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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)
65/18/2012 2:23:48 PM SBCO0074 - LC - PCP
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