Diagnostic Value of Angiography-Derived IMR for Coronary Microcirculation and Its Prognostic Implication After PCI

Abstract

Background: Angiography-derived index of microcirculatory resistance (angio-IMR) is an emerging pressure-wire-free index to assess coronary microvascular function, but its diagnostic and prognostic value remains to be elucidated. Methods and Results: The study population consisted of three independent cohorts. The internal diagnostic cohort enrolled 53 patients with available hyperemic microcirculatory resistance (HMR) calculated from myocardial blood flow and pressure. The external diagnostic cohort included 35 ischemia and no obstructive coronary artery disease (INOCA) patients and 45 controls. The prognostic cohort included 138 coronary artery disease (CAD) patients who received PCI. Angio-IMR was calculated after the estimation of angiography-derived fractional flow reserve (angio-FFR) using the equation of angio-IMR = estimated hyperemic Pa × angio-FFR × [vessel length/(K × Vdiastole)]. The primary outcome was a composite of cardiac death or readmission due to heart failure at 28 months after index procedure. Angio-IMR demonstrated a moderate correlation with HMR (R = 0.74, p < 0.001) and its diagnostic accuracy, sensitivity, specificity, and area under the curve to diagnose INOCA were 79.8, 83.1, 78.0, and 0.84, respectively, with a best cut-off of 25.1. Among prognostic cohort, patients with angio-IMR ≥25.1 showed a significantly higher risk of cardiac death or readmission due to heart failure than those with an angio-IMR <25.1 (18.6 vs. 5.4%, adjusted HR 9.66, 95% CI 2.04-45.65, p = 0.004). Angio-IMR ≥25.1 was an independent predictor for cardiac death or readmission due to heart failure (HR 11.15, 95% CI 1.76-70.42, p = 0.010). Conclusions: Angio-IMR showed a moderate correlation with HMR and high accuracy to predict microcirculatory dysfunction. Angio-IMR measured after PCI predicts the risk of cardiac death or readmission due to heart failure in patients with CAD. Clinical Trial Registration: Diagnostic and Prognostic Value of Angiography-derived IMR (CHART-MiCro), NCT04825028.

Keywords: INOCA; coronary microcirculation; functional angiography; index of microcirculatory resistance; prognosis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Dai, Che, Liu, Zhang, Yin, Xu, Xu, Duan, Yu, Li, Yao, Huang and Ge.

Figures

Figure 1

Study flow. The study population was composed of internal and external diagnostic cohorts and prognostic cohort. Internal diagnostic cohort was used to evaluate the correlation between angio-IMR and HMR; external diagnostic cohort was used to evaluate the diagnostic performance of angio-IMR to diagnose INOCA. Prognostic cohort was used to evaluate the prognostic implication of angio-IMR in CAD patients after PCI. Angio-IMR, angiography-derived index of microcirculatory resistance; CAD, coronary artery disease; HMR, hyperemic microcirculatory resistance; INOCA, ischemia and no obstructive coronary artery disease; PCI, percutaneous coronary intervention.

Figure 2

Case examples of angiography-derived physiologic indices. A representative case of CZT-SPECT MBF, pressure wire FFR, and angio-IMR measurements, as well as how HMR are calculated from MBF and coronary pressure, are shown. (A) Coronary angiography; (B) CZT-SPECT MBF; (C) Pressure wire– measured FFR; (D) Calculation of HMR using coronary pressure and MBF data; (E) Angiography-derived FFR and IMR. CZT-SPECT, cadmium–zinc–telluride single-photon emission computed tomography; FFR, fractional flow reserve; HMR, hyperemic microcirculatory resistance; IMR, index of microcirculatory resistance; MBF, myocardial blood flow.

Figure 3

Correlation of angiography-derived FFR with invasive FFR and angiography-derived IMR and HMR in diagnostic cohort. The correlation and agreement between (A) angio-FFR and pressure wire–derived FFR, and (B) angio-IMR and coronary pressure and myocardial blood flow calculated HMR. Abbreviations are listed in Figures 1, 2.

Figure 4

Diagnostic accuracy of angiography-derived IMR to diagnose INOCA in external validation cohort. (A) Mean angio-IMR values in vessels with abnormal (INOCA) and normal (internal controls) corresponding CZT-SPECT perfusion territory among INOCA patients and in vessels among patients with normal CZT-SPECT perfusion imaging and angiography (normal controls); (B) ROC of angio-IMR to diagnose INOCA and (C) diagnostic performances of angio-IMR to diagnose INOCA are shown. AUC, area under curve; BCV, best cut-off value; LR, likelihood ratio; NPV, negative predictive value; PPV, positive predictive value; others are with Figure 1.

Figure 5

Comparison of primary and secondary outcomes at 28 months after index procedure according to angiography-derived IMR. Cumulative incidences of cardiac death or readmission due to (A) heart failure; (B) cardiac death or readmission due to heart failure and angina; (C) readmission due to heart failure; and (D) readmission due to angina at 28 months are presented according to the best cut-off value of angio-IMR. CI, confidence intervals; HRadj, multivariable adjusted hazard ratios; others are with Figure 1.

Figure 6

Diagnostic Value of Angiography-derived Index of Microcirculatory Resistance for Coronary Microcirculation and Its Prognostic Implication after PCI in CAD Patients. The current study evaluated diagnostic and prognostic implications of angiography-derived IMR. In diagnostic cohorts, angio-IMR showed a close correlation with HMR calculated as the ratio of hyperemic coronary pressure to myocardial blood flow, and a high diagnostic accuracy to predict patients with microcirculatory dysfunction. In prognostic cohort, patients with post-PCI impaired microcirculatory function assessed by angio-IMR ≥ 25.1U showed significantly higher risk of cardiac death or readmission due to heart failure than those with preserved microcirculatory function assessed by angio-IMR