1. Acute Heart Failure Kendra Marsh, MD Clinical Instructor, Cardiology Fellow Department of Cardiology University of Illinois at Chicago

2. Objectives Definitions Definitions Epidemiology Epidemiology Pathophysiology Pathophysiology Diagnosis Diagnosis Management Management Summary of Guidelines Summary of Guidelines Recommended Reading Recommended Reading

3. Definitions Definitions Epidemiology Epidemiology Pathophysiology Pathophysiology Diagnosis Diagnosis Management Management Summary of Guidelines Summary of Guidelines Recommended Reading Recommended Reading

4. Acute Heart Failure Rapid onset of symptoms and signs related to abnormal cardiac function Rapid onset of symptoms and signs related to abnormal cardiac function As a result of Systolic Dysfunction, Diastolic Dysfunction, Arrhythmias, or Preload-After load Mismatch As a result of Systolic Dysfunction, Diastolic Dysfunction, Arrhythmias, or Preload-After load Mismatch

5. Related Clinical Conditions De Novo or Chronic Decompensated De Novo or Chronic Decompensated Hypertensive Hypertensive Pulmonary Edema Pulmonary Edema Cardiogenic Shock Cardiogenic Shock High Output Heart Failure: Arrhythmias, Thyrotoxicosis, Anemia, Paget’s Disease High Output Heart Failure: Arrhythmias, Thyrotoxicosis, Anemia, Paget’s Disease Right Heart Failure Right Heart Failure

6. Killips Classification Stage I: No Heart Failure Stage I: No Heart Failure Stage II: Heart Failure Stage II: Heart Failure S3 gallop, Pulmonary venous Hypertension, Rales <1/2 of the lung fields S3 gallop, Pulmonary venous Hypertension, Rales <1/2 of the lung fields Stage III: Severe Heart Failure Stage III: Severe Heart Failure Frank pulmonary Edema, rales through out the lung field Frank pulmonary Edema, rales through out the lung field Stage IV: Cardiogenic Shock Stage IV: Cardiogenic Shock Systemic hypotension, peripheral vasoconstriction, endorgan failure, cyanosis, diaphoresis Systemic hypotension, peripheral vasoconstriction, endorgan failure, cyanosis, diaphoresis This classification system uses the clinical exam to determine the degree of cardiomyopathy after an acute MI.

7. Clinical Severity Classification PERFUSION PERFUSION CONGESTION CONGESTION –Auscultation of the lungs Warm/Dry Cold/Dry Warm/Wet Cold/Wet

8. Definitions Definitions Epidemiology Epidemiology Pathophysiology Pathophysiology Diagnosis Diagnosis Management Management Summary of Guidelines Summary of Guidelines Recommended Reading Recommended Reading

9. Epidemiology We have greatly improved our management of acute myocardial infarctions. We have greatly improved our management of acute myocardial infarctions. Large component of care is inpatient Large component of care is inpatient Expensive to manage Expensive to manage High mortality in patients status post MI. High mortality in patients status post MI. The leading cause of hospitalization in patients over 65 The leading cause of hospitalization in patients over 65 1 million hospitalizations per year with HF as primary diagnosis 1 million hospitalizations per year with HF as primary diagnosis 2.5 million hospitalizations with heart failure as secondary diagnosis 2.5 million hospitalizations with heart failure as secondary diagnosis

10. Definitions Definitions Epidemiology Epidemiology Pathophysiology Pathophysiology Diagnosis Diagnosis Management Management Summary of Guidelines Summary of Guidelines Recommended Reading Recommended Reading

11. A Vicious Circle

12. In an effort to maintain adequate tissue perfusion the body has three defenses: increase heart rate, vascular tone and circulating volume.

