CHF: Systolic Vs. Diastolic Dysfunction: Dx & Rx Eman Hamad MD, FACC, FHFSA Assistant Professor of Medicine Medical Director Mechanical circulatory support program Associate Program Director General Cardiology & Heart Failure Fellowships

Temple University Hospital 11.8.2016

CHF: Systolic Vs. Diastolic Dysfunction: Dx & Rx

Disclosures:  I have no conflict of interest in relation to this

presentation.  Will not be discussing any off label use of any medications or devices

Outline  Background & scope of Problem  Definition & Etiology  Pathophysiology  Classification of heart failure  Risk factors  Signs, Symptoms  Diagnosis  Approach to management of HF  Clinical Trials & guidelines

Background & Scope of Problem

Heart Failure Expected to Become More Common as Population Ages Heart Failure Patients in US (Millions)

12

10

10

 4.7 million symptomatic

patients; estimated 10 million in 2037

8 6 4

 550,000 new cases/year

4.7 3.5

2 0 1991

2000

2037*

*Rich M. J Am Geriatric Soc. 1997;45:968–974. Outlook for Heart Failure: Five-year Technology and Business Assessment. The Advisory Board; 2007 American Heart Association. 2001 Heart and Stroke Statistical Update. 2000.

Survival after the onset of CHF in Framingham Heart Study Subjects….Poor Prognosis

Overall 50% 5-year mortality

50%

Years

Median survival was 1.7 years for men with CHF and 3.2 year for women AHA, 1998 Heart and Statistical Update NCHS, National Center for Health Statistics

Ho Circulation 1993;88:107-115

Projected Mortality for Advanced HF Exceeds Other Terminal Diseases

More deaths from heart failure than from all forms of cancer combined •Rose EA, et al. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med. 2001 Nov 15;345(20):1435-43.

Recurrent admissions and Survival in Heart Failure

•

J Am Coll Cardiol. 2013;61(12):1209-1221. doi:10.1016/j.jacc.2012.08.1029

Causes of Hospital Readmission for Congestive Heart Failure

Over 2/3 of HF Hospitalizations Preventable Diet Noncompliance 24%

16% Inappropriate Rx

Rx Noncompliance 24%

19% Failure to Seek Care

Annals of Internal Medicine 122:415-21, 1995

17% Other

What is the Prognosis of HFpEF?  Annual death rate ≈5%  ≈50% die of non-cardiovascular diseases  Risk factors for mortality in HFpEF  Increasing age, male gender  Higher natriuretic peptide levels, higher NYHA class  Coronary artery or peripheral vascular disease  Diabetes mellitus, chronic renal insufficiency  Lower EF, restrictive filling pattern on Doppler ECHO  Low and very high BMI (in HFpEF)

Massie BM et al for I-PRESERVE Investigators, NEJM. 4;359(23):2456-67. 2008 Nov 11.

Impact of HF • As our population ages, the epidemic continues to grow. • Single largest expense for Medicare • Heart failure care ranks among the leading U.S. healthcare expenditures.

Major public health problem resulting in substantial morbidity and mortality… Projected to reach 44.6 billion in 2016

•Lloyd-Jones D, Adams R, Carnethon M, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119(3):480-6. • Adams KF, Zannad F. Clinical definition and epidemiology of advanced heart failure. Am Heart J 1998;135:S204-S215. •Roger VL .Circulation AHA online 12/15/10; ACS, Cancer Facts and Figures 2010

Definition & Etiology

Definition  ”HF is a complex clinical syndrome that

results from any structural or functional impairment of ventricular filling or ejection of blood.“  Ventricular filling Diastole  Ejection of blood Systole Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol.2013;62(16):1495-1539

Systolic and Diastolic Dysfunction

Definition of Heart Failure –ACCF/AHA Guideline Classification

Ejection Fraction ≤40%

I. Heart Failure with Reduced Ejection Fraction (HFrEF) II. Heart Failure with ≥50% Preserved Ejection Fraction (HFpEF)

Description systolic HF. Randomized clinical trials HFrEF efficacious therapies have been demonstrated referred to as diastolic HF.

a. HFpEF, Borderline

41% to 49%

Their characteristics, treatment patterns, and outcomes appear similar to HFpEF.

b. HFpEF, Improved

>40%

subset of patients with HFpEF previously had HFrEF. may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize these patients.

Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol.2013;62(16):1495-1539

Etiology    

Ischemic- Cardiomyopathy (CM) Hypertensive HD Valvular HD-CM (AS/AR/MR) Metabolic: −

↑/↓ thyroid/pheochromocytoma

−

Anthracyclines/Etoh/cocaine/amphetamines



Viral CM/ familial

 Toxins:

 Idiopathic Dilated CM

Infiltrative -hemochromatosis/ amyloid HCM PPCM Congenital Some are reversible (tachy, Etoh)  Biventricular Failure/ RV failure    

Heart Failure- Risk Factors  Primary risk factors  

Coronary artery disease (CAD) Advancing age

 Contributing risk factors      

Hypertension Diabetes Tobacco use Obesity High cholesterol Valvular heart disease

Anemias  Congenital heart defects  Hyperthyroid, Fever, infection, stress  Cardiotoxic Chemo, radiation 

Pathophysiology

The Vicious Cycle of Heart Failure

Cardiac Remodeling and the Myocyte Myocardial infarction

Pressure overload

Inflammatory heart muscle disease

Idiopathic dilated cardiomyopathy

Volume overload

Gross Changes During Remodeling • As the heart remodels, the geometry changes • The heart is less elliptical and more spherical to optimize the relationship between LV volume and cardiac output • Over time, changes in ventricular mass, composition and volume develop

Classification of Heart Failure

New York Heart Association (NYHA) Classification of HF 1994 Class

Description

I

Patient has no limitation of physical activity. No symptoms arise from ordinary physical activity.

