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Chronic Heart Failure When Should You be Worried?

Chronic Heart Failure When Should You be Worried?. James C. Fang, MD Heart Failure, Transplantation, and Circulatory Assistance Program University Hospitals/Case Medical Center. Stage A At high risk for HF but no structural heart disease

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Chronic Heart Failure When Should You be Worried?

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  1. Chronic Heart FailureWhen Should You be Worried? James C. Fang, MD Heart Failure, Transplantation, and Circulatory Assistance Program University Hospitals/Case Medical Center

  2. Stage A At high risk for HF but no structural heart disease Stage B Structural heart disease but w/o signs or symptoms of HF Stage C Structural heart disease with prior or current symptoms Stage D Refractory HF requiring specialized interventions HTN, DM, CAD, cardiotoxins LVH, LVSD, MI, asx valve dz Sx LVSD or asx on Tx Recurrent hosp, need for Tx/VAD Heart Failure Progressive, incurable, and ultimately fatal Hunt et al., Circulation 2001;104:2996

  3. Heart Failure is Increasing Baker, WH et al. Circulation, Feb 2006; 113: 799 - 805

  4. And Heart Failure Mortality Remains High Levy D et al. N Engl J Med 2002;347:1397-1402

  5. Mortality in End-Stage Heart Failure One-year survival rates • AIDS: 90% • Leukemia: 64% • Lung cancer: 42% • Pancreatic cancer: 21% • End-stage heart failure with optimum medical management: 25%

  6. 53 year old man admitted with weight gain and dyspnea despite increasing loop diuretics • Third admission this year • Idiopathic CMP (EF 25%) • PAF w/ inappropriate ICD shocks • CRT 6 months prior • Meds: carvedilol, digoxin, torsemide, aldactone, coumadin • No ACEI/ARB because of worsening renal function • BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR, loud P2, palp liver edge, distended abd, no edema • Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec

  7. HF hospitalization is ominous Risk of death increases three-fold after HF hospitalization Solomon SD, et al. Circulation 2007;116:1482-1487

  8. 53 year old man admitted with weight gain and dyspnea despite increasing loop diuretics • Third admission this year • Idiopathic CMP (EF 25%) • PAF w/ inappropriate ICD shocks • CRT 6 months prior • Meds: carvedilol, digoxin, torsemide, aldactone, coumadin • No ACEI/ARB because of worsening renal function • BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR, loud P2, palp liver edge, distended abd, no edema • Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec

  9. CRT NonrespondersSo What? • For CRT nonresponders, • Consider • It’s common (25-33%) • Definition of NR • Lead review or revision • Reprogramming • Advanced HF referral Cha, Yong-Mei, et al. J Cardiovasc Electrophysiol 2007;18:1015-1019

  10. 53 year old man admitted with weight gain and dyspnea despite increasing loop diuretics • Third admission this year • Idiopathic CMP (EF 25%) • PAF w/ inappropriate ICD shocks • CRT 6 months prior • Meds: carvedilol, digoxin, torsemide, aldactone, coumadin • No ACEI/ARB because of worsening renal function • BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR, loud P2, palp liver edge, distended abd, no edema • Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec

  11. 259 consecutive HF admissions to BWH 23% not on ACEI at d/c due to circulatory-renal limitations: symptomatic  BP renal insufficiency hyperkalemia ACEI No ACEI Age 55 60 CAD 43% 65% Duration 2 5 NYHA 3-4 50% 82% Creatinine 1.2 2.5 Death* 22% 57% ACE Inhibitor Intolerance: Marker of Severe Disease If they can’t tolerate RAS antagonists, Be very worried *median follow-up, 8.5 months Pinto et al., JACC 2003

  12. 53 year old man admitted with weight gain and dyspnea despite increasing loop diuretics • Third admission this year • Idiopathic CMP (EF 25%) • PAF w/ inappropriate ICD shocks • CRT 6 months prior • Meds: carvedilol, digoxin, torsemide, aldactone, coumadin • No ACEI/ARB because of worsening renal function • BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR, loud P2, palp liver edge, distended abd, no edema • Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec

  13. If you hear a third heart sound in the office… • SOLVD treatment Trial • 2569 pts w/ CHF • Enalapril vs placebo • Baseline examinations • Death or Hospitalization for CHF • RR 1.30 (1.11-1.53, p<0.005) • Adjusted for EF, NYHA, BP, HR, • Na, Cr, Age Drazner MH, NEJM 2001;345:574

