TY - JOUR

T1 - Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction

AU - Andersen, Mads J

AU - Ersbøll, Mads

AU - Axelsson, Anna

AU - Gustafsson, Finn

AU - Hassager, Christian

AU - Køber, Lars

AU - Borlaug, Barry A

AU - Boesgaard, Søren

AU - Skovgaard, Lene T

AU - Møller, Jacob E

PY - 2013/3/19

Y1 - 2013/3/19

N2 - 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.

AB - 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.

KW - Aged

KW - Blood Pressure

KW - Diastole

KW - Double-Blind Method

KW - Exercise

KW - Female

KW - Hemodynamics

KW - Humans

KW - Male

KW - Middle Aged

KW - Myocardial Infarction

KW - Phosphodiesterase 5 Inhibitors

KW - Piperazines

KW - Pulmonary Wedge Pressure

KW - Purines

KW - Rest

KW - Stroke Volume

KW - Sulfones

KW - Vascular Resistance

U2 - 10.1161/CIRCULATIONAHA.112.000056

DO - 10.1161/CIRCULATIONAHA.112.000056

M3 - Journal article

C2 - 23406672

VL - 127

SP - 1200

EP - 1208

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 11

ER -