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PROspective evaluation of coronary FLOW reserve and molecular biomarkers in patients with established coronary artery disease the PROFLOW-trial: cross-sectional evaluation of coronary flow reserve

Authors Haraldsson I, Gan LM, Svedlund S, Torngren K, Westergren HU, Redfors B, Lagerström-Fermér M, Angerås O, Råmunddal T, Petursson P, Odenstedt J, Albertsson P, Erlinge D, Omerovic E

Received 17 March 2019

Accepted for publication 13 August 2019

Published 28 August 2019 Volume 2019:15 Pages 375—384

DOI https://doi.org/10.2147/VHRM.S209003

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Daniel Duprez


Inger Haraldsson,1,2 Li-Ming Gan,1–3 Sara Svedlund,1,4 Kristina Torngren,5 Helena U Westergren,6 Björn Redfors,1,2 Maria Lagerström-Fermér,3 Oskar Angerås,1,2 Truls Råmunddal,1,2 Petur Petursson,1,2 Jacob Odenstedt,1,2 Per Albertsson,1,2 David Erlinge,5 Elmir Omerovic1,2

1Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Early Clinical Development, IMED Biotech Unit, AstraZeneca R&D, Gothenburg, Sweden; 4Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; 6Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca R&D, Gothenburg, Sweden

Correspondence: Elmir Omerovic
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Bruna stråket 16
, 41345 Gothenburg, Sweden
Tel +46 31 342 2950
Fax +46 3 182 3762
Email elmir@wlab.gu.se

Background: Survivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI.
Methods: PROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140 μg/kg/min). Independent predictors of CFR were assessed with multiple linear regression.
Results: We included 619 patients. The median age was 69 (IQR 65–73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean ± SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angiotensin receptor blockers were independent predictors of CFR.
Conclusion: In this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.

Keywords: coronary flow reserve, myocardial infarction, secondary prevention, Doppler echocardiography, prognosis

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