  14. 53 year old man admitted with weight gain and dyspnea despite increasing loop diuretics • Third admission this year • Idiopathic CMP (EF 25%) • PAF w/ inappropriate ICD shocks • CRT 6 months prior • Meds: carvedilol, digoxin, torsemide, aldactone, coumadin • No ACEI/ARB because of worsening renal function • BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR, loud P2, palp liver edge, distended abd, no edema • Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec

  15. Escalating Creatinine in Heart Failure Populations

  16. 1) BUN > 43 mg/dL Mortality Risk of Decompensated Heart Failure 2) SBP <115 mmHg 1) BUN > 43 mg/dL 2) SBP <115 mmHg 3) SCr > 2.75 mg/dL 3) SCr > 2.75 mg/dL Fonorow G, et al. JAMA 2005

  17. Decompensated Heart FailureCART analysis Azotemia confers a high mortality Fonorow G, et al. JAMA 2005

  18. Prognostic Significance of Worsening Renal Function During HF Admission *Worsening Renal Function = Cre   0.3 Gottlieb et al., J Card Failure 2002:8;136

  19. When the Creatinine Rises… • Patient can’t go home • Diuretic doses are often decreased • ACE inhibitors/ARBs are often discontinued • Other medications are renally dosed • Inotropes may be initiated • PA catheter may be placed • Foley catheter may be re-placed • Cardiac US may be ordered • Renal US may be ordered (and is rarely helpful)

  20. Risk Factor Hazard Ratio Weight Score % WRF RR 0 9.8 1.0 H/o CHF 1.3 1 1 18.7 1.9 DM 1.4 1 2 20.3 2.1 SBP>160 1.4 1 1.5 ≤ Cr ≤ 2.5 2.1 2 3 30.3 3.1 Cr ≥ 2.5 3.5 3 4+ 52.8 5.4 Worsening Renal Function and CHFWho’s at risk? P<0.001 Forman, JACC 04

  21. 15 N = 16 NYHA III LVEF = 28% Placebo 10 5 0 GFR (% change) -5 80 mg IV Furosemide -10 -15 -20 -25 0 500 1000 1500 2000 2500 Cumulative Urine Output, 0–8 h (mL) Diuretics Decrease GFR in HF Gottlieb et al., Circulation 2002;105:1348

  22. Hemodynamic Response to IV Furosemide in Heart Failure 20 min after Hemodynamic Baseline Lasix 40 mg IV P PAWP (mm Hg) 28 ± 7 33 ± 9<0.01 SVI (mL/min/m2) 27 ± 8 24 ± 7 <0.01 HR (bpm) 87 ± 13 91 ± 16 <0.01 MAP (mm Hg) 90 ± 15 96 ± 15 <0.01 SVR (dyne • s/cm5) 1454 ± 394 1676 ± 415 <0.01 PRA (ng/mL) 9.9 ± 8.5 17.8 ± 16 <0.05 PNE (pg/mL) 667 ± 390 839 ± 368 <0.01 Francis et al., Ann Int Med 1985;103:1

  23. Diuretics and arrhythmic death? Cooper HA, et al. Circulation 1999;100:1311-1315

  24. Diuretic Resistance “a clinical state in which diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reached” “Braking Phenomenon” A decrease in response to a diuretic after the first dose Mechanisms • Poor oral bioavailability • Tubular hypertrophy to compensate for salt loss • Renal insufficiency • Neurohormonal mechanisms • Reduced renal blood flow Brater DC. N Engl J Med. 1998;339:387

  25. When the Diuretics Don’t Work…. • Restrict daily fluid intake (1.0-1.5 L) • Aggressive restriction of daily salt intake (≤2 g) • Stop NSAIDs • Decrease beta blockade • Give PO short-acting loop diuretic in several divided(and increasing) doses, bolus, or continuous IV administration • ?Nesiritide • Use sequential nephron blockade by adding to loop diuretic • thiazide diuretic • Aldosterone antagonist • short-term acetazolamide

  26. More than 50% of Patients Have Little or no Weight Loss During Hospitalization Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21

  27. Inotropic Therapy: Variable Effects Colucci et al., Circulation 1986;73:III175

  28. Mortality in Large Placebo-Controlled Trials of Inotropes for Heart Failure TrialInotropeNYHA NMortality vs Placebo PROMISE Milrinone III, IV 1088 28% Increase VEST Vesnarinone III, IV 3833 11% Increase Xamoterol Xamoterol III, IV 516 Hazard ratio: 2.5 PRIME II Ibopamine III, IV 1906 Hazard ratio: 1.26 PICO Pimodendan II, III 317 Hazard ratio: 1.8 • Inotropes should not be used for the • routine management of the cardiorenal syndrome PROMISE = Prospective Randomized Milrinone Survival Evaluation; VEST = Vesnarinone Trial; PRIME = Prospective Randomized Ibopamine Mortality Evaluation; PICO = Pimobendan in Congestive Heart Failure Felker GM, O’Connor CM. Am Heart J. 2001;142:393–401.

