Heart Failure in 2012
Patricia P. Chang, MD MHS FACC
Associate Professor, Medicine
Director, Heart Failure & Transplant Program
February 25, 2012
Disclosures
• No relationships to disclose
• I will discuss products that are
investigational or used off-label
Case
• 55 yo BW presented to PCP with palpitations,
ECG “abnormal”
– Stress thallium (2003): no ischemia, LVEF 20%.
– Exercises on treadmill 2 miles, 33 minutes, 3-4
d/week. No SOB, cp. Frequently naps during the
day. Exam unremarkable except BMI 33.
– PMH: carpal tunnel syndrome. No HTN, DM, h/o
diet-controlled hyperlipidemia
– FH: Father died MI age 67. No other CVD/HF/SCD
• Presents to HF Clinic for further E/M
• ACC/AHA Stage B, NYHA Class I
• Further w/u? Treatment? Prognosis?
Topics
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Epidemiology
Evaluation: etiology, testing
Common comorbidities
Therapies and timing
Disclaimer: More focus on Systolic HF vs HF with preserved EF
Topics
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Epidemiology
Evaluation: etiology, testing
Common comorbidities
Therapies and timing
HF Estimates
• HF affects 5.7 Million: 3.1 M men, 2.6 M
women (self-report, age ≥20yo, NHANES-2008)
• Lifetime risk 20% (≥40yo, Framingham[FHS])
• Hospitalizations > 1 M / year
• Prevalence and Incidence of HF
increases with age
– 670,000 new cases age ≥45yo (FHS)
– 56,000 deaths; 1 in 9 deaths (NCHS)
• ≥50% diagnosed w/ HF die within 5 yrs
(Olmsted)
Roger V et al. Heart Disease and Stroke Statistics—2011 Update. Circulation 2011;123(4):e18-e209.
“Diastolic” vs Systolic HF
Aurigemma GP, Gaasch WH. NEJM 2004;351:1097-105.
Systolic HF vs HFpEF
4596 HF patients, Mayo Clinic
Owan TE et al, NEJM 2006; 355(3):254
Survival by HF type
Owan TE et al, NEJM 2006; 355(3):254
Survival by Gender
• Olmstead County: N=4537 HF patients
(1979-2000) by ICD-9-CM codes (98% (+) Framingham criteria)
MEN
Rogers VL et al, JAMA 2004;292:344
WOMEN
Survival by Race & Gender
Study
Loehr L, Rosamond W, Chang PP, et al. Am J Cardiol 2008;101(7):1016-1022
SHF Survival by Etiology & Gender
5 RCTs (N=11642 [2851 F]): PRAISE, PRAISE-2, MERIT-HF, VEST, PROMISE
Etiology may be more important
Nonischemic
Ischemic
Frazier CG et al, JACC 2007;49(13):1450-8.
Topics
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Epidemiology
Evaluation: etiology, testing
Common comorbidities
Therapies and timing
Practice Guidelines
• ACC/AHA: 1995, 2001, 2005, 2009
my.americanheart.org
Heart Failure: Stage vs Class
Hunt SA et al. ACC/AHA Guidelines 2005 & 2001; Circulation 2001;104:2996.
Farrell MH, Foody JM, Krumholz HM. JAMA 2002;287:890
Practice Guidelines
• HFSA: 1999, 2006, 2010
www.hfsa.org
• ESC: 2001, 2005, 2008 (2010)
Etiology of Systolic HF
• Coronary artery disease
2/3
(“ischemic cardiomyopathy”)
• Hypertension
(“hypertensive cardiomyopathy”)
• Valvular disease (“valvular CM”)
• Infectious (e.g., viral myocarditis, Chagas)
• Cardiotoxins (e.g., alcohol, chemotherapy)
• Infiltrative (e.g., amyloidosis, sarcoidosis,
hemochromatosis, Wilson’s)
• Peripartum CM
• Stress-induced CM
• Genetic (Familial)
• Idiopathic (Dilated) CM
Evaluation of New HF
(after a good H&P)
• Cardiac function/structure
– ECHO (Cardiac MRI, MUGA)
• Etiology
– R/O CAD: cath vs stress vs CT
– Serologies: TSH, ANA, Ferritin, HIV,
SPEP/UPEP
– Cardiac MRI
– Family Hx: Genetic testing?
