Diagnosis and Treatment of Acute Heart Failure :Diagnosis and Treatment of Acute Heart Failure August 9, 2006 JoAnn Lindenfeld, MD


Hospitalization: The Predominant Contributor to HF Costs38.1 billion (5.4% of healthcare) :Hospitalization: The Predominant Contributor to HF Costs38.1 billion (5.4% of healthcare) 60.6% Inpatient care 38.6% Outpatient care (3.4 visits/year /patient) 0.7% Transplants $270 million (O’Connell JB et al. J Heart Lung Transplant. 1994;13:S107-S112) 23.1 billion 14.7 billion


Similarities Between Acute MI and Acute Decompensated HF in the US :Similarities Between Acute MI and Acute Decompensated HF in the US (Gheorghiade M, et al. Circulation 2005;112:3958-68)


Slide 4:I pretty much try to stay in a constant state of confusion just because of the expression it leaves on my face. - Johnny Depp


Hospital discharges for HF by age: 1990 vs 2000 :Hospital discharges for HF by age: 1990 vs 2000 ?53% ?42% ?32% ?84% ?44% ?44%


Natural History of Chronic and Acute Heart Failure :Natural History of Chronic and Acute Heart Failure Initial phase Last year Normal heart Chronic heart failure5 million in the US10 million in Europe Death Initial myocardial injury First ADHF episode:Pulmonary edemaER admission Later ADHF episodes:Rescue therapyICU admission What if fluid overload causes progressive HF? Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G. Heart Viability


Mechanism of Worsening HF with Renal Dysfunction :Mechanism of Worsening HF with Renal Dysfunction Renal dysfunction (Schrier RW. JACC 2006;47:1-8)


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


Slide 9:Copyright restrictions may apply. Fonarow, G. C. et al. JAMA 2005;293:572-580. Predictors of In-Hospital Mortality


Heart Failure Risk Scoring System :Heart Failure Risk Scoring System Lee, D. S. et al. JAMA 2003;290:2581-2587.


Slide 11:Lee, D. S. et al. JAMA 2003;290:2581-2587. Mortality Rates in Acutely Decompensated Heart Failure by Risk Score


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


Epidemiology of HF :Epidemiology of HF (Gheorghiade M, et al. Circulation 2005;112:3958-68)


Epidemiology of HF :Epidemiology of HF (Gheorghiade M, et al. Circulation 2005;112:3958-68)


Congestion in HF: Most Admitted Patients are “Wet” :Congestion in HF: Most Admitted Patients are “Wet” (ADHERE Registry. 3rd Qtr 2003 National Benchmark Report.)


ADHERE: Diuresis During ADHF Hospitalization :ADHERE: Diuresis During ADHF Hospitalization N=26,757 Men - 3.5 kg Women -2.5 kg


Time Course of Events Preceding ADHF Hospitalization :I I I I I I I I I Time Course of Events Preceding ADHF Hospitalization -90 -25 -20 -15 -10 -5 0 5 10 I I I I II I I I I I I I I I I I I I I I I I I I I I I I I Days Admission Dyspnea (8-9) Cough (10) Weight gain (11) Edema (12) Edema, Cough, Fatigue (7) Dyspnea (3) (-89 to -1) (-25 to -5) (-21 to ?) ePAD (19) Thoracic Impedance (15) SDAAM (16)


Rapid Assessment of Hemodynamic Status :Rapid Assessment of Hemodynamic Status Congestion at Rest Low Perfusion at Rest NO NO YES YES Signs/Symptoms of Congestion: Orthopnea / PND JV Distension Hepatomegaly Edema Rales (rare in chronic heart failure) Elevated est. PA systolic( loud P2 and RV lift) Valsalva square wave Abdominojugular reflux S3 Possible Evidence of Low Perfusion: Narrow pulse pressure Cool extremities Sleepy / obtunded Hypotension with ACE inhibitor Low serum sodium Renal Dysfunction (one cause) Elevated LFTs Pulsus alternans


Value of Proportional Pulse Pressure to predict low cardiac output :Value of Proportional Pulse Pressure to predict low cardiac output Pulse Presssure Systolic BP- Diastolic BP Proportional Blood Pressure Systolic BP – Diastolic BP = = 25% Systolic BP = CI = 2.2 L/min/M2 (JAMA 1989;261:884)


