Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

Prognostic Value of Microvascular Resistance Reserve Measured Immediately After PCI in Stable Coronary Artery Disease.

BACKGROUND: Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease. METHODS: This study included 502 patients with stable coronary artery disease who underwent elective PCI and coronary physiological measurements, including pressure and flow estimation using a bolus thermodilution method after PCI. MRR was calculated as coronary flow reserve divided by fractional flow reserve times the ratio of mean aortic pressure at rest to that at maximal hyperemia induced by hyperemic agents. An abnormal MRR was defined as ≤2.5. Major adverse cardiac events (MACEs) were defined as a composite of all-cause mortality, any myocardial infarction, and target-vessel revascularization. RESULTS: During a median follow-up of 3.4 years, the cumulative MACE rate was significantly higher in the abnormal MRR group (12.5 versus 8.3 per 100 patient-years; hazard ratio 1.53 [95% CI, 1.10-2.11]; P<0.001). A higher all-cause mortality rate primarily drove this difference. On multivariable analysis, a higher MRR value was independently associated with lower MACE and lower mortality. When comparing 4 subgroups according to MRR and the index of microcirculatory resistance, patients with both abnormal MRR and index of microcirculatory resistance (≥25) had the highest MACE rate. CONCLUSIONS: An abnormal MRR measured immediately after PCI in patients with stable coronary artery disease is an independent predictor of MACE, particularly all-cause mortality.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

Role of Cardiac Magnetic Resonance Imaging and Troponin T in Definitive Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: It is unknown whether the degree of high-sensitivity troponin T (hsTropT) elevation in patients with suspected myocardial infarction without obstructive coronary arteries (MINOCA) presentations can help predict the likelihood of an abnormal cardiac magnetic resonance (CMR) scan. In this study we describe the diagnostic utility of CMR in patients with MINOCA and assesses the effect of peak hsTropT levels at presentation on CMR diagnostic yield. METHODS: Records of consecutive patients (n = 1407) referred for CMR at a tertiary referral hospital between January 2016 and September 2021 were reviewed. A total of 70 patients met the criteria of MINOCA including ischemic chest pain, elevated peak hsTropT, and nonobstructive coronary artery disease (< 50% stenosis). The peak hsTropT levels within 72 hours of admission were identified. CMR images were generated using a 3.0 T Siemens scanner. Predictors of having an abnormal CMR were evaluated. RESULTS: CMR established a diagnosis in 71% (n = 50) of patients, with the most common CMR diagnosis being myopericarditis (n = 27; 39%). Time to CMR was an independent predictor of a normal CMR scan (odds ratio, 0.98; 95% confidence interval, 0.97-0.999). Peak hsTropT had a high diagnostic accuracy for identifying patients with an abnormal CMR scan (area under the receiver operator characteristic curve, 0.81; P < 0.001). The optimal hsTropT cutoff was 166 ng/L, with 72% sensitivity and specificity. A troponin value ≥ 166 ng/L was independently predictive of an abnormal CMR scan (odds ratio, 4.76; 95% confidence interval, 1.32-17.11). CONCLUSIONS: HsTropT and early CMR imaging are independently predictive of an abnormal CMR scan in patients with MINOCA. Additionally, the use of a hsTropT cutoff provides incremental predictive value to clinical parameters and time to CMR scanning in determining an abnormal scan.

Haemodynamic and metabolic adaptations in coronary microvascular disease.

OBJECTIVE: We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD). METHODS: Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12). RESULTS: The mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03). CONCLUSIONS: Patients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups).

Fractional Flow Reserve and Instantaneous Wave-Free Ratio Predict Pathological Wall Shear Stress in Coronary Arteries: Implications for Understanding the Pathophysiological Impact of Functionally Significant Coronary Stenoses.

Background The pathophysiological mechanism behind adverse outcomes associated with ischemia-inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave-free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (ß) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (ß=-0.44; 95% CI, -0.62 to -0.25; P<0.001) and maximum lesion WSS (ß=-0.53; 95% CI, -0.70 to -0.36; P<0.001) after adjusting for percentage diameter stenosis and index of microcirculatory resistance. Similarly, instantaneous wave-free ratio also independently predicted the total area of low WSS (ß=-0.45; 95% CI, -0.62 to -0.28; P<0.001) and maximum lesion WSS (ß=-0.58; 95% CI, -0.73 to -0.43; P<0.001). The index of microcirculatory resistance did not predict either low or high WSS. Conclusions Fractional flow reserve and instantaneous wave-free ratio independently predicted the total burden of low WSS and maximum lesion WSS in coronary arteries. No relationship was found between microcirculatory dysfunction and WSS.