Genomic Locations of Genetic Variants
Associated with the Risk of MI and HF
O'Donnell CJ, Nabel EG. N Engl J Med 2011;365:2098-2109
Representative Genomewide Association
Studies (GWAS) of Common CVDs
O'Donnell CJ, Nabel EG. N Engl J Med 2011;365:2098-2109
Familial DCM
• New Idiopathic DCM dx = Familial in 20-35%
(when 1st degree family members screened)
• Point mutations in 31 autosomal and 2 Xlinked genes
– But only account only for 30-35% genetic causes
Hershberger RE, Siegfried JD, JACC 2011;57(16):1641-9
Genetic Testing
• Genetics Clinic at UNC (Meadowmont)
• Familion “send out” (www.familion.com)
Topics
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Epidemiology
Evaluation: etiology, testing
Common comorbidities
Therapies and timing
Comorbidities
• Affect sxs, Rx, prognosis
• Cardiovascular
– CHD & CHD risk factors: HTN, DM,
metabolic syndrome, obesity
– Valvular disease
– Arrhythmias
– Other atherosclerotic disease: PAD, stroke
• Noncardiac comorbidities
– Too many to list… but will highlight:
• Anemia
• Sleep apnea
Anemia
• ~25% in HF population
– Etiology: hemodilution, Fe or Epo deficiency,
CKD
• 1-g/dL Hgb reduction associated with a
20% increase in risk of death
Tang WH et al, JACC 2008;51:569-576; Anand I et al, Circulation 2004;110:149-154
• Treatment is relatively easy
– Iron supplementation
– IV iron (short-term)
– Erythropoiesis-stimulating agents (short term)
Obstructive Sleep Apnea (OSA)
• Similar sxs as HF
• Common (12-53%) but under-diagnosed
• Thus undertreated
Mild to No OSA
Untreated OSA
Wang H et al, JACC 2007;49(15):1625-31.
Kasai T, Bradley TD, JACC 2011;57(2):119-27 [REVIEW]
Topics
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•
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•
Epidemiology
Evaluation: etiology, testing
Common comorbidities
Therapies and timing
Standard HF Therapy
• Guidelines
(Systolic HF > HFpEF)
– ACC/AHA: 1995, 2001, 2005, 2009
– HFSA: 1999, 2006, 2010
• Medications
– Diuretics, ACE inhibitors* &/or Angiotensin receptor blockers* &/ or
Hydralazine/Nitrates*, Beta-blockers*, Aldosterone antagonists*,
Digoxin
• Electrophysiology (EP) Devices
– Implantable cardioverter defibrillator (ICD)
– Biventricular pacemaker (CRT)
• Surgery
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Revascularization
Ventricular restoration (Dor procedure)
Mitral valve surgery
Cardiac transplantation
Mechanical circulatory support (VAD)
HF Stages and Therapies
Stem cells?
Hemofiltration?
