1. Diastolic Heart Failure, HFpEF, HFnEF: What are we treating anyway? Charles M. Rasmussen, MD FACC

2. Disclosures None

3. Objectives Semantics, Semantics, Semantics Definitions Clinical Problem Demographics of HFpEF Treatment Recommendations

5. Date of download: 1/4/2015 Copyright © The American College of Cardiology. All rights reserved. From: What If We Could Prevent Heart Failure? J Am Coll Cardiol Img. 2012;5(9):881-883. doi:10.1016/j.jcmg.2012.06.005 Stages in the Development of Heart Failure/Recommended Therapy by Stage ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; EF = ejection fraction; FHx CM = family history of cardiomyopathy; HF = heart failure; LV = left ventricular; LVH = left ventricular hypertrophy; MI = myocardial infarction. Figure Legend:

6. Definitions Diastolic Dysfunction: Pathophysiologic condition associated with impaired myocardial relaxation and elevated LV filling pressure. Diastolic Heart Failure: Signs and symptoms of Heart Failure due to abnormalities in LV relaxation and or stiffness. HFpEF: Signs and symptoms of heart failure with preserved EF

7. Why the Need for a change in Semantics?

8. Aurigemma GP, et al. Circulation 2006; 113: 296–304 Systolic HF Normal heart Diastolic HF Pathophysiology

9. PHYSIOLOGY

10. Diastolic physiology. Rosenberg M A, and Manning W J Circulation. 2012;126:2353-2362 Copyright © American Heart Association, Inc. All rights reserved.

11. Figure 2 Trans-mitral valve spectral Doppler flow pattern in a normal subject (upper panel), in a patient with mild diastolic dysfunction (abnormal relaxation; middle panel), and in a patient with severe (restrictive) diastolic dysfunction (lower panel) Figure 2 Trans-mitral valve spectral Doppler flow pattern in a normal subject (upper panel), in a patient with mild diastolic dysfunction (abnormal relaxation; middle panel), and in a patient with severe (restrictive) diastolic dysfunction (lower panel) Clinical Science (2004) 107, 539-557 - Clinical Science (2004) 107, 539-557 - www.clinsci.org

12. Diastolic Dysfunction Diastolic Heart Failure Systolic Heart Failure

13. HFpEF does not equal HFnEF

14. Figure 1. Cardiovascular responses at matched low-level exercise (A) and peak exercise (B) for HFpEF patients and matched control subjects. Borlaug B A et al. Circulation. 2006;114:2138-2147 Copyright © American Heart Association, Inc. All rights reserved.

15. Systolic vs. Diastolic Heart Failure Patients with systolic heart failure have parameters of diastolic dysfunction Elevated filling pressure, fibrosis Patients with diastolic heart failure do not have normal systolic function Diminished reserve Contractility does not increase exercise.

16. Definitions HFrEF Ejection Fraction <40% HFpEF Ejection Fraction>50% HFpEF Ejection Fraction 41-49% Borderline HFpEF improved 2013 ACCF/AHA Guidelines

17. Signs and Symptoms Dyspnea Reduced exercise tolerance Edema Elevated BNP

18. Epidemiology 40% to 60% of patients with HF Increasing prevalence Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479. Owan T, et al. NEJM. 2006;355:251-9

19. Bhatia et al, NEJM 2006

20. Characteristics of HFpEF patients Older More likely female More likely hypertensive Less likely to have CAD More likely to have atrial fibrillation More likely to be anemic

21. Date of download: 11/30/2014 Copyright © The American College of Cardiology. All rights reserved. From: Characteristics, Treatments, and Outcomes of Patients With Preserved Systolic Function Hospitalized for Heart Failure: A Report From the OPTIMIZE-HF Registry J Am Coll Cardiol. 2007;50(8):768-777. doi:10.1016/j.jacc.2007.04.064 Survival After Hospital Discharge in Patients With LVSD Compared With PSF Kaplan-Meier survival curves after hospital discharge in patients with left ventricular systolic dysfunction (LVSD) compared with patients with preserved systolic function (PSF) in the follow-up cohort. Figure Legend:

22. Owan T et al. N Engl J Med 2006;355:251-259 TEMPORAL TRENDS

23. Is HFpEF and HFrEF different phenotypes of the same disease process?

24. Single syndrome hypothesis Ouzounian M. Nature Clin Pract Cardiovasc Med. 2008; 5(7): 375-86

25. Bimodal Distribution Borlaug and Redfield: Circ 2011

26. Medications in Heart Failure Angiotensin Converting Enzyme Inhibitors Beta Blockers Angiotensin Receptor Blockers Hydralazine/Isordil Spironolactone Diuretics Digoxin

27. ACE Inhibitors in HFpEF

28. ARBs in HFpEF Massie et al NEJM 2008

29. ARBs and Hospitalizations Yasuf et el; Lancet 2003

30. OPTIMIZE – HF: Beta blockers Hernandez, et al. JACC. 2009 Jan 13;53(2):184-92

31. Beta Blockers Berkstrom et al Eur Hrt J; 2004

32. Differential Response to Medications Borlaug and Redfeld: Circ; 2011

34. TOPHAT

35. Age Related Changes Rising Systolic BP Increasing LV wall thickness Decreasing ventricular size Increasing myocardial fibrosis Increasing left atrial size Prolonged relaxation

36. Date of download: 1/11/2015 Copyright © The American College of Cardiology. All rights reserved. From: The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure J Am Coll Cardiol. 2003;42(4):736-742. doi:10.1016/S0735-1097(03)00789-7 Proportion of death attributed to specific causes of death across left ventricular ejection fraction groups. HF = heart failure. Figure Legend:

37. Cause of Death Different HFrEF HFpEF Pump Failure Co-Morbid Conditions Arrhythmias Non-Cardiac CV Comp.

38. Comorbidities Diabetes Obesity Pulmonary Disease Sleep Apnea Renal Failure Cerebral vascular disease Anemia Coronary Disease

39. Treat the Comorbidities Shaw et al: JAMA 2000

40. Treatment Recommendations COR LOE Control Systolic and Diastolic BP I B Diuretics for relief of symptoms I C Coronary Revascularization if symp IIa C Manage AFIB IIa C B blockers, ACEI, ARBs for HTN IIa C ARBs might reduce hospitalizations IIa B Nutritional Supplementations not rec. IIa C

41. Conclusions The terms systolic and diastolic heart failure: Do not adequately divide the heart failure population Are not based on actual pathophysiology

42. Conclusions HFpEF: Is a growing clinical problem in our aging population Etiology and pathophysiology are incompletely understood Associated with many comorbidities Poor prognosis No treatment has been demonstrated to directly alter outcome

43. QUESTIONS?