Relationship of Subendocardial Perfusion to Myocardial Injury, Cardiac Structure, and Clinical Outcomes Among Patients With Hypertension

BACKGROUND: Coronary microvascular dysfunction has been implicated in the development of hypertensive heart disease and heart failure, with subendocardial ischemia identified as a driver of sustained myocardial injury and fibrosis. We aimed to evaluate the relationships of subendocardial perfusion with cardiac injury, structure, and a composite of major adverse cardiac and cerebrovascular events consisting of death, heart failure hospitalization, myocardial infarction, and stroke. METHODS: Layer-specific blood flow and myocardial flow reserve (MFR; stress/rest myocardial blood flow) were assessed by 13 N-ammonia perfusion positron emission tomography in consecutive patients with hypertension without flow-limiting coronary artery disease (summed stress score <3) imaged at Brigham and Women’s Hospital (Boston, MA) from 2015 to 2021. In this post hoc observational study, biomarkers, echocardiographic parameters, and longitudinal clinical outcomes were compared by tertiles of subendocardial MFR (MFR subendo ). RESULTS: Among 358 patients, the mean age was 70.6±12.0 years, and 53.4% were male. The median MFR subendo was 2.57 (interquartile range, 2.08–3.10), and lower MFR subendo was associated with older age, diabetes, lower renal function, greater coronary calcium burden, and higher systolic blood pressure ( P <0.05 for all). In cross-sectional multivariable regression analyses, the lowest tertile of MFR subendo was associated with myocardial injury and with greater left ventricular wall thickness and volumes compared with the highest tertile. Relative to the highest tertile, low MFR subendo was independently associated with an increased rate of major adverse cardiac and cerebrovascular events (adjusted hazard ratio, 2.99 95% CI, 1.39–6.44; P =0.005) and heart failure hospitalization (adjusted hazard ratio, 2.76 [95% CI, 1.04–7.32; P =0.042) over 1.1 (interquartile range, 0.6–2.8) years median follow-up. CONCLUSIONS: Among patients with hypertension without flow-limiting coronary artery disease, impaired MFR subendo was associated with cardiovascular risk factors, elevated cardiac biomarkers, cardiac structure, and clinical events.