HEART FAILURE INHEART FAILURE IN THE GERIATRIC POPULATIONRoss Zimmer M.D., F.A.C.C.Clinical Assistant Professor of Medicine

Director, Heart Failure Program, g

Medical Director, VAD Program

UPHS/Presb terian Medical CenterUPHS/Presbyterian Medical Center

Our Aging Population

Projected Increases in the U.S. Population 65 Years of Age or Older.

NEJM 2002;347:1349

Data are from the U.S. Census Bureau.

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Unique Aspects of Aging and Heart FailureFailure• Increased myocardial stiffness and diastolic

dysfunctiondysfunction

• More exposure to standard comorbidities that l d t CAD d t li d f tilead to CAD and systolic dysfunction

• Less data based decision making (older g (population is under represented)

• More dangerous drug-drug-interactionsMore dangerous drug drug interactions

• More complex psycho-social issues

• Greater procedural/surgical risk

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Identifying the Patient With Heart FailureHeart Failure • Symptoms (more vague/difficult in the elderly)

Exertional dyspnea or fatigue– Exertional dyspnea or fatigue– Orthopnea, paroxysmal nocturnal dyspnea

• Physical findings– Elevated jugular venous pressure, third heart

d l t ll di l d i l i lsound, laterally displaced apical impulse, rales, edema, cardiomegaly on chest X-ray -findings may be minimal with more chronicfindings may be minimal with more chronic disease

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Identifying the Patient With Heart FailureHeart Failure

• Assess cardiac function– Echocardiography remains best g p y

assessment of EF/valve disease/pericardial diseasep

– Role of BNP is expanding (although may be less helpful in the elderly)p y)

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BNP Levels of Patients Diagnosed Without CHF, With Baseline Left Ventricular Dysfunction and With CHFDysfunction, and With CHF

1076+/-138

1000

1200

600

800

NP

pg/m

l

38+/-4141+/-31

200

400BN

0No CHF LV Dysfunction

No acute CHFCHF

N=139 N=14 N=97Dao, Q., Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001

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Left Ventricular Dysfunction

• Systolic: Impaired contractility/ejectionApproximately two thirds of heart failure patients have– Approximately two-thirds of heart failure patients have systolic dysfunction

• Diastolic: Impaired filling/relaxation

30%30%

• Diastolic: Impaired filling/relaxation

30%30%

70%70%

(EF < 40%)(EF < 40%)(EF > 40 %)(EF > 40 %)

70%70%

Di t li D f tiDi t li D f tiDiastolic DysfunctionDiastolic DysfunctionSystolic DysfunctionSystolic Dysfunction

Heart Failure/Hypertension -Lifestyle Modifications

• Reduce weight • Moderate consumption• Reduce weight • Moderate consumption of:

• alcohol sodium (less than 2g)• sodium (less than 2g)

• saturated fat/cholesterol

• Maintain adequate intake of

• WalkJ

qdietary:

• potassium• calcium

• Avoid

• Jog• Swim

calcium • magnesium

tobacco(JNC VI. Arch Intern Med. 1997)

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Diastolic Dysfunction with Heart Failure in the Elderly - TreatmentFailure in the Elderly - Treatment• Sodium restriction

• Diuretics

• Beta blockers• Beta blockers

• ACE-Inhibitors or Angiotensin Receptor blockers

• Rate control of atrial fibrillation

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CHARM-PreservedSummary

• candesartan reduced the number of patients

y

In patients with symptoms of HF and preserved LVEF (>40%)• candesartan reduced the number of patients

hospitalized for HF (P=.017) as well as the total number of HF hospitalizations (P=0.014)

• cardiovascular death did not differ between placebo and candesartan groups

• candesartan reduced the risk of new-onset diabetes by 40% (P=0.005)

• there was a greater incidence of permanent study drug discontinuations with candesartan due to hypotension(2.4% vs 1.1%), hyperkalemia (1.5% vshypotension(2.4% vs 1.1%), hyperkalemia (1.5% vs 0.6%) and increased creatinine (4.8% vs 2.4%)

HF, heart failure.Yusuf S et al. Lancet. 2003;362:777-781.

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Systolic Dysfunction in the Geriatric Population - EtiologyPopulation - Etiology• Coronary Artery Disease

• Hypertension

• Thyroid Disease• Thyroid Disease

• Systemic causes (amyloid/sarcoid)

• Idiopathic

Heart Failure PathophysiologyMyocardial Injury Fall in LV Performance

Activation of RAAS, SNS, ET,and Others

Peripheral VasoconstrictionANPMyocardial Toxicity

Peripheral VasoconstrictionHemodynamic Alterations

ANPBNP

Remodeling andProgressive

Worsening ofLV F iLV Function Heart Failure SymptomsMorbidity and Mortality

Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2–S6.

