Hemodynamic phenotyping in ME/CFS and ANOCA: complementary insights from coronary function testing and invasive cardiopulmonary exercise testing

This single-center cohort study sought to evaluate the association between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and angina with nonobstructive coronary arteries (ANOCA), by determining the observed frequency of ME/CFS among patients with ANOCA diagnosed by coronary function testing (CFT). In addition, we performed an exploratory analysis of the diagnostic utility of invasive cardiopulmonary exercise testing (iCPET) in ME/CFS patients with CFT-confirmed ANOCA, with the aim of identifying the predominant physiological mechanism responsible for exertional limitation in this population. Systematic medical record review of 261 patients with CFT-confirmed ANOCA was performed using standardized diagnostic criteria to identify concurrent ME/CFS diagnosis. ME/CFS was identified in 47 patients, representing an observed frequency of 18%. The only statistically significant difference between ANOCA patients with and without ME/CFS was a higher frequency of connective tissue disease in the ME/CFS group (P = 0.0221). In a separate cohort of 27 patients with ME/CFS who underwent iCPET, 24 patients (89%) had CFT-confirmed ANOCA. The diagnosis of ANOCA by CFT prompted a change in medical management in 81% of patients in this cohort. iCPET revealed a primary peripheral limitation to exercise, characterized by impaired peak systemic oxygen extraction despite normal peak oxygen delivery. This study demonstrates a clinically significant association between ME/CFS and ANOCA. These findings underscore the clinical value of CFT in patients with ME/CFS and exertional chest pain and highlight iCPET as a complementary tool for hemodynamic phenotyping in this population. Prospective studies incorporating simultaneous CFT and iCPET with molecular phenotyping are warranted.NEW & NOTEWORTHY This study demonstrates a clinically significant association between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and angina with nonobstructive coronary arteries (ANOCA), with 18% of patients with coronary function testing-confirmed ANOCA meeting diagnostic criteria for ME/CFS. Invasive cardiopulmonary exercise testing (iCPET) in patients with concurrent ME/CFS and ANOCA reveals a primary peripheral, not cardiac, limitation to exercise. These findings highlight the complementary roles of coronary function testing and iCPET for hemodynamic phenotyping in this underrecognized patient population.