decompensated heart failure: lessons learned from the adhere regisry

1. DECOMPENSATED HEART FAILURE:LESSONS LEARNED FROM THE ADHERE REGISRY Maria Rosa Costanzo, M.D. Midwest Heart Specialists Medical Director, Edward Center for Advanced Heart Failure Naperville, Illinois, U.S.A.

3. Observational Studies Advantages All inclusive. Patients with co-morbidities, women of child bearing potential, elderly included. “Real-world” Can provide detailed information of patient characteristics, treatment strategies, and outcomes of interest With large numbers of patients can allow assessment of infrequent events or unusual patient populations Multiple analyses can be performed on same cohort. Assess interventions with and without commercial value Disadvantages Potential selection, observational, and investigator bias and can be confounded by variety of factors The ADHERE (Acute Decompensated Heart Failure National Registry) Registry Phase IV Multicenter Observational Open label Electronic web-based Registry of the management of patients treated in hospitals for acutely decompensated heart failure in the US

4. Goals of the ADHERE Registry Describe demographics and clinical characteristics of patients hospitalized with acutely decompensated heart failure (AHF) Characterize current management of hospitalized patients with AHF Define treatment strategies associated with best clinical outcomes and most efficient use of resources Assist in evaluating and improving the quality of care Slide 17 The ADHERE registry and tool kit will have a tremendous impact on improving the quality of care of patients hospitalized with heart failure, and fulfill the goals that we have set out for the ADHERE registry. Slide 17 The ADHERE registry and tool kit will have a tremendous impact on improving the quality of care of patients hospitalized with heart failure, and fulfill the goals that we have set out for the ADHERE registry.

5. The ADHERE Registry

6. Characteristics of Heart Failure Patients Enrolled in the ADHERE Registry Average age: 72.5 years Women: 52% Ischemic etiology (CAD): 60% Renal insufficiency: 30% Diabetes: 44% Preserved LV systolic function: ?50% Atrial fibrillation: 31% Diabetes: 44%

7. Crucial Link Between LV Assessment and ACEI Use

8. Utilization of Evidence-based Therapies in Heart Failure

9. ADHERE: Variation in ACEI Use

11. First (Geographic) Point of Care at Registry Hospital

12. IV Vasoactive Use

13. IV Vasoactive Use—Important Where Begun

14. IV Vasoactive Use—Important Where Begun

15. Most Common IV Medications All Enrolled Discharges (n=105,388) October 2001 to January 2004

16. IV Diuretic Use

17. Complications of Diuretic Therapy for Heart Failure Diuretic use in patients with heart failure is associated with a number of significant complications. When acutely decompensated heart failure is treated with IV diuretics without vasodilator therapy, there is reflex activation in the neurohumoral systems (SNS and RAAS), leading to vasoconstriction and elevation of SVR. The rise in SVR and the increased afterload lead to a fall in cardiac index and renal blood flow. This limits the ability to reduce PCWP to optimal levels. The reflex neurohumoral activation is also deleterious.1 Combining IV vasodilators with diuretics in the initial treatment of acutely decompensated heart failure limits the reflex vasoconstriction and prevents the fall in cardiac index. This allows for rapid relief of symptoms and achieves compensation. Diuretic use in patients with heart failure is associated with a number of significant complications. When acutely decompensated heart failure is treated with IV diuretics without vasodilator therapy, there is reflex activation in the neurohumoral systems (SNS and RAAS), leading to vasoconstriction and elevation of SVR. The rise in SVR and the increased afterload lead to a fall in cardiac index and renal blood flow. This limits the ability to reduce PCWP to optimal levels. The reflex neurohumoral activation is also deleterious.1 Combining IV vasodilators with diuretics in the initial treatment of acutely decompensated heart failure limits the reflex vasoconstriction and prevents the fall in cardiac index. This allows for rapid relief of symptoms and achieves compensation.

