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Editorial Comment High-Risk Coronary Anatomy Versus High-Risk Physiology as Outcome Predictors in Acute Coronary Syndromes Ernesto Ruiz-Rodriguez, MD and David J. Moliterno,* MD Division of Cardiovascular Medicine, Gill Heart Insti- tute, University of Kentucky , Lexington, Kentucky Current practice guidelines recommend an early inva- sive strategy for intermediate to high-risk non-ST eleva- tion acute coronary syndrome (NSTE-ACS) patients. Given the increasing incidence of NSTE-ACS over the past decade and the substantial associated morbidities, the use of risk prediction scores has become essential in the identification of patients most likely to benefit from an invasive approach. The Global Registry of Acute Cor- onary Events (GRACE), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (PURSUIT) and Thrombolysis In Myocardial Infarction (TIMI) scores are well-validated models that integrate multiple clinical variables to predict outcomes in this population [1]. In contrast, the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score is an anatomical-based model similar to the ACC/AHA Classi- fication System for angiographic prediction of outcome and is designed to help in deciding the optimal strategy of revascularization in complex coronary artery disease (CAD) [2]. The Acute Catheterization and Urgent Inter- vention Triage strategY (ACUITY) trial, subgroup of NSTE-ACS patients treated with urgent percutaneous re- vascularization, showed that the SYNTAX score was an independent predictor of 1-year mortality, cardiac death, acute MI, and target vessel revascularization on multivari- ate analysis. Furthermore, the Clinical SYNTAX score [3], achieved by combining the SYNTAX Score with a modified age, creatinine, and ejection fraction (ACEF) score has been shown to perform better than purely clini- cal scores in predicting cardiac death, major adverse car- diac and cerebrovascular events (MACCE), stent thrombosis, MI, and target vessel revascularization in the ACUITY trial [4]. Although the utility of these various models in risk assessment is well proven, they are not designed to predict the severity of CAD, a variable that intuitively can be meaningfully associated with outcomes. In this issue of Catheterization and Cardiovascular Interventions, Beigel et al. [5] point out that current risk scores for NSTE-ACS may fail to identify some patients with severe CAD. The study aims at identifying predictors of high-risk coronary anatomy (HRCA)—defined as left main disease >50% diameter stenosis, proximal left ante- rior descending (LAD) lesion >70%; or 2–3 vessel disease involving the LAD—and evaluating their impact on prog- nosis. This retrospective study based on the nationwide registry Acute Coronary Syndrome Israeli Survey included 923 patients with NSTE-ACS who underwent coronary ar- teriography. Multivariable analysis revealed that the pres- ence of peripheral vascular disease, GRACE score > 140, and chronic renal disease were the strongest predictors of HRCA. Among 370 patients found to have HRCA, 85 patients (23%) did not meet criteria for an early invasive strategy solely using GRACE score > 140, ST-segment depressions on electrocardiography, positive cardiac bio- markers, or Killip Class 2 on admission. The prognostic implications of these findings are important as patients with HRCA had more in-hospital complications such as cardio- genic shock and pulmonary edema and higher frequency of moderate to severe mitral regurgitation, need for surgical revascularization, MACCE at 30 days, and mortality at 30 days and at 1 year. Based on multivariate analysis, HRCA was the strongest predictor of MACCE at 30 days. This study raises the issue that relying solely on individ- ual risk stratification scores may fail to identify some patients with severe CAD who would benefit from an early invasive strategy. It makes sense that the “extent of dis- ease” can be distinct from “acuity of disease” with each having important clinical implications. A few thought- provoking questions arise from this study. Should we rou- tinely assess HRCA scores in NSTE-ACS patients? Is it essential to identify patients early with low-risk clinical scores but high-risk HRCA scores to improve outcomes, or Conflict of interest: Nothing to report. *Correspondence to: David J. Moliterno, MD, Department of Internal Medicine, University of Kentucky, 900 South Limestone Avenue, 329 Wethington Building, Lexington, KY 40536-0200. E-mail: [email protected] Received 10 February 2014; Revision accepted 10 February 2014 DOI: 10.1002/ccd.25437 Published online 19 March 2014 in Wiley Online Library (wileyonlinelibrary.com) V C 2014 Wiley Periodicals, Inc. Catheterization and Cardiovascular Interventions 83:684–685 (2014)

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Editorial Comment

High-Risk Coronary AnatomyVersus High-Risk Physiology asOutcome Predictors in AcuteCoronary Syndromes

Ernesto Ruiz-Rodriguez, MD andDavid J. Moliterno,* MD

Division of Cardiovascular Medicine, Gill Heart Insti-tute, University of Kentucky, Lexington, Kentucky

