1. Improving Evidence-Based Care for Heart Failure in Outpatient Cardiology Practices: Primary Results of the Registry to Improve Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) Gregg C. Fonarow, Nancy M. Albert, Anne B. Curtis, Wendy Gattis Stough, Mihai Gheorghiade, J. Thomas Heywood, Mark L. McBride, Patches Johnson Inge, Mandeep R. Mehra, Christopher M. O'Connor, Dwight Reynolds Mary N. Walsh, Clyde W. Yancy Fonarow GC et al. Circulation. 2010;122:585-596

2. Disclosures Medtronic provided financial/material support for the IMPROVE HF registry but had no role or input into selection of endpoints or quality measures used in the study. Outcome Sciences, Inc, a contract research organization, independently performed the practice site chart abstractions for IMPROVE HF, stored the data, and provided benchmarked quality of care reports to practice sites. Outcome Sciences received funding from Medtronic. Individually identifiable practice site data were not shared with either the steering committee or the sponsor. Individual author disclosures are provided in the manuscript. Fonarow GC, et al. Circulation. 2010;122:585-596.

3. Heart Failure Care in the Outpatient Cardiology Practice Setting There are well documented gaps, variations, and disparities in the use of evidence-based, guideline recommended therapies for heart failure in inpatient and outpatient care settings. As a result many heart failure patients may have hospitalizations and fatal events that might have been prevented. Hospital-based performance improvement programs have improved the quality of care for heart failure patients. Similar programs in the outpatient setting have not been tested. Fonarow GC, et al. Circulation. 2010;122:585-596.

4. ACC/AHA 2005 HF Guidelines: Implementation of Guidelines Academic detailing or educational outreach visits are useful to facilitate the implementation of practice guidelines Chart audit and feedback of results can be effective to facilitate implementation of practice guidelines The use of reminder systems can be effective to facilitate implementation of practice guidelines The use of performance measures based on practice guidelines may be useful to improve quality of care Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org. I IIa IIb III

5. IMPROVE HF Study Overview Largest, most comprehensive performance improvement study for HF patients in the outpatient setting Designed to enhance quality of care of HF patients by facilitating adoption of evidence-based, guideline- recommended therapies: –Evaluate utilization rates of evidence-based, guideline- recommended HF therapies at baseline and over the course of the performance improvement intervention (chart audit and feedback; use of performance measures) –Multifaceted, practice-specific performance improvement toolkit including clinical decision support tools (reminder systems) –Sites attended an educational workshop to set treatment goals and develop a customized clinical care pathway (educational outreach) Fonarow GC et al. Am Heart J, 2007;154:12-38.

6. Methods: Guideline-Recommended Quality Measures Seven quality measures with strong evidence prospectively selected: –Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB)* –ß-blocker* –Aldosterone antagonist –Anticoagulation therapy for atrial fibrillation/flutter (AF)* –Cardiac resynchronization therapy with or without ICD (CRT) –Implantable cardioverter defibrillator with or without CRT (ICD) –Heart failure (HF) education* Patients deemed eligible for individual quality measure based on meeting guideline criteria, without contraindications, intolerance, or other documented reasons for non-treatment. Steering committee selected quality measures based on potential to improve patient outcomes, definition precision, construct and content validity, feasibility. * Included as ACC/AHA outpatient HF performance measure, endorsed by National Quality Forum. Fonarow GC, et al. Circulation. 2010;122:585-596.

7. Methods: Patient Selection, Practice Selection, Data Collection and Management Patient Inclusion: –Clinical diagnosis of HF or prior MI with at least 2 prior clinic visits within 2 years –LVEF ≤ 35% or moderate to severe left ventricular dysfunction Patient Exclusion: –Cardiac transplantation –Estimated survival <1 year from non-cardiovascular condition Average of 90 eligible patients per practice randomly selected for each of 3 study cohorts Practices: Outpatient cardiology (single specialty or multi-specialty) practices from all regions of the country Data quality measures –34 trained, tested chart review specialists –Training oversight by study steering committee members –Monthly quality reports –Automated data field range, format, unit checks Chart abstraction quality –Interrater reliability averaged 0.82 (kappa statistic) –Source documentation audit sample concordance rate range of 92.3% to 96.3% Coordinating center: Outcome Sciences, Inc. (Cambridge, MA) –Individual practice data not shared with sponsor or steering committee Fonarow GC, et al. Circulation. 2010;122:585-596.

