Influence of felodipine on left ventricular hypertrophy and systolic function in orthotopic heart transplant recipients: possible interaction with cyclosporine medication.
BACKGROUND
Concentric left ventricular (LV) hypertrophy develops early in orthotopic heart transplant (OHT) recipients. To compare the effects of a calcium channel blocker, felodipine, versus diuretics on LV hypertrophy and LV systolic function repeated magnetic resonance imaging studies were performed in OHT recipients. Cyclosporine levels and neurohormones were also measured to explore potential interactions with treatment.


METHODS
Twenty-two patients were randomized at baseline (2 months after OHT) to receive felodipine or diuretic treatment. Before and after 4 months of treatment (n = 19), LV dimensions and LV mass (Simpson's rule) were measured. The relationship between circumferential fiber shortening (two-shell cylindrical model) and end-systolic wall stress was used as a measure of load-independent LV contractility. Neurohormones were measured at the beginning and end of the treatment period, and cyclosporine levels and blood pressures were additionally measured during treatment.


RESULTS
At baseline, the felodipine and diuretic groups did not differ in LV mass, wall stress, and fiber shortening. During felodipine treatment LV mass decreased (p < 0.01) and tended to increase during diuretics treatment (p = 0.06). Afterload-corrected fiber shortening did not change during felodipine treatment, but decreased (p < 0.01) with diuretics. Changes in LV mass were positively correlated with cyclosporine levels (r = 0.70) in the diuretics group, but not in the felodipine group.


CONCLUSIONS
In OHT recipients during diuretic treatment, progression of LV hypertrophy occurs in relation to cyclosporine plasma levels and is accompanied by impairment of systolic contractile function. Felodipine induces regression of LV hypertrophy, while systolic contractile function is preserved. During felodipine treatment, regression of LV hypertrophy is unrelated to cyclosporine levels. Thus, felodipine seems to attenuate the hypertrophic effect of cyclosporine on transplanted hearts.
Schwitter
J
J
Department of Radiology, University of California, San Francisco 94143-0628, USA.
De Marco
T
T
Globits
S
S
Sakuma
H
H
Klinski
C
C
Chatterjee
K
K
Parmley
W W
WW
Higgins
C B
CB
D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004347:Drug Interactions; D015736:Felodipine / Q000627:therapeutic use*; D005260:Female; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology* / Q000706:statistics & numerical data; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016014:Linear Models; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D013599:Systole / Q000187:drug effects
D000959:Antihypertensive Agents; D004232:Diuretics; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015736:Felodipine