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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.

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Heart Failure in 2012

Patricia P. Chang, MD MHS FACC

Associate Professor, Medicine

Director, Heart Failure & Transplant Program

February 25, 2012

  • No relationships to disclose
  • I will discuss products that are investigational or used off-label
  • 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?
  • Epidemiology
  • Evaluation: etiology, testing
  • Common comorbidities
  • Therapies and timing

Disclaimer: More focus on Systolic HF vs HF with preserved EF

  • Epidemiology
  • Evaluation: etiology, testing
  • Common comorbidities
  • Therapies and timing
hf estimates
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
“Diastolic” vs Systolic HF
  • Aurigemma GP, Gaasch WH. NEJM 2004;351:1097-105.
systolic hf vs hfpef
Systolic HF vs HFpEF

4596 HF patients, Mayo Clinic

Owan TE et al, NEJM 2006; 355(3):254

survival by hf type
Survival by HF type

Owan TE et al, NEJM 2006; 355(3):254

survival by gender
Survival by Gender
  • Olmstead County: N=4537 HF patients (1979-2000) by ICD-9-CM codes (98% (+) Framingham criteria)



Rogers VL et al, JAMA 2004;292:344

survival by race gender study
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
SHF Survival by Etiology & Gender


Etiology may be more important



  • Frazier CG et al, JACC 2007;49(13):1450-8.


Evaluation: etiology, testing

Common comorbidities

Therapies and timing

practice guidelines
Practice Guidelines
  • ACC/AHA: 1995, 2001, 2005, 2009
heart failure stage vs class
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 guidelines1
Practice Guidelines
  • HFSA: 1999, 2006, 2010
  • ESC: 2001, 2005, 2008 (2010)
etiology of systolic hf
Etiology of Systolic HF


  • Coronary artery disease (“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
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
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
Representative Genomewide Association Studies (GWAS) of Common CVDs

O'Donnell CJ, Nabel EG. N Engl J Med 2011;365:2098-2109

familial dcm
Familial DCM
  • New Idiopathic DCM dx = Familial in 20-35% (when 1st degree family members screened)
  • Point mutations in 31 autosomal and 2 X-linked genes
    • But only account only for 30-35% genetic causes
  • Hershberger RE, Siegfried JD, JACC 2011;57(16):1641-9
genetic testing
Genetic Testing
  • Genetics Clinic at UNC (Meadowmont)
  • Familion “send out” (


Evaluation: etiology, testing

Common comorbidities

Therapies and timing

  • 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
  • ~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
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]


Evaluation: etiology, testing

Common comorbidities

Therapies and timing

standard hf therapy systolic hf hfpef
Standard HF Therapy(Systolic HF > HFpEF)
  • Guidelines
    • 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
    • Revascularization
    • Ventricular restoration (Dor procedure)
    • Mitral valve surgery
    • Cardiac transplantation
    • Mechanical circulatory support (VAD)
hf stages and therapies
HF Stages and Therapies

Stem cells?


ARB, H/I in some.



  • Jessup M, Brozena S. NEJM 2003;348:2007
stepwise therapy for hf
Stepwise Therapy for HF

, B-blockers

Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574

hf specific management
HF Specific Management
  • Identify and avoid exacerbating factors for HF
  • Behavioral management
    • Fluid restriction (2 L = ½ gallon)
    • Salt restriction (2 g)
    • Daily weights (?sliding scale diuretics for the savvy)
    • Exercise
    • Medical adherence
    • No smoking
  • Biomarkers: BNP/NT-proBNP
    • New ones but not commonly available (ST2, endoglin, galectin-3, cystatin C, neutrophil gelatinase-associated lipocalin, midregional pro-adrenomedullin, chromogranin A, adiponectin, resistin, leptin)
  • “Baseline/dry” weights & NTproBNP helpful

a.k.a. HF Core Measures

timing medications
Timing: Medications
  • Begin with ACC/AHA Stage A
  • Optimize for Stages B-D
timing medications1
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
Aim for Target Doses

Enalapril (Vasotec)

Captopril (Capoten)

Ramipril (Altace)

Lisinopril (Prinivil, Zestril)

Trandolapril (Mavik)

Quinapril (Accupril)

10 mg bid

50 mg tid*

5 mg bid

20 mg qd

4 mg qd

20-40 mg bid §



Bisoprolol (Zebeta)

Carvedilol (Coreg)

Metoprolol XL/CR (Toprol XL)

Metoprolol (Lopressor)

Atenolol (Tenormin)