8. Methods: Study Objectives Practice Level Patient Level Primary Analyses of Quality Measures: Changes for each of the 7 quality measures at 24 months XX ≥ 20% relative improvement in 2 or more quality measures at 24 months XXaXa Changes in 7 quality measures patients with both baseline and 24 month data XX Other Analyses: Changes in 2 summary care measures at 24 months XX Changes in 7 quality measures in single-time point cohorts compared with baseline XX Practice level analysis: proportion of eligible patients receiving therapy for each practice Patient level analysis: proportion of eligible patients receiving therapy for aggregate of all practices Fonarow GC, et al. Circulation. 2010;122:585-596. a Pre-specified primary objective

9. Methods: Study Design and Patient Disposition Longitudinal Cohort Two Single- Time-Point Cohorts Process Improvement Intervention (165 sites) Baseline Chart Review 167 sites 15,177 patients 12 Month Chart Review 155 sites 9,386 patients 24 Month Chart Review 155 sites 7,605 patients 6 Month Chart Review 154 sites 9,992 patients Total Sites167 Patients Enrolled34,810 Total Chart Reviews63,143 Total # of Site Visits782 18 Month Chart Review 151 sites 9,641 patients Longitudinal cohort included the same patients reviewed at 3 time points. Single-time-point cohorts included separate patients from the same practices and unique from the longitudinal cohort, as well as from each other. Fonarow GC, et al. Circulation. 2010;122:585-596.

10. Methods: Practice Specific Performance Improvement Intervention 1-day workshop after baseline data collected Included study goals, guidelines, intervention tool kit, performance improvement methods, tips to promote practice change, effective use of collected data. Guideline-based, clinical decision tool kit* Treatment algorithms, clinical pathways, standardized encounter forms, checklists, pocket cards, chart stickers, patient education materials. Tools available at www.ImproveHF.com. Web-based quality of care reports* Practice specific reports from chart audit data with benchmarking capability. Bimonthly educational, collaborative Web based seminars* Practice Survey: 96% adopted one or more performance improvement strategies 85% used benchmarked quality reports 60% employed one or more IMPROVE HF tools * Use or participation was encouraged but not mandatory. Practices could adopt or modify tools. Fonarow GC, et al. Circulation. 2010;122:585-596.

11. IMPROVE HF Practice Specific Education and Implementation Tools www.improvehf.com Evidence Based Algorithms and Pocket Cards Patient Education Materials Clinical Assessment and Management Forms Clinical Trials and Current Guidelines Dissemination of best practices: - Webcasts - Online Education - Newsletters

12. IMPROVE HF Performance Intervention: Benchmarked Practice Profile Report Benchmarking On-Demand Performance Measures across all physicians within practice Benchmarking Capability: region, practice, individual physician Practice or Single Physician Adherence to Guidelines

13. Patient Characteristics Longitudinal Cohort 18-Month Cohort N = 9,641 Characteristic All Patients N = 15,177 24-Month N = 7,605 Age, median, years70.071.070.0 Male, %71.171.370.7 Race: White, black, unavailable, %42.4, 9.2, 46.742.6, 9.0, 46.555.9, 11.5, 31.0 Insured, not documented, uninsured, %92.2, 6.3, 1.295.2, 3.7, 1.090.6, 7.6, 1.8 Heart failure origin, ischemic, %65.467.065.9 Prior MI, %40.051.741.6 History of CABG, %31.234.131.2 History of PCI, %25.630.029.1 History of atrial fibrillation/flutter, %30.741.234.0 History of peripheral vascular disease, %11.516.012.3 History of diabetes, %34.137.835.6 History of hypertension, %62.2 75.1 69.7 History of COPD, %16.721.818.0 History of depression, %9.015.710.7 Fonarow GC, et al. Circulation. 2010;122:585-596.

