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Observational Study
. 2024 Oct;150(14):1075-1086.
doi: 10.1161/CIRCULATIONAHA.123.067083. Epub 2024 Aug 21.

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

Xiaolei Xu  1   2   3 , Sanjay Divakaran  2   4 , Brittany N Weber  2   4 , Jon Hainer  2 , Shelby S Laychak  2 , Benjamin Auer  2 , Marie Foley Kijewski  2 , Ron Blankstein  2   4 , Sharmila Dorbala  2 , Ludovic Trinquart  5   6 , Piotr J Slomka  7 , Li Zhang #  1   3 , Jenifer M Brown #  2   4 , Marcelo F Di Carli #  2   4
Affiliations
Observational Study

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

Xiaolei Xu et al. Circulation. 2024 Oct.

Abstract

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 13N-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 (MFRsubendo).

Results: Among 358 patients, the mean age was 70.6±12.0 years, and 53.4% were male. The median MFRsubendo was 2.57 (interquartile range, 2.08-3.10), and lower MFRsubendo 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 MFRsubendo 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 MFRsubendo 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 MFRsubendo was associated with cardiovascular risk factors, elevated cardiac biomarkers, cardiac structure, and clinical events.

Keywords: heart failure; hypertension; perfusion imaging; ventricular remodeling.

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Conflict of interest statement

B.W. reports consulting fees from Horizon Therapeutics, Kiniksa Pharmaceuticals, and Novo Nordisk. B.A. reports consulting fees from Spectrum Dynamics Medical. S. Dorbala reports grant support from Attralus, Pfizer, GE Healthcare, Phillips, and Siemens; S. Dorbala has consulted with Novo Nordisk and Alexion. R.B. reports research support from Amgen and Novartis and has consulted for Caristo Inc and Elucid Inc. P.J.S. reports consulting fees from Synektik, SA, research support from Siemens, and software royalties from Cedars-Sinai licensing. J.M.B. reports consulting fees from Bayer AG and AstraZeneca. M.F.D.C. reports grant support from Gilead Sciences, in-kind research support from Amgen, and consulting fees from MedTrace and Sanofi. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.. Layer-specific myocardial blood flow and flow reserve.
Top panel: Selected short axis views of stress and rest myocardial perfusion PET images of two patients without obstructive CAD showing low (left) and high (right) subendocardial flow reserve. The images on the left show mild transient LV cavity dilatation during stress resulting from concentric subendocardial ischemia. Lower panel: Corresponding parametric polar maps of stress and rest subendocardial and subepicardial myocardial blood flow (in mL/min/g of myocardium) and flow reserve (ratio of stress over rest myocardial blood flow).
Figure 2.
Figure 2.. Association between subendocardial myocardial flow reserve and myocardial stress and injury.
The stepwise relationship of lower subendocardial flow reserve with more severe myocardial stress (NT-proBNP, Panel A) and injury (hsTnT, Panel B) is shown. *** indicates p<0.001. hsTnT, high-sensitivity cardiac troponin T; MFRsubendo, subendocardial myocardial flow reserve; NT-proBNP, N-terminal pro B-type natriuretic peptide.
Figure 3.
Figure 3.. Association between subendocardial myocardial flow reserve and left ventricular structure
Lower subendocardial flow reserve demonstrated a stepwise relationship with more adverse chamber dimensions including higher interventricular septal (A) and posterior wall thickness (B) and greater end-diastolic and end-systolic dimensions at rest (panels C & E) and stress (panels D & F). * indicates p<0.05. ** indicates p<0.01. *** indicates p<0.001. IVS, Interventricular septum. PWT, Posterior wall thickness. EDVi, End-diastolic volume indexed to body surface area. ESVi, End-systolic volume indexed to body surface area.
Figure 4.
Figure 4.. Event-free survival by tertile of subendocardial myocardial flow reserve
The Kaplan–Meier curves for MACCE (A) and overall survival (B) according to tertile group of subendocardial flow reserve are shown. Lower tertile of subendocardial MFR indicated worse long-term prognosis. HF, heart failure; MACCE, major adverse cardiovascular and cerebrovascular events (all-cause death, HF hospitalization, nonfatal myocardial infarction, nonfatal stroke); MFR, myocardial flow reserve.
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