Current practice guidelines recommend an early inva-sive strategy for intermediate to high-risk non-ST eleva-tion acute coronary syndrome (NSTE-ACS) patients.Given the increasing incidence of NSTE-ACS over thepast decade and the substantial associated morbidities,the use of risk prediction scores has become essential inthe identification of patients most likely to benefit froman invasive approach. The Global Registry of Acute Cor-onary Events (GRACE), Platelet glycoprotein IIb/IIIa inUnstable angina: Receptor Suppression Using Integrilin(PURSUIT) and Thrombolysis In Myocardial Infarction(TIMI) scores are well-validated models that integratemultiple clinical variables to predict outcomes in thispopulation [1]. In contrast, the Synergy Between PCIWith Taxus and Cardiac Surgery (SYNTAX) score is ananatomical-based model similar to the ACC/AHA Classi-fication System for angiographic prediction of outcomeand is designed to help in deciding the optimal strategy ofrevascularization in complex coronary artery disease(CAD) [2]. The Acute Catheterization and Urgent Inter-vention Triage strategY (ACUITY) trial, subgroup ofNSTE-ACS patients treated with urgent percutaneous re-vascularization, showed that the SYNTAX score was anindependent predictor of 1-year mortality, cardiac death,acute MI, and target vessel revascularization on multivari-ate analysis. Furthermore, the Clinical SYNTAX score[3], achieved by combining the SYNTAX Score with amodified age, creatinine, and ejection fraction (ACEF)score has been shown to perform better than purely clini-cal scores in predicting cardiac death, major adverse car-diac and cerebrovascular events (MACCE), stentthrombosis, MI, and target vessel revascularization in theACUITY trial [4]. Although the utility of these variousmodels in risk assessment is well proven, they are notdesigned to predict the severity of CAD, a variable thatintuitively can be meaningfully associated with outcomes.

In this issue of Catheterization and CardiovascularInterventions, Beigel et al. [5] point out that current riskscores for NSTE-ACS may fail to identify some patientswith severe CAD. The study aims at identifying predictorsof high-risk coronary anatomy (HRCA)—defined as leftmain disease >50% diameter stenosis, proximal left ante-rior descending (LAD) lesion >70%; or 2–3 vessel diseaseinvolving the LAD—and evaluating their impact on prog-nosis. This retrospective study based on the nationwideregistry Acute Coronary Syndrome Israeli Survey included923 patients with NSTE-ACS who underwent coronary ar-teriography. Multivariable analysis revealed that the pres-ence of peripheral vascular disease, GRACE score> 140,and chronic renal disease were the strongest predictors ofHRCA. Among 370 patients found to have HRCA, 85patients (23%) did not meet criteria for an early invasivestrategy solely using GRACE score> 140, ST-segmentdepressions on electrocardiography, positive cardiac bio-markers, or Killip Class �2 on admission. The prognosticimplications of these findings are important as patients withHRCA had more in-hospital complications such as cardio-genic shock and pulmonary edema and higher frequency ofmoderate to severe mitral regurgitation, need for surgicalrevascularization, MACCE at 30 days, and mortality at 30days and at 1 year. Based on multivariate analysis, HRCAwas the strongest predictor of MACCE at 30 days.

This study raises the issue that relying solely on individ-ual risk stratification scores may fail to identify somepatients with severe CAD who would benefit from an earlyinvasive strategy. It makes sense that the “extent of dis-ease” can be distinct from “acuity of disease” with eachhaving important clinical implications. A few thought-provoking questions arise from this study. Should we rou-tinely assess HRCA scores in NSTE-ACS patients? Is itessential to identify patients early with low-risk clinicalscores but high-risk HRCA scores to improve outcomes, or

Conflict of interest: Nothing to report.

*Correspondence to: David J. Moliterno, MD, Department of Internal

Medicine, University of Kentucky, 900 South Limestone Avenue,

329 Wethington Building, Lexington, KY 40536-0200.

E-mail: [email protected]

Received 10 February 2014; Revision accepted 10 February 2014

DOI: 10.1002/ccd.25437

Published online 19 March 2014 in Wiley Online Library

(wileyonlinelibrary.com)

VC 2014 Wiley Periodicals, Inc.

Catheterization and Cardiovascular Interventions 83:684–685 (2014)

is this a subpopulation that will be identified with othermodalities like stress testing and, therefore, still be revascu-larized as needed? CAD and NSTE-ACS are complex mul-tivariable processes and using a comprehensive evaluativeapproach by combining clinical and anatomical variables topredict outcome is logical. With the evolving technologyand advances in treatment options, it is essential to con-stantly reevaluate our predictive models to improve ourability to quickly identify patients at risk of worse out-comes. A well-designed prospective study looking at theimplications of HRCA would help to further delineate thepredictive value of high-risk anatomy versus high-riskphysiology in NSTE-ACS.

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Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).