18. Marked Activation of the RAAS by Loop Diuretics Treatment of decompensated heart failure with loop diuretics increases plasma renin activity.1 Treatment of decompensated heart failure with loop diuretics increases plasma renin activity.1

19. Diuretic Therapy Significantly Decreases Glomerular Filtration Rate* This graph shows the relationship between the change in urine volume and creatinine clearance. When taken alone, furosemide caused an increase in urine output but a decrease in the glomerular filtration rate. Other studies also have shown this to be the case. It is hypothesized that adenosine release in the kidneys may cause these effects. This is consistent with the clinical observation that diuresis is mediated by worsening of renal function.1 This graph shows the relationship between the change in urine volume and creatinine clearance. When taken alone, furosemide caused an increase in urine output but a decrease in the glomerular filtration rate. Other studies also have shown this to be the case. It is hypothesized that adenosine release in the kidneys may cause these effects. This is consistent with the clinical observation that diuresis is mediated by worsening of renal function.1

20. Vasodilation Is Required to Normalize Ventricular Filling Pressures Decompensated heart failure is characterized by increased systemic vascular resistance (SVR). When intravenous (IV) diuretics are administered, there is further increase in SVR. Thus, stroke volume decreases as pulmonary capillary wedge pressure (PCWP) falls. As cardiac index decreases, renal blood flow/glomerular filtration rate falls and further diuresis becomes more difficult. It was commonly believed that patients with advanced heart failure should be maintained at high filling pressures because cardiac index would be too low if the PCWP was reduced below 20 to 24 mm Hg. When an IV vasodilator (in this study, nitroprusside) was administered with IV diuretics to reduce SVR to 1200 dyne • s/cm5, cardiac index increased as PCWP was reduced. Using radionuclide measurements of stroke volume, a reduction in mitral regurgitation was associated with an increase in forward stroke volume. To normalize left ventricular (LV) filling pressures, in most cases, an IV vasodilator or nesiritide must be provided to the patient. Incomplete reduction of LV filling pressures may play an important role in high readmission rates and adverse outcomes after hospitalization for decompensated heart failure. Decompensated heart failure is characterized by increased systemic vascular resistance (SVR). When intravenous (IV) diuretics are administered, there is further increase in SVR. Thus, stroke volume decreases as pulmonary capillary wedge pressure (PCWP) falls. As cardiac index decreases, renal blood flow/glomerular filtration rate falls and further diuresis becomes more difficult. It was commonly believed that patients with advanced heart failure should be maintained at high filling pressures because cardiac index would be too low if the PCWP was reduced below 20 to 24 mm Hg. When an IV vasodilator (in this study, nitroprusside) was administered with IV diuretics to reduce SVR to 1200 dyne • s/cm5, cardiac index increased as PCWP was reduced. Using radionuclide measurements of stroke volume, a reduction in mitral regurgitation was associated with an increase in forward stroke volume. To normalize left ventricular (LV) filling pressures, in most cases, an IV vasodilator or nesiritide must be provided to the patient. Incomplete reduction of LV filling pressures may play an important role in high readmission rates and adverse outcomes after hospitalization for decompensated heart failure.

21. Diuretic Use and the Risk of Mortality in Patients with Left Ventricular Dysfunction Slide 63 This study compared the arrhythmogenicity of dobutamine with nesiritide in patients with heart failure Two doses of nesiritide (0.015 and 0.030) were compared to dobutamine in 305 hospitalized patients with symptomatic decompensated HF, NYHA Functional Class III or IV. During study drug infusion patients had continuous clinical hemodynamic and electrocardiographic monitoring. The dobutamine and nesiritide patients had similar baseline characteristics and baseline use of antiarrhythmic agents. Serious arrhythmias and the incidence of cardiac arrest were more frequent in patient given dobutamine as compared to nesiritide. Slide 63 This study compared the arrhythmogenicity of dobutamine with nesiritide in patients with heart failure Two doses of nesiritide (0.015 and 0.030) were compared to dobutamine in 305 hospitalized patients with symptomatic decompensated HF, NYHA Functional Class III or IV. During study drug infusion patients had continuous clinical hemodynamic and electrocardiographic monitoring. The dobutamine and nesiritide patients had similar baseline characteristics and baseline use of antiarrhythmic agents. Serious arrhythmias and the incidence of cardiac arrest were more frequent in patient given dobutamine as compared to nesiritide.

22. Renal Insufficiency & Chronic Diuretic Therapy Mortality Both high creatinine use and chronic diuretic use had significant increasing relationship to in-hospital mortality, with the lowest rate occurring in patients with creatinine < 2.0 who were not receiving chronic diuretic therapy. The highest rate was in patients with creatinine > 2.0 who were receiving chronic diuretic therapy. Both high creatinine use and chronic diuretic use had significant increasing relationship to in-hospital mortality, with the lowest rate occurring in patients with creatinine < 2.0 who were not receiving chronic diuretic therapy. The highest rate was in patients with creatinine > 2.0 who were receiving chronic diuretic therapy.

