International Society for Heart and Lung Transplantation (ISHLT) Registries

Supplementary document.

This document provides a brief outline of the structure, aims and future goals of five prominent and representative registries in the cardiac, pulmonary and vascular fields.

The aim is not to provide comprehensive coverage of different registries, but to identify successful approaches, best practices and opportunities for registries in the current era.

International Society for Heart and Lung Transplantation (ISHLT) Registries.

The history and structure of the ISHLT International Registry for Heart and Lung

Transplantation has been reviewed previously [1]. The Registry was presciently started by the Society shortly after its founding in 1983, recognizing the relative rarity of heart and lung transplantation procedures and the need to collaborate globally to advance this new clinical field. The Registry has since become the largest repository for thoracic transplantation data in the world - forty countries have contributed data on close to

200,000 thoracic transplant procedures. Participation in the Registry takes place either through partnerships with national or regional transplant organizations, which collect and then submit to ISHLT data for multiple transplant centers, or through individual center participation in countries where national or regional transplant registries are not well established. Participation in the registry is voluntary and participating centers absorb data entry costs, often by closely integrating data entry with routine care, whereas the ISHLT covers operating costs for the Registry.

The ISHLT has also initiated registry initiatives beyond heart and lung transplant care.

The expanding clinical application of mechanical circulatory support (MCS) in the 1990s lead to an acute clinical need to gather information, beyond what was available through

MCS clinical trials, to learn more about patient and device selection, treatment processes and benchmarks for this rapidly evolving field. The ISHLT Mechanical

Circulatory Support Device Database was established in 2001 and has since been superseded by the ISHLT International Mechanically Assisted Circulatory Support

Registry (IMACS). IMACS collects data through an approach similar to the Thoracic

Transplant Registry, and has collected data on >10,000 patients who received treatment with durable MCS, for indications not limited to bridge to transplant therapy, and including permanent (destination) therapy and bridge to recovery [2].

The ISHLT has established a formal process for establishing new registries and has formed a Registries and Databases Committee that oversees registry activities of the

Society and works closely with the individual registry Steering Committees. New areas have been identified as in need of information best obtained through coordinated registry work; ISHLT has initiated a Donation after Circulatory Death (DCD) Registry and an International Pediatric Heart Failure Registry (iPHFR) [2-7]. Results of registry work are presented through annual reports [8], and through in depth hypothesis driven analyses led by investigators throughout the world. The ISHLT strategic planning process also provided the registries with goals to further enhance the value of the registries to individual hospitals and explore joint initiatives with industry.

Society for Vascular Surgery Vascular Quality Initiative.

The Society for Vascular Surgery (SVS) has taken a somewhat different approach to creating registry initiatives in vascular care. In 2011, the SVS launched the Vascular

Quality Initiative® (VQI) in the US with a mission to improve the quality, safety, effectiveness and cost of vascular healthcare by collecting and exchanging information

[9]. VQI uses 12 distinct registries to collect granular clinical data for major vascular procedures used to treat carotid, aortic and lower extremity arterial disease, dialysis access, venous embolism and varicose veins. The VQI was organized as a Patient

Safety Organization (PSO) to ensure a focus on quality improvement and to provide important safeguards for data confidentiality, and is structured as a network of 18 regional quality improvement groups [10]. The regional groups meet semi-annually to discuss center variation in practices and outcomes, and develop and coordinate regional quality improvement initiatives. This structure gives the members a ‘voice' and ability to translate national registry data into quality projects and practice change, in a personal and effective manner. In partnership with M2S, Inc., VQI uses a web-based platform to collect data which is then converted to aggregate benchmark reports for participating centers and physicians. Composite data identify center variation in practices and outcome, and are used to develop regional quality improvement projects.

Nearly 400 centers with over 3,000 physicians in the US participate in VQI. Since 2011, data from over 300,000 vascular procedures, including 1-year follow-up, have been collected and audited against claims data to insure completeness of submissions.

Participation in the VQI is voluntary and is funded by participating centers or physician groups. The VQI work is enabled by a number of committees, registry staff and the activities are overseen by a Governing Council. The SVS PSO provides numerous reports to centers, physicians and regional groups to stimulate quality improvement, for example by identifying patient, physician and procedural factors associated with optimal outcome, and providing each center with their individualized actionable report that identifies specific targets for improvement. The PSO structure of VQI protects comparative benchmarking reports from discovery in courts, which promotes accurate reporting of baseline data and outcomes, and also waives the requirement of institutional review board approval and need for patient informed consent, which reduces administrative burden to the participating centers. The VQI has to date completed more than 200 quality improvement projects and this work has resulted in

100 peer-reviewed publications [11]. VQI has also partnered with the FDA and industry to provide registry data to help meet regulatory requirements providing the value of VQI registry activities to additional stakeholders.