14. Patient Characteristics (Continued) Longitudinal Cohort 18-Month Cohort N = 9,641 Characteristic Baseline N = 15,177 24-Month N = 7,605 NYHA I, II, III, IV, unavailable, % 34.7, 36.6, 20.7, 2.6, 5.5 38.0, 43.5, 16.4, 1.4, 0.7 32.0, 44.8, 21.1, 1.6, 0.5 LVEF, median, %25.030.025.0 Systolic blood pressure, median, mmHg120 Diastolic blood pressure, median, mmHg70 Resting heart rate, median, bpm717072 Sodium, median, mEq/L139 Blood urea nitrogen, median, mg/dL22 21 Creatinine, median, mg/dL1.2 BNP, median, pg/mL387314373 QRS duration, median, ms 124 (n = 10,225) 132 (n = 3,788) 122 (n = 7,511) Fonarow GC, et al. Circulation. 2010;122:585-596.

15. IMPROVE HF Practice Characteristics CharacteristicPractice Sites (N = 167*) Census region: South, Northeast, Central, West, Missing, % 38.9, 32.3, 15.6, 12.0, 1.2 Practice setting: University, Non-university teaching, Non- university, non-teaching, % (n=157) 7.8, 21.6, 64.7 Multispecialty, % 24.0 Hospital-based, % 27.5 Transplant center, % 9.6 Suburban or rural location, % 71.3 HF clinic in practice, % (n=163) 41.3 HF nurse in practice, % 34.7 Device clinic in practice, % 78.4 No. of physicians in practice, 1-10, 11-20, >20, % 48.5, 27.5, 18.0 Number of electrophysiologists in practice, median 1.0 Interventionalist in practice, % 87.4 Annual number of patients managed by practice, median 1837.5 *Two sites did not provide any survey data. N=165 for these characteristics unless otherwise noted. Fonarow GC, et al. Circulation. 2010;122:585-596.

16. Results: Improvement in Quality Measures at 24 Months (Practice Level Analysis) Quality Measure Baseline (95% CI) N = 167 24 Months (95% CI) N = 155 Absolute Improvement (95% CI) Relative Improvement (95% CI) P-value ACEI/ARB 78.3% ( 76.5 – 80.2) 85.1% (83.4 – 86.8) + 6.8% (4.8 – 8.8) + 19.4% (-1.1 – 39.8) 0.063 ß -blocker 86.0% (84.3 – 87.7) 92.2% (90.6 – 93.8) + 6.2% (4.8 – 7.6) + 7.6% (5.1 – 10.2) <0.001 Aldosterone antagonist 34.5% (31.5 – 37.4) 60.3% (56.1 – 64.4) + 25.1% (20.7 – 29.6) + 86.5% (67.1 – 105.9) <0.001 Anticoagulation for AF 68.0% (65.5 – 70.5) 67.8% (65.0 – 70.7) - 0.1% (-3.0 – 2.8) + 1.0% (-3.6 – 5.5) 0.673 CRT-P/CRT-D 37.2% (32.2 – 42.2) 66.3% ( 61.6 – 71.1) + 29.9% (23.6 – 36.2) + 124.5% (85.5 – 163.5) <0.001 ICD/CRT-D 50.1% (47.3 – 52.8) 77.5% (74.8 – 80.1) + 27.4% (24.6 – 30.2) + 70.9% (61.0 – 80.8) <0.001 HF education 59.5% (55.7 – 63.2) 72.1% (68.3 – 75.9) + 12.6% (8.2 – 17.0) + 50.6% (27.1 – 74.2) <0.001 Longitudinal Cohort 123 of 155 practices (79%) with ≥ 20% relative improvement in 2 or more care measures Fonarow GC, et al. Circulation. 2010;122:585-596.

