Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy

N Engl J Med. 2003 Sep 11;349(11):1027-35. doi: 10.1056/NEJMoa025050.

Abstract

Background: Microvascular dysfunction, reflected by an inadequate increase in myocardial blood flow in response to dipyridamole infusion, is a recognized feature of hypertrophic cardiomyopathy. Its long-term effect on the prognosis is unknown. We prospectively evaluated a cohort of patients with hypertrophic cardiomyopathy after they had undergone quantitative assessment of myocardial blood flow by positron-emission tomography (PET).

Methods: Fifty-one patients (New York Heart Association class I or II) were followed for a mean (+/-SD) of 8.1+/-2.1 years after PET. Twelve subjects with atypical chest pain served as controls. Measurement of flow was performed at base line and after the infusion of the coronary vasodilator dipyridamole, with the use of nitrogen-13-labeled ammonia. Patients were then divided into three equal groups with increasing values of myocardial blood flow.

Results: The response of myocardial blood flow to dipyridamole was severely blunted in the patients, as compared with the controls (1.50+/-0.69 vs. 2.71+/-0.94 ml per minute per gram of tissue, P<0.001). Sixteen patients (31 percent) had an unfavorable outcome (death from cardiovascular causes, progression to New York Heart Association class III or IV, or sustained ventricular arrhythmias requiring the implantation of a cardioverter-defibrillator) 2.2 to 9.1 years after PET. Reduced blood flow in response to dipyridamole was strongly associated with an unfavorable outcome. Multivariate analysis showed that among patients in the lowest of the three flow groups the age-adjusted relative hazard of death from cardiovascular causes was 9.6 (P=0.02) and the relative hazard of an unfavorable outcome (a combined end point) was 20.1 (P=0.003), as compared with patients in the two other flow groups. Specifically, all four patients who died from heart failure and three of five who died suddenly were in this subgroup.

Conclusions: In patients with hypertrophic cardiomyopathy, the degree of microvascular dysfunction is a strong, independent predictor of clinical deterioration and death. Severe microvascular dysfunction is often present in patients with mild or no symptoms and may precede clinical deterioration by years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Cardiomyopathy, Hypertrophic / diagnostic imaging
  • Cardiomyopathy, Hypertrophic / physiopathology*
  • Cohort Studies
  • Coronary Circulation / drug effects*
  • Coronary Circulation / physiology
  • Dipyridamole / pharmacology*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Microcirculation / drug effects
  • Microcirculation / physiopathology
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Risk Factors
  • Survival Analysis
  • Tomography, Emission-Computed
  • Ultrasonography
  • Vasodilator Agents / pharmacology*

Substances

  • Vasodilator Agents
  • Dipyridamole