Prognostic Value of Microvascular Function in Takotsubo Syndrome: A Pooled Analysis of Individual Patient Data

Coronary microvascular dysfunction appears to play a major role in the pathogenesis of Takotsubo syndrome (TTS). However, the prognostic value of microvascular function measured in the acute phase of TTS is unclear.

This study sought to assess the prognostic value of microvascular function measured invasively in the acute phase of TTS.

In a collaborative, pooled analysis of individual patient data from 9 prospective TTS cohorts, invasive assessment of coronary microvascular function was performed, including the index of microcirculatory resistance (IMR), coronary flow reserve, and microvascular resistance reserve. The primary endpoint was all-cause mortality. Secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE) defined as the composite of all-cause death, recurrence of TTS, stroke, transient ischemic attack, or myocardial infarction.

A total of 166 patients with TTS were included, in whom 130 (78%) had the typical (apical) TTS variant and 36 (22%) had an atypical variant. During a median follow-up of 20.6 [4.3-60.0] months, all-cause mortality occurred in 17 patients (10.2%) and MACCE in 29 patients (17.5%). IMR, coronary flow reserve, and microvascular resistance reserve were associated with all-cause mortality. After adjustment for baseline differences, IMR was the only independent predictor of both all-cause mortality (aHR: 3.9; 95% CI: 1.39-10.88; P = 0.010; c-statistic 0.817; 95% CI: 0.711-0.923) and MACCE (aHR: 2.6; 95% CI: 1.17-5.67; P = 0.018; c-statistic 0.719; 95% CI: 0.612-0.826).

In this pooled analysis of individual patient data from 9 prospective TTS cohorts, microvascular dysfunction measured in the acute phase was associated with all-cause mortality. In particular, an elevated microvascular resistance, as assessed by IMR, was the only independent predictor of both mortality and MACCE.