ARB, H/I in some. ICD
all
Jessup M, Brozena S. NEJM 2003;348:2007
Stepwise Therapy for HF
, B-blockers
Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574
HF Specific Management
• Identify and avoid exacerbating factors for HF
• Behavioral management
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Fluid restriction (2 L = ½ gallon)
Salt restriction (2 g)
Daily weights (?sliding scale diuretics for the savvy)
Exercise
a.k.a. HF Core Measures
Medical adherence
No smoking
• Biomarkers: BNP/NT-proBNP
– New ones but not commonly available
(ST2, endoglin, galectin3, cystatin C, neutrophil gelatinase-associated lipocalin, midregional proadrenomedullin, chromogranin A, adiponectin, resistin, leptin)
• “Baseline/dry” weights & NTproBNP helpful
Timing: Medications
• Begin with ACC/AHA Stage A
• Optimize for Stages B-D
Timing: Medications
• Lots of meds with good data, but challenges
of polypharmacy
– Compliance, cost, HF severity
• Priorities
– B-blocker, ACE-I for all (aim for target doses)
– ARB as ACE-I alternative or if congested/
hypertensive
– Hydralazine/nitrate if African-American or
congested/hypertensive
– Diuretic PRN and/or Aldosterone blocker
– Digoxin if recurrent hospitalization
Aim for Target Doses
ACE-I
BB
Enalapril (Vasotec)
Captopril (Capoten)
Ramipril (Altace)
Lisinopril (Prinivil, Zestril)
Trandolapril (Mavik)
Quinapril (Accupril)
Bisoprolol (Zebeta)
Carvedilol (Coreg)
Metoprolol XL/CR (Toprol XL)
Metoprolol (Lopressor)
Atenolol (Tenormin)
10 mg bid
50 mg tid*
5 mg bid
20 mg qd
4 mg qd
20-40 mg bid §
10 mg qd
25-50 mg bid **
200 mg qd
100 mg bid § ‡
100 mg qd § ‡
*affected by food, ** depends on weight
§ no mortality data, ‡ not in guideline
Hospitalized Pt: ADHF
• IV diuretics
– Bolus or continuous
• IV vasodilators
– Nitroglycerin, Nesiritide, Nitroprusside
• IV inotropes
Advanced,
– Milrinone, Dobutamine, Dopamine End-stage
• Optimize PO regimen
Systolic HF
Hunt SA, et al. ACC/AHA HF Guidelines Update. Circulation 2009;119(14):e391-479.
Alternatives to Drugs
• Ultrafiltration (aquapheresis therapy):
– Peripheral or central venous access, ≤4 L off in
≤8 hrs, max removal rate 500 mL/hour
– UNLOAD trial: n=200, RCT, UF vs IV diuretics
• At 48 hrs, UF group had 38%  weight loss, 28%  net
fluid loss
• At 90 days after hospital d/c, UF had  HF rehospitalizations,  ED or clinic visits
Costanzo MR et al. JACC 2007;49(6):675-83
• EECP (enhanced external counterpulsation)
– Already used for angina pts
– PEECH trial: n=187, RCT, EECP vs usual care
• EECP pts had  exercise time, QOL, NYHA Class, but
no difference in peak VO2 changes
Feldman AM et al. JACC 2006;48(6):1198-205
Implantable Cardioverter Defibrillator
LVEF ≤35%
• 2° Prevention
– AVID (1997)
• 1° Prevention
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MADIT (1996)
MUSTT (1999) (EF 35-40%, +EPS)
MADIT II (2002)
SCD-HeFT (2004)
ACC/AHA/ESC guidelines
• Class I: LVEF ≤ 35%, NYHA II-III,
ICM LVEF ≤ 30%, NYHA I
• Class II: NICM LVEF ≤ 30% NYHA I
Timing: ICD
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40+ days post-MI/revascularization
>3 months for NICM on optimal therapy
Life expectancy >1 year
Still, low referral rate
– 42% (LVEF≤35%) & 49% (LVEF≤30%)
eligible pts were referred (1 center, 2002-2006)
Bradfield J et al, PACE 2009; 32:S194–S197
– Why? NNT = 6 (MADIT-II) to 14 (SCD-HeFT)
• Patient vs Doctor?
ICD implant rates overall low
MADIT II eligible pts in GWTG hospitals –Implanted or Planned
Implant rate:
20% overall
<1% lowest tertile
35% highest tertile
Shah B et al, JACC 2009;53(5):416-22
ICD Implant Rates
Highest in large
centers with
sophisticated
cardiac facilities
Shah B et al JACC 2009;53(5):416-22
Reiterate the Message?