II

Patient has slight limitation of physical activity due to mild symptoms (fatigue, shortness of breath, palpitations and/or angina) during ordinary activity. Patient is comfortable at rest.

III

Patient has marked limitation of physical activity due to symptoms even at less-thanordinary activity. Patient is comfortable at rest.

IV

Patient is unable to do any physical activity without discomfort. Symptoms experienced at rest.

Patient Population per NYHA Class

The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.

ACC/AHA HF Staging 1-Year Mortality >50%

D Refractory, symptoms at rest and recurrent hospitalizations

C

15%-30%

Structural heart disease, prior or current symptoms

B

5%-10%

Structural heart disease, asymptomatic: left ventricular hypertrophy, myocardial infarction, low LVEF, dilatation, valvular disease

A

2%-3%

High-risk patients with no structural or symptomatic disease: hypertension, atherosclerotic disease, diabetes mellitus, coronary artery disease, family history, cardiotoxic drugs/Chemo

Hunt SA et al. J Am Coll Cardiol 2009;53;e1-e90.

Signs and symptoms

FACES of Heart Failure  Fatigue  Activity decrease  Cough (especially supine)  Edema  Shortness of breath

Symptoms

Signs of Heart Failure  ↑ JVP  Rales  S3  Edema  Crackles or decreased breath sounds  Cardiomegaly  Ascites  Cool Extremities

Diagnosis

Lab Analysis in Heart Failure  CBC

Since anemia can exacerbate heart failure Serum electrolytes and creatinine  before starting high dose diuretics Fasting Blood glucose  To evaluate for possible diabetes mellitus Fasting lipid profile Liver Function tests Thyroid function tests  Thyrotoxicosis can result in A. Fib, & hypothyroidism can results in HF. Iron studies  To screen for hereditary hemochromatosis as cause of heart failure. ANA  To evaluate for possible lupus Antiphospholipids Viral studies  If viral myocarditis suspected  HIV 

        

Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol.2013;62(16):1495-1539.

BNP Diagnostic values for CHF BNP > 400 pg/L – acute CHF present BNP 100 pg/L – 400 pg/L  Diagnostic of CHF with    

Sensitivity 90% Specificity 76% Predictive accuracy 83% R/O pulmonary embolism, LV dysfunction without acute CHF or cor pulmonale or other reasons for elevated BNP

BNP < 100 pg/L – 98% negative predictive accuracy JACC 2001;37(2):379-85.

Chest X-ray in Heart Failure  Cardiomegaly  Cephalization of the pulmonary vessels  Kerley B-lines  Pleural effusions

Cardiac Testing in Heart Failure  Electrocardiogram:  May show specific cause of heart failure: Ischemic heart disease  Dilated cardiomyopathy: first degree AV block, LBBB, Left anterior fascicular block  LVH 

 Echocardiogram:  Left ventricular ejection fraction  Structural/valvular abnormalities  Diastolic function  RV function and PH

Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol.2013;62(16):1495-1539.

Cardiac stress Testing in Heart Failure Treadmill Exercise Machine

For HF patients, the treadmill exercise test is used to:  Evaluate tolerance for exercise  Assess response to treatment  Evaluate for ischemic changes 

Nuclear Cardiac Scan • Evaluate: o Ischemia o viability

o Function

Cardiac MRI • Used to diagnose many conditions including: o Coronary heart disease o Viability o Ejection fraction and volume o Pericarditis (the membrane around the heart is inflamed) o Valvular disease o Congenital heart defects o Cardiac tumors o Amyloid, sarcoid , other infiltrative o Myocarditis

Cardiac Catheterization  Left and Right heart Catheterization o Visualizing coronary arteries o Hemodynamics (NOT for routine use) o uncertain fluid status, perfusion, or systemic or pulmonary vascular resistance o Symptomatic hypotension not responding to therapy o Renal function is worsening with therapy o Inotrope use or MCS /Transplant eval



Endomyocardial biopsy (NOT for routine use)  If a specific diagnosis is suspected that would change therapy

Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol.2013;62(16):1495-1539.