Upcoming VQI initiatives will include the use of Centers for Medicare and Medicaid

(CMS) claims data matched with VQI clinical data to determine outcome events beyond

1 year follow-up; capture of hospital billing data to derive procedural and device costs that allow value and cost-effectiveness calculations; extraction of data directly from electronic health records (EHR), and development of measures that focus on appropriateness as well as quality of care.

Society of Thoracic Surgeons National Database.

The Society of Thoracic Surgeons National Database (STS-ND) was established in

1989 as an initiative to enhance the quality and safety of cardiothoracic surgery and to provide an accurate and valid basis for measuring performance in cardiothoracic surgical care [12]. The STS-ND has three major component databases: the Adult

Cardiac Surgery Database (ACSD), the Congenital Heart Surgery Database (CHSD), and the General Thoracic Surgery Database (GTSD) [13, 14]. STS-ND also collaborates with the American college of Cardiology (ACC) to maintain the

Transcatheter Valve Therapy (TVT) Registry, which captures data about practice patterns and patient outcomes for transcatheter valve replacement and repair procedures. ACSD and CHSD capture data from over 90% of US hospitals that perform adult and pediatric cardiac surgery. In addition, a number of international hospitals also participate in data collection (Table 1).

Several STSND Task Forces (Figure A) actively interact with the three component databases, as well as the different STS councils, which allows for standardization and harmonization of data fields across the component databases - all data fields are explicitly defined, allowing for standard interpretation. The importance of harmonization is well illustrated by the definition of the seemingly self-explanatory data field of operative mortality as (1) all deaths, regardless of cause, occurring during the hospitalization in which the operation was performed, even if after 30 days (including patients transferred to other acute care facilities); and (2) all deaths, regardless of cause, occurring after discharge from the hospital, but before the end of the 30th postoperative day [15, 16].

The Duke Clinical Research Institute (DCRI) is the data warehouse and analytic center for all STS databases. Participating sites pay a fee to participate in STS-ND.

The STS-ND supports research, quality improvement, and the transparent sharing of data via public reporting. STS-ND work has generated multiple funded research awards and several hundred peer reviewed publications [17, 18]. Importantly, research focused on outcomes has highlighted variations of care among centers participating in STS-ND

(Figure B) [19], which in turn has informed quality improvement initiatives. The leadership of STS in the area of quality measurement is demonstrated by the commitment of STS to obtain endorsement for all its performance measures by the

National Quality Forum (NQF). STS is currently the steward of 34 NQF-endorsed measures – more than any other specialty based medical professional organization [12].

Participating sites receive regular Feedback Reports that compare their outcomes to national aggregate outcomes. Finally, STS-ND functions as a platform for public reporting of cardiothoracic surgical outcomes [20]. As of March 2016, 49% of participants in ACSD and 60% of participants in CHSD have agreed to publicly report their outcomes trough the STS Public Reporting Online website [21].

Some of the goals for the future include transforming of STS-ND into a platform for long- term longitudinal follow-up, utilizing STS-ND for longitudinal device surveillance, adding links to multiple new sources of complementary data (e.g. CMS Medicare data, data from the National Index and Social Security Death master File) to support longitudinal comparative effectiveness research and health care economics research, and adding patient reported outcomes and longitudinal functional status to increase the patient- centeredness of STS-ND.

European Society of Cardiology EURObservational Research Programme.

The European Society of Cardiology (ESC) operates the EURObservational Research

Programme (EORP), started in 2008. The EORP goals are to describe Cardiology practice in Europe through partnership with ESC constituent bodies – national societies, associations and working groups. The key opportunities of this work are to evaluate implementation of safe and effective care as reflected in the ESC Guidelines in Europe and to become the reference center for European authorities and agencies for issues concerning cardiac care.

EORP runs three types of registries with distinct goals (Figure C): 1. General registries assess the management of diseases with major epidemiologic impact. Participation in this activity is assigned through national bodies to achieve a representative sample of patients across Europe. Data is entered through electronic case report forms (CRFs).

