Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis

Abstract

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 PARTICIPANTSIn 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 MEASURESLV 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 RELEVANCEIn 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.

Coronary blood flow in heart failure: cause, consequence and bystander

“…The magnitude of coronary reserve reduction was related to greater hypertrophy and left ventricular dysfunction and also to plasma hs-troponin T concentration as an injury marker, [282] and it was a marker of worse prognosis on follow-up [280]. The impairment of coronary reserve was reversible on transcatheter or surgical aortic valve replacement with regression of hypertrophy on follow-up [133,282].…”

“…On PET, the decrease in dipyridamole-recruitable coronary reserve was related to the severity of aortic stenosis and more pronounced in subendocardial than in subepicardial layers [ 188 ]. The magnitude of coronary reserve reduction was related to greater hypertrophy and left ventricular dysfunction and also to plasma hs-troponin T concentration as an injury marker, [ 282 ] and it was a marker of worse prognosis on follow-up [ 280 ]. The impairment of coronary reserve was reversible on transcatheter or surgical aortic valve replacement with regression of hypertrophy on follow-up [ 133 , 282 ].…”

Multiparametric MRI identifies subtle adaptations for demarcation of disease transition in murine aortic valve stenosis

“…Together, the induced myocardial adjustments seem to be sufficient to keep LV function at this moment in a compensated state reflecting the latent asymptomatic period of AS also known from human pathophysiology [ 9 ]. Nevertheless, despite a trend to an enhanced myocardial capillarization in AS mice, we observed in vivo and ex vivo a significant restriction in coronary flow reserve well known to be associated with AS in humans [ 23 , 35 , 60 ] and as well a mild increase in circulating troponin levels. Obviously, the current time point represents a period of transition, where a variety of compensation mechanisms still keeps cardiac function in balance but the persisting increased afterload already leads to incipient impairment of coronary flow and cardiomyocyte ultrastructure.…”

Novel nuclear medical procedures in the detection of microvascular dysfunction

“…42 MFR and stress MBF were associated with markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation in patients with aortic stenosis. 42 Patients with no failing arrhythmogenic right ventricular cardiomyopathy had also significantly reduced hyperemic MBF and increased coronary vascular resistance. 32 Based on this, recent American and European guidelines have recommended PET MPI with myocardial blood flow in patients with suspected CAD in the intermediate to high likelihood category and offer the additional benefit of identifying microvascular CAD, which is especially important in symptomatic diabetic and female patients.…”

“…PET was also used to assess MVD in myocardial and valvular diseases such as aortic stenosis and hypertrophic cardiomyopathy 42 . MFR and stress MBF were associated with markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation in patients with aortic stenosis 42 .…”