Clinical Trials Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Dec 26, 2017; 9(12): 813-821
Published online Dec 26, 2017. doi: 10.4330/wjc.v9.i12.813
Delineation of epicardial stenosis in patients with microvascular disease using pressure drop coefficient: A pilot outcome study
Ullhas Udaya Hebbar, Mohamed A Effat, Srikara V Peelukhana, Imran Arif, Rupak K Banerjee
Ullhas Udaya Hebbar, Department of Mechanical and Materials Engineering, University of Cincinnati, Cincinnati, OH 45221, United States
Mohamed A Effat, Imran Arif, Division of Cardiovascular Diseases, University of Cincinnati Medical Center, Veteran Affairs Medical Center, Cincinnati, OH 45221, United States
Srikara V Peelukhana, Department of Mechanical and Materials Engineering, University of Cincinnati, Veteran Affairs Medical Center, Cincinnati, OH 45221, United States
Rupak K Banerjee, Department of Mechanical and Materials Engineering, Veteran Affairs Medical Center, Cincinnati, OH 45221, United States
Author contributions: Hebbar UU, Effat MA, Peelukhana SV and Banerjee RK designed the research; Effat MA and Arif I performed the interventions; Banerjee RK assimilated the data; Hebbar UU and Peelukhana SV performed the data analysis; Hebbar UU, Effat MA, Peelukhana SV and Banerjee RK wrote the paper.
Supported by VA Merit Review Grant, Department of Veteran Affairs (PI: Dr. Rupak K Banerjee), No. I01CX000342-01.
Institutional review board statement: The study protocol was approved by the institutional review board at University of Cincinnati (UC) and the research and development committee at the Cincinnati Veteran Affairs Medical Center (CVAMC).
Clinical trial registration statement: The study was registered with Clinicaltrials.gov. The registration identification number is NCT01719016.
Informed consent statement: All study participants provided informed written consent prior to the study enrolment.
Conflict-of-interest statement: The authors report no financial relationships or conflicts of interest regarding the content herein.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Rupak K Banerjee, PhD, PE, Professor, Department of Mechanical and Materials Engineering, Veteran Affairs Medical Center, 598 Rhodes Hall, PO Box 0072, Cincinnati, OH 45221, United States. rupak.banerjee@uc.edu
Telephone: +1-513-5562124 Fax: +1-513-5563390
Received: July 21, 2017
Peer-review started: July 27, 2017
First decision: September 5, 2017
Revised: September 29, 2017
Accepted: October 29, 2017
Article in press: October 29, 2017
Published online: December 26, 2017
Processing time: 148 Days and 12.9 Hours
ARTICLE HIGHLIGHTS
Research background

Accurate assessment of coronary stenosis is an important aspect of interventional cardiology. Although existing functional diagnostic indices such as fractional flow reserve (FFR) and coronary flow reserve (CFR) have been validated extensively via clinical trials, their efficacy is limited in the presence of concomitant microvascular disease (MVD) as they depend solely on pressure or flow measurements. This pilot study explores the efficacy of a combined pressure-flow diagnostic endpoint, pressure drop coefficient (CDP) compared to pressure-based FFR. It was hypothesized that CDP would show better clinical outcomes compared to FFR for patient subgroups with MVD.

Research motivation

Diagnosis of epicardial stenosis (ES) with concomitant MVD is a challenge with existing diagnostic indices (such as FFR, CFR) as they depend solely on pressure or flow. Pressure-based FFR can be overestimated in the presence of concomitant MVD, leading to possible misdiagnosis of severity of the stenosis, while CFR cannot differentiate between the effects of the stenosis and MVD. There is a need for combined pressure-flow diagnostic endpoints (such as CDP) to better diagnose coronary stenosis, particularly in the presence of MVD.

Research objectives

The primary objective of this research was to compare the clinical outcomes of patients with stenosis and possible MVD evaluated using FFR and CDP. Secondly, CDP was correlated with an existing index (HMR) used to evaluate the severity of MVD. CDP showed better clinical outcomes compared to FFR, as well as longer survival times for the patients. Also, CDP showed significant correlation with HMR, validating its efficacy at evaluation of MVD. It is to be noted that larger sample sizes and a randomized clinical trial is required to further confirm the results of this exploratory pilot study.

Research methods

Patients from our clinical trial was divided into two subgroups with: (1) cut-off of CFR < 2.0; and (2) diabetes. First, correlations were performed for both subgroups between CDP and HMR, a diagnostic parameter for assessing the severity of MVD. Linear regression analysis was used for these correlations. Further, in each of the subgroups, comparisons were made between FFR < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events (MACE: primary outcome). Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups. Two tailed chi-squared and Fischer’s exact tests were performed for comparison of the primary outcomes, and the log-rank test was used to compare the Kaplan-Meier survival curves. P < 0.05 for all tests was considered statistically significant.

Research results

Significant linear correlations were observed between CDP and HMR for both CFR < 2.0 (r = 0.58, P < 0.001) and diabetic (r = 0.61, P < 0.001) patients. In the CFR < 2.0 subgroup, the %MACE (primary outcomes) for CDP > 27.9 group (7.7%, 2/26) was lower than FFR < 0.75 group (3/14, 21.4%); P = 0.21. Similarly, in the diabetic subgroup, the %MACE for CDP > 27.9 group (12.5%, 2/16) was lower than FFR < 0.75 group (18.2%, 2/11); P = 0.69. Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group (n = 26) when compared with FFR < 0.75 group (n = 14); P = 0.10. Similarly, for the diabetic subgroup, CDP > 27.9 group (n = 16) showed higher survival times compared to FFR group (n = 11); P = 0.58.

Research conclusions

CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR. These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.

Research perspectives

This study highlights the ability of CDP in delineating MVD in patients with or without ES. In this patient subgroup analysis, CDP showed better clinical outcomes and higher survival rates compared to FFR, which is the current gold standard in functional diagnosis of coronary artery disease. There is a clear need for functional diagnostic endpoints which can better evaluate ES with concomitant MVD. In future, a large scale randomized clinical trial comparing the outcomes of CDP and FFR is required.