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Sites of Action of ACEIs and ARBs

ReninRenin

AngiotensinogenAngiotensinogen

Angiotensin IAngiotensin I

ChymaseChymaseTrypsinTrypsin ACEACE--Kininase IIKininase II

ACEIACEI BradykininBradykinin

XX XX XXTrypsinTrypsinPeptidasePeptidase

Angiotensin IIAngiotensin II

ACEACE Kininase IIKininase II

InactiveInactivedegradation degradation

productsproducts

BK IIBK II--receptorreceptor

ATAT11 --receptorreceptorbl kbl k

XX XX XX

productsproducts

ATAT11 --receptorreceptor ATAT22 --receptorreceptor

blockerblocker

XX NONO

VasoconstrictionVasoconstrictionSalt/water retentionSalt/water retentionR d liR d li

AntiAnti--proliferationproliferationCell differentiationCell differentiation

VasodilationVasodilationNatriuNatriu--/diuresis/diuresis

RemodelingRemodeling Tissue repairTissue repair AntiAnti--remodelingremodeling

Willenheimer, R, et al., Willenheimer, R, et al., Europ Heart Journ Europ Heart Journ 1999 (20):9971999 (20):997--10081008

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Survival Rates in Patients Receiving ACE Inhibitors Across NYHA ClassesACE Inhibitors Across NYHA Classes

1.0

0.8SOLVD-Prevention

0.8

Survival

PROMISESOLVD-Treatment

0.6

0.5 CONSENSUSPRAISE

DIG

V-HeFT

00 21 3 4 5

Year

ACE inhibitor arms of CONSENSUS, V-HeFT, and SOLVD trials.Placebo arms of PRAISE, PROMISE, and DIG trials (all receiving ACE inhibitors).

CHARMCHARM--AlternativeAlternativeP i E d i tP i E d i tPrimary EndpointPrimary Endpoint

40

50Placebo 406 (40.0%)

23% i k d ti

30

40

CV death or HF

334 (33.0%)23% risk reduction

20CandesartanCV death or HF

hospitalization (%)

0

10

Number at

HR 0.77 (95% CI 0.67-0.89), P=0.0004Adjusted HR 0.70, P<0.0001

0 1 2 30

3.5

1013 929 831 434 122

risk:Candesartan

PlaceboTime

(years)

F, heart failure; HR, hazard ratio; CI, confidence interval.Granger CB et al. Lancet. 2003;362:772-776.

1015 887 798 427 126Placebo (y )

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Carvedilol Reduces Hospitalizations

33% 38%Severe CHFMild to Moderate CHF

(P <.05)

33% 38%10 40

(P =.0001)

20%% 5

00Heart Failure Hospitalizations

Duration of therapy: 10.4 months (mean)

Heart Failure Hospitalizations

Duration of therapy: 6.5 months (median)

00

Placebo (n = 398)(+ ACEI, diuretic)

Fowler MB et al. J Am Coll Cardiol. 2001;37:1692–1699; 2Fowler MB et al. Circulation. 2001;104(Abstract 3548):II-753.

Carvedilol (n = 696)(+ ACEI, diuretic)

Placebo (n = 1133)(+ ACEI, diuretic)

Carvedilol (n = 1156)(+ ACEI, diuretic)

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Effect of -Blockade on Outcomes in Heart Failure

TargetHF Dosage

Heart Failure

HF DosageStudy Drug Severity (mg/day) Outcome

US Carvedilol carvedilol mild/ 6.25 to 25 48% disease progressionmoderate bid (P=.001)moderate bid (P .001)

CIBIS-II bisoprolol moderate/ 10 qd 34% mortalitysevere (P<.0001)

MERIT-HF metoprolol mild/ 200 qd 34% mortalitysuccinate moderate (P=.0062)

COPERNICUS carvedilol severe 25 bid 35% mortalityCOPERNICUS carvedilol severe 25 bid 35% mortality(P=.0014)

Colucci WS et al. Circulation. 1996;94:2800–2806.CIBIS II Investigators and Committees. Lancet. 1999;353:9–13.MERIT-HF Study Group. Lancet. 1999;353:2001–2007.Packer M et al. N Engl J Med. 2001;344:1651–1658.

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Effects of Adding -Blockers or Angiotensin Receptor Blockers vs Increasing ACE Inhibitor Dose in HF

Symptoms Morbidity Mortality

Blockers vs Increasing ACE Inhibitor Dose in HF

Symptoms Morbidity Mortality

Increase dose No 10-15% NSof ACE inhibitor1 effectof ACE inhibitor effect

Add angiotensin 10-15% NoAdd angiotensin 10 15% Noreceptor blocker*2 effect

Add -blockade3 20-35% 35%

Packer M et al. Circulation. 1999;100:2312–2318.Cohn JN et al. N Engl J Med. 2001;345:1667–1675.Lechat P et al. Circulation. 1998;98:1184–1191.

DIGOXINDIGOXIN

5050

4040MortalityMortality

3030PlaceboPlacebo

Mortality%Mortality%

2020

1010

n=3403n=3403 p = 0.8p = 0.8

1010

00

Digoxinn=3397Digoxinn=3397

00484800 1212 2424 3636

N Engl J Med 1997;336:525N Engl J Med 1997;336:525 MonthsMonths

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Randomized AldactoneEvaluation Study (RALES)

1.00

0.95

Evaluation Study (RALES)

val

0.95

0.90

0.85

0 80

bilit

y of

Sur

vi

Spironolactone*

0.80

0.75

0.70

Placebo

Pro

bab

0.65

0.60

0.55P<.001

0.50

0.45

0.00

Pitt B., et al. N Engl J Med. 1999;341:709–717.