2. Sentinel Registries assess the impact of new tools or therapeutic and diagnostic procedures. Participation is center-based, and the key goals are to address safety, efficacy, and cost-effectiveness of the new approaches of interest. 3. Specific Registries assess orphan/rare or highly demanding syndromes as far as high risk for morbidity or mortality, high costs or complex management. Participation is center-based and the goal is to establish best practices for these syndromes. In addition, EORP is in charge of the EUROASPIRE registry on cardiovascular prevention.

EORP is governed by an Oversight Committee, a central registry operation directed by the Executive Committee of the ESC. Data collection at a national or center level is overseen by Steering Committees. Data collection is centralized at the ESC Heart

House, where EORP staff are responsible for providing organizational support to the centers, preparation of electronic CRFs, data quality control, communication between all stakeholders, and scientific and statistical analyses. While the Executive and Oversight

Committees of EORP oversees analysis and publication of composite data (more than

50 publications have resulted from this work), the national databases are available for local analysis and publication. Recent examples of EORP scientific work include a report from the heart failure long-term registry [22], assessment of risk of pregnancy in women with cardiac disease [23] and assessment of guideline adherence in atrial fibrillation [24]. EORP activities are funded through ESC and through industry sponsorship. To maintain academic independence, industry sponsors are not able to support individual registries, but are encouraged to provide sponsorship for the overall

EORP initiative for a minimum of three years.

Future goals for EORP include even more integrated role in the ESC ‘virtuous circle’ of collaboration among three ESC entities: ESC Guidelines and Textbook, Education and

Registries. ESC Guidelines and Textbook represents the core of the knowledge, based on which educational material is developed in order to best implement the ESC

Guidelines. Registries will be planned to run in 2-year cycles, focusing on the topic of each main ESC guideline. The overall aim is to evaluate gaps in the implementation of these guidelines, as well as to assess performance outcomes. The registries will then serve to assess the needs for the next set of guidelines.

American College of Cardiology National Cardiovascular Data Registry

The National Cardiovascular Data Registry (NCDR), sponsored by the ACC in partnership with other professional societies, is comprised of 10 national cardiovascular quality programs (Table 2) [25]. The first, CathPCI, was established in 1998 to focus on the quality of care for patients undergoing cardiac catheterization and percutaneous coronary interventions (PCI). Since then, NCDR has expanded to include other common cardiovascular procedures, high-impact conditions, and ambulatory care. These programs are now deployed in more than 2,000 US hospitals and 540 ambulatory practices, and include more than 59 million clinical records. The NCDR programs are also used internationally, currently in 17 institutions in 9 countries beyond the US.

The mission of the NCDR is ‘to improve the quality of cardiovascular patient care by providing information, knowledge and tools; implementing quality initiatives; and supporting research that improves patient care and outcomes’. The principal role of the programs is to provide feedback with national benchmarks on a broad range of process and outcomes metrics to participating sites as a means of stimulating quality improvement. NCDR has also supported national quality initiatives, such as the Door-to-

Balloon (D2B) program which focused on improving the time to PCI in patients with ST segment elevation myocardial infarction [26]. The programs have also generated health outcomes and quality research in cardiovascular disease, identifying gaps in evidence- based care [27], assessing observational effectiveness of therapies [28], and characterizing the incidence and risk factors for adverse outcomes [29-31]. More recently, the roles of NCDR have expanded to include support for stakeholders participating in post-market device approval and surveillance studies [32], CMS coverage with evidence decisions, state mandated reporting, health plan quality measurement, and randomized clinical trials [33].

Data for the NCDR hospital programs are collected by a combination of data capture from existing electronic systems and in some cases abstraction of medical records by quality personnel at participating sites. Data are submitted to the NCDR through data exports from certified electronic vendor platforms (e.g. catheterization laboratory hemodynamic systems). The two ambulatory programs extract data directly from EHR systems, employing a “system integrator” to standardize data across practices to the extent possible. The NCDR employs a rigorous data quality program, which includes abstractor training and support, completeness and range checks of submitted data, and audits of medical records [34].

To build on the past successes of NCDR, the ACC will continue to support local and national quality improvement initiatives; enhance integration with EHRs to reduce the burden of data collection for participants; expand the data quality program; continue collaboration with stakeholders in post-market approval and surveillance efforts; develop and deploy risk models to facilitate individualized decision-making; further conduct of timely quality of care and outcomes research; and support clinicians and hospitals in the transition to value-based reimbursement that will occur with the

Medicare Access & CHIP Reauthorization Act of 2015 (MACRA) [35]. Table legends.

