Hypertensive coronary microvascular dysfunction: a subclinical marker of end organ damage and heart failure

Abstract

Aims: Hypertension is a well-established heart failure (HF) risk factor, especially in the context of adverse left ventricular (LV) remodelling. We aimed to use myocardial flow reserve (MFR) and global longitudinal strain (GLS), markers of subclinical microvascular and myocardial dysfunction, to refine hypertensive HF risk assessment.

Methods and results: Consecutive patients undergoing symptom-prompted stress cardiac positron emission tomography (PET)-computed tomography and transthoracic echocardiogram within 90 days without reduced left ventricular ejection fraction (<40%) or flow-limiting coronary artery disease (summed stress score ≥ 3) were included. Global MFR was quantified by PET, and echocardiograms were retrospectively analysed for cardiac structure and function. Patients were followed over a median 8.75 (Q1-3 4.56-10.04) years for HF hospitalization and a composite of death, HF hospitalization, MI, or stroke. Of 194 patients, 155 had adaptive LV remodelling while 39 had maladaptive remodelling, which was associated with lower MFR and impaired GLS. Across the remodelling spectrum, diastolic parameters, GLS, and N-terminal pro-B-type natriuretic peptide were independently associated with MFR. Maladaptive LV remodelling was associated with increased adjusted incidence of HF hospitalization and death. Importantly, the combination of abnormal MFR and GLS was associated with a higher rate of HF hospitalization compared to normal MFR and GLS [adjusted hazard ratio (HR) 3.21, 95% confidence interval (CI) 1.09-9.45, P = 0.034), including in the adaptive remodelling subset (adjusted HR 3.93, 95% CI 1.14-13.56, P = 0.030).

Conclusion: We have demonstrated important associations between coronary microvascular dysfunction and myocardial mechanics that refine disease characterization and HF risk assessment of patients with hypertension based on subclinical target organ injury.

Keywords: Coronary microvascular dysfunction; Heart failure; Hypertension.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Patient flow diagram.

Figure 2

Myocardial flow reserve is associated with global longitudinal strain (A), E/e′ (B), and log NT-proBNP (C) independent of clinical risk factors and systolic function. *Adjusted for age, sex, body mass index, history of diabetes, history of coronary artery disease (myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting), and left ventricular ejection fraction. GLS, global longitudinal strain; MFR, myocardial flow reserve.

Figure 3

Adjusted* median annualized rates of heart failure hospitalization by left ventricular structure or function and myocardial flow reserve. *Adjusted for age, sex, history of diabetes, and history of coronary artery disease (myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting). Myocardial flow reserve: normal myocardial flow reserve ≥ 1.8, abnormal myocardial flow reserve E/e′ ≤ 15, abnormal E/e′ > 15. Global longitudinal strain: normal GLS ≤ −18%, abnormal GLS > −18%.

Figure 4

Freedom from heart failure hospitalization over a median follow-up time of 8.75 years. *Adjusted for age, sex, history of diabetes, and history of coronary artery disease (myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting), left ventricular ejection fraction, and left ventricular remodelling type. The Kaplan–Meier survival curves are shown for heart failure hospitalization with patients categorized by normal vs. abnormal myocardial flow reserve (MFR ≥ 1.8 vs. −18%). Hazard ratios and P-values are displayed from Cox proportional hazard models comparing those with both abnormal vs. both normal myocardial flow reserve and global longitudinal strain.

Take home figure

The Kaplan–Meier survival curves heart failure HF hospitalization based on adaptive vs. maladaptive remodelling. *Adjusted for age, sex, history of diabetes, and history of coronary artery disease (myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting), and left ventricular ejection fraction. The presence of subclinical injury is associated with a higher risk of heart failure hospitalization in the context of adaptive remodelling (left panel) but not once maladaptive remodelling has developed (right panel).