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Patricia P. Chang, MD MHS FACC Associate Professor, Medicine

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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Patricia P. Chang, MD MHS FACC Associate Professor, Medicine

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  1. Heart Failure in 2012 Patricia P. Chang, MD MHS FACC Associate Professor, Medicine Director, Heart Failure & Transplant Program February 25, 2012

  2. Disclosures • No relationships to disclose • I will discuss products that are investigational or used off-label

  3. 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?

  4. Topics • Epidemiology • Evaluation: etiology, testing • Common comorbidities • Therapies and timing Disclaimer: More focus on Systolic HF vs HF with preserved EF

  5. Topics • Epidemiology • Evaluation: etiology, testing • Common comorbidities • Therapies and timing

  6. 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.

  7. “Diastolic” vs Systolic HF • Aurigemma GP, Gaasch WH. NEJM 2004;351:1097-105.

  8. Systolic HF vs HFpEF 4596 HF patients, Mayo Clinic Owan TE et al, NEJM 2006; 355(3):254

  9. Survival by HF type Owan TE et al, NEJM 2006; 355(3):254

  10. Survival by Gender • Olmstead County: N=4537 HF patients (1979-2000) by ICD-9-CM codes (98% (+) Framingham criteria) MEN WOMEN Rogers VL et al, JAMA 2004;292:344

  11. Survival by Race & Gender Study Loehr L, Rosamond W, Chang PP, et al. Am J Cardiol 2008;101(7):1016-1022

  12. 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.

  13. Topics Epidemiology Evaluation: etiology, testing Common comorbidities Therapies and timing

  14. Practice Guidelines • ACC/AHA: 1995, 2001, 2005, 2009 my.americanheart.org

  15. 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

  16. Practice Guidelines • HFSA: 1999, 2006, 2010 www.hfsa.org • ESC: 2001, 2005, 2008 (2010)

  17. Etiology of Systolic HF 2/3 • 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

  18. 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?

  19. 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

  20. Representative Genomewide Association Studies (GWAS) of Common CVDs O'Donnell CJ, Nabel EG. N Engl J Med 2011;365:2098-2109

  21. 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

  22. Genetic Testing • Genetics Clinic at UNC (Meadowmont) • Familion “send out” (www.familion.com)

  23. Topics Epidemiology Evaluation: etiology, testing Common comorbidities Therapies and timing

  24. 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

  25. 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)

  26. 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]

  27. Topics Epidemiology Evaluation: etiology, testing Common comorbidities Therapies and timing

  28. 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)

  29. HF Stages and Therapies Stem cells? Hemofiltration? ARB, H/I in some. ICD all • Jessup M, Brozena S. NEJM 2003;348:2007

  30. Stepwise Therapy for HF , B-blockers Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574

  31. 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

  32. Timing: Medications • Begin with ACC/AHA Stage A • Optimize for Stages B-D

  33. 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

  34. 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 § ACE-I BB 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

  35. 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.

  36. 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

  37. 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

  38. 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

  39. 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

  40. ICD Implant Rates Highest in large centers with sophisticated cardiac facilities Shah B et al JACC 2009;53(5):416-22

  41. Reiterate the Message? • Life-saving • Prognostically Important

  42. 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

  43. ICD Shocks = Poor Prognosis

  44. 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 battery • MUSTIC (QRS >150 ms)(2001) • MIRACLE (QRS >130 ms)(2002) • COMPANION (QRS >120 ms)(2004) • CARE-HF (QRS >120 ms) (2005)*

  45. 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)

  46. 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

  47. 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

  48. 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.

  49. 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.

  50. CRT “Subgroups” • Pts who seem to benefit more: • QRS >150 msec (MADIT-CRT, RAFT) • Women (MADIT-CRT)

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