Heart Failure with Preserved Ejection Fraction (HFpEF): Natural History and Contemporary Management

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1 Heart Failure with Preserved Ejection Fraction (HFpEF): Natural History and Contemporary Management Jason L. Guichard, MD, PhD Greenville Health System Department of Medicine, Carolina Cardiology Consultants Clinical Assistant Professor, University of South Carolina School of Medicine Greenville

2 Educational Objective Describe the epidemiology of heart failure with preserved ejection fraction (HFpEF) and the current strategies for management.

3 Heart Failure Clinical Syndrome of Heart Failure Echocardiogram (TTE) HFrEF ( reduced ) HFpEF ( preserved ) Ischemic (ICM) Non-ischemic (NICM)

4 HFpEF, HFmr(b)EF, and HFrEF

5 What is HFpEF? The clinical syndrome of heart failure in the setting of a normal LVEF. Although estimates vary, nearly half (45-50%) of patients with heart failure have HFpEF. HFpEF was historically considered to be caused by left ventricular diastolic dysfunction, so-called diastolic heart failure. So, what is diastolic dysfunction? Nat Rev Cardiol Sep;11(9):507-15

6 J Am Soc Echocardiogr Apr;29(4):

7 Presence of Diastolic Dysfunction is Variable in HFpEF J Am Coll Cardiol Oct 24;70(17):

8 So, HFpEF Is Not Just Diastolic Dysfunction Several other contributory factors have been identified in HFpEF, including limitations in left ventricular systolic reserve systemic and pulmonary vascular function nitric oxide bioavailability chronotropic reserve right heart function autonomic tone left atrial function and, other peripheral impairments Nat Rev Cardiol Sep;11(9):507-15

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10 HFpEF, Current State Current evidence shows that there is a lack of significant benefit (e.g. mortality or quality of life) with neurohormonal (i.e. adrenergic or renin-angiotensin-aldosterone) antagonism in HFpEF. Unfortunately, HFpEF is a large and very heterogenous heart failure population with limited treatment options. Nat Rev Cardiol Sep;11(9):507-15

11 HFpEF, What Can We Do? #1 Obtain the Diagnosis #2 Apply Therapeutic Strategies #3 Identify a Cause (?)

12 HFpEF, What Can We Do? #1 It is important to apply effective diagnostic strategies. An elevated LVEDP, LAP, or PCWP at rest or with exercise, in the setting of a normal LVEF, confirms the diagnosis of HFpEF.

13 J Am Soc Echocardiogr Apr;29(4):

14 Further Testing Diastolic stress test (i.e. exercise/supine bicycle echocardiogram) Right heart catheterization (RHC) with or without exercise/supine bicycle Left heart catheterization (LHC) with an LVEDP, especially if considering CAD, although not able to exercise a patient

15 Patient Examples from November 1-15 th, 2017 Ms. KB is a 29 yo WF, BMI 52.5 LVEF 55-65% with normal diastolic function LHC: Normal coronary arteries with LVEDP 29 mm Hg Ms. TG is a 43 yo WF, BMI 38.1 and HTN LVEF 55-65% with normal diastolic function LHC: Normal coronary arteries with LVEDP 34 mm Hg Ms. MG is a 48 yo WF, BMI 46.5 and HTN/DM2 LVEF 55-65% with normal diastolic function LHC: Normal coronary arteries with LVEDP 25 mm Hg

16 Ms. BH is a 48 yo WF, BMI 33.8 and HTN LVEF 55-65% with grade II diastolic dysfunction RHC: At Rest = RA 10, PA 33/17(23), PW 14 (V-wave 18) With Exercise = RA 12, PA 50/25(35), PW 22 (V-wave 31) Exercise-induced diastolic dysfunction with secondary pulmonary hypertension Mr. LL is a 69 yo WM, BMI 40.5 and HTN/DM LVEF 55-65% with indeterminate diastolic function RHC: At Rest = RA 18, PA 58/23(37), PW 27 (V-wave 41) Post-Nitro = RA 13, PA 48/20(29), PW 19 (V-wave 29)

17 Ms. DG is a 60 yo WF, BMI 44.8 and HTN LVEF 55-65% with normal diastolic function RHC: At Rest = RA 2, PA 33/11(17), PW 6 With Exercise = RA 2, PA 38/14(23), PW 7 Patient had profound hypoxia (SatO2 71%) with minimal exercise that corrected with supplemental oxygen Watch out for anemia! In the past 3 months, two patients had a Hgb of 4.0 pre-procedure for RHC.

