Background— A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking. Methods and Results— By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9±6.5 U to 25.9±14.4 U, P =0.002) and TMR (0.51±0.14 to 0.79±0.32 mm Hg · mL ⁻¹ · min ⁻¹ , P =0.0001), as well as the % change in IMR (147±66%) and TMR (159±105%, P =NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR. Conclusion— Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.

Background—: Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention, is predictive of death and rehospitalization for heart failure. Methods and Results—: IMR was measured immediately after primary percutaneous coronary intervention in 253 patients from 3 institutions with the use of a pressure–temperature sensor wire. The primary end point was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared with coronary flow reserve, TIMI myocardial perfusion grade, and clinical variables. The mean IMR was 40.3±32.5. Patients with an IMR >40 had a higher rate of the primary end point at 1 year than patients with an IMR ≤40 (17.1% versus 6.6%; P =0.027). During a median follow-up period of 2.8 years, 13.8% experienced the primary end point and 4.3% died. An IMR >40 was associated with an increased risk of death or rehospitalization for heart failure (hazard ratio [HR], 2.1; P =0.034) and of death alone (HR, 3.95; P =0.028). On multivariable analysis, independent predictors of death or rehospitalization for heart failure included IMR >40 (HR, 2.2; P =0.026), fractional flow reserve ≤0.8 (HR, 3.24; P =0.008), and diabetes mellitus (HR, 4.4; P 40 was the only independent predictor of death alone (HR, 4.3; P =0.02). Conclusions—: An elevated IMR at the time of primary percutaneous coronary intervention predicts poor long-term outcomes.

Background—: More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a “normal” angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis. Methods and Results—: In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ≤0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging. Conclusions—: The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.

Background—: The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study demonstrated significantly improved health outcomes at 1 year in patients randomized to multivessel percutaneous coronary intervention guided by fractional flow reserve (FFR) compared with percutaneous coronary intervention guided by angiography alone. The economic impact of routine measurement of FFR in this setting is not known. Methods and Results—: In this study, 1005 patients were randomly assigned to FFR-guided or angiography-guided percutaneous coronary intervention and followed up for 1 year. A prospective cost-utility analysis comparing costs and quality-adjusted life-years was performed with a time horizon of 1 year. Quality-adjusted life-years were calculated with the use of utilities determined by the EuroQuol 5 dimension health survey with US weights. Direct medical costs included those of the index procedure and hospitalization and costs for major adverse cardiac events during follow-up. Confidence intervals for both quality-adjusted life-years and costs were estimated by the bootstrap percentile method. Major adverse cardiac events at 1 year occurred in 13.2% of those in the FFR-guided arm and 18.3% of those in the angiography-guided arm ( P =0.02). Quality-adjusted life-years were slightly greater in the FFR-guided arm (0.853 versus 0.838; P =0.2). Mean overall costs at 1 year were significantly less in the FFR-guided arm ($14 315 versus $16 700; P <0.001). Bootstrap simulation indicated that the FFR-guided strategy was cost-saving in 90.74% and cost-effective at a threshold of US $50 000 per quality-adjusted life-years in 99.96%. Sensitivity analyses demonstrated robust results. Conclusion—: Economic evaluation of the FAME study reveals that FFR-guided percutaneous coronary intervention in patients with multivessel coronary disease is one of those rare situations in which a new technology not only improves outcomes but also saves resources. Clinical Trial Registration—: URL: http://ClinicalTrials.gov . Unique identifier: NCT00267774.

Background: Previous studies found that percutaneous coronary intervention (PCI) does not improve outcome compared with medical therapy (MT) in patients with stable coronary artery disease, but PCI was guided by angiography alone. FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared PCI guided by fractional flow reserve with best MT in patients with stable coronary artery disease to assess clinical outcomes and cost-effectiveness. Methods: A total of 888 patients with stable single-vessel or multivessel coronary artery disease with reduced fractional flow reserve were randomly assigned to PCI plus MT (n=447) or MT alone (n=441). Major adverse cardiac events included death, myocardial infarction, and urgent revascularization. Costs were calculated on the basis of resource use and Medicare reimbursement rates. Changes in quality-adjusted life-years were assessed with utilities determined by the European Quality of Life–5 Dimensions health survey at baseline and over follow-up. Results: Major adverse cardiac events at 3 years were significantly lower in the PCI group compared with the MT group (10.1% versus 22.0%; P <0.001), primarily as a result of a lower rate of urgent revascularization (4.3% versus 17.2%; P <0.001). Death and myocardial infarction were numerically lower in the PCI group (8.3% versus 10.4%; P =0.28). Angina was significantly less severe in the PCI group at all follow-up points to 3 years. Mean initial costs were higher in the PCI group ($9944 versus $4440; P <0.001) but by 3 years were similar between the 2 groups ($16 792 versus $16 737; P =0.94). The incremental cost-effectiveness ratio for PCI compared with MT was $17 300 per quality-adjusted life-year at 2 years and $1600 per quality-adjusted life-year at 3 years. The above findings were robust in sensitivity analyses. ConclusionS: PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable coronary artery disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01132495.