17. Definitions Definitions Epidemiology Epidemiology Pathophysiology Pathophysiology Diagnosis Diagnosis Management Management Summary of Guidelines Summary of Guidelines Recommended Reading Recommended Reading

22. Definitions Definitions Epidemiology Epidemiology Pathophysiology Pathophysiology Diagnosis Diagnosis Management Management Summary of Guidelines Summary of Guidelines Recommended Reading Recommended Reading

23. General Therapeutic Approach

25. Oxygen Class I, C Class I, C –Improves oxygen delivery and tissue perfusion –Goal Saturation should be 95-98%, beyond that there is no indication for increased FIO2 –Always consider CPAP first or Non Invasive Positive Pressure Ventilation First –Endotrachial Intubation as a last resort

26. Pharmacotherapy Morphine Morphine Anticoagulation Anticoagulation Vasodilators Vasodilators Diuretics Diuretics Beta Antagonists Beta Antagonists Inotropic Agents Inotropic Agents

27. Morphine Class IIb, B Class IIb, B –Great Early in management –Venodilation –Mild Arterial Dilation –Slows Heart rate

28. Anticoagulation No evidence to support anticoagulation for Acute Heart Failure alone No evidence to support anticoagulation for Acute Heart Failure alone Yes in the case of Atrial Fibrillation Yes in the case of Atrial Fibrillation Yes in the case of LV thrombus Yes in the case of LV thrombus Large Placebo Control Trial with Enoxiparin at 40mg SC showed no mortality benefit Large Placebo Control Trial with Enoxiparin at 40mg SC showed no mortality benefit

29. Vasodilators Nitrates: Class I, B Nitrates: Class I, B –Improves Cardiac Output and decreases PCWP –Best with diuretics –Low doses, venodilation –High doses, arterial dilation –Preload and Afteroad –Good for 16-24 hours Sodium Nitroprusside: Class I, C Sodium Nitroprusside: Class I, C –Severe Heart Failure with Hypertension –Primarily arterial dilation –Need for arterial invasive monitoring –Stop if active ischemia due to coronary steal phenomenon

30. Niseritide Recombinant B-type Brain Naturetic Peptide Recombinant B-type Brain Naturetic Peptide Venous, Arterial and coronary affects Venous, Arterial and coronary affects Enhanced sodium excretion Enhanced sodium excretion Suppresses RAAS and sympathetic system Suppresses RAAS and sympathetic system

31. Vasodilators in the Management of Acute Heart Failure Trial (VAMC) DesignEnrolledAgents Primary End Point Outcomes Randomized Double- Blinded Control Effects at 3 hours 489 Acute CHF PCWP> 20mmHg Niseritide Bolus 2 micr/kg Nitroglycerine IV Change in PCWP from baseline Reduced dyspnea compared to standard therapy alone Significant reduction in dyspnea score and PCWP with addition of NIseritide to standard therapy No good data to support adverse affects on renal function and niseritide No good data to support adverse affects on renal function and niseritide Retrospective analysis of VMAC showed potential for increased creatinin with increasing niseritide dose. Retrospective analysis of VMAC showed potential for increased creatinin with increasing niseritide dose.

32. Summary of Vasodilators

33. Diuretics Class I, B Class I, B

34. Diuretic Resistance can be associated with increased mortality.

35. Ultrafiltration RAPID-CHF Trial RAPID-CHF Trial –40 patients –ADHF and Renal Insufficiency (Cr >1.5) –Ultrafiltration had significant increase in fluid removal after 24 hours –4650 L vs 2838L UNLOAD Trial UNLOAD Trial –200 patients –Renal insufficiency was not a criteria for inclusion –Standard care vs ultra filtration –48 Hours 4.6 L vs 3.3L –90 Days fewer rehospitalizations.22 vs.46 and fewer unscheduled clinic visits 21 vs 44 Option in the setting of failed diuretic and vasodilator therapy

36. Beta Blockers No data to support benefits in AHF No data to support benefits in AHF Traditionally considered a contra indication Traditionally considered a contra indication Consider if there is active ischemia and blood pressure tolerates. Consider if there is active ischemia and blood pressure tolerates. Ischemia and Tachycardia, Class IIb, C Ischemia and Tachycardia, Class IIb, C Acute MI after stabilization, Class IIa, B Acute MI after stabilization, Class IIa, B Chronic CHF after stabilization, Class I, A Chronic CHF after stabilization, Class I, A