23. Renal Insufficiency & Chronic Diuretic Therapy Odds Ratio of Mortality Logistic regression analyses show that creatinine level is the strongest predictor of mortality. Nevertheless, when creatinine is controlled for, chronic oral diuretic use is still significantly associated with significantly higher mortality. Thus, creatinine level and chronic oral diuretic use are independent predictors of mortality. Logistic regression analyses show that creatinine level is the strongest predictor of mortality. Nevertheless, when creatinine is controlled for, chronic oral diuretic use is still significantly associated with significantly higher mortality. Thus, creatinine level and chronic oral diuretic use are independent predictors of mortality.

24. Most Common IV Medications All Enrolled Discharges (n=105,388) October 2001 to January 2004

25. Intravenous Inotropic Agents During Hospitalization for Decompensated Heart Failure Despite this trial providing compelling evidence of a significant increase in adverse events, large numbers of patients hospitalized with acutely decompensated heart failure in the absence of cardiogenic shock or systemic hypoperfusion continue to be treated with inotropic agents. Despite this trial providing compelling evidence of a significant increase in adverse events, large numbers of patients hospitalized with acutely decompensated heart failure in the absence of cardiogenic shock or systemic hypoperfusion continue to be treated with inotropic agents.

26. Slide 78 The reduction in the PCWP with nesiritide was statistically superior than with nitroglycerine over the first 24 hours period in the VMAC trial. Slide 78 The reduction in the PCWP with nesiritide was statistically superior than with nitroglycerine over the first 24 hours period in the VMAC trial.

27. Slide 77 At 3 hours, the beneficial effect of nesiritide on dyspnea was significant as compared to standard therapy plus placebo, in all subjects (p=0.034) as well as in the catheterized stratum (p=0.030) in the VMAC trial. Slide 77 At 3 hours, the beneficial effect of nesiritide on dyspnea was significant as compared to standard therapy plus placebo, in all subjects (p=0.034) as well as in the catheterized stratum (p=0.030) in the VMAC trial.

28. Adverse Events in VMAC During Placebo-Controlled Period Slide 80 The two treatment groups in the VMAC trial experienced mild adverse events during the placebo-controlled period in the nesiritide-treated group (18%) and the nitroglycerin (NTG) group (27%). Adverse events were primarily headache, hypotension, and abdominal pain. Slide 80 The two treatment groups in the VMAC trial experienced mild adverse events during the placebo-controlled period in the nesiritide-treated group (18%) and the nitroglycerin (NTG) group (27%). Adverse events were primarily headache, hypotension, and abdominal pain.

29. Mortality Data Risk Adjustment Process

30. ADHERE: In-Hospital Mortality and Use of Parenteral Vasoactive Medications

31. Predictors of Mortality in ADHERE ADHERE is one of the largest and the most comprehensive datasets on patients hospitalized with acutely decompensated heart failure CART (Classification and Regression Tree) analysis to identify clinical variables predictive of lower, intermediate, and higher mortality risk Covariate and Propensity Adjusted Analysis of Mortality Analysis by IV Therapy Analysis of Variation in Processes of Care and Relationship to Clinical Outcomes

32. CART Analysis: Variables Analyzed 45 variables were considered for the CART analysis. 45 variables were considered for the CART analysis.

33. ADHERE CART: Predictors of Mortality

34. Mortality Rates Comparison Low-mortality risk patients (BUN <43 and SBP =115; n=20,834) had a mortality rate of 2.14%, whereas high-mortality risk patients (BUN =43, SBP <115, and Cr =2.75; n=620) had a 21.94% mortality rate in the derivation data set. Low-mortality risk patients (BUN <43 and SBP =115; n=20,834) had a mortality rate of 2.14%, whereas high-mortality risk patients (BUN =43, SBP <115, and Cr =2.75; n=620) had a 21.94% mortality rate in the derivation data set.

