Impaired myocardial perfusion is associated with increasing end-systolic- and end-diastolic volumes in patients with non-ischemic systolic heart failure: a cross-sectional study using Rubidium-82 PET/CT

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 (82Rb-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 82Rb-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/m2) 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/m2; 95% confidence interval [CI] -5.6 to - 1.8; P < 0.001) and increasing EDVI (estimate - 3.5%/10 ml/m2; 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/m2); 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/m2); 95% CI 1.6 to 3.8; r = 0.37; P < 0.0001).

Conclusions: Impaired MFR assessed by 82Rb-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 .

Keywords: End diastolic volume; End systolic volume; Myocardial flow reserve; Myocardial perfusion imaging; Non-ischemic systolic heart failure.

Conflict of interest statement

Ethics approval and consent to participate

All patients had given informed oral and written consents, and the Scientific Ethics Committee of the Capital Region of Denmark and the Danish Data Protection Agency approved the protocol. (protocol number H-15000346).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Inclusion flow chart. DANISH [15] Centre 1 and 2: Rigshospitalet and Gentofte Hospital, Copenhagen, Denmark. COPD chronic obstructive pulmonary disease

Fig. 2

Myocardial flow reserve as a function of end-systolic volume/body surface area (a) and end-diastolic volume/body surface area (b) with 95% confidence bands of the best-fit line

Fig. 3

Coronary vascular resistance (CVR) as a function of end-systolic volume/body surface area at rest (a) and during stress (b) and as a function of end-diastolic volume/body surface area at rest (c) and during stress (d) with 95% confidence bands of the best-fit line