Rapid Assessment of Hemodynamic Status :Rapid Assessment of Hemodynamic Status Congestion at Rest Low Perfusion at Rest NO NO YES YES Warm & Dry Warm & Wet Cold & Wet Cold & Dry Nohria,J Cardiac Failure 2000;6:64 67% 28% 5%


Physical Findings for PCW > 22 mm Hgat admission in ADHF :Physical Findings for PCW > 22 mm Hgat admission in ADHF


Valsalva Maneuver :Valsalva Maneuver Normal Abnormal


Potential Endpoints of Therapy in ADHF :Potential Endpoints of Therapy in ADHF Resting symptoms JVD Rales Edema PCW or Cardiac Output BNP Echo (mitral regurgitation or PA pressure) (Drazner M, et al. J Heart Lung Tx 1999;1126. Rosario, et al. JACC 1998;1819-24. Johnson, et al. Ciruclation 1998 [abstract])


Is the Swan-Ganz Catheter Useful in the Patient with Acute Decompensated HF? :Is the Swan-Ganz Catheter Useful in the Patient with Acute Decompensated HF? (Stevenson, et al. JAMA 2005;294:1625-1633) NO


Clinical outcomes in the ESCAPE trial :Shah M. American Heart Association Scientific Sessions 2004. Clinical outcomes in the ESCAPE trial p=NS for all PAC=pulmonary artery catheterization; clinical=clinically guided therapy only


ESCAPEIn-hospital complications and adverse events :ESCAPEIn-hospital complications and adverse events Shah M. American Heart Association Scientific Sessions 2004. Nov 7-10, 2004;


Slide 27:0 6 12 18 24 Months 0 10 20 30 40 50 60 Total Mortality Risk% 199 257 PCW > 16 mmHg PCW 2.6 L/min-M2 Cardiac Index < 2.6 L/min/M2 Early Response of PCW but not CI Predicts Subsequent Mortality in Advanced Heart Failure Final hemodynamic measurement in 456 advanced HF patients after tailored vasodilator therapy P=NS (Fonarow G Circulation 1994;90:I-488)


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


Structure and Cleavage of proBNP :Structure and Cleavage of proBNP T ½ = 2 hours T ½ = 22 minutes Both digested by NEPs and cleared renally


BNP is Increased with HF and Systolic or Diastolic Dysfunction :BNP is Increased with HF and Systolic or Diastolic Dysfunction Maisel AS, et al. JACC 2003;41:2010


BNP Levels Pre-discharge Predict Mortality and Readmisssion :BNP Levels Pre-discharge Predict Mortality and Readmisssion (Logeart D, et al. JACC 20042;40:976-82)


BNP on admission is a poor predictor of PCW :BNP on admission is a poor predictor of PCW (Forfia PR, et al. J Am Cardiol 2005;45:1667-71)


STARBRITE TRIAL :STARBRITE TRIAL


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


Slide 35:Sodium Reabsorption Sites in the Nephron Proximal Tubule 70% Distal Tubule 20% 5% 1-4% Loop of Henle Collecting Tubule Glomerulus Thiazide Diuretics Loop Diuretics


Slide 36:Sodium Excretion Rate Maximal Response Dose Bioavailability Tubular secretory capacity Rate of absorption Time course of delivery Efficiency Threshold Altered dose-response relationship Braking phenomenon Loop Diuretic Excretion Rate A B Determinants of Diuretic Response


Bioavailability of Loop Diuretics :Bioavailability of Loop Diuretics 100% 80% 50% 10% - - - - furosemide torsemide bumetanide


Ceiling Doses of Loop Diuretics (mg) :Ceiling Doses of Loop Diuretics (mg) (Adapted from Brater C. New Engl J Med 1999)


Bioavailability of Loop Diuretics :Bioavailability of Loop Diuretics 100% 80% 50% 10% - - - - furosemide torsemide bumetanide


Usefulness of Torsemide after Admission for ADHF :Usefulness of Torsemide after Admission for ADHF 234 pts admitted for ADHF torsemide furosemide 52% ? HF Hospitalization (Murray, et al. Am J Med 2000;111:513-521) Randomized on Discharge


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


Slide 42:(de Silva, R. et al. Eur Heart J 2006 27:569-581) Baseline Renal Dysfunction and Worsening Renal Function (WRF) are Additive in Predicting Mortality in HF Patients sCreatinine =1.2 1.2-2.0 =2.0 =1.2 1.2-2.0 =2.0 WRF (>0.3mg/dL) no no no yes yes yes And a fall in sCr of > 0.3 mg/dL was associated with improved mortality Predictors of WRF were thiazide diuretics, increased BUN, and vascular disease