Table 1. Participation in the STS National Database

Table 2. NCDR Programs. CAD – coronary artery disease; HF – heart failure; LAA – left atrial appendage; NSTEMI – non-ST-elevation myocardial infarction; STEMI – ST- elevation myocardial infarction

Figure Legends.

Figure A. The STS National Database cross-cutting, functional task forces.

Figure B. Standardized incidence ratio of mortality or major morbidity after lung cancer resection among STS National Database participating sites.

Figure C. Structure of the EURObservational Research Programme. References. 1. Stehlik, J., et al., ISHLT International Registry for Heart and Lung Transplantation - three decades of scientific contributions. Transplantation reviews, 2013. 27(2): p. 38-42. 2. Kirklin, J.K., et al., First Annual IMACS Report: A global International Society for Heart and Lung Transplantation Registry for Mechanical Circulatory Support. J Heart Lung Transplant, 2016. 35(4): p. 407-12. 3. Stehlik, J., et al., The International Society for Heart and Lung Transplantation Registries in the Era of Big Data With Global Reach. J Heart Lung Transplant, 2015. 34(10): p. 1225-32. 4. Dipchand, A.I., et al., The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant, 2015. 34(10): p. 1233-43. 5. Goldfarb, S.B., et al., The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant, 2015. 34(10): p. 1255-63. 6. Yusen, R.D., et al., The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant, 2015. 34(10): p. 1264-77. 7. Cypel, M., et al., International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report. J Heart Lung Transplant, 2015. 34(10): p. 1278-82. 8. Lund, L.H., et al., The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant, 2015. 34(10): p. 1244-54. 9. Cronenwett, J.L., L.W. Kraiss, and R.P. Cambria, The Society for Vascular Surgery Vascular Quality Initiative. J Vasc Surg, 2012. 55(5): p. 1529-37. 10. Woo, K., et al., Regional quality groups in the Society for Vascular Surgery(R) Vascular Quality Initiative. J Vasc Surg, 2013. 57(3): p. 884-90. 11. De Martino, R.R., et al., Preoperative antiplatelet and statin treatment was not associated with reduced myocardial infarction after high-risk vascular operations in the Vascular Quality Initiative. J Vasc Surg, 2016. 63(1): p. 182-9 e2. 12. Jacobs, J.P., et al., Introduction to the STS National Database Series: Outcomes Analysis, Quality Improvement, and Patient Safety. Ann Thorac Surg, 2015. 100(6): p. 1992-2000. 13. 2. STS National Database. [http://www.sts.org/national-database%5D. Accessed July 20, 2016. 14. Grover, F.L., et al., The STS National Database. Ann Thorac Surg, 2014. 97(1 Suppl): p. S48-54. 15. Overman, D.M., et al., Report from the Society of Thoracic Surgeons National Database Workforce: clarifying the definition of operative mortality. World J Pediatr Congenit Heart Surg, 2013. 4(1): p. 10-2. 16. Jacobs, J.P., et al., What is operative mortality? Defining death in a surgical registry database: a report of the STS Congenital Database Taskforce and the Joint EACTS-STS Congenital Database Committee. Ann Thorac Surg, 2006. 81(5): p. 1937-41. 17. Wright, C.D., et al., Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. J Thorac Cardiovasc Surg, 2009. 137(3): p. 587-95; discussion 596. 18. Costello, J.M., et al., Gestational age at birth and outcomes after neonatal cardiac surgery: an analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Circulation, 2014. 129(24): p. 2511-7. 19. Kozower, B.D., et al., STS database risk models: predictors of mortality and major morbidity for lung cancer resection. Ann Thorac Surg, 2010. 90(3): p. 875- 81; discussion 881-3. 20. Shahian, D.M., et al., The Society of Thoracic Surgeons voluntary public reporting initiative: the first 4 years. Ann Surg, 2015. 262(3): p. 526-35; discussion 533-5. 21. http://www.sts.org/quality-research-patient-safety/sts-public-reporting-online. Accessed July 20, 2016. 22. Crespo-Leiro, M.G., et al., European Society of Cardiology Heart Failure Long- Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail, 2016. 18(6): p. 613-25. 23. van Hagen, I.M., et al., Global cardiac risk assessment in the Registry Of Pregnancy And Cardiac disease: results of a registry from the European Society of Cardiology. Eur J Heart Fail, 2016. 18(5): p. 523-33. 24. Lip, G.Y., et al., Improved outcomes with European Society of Cardiology guideline-adherent antithrombotic treatment in high-risk patients with atrial fibrillation: a report from the EORP-AF General Pilot Registry. Europace, 2015. 17(12): p. 1777-86. 25. Li, J., et al., China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design. Chin Med J (Engl), 2016. 129(1): p. 72-80. 26. Bradley, E.H., et al., National efforts to improve door-to-balloon time results from the Door-to-Balloon Alliance. J Am Coll Cardiol, 2009. 54(25): p. 2423-9. 27. Masoudi, F.A., et al., Cardiovascular care facts: a report from the national cardiovascular data registry: 2011. J Am Coll Cardiol, 2013. 62(21): p. 1931-47. 28. Masoudi, F.A., et al., Comparative effectiveness of cardiac resynchronization therapy with an implantable cardioverter-defibrillator versus defibrillator therapy alone: a cohort study. Ann Intern Med, 2014. 160(9): p. 603-11. 29. Tsai, T.T., et al., Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry. JACC Cardiovasc Interv, 2014. 7(1): p. 1-9. 30. Rao, S.V., et al., An updated bleeding model to predict the risk of post-procedure bleeding among patients undergoing percutaneous coronary intervention: a report using an expanded bleeding definition from the National Cardiovascular Data Registry CathPCI Registry. JACC Cardiovasc Interv, 2013. 6(9): p. 897- 904. 31. Peterson, E.D., et al., Contemporary mortality risk prediction for percutaneous coronary intervention: results from 588,398 procedures in the National Cardiovascular Data Registry. J Am Coll Cardiol, 2010. 55(18): p. 1923-32. 32. Carroll, J.D., et al., The STS-ACC transcatheter valve therapy national registry: a new partnership and infrastructure for the introduction and surveillance of medical devices and therapies. J Am Coll Cardiol, 2013. 62(11): p. 1026-34. 33. Rao, S.V., et al., A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial. JACC Cardiovasc Interv, 2014. 7(8): p. 857-67. 34. Messenger, J.C., et al., The National Cardiovascular Data Registry (NCDR) Data Quality Brief: the NCDR Data Quality Program in 2012. J Am Coll Cardiol, 2012. 60(16): p. 1484-8. 35. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment- Instruments/Value-Based-Programs/MACRA-MIPS-and-APMs/MACRA-MIPS- and-APMs.html accessed 07.16.16.

