Prognostic significance of endogenous-type coronary microvascular dysfunction following elective percutaneous coronary intervention

Background Coronary microvascular dysfunction (CMD) can be classified into two endotypes: endogenous and classical.1 The first subtype, termed "endogenous-type" CMD, is characterized by a relatively high baseline flow with a reduced coronary flow reserve (CFR). The "classical-type" CMD, exhibits elevated hyperemic resistance and a reduced CFR. While the presence of CMD post-percutaneous coronary intervention (PCI) has been reported to be linked to worse outcomes, the differential impact of these distinct CMD subtypes remains largely unexplored. Purpose This study aimed to evaluate the prognostic implications of these two CMD endotypes, classified using stress transthoracic doppler echocardiography (S-TDE)-derived flow velocity, in patients with chronic coronary syndrome after PCI. Methods We retrospectively studied 205 patients who underwent elective PCI for lesions in left anterior descending artery (LAD). Coronary diastolic peak flow velocity (DPV) in LAD was measured at rest and during hyperemia using S-TDE. Post-PCI CMD was defined as coronary flow velocity reserve (CFVR) ≤ 2.0 and further classified into endogenous or classical types based on resting DPV cutoff of 33 cm/s. This cutoff was determined based on the 34.6th percentile of sorted DPV values, corresponding to reduced CFVR (≤ 2.0) distribution. (Figure 1) We assessed the association between post-PCI CMD endotypes and major adverse cardiac events (MACE), defined as composite of cardiac death, myocardial infarction, heart failure hospitalization, and target vessel revascularization. Results During median follow-up of 2.3 years, 30 (14.6%) patients experienced MACE. The cumulative MACE rate was significantly worse in the CMD group with low CFVR (P=0.037). Among endogenous-type CMD, classical-type CMD, and non-CMD, prognosis was significantly different (P<0.001). Post-hoc analysis revealed worse prognosis for endogenous-type CMD compared to classical-type (P=0.033) and non-CMD (P=0.0018). (Figure 2) Multivariate Cox proportional hazard analysis showed endogenous-type CMD was independently associated with MACE (hazard ratio (HR), 3.28; 95% confidence interval (CI), 1.53-7.04; P=0.0022). Multivariate logistic regression analysis showed pre-PCI resting DPV (HR, 1.05; 95% CI, 1.02-1.09; P=0.0012) and pre-PCI average E/e’ (HR, 1.08; 95% CI, 1.01-1.16; P=0.029) were independently associated with post-PCI endogenous-type CMD. Conclusions Endogenous-type CMD, compared with classical type CMD, is independently associated with MACE. The use of pre-PCI S-TDE measurements, especially resting DPV and average E/e’, may help identify individuals at high risk of developing endogenous-type CMD post-PCI. Identification of CMD endotype post-PCI using S-TDE may help identify high-risk patients for MACE and guide personalized management strategies following FFR-guided PCI.