Management and Goals of Treatment • • •

PREVENTION DRUGS & DEVICES CLINICAL TRIALS & GUIDELINES

Goals of Care  Improve symptoms  Improve quality of life  Prevent progression of LV

dysfunction 

Reverse remodeling

 Reduce hospitalization

and morbidity  Reduce mortality 

Sudden death

Prevention  Hypertension  Diabetes mellitus  Obesity  Metabolic syndrome  Coronary artery disease  Prior myocardial infarction  Left ventricular hypertrophy  Smoking /toxins  Advanced age

Reducing Risk Factors

Risk factors for HFpEF? •

For HFpEF • Older, more hypertensive, and higher prevalence of AF (than in HFrEF) •

CAD prevalence comparatively lower

•

More common in women (by 2:1)

•

Interventions that can help in the prevention of HFpEF?

•

Blood Pressure Control

•

Both BP/HR and Volume management can help symptoms

Treating Hypertension to Prevent HF  Aggressive blood

pressure control: Decreases risk of new HF by ~ 50% 56% in DM2

Lancet 1991;338:1281-5 (STOP-Hypertension JAMA 1997;278:212-6 (SHEP) UKPDS Group. UKPDS 38. BMJ 1998;317:703-713

 Aggressive BP

control in patients with prior MI: Decreases risk of new HF by ~ 80%

CHF Incidence Comparing the diabetic and Non-diabetic Non-Diabetic

Diabetic

Gregory A. Nichols et al. Dia Care 2004;27:1879-1884 ©2004 by American Diabetes Association

Management of Non-Cardiac Comorbidities Cognitive dysfunction Anemia

Renal dysfunction

Respiratory Disorders

Depression

Arthritis

Polypharmacy

Drugs, Devices & Clinical Trials

β-Blocker Saves Lives in Heart Failure? β–blocker is the most important progress in Heart Failure …. It actually helps the heart !!

Standard Treatment ACE-I Beta Blocker Symptomatic relief

ARB Aldosterone I Isordil/Hydralaz ine Devices

ACE Inhibitors in CVD But No HF  Treatment with ACE

inhibitors decreases the risk of CV death, MI, stroke, or cardiac arrest.

Placebo

HOPE

16 14 12 % MI, 10 Stroke, 8 CV Death 6 4 2 0

Ramipril 22% rel. risk red. p < .001 0

1

2

3

4

Years

20% risk reduction EUROPA

15

Placebo

12

% MI, CV Death, 9 Cardiac 6 Arrest

Perindopril 20% rel. risk red. p = .0003

3 0 0

1

2

3

Years

NEJM 2000;342:145-53 (HOPE)

Lancet 2003;362:782-8 (EUROPA

4

5

Treatment of Post-MI Patients with Asymptomatic LV Dysfunction (LVEF ≤ 40%)  SAVE Study

All-cause mortality ↓19%  CV mortality ↓21%  HF development ↓37%  Recurrent MI ↓25% 

0.3

Mortality Rate

Placebo

0.2

Captopril 0.1

19% rel. risk reduction p = 0.019

0 0

0.5

1

1.5

2

2.5

3

3.5

4

Years

Pfeffer et al. NEJM 1992;327:669-77

Enalapril in Asymptomatic LVD to Severe HF  SOLVD Prevention

(Asymptomatic LVD)  20%  29%

death or HF hosp. death or new HF

 CONSENSUS

(Severe

Heart Failure)  40%  31%  27%

mortality at 6 mos. mortality at 1 year mortality at end of

study

SOLVD Treatment (Chronic Heart Failure) 16%



No difference in incidence of sudden cardiac death

mortality

SOLVD Investigators. N Engl J Med 1992;327:685-91 SOLVD Investigators. N Engl J Med 1991;325:293-302 CONSENSUS Study Trial Group. N Engl J Med 1987;316:1429-35

HFSA 2010 Practice Guideline Pharmacologic Therapy: ACE Inhibitors  ACE inhibitors are recommended for

symptomatic and asymptomatic patients with an LVEF ≤ 40%. 

Strength of Evidence = A

 ACE inhibitors should be titrated to

target doses as tolerated used in clinical trials (as tolerated Srength of Evidence = C

 ACE inhibitors are recommended as

routine therapy for asymptomatic patients with an LVEF ≤ 40%. 

Post MI 



Strength of Evidence = B

Non Post-MI 

Strength of Evidence = C

Benazepril (Lotensin) Enalapril (Vasotec) Lisinopril (Zestril) Quinapril (Accupril) Ramipril (Altace) Others

HFSA 2010 Practice Guideline Pharmacologic Therapy: Substitutes for ACEI  It is recommended that other therapy be substituted

for ACE inhibitors in the following circumstances:  In

patients who cannot tolerate ACE inhibitors due to cough, ARBs are recommended.



Strength of Evidence = A

 Patients

intolerant to ACE inhibitors from hyperkalemia or renal insufficiency are likely to experience the same side effects with ARBs. In these cases, the combination of hydralazine and an oral nitrate should be considered.



Strength of Evidence = C

Effect of Beta Blockade on Outcome in Patients With Heart Failure Post-MI HF Severity

Target Dose (mg)

Outcome

Study

Drug

US Carvedilol1

carvedilol

mild/ moderate

6.2525 BID

↓48% disease progression (p= .007)

CIBIS-II2

bisoprolol

moderate/ severe

10 QD

↓34% mortality (p