Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome

N Engl J Med. 1994 May 12;330(19):1335-41. doi: 10.1056/NEJM199405123301902.

Abstract

Background: The aortic root enlarges progressively in Marfan's syndrome, and this enlargement is associated with aortic regurgitation and dissection. Long-term treatment with beta-adrenergic blockade, by reducing the impulse (i.e., the rate of pressure change in the aortic root) of left ventricular ejection and the heart rate, may protect the aortic root.

Methods: We conducted an open-label, randomized trial of propranolol in adolescent and adult patients with classic Marfan's syndrome (32 treated and 38 untreated [control] patients). Aortic-root dimensions and clinical end points (aortic regurgitation, aortic dissection, cardiovascular surgery, congestive heart failure, and death) were monitored for an average of 9.3 years in the control group and 10.7 years in the treatment group. All 70 patients were included in the analysis according to the intention-to-treat principle.

Results: The dose of propranolol was individualized; the mean (+/- SE) dose was 212 +/- 68 mg per day. The mean slope of the regression line for the aortic-root dimensions, which reflect the rate of dilatation, was significantly lower in the treatment group than in the control group (0.023 vs. 0.084 per year, P < 0.001). Clinical end points were reached in five patients in the treatment group and nine in the control group. The Kaplan-Meier survival curve for the treatment group differed significantly from that for the control group during the middle years of the trial and remained better for the treatment group throughout the study.

Conclusions: Prophylactic beta-adrenergic blockade is effective in slowing the rate of aortic dilatation and reducing the development of aortic complications in some patients with Marfan's syndrome.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aorta / pathology*
  • Aortic Aneurysm / etiology
  • Aortic Aneurysm / pathology*
  • Aortic Dissection / etiology
  • Aortic Valve Insufficiency / etiology
  • Dilatation, Pathologic
  • Female
  • Follow-Up Studies
  • Heart Failure / etiology
  • Humans
  • Male
  • Marfan Syndrome / complications
  • Marfan Syndrome / drug therapy*
  • Marfan Syndrome / mortality
  • Morbidity
  • Propranolol / adverse effects
  • Propranolol / therapeutic use*

Substances

  • Propranolol