1. Heart Failure John Lynn Jefferies, MD, MPH, FAAP, FACC Director, Cardiomyopathy, Advanced Heart Failure, and Ventricular Assist Device Programs Co-Director, Cardiovascular Genetics Associate Professor, Pediatric Cardiology and Adult Cardiovascular Diseases The Heart Institute Cincinnati Children’s Hospital

2. HEART FAILURE DEFINED “Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.” Hunt SA et al. Circulation. 2001;104:2996

3. Heart Failure: Why the Concern? One in 8 deaths in the US has HF listed on the death certificate Cost to the US for HF treatment was 39.2 billion dollars in 2010 To deliver more specialized care in this area, most adult programs have developed HF programs

4. Heart Failure: Why the Concern? More than 5 million people in the US with the diagnosis of HF Over 600,000 new diagnoses each year Underestimates the pediatric and ACHD population Many insurers are recognizing the importance of specialized care in their reimbursement

5. Heart Failure Heart Failure is a common problem world- wide Historically thought of as volume overload Current thought that this is a clinical syndrome Should never be thought about as a “stand alone” diagnosis Causes can be numerous May have multiple etiologies in any patient

6. Symptoms Can be quite variable based on age of patient and phenotype – Swelling – Dyspnea on exertion – Palpitations – Weight gain – Syncope Most common symptom in pediatric population – None – Failure to thrive, not meeting milestones

7. Jefferies and Towbin. Lancet 2010;375:752-62.

8. ANP BNP Myocardial Injury Fall in LV Performance Activation of RAAS and SNS (endothelin, AVP, cytokines ) Myocardial Toxicity Change in Gene Expression Peripheral Vasoconstriction Sodium/Water Retention HF Symptoms Morbidity and Mortality Remodeling and Progressive Worsening of LV Function Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2 The Heart Failure Syndrome

9. E Braunwald. NEJM 2008;358:2148-59.

10. The Heart Failure Syndrome Bowles et al. Herz 2000;28:169-175.

11. 11 Final Common Pathways ACTC Impaired force transmission Impaired force transmission MYH7 TNNC1 TNNT2 TPM1 MYH7 TNNC1 TNNT2 TPM1 Impaired force generation Impaired force generation LMNA Changes in nuclear structure and function LDB3 Changes in stretch sensor machinery PLN Calcium regulation DILATED CARDIOMYOPATHY SCN5A Sodium regulation

12. Ronco et al. J Am Coll Cardiol 2008;52:1527-39.

14. Cardiomyopathies Hypertrophic Cardiomyopathy (HCM) Dilated Cardiomyopathy (DCM) Restrictive Cardiomyopathy (RCM) Left Ventricular Noncompaction (LVNC) Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

16. Systolic Heart Failure Depressed ventricular function Classically describing the left ventricle Increasingly described in the right ventricle or in both ventricles Noninvasive imaging typical mode of diagnosis – Echocardiography, CT, MRI, Nuclear, Invasive Angiography In adults, typical cause is ischemic In children, infectious or genetic more common

18. Heart Failure With Preserved Ejection Fraction (HFpEF) Formerly known as diastolic heart failure 50% of adult heart failure cases – Unknown prevalence in children Outcome similar to those patients with HF and systolic dysfunction Increasing in incidence compared to HFrEF Treatment options not as robust Continuum of myocardial dysfunction?

20. Mechanism of HFpEF Borlaug and Paulus. Eur Heart J 2011;32:670-679.

22. Right Ventricular Heart Failure Haddad et al. J Cardiac Fail 2011;17:533-539.

23. Waldum et al. J Cardiac Fail 2010;16:374-380. Renal Function in Chronic Heart Failure

24. Waldum et al. J Cardiac Fail 2010;16:374-380. Renal Function in Chronic Heart Failure

25. Price et al. Pediatr Crit Care Med 2008;9:279-84. Cardiorenal Syndrome in Pediatrics

26. The Big Picture of Heart Failure Setaguchi et al. Am Heart J 2007;154:260-6

27. Increasing Need Difficult to assess the prevalence of cardiomyopathy accurately ~5 million Americans suffer from symptomatic heart failure Estimated 50 million Americans meet criteria for Stage A or B We expect this underestimates the at risk populations – Underuse of appropriate screening for at risk populations

28. Conclusions Heart failure is a complex clinical syndrome Proper management dependent on recognition of appropriate components of care – Not just diuresis and inotropes Understanding etiology often more challenging in pediatric populations Collaborative approach with multiple disciplines including Nephrology leads to best outcome