35. ADHERE CART Analysis ADHF patients at low, medium, and highin-hospital mortality risk are easily identifiable from vital sign and laboratory data obtained on presentation This ADHERE Risk Tree provides a practical beside tool for mortality risk stratification Three variables are the strongest predictors: BUN > 43 mg/dL SBP < 115 mmHg Serum creatinine > 2.75 mg/dL Heart failure patients at low, medium, and high risk for in-hospital mortality can be easily identified using vital sign and laboratory data obtained on hospital admission The 3 most predictive variables for in-hospital mortality are: BUN = 43 SBP < 115 Serum creatinine = 2.75Heart failure patients at low, medium, and high risk for in-hospital mortality can be easily identified using vital sign and laboratory data obtained on hospital admission The 3 most predictive variables for in-hospital mortality are: BUN = 43 SBP < 115 Serum creatinine = 2.75

36. ADHERE CART Analysis The ADHERE CART analysis provides insights into individual risk variables for in-hospital mortality Renal insufficiency, volume status, and systemic perfusion have major prognostic importance The cardiorenal syndrome is a key determinate of ADHF prognosis This research sets the stage to define optimal treatment strategies to improve outcomes for ADHF patients at intermediate and high risk The major prognostic importance of renal insufficiency, volume status, and systemic perfusion was evident with BUN and creatinine as two of the three strongest independent predictors of mortality. This risk tree based on ADHERE registry data provides a practical bedside tool for mortality risk stratification. These data provide insights into individual risk variables for in-hospital mortality and further research should focus on identifying strategies to improve outcomes in those patients identified to be at intermediate and high risk. The major prognostic importance of renal insufficiency, volume status, and systemic perfusion was evident with BUN and creatinine as two of the three strongest independent predictors of mortality. This risk tree based on ADHERE registry data provides a practical bedside tool for mortality risk stratification. These data provide insights into individual risk variables for in-hospital mortality and further research should focus on identifying strategies to improve outcomes in those patients identified to be at intermediate and high risk.

37. Goals of the ADHERE Registry Describe demographics and clinical characteristics of patients hospitalized with acutely decompensated heart failure (AHF) Characterize current management of hospitalized patients with AHF Define treatment strategies associated with best clinical outcomes and most efficient use of resources Assist in evaluating and improving the quality of care Slide 17 The ADHERE registry and tool kit will have a tremendous impact on improving the quality of care of patients hospitalized with heart failure, and fulfill the goals that we have set out for the ADHERE registry. Slide 17 The ADHERE registry and tool kit will have a tremendous impact on improving the quality of care of patients hospitalized with heart failure, and fulfill the goals that we have set out for the ADHERE registry.

38. Impediments to the Uptake of Evidence Based Medicine Inconsistent definition of heart failure No AHA/ACC/HFSA guidelines for acute heart failure Once patient’s symptoms have improved often viewed as no longer having heart failure Under-recognition that patients are at high-risk for disease progression Poor communication between EMC physician, cardiologist and primary care physician, expect therapies to be started as outpatient, but does not happen Lack of systems

39. Performance Indicators for Heart Failure Patient Care (JCAHO) Slide 3 The Joint Commission developed quality indicators for heart failure patient care prior to hospital discharge. This data shows for the Nation’s hospitals that 27% of ideal heart failure patients are discharged without ACE inhibitor therapy, that 71% are discharged without having received standard heart failure patient instructions, and 64% of heart failure patients who were current smokers had not been advised that it was a good idea to quit smoking. The ADHERE Registry demonstrates that the performance on these quality indicators is below what is desired. ADHERE provides compelling evidence that we can do more to improve the quality of care for patients hospitalized with acutely decompensated heart failure. Slide 3 The Joint Commission developed quality indicators for heart failure patient care prior to hospital discharge. This data shows for the Nation’s hospitals that 27% of ideal heart failure patients are discharged without ACE inhibitor therapy, that 71% are discharged without having received standard heart failure patient instructions, and 64% of heart failure patients who were current smokers had not been advised that it was a good idea to quit smoking. The ADHERE Registry demonstrates that the performance on these quality indicators is below what is desired. ADHERE provides compelling evidence that we can do more to improve the quality of care for patients hospitalized with acutely decompensated heart failure.

