Poster TitleAngiographic Validation of the American College of Cardiology Foundation-The Society of Thoracic

Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies (ASCERT) StudyAnjan K. Chakrabarti, M.D.; Maria V Grau-Sepulveda, M.D., M.P.H.; Sean O’ Brien, Ph.D.; Cassandra Abueg, M.P.H.; Angelo Ponirakis, Ph.D.; Elizabeth Delong, Ph.D.; Eric Peterson, M.D.; Kirk N. Garratt, M.Sc., M.D.;

William S. Weintraub, M.D.; C. Michael Gibson, M.S., M.D.*From the Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (AC, CMG); PERFUSE Angiographic Core Laboratories and Data Coordinating Center, Beth Israel Deaconess Medical Center, Boston, MA (AC, CA, CMG); Duke Clinical Research Institute,

Duke University, Durham, NC (MVG-S, SO, ED, EP); American College of Cardiology, Washington, DC (AP); Northshore-LIJ/Lenox Hill Hospital, New York, NY (KG); Christiana Care Health System (WSW)

ABSTRACT

• Background: The goal of this study was to compare angiographic interpretation of coronary arteriograms by sites in community practice versus those made by a centralized angiographic core laboratory.

• Methods: The primary analysis compared Registry (NCDR®) defined 2- and 3-vessel disease vs. those from an angiographic core laboratory analysis.

• Results: Vessel-level kappa coefficients suggested moderate agreement between NCDR® and core lab analysis, ranging from kappa = 0.39 (95% CI 0.32-0.45) for the left anterior descending artery to kappa = 0.59 (95% CI 0.55-0.64) for the right coronary artery. Overall, 6.3% (n= 127/2013) of those patients identified with multi-vessel disease at NCDR® sites had had 0- or 1-vessel disease by core lab reading. There was no direction bias with regard to “overcall.”

• Conclusions: There was only modest agreement between angiographic readings in clinical practice and those from an independent core laboratory.

OBJECTIVES

• Prior analyses of the appropriateness of coronary interventions have assumed that the clinical site’s assessment of disease extent and left main severity are accurate, and the angiograms have generally not been independently verified by a core laboratory.1-5

• The American College of Cardiology Foundation (ACCF), the Society of Thoracic Surgeons (STS), and the Duke Clinical Research Institute (DCRI) are collaborating on a comparative effectiveness study (ASCERT) of coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI).6,7

• An additional aim of ASCERT is to develop novel, long-term mortality risk prediction models for CABG and PCI.8,9 The clinical sites’ assessment of disease extent is included in these models, and the quality of the sites clinical interpretation of the angiogram is therefore integral to the validity of this model.

• The goal of the present study was to assess the rate of concordance between clinical sites and an independent angiographic core laboratory in their interpretation of the angiogram, and to determine if discordance among interpreters served as a marker for poor clinical outcomes.

RESULTS

CONCLUSION

REFERENCES

METHODS

Disclosures: The primary author has no conflicts of interest to disclose. Dr. Peterson has received consulting fees and honoraria from Janssen, Genentech, Boehringer Ingelheim as well as research grants from Eli Lilly, Janssen. Dr.. Weintraub has received consulting fees and honoraria from Eli Lilly, Bristol Myers Squibb, Pfizer, and Amarin. Dr. Gibson has received consulting fees and honoraria from Johnson & Johnson Corp., Bayer Corporation, Ischemix, Inc., BCRI, Sanofi-Aventis Corp., Genentech, Inc. , Merck & Co., CSL Behring, Biogen Idec, Daiichi Sankyo, Inc., Bristol Meyer Squibb, The Medicines Company, Janssen Pharmaceuticals, Inc, Regado Biosciences, Inc., St. Jude Medical Corp., Ortho McNeil, Portola Pharmaceuticals, Eli Lilly and Company, and GlaxoSmithKline, as well as research grants from Lantheus Medical Imaging, Janssen Pharmaceuticals, Inc, Bayer Corporation, Genentech Inc., Merck & Co. , Atrium Medical Systems, Roche Diagnostics, Ikaria, Inc., Portola Pharmaceuticals, Johnson & Johnson Corp., Angel Medical Corporation, Volcano Corp., Stealth Peptides, Sanofi-Aventis, Walk Vascular , and St. Jude's Medical, as well as other financial support from UpToDate in Cardiovascular Medicine. All other co-authors have no conflicts to disclose.