  29. Decompensated HF No Standard of Care • Wide variability in clinical practice • Few randomized controlled trials • Guidelines focus on: • stable outpatients • systolic (“low EF”) HF • Intravenous versus oral agents • Unclear endpoints to hospitalization • What is appropriate post-discharge care?

  30. What are the options? • Hemodynamic guided management • Vasopression antagonists (“Vaptans”) • Adenosine antagonists • Natriuretic peptides • Ultrafiltration • Advanced HF referral

  31. Ultrafiltration for Fluid Retentionin Heart Failure • Acute reductions in filling pressures • CO - no change or increased • Serum norepinephrine levels decreased • Improved lung compliance • Improved exercise capacity • Mixed effects on renal function Guazzi et al 1987,1990 Fauchald et al, 1986 Simpson et al,1985 Agostini et al,1993 Inoue et al, 1992

  32. UF in refractory CHF • 24 pts with Class IV HF • >5 kg weight gain • oliguria • Single UF session in CCU • mean time 9 hours • mean volume removed 4,880 ml • Results • No hypotension • Increased CO • Decrease SVR Marenzi JACC 2001

  33. Ultrafiltration in Diuretic ResistanceDecreasing Length of Stay • EUPHORIA Trial • 19 pts w/ CHF and diuretic • resistant • Furosemide > 80 mg • SCr > 1.5 mg/dl • Before IV diuretics • Avg 8367  4232 cc removed • 2.6 treatments • No readm w/in 30d

  34. CHF Solutions • Ultrafiltration, not dialysis • Two Peripheral IVs (CL preferred) • 100-500 ml/hr fluid removal over 24 hrs • Extracorporeal blood volume ~ 40 ml • Little hemodynamic effect • Systemic anticoagulation suggested • Limited need for nursing support • Minimal electrolyte shifts (isotonic filtrate) • Greater total body Na removal than diuretics for given volume

  35. The UNLOAD Trial

  36. The UNLOAD Trial • Ultrafiltration arm • Ultrafiltration rate ≤ 500 cc/hour • Duration/rate of fluid removal decided by treating physicians • IV diuretics prohibited during ultrafiltration • Standard Care arm • IV diuretics as bolus or continuous infusions • IV doses ≥ 2 times daily PO dose for the first 48 hours after randomization

  37. Primary End PointWeight Loss at 48 Hr Primary End PointWeight Loss at 48 Hr

  38. Freedom From Re-hospitalization for Heart Failure • UF decreased: • 1) % pts requiring re-hospitalization • 2) Number of HF re-hospitalizations • 3) Days of re-hospitalization for HF • 4) ED and unscheduled office visits

  39. Safety End Points: Change in Serum Creatinine

  40. 53 year old man admitted with weight gain and dyspnea despite increasing loop diuretics • Third admission this year • Idiopathic CMP (EF 25%) • PAF w/ inappropriate ICD shocks • CRT 6 months prior • Meds: carvedilol, digoxin, torsemide, aldactone, coumadin • No ACEI/ARB because of worsening renal function • BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR, loud P2, palp liver edge, distended abd, no edema • Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec

  41. When to get worried… • Recurrent hospitalizations • CRT nonresponders • Persistence of third heart sound on exam • Inability to tolerate RAS antagonists and/or beta blockers • Renal insufficiency is present • Poor or worsening functional capacity • RV dysfunction is present • High BNP levels • Recurrent ventricular arrhythmias • “Diastolic HF” in absence of hypertension (It won’t get better with time)

  42. Medically Refractory Heart Failure? • Persistent symptoms despite: • RAS antagonism with ACEI/ARB/Aldo antagonists • Beta blockers titrated to target doses • Device therapy (ie. ICD/CRT) • Addressing comorbidities (e.g. sleep apnea, anemia, etc.) • Participation in HF Disease Management Program • Inability to establish euvolemia without aggravating renal function • Inability to keep out of the hospital

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