Months0 3 6 9 12 15 18 21 24 27 30 33 36

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Heart Failure - Procedural/Surgical Options in the Geriatric PopulationOptions in the Geriatric Population• Biventricular Pacemaker

• ICD

• CABG• CABG

• MV Repair

• Aortic Valve Replacement

Transplant (age maximum typically 65 years old)• Transplant (age maximum typically 65 years old)

• Destiantion Left Ventricular Assist Device

CARDIAC RESYNCHRONIZATION:Change in NYHA Functional Class InSync III vs. MIRACLE Control

80% P < 0.0001

59%

73%60%70%

% P 0.0001

38%

59%

30%40%50%

ropo

rtion

38%

4%

26%

1%10%20%30%Pr

4% 1%0%

10%

Improved No Change Worsened

Control N=169 InSync III N=176

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MADIT II – Secondary Prevention for SCD

0.78

0.690.69

P=0.007

(probability of survival)(probability of survival)

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AGE DISTRIBUTIONOF HEART RECIPIENTS (1/1982-6/2006)( )

35

40

tsts 25

30

35

rrans

plan

nspl

an

15

20

% o

f Tr

% o

f Tr

5

10

00-9 10-19 20-29 30-39 40-49 50-59 60+

Recipient AgeRecipient Age

ISHLT2008

Last updated based on data as of December 2006J Heart Lung Transplant 2008;27: 937-983

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HeartMate II LVAS

• Small, advanced blood pump, designed to improve patientdesigned to improve patient outcomes and quality of life.

• 60 percent smaller pocket i t d 44 trequirement and 44 percent

shorter surgical time than older model

• Electrically powered– Batteries and line power

• Home discharge• Home discharge

The Future of Ventricular Assist DevicesDevices

• Fully implantable rotary pump*

• Eliminate all skin penetrations

• Expand the benefits of implanted ventricular assistance to children and small adults

*Currently under development

Improving LVAD Outcomes

8090

10085 + 5%

Surv

ival

0607080

59 + 8%

70 + 8%

56 + 8%

Perc

ent S

304050 Late Experience June 2007 - April 2009 (n=55)

Overall Experience March 2005 - April 2009 (n=93)Early experience March 2005 - May 2007 (n=38)(Included in Slaughter, Rogers, Milano et al NEJM 2009)

01020

Remaining at Risk: 55 43 1293 64 30 38 21 18

Months0 6 12 18 24

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Heart Failure: End-of-life issues

• Non cardiac problems, such as renal or cognitive dysfunction often drive end of life decisionsdysfunction, often drive end of life decisions.

• Age may limit “aggressive” options such as di l i lth h di t l tsurgery or dialysis, although cardiac transplant

has been performed in 70 year old patients and aortic valve replacement surgery is offered toaortic valve replacement surgery is offered to many in their 80s.

• Early discussion of code status and level of• Early discussion of code status and level of aggressiveness remains critical.

Case #1295/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• Mrs. B is an 84 year old woman living in an Assisted Living Home She has a history ofAssisted Living Home. She has a history of hypertension and diabetes and has a creatinine of 1.6. She smoked a pack of cigarettes a day p g yuntil her children hid them from her.

• She has had progressive dyspnea over the last 3She has had progressive dyspnea over the last 3 months and was hospitalized once with lower extremity edema. Her echocardiogram revealed a normal ejection fraction.

Case #1305/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• What therapies should be considered in this patient?patient?– Diuretics– Beta-BlockersBeta Blockers– ACE-Inhibitors– All of the aboveAll of the above– None of the above

Case #1315/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• What therapies have been proven to improve mortality in this patient?mortality in this patient?– Diuretics– Beta-BlockersBeta Blockers– ACE-Inhibitors– All of the aboveAll of the above– None of the above

Case #2325/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• Mr. B is a 71 year old gemtelman with aprior MI and progressive class III IV heart failure with anand progressive class III-IV heart failure with an ejection fraction of 20%.

Hi ti i i 1 6 d h i k H• His creatinine is 1.6 and he is a non-smoker. He has a supportive wife and still works part time but is slowing down despite compliance withis slowing down despite compliance with medications and diet.

Case #2335/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• What therapies should be considered in this patient?patient?– Diuretics– Beta-BlockersBeta Blockers– ACE-Inhibitors– DigoxinDigoxin– All of the above

Case #2345/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• What therapies have been proven to improve mortality in this patient?mortality in this patient?– Diuretics– Beta-BlockersBeta Blockers– ACE-Inhibitors– Beta-Blockers and ACE-inhibitors onlyBeta Blockers and ACE inhibitors only– All of the above

Case #2355/18/2012 2:23:48 PM SBCO0074 - LC - PCP

• What high-end options should be realistically evaluated that could potentially improveevaluated that could potentially improve mortality?– Home Inotropes (milrinone)Home Inotropes (milrinone)– Cardiac Transplantation– Destination Left Ventricular Assist Device– None of the above