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
Hospitalized Pt: ADHF
  • IV diuretics
    • Bolus or continuous
  • IV vasodilators
    • Nitroglycerin, Nesiritide, Nitroprusside
  • IV inotropes
    • Milrinone, Dobutamine, Dopamine
  • Optimize PO regimen
  • Advanced,End-stage
  • Systolic HF

Hunt SA, et al. ACC/AHA HF Guidelines Update. Circulation 2009;119(14):e391-479.

alternatives to drugs
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 re-hospitalizations,  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
Implantable Cardioverter Defibrillator LVEF ≤35%
  • 2° Prevention
    • AVID (1997)
  • 1° Prevention
    • 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
Timing: ICD
  • 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)
    • Why? NNT = 6 (MADIT-II) to 14 (SCD-HeFT)
      • Patient vs Doctor?

Bradfield J et al, PACE 2009; 32:S194–S197

icd implant rates overall low
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
ICD Implant Rates

Highest in large centers with sophisticated cardiac facilities

Shah B et al JACC 2009;53(5):416-22

reiterate the message
Reiterate the Message?
  • Life-saving
  • Prognostically Important
icd shocks poor prognosis
ICD Shocks = Poor Prognosis

Any shock is bad

  • 33% SCD-HeFT pts received ≥1 ICD shock (128 pts appropriate, 87 inappropriate, 54 both types)
  • Most common cause of death = progressive HF

More shocks are worse

Poole JE et al, NEJM 2008;359:1009-17

cardiac resynchronization therapy
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
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 trial1
  • ~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.

  • 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
CRT “Subgroups”
  • Pts who seem to benefit more:
    • QRS >150 msec (MADIT-CRT, RAFT)
    • Women (MADIT-CRT)
reverse remodeling madit crt
Reverse RemodelingMADIT-CRT
  • Responders: LA volume <40 ml/m2, women, nonischemic CM, LBBB, QRS ≥150, LVEDV ≥125 ml/m2, prior hospitalization for HF

Moss AJ et al, N Engl J Med 2009;361:1329-38.

Goldenberg I et al, Circulation 2011;124(14):1527-36

crt limitations
CRT Limitations

~30% do not respond to CRT (PROSPECT, Bax JJ et al, JACC 2009;53:1933-1943)

HF does ultimately progress

patient preferences
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
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
Transplant Eligibility
  • Objective assessment of functional capacity (limitation)
    • 6 minute walk
    • Cardiopulmonary exercise stress test (CPX)
      • Peak exercise O2 consumption (VO2)

J Heart Lung Transplant 2006;25:1024–42.

the problem organ shortage
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
    • 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
Timing: Transplant / VAD
  • 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
timing transplant vad1
Timing: Transplant / VAD
  • Clinical Risk Factors for 1-yr Mortality

Russell SD, Miller LW, Pagani FD, CHF 2008;14(6):316-21

    • 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
Heart Failure Survival Score

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

For 1-year event-free survival

seattle heart failure model
Seattle Heart Failure Model

  • Levy WC et al. Circulation 2006;113:1424-1433
systolic hf multidisplinary care
Systolic HF: Multidisplinary Care
  • Primary Care Provider
  • Cardiac Surgeon
  • General Cardiologist
  • EP Cardiologist
  • Heart Failure Cardiologist

Systolic HF is common

Always R/O CAD

Do thorough FH

R/O and Rx sleep apnea and anemia

Aim for target doses for evidence-based HF pharmacologic therapies

stepwise therapy for shf
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 Stage D

Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574

  • 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
UNC Heart Failure Team

Cardiology (ph 919-843-5214)

Pager 919-123-HEART (123-4327)

Cardiothoracic Surgery (ph 919-966-3381)

Brett Sheridan, MD

Patricia Chang, MD MHS

Andy Kiser, MD

Brian Jensen, MD

Tracy Vernon-Platt, ANP

Carla Sueta, MD PhD

Michael Mill, MD

Kirkwood Adams Jr, MD

Transplant Coordinators (ph 919-966-4728)

Jana Glotzer, ACNP

Scott Kowalczyk, RN BSN CCTC

Katie McMahon, RN BSN

Jason Katz, MD MHS

VAD Coordinators (pgr 919-216-2095)

Mandy Bowen, RN BSN

Danielle Miller, RN BSN

Heart Failure NP

Sarah Waters, ANP

1-866-862-4327 = 866-UNC-HEART

UNC Center for Heart and Vascular Care

One Call Referral Service