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

Disclosures None

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

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): doi: /j.jcmg 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:

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

Why the Need for a change in Semantics?

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

PHYSIOLOGY

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

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, Clinical Science (2004) 107,

Diastolic Dysfunction Diastolic Heart Failure Systolic Heart Failure

HFpEF does not equal HFnEF

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: Copyright © American Heart Association, Inc. All rights reserved.

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.

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

Signs and Symptoms Dyspnea Reduced exercise tolerance Edema Elevated BNP

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

Bhatia et al, NEJM 2006

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

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): doi: /j.jacc 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:

Owan T et al. N Engl J Med 2006;355: TEMPORAL TRENDS

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

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

Bimodal Distribution Borlaug and Redfield: Circ 2011

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

ACE Inhibitors in HFpEF

ARBs in HFpEF Massie et al NEJM 2008

ARBs and Hospitalizations Yasuf et el; Lancet 2003

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

Beta Blockers Berkstrom et al Eur Hrt J; 2004

Differential Response to Medications Borlaug and Redfeld: Circ; 2011

TOPHAT

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

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): doi: /S (03) Proportion of death attributed to specific causes of death across left ventricular ejection fraction groups. HF = heart failure. Figure Legend:

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

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

Treat the Comorbidities Shaw et al: JAMA 2000

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

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

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

QUESTIONS?