Philip B. Adamson MD, MSc, FACC Director, Oklahoma Foundation for Cardiovascular Research

1. Diagnosis and Management of Chronic Heart Failure: What is the Standard of Care and What Will Become Standard Philip B. Adamson MD, MSc, FACC Director, Oklahoma Foundation for Cardiovascular Research Director, Heart Failure Institute at Oklahoma Heart Hospital Associate Professor of Physiology, University of Oklahoma Health Sciences Center Oklahoma City, OK

2. Initial Diagnosis and Evaluation • Symptoms of left heart failure • Dyspnea on exertion or at rest • Orthopnea, Paroxysmal Nocturnal Dyspnea • Lung Crackles, S3 • Symptoms of right heart failure • Swelling • Ascites, liver congestion • Anorexia • Elevated JVP, Hepatomegaly, AJR, edema

3. Initial Diagnosis and Evaluation • Evaluation of ventricular structure and function (estimate LVEF) • Echocardiogram, NVG, Chest X-Ray, ECG • Heart Failure with: • Preserved ejection fraction • Reduced ejection fraction • Renal function, potassium, magnesium, TSH • WHY, WHY, WHY, WHY is this ventricle damaged?!?!?!

4. Left Ventricular Ejection Fraction Left ventricular Ejection Fraction = (LVEDV – LVESV)/LVEDV x 100 Normal is 55-70% Systolic Heart Failure <40%

5. Ao PA 120/80 24/12 LA 12 RA 6 120/12 24/6 LV RV Heart Failure Causes Left Heart Failure 1.Myocardial Infarction 2. Hypertension 3. Valvular failure 4. Viral 5. Genetic 6. Idiopathic Right Heart Failure 1. Left heart failure 2. Pulmonary Hypertension 3. RV infarction 4.Sleep apnea 5. Left to right shunts

6. NYHA Class vs. Stage NYHA Classification • I – no symptoms • II – symptoms with significant exertion • III – symptoms with mild exertion • IV – symptoms at rest ACC/AHA Stages • A – at risk for heart failure • B – LV dysfunction never had symptoms • C – LV dysfunction with symptoms • D – Refractory heart failure

7. Goals of Heart Failure Management • Relieve Symptoms • “Make you feel better” • Prevent Progression of Disease • “Help your heart get better” • Prolong life • Obvious

8. Two Sides of Pathophysiology • Hemodynamic Mechanisms • Increased left ventricular end-diastolic pressure • “Backline pressures” increase • Symptoms of heart failure • Neurohormonal Mechanisms • Sympathetic and parasympathetic responses • Renin-angiotensin and aldosterone responses • Fibrosis • Genetic control • Worsening systolic and diastolic function

9. Ao PA 120/80 24/12 LA 12 RA 6 120/12 24/6 LV RV Heart Failure Symptoms Left Ventricular Failure Lung Congestion Dyspnea Orthopnea Paroxysmal Nocturnal Dyspnea Right Ventricular Failure Liver Congestion Ascites Gut edema Leg edema

10. Evaluating Jugular Venous Pressure Photo Courtesy of Dr. J. Thomas Heywood

11. Neural Hormonal Activation Neural Hormonal Activation ↓SV ↑LVEDP

12. Acute MI (hours) Infarct expansion (hours to days) Global remodeling (days to months) Example of Adverse Remodeling • Apical infarction from total occlusion LAD,remainder of coronaries without obstruction

13. Pathologic Progression of CV Disease Electrical Remodeling Sudden Death Coronary artery disease Left ventricularinjury Hypertension Ventricular Dysfunction Pathologicremodeling Death Diabetes Cardiomyopathy Pump failure Valvular disease Symptoms:DyspneaFatigueEdema Chronicheartfailure Sympathetic Activation Parasympathetic withdrawal Renin Angiotensin Activation Aldosterone Activation Renal Reabsorption • Neurohormonalstimulation • Endothelial dysfunction • Myocardial toxicity Adapted from Cohn JN. N Engl J Med. 1996;335:490–498.

14. Pathologic Progression of CV Disease Electrical Remodeling Sudden Death Coronary artery disease Left ventricularinjury Hypertension Ventricular Dysfunction Pathologicremodeling Death Diabetes Cardiomyopathy Pump failure Valvular disease Symptoms:DyspneaFatigueEdema Chronicheartfailure Sympathetic Activation Parasympathetic withdrawal Renin Angiotensin Activation Aldosterone Activation Renal Reabsorption • Neurohormonalstimulation • Endothelial dysfunction • Myocardial toxicity Adapted from Cohn JN. N Engl J Med. 1996;335:490–498.

