Prognostic Impact of Coronary Flow Reserve in Patients With Reduced Left Ventricular Ejection Fraction

Abstract

Background Intracoronary physiologic indexes such as coronary flow reserve (CFR) and left ventricular ejection fraction (LVEF) have been regarded as prognostic indicators in patients with coronary artery disease. The current study evaluated the association between intracoronary physiologic indexes and LVEF and their differential prognostic implications in patients with coronary artery disease. Methods and Results A total of 1889 patients with 2492 vessels with available CFR and LVEF were selected from an international multicenter prospective registry. Baseline physiologic indexes were measured by thermodilution or Doppler methods and LVEF was recorded at the index procedure. The primary outcome was target vessel failure, which was a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization over 5 years of follow-up. Patients with reduced LVEF <50% (162 patients [8.6%], 202 vessels [8.1%]) showed a similar degree of epicardial coronary artery disease but lower CFR values than those with preserved LVEF (2.4±1.2 versus 2.7±1.2, P<0.001), mainly driven by the increased resting coronary flow. Conversely, hyperemic coronary flow, fractional flow reserve, and the degree of microvascular dysfunction were similar between the 2 groups. Reduced CFR (≤2.0) was seen in 613 patients (32.5%) with 771 vessels (30.9%). Reduced CFR was an independent predictor for target vessel failure (hazard ratio, 2.081 [95% CI, 1.385-3.126], P<0.001), regardless of LVEF. Conclusions CFR was lower in patients with reduced LVEF because of increased resting coronary flow. Patients with reduced CFR showed a significantly higher risk of target vessel failure than did those with preserved CFR, regardless of LVEF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.

Keywords: coronary flow reserve; coronary physiology; left ventricular ejection fraction; prognosis.

Figures

Figure 1. Study flow.

Study flow is presented. Among the total population of the ILIAS registry (2322 patients with 3046 vessels), patients with unavailable baseline LVEF or CFR data and without follow‐up data were excluded for the current study, leaving 1889 patients with 2492 vessels with clinical outcomes during 5 years of follow‐up. CFR indicates coronary flow reserve; ILIAS (Inclusive Invasive Physiological Assessment in Angina Syndromes) registry; LVEF, left ventricular ejection fraction; and TVF, target vessel failure.

Figure 2. Comparison of flow‐derived physiologic indexes according to LVEF.

Comparison of A, CFR, B, Resting Tmn, C, Hyperemic Tmn, D, IMR, E, Resting APV, F, Hyperemic APV, G, BMR, H, HMR are shown according to LVEF. Data are expressed as mean±SD or median (interquartile range). APV indicates averaged peak velocity; BMR, basal microvascular resistance; CFR, coronary flow reserve; HMR, hyperemic microvascular resistance; IMR, index of microcirculatory resistance; LVEF, left ventricular ejection fraction; and Tmn, mean transit time.

Figure 3. Comparison of physiologic indexes of epicardial coronary stenosis according to LVEF.

A, Resting Pd/Pa, B, FFR, C, Basal Stenosis Resistance, D, Hyperemic Stenosis Resistance are compared between patients with preserved and reduced LVEF. Data are expressed as mean±SD or median (interquartile range). FFR indicates fractional flow reserve; resting Pd/Pa, resting distal coronary pressure/aortic pressure; and LVEF, left ventricular ejection fraction.

Figure 4. Comparison of TVF According to LVEF and CFR.

Cumulative incidence of TVF at 5 years are compared among 4 groups classified according to LVEF and CFR. Multivariable marginal Cox proportional hazard regression was used to calculate adjusted HR and 95% CI. The adjusted covariables were age, sex, diabetes, previous myocardial infarction, clinical presentation, multivessel disease, target vessel intervention, pre‐PCI diameter stenosis, pre‐PCI FFR≤0.80, and increased microcirculatory resistance (IMR≥25 or HMR≥2.5). CFR indicates coronary flow reserve; FFR, fractional flow reserve; HMR, hyperemic microvascular resistance; HR, hazard ratio; IMR, index of microvascular resistance; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; and TVF, target vessel failure.

Figure 5. Comparison of target vessel failure according to different patterns of depressed CFR.

Cumulative incidence of TVF at 5 years is compared according to different patterns in resting and hyperemic coronary flow among depressed CFR cohort. In this analysis, 305 vessels with missing value in resting and hyperemic Tmn (19.4% of thermodilution technique) were excluded. Regardless of different patterns in resting and hyperemic flow, the depressed CFR cohort showed significantly higher risk of TVF than the preserved CFR cohort. CFR indicates coronary flow reserve; Tmn, mean transit time; and TVF, target vessel failure.