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What’s New in Heart Failure

Dana McGlothlin, MDAssociate Professor of Medicine

Advanced Heart Failure and Transplant ProgramMedical Director, CCU

Disclosures

I have no relevant disclosures to reportI will discuss investigational and off-label therapies

A complex clinical syndrome that can result from an y structural or functional cardiac disorder that impa irs the ability of the ventricle to fill with or eject blood

Two main clinical types– Systolic HF (HFREF)– Diastolic HF (HFPEF)

Severity of clinical symptoms may vary substantiall y during course of the disease process and may not correlate with changes in underlying cardiac functi on

Definition of Heart Failure “Heart Failure” vs. “Congestive Heart Failure”

Because not all patients have volume overload atthe time of initial or subsequent evaluation, theterm “heart failure” is preferred over the older term “congestive heart failure”

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Heart Failure: Scope of the Problem

US prevalence*: 5.8 millionUS annual incidence: 670,000

Annual mortality: 282,754– 5-10% depending on severity

Cost: $39.2 billion– 53% of cost due to

hospitalization

Circulation 2010;121:e46-e215

1991 2001 2037

3.54.8

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0

2

4

6

8

10

Pat

ient

s in

US

(mill

ions

)

0

15

%

50’s 60’s 70’s >80

HF increases with age

Rich M. J Am Geriatric Soc. 1997;45:968–974.Croft JB et al. J Am Geriatr Soc. 1997;45:270–275.AHA. Heart Disease and Stroke Statistics—2004 Update

Classification of Heart Failure

IV. Cardiac disease resulting in inability to carry out any physical activity without discomfort. Sx @ rest

III. Cardiac disease resulting in marked limitation of physical activity. Modest activity causes HF symptoms

II. Cardiac disease resulting in slight limitation of physical activity

I. Presence of cardiac disease without limitations on physical activity

NYHA Functional Classification of

HF2

D.Refractory heart failure requiring specialized interventions

C.Symptomatic heart failure; structural heart disease

B.Structural heart disease; high risk for developing heart failure

A.High risk for developing heart failure

ACC/AHA HF Stages 1

NYHA=New York Heart Association.

1. Hunt SA et al. Circulation. 2005;112:e154-e235.2. American Heart Association. Available at: http://www.americanheart.org. Accessed January 16, 2006.

Less severe Asymptomatic

Symptomatic at rest

More severe

Biomarkers in Heart Failure

Natriuretic PeptidesBrain natriuretic peptide (BNP) and NT pro-BNP are polypeptides secreted by the ventricles in response to excessive stretching of cardiomyocytes – BNP biological effects are vasodilation and natriuresis– NT pro-BNP is biologically inactive

BNP and NT pro-BNP equally effective in aiding the diagnosis of HF in patients with dyspnea presenting to the EDNT pro-BNP slightly better in detecting less severe cardiomyopathyBNP may be better at predicting 90 day adverse events than ED physician (REDHOT study)BNP and NT pro-BNP are strong predictors of mortality– Change in levels most predictive

Levels must be interpreted in the context of other clinical conditions and confoundersBNP analysis should be adjunctive and should not replace good clinical judgement

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Galectin-3:New Biomarker for

Heart Failure

HF ACTION Sub-study

COACH Sub-study

Galectin-3 levels:Gal-3 is a lectin is a key mediator involved in myocardial fibrosis and remodelingGal-3 levels (ELISA) reflect underlying disease, NOT affected by acute decompensationGalectin-3 levels over 17.8 ng/mL are associated with an increased risk of adverse outcomesNOT to be used to monitor pharmacologic therapies for HFProvides independent and complementary information to BNP on the prognosis in patients with HFFDA approved, but not in guidelines yet

36.5%

6.9%

15.6%19.3%

Therapies for Chronic Heart Failure

Approach for the Prevention and Treatment of Heart Failure

Stage A

At high risk, no structural disease

Stage B

Structural heart disease,

asymptomatic

Stage D

Refractory HF requiring

specialized interventions

Therapy

• Treat Hypertension

• Treat lipid disorders

• Encourage regular exercise

• Discourage alcohol intake

• Discourage smoking

• ACE inhibition

Therapy

• All measures under stage A

• ACE inhibitors in appropriate patients

• Beta-blockers in appropriate patients

• Aldosterone ant. in post-MI with LVD

• ICD for post-MI LVD

Therapy

• All measures under stage A

Drugs:

• Diuretics

• ACE inhibitors

• Beta-blockers

• Digitalis

• Dietary salt restriction

• Aldosterone ant.