18 HFpEF, What Can We Do? #2 It is important to apply targeted therapeutic strategies. Treatment options for HFpEF are limited, but can be effective in improving symptoms and reducing HF hospitalizations.

19 Treatment Options Lifestyle Changes CardioMEMS HF System Aldactone (spironolactone)

20 Lifestyle Changes Treatment of HFpEF remains centered around controlling: Weight loss, referral to a Bariatric Clinic Regular mild-to-moderate exercise Smoking cessation Salt restriction Blood pressure, work-up for resistant hypertension Diabetes Dyslipidemia OSA, with CPAP COPD Volume status, with diuretics Of note, exercise training in patients with HFpEF appears to be safe and is associated with an improvement in cardiorespiratory fitness and quality of life (Circ Heart Fail Jan;8(1):33-40). J Am Coll Cardiol Mar 13;59(11): , JAMA Jan 5;315(1):36-46, Mayo Clin Proc Jun;86(6):531-9

21 CardioMEMS HF System The first and only FDA-approved therapy proven to reduce HF hospitalizations and improve quality of life in HFpEF patients. Simple implantation criteria: one HF hospitalization in the past 12 months current HF symptoms Lancet Feb 19;377(9766):658-66

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24 Aldactone (spironolactone) The results of the TOPCAT trial indicate that spironolactone is not superior to placebo in improving CV outcomes in patients with HFpEF. The reduction in HF hospitalizations with spironolactone is hypothesis generating and deserves further study.

25 Circulation Jan 6;131(1):34-42

26 Primary Composite Outcome: - time to cardiovascular death - aborted cardiac arrest - hospitalization HF This analysis was based on the observation of an unusually large difference in the placebo event rates between the sites conducting TOPCAT in the 4 countries in the Americas compared with those in Russia and Georgia. This analysis demonstrated possible clinical benefits with spironolactone in patients with HFpEF from the Americas.

27 It is likely that the patients in Eastern Europe did not have HFpEF. Unfortunately, it is unlikely that this trial can ever be repeated. While the trial was negative and spironolactone cannot be FDA-approved for the treatment of HFpEF, most experts agree that spironolactone does offer some benefit in patients with HFpEF.

28 HFpEF, What Can We Do? #3 It is important to identify the unique causes of HFpEF. Be aware of the restrictive, infiltrative, mitochondrial, and lysosomal storage diseases. Recognize when the pattern doesn t fit: HFpEF without risk factors LVH without hypertension Q-waves without CAD

29 Prevalence of wtttr Cardiac Amyloidosis at HFpEF Diagnosis JACC Heart Fail Apr;2(2):113-22

30 Application Be suspicious for HFpEF in a patient with heart failure symptoms, especially dyspnea on exertion (DOE), but with a normal LVEF. You will not always see echocardiographic evidence of diastolic dysfunction in HFpEF, especially at rest. An elevated LVEDP, LAP, or PCWP at rest or with exercise, in the setting of a normal LVEF, confirms the diagnosis of HFpEF. Treatment options for HFpEF are limited, but can be effective in improving symptoms and reducing hospitalizations.

31 Interactive Audience Question Approximately what percent (%) of HFpEF patients, enrolled in the 3 major randomized clinical trials for HFpEF, actually had echocardiographic evidence of grade II or III diastolic dysfunction (i.e. elevated left atrial pressures)? A. 100% B. 75% C. 50% D. 25%

32 Questions? Jason Guichard Sarah Matthews

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34 Presence of Left Atrial Dilation is Variable J Am Coll Cardiol Oct 24;70(17):

35 Left Atrial Size Versus Left Atrial Pressure

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