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Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction in Patients With Preserved Ejection Fraction: The Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction (SIDAMI) Trial
Study Questions:
Diastolic dysfunction is frequently seen after myocardial infarction (MI) and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. Does sildenafil reduce filling pressure during exercise in patients with diastolic dysfunction after MI?
Methods:
In the SIDAMI (Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction in Patients With Preserved Ejection Fraction) trial, 70 patients with diastolic dysfunction and near normal left ventricular (LV) ejection fraction (HFpEF) 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. The primary endpoint was pulmonary capillary wedge pressure (PCWP). The secondary endpoints comprised cardiac index (CI) and pulmonary arterial pressure at rest and during exercise after 9 weeks.
Results:
After 9 weeks, there were no differences in PCWP at rest (13 ± 4 vs. 13 ± 3 mm Hg, p = 0.25) or at peak exercise (35 ± 8 mm Hg vs. 31 ± 7 mm Hg, p = 0.07). However, with treatment, CI 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 LV end-diastolic volume index increased (p = 0.001) within the sildenafil group, but was unchanged in the placebo group.
Conclusions:
The investigators concluded that sildenafil did not decrease filling pressure at rest or during exercise in post-MI patients with diastolic dysfunction. However, there were effects on secondary endpoints, which require further studies.
Perspective:
The findings are surprising, but in a previous study that demonstrated sildenafil had a beneficial hemodynamic effect in HFpEF, the patients had a high pulmonary vascular resistance (PVR) and severely decreased right ventricular function. In this study, the PVR was normal at rest and with exercise. PCW was measured at end expiration rather than the mean over 3 respiratory cycles. The former technique results in an exaggerated PCW, which may explain the failure of the PVR to rise with exercise in either group. Further studies of the phosphodiesterase-5 inhibitors (a very safe class of drugs) are needed to assess long-term effect on quality of life, exercise V02, and hospitalization for heart failure in the very common HFpEF cohort with and without coronary artery disease and associated with hypertension and diabetes.
Keywords: Ventricular Function, Right, Myocardial Infarction, Coronary Artery Disease, Pulmonary Wedge Pressure, Purines, Arterial Pressure, Cardiac Catheterization, Blood Pressure, Piperazines, Sulfones, Heart Failure, Vascular Resistance, Stroke Volume
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