A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention.

BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort. METHODS AND RESULTS: All patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20-0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07-0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07-0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25-0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27-0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08-0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09-0.83, P = 0.02). CONCLUSIONS: In this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.

Association of hypertension with mortality in patients hospitalised with COVID-19.

OBJECTIVE: To assess whether hypertension is an independent risk factor for mortality among patients hospitalised with COVID-19, and to evaluate the impact of ACE inhibitor and angiotensin receptor blocker (ARB) use on mortality in patients with a background of hypertension. METHOD: This observational cohort study included all index hospitalisations with laboratory-proven COVID-19 aged ≥18 years across 21 Australian hospitals. Patients with suspected, but not laboratory-proven COVID-19, were excluded. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs. RESULTS: 546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (adjusted OR (aOR) 1.09, 95% CI 1.07 to 1.12, p<0.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13 to 6.53, p=0.026), chronic kidney disease (aOR 2.33, 95% CI 1.02 to 5.32, p=0.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06 to 4.85, p=0.035). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48 to 1.77, p=0.81). Among patients with hypertension, ACE inhibitor (aOR 1.37, 95% CI 0.61 to 3.08, p=0.61) and ARB (aOR 0.64, 95% CI 0.27 to 1.49, p=0.30) use was not associated with mortality. CONCLUSIONS: In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.

Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging.

BACKGROUND: Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB. METHODS AND RESULTS: A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = -0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT. CONCLUSIONS: Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

Association of microvascular dysfunction with clinical outcomes in patients with non-flow limiting fractional flow reserve after percutaneous coronary intervention.

BACKGROUND: We sought to investigate prognostic implication of microvascular dysfunction as assessed by the index of microcirculatory index (IMR) in patients without residual obstructive CAD with non-flow limiting fractional flow reserve (FFR) (>0.80) following percutaneous coronary intervention (PCI). METHODS: A total of 570 patients who had both post-PCI FFR and IMR values were included in the present analysis; of these, 65 patients had FFR ≤ 0.80 and 505 had FFR > 0.80. Of the 505 patients with FFR > 0.80, 137 had high IMR and 368 had low IMR. The primary outcome of the present analysis is a composite of all-cause death, spontaneous myocardial infarction, or target-vessel revascularization. Impaired microvascular function was defined as IMR ≥ 25 (high IMR). RESULTS: During a median follow-up duration of 4.0 years, those with FFR > 0.80 and low IMR demonstrated lower rate or primary outcome event than those with FFR ≤ 0.80 (hazard ratio 0.49 [95% confidence interval 0.27-0.92], p = 0.026) and those with FFR > 0.80 and high IMR (hazard ratio 1.60 [0.99-2.16], p = 0.056). The patients with FFR > 0.80 and IMR ≥ 25 had similar rate of primary outcome event compared with those with FFR ≤ 0.80 (p = 0.49). CONCLUSION: Microvascular dysfunction following PCI is not rare and is associated with adverse events even in the setting of a non-flow limiting FFR; these results suggest that when performing coronary physiologic assessment following PCI, interrogating not only the epicardial vessel, but also the microvasculature is useful for the risk stratification in patients undergoing PCI.

Efficacy and Safety Outcomes of Short Duration Antiplatelet Therapy with Early Cessation of Aspirin Post Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.

BACKGROUND: The optimal duration of dual antiplatelet therapy is a matter of ongoing research. Clinical studies are assessing the optimal duration with the most favourable risk to benefit ratio. The efficacy of P2Y12 receptor inhibitors comparable to aspirin in preventing recurrent ischaemic events in patients with coronary artery diseases. OBJECTIVES: To investigate the outcomes of short-duration dual antiplatelet therapy after PCI with early discontinuation of aspirin while maintaining patients on P2Y12 inhibitor through systematic review and meta-analysis of available literature. METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. We included randomized controlled studies that measured clinical outcomes of efficacy (mortality and ischaemic events) and safety (bleeding) of short and standard-duration dual antiplatelet therapy. The protocol of this study was registered in the international prospective register of systematic reviews PROSPERO registry (CRD42020171468). RESULTS: Four randomized controlled trials were included; GLOBAL LEADERS, SMARTCHOICE, STOPDAPT-2, and TWILIGHT. The total number of patients was 29,089. The safety outcomes showed a significant reduction in major bleeding events with short-duration dual antiplatelet therapy; the risk ratio was 0.61 (95% CI 0.38-0.99; z=2,00, p=0.05). There was no difference between short and standard-duration dual antiplatelet therapy regarding efficacy outcomes (all- cause death, major adverse cardiovascular events, myocardial infarction, stroke, and stent thrombosis). CONCLUSION: Short-duration dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy after PCI is a feasible option and can be adopted, especially in patients with a high risk of bleeding.

