BACKGROUND:Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction. METHODS AND RESULTS:Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg, P=0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg, P=0.07). However, with treatment cardiac index increased at rest (P=0.006) and peak exercise (P=0.02) in the sildenafil group, and systemic vascular resistance index (resting, P=0.0002; peak exercise, P=0.007) and diastolic blood pressure (resting, P=0.005; peak exercise, P=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (P=0.001) within the sildenafil group but was unchanged in the placebo group. CONCLUSIONS:Sildenafil did not decrease filling pressure at rest or during exercise in post-myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies.
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BACKGROUND:Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction. METHODS AND RESULTS: Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg, P=0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg, P=0.07). However, with treatment cardiac index increased at rest (P=0.006) and peak exercise (P=0.02) in the sildenafil group, and systemic vascular resistance index (resting, P=0.0002; peak exercise, P=0.007) and diastolic blood pressure (resting, P=0.005; peak exercise, P=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (P=0.001) within the sildenafil group but was unchanged in the placebo group. CONCLUSIONS:Sildenafil did not decrease filling pressure at rest or during exercise in post-myocardial infarctionpatients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies.
Authors: Enrico Patrucco; Katrin Domes; Mauro Sbroggió; Anne Blaich; Jens Schlossmann; Matthias Desch; Sergei D Rybalkin; Joseph A Beavo; Robert Lukowski; Franz Hofmann Journal: Proc Natl Acad Sci U S A Date: 2014-08-19 Impact factor: 11.205