Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy.

OBJECTIVES: This study sought to evaluate whether the entity of microvascular dysfunction, assessed by positron emission tomography (PET), predicts the long-term development of left ventricular (LV) remodeling and systolic dysfunction in hypertrophic cardiomyopathy (HCM). BACKGROUND: A subgroup of patients with HCM developed LV dilation and systolic impairment. A causal role of coronary microvascular dysfunction has been suggested as the underlying pathophysiological mechanism. METHODS: Fifty-one patients (New York Heart Association functional class I to II) were followed up for 8.1 +/- 2.1 years after measurement of resting and dipyridamole (Dip) myocardial blood flow (MBF). Left ventricular systolic dysfunction was defined as an ejection fraction (LVEF) <50%. RESULTS: The Dip-MBF was blunted in HCM patients compared with a group of healthy control patients (1.50 +/- 0.69 ml/min/g vs. 2.71 +/- 0.94 ml/min/g; p < 0.001). At final evaluation, 11 patients (22%) had an LVEF <50%; in most (n = 7), systolic dysfunction was associated with a significant increase in LV cavity dimensions (>5 mm) during follow-up. These 11 patients showed lower Dip-MBF than the 40 with preserved LV function (1.04 +/- 0.38 ml/min/g vs. 1.63 +/- 0.71 ml/min/g, respectively; p = 0.001); Dip-MBF was particularly blunted in five patients with clinical progression to severe heart failure symptoms or death (Dip-MBF 0.89 +/- 0.15 ml/min/g). At multivariate analysis, the two independent predictors of systolic dysfunction were Dip-MBF in the lowest tertile (<1.1 ml/min/g; relative hazard, 7.5; p = 0.038) and an end-diastolic LV dimension in the highest tertile (>45 mm; relative hazard, 12.3; p = 0.031). CONCLUSIONS: Severe microvascular dysfunction is a potent long-term predictor of adverse LV remodeling and systolic dysfunction in HCM. Our findings indicate microvascular dysfunction as a potential target for prevention of disease progression and heart failure in HCM.

Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy.

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.