Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction in Patients With Preserved Ejection Fraction - SIDAMI

Description:

The goal of the trial was to evaluate treatment with sildenafil compared with placebo among patients with diastolic dysfunction and preserved ejection fraction after acute myocardial infarction.

Hypothesis:

Sildenafil will improve filling pressure.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Patients ≥50 years of age with diastolic dysfunction after revascularization of an ST or non-STEMI
  • Diastolic dysfunction defined as E/e’ ≥8, left atrial volume index ≥34 ml/m2, and left ventricular ejection fraction ≥45%

    Number of screened applicants: 1,310
    Number of enrollees: 70
    Duration of follow-up: 9 weeks
    Mean patient age: 63 years
    Percentage female: 11%
    Ejection fraction: 55%
    New York Heart Association class: I to II-100%

Exclusions:

  • Atrial fibrillation
  • Cardiomyopathy
  • Moderate to severe valve disease
  • Obstructive or restrictive pulmonary disease
  • Inability to perform exercise testing
  • Poor acoustic window

Primary Endpoints:

  • Change in PCWP at rest and at peak exercise

Secondary Endpoints:

  • Change in cardiac index from rest to peak exercise
  • End-diastolic volume index
  • End-systolic volume index

Drug/Procedures Used:

Patients with diastolic dysfunction after revascularization for myocardial infarction were randomized to sildenafil 40 mg 3 times daily for 9 weeks (n = 35) versus placebo (n = 35).

Right heart catheterization and stress echocardiography were performed at baseline and after the treatment period.

Principal Findings:

Overall, 70 patients were randomized. The mean age was 63 years, 11% were women, mean body mass index was 27 kg/m2, 9% had diabetes, 86% presented as an ST-segment elevation myocardial infarction (STEMI), 20% had multivessel disease, and the mean left ventricular ejection fraction was 55%.

There was no difference in the resting pulmonary capillary wedge pressure (PCWP) between treatment groups at 9 weeks: 13 mm Hg versus 13 mm Hg (p = 0.25), or in the PCWP at peak exercise between treatment groups at 9 weeks: 35 mm Hg versus 31 mm Hg (p = 0.07), respectively, for sildenafil versus placebo.

There was an increase in cardiac index at 9 weeks in the sildenafil group versus placebo group at rest: 2.8 versus 2.6 L/min/m2 (p < 0.05) and at peak exercise: 7.8 vs. 7.0 L/min/m2 (p < 0.05). At 9 weeks, left ventricular end-diastolic volume index increased (+6 ml/m2, p = 0.001) in the sildenafil group, but not in the placebo group (0 ml/m2, p = 0.92), whereas end-systolic volume index remained the same in the sildenafil group (p = 0.99), but not in the placebo group (p = 0.29). There was no difference in metabolic equivalents (METs) or 6-minute walk test between treatment groups.

Interpretation:

Among patients with diastolic dysfunction after acute myocardial infarction, sildenafil did not decrease filling pressure (PCWP) at rest or during peak exercise. This lack of association was likely not due to lack of power. Some parameters were improved after treatment with sildenafil (cardiac index and end-diastolic volume index); however, these were secondary outcomes and would need to be prospectively studied.

References:

Andersen MJ, Ersbøll M, Axelsson A, et al. 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. Circulation 2013;127:1200-8.

Presented by Dr. Mads Andersen at the American Heart Association Scientific Sessions, Los Angeles, CA, November 6, 2012.

Clinical Topics: Noninvasive Imaging, Echocardiography/Ultrasound

Keywords: Myocardial Infarction, Pulmonary Wedge Pressure, Follow-Up Studies, Phosphodiesterase 5 Inhibitors, Echocardiography, Stress, Purines, Cardiac Catheterization, Human Rights, Piperazines, Sulfones, Vasodilator Agents, Rest, Urological Agents, Body Mass Index, Stroke Volume, Metabolic Equivalent, Diabetes Mellitus


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