Abstract
BACKGROUND: Myocardial flow reserve (MFR, stress/rest myocardial blood flow) is a strong marker of myocardial vasomotor function. MFR is a predictor of adverse cardiac events in patients with non-ischemic systolic heart failure and previous studies using different methods have found association between myocardial blood flow and left ventricular dilatation. The aim of this study was to investigate whether there is an association between increasing end-systolic- and end-diastolic volumes (ESV and EDV) and MFR in these patients measured with Rubidium-82 positron emission tomography computed tomography ((82)Rb-PET/CT) as a quantitative myocardial perfusion gold-standard. METHODS: We scanned 151 patients with non-ischemic heart failure with initial left ventricular ejection fraction ≤35% with (82)Rb-PET/CT at rest and adenosine-induced stress to obtain MFR and volumes. To account for differences in body surface area (BSA), we used indexed ESV (ESVI): ESV/BSA (ml/m(2)) and EDV (EDVI). We identified factors associated with MFR using multiple regression analyses. RESULTS: Median age was 62 years (55-69 years) and 31% were women. Mean MFR was 2.38 (2.24-2.52). MFR decreased significantly with both increasing ESVI (estimate - 3.7%/10 ml/m(2); 95% confidence interval [CI] -5.6 to - 1.8; P < 0.001) and increasing EDVI (estimate - 3.5%/10 ml/m(2); 95% CI -5.3 to - 1.6; P < 0.001). Results remained significant after multivariable adjustment. Additionally, coronary vascular resistance during stress increased significantly with increasing ESVI (estimate: 3.1 mmHg/(ml/g/min) per (10 ml/m(2)); 95% CI 2.0 to 4.3; r = 0.41; P < 0.0001) and increasing EDVI (estimate: 2.7 mmHg/(ml/g/min) per (10 ml/m(2)); 95% CI 1.6 to 3.8; r = 0.37; P < 0.0001). CONCLUSIONS: Impaired MFR assessed by (82)Rb-PET/CT was significantly associated with linear increases in ESVI and EDVI in patients with non-ischemic systolic heart failure. Our findings support that impaired microvascular function may play a role in heart failure development. Clinical trials investigating MFR with regard to treatment responses may elucidate the clinical use of MFR in patients with non-ischemic systolic heart failure. TRIAL REGISTRATION: Sub study of the randomized clinical trial: A DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillator in patients with non-ischemic Systolic Heart failure on mortality (DANISH), ClinicalTrials.gov Identifier: NCT00541268 .