17. Results: Improvement in Quality Measures at 24 Months (Patient Level Analysis) Quality Measure Baseline (95% CI) N = 15,177 24 Months (95% CI) N = 7,605 Absolute Improvement (95% CI) Relative Improvement (95% CI) P-value ACEI/ARB 79.8% ( 79.2 – 80.5) 86.5% (85.6 – 87.3) + 6.7% (5.6 – 7.8) + 8.4% (7.0 – 9.7) <0.001 ß -blocker 86.2% (85.6 – 86.8) 93.6% (93.0 – 94.2) + 7.4% (6.6 – 8.2) + 8.6% (7.7 – 9.6) <0.001 Aldosterone antagonist 34.4% (32.7 – 36.1) 61.8% (59.2 – 64.5) + 27.4% (24.3 – 30.6) + 79.7% (70.5 – 89.0) <0.001 Anticoagulation for AF 68.6% (67.2 – 70.0) 69.3% (67.5 – 71.0) + 0.7% (-1.5 – 2.9) + 1.0% (-2.2 – 4.2) 0.546 CRT-P/CRT-D 37.7% (35.2 – 40.1) 68.5% ( 65.8 – 71.3) + 30.9% (27.2 – 34.5) + 81.9% (72.2 – 91.7) <0.001 ICD/CRT-D 48.8% (47.8 – 49.8) 79.1% (78.0 – 80.2) + 30.3% (28.8 – 31.8) + 62.1% (59.1 – 65.1) <0.001 HF education 61.8% (61.0 – 62.5) 70.8% (69.8 – 71.9) + 9.1% (7.8 – 10.4) + 14.7% (12.6 – 16.8) <0.001 Longitudinal Cohort Prespecified primary objective met: Relative improvement ≥ 20% in 3 quality measures Fonarow GC, et al. Circulation. 2010;122:585-596.

18. Results: Improvement in Quality Measures at 24 Months (Patient Level Analysis) Eligible Patients Treated Fonarow GC, et al. Circulation. 2010;122:585-596. * P<0.001 vs. baseline Significant Improvement in 6 of 7 Quality Measures at 12 and 24 Months Pre-specified Primary Objective Met: Relative Improvement ≥ 20% in 3 Quality Measures P-values are for relative change

19. Longitudinal Cohort with Complete Follow-up at 24 Months: Modified Intention to Treat Analyses Quality Measure Baseline (95% CI) N = 7,605 24 Months (95% CI) N = 7,605 Absolute Improvement (95% CI) Relative Improvement (95% CI) P-value ACEI/ARB 83.0% ( 82.1 – 83.8) 86.5% (85.6 – 87.3) + 3.5% (2.3 – 4.8) + 4.3% (2.8 – 5.7) <0.001 ß -blocker 88.5% (87.7 – 89.2) 93.6% (93.0 – 94.2) + 5.1% (4. – 6.1) + 5.8% (4.7 – 6.9) <0.001 Aldosterone antagonist 35.4% (32.8 – 38.1) 61.8% (59.2 – 64.5) + 26.4% (22.6 – 30.1) + 74.4% (63.9 – 84.9) <0.001 Anticoagulation for AF 72.2% (70.3 – 74.1) 69.3% (67.5-71.0) - 2.9% ( - 5.5 – - 0.3) - 4.1% -7.7 – - 0.5) 0.026 CRT-P/CRT-D 41.2% (37.4 – 44.9) 68.5% ( 65.8 – 71.3) + 27.4% (22.7 – 32.0) + 66.5% (55.2 – 77.7) <0.001 ICD/CRT-D 54.4% (53.0 – 55.8) 79.1% (78.0 – 80.2) + 24.7% (23.0 – 26.5) + 45.4% (42.4 – 48.6) <0.001 HF education 59.7% (58.6 – 60.8) 70.8% (69.8 – 71.9) + 11.2% (9.7 – 12.7) + 18.7% (16.2 – 21.2) <0.001 Patient Level Analysis Improvement in 6 of 7 Quality Measures Fonarow GC, et al. Circulation. 2010;122:585-596.

20. Newly Documented Contraindications/Intolerance and Newly Treated patients at 24 months—Paired Longitudinal Cohort Quality Measure Newly documented contraindication/ Intolerance at 24 mo. in patients initially eligible at baseline (N=7,605), % Newly treated at 24 mo. in patients initially eligible at baseline (N=7,605), % Newly treated at 24 mo. in patients not initially eligible at baseline, but eligible at 24 mo. ACEI/ARB9.8% ( 699/7138) 7.6% (546/7138) 67.1% (49/73) ß -blocker 5.5% (381/6905) 6.3% (434/6905) 83.9% (208/248) Aldosterone antagonist 16.4% (210/1278) 10.3% (132/1278) 54.2% (396/730) Anticoagulation for AF 8.8% (181/2061) 6.9% (143/2061) 58.1% (493/848) CRT-P/CRT-D1.8% (12/673) 23.5% ( 158/673) 59.3% (377/636) ICD/CRT-D3.9% (198/5028) 15.3% (769/5028) 71.1% (857/1205) HF education0.0% (0/7605) 26.3% (2003/7605) 0.0% (0/0) Fonarow GC, et al. Circulation. 2010;122:585-596.

