Diastolic Heart Failure: The Other Heart Failure (Heart Failure with Preserved EF, or HFpEF) • Mariell Jessup MD, FAHA, FACC • Professor of Medicine • University of Pennsylvania • Philadelphia, Pennsylvania

Mariell Jessup MD • No conflicts to report • I will discuss some off-label uses of drugs

Outline • Semantics/Definitions • Epidemiology • Pathophysiology/Mechanisms – Diastolic Dysfunction (types) – Ventriculo-Vascular Coupling – Impaired systolic reserve

• Evaluation • Treatment (current and emerging)

A case of “old lady legs” • 71 year old woman with well controlled hypertension, chronic atrial fibrillation, and diabetes was seen for her yearly check-up. • She denied angina, palpitations or dizziness. • Her only complaint was progressive swelling of her legs during the day-reminding her of her mother’s legs as she aged. • When prompted, she did admit she was more breathless while walking her small dog.

A case of “old lady legs” • • • • •

BP: 150/95mmHg, HR: 95 bpm, irreg No JVD, no carotid bruits Lungs clear, abdomen mildly obese Heart: soft systolic murmur, no S3+ 1+ edema of both lower legs, pulses intact

• EKG: atrial fibrillation, LVH, non-specific STTW • Echo: LVEF normal, RV normal, LA enlarged • Labs: mild elevation of BUN, BNP elevated x 2

Semantics and Related Questions

• If not systolic HF, must it be diastolic HF?

• Is LVEF the best determinant of systolic HF?

• What is a “reduced” LVEF?

Heart Failure with Preserved Ejection Fraction (HFPEF) • HFPEF is defined by a normal or near-normal EF (>0.50 or 0.45). This cut point does not exclude systolic dysfunction, but is not usually associated with heart failure symptoms in the absence of other factors. Hence the term “preserved systolic function”. • HFPEF is not a specific diagnosis or syndrome. It is a constellation of findings caused by diverse etiologies for which non-cardiac etiologies are excluded. • HFPEF is often equated with diastolic heart failure.

HF-pEF Epidemiology: Olmsted County, MN

• • • •

~50% of all patients with HF have an LVEF ≥ 50% Average age 74±14 years 56% female, 44% male Relatively high rates of co-morbidities: – Hypertension: 63% – CAD: 53% – AFib: 41% – Obesity: 41% – Diabetes: 33%

Owan TE…Redfield MM. N Engl J Med 355:251-9, 2006

Prevalence of Heart Failure USA

10

Finland

England

(CHS) (Helsinki) (Poole)

Sweden

Den.

prevalence %

Portugal Nether.

(Vasteras) (Copen.) (Asturias) (EPICA)

9

(Rotter.)

Proportion with decreased LV systolic function Proportion with preserved LV systolic function

8 7

6

Spain

8.8

8.2

7.5

6.7

6.4

5 4

4.9

3

4.2

2 1

2.1 4.8

4.2

5.1

3.1

4.5

2.9

1.7

1.5

0 age range

66-103 75-86

70-84

75

> 50

> 40

>25

55-95

mean age

78

76

75

-

60

68

65

-

Secular Trends in HF-pEF Prevalence

Associated with increasing prevalence of AFib (2941%) and Diabetes (3236%), but no change in CAD 5959%) Owan TE…Redfield MM. N Engl J Med 355:251-9, 2006

Audience Question #1 The prognosis for patients with diastolic heart failure is significantly better than for patients with systolic heart failure. 1. True 2. False

41% 59%

Prognosis of Patients with HF-pEF After 1st Hospitalization

Overall

Bhatia RS...Liu PP.

Owan TE…Redfield MM.

N Engl J Med 355:260-9, 2006

N Engl J Med 355:251-9, 2006

Effect of LVEF on In-Hospital Outcomes for ADHF

• Data from >100,000 hospitalizations of the Acute Decompensated Heart Failure Registry (ADHERE)

• CHF-pEF present in 50.4% of patients • Patients with CHF-pEF were older, women, and hypertensive; less likely to have prior MI

• In-hospital mortality was 2.8% for patients with CHF-pEF and 3.9% for patients with reduced EF

Yancy CW et al. (ADHERE). J Am Coll Cardiol 47:76-84, 2006

Effect of LVEF on Post-Hospital Outcomes for ADHF

• The OPTIMIZE Registry examined 90-day follow up of 20,118 patients admitted with HF and LVEF50% & LVEDVI>97 mL/m2

+

Evidence of Abnormal LV relaxation, filling or stiffness or Catheterization mPCW >12 mmHg LVEDP >15 mmHg Tau > 48 ms

or TD E/E’>15

or TD 8160 mm Hg; prior EF 2.5, Hb 35% • Appeared to be beneficial but need more data about the subgroup with preserved EF • Will need another trial specific to HFpEF Eur. Heart J. 26 (2005), pp. 215–225

COHERE - Hospitalizations before and after Carvedilol, by EF HF Hosp. prior yr

40

HF Hosp. 1 yr f/u

*

35

P = 0.001 vs. prior year

30

% of Patients

25 20

*

15

*

10

*

*

5 0 40

Common Sense HF-pEF Management • Address underlying diseases (CAD, HTN, renal dysfunction, DM, obesity & sleep apnea) • Avoidance of excessive tachycardia – especially Afib with rapid ventricular response

• Careful volume status management (education, weights, BNP tracking, implanted monitoring devices)

Patients With Heart Failure and Normal Left Ventricular Ejection Fraction Normal Left Ventricular Ejection Fraction I IIa IIb III

Physicians should control systolic and diastolic hypertension in patients with HF and normal LVEF, in accordance with published guidelines. NO CHANGE

I IIa IIb III

Physicians should control ventricular rate in patients with HF and normal LVEF and atrial fibrillation. NO CHANGE I IIa IIb III Physicians should use diuretics to control pulmonary

congestion and peripheral edema in patients with HF and normal LVEF. NO CHANGE

ESC 2005 Chronic HF Guidelines

Emerging Strategies for Pathophysiological Targeting for HF-pEF Mechanism

Approach

Possible Agents

Abnormal LV Relaxation

Increase myocyte Ca2+ uptake rates

SERCA agonists Ranolazine PDE-5 inhibitors Ivabradine

Slow heart rate Increased LV Stiffness

↓ Collagen X-links ↓ AGEs ↓ fibrosis

TGFβ inhibitors Aminoguanidine Alagebrium Aldosterone Antag.

↑ Vascular Stiffness

↓ Atherosclerosis ↓ Aortic Stiffness

Statins Nitrates Aminoguanidine Alagebrium

↓ Vascular Capacitance

Improved volume management

Implantable monitors (± interventions)

Summary • HF-pEF accounts for ~50 of HF, is increasingly prevalent, and carries a prognosis that is nearly as poor as for patients with “systolic HF” • Patients with HF-pEF usually have LV diastolic function abnormalities, however, these abnormalities are also present in elderly and hypertensive patients without heart failure • Coexistant increases in arterial stiffness, impaired systolic reserve and co-morbid factors like atrial fibrillation, HTN and CAD contribute to HF-pEF • Ang-II antagonists may reduce hospitalization in HF-pEF, but do not affect mortality.

Conclusions • Combined increases in LV and arterial stiffness likely account for the exaggerated volume sensitivity of patients with HF-pEF • Differences in pathophysiology and heterogeneity among patients with HF-pEF may account for underwhelming responses to therapies that have been effective for patients with systolic HF • Treatment strategies to achieve improved volume management and target ventricular and vascular abnormalities will be required to address the increasing prevalence of HF-pEF