15. ACE Inhibitors • Block conversion of Angiotensin I to Angiotensin II (among other things) • Prevent adverse remodeling • ~21% mortality risk reduction • Protect renal function in diabetics • High dose (lisinopril 40 mg) may be better than low dose • Class effect (NYHA Class I-IV, Stage A-D) • Complications: Hyperkalemia, worsening renal function, hypotension, cough

16. Angiotensin Receptor Blockers • As the name implies • Same expectations as ACE inhibitors except no cough • Class effect (NYHA Class I-IV, Stage A-D) • Complications: Hypotension, hyperkalemia, worsening renal function

17. Beta-Blockers • Antagonize beta-receptors • Reduce fibrosis, adverse remodeling • 34% mortality risk reduction • Improvement in LV function (NYHA Class I-IV, Stage A-D) • NOT a class effect • Carvedilol 6.25 mg BID to 25 mg BID • Metoprolol SUCCINATE 25 mg qD to 200 mg qD • Bisoprolol 2.5 mg daily to 10 mg daily • Complications: bradycardia, hypotension

18. Aldosterone Antagonists • Block the hormone Aldosterone • Decrease fibrosis and remodeling • ~34% mortality risk reduction • Eplerenone and spironolactone 25-50 mg qD • NYHA Class II-IV, Stage C-D • COMPLICATIONS: HYPERKALEMIA! • MUST check potassium at baseline, day 1, day 7 and day 30.

19. Device Therapies • Sudden Cardiac Death (due to ventricular fibrillation) • Risk increases as LVEF declines (<35%) • Beta-blockers effective • Implantable Cardioverter Defibrillators • Ventricular Dyssynchrony • Wide QRS on ECG • Increases risk for sudden death and adverse remodeling • Cardiac Resynchronization (biventricular pacing)

21. Is there a relationship between LV diastolic volume and LV diastolic pressure? 1. Yes, it is linear: as volume increases pressure increases, Pressure = A x volume + B. 2. Yes, it is exponential: as volume increases pressure increases, Pressure = A e volume B + C. 3. No, there is no relationship: volume Δ is independent of pressure Δ. 4. I’m looking forward to a long weekend: and frankly Scarlette I don’t care.

22. 14 10 LV Diastolic Pressure (mmHg) Pres x 3 6 (3) Vol 2 ΔPressure (7) 2 (1) ΔVolume (15) 50 82 89 65 70 40 100 LV Diastolic Volume (ml)

23. Acutely Decompensated Heart Failure Hemodynamic Mechanisms

24. Acutely Decompensated Heart Failure PAD PCWP Intravascular Pressure >>> Extravascular Pressure Diastolic Pressures

25. Acutely Decompensated Heart Failure Diastolic Volume Diastolic Pressures Hemodynamic Mechanism ?

26. Acutely Decompensated Heart Failure Relationship Diastolic Volume vs. Diastolic Pressure

27. Acutely Decompensated Heart Failure ↑ Intravascular Diastolic Volume ↑ Intravascular Diastolic Pressure Hyper “VOL” emia Hyper “PRESS” emia Hemodynamic Mechanisms ?

28. What is the mechanism (s) causing acutely decompensated heart failure in SHF vs. DHF ? 1. In SHF there is a dominant ↑ in LV Volume. 2. In DHF there is a dominant ↑ in LV Pressure. 3. The mechanism is the same in SHF vs. DHF. 4. I refuse to answer any more questions until you explain the differences between DHF and SHF.

29.  Diastolic Distensibility Circulation 2006; 113: 296-304  Diastolic Distensibility

30. DHF SHF

32. Hospitalization Intrathoracic Impedance Changes Symptoms Filling pressures Increase Weights Change Autonomic Adaptation Pathophysiology of Congestion -30 -20 0 Days - 10 Adamson PB: Current Heart Fail Reports 2009;287-292

33. Close monitoring of Heart Failure Patients Avoiding Clinical Events Averted Heart Failure Event Medical Intervention Reducing High Filling Pressures Days -21 -14 - 7 0 Proactive Adamson PB Curr Heart Fail Reports 2009;6:287 33

34. Status of Hemodynamic Monitors • 3 sensors tested in prospective trials, one trial ongoing (LAPTOP-HF). • 1 sensor being evaluated by FDA • None currently have FDA approval for use in the US. CE mark is in place for one.

35. MEMS-based pressure sensor Experimental Hemodynamic Monitors Right Ventricle Pulmonary Artery