Androgens Stimulate EPC-Mediated Neovascularization and Are Associated with Increased Coronary Collateralization.

Endothelial progenitor cells (EPCs) play a key role in neovascularization and have been linked to improved cardiovascular outcomes. Although there is a well-established inverse relationship between androgen levels and cardiovascular mortality in men, the role of androgens in EPC function is not fully understood. In this study, we investigated the effects of androgens on 2 subpopulations of EPCs, early EPCs (EEPCs) and late outgrowth EPCs (OECs), and their relationships with coronary collateralization. Early EPCs and OECs were isolated from the peripheral blood of young healthy men and treated with dihydrotestosterone (DHT) with or without androgen receptor (AR) antagonist, hydroxyflutamide, in vitro. Dihydrotestosterone treatment enhanced AR-mediated proliferation, migration, and tubulogenesis of EEPCs and OECs in a dose-dependent manner. Furthermore, DHT augmented EPC sensitivity to extracellular stimulation by vascular endothelial growth factor (VEGF) via increased surface VEGF receptor expression and AKT activation. In vivo, xenotransplantation of DHT pretreated human EPCs augmented blood flow recovery and angiogenesis in BALB/c nude male mice, compared to mice receiving untreated EPCs, following hindlimb ischemia. In particular, DHT pretreated human OECs exhibited higher reparative potential than EEPCs in augmenting postischemic blood flow recovery in mice. Furthermore, whole blood was collected from the coronary sinus of men with single vessel coronary artery disease (CAD) who underwent elective percutaneous intervention (n = 23). Coronary collateralization was assessed using the collateral flow index. Serum testosterone and EPC levels were measured. In men with CAD, circulating testosterone was positively associated with the extent of coronary collateralization and the levels of OECs. In conclusion, androgens enhance EPC function and promote neovascularization after ischemia in mice and are associated with coronary collateralization in men.

Prognostic Value of Coronary Microvascular Function Measured Immediately After Percutaneous Coronary Intervention in Stable Coronary Artery Disease: An International Multicenter Study.

BACKGROUND: The prognostic impact of coronary microvascular dysfunction after percutaneous coronary intervention (PCI) remains unclear in patients with stable coronary artery disease. This study sought to investigate the prognostic value of microvascular function measured immediately after PCI in patients with stable coronary artery disease. METHODS: We enrolled 572 patients with stable coronary artery disease who underwent PCI and elective measurement of the index of microcirculatory resistance (IMR) immediately after PCI from 8 centers in 4 countries. Impaired microvascular function was defined as IMR≥25 (high IMR). Major adverse cardiac events, including death, myocardial infarction (MI) and target vessel revascularization, were evaluated. RESULTS: During a median follow-up duration of 4.0 years, the cumulative major adverse cardiac events rate was significantly higher in the high IMR group (n=66/148) compared with the low IMR group (n=128/424; hazard ratio [HR], 1.56; 95% CI, 1.16-2.105; P=0.001), primarily due to a higher rate of periprocedural MI (HR, 1.59; 95% CI, 1.11-2.28; P=0.004) but also due to higher rates of mortality (HR, 1.59; 95% CI, 0.76-3.35; P=0.22), spontaneous MI (HR, 2.10; 95% CI, 0.67-6.63; P=0.20) and target vessel revascularization (HR, 1.40; 95% CI, 0.77-2.54; P=0.27). Cumulative risk for death, spontaneous MI, and target vessel revascularization was higher in the high IMR group (HR, 1.55; 95% CI, 0.99-2.43; P=0.056), as was death and spontaneous MI alone (HR, 1.79; 95% CI, 0.96-3.36; P=0.065). On multivariable analysis, high IMR post-PCI was an independent predictor of major adverse cardiac events. CONCLUSIONS: IMR measured immediately after PCI predicts adverse events in patients with stable coronary artery disease.