• Hyd/nit for AA pts

CRT + D for select patients

Stage C

Structural heart disease with prior/current

symptoms of HF

Hunt SA, et al. Circ 2005 (modified)

Therapy

• All measures under stages A,B, and C

• Mechanical assist devices

• Heart transplantation

• Continuous (not intermittent) IV inotropic infusions for palliation

• Hospice care

Treatment of HF with Preserved Ejection Fraction

(HFPEF)Identify and address underlying etiology– Surgery where indicated– Aggressive blood pressure management

Agents that promote regression of LVH

Relieve symptoms:– Diuretics– Nitrates

Slow heart rate to improve diastolic filling:– β-blockers– CCB: diltiazem, verapamil

Maintain sinus rhythm; chronotropic competenceARB to reduce HF hospitalizations (CHARM trial)

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Audience Response Question32 y/o AA male with NIDCM, LV EF 30%, NYHA

FC II symptoms. Which HF therapy is not recommended in the current ACC/AHA guidelines?

Core

g S

pironola

ctone

Lis

inopr

il H

ydra

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ne A

ll ar

e indi

ca...

8%9%

38%

42%

3%

A. CoregB. Spironolactone

C. Lisinopril

D. HydralazineE. All are indicated for this patient

Eplerenone is Effective for Mild HF: EMPHASIS-HF Trial

Outcome Eplerenone (%)

Placebo (%) Adjusted hazard ratio (95% CI)

p

Cardiovascular death/heart-failure hospitalization

18.3 25.9 0.63 (0.54–0.74) <0.001

Cardiovascular death 10.8 13.5 0.76 (0.61–0.94) 0.01

Heart-failure hospitalization 12.0 18.4 0.58 (0.47–0.7 0) <0.001

Hospitalization for hyperkalemia 0.3 0.2 1.15 (0.25–5. 31) 0.85

•37% relative risk reduction in combined CV death or HF hospitalization•24% reduction in cardiovascular death•42% reduction in hospitalization for HF

Conclusions:Aldosterone antagonism in mildly symptomatic systol ic HF results in:

N-2737 patients with systolic HF (LV EF <35%) and m ild symptoms (FC II)

Zannad F. et al. N Engl J Med. 2011 Jan 6;364(1):11-21

Pharmacologic Management of Chronic Systolic Heart Failure

(HFREF)

* In selected patients

** ARB or Hyd/nitrates for ACE-I intolerance

ACE-Inhibitors** + ββββ-blockers

Digoxin

Spironolactone (advanced HF)Eplerenone (post-MI LVD)

Hydralazine/Nitrates in AA pts

Control Volume

Slow disease progressionReduce morbidity and mortality

Treat residual symptoms

Diuretics(loop, thiazide )

Sodium restriction

Education

AquareticsUltrafiltration*

Renal Replacement Therapy*

Hunt SA, et al. Circ 2001;104(24):2996-3007Pitt B, et al N Engl J Med. 2003; 348:1309-1321Taylor AL, et al. N Engl J Med 2005;352:1276

Acute Decompensated Heart Failure

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Hospital Admissions for CHF

1,000,000 hospitalizations / year in U.S.– Rising hospitalization rates– Single largest expense for Medicare

In-hospital mortality: 4.1%Mean length of hospital stay: 6.5 daysMortality– 10% at 30 days– 20%-40% at 12 months

Hospital readmissions– 20-30% at 30 days– 50% at 6-12months– 50% may be preventable

Hunt SA J Am Coll Cardiol. 2001;38:2101

Ann

ual

Dis

char

ges

Year'990

100,000200,000300,000400,000500,000600,000

'79 '81'83 '85'87 '89'91'93'95'97

WomenMen

Overview of Treatment of ADHF

Fluid and sodium restrictionDiuretics– Loop– Thiazide

Ultrafiltration for diuretic resistance

Renal replacement therapy

Parenteral vasodilators– Nitroglycerine, nitroprusside, nesiritide

Inotropes (milrinone or dobutamine)

High vs Low Dose and Continuous vs Intermittent Diuretic Dosing:

