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Brief Report
September 15, 2021

Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis: The Microvascular Disease in Aortic Stenosis (MIDAS) Study

Author Affiliations
  • 1Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Division of Cardiac Surgery, Heart and Vascular Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Cardiology Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
  • 3Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
  • 4Division of Cardiovascular Medicine, Stanford University, Palo Alto, California
  • 5Division of Artificial Intelligence in Medicine, Department of Medicine and Cardiology, Cedars Sinai Medical Center, Los Angeles, California
  • 6Deputy Managing Editor, JAMA Cardiology
JAMA Cardiol. 2022;7(1):93-99. doi:10.1001/jamacardio.2021.3396
Key Points

Question  In aortic stenosis, are myocardial flow reserve and stress myocardial blood flow assessed by positron emission tomography perfusion imaging associated with adverse left ventricular characteristics, including myocardial stress and injury?

Findings  In this observational study of patients with aortic stenosis and matched control individuals, myocardial flow reserve was independently associated with left ventricular ejection fraction and global longitudinal strain on echocardiography, and stress myocardial blood flow was associated with circulating high-sensitivity troponin T and N-terminal pro–B-type natriuretic peptide.

Meaning  Myocardial flow reserve was associated with adverse myocardial characteristics and stress myocardial flow reserve was associated with markers of myocardial stress and injury, suggesting that these indices may be early sensitive markers of left ventricular decompensation.


Importance  Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS).

Objective  To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR).

Design, Setting, and Participants  In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days.

Exposures  MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging.

Main Outcomes and Measures  LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro–B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity.

Results  There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (β,−0.31; P = .03; β, 0.41; P = .002, respectively). Stress MBF was associated with hs-cTnT (unadjusted β, −0.48; P = .005) and log NT-pro BNP (unadjusted β, −0.37; P = .045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P = .008; 0.62 vs 0.46; P = .02; and −13.47 vs −17.11; P = .006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P = .008).

Conclusions and Relevance  In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.

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