• Life-saving
• Prognostically Important
ICD Shocks = Poor Prognosis
Any shock is bad
More shocks are worse
• 33% SCD-HeFT pts received ≥1 ICD shock (128 pts
appropriate, 87 inappropriate, 54 both types)
• Most common cause of death = progressive HF
Poole JE et al, NEJM 2008;359:1009-17
ICD Shocks = Poor Prognosis
Cardiac Resynchronization Therapy
• 30% with chronic HF have
Ventricular Dyssynchrony
• CRT with biventricular pacemakers can
improve symptoms & survival*:
NYHA Class III-IV, LVEF <35%, basal QRS
duration of >120 msec
– MUSTIC (QRS >150 ms) (2001)
– MIRACLE (QRS >130 ms) (2002)
– COMPANION (QRS >120 ms) (2004)
– CARE-HF (QRS >120 ms) (2005)*
Timing: CRT
• After medical therapy optimized
• CRT has been mostly studied in the
NYHA III-IV population
– If CRT, HF = “Advanced”
• Consider CRT earlier? (earlier than
NYHA Class III)
– REVERSE Trial (2008)
– MADIT-CRT Trial (2009)
– RAFT Trial (2010)
REVERSE Trial
• 610 pts NYHA Class I-II, QRS ≥120, LVEF ≤40%:
CRT-ON ▲ vs CRT-OFF ●
Linde C et al, JACC 2008;52:1834-43
REVERSE Trial
• ~96% on ACEi/ARB and BB; ~35% at target BB dose
• ~80% NYHA II
Linde C et al., JACC 2008;52:1834-43
MADIT-CRT
• 1820 pts NYHA I-II, QRS≥130, LVEF≤30%: CRT-ICD vs ICD
• ~40% NYHA II; 10% NYHA III-IV prior to enrollment
Moss AJ et al, N Engl J Med 2009;361:1329-38.
RAFT
• 1789 pts, NYHA II-III,
LVEF ≤30, QRS ≥120
or ≥200 paced:
CRT-ICD or ICD
Tang AS et al, N Engl J Med 2010;363:2385-95.
CRT “Subgroups”
• Pts who seem to benefit more:
– QRS >150 msec (MADIT-CRT, RAFT)
– Women (MADIT-CRT)
Reverse Remodeling
MADIT-CRT
Moss AJ et al, N Engl J Med 2009;361:1329-38.
• Responders: LA volume <40 ml/m2, women,
nonischemic CM, LBBB, QRS ≥150, LVEDV
≥125 ml/m2, prior hospitalization for HF
Goldenberg I et al, Circulation 2011;124(14):1527-36
CRT Limitations
• ~30% do not respond to CRT
JACC 2009;53:1933-1943)
• HF does ultimately progress
(PROSPECT, Bax JJ et al,
Patient Preferences
• Time trade (survival
time vs perfect
health)
• Baseline: median
trade for better quality
= 3 months' survival
time
• Preferences in favor
of survival for many
pts despite advanced
HF sxs, stable over
time, but increase
after hospitalization in
68%
Stevenson LW et al,
JACC 2008;52:1702-8
Heart Transplantation
• The only “cure”
• >89,000 Heart Tx worldwide, >50,000 in US (1988-)
Hunt SA, Haddad F, JACC 2008:52:587-98. Hunt SA. NEJM 2006;355:3
Transplant Eligibility
J Heart Lung Transplant 2006;25:1024–42.
• Objective assessment of functional
capacity (limitation)
– 6 minute walk
– Cardiopulmonary exercise stress test (CPX)
• Peak exercise O2 consumption (VO2)
The Problem: Organ Shortage
• 4,000 pts are listed annually
• Yearly wait list mortality 10%
Gridelli and Remuzzi, NEJM 2000;303:404.
Mechanical Circulatory Support:
Ventricular Assist Devices: Bridge to Tx, Destination Therapy
• Volume Displacement
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–
–
–
Thoratec
Novacor
Heartmate LVAS
Abiomed
• Axial Flow
– Heartmate II
– Jarvik
• Centrifugal
– CentriMag
– Heartware
Baughman KL, Jarcho JA. NEJM 2007;379(9):846-9.