DOSE HF Study

(p = 0.89)

Net volume loss

0

2500

5000

ml

4237 4249

ml

(p = 0.001)

3575

48995000

2500

0

Q12 bolus

High dose

Continuous infusion

Low dose

• Q12 and continuous infusion of furosemide similar for all outcomes assessed

• High dose intensification (2.5x oral dose) resulted in brisker diuresis at 72 hours, vs. with low dose (1x oral dose), but associated with transient worsening of renal function

• Clinical endpoints similar with both strategies

• Net volume loss similar with Q12 and continuous infusion, but higher with high vs. low dose intensification (4899 vs. 3575 ml)

• % increase in creatinine >0.3 mg/dl in 72 hours same with both infusion strategies, but ↑in high dose intensification arm (p = 0.04)

• Death/hospitalization/ED visit similar with infusion (p = 0.3) and dosing (p = 0.28)

Conclusions

Results

Felker GM, et al. N Engl J Med 2011;364:797-805

Audience Response QuestionThe use of nesiritide in patients with acute

decompensated HF is associated with which of the following?

Reduce

d eG

FR In

crea

sed m

ort...

Short

er hosp

it...

Impro

ved d

yspn...

Both

A a

nd B

3%5%

43%

14%

35%1. Reduced eGFR2. Increased mortality

3. Shorter hospital length of stay

4. Improved dyspnea5. Both A and B

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Nesiritide in ADHF: speculations put to rest in ASCEND-HF Trial

N=7141 patients with ADHF randomized to nesiritide vs placebo

End points Placebo (%), n=3511 Nesiritide (%), n=3496

p

30-d death/HF hospitalization* 10.1 9.4 0.31

Dyspnea at 6 h* 42.1 44.5 0.030

Dyspnea at 24 h* 66.1 68.2 0.007

>25% decrease eGFR 29.5 31.4 0.11

Conclusions:*Nesirtide was safe but is NOT effective in patients

with ADHF

Acute HF—Discharge Criteria HFSA 2010 Practice Guideline

Recommended for all HF patients

Exacerbating factors addressedNear optimal volume status observedTransition from intravenous to oral diuretic succes sfully completedPatient and family education completed, including c lear discharge instructionsNear optimal pharmacologic therapy achieved, includ ing ACEI and BB (for patients with reduced LVEF) or intolera nce documentedFollow-up clinic visit scheduled, usually for 7-10 days

Should be considered for patients with advanced HF or recurrent admissions for HF

Oral medication regimen stable for 24 hoursNo intravenous vasodilator or inotropic agent for 2 4 hoursAmbulation prior to discharge to assess functional capacity after therapyPlans for post-discharge management (scale present in home, visiting nurse or telephone follow up general ly no longer than 3 days after discharge)

Referral for disease management, if available

Strategies to Prevent Readmissions for HF

Telemonitoring is not effective– Tele-HF (n=1653), TIM-HF (n=710), TEHAF (n=382)

Transition of care and early follow-up visit are key!– Ideally within 7 days

Disease management programs are recommended– MDs, NPs, pharmacists, nutritionists

Current Initiatives to reduce hospital readmissions– BOOST, H2H, BEAT-HF, etc.

CMS is considering reducing payments to hospitals with high readmission rates starting 2012

Ingris, Cochrane 2010Chaudhry SI, et al. NEJM 2010;363(24):2301-9.

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Abraham W. Lancet Feb 2011

HR 0.64 (95% CI 0.55-0.75) p<.0001

30% in hospitalizations after 6 months

Device Therapies for Systolic HF

Indications for ICD Device

Nonischemic cardiomyopathy :– NYHA class II to III sx– LVEF < 35%

Ischemic cardiomyopathy :– NYHA class II to III sx– LVEF < 35%– At least 40 days post-MI (DINAMIT)– No reversible ischemia– No recent revascularization

Bardy GH et al. NEJM 2005. 20;352(3):225-37.

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Re-synchronizes intra- and interventricular contraction

Improves:– Symptoms– Exercise capacity– Quality of life– Reduce hospitalization

– Reduce the risk of death

Cardiac ResynchronizationTherapy for Heart Failure CRT: Recommendations

Indicated for patients with LBBB or IVCD and:– LVEF < 35%– Sinus rhythm– NYHA III-IV symptoms despite optimal medical mgmt

These patients are also candidates for ICD placement and should be considered for a dual-function device (CRT-D)

J Am Coll Cardiol. 2005 Sep 20;46(6):1116-43.