37. Inotropic Agents Peripheral Hypoperfusion refractory to vasodilators and diuretics, Class IIa, C Peripheral Hypoperfusion refractory to vasodilators and diuretics, Class IIa, C Danger: May increase oxygen demand and calcium loading Danger: May increase oxygen demand and calcium loading

38. Dopamine and Dobutamine Dopamine: Dopamine: –Vasodilator of Renal, Coronary, splanchnic and Cerebral Vascular beds –Hypotensive patients –Drawbacks: arrhythmia, increased pulmonary vascular resistance and increased afterload Dobutamine, Class IIa, C Dobutamine, Class IIa, C –Hypotension and low Urine output –Beta 1 and 2 agonist –At high doses increases SVR –Additive effect with Phosphodiesterase inhibitors –Draw Backs- arrhythmia, reflex decrease in sympathetic tone

39. Phosphodiesterase Inhibitors Milrinone and Enoximone Milrinone and Enoximone –Hypoperfusion despite Diuretics and Vasodilators with good blood pressure. Class IIb, C –Lucitropic, Inotropic, vasodilator –Inhibits degredation of Cyclic AMP –Increase CO, CI, Stroke Volume, –Decrease PAP, PVR and PCWP –Immediate Action –Effect is Distal to Beta receptors, can be used in the setting Beta Blocker therapy. Class IIa, C

40. Outcomes of a Prospective Trial of Intravenous Milrinone For Exacerbations of Congestive Heart Failure OPTIME-CHF JAMA 2002 Design Randomized, Control, Double Blinded Milrinone versus Placebo Enrolled Broad Population with systolic dysfunction Without low output syndrome 949 patients Primary Endpoints Repeat hospitalization for cardiovascular causes within 60 days of discharge. Outcomes No difference in primary end point between Milrinone and placebo. Higher instance of atrial arrhythmia and hypotension with Milrinone. Milrinone is associated a 30% increase in mortality Conclusions Not indicated in routine use with standard medica therapy.

41. Levosimendan Calcium ion sensitization Calcium ion sensitization Also Pimobendon Also Pimobendon Increases Contractility Increases Contractility A little PDI activity as well A little PDI activity as well Severe dysfunction with preserved blood pressure Severe dysfunction with preserved blood pressure Drawback: very pro- arrhythmogenic Drawback: very pro- arrhythmogenic

42. Clinical Trials LIDO Trial LIDO Trial –Levosimendan 24 hr infiusionvs Dobutamine –203 Patients –Severe Decompensated HF, AHF, HF after CABG –Excluded if cardiogenic shock –Endpoints, increased CI (35% vs 25%) and reduced PCWP (28% vs 15%) in favor of Levosimendan SURVIVE Trial SURVIVE Trial Levosimendan vs Dobutamine 24 hour therapy Levosimendan vs Dobutamine 24 hour therapy 1327 patients 1327 patients Endpoints symptomatic relief and BNP Endpoints symptomatic relief and BNP Levosimendan Greater reduction in BNP but no difference in symptomatic relief Levosimendan Greater reduction in BNP but no difference in symptomatic relief

43. Pressors Vasopressin: Cardiogenic shock in conjunction with inotropic therapy Vasopressin: Cardiogenic shock in conjunction with inotropic therapy Epinephrine B1 and B2, Epinephrine B1 and B2, Norepinephrine alpha receptors Norepinephrine alpha receptors Cardiac Glycosides: Inhibit cardiac Na/K ATPase, increases Ca/Na exchange mechanism. Tachycardia induced Cardiomyopathy. Cardiac Glycosides: Inhibit cardiac Na/K ATPase, increases Ca/Na exchange mechanism. Tachycardia induced Cardiomyopathy.