40. ADHERE Critical PathwaysPerformance Improvement Process Slide 16 The ADHERE Registry and tool kit provide hospitals with everything they need to do rapid cycle quality improvement. An outline of the performance improvement process cycle is shown in this slide. It is important for hospital teams to constantly assess the impact of the changes made. Following the quarterly reports in ADHERE the hospital teams will be able to determine if their efforts are successful and facilitate the identification of areas that need additional process changes. Why commit the time and effort to improve the quality care for patients with heart failure? There is compelling data as to why every ADHERE hospital team should be implementing this initiative. Outcomes will clearly improve if the quality of care is improved. An additional important incentive is to be able to show JCAHO compliance. Every hospital wants to do well on their accreditation score. It has also been announced that starting next year, Medicare is going to publish data on each hospital on heart failure performance compared to other local hospitals. No hospital is going to want to be reported as a low-quality provider in the local newspaper, based on poor performance for these indicators. The ADHERE tool kit can help hospitals in their programs to improve performance and so that they can be viewed as providing high quality of care for heart failure.Slide 16 The ADHERE Registry and tool kit provide hospitals with everything they need to do rapid cycle quality improvement. An outline of the performance improvement process cycle is shown in this slide. It is important for hospital teams to constantly assess the impact of the changes made. Following the quarterly reports in ADHERE the hospital teams will be able to determine if their efforts are successful and facilitate the identification of areas that need additional process changes. Why commit the time and effort to improve the quality care for patients with heart failure? There is compelling data as to why every ADHERE hospital team should be implementing this initiative. Outcomes will clearly improve if the quality of care is improved. An additional important incentive is to be able to show JCAHO compliance. Every hospital wants to do well on their accreditation score. It has also been announced that starting next year, Medicare is going to publish data on each hospital on heart failure performance compared to other local hospitals. No hospital is going to want to be reported as a low-quality provider in the local newspaper, based on poor performance for these indicators. The ADHERE tool kit can help hospitals in their programs to improve performance and so that they can be viewed as providing high quality of care for heart failure.

41. Trends in Treatment for AHF in ADHERE: Q1 2002 to Q4 2003

42. Trends in Clinical Outcomes for AHF in ADHERE: Q1 2002 to Q4 2003 Need for mechanical ventilation decreased from 5.3% to 3.6% (RR 0.73, P<0.0001) ICU LOS decreased from mean 4.4 to 3.4 days (P<0.0001) Hospital LOS decreased from mean 6.3 to 5.8 days (P<0.0001) In-hospital mortality decreased from 4.5% to 3.9% (RR 0.86, P=0.03)

43. Trends in Quality of Care at Discharge in ADHERE: Q1 2002 to Q4 2003

44. Key Elements to Quality Improvement Why Do Some Hospitals Succeed? Access to current and accurate data on treatment and outcomes Have stated goals Administrative support Physician champion, support among clinicians Use of pre-printed orders, care maps Use of data to provide feedback Slide 18 Access to current and accurate data is the catalyst for which some hospitals succeed in improving patient care and outcomes and others don’t. The ADHERE Registry shows a large variation in the treatment and outcomes of decompensated heart failure patients. Why do some hospitals succeed when others fail to improve the quality of care? It is important to have stated goals; administrative support; support among clinicians; use of the comprehensive tools that are being provided; and using the ADHERE data to provide feedback. If it sits in a closet or you only talk to one physician or nurse, the rest of the staff of that hospital are not aware of the data, it's not being used to its full potential. This needs to be disseminated widely in creating the motivation to change.   Slide 18 Access to current and accurate data is the catalyst for which some hospitals succeed in improving patient care and outcomes and others don’t. The ADHERE Registry shows a large variation in the treatment and outcomes of decompensated heart failure patients. Why do some hospitals succeed when others fail to improve the quality of care? It is important to have stated goals; administrative support; support among clinicians; use of the comprehensive tools that are being provided; and using the ADHERE data to provide feedback. If it sits in a closet or you only talk to one physician or nurse, the rest of the staff of that hospital are not aware of the data, it's not being used to its full potential. This needs to be disseminated widely in creating the motivation to change.  

45. Goals of the ADHERE Registry Slide 17 The ADHERE registry and tool kit will have a tremendous impact on improving the quality of care of patients hospitalized with heart failure, and fulfill the goals that we have set out for the ADHERE registry. Slide 17 The ADHERE registry and tool kit will have a tremendous impact on improving the quality of care of patients hospitalized with heart failure, and fulfill the goals that we have set out for the ADHERE registry.