CRT Effective in Mildly Symptomatic HF with IVCD:

RAFT TrialN= 1798 patientsNYHA class 2 or 3 HFLV EF <30% and QRS duration >120 ms (or paced QRS >200 ms)Randomized to ICD therapy alone or CRT-D

Tang, A et al. NEJM. 2010;363(25):2385-95.

Advanced Therapies for Stage D Heart Failure

• Transplantation• Mechanical Circulatory Devices

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Heart Transplantation

Survival:� 1 -year: 86%

� 5 -year: 70%

� 10-year: 50%� 15-year: 30%

Taylor et al. J Heart Lung Transplant 2003;22:616ISHLT Registry

Heart Transplantation� Donor heart shortage limits its use

Number of Heart Transplant Reported by Year

• Estimated need for Tx > 25,000 patients• Selection important

J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

2010

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Mechanical Circulatory Devices

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Indications for Ventricular Assist Devices

• Often designations not defined at implantation

• Designations can change during therapy

Bridge to Recovery/Remission Short term support during acute cardiogenic shock or with potentially reversible cases of heart failure

Bridge to Transplantation Short to intermediate term support while awaiting transplant

Destination Therapy Long term support as replacement therapy in patients with contraindication to heart transplant

2.5 –5 L/min5-10 day

Impella

-Percutaneous insertion-Continuous flow

Tandem HeartShort Term Devices

CentriMag

Continuous Flow, Magnetically Levitated, Centrifugal Pump

Short Term Extracorporeal Devices

HeartMate II

Controller

Batteries

PercutaneousLead

ImplantablePump

Long Term Devices - Implantable• Continuous flow,

axial pump

• Small, quiet

• One moving part: incr durability

• 38% reduction in hospital admissions

• Imp. QOL

• INR goals 1.5-2.5

• FDA approved

for BTT & DT

Miller, Pagani, Russell et. al. N Engl J Med 2007;357:885-96.

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HeartMate II BTT Long-term Results

(n=281)Kaplan-Meier Survival

Pagani F, Miller L, Russell S, JAAC: Vol 54, No 4, 2009.

Real World Results of HMII as BTT

169 HM II vs 169 COMP LVAD BTT recipients in INTERMACS RegistryCOMP group slightly sickerOperative mortality 4% in HM II vs 11% in COMP group (p=0.012)12 month survival 85% for HM II vs 70% for COMP group (p<0.001)QoL improved for both

Starling RC et al. JACC 2011;57(19):1890-8.

K-M Survival

Destination Therapy Trials

Fang JC NEJM 2009

Infection-driveline infection-LVAD pocket infection-intravascular device infection

Bleeding from anticoagulation and acquired vWF deficiency

Thromboembolism

Device malfunction-early vads -> bioprosthetic valve and bearing wear

Complications Associated with VADs

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Future of VAD Therapies: What’s

Coming?Third Generation VAD technology and beyond

Centrifugal device

Completely implantable within the pericardium- no abdominal pocket

Up to 10 L/min flow

Magnetic and hydrodynamic levitated rotors which eliminate mechanical wear

1-yr survival rates in ADVANCE and CAP were 86% and 92%, respectively in total of 240 BTT pts

Heartware HVAD

Aaronson K et al. AHA 2010Slaughter, M et al. 2011 ISHLT

Future Technologies

Three MVAD designs all showing strong results in preclinical studies

Wide bladed, axial flow technology allows significant miniaturization

Partial or full support attainable in all designs

All versions can eliminate sternotomy

Wear-less impeller suspension

Design principle:

Decrease invasiveness and morbidity without decreasing efficacy

ConclusionsThe prevalence of HF is increasing rapidly as the population grows older

Role of biomarkers in diagnosing, predicting, and guiding therapy of HF is evolving

Efficacy of aldosterone antagonists and CRT (pts with IVCD) have now been established in NYHA FC II pts with systolic HF

Efforts to reduce hospital readmissions for HF are becoming ever more important

Transplant has the best outcomes for treatment of advanced stage D HF

VAD technology is improving and use will continue to increase

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Thank You!