Impaired coronary microvascular reactivity in women with apical ballooning syndrome (Takotsubo/stress cardiomyopathy)

Aims: The pathophysiology of apical ballooning syndrome (ABS) remains to be elucidated. The aim of this study was to evaluate the coronary vascular reactivity of patients who were previously diagnosed with ABS. Methods and results: A total of 228 cases of ABS were prospectively identified, and of these, 10 patients (median age 61 years (IQR 48-75); all females) who underwent coronary vasomotion testing were included in the study. Coronary epicardial and microvascular responses to intracoronary acetylcholine (ACH; % change in diameter and % change in blood flow at doses of 10(-6)-10(-4) mol/l), nitroglycerin (200-300 mg), and adenosine (36-60 mu g) were evaluated. The median change in diameter with ACH was -9.3% (IQR -36.4, 3.2) with six patients (60%) demonstrating epicardial coronary constriction. The median increase in peak coronary blood flow in response to ACH was 13.1% (IQR -18.6, 55.0). This was markedly lower than the blood flow response seen in a reference group of 211 women from our laboratory (mean age 60 years) with normal microvascular responses to ACH: 103% (IQR 75, 149). Seven (70%) patients had <50% increase in coronary blood flow indicating abnormal microvascular response to ACH. 70% had either abnormal epicardial or microvascular response to ACH. Median coronary flow reserve was abnormal at 2.2% (IQR 2.0, 3.4; normal >2.5), and 90% had at least one abnormal measure of microvascular vasomotion. Conclusion: The novel observation is that coronary microvascular dysfunction is highly prevalent in patients with ABS. Thus, chronically impaired coronary vascular reactivity, especially involving the microcirculation, may be a central feature of the pathophysiology of ABS.