• The sampling scheme for the SYNTAX substudy is described in Figure 2.

• The primary endpoint was a vessel-based analysis evaluating the rate of concordance (i.e. the kappa coefficient) between the site and the core laboratory as to whether a significant (>50%) lesion was present by visual assessment anywhere in the vessel.

• Clinical outcomes including death and recurrent myocardial infarction (MI) were evaluated for patients with “overcalled” left main disease (i.e. patients with left main disease by registry analysis but not by core-lab analysis) compared to those with left main agreement.

Figure 2: Study population. Records available from SYNTAX study with angiographic analysis performed at the PERFUSE angiographic core lab.

• There was no direction bias with regard to “overcall,” i.e. 12.3% of cases read as 3-vessel disease by the sites were read as < 3-vessel disease by the core lab and 13.9% of core lab 3-vessel cases were read as <3-vessel by the sites.

Table 1: Analysis of agreement on vessel-level results. Kappa coefficients are presented demonstrating whether there is agreement regarding the showing presence/absence of stenosis as determined by PERFUSE vs. CATHPCI.

*Disease is defined as vessel stenosis >50%

• Vessel-level data focusing on left main disease demonstrated that 11.2% (17/152) of the cases called as left main disease by the core lab were deemed normal by registry data (core-lab “overcall”), whereas 56.7% (177/312) that were read as left main disease by the registry but had no left main lesion by core-lab analysis (registry “overcall”).

• Survival analysis was performed evaluating the clinical outcomes of death and recurrent MI as they relate to both negatively concordant left main disease and registry “over-call” of left main disease (Figure 3A and 3B). There was no statistically significant difference between groups

Figure 3A and 3B: Analysis of clinical outcomes by left main agreement. Survival curves were estimated using the Kaplan-Meier method for censored data. Follow-up time was administratively censored on 31st December 2008. For MI, patients who died were retained in the denominator, i.e, these patients were not censored on date of death. The resulting KM curves are interpreted as “actual” rather than “actuarial” probabilities. The log-rank test evaluates if there is difference between the survival curves. (A) is the Kaplan-Meier curve for the outcome of death, and (B) is the curve for recurrent myocardial infcarction.

There was modest agreement between angiographic readings in clinical practice and those from an independent core laboratory. Further study will be needed as the implications for patient management are uncertain.

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appropriateness and in-hospital procedural outcomes: Insights from the ncdr. Circ Cardiovasc Qual Outcomes. 2012;5:290-2975. Marso SP, Teirstein PS, Kereiakes DJ, Moses J, Lasala J, Grantham JA. Percutaneous coronary intervention use in the united states: Defining measures of appropriateness.

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Shahian DM, Grover FL, Mayer JE, Shewan CM, Garratt KN, Moussa ID, Dangas GD, Edwards FH. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366:1467-1476

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8. Weintraub WS, Grau-Sepulveda MV, Weiss JM, Delong ER, Peterson ED, O'Brien SM, Kolm P, Klein LW, Shaw RE, McKay C, Ritzenthaler LL, Popma JJ, Messenger JC, Shahian DM, Grover FL, Mayer JE, Garratt KN, Moussa ID, Edwards FH, Dangas GD. Prediction of long-term mortality after percutaneous coronary intervention in older adults: Results from the national cardiovascular data registry. Circulation. 2012;125:1501-1510

9. Shahian DM, O'Brien SM, Sheng S, Grover FL, Mayer JE, Jacobs JP, Weiss JM, Delong ER, Peterson ED, Weintraub WS, Grau-Sepulveda MV, Klein LW, Shaw RE, Garratt KN, Moussa ID, Shewan CM, Dangas GD, Edwards FH. Predictors of long-term survival after coronary artery bypass grafting surgery: Results from the society of thoracic surgeons adult cardiac surgery database (the ascert study). Circulation. 2012;125:1491-1500Figure 1: Left Main Disease. Is there greater than 50% LM disease? This angiogram illustrates the potential of intra-

and inter-observer variability

• Table 1 depicts agreement between NCDR and core lab data at the vessel level. All kappa coefficients presented fall in the range of at most moderate agreement, with the highest kappa values occurring in right coronary artery group (kappa = 0.59, 95% CI 0.55-0.64).