What to do when the creatinine begins to increase? :What to do when the creatinine begins to increase? Check volume status Check blood pressure (especially at peak onset of vasodilators) Restrict sodium intake (and water if hyponatremic) Check for renal problems (obstructions, prooteinuria, interstitial nephritis) Consider vasodilators or inotropes Consider ultrafiltration


UNLOAD Trial :UNLOAD Trial Costanzo MR. American College of Cardiology 2006 Scientific Sessions; March 12, 2006; Atlanta, GA. n = 200 with ADHF IV Diuretics Ultrafiltration for 48 hours


Ultrafiltration Improved Weight Loss But Not Symptoms :Ultrafiltration Improved Weight Loss But Not Symptoms Costanzo MR. American College of Cardiology 2006 Scientific Sessions; March 12, 2006; Atlanta, GA.


Ultrafiltration Decreased Rehospitalization :Ultrafiltration Decreased Rehospitalization Costanzo MR. American College of Cardiology 2006 Scientific Sessions; March 12, 2006; Atlanta, GA.


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


IMPACT - HF :IMPACT - HF n = 363 with ADHF Symptomatic hypotension Recent inotropes AV Block or SSS Hepatic impairment Randomized Pre-discharge carvedilol Post-discharge carvedilol (Galtis WA, et al. JACC 2004;43:1534)


IMPACT - HF :IMPACT - HF (Galtis WA, et al. JACC 2004;43:1534)


ACE-inhibitor or Beta-blocker First?CIBIS-III :ACE-inhibitor or Beta-blocker First?CIBIS-III (Willenheimer R, et al. Circulation 2005;112:2426-2435)


ACE-inhibitor or Beta-blocker First?CIBIS-III :ACE-inhibitor or Beta-blocker First?CIBIS-III (Willenheimer R, et al. Circulation 2005;112:2426-2435) Bisoprolol first Enalapril first (HR 0.94, CI = 077-1.16, = = 0.0.019 for noninferiority)


ACE-inhibitor or Beta-blocker First?CIBIS-III :ACE-inhibitor or Beta-blocker First?CIBIS-III (Willenheimer R, et al. Circulation 2005;112:2426-2435) (HR 0.88, CI = 0.63-1.22, p = 0.44) Bisoprolol first Enalapril first Survival


ACE-inhibitor or Beta-blocker First?CIBIS-III :ACE-inhibitor or Beta-blocker First?CIBIS-III (Willenheimer R, et al. Circulation 2005;112:2426-2435) Freedom from hospitalization for worsening HF Bisoprolol first Enalapril first (HR = 1.25, CI = 0.87-1.81, p = 0.23)


Current Treatment of Heart Failure :Acutely Decompensated Heart Failure (ADHF) ? How to predict mortality? ? What do these patients look like? ? How do you know how much to diurese? ? Is BNP useful in judging diuresis? ? How to use diuretics ? What do you do when the creatinine increases? ? Is ultrafiltration useful? ? ACE-inhibitors or beta-blockers first? ? Should beta-blockers be started in hospital? ? When should you use intravenous therapy? Current Treatment of Heart Failure


Rapid Assessment of Hemodynamic Status :Rapid Assessment of Hemodynamic Status Congestion at Rest Low Perfusion at Rest NO NO YES YES Warm & Dry Warm & Wet Cold & Wet Cold & Dry Nohria,J Cardiac Failure 2000;6:64 67% 28% 5%


Goals in the Treatment of the Patient with Acutely Decompensated HF :Goals in the Treatment of the Patient with Acutely Decompensated HF


Enoximone or Milrinone are preferable to Dobutamine in Patients on Beta-blockers :Enoximone or Milrinone are preferable to Dobutamine in Patients on Beta-blockers Metra M et al; JACC 2002


Enoximone or Milrinone are preferable to Dobutamine in Patients on Beta-blockers :Enoximone or Milrinone are preferable to Dobutamine in Patients on Beta-blockers Metra M et al; JACC 2002


Before I came here I was confused about this subject. Having listened to your lecture I am still confused. But on a higher level.-Enrico Fermi :Before I came here I was confused about this subject. Having listened to your lecture I am still confused. But on a higher level.-Enrico Fermi