Timing: Transplant / VAD
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On optimal therapy (meds, EP devices)
Progressive “advanced” HF (NYHA III-IV)
Before truly “end stage”
Failure of maximal medical therapy
– Progressive HF symptoms
– More arrhythmias
• Evaluation is multidisciplinary, similar to
transplant
• Goal: ↑ quality and quantity of life
Real Patients
Timing: Transplant / VAD
• Clinical Risk Factors for 1-yr Mortality
Russell SD, Miller LW, Pagani FD, CHF 2008;14(6):316-21
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Walk <1 block without dyspnea
Na <136 mEq ⁄ L
BUN >40 mg ⁄dL or creatinine >1.8 mg ⁄dL
Can’t tolerate ACEI ⁄ ARB ⁄ BB
Diuretic dose >1.5 mg ⁄ kg ⁄ d
HF admission in past 6 months
No clinical improvement with CRT therapy, or no
CRT and QRS >140 ms
– Hematocrit <35%
• Multiple risk models
Heart Failure Survival Score
For 1-year event-free survival
Aaronson KD et al, Circulation 1997;95(12):2660-7
Reference for Table: Mehra MR et al, J Heart Lung Transplant. 2006:1024-42.
This pt’s
abs value
sum score
= 7.28
Seattle Heart Failure Model
Levy WC et al. Circulation 2006;113:1424-1433
www.SeattleHeartFailureModel.org
Systolic HF: Multidisplinary Care
• Primary Care Provider
• General
Cardiologist
• Heart Failure
Cardiologist
• Cardiac
Surgeon
• EP
Cardiologist
Summary
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Systolic HF is common
Always R/O CAD
Do thorough FH
R/O and Rx sleep apnea and anemia
Aim for target doses for evidencebased HF pharmacologic therapies
Stepwise Therapy for SHF
Start Rx for ACC/AHA Stage A
Optimize Rx for Stages B-D as follows:
, behavioral modifications
, B-blockers
Stage B
Stage C
Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574
Stage D
Summary
• Aim for target doses for evidence-based HF
pharmacologic therapies
• ICDs underutilized, yet prognostically important
• CRT can be considered earlier than “advanced
stage”, but certain subgroups respond better
• If still symptomatic beyond optimal behavior,
meds, and EP devices, consider HTx and VAD
– Always better to consider these therapies early vs
too late
UNC Heart Failure Team
www.uncheartandvascular.org
Cardiology (ph 919-843-5214)
Cardiothoracic Surgery
Pager 919-123-HEART (123-4327)
(ph 919-966-3381)
Brett Sheridan, MD
Patricia Chang, MD MHS
brett_sheridan@med.unc.edu
patricia_chang@med.unc.edu
Andy Kiser, MD
Brian Jensen, MD
andy_kiser@med.unc.edu
brian_jensen@med.unc.edu
Tracy Vernon-Platt, ANP
Carla Sueta, MD PhD
tvernon@unch.unc.edu
carla_sueta@med.unc.edu
Michael Mill, MD
Kirkwood Adams Jr, MD
Jana Glotzer, ACNP
jana_glotzer@med.unc.edu
michael_mill@med.unc.edu
Transplant Coordinators (ph 919-966-4728)
Scott Kowalczyk, RN BSN CCTC
skowalc@unch.unc.edu
Katie McMahon, RN BSN
Jason Katz, MD MHS
kmcmahon@unch.unc.edu
jason_katz@med.unc.edu
VAD Coordinators (pgr 919-216-2095)
Mandy Bowen, RN BSN
abowen@unch.unc.edu
Heart Failure NP
Sarah Waters, ANP
sarah_waters@med.unc.edu
Danielle Miller, RN BSN
drmiller@unch.unc.edu
1-866-862-4327 = 866-UNC-HEART
UNC Center for Heart and Vascular Care
One Call Referral Service