and compared with left ventricular relaxation observed in normal control subjects exercised to the same heart rate. Moreover, the response of left ventricular relaxation of the cardiac allograft to beta-adrenoreceptor stimulation, to reduced left ventricular afterload, and to increased myocardial activator calcium was investigated by infusion of dobutamine and of nitroprusside and by postextrasystolic potentiation.

METHODS AND RESULTS
Twenty-seven transplant recipients were studied 1 year (n = 17), 2 years (n = 7), 3 years (n = 2), and 4 years (n = 1) after transplantation. All patients were free of rejection and of significant graft atherosclerosis at the time of study. Tip-micromanometer left ventricular pressure recordings and cardiac hemodynamics were obtained at rest, during supine bicycle exercise stress testing (n = 27), during dobutamine infusion at a heart rate matching the heart rate at peak exercise (n = 8), during nitroprusside infusion (n = 9), and after postextrasystolic potentiation (n = 10). Tip-micromanometer left ventricular pressure recordings were also obtained in a normal control group (n = 9) at rest and during supine bicycle exercise stress testing to a heart rate, which matched the heart rate of the transplant recipient group at peak exercise. Left ventricular relaxation rate was measured by calculation of a time constant of left ventricular pressure decay (T) derived from an exponential curve fit to the digitized tip-micromanometer left ventricular pressure signal. In the transplant recipients, exercise abbreviated T from 43 +/- 6 to 40 +/- 8 msec (p less than 0.01) and caused a rise of left ventricular minimum diastolic pressure (LVMDP) from 5 +/- 2 to 9 +/- 6 mm Hg (p less than 0.001). In normal control subjects, exercise induced a 2.5 times larger abbreviation of T (from 42 +/- 7 to 34 +/- 6 msec; p less than 0.001) and a small drop in LVMDP from 5 +/- 2 to 4 +/- 3 mm Hg (p less than 0.05). In the transplant recipients, the change in T (delta T) from rest to exercise was variable ranging from an abbreviation, as observed in normal controls, to a prolongation and was significantly correlated with the change in RR interval (delta RR) and the change in left ventricular end-diastolic pressure (delta LVEDP) (delta T = 0.068 delta RR + 0.58 delta LVEDP-2.2; r = 0.76; p less than 0.001). In a first subset of transplant recipients (n = 8), dobutamine infusion resulted in a heart rate equal to the heart rate at peak exercise, a left ventricular end-diastolic pressure (8 +/- 7 mm Hg) lower than at peak exercise (22 +/- 6 mm Hg; p less than 0.05) and a T value (32 +/- 9 msec), which was shorter than both resting value (44 +/- 5 msec; p less than 0.005) and value observed at peak exercise (40 +/- 8 msec; p less than 0.01). In a second subset of transplant recipients (n = 9), nitroprusside infusion and postextrasystolic potentiation resulted in a significant prolongation of T from 41 +/- 7 to 56 +/- 10 msec (p less than 0.05) and a characteristic negative dP/dt upstroke pattern with downward convexity as previously observed in left ventricular hypertrophy.

CONCLUSIONS
Exercise after cardiac transplantation resulted in a smaller acceleration of left ventricular relaxation than in a normal control group exercised to the same heart rate...