STS National Database STS Adult Cardiac STS Congenital Heart STS General Thoracic Participation Surgery Database Surgery Database Database

Hospitals in USA (N) 1,105 124 353

Surgeons in USA (N) 2,937 361 883 Operations in USA 5,697,522 344,202 416,984 >90% of hospitals that Estimated penetrance at >95% of hospitals that perform perform adult heart Unknown hospital level in USA pediatric heart surgery surgery Percentage of programs Public reporting that voluntarily publicly 49% 60% planned for 2017 report Total countries, including 9 5 4 USA Hospitals outside USA 18 9 3 Surgeons outside USA 39 15 9 Operations outside USA 43,967 10,644 0 NCDR Program Sites Records Clinical Focus Clinical Setting (year established) (N) (N)

Percutaneous coronary intervention; Hospital or free-standing CathPCI (1998) 1,771 20,000,000 diagnostic coronary angiography catheterization laboratory

ICD (2005) Implantable cardioverter defibrillators Hospital 1,848 2,000,000 Peripheral arterial revascularization Hospital, free-standing PVI (2006) (including carotid artery stenting and catheterization laboratory 229 350,000 surgery) or vascular center ACTION-GWTG Acute coronary syndromes Hospital and Emergency 1,076 1,200,000 (2007) (STEMI and NSTEMI) Medical Services PINNACLE (2008) & Ambulatory patients with CAD, HF, 486 practices Diabetes Collaborative atrial fibrillation, hypertension, or Outpatient clinic 35,000,000 6,876 providers (2014) peripheral arterial disease Congenital heart disease, IMPACT (2009) undergoing cardiac catheterization Hospital 103 70,000 and/or structural intervention

STS/ACC TVT (2011) Transcatheter valve therapy Hospital 462 75,000

Diabetes Collaborative 329 practices Diabetes and cardiometabolic care Outpatient clinic 1,000,000 (2014) 4182 providers

LAAO (2016) LAA occlusion devices Hospital 159 N/A

AFAR (2016) Atrial fibrillation ablation Hospital 41 N/A