45. Cardiac and Ventricular Assist Devices

46. Temporary Devices IABP IABP Tandem Heart Tandem Heart ECMO ECMO Ventricular Assist Devices Ventricular Assist Devices

47. IABP

48. ECMO ECMO removes carbon dioxide from and adds oxygen to venous blood via an artificial membrane lung ECMO removes carbon dioxide from and adds oxygen to venous blood via an artificial membrane lung Severe respiratory failure Cardiac Failure with inability to wean off Bypass Bridge to Cardiac Transplant

49. Temporary Devices: Tandem Heart pVAD Continuous-flow centrifugal assist device placed extracorporeally Continuous-flow centrifugal assist device placed extracorporeally Cannula in femoral vein through intraatrial septum into LA Cannula in femoral vein through intraatrial septum into LA Pump withdraws oxygenated blood from the left atrium, propels it by a magnetically driven impeller through the outflow port Pump withdraws oxygenated blood from the left atrium, propels it by a magnetically driven impeller through the outflow port Blood returns into femoral artery via arterial cannula Blood returns into femoral artery via arterial cannula

50. Longer-term implantable devices Novacor Novacor HeartMate XVE HeartMate XVE HeartMate II HeartMate II Next Generation Devices Next Generation Devices

52. Operative Mortality Prediction Score Requirement for ventilator support — 4 points Requirement for ventilator support — 4 points Clinical picture of post-cardiotomy shock — 2 points Clinical picture of post-cardiotomy shock — 2 points Use of temporary LVAD prior to Heart-Mate insertion — 2 points Use of temporary LVAD prior to Heart-Mate insertion — 2 points Central venous pressure >16 mmHg — 1 point Central venous pressure >16 mmHg — 1 point Prothrombin time >16 seconds — 1 point Prothrombin time >16 seconds — 1 point Scoring Scoring –0-5: Low risk Mortality 8% –5-7: Intermediate Risk Mortality 32% –8-10: High Risk Mortality 49%

53. Novacor- Long-term Device Cardiac Replacement Bridge to Transplant Magnetic Actuator Blood Propelled via collapsing bladder and to prosthetic valves One Year Survival No risk factors, 60% 1 Risk factor, 24% 25% risk of Thromboembolic Event

54. Heart-mate Rehabilitation and hospital discharge Rehabilitation and hospital discharge $70,000 $70,000 LV apex to ascending aorta LV apex to ascending aorta Textured surface allows for endotheliazation to reduce need for anticoagulation Textured surface allows for endotheliazation to reduce need for anticoagulation Improves perfusion: decrease renal failure and pulmonary HTN Improves perfusion: decrease renal failure and pulmonary HTN Complications: infection, bleeding, monomorphic VT, RV failure and Aortic Stenosis Complications: infection, bleeding, monomorphic VT, RV failure and Aortic Stenosis

55. HeartMate II

60. Suggested Reading Randomized evaluation of Mechanical Assistance for Treatment of Chronic Heart Failure (Rose et al. NEJM 2001) Randomized evaluation of Mechanical Assistance for Treatment of Chronic Heart Failure (Rose et al. NEJM 2001) Evaluation and management of patients with acute decompensated heart failure. Journal of Cardiac Failure. Vol.12 No. 1 2006 Evaluation and management of patients with acute decompensated heart failure. Journal of Cardiac Failure. Vol.12 No. 1 2006 Medical Management of Advanced Heart Failure. JAMA, February 6,2002- Vol. 27, No. 5 Medical Management of Advanced Heart Failure. JAMA, February 6,2002- Vol. 27, No. 5 http://www.med.umich.edu/AnesCriticalCare/Documents /Rosenberg_Circulatory_Assist_Devices.pdf http://www.med.umich.edu/AnesCriticalCare/Documents /Rosenberg_Circulatory_Assist_Devices.pdf http://www.med.umich.edu/AnesCriticalCare/Documents /Rosenberg_Circulatory_Assist_Devices.pdf http://www.med.umich.edu/AnesCriticalCare/Documents /Rosenberg_Circulatory_Assist_Devices.pdf http://texasheart.org/Research/Devices/thoratec_heartm ateii.cfm http://texasheart.org/Research/Devices/thoratec_heartm ateii.cfm

61. Thank you! Special Thanks to Special Thanks to –Dr. Chad Feldman, Associate Director of Medicine Advocate Christ Hospital –Dr. Ali Zadi, Clinical Instructor, Cardiology Fellow –Dr. Saba Khan, Heart Failure Fellow