21. Results: Summary Measures Significantly Improved at the Patient Level Fonarow GC, et al. Circulation. 2010;122:585-596.

22. Single Time Point Cohorts: Improvement at 18 Months Quality Measure Baseline (95% CI) N = 15,177 18 Months (95% CI) N = 7,605 Absolute Improvement (95% CI) Relative Improvement (95% CI) P-value ACEI/ARB 79.8% ( 79.2 – 80.5) 81.3% (80.5 – 82.1) + 1.5% (0.4 – 2.5) + 1.9% (0.5 – 3.2) 0.006 ß -blocker 86.2% (85.6 – 86.8) 91.9% (91.3 – 92.5) + 5.7% (4.9 – 6.6) + 6.7% (5.7 – 7.6) <0.001 Aldosterone antagonist 34.4% (32.7 – 36.1) 38.0% (35.8 – 40.3) + 3.6% (0.8 – 6.5) + 10.6% (2.3 – 18.8) 0.012 Anticoagulation for AF 68.6% (67.2 – 70.0) 69.9% (68.2 – 71.5) + 1.3% ( - 0.9 – 3.5) + 1.9% ( - 1.3 – 5.1) 0.237 CRT-P/CRT-D 37.7% (35.2 – 40.1) 44.1% ( 41.1 – 47.1) + 6.4% (2.6 – 10.3) + 17.1% (6.8 – 27.4) 0.001 ICD/CRT-D 48.8% (47.8 – 49.8) 55.9% (54.7 – 57.0) + 7.0% (5.5 – 8.6) + 14.4% (11.3 – 17.6) <0.001 HF education 61.8% (61.0 – 62.5) 75.8% (75.0 – 76.7) + 14.1% (12.9 – 15.2) + 22.8% (20.9 – 24.7) <0.001 Fonarow GC, et al. Circulation. 2010;122:585-596. Patient level analysis Directionally similar, smaller magnitude improvements than longitudinal cohort

23. Study Limitations Patient eligibility and utilization rates determined by accuracy and completeness of medical records and their abstraction –Reasons for preventing treatment may not have been documented Potential for ascertainment bias –Self-selected cardiology practices, primary care setting not included Not randomized—secular trends may have influenced results Follow-up not available for all patients –Practices dropped out, patients died or were lost to follow-up –Paired analyses revealed similar improvements Clinical outcomes could not be evaluated with the design Unable to measure use of therapies outside of guidelines Relative efficaciousness of intervention components could not be determined Fonarow GC, et al. Circulation. 2010;122:585-596.

24. Conclusions IMPROVE HF is the largest outpatient cardiology heart failure practice performance improvement program. Implementation of a defined and scalable performance improvement intervention may improve the use of evidence-based, guideline-recommended heart failure therapies in real-world cardiology practices. Study findings may serve as a model for existing and future performance improvement programs. Fonarow GC, et al. Circulation. 2010;122:585-596.

25. Clinical Implications Implementation of a defined and scalable practice specific performance improvement intervention enhances use of evidence-based, guideline-recommended HF therapies demonstrated to improve outcomes In all care settings where HF patients are managed, programs to provide practitioners with useful reminders based on the guidelines and to continuously assess the success achieved in providing these recommended therapies to the patients who can benefit from them should be implemented Fonarow GC, et al. Circulation. 2010;122:585-596.

26. IMPROVE HF Performance Improvement Tools As part of an enhanced treatment plan, IMPROVE HF provided evidence-based best-practices algorithms, clinical pathways, standardized encounter forms, checklists, pocket cards, chart stickers, and patient education and other materials to facilitate improved management of outpatients with HF. The materials can be downloaded from www.improvehf.com www.improvehf.com The materials are also included in the Circulation online-only Data Supplement Fonarow GC, et al. Circulation. 2010;122:585-596.