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Treatment Strategies for ADHF Associated AKI

Treatment Strategies for ADHF Associated AKI. 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

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Treatment Strategies for ADHF Associated AKI

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  1. Treatment Strategies for ADHF Associated AKI 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. Jessup et al. Circulation 2009;119:1977-2016.

  3. Pharmacologies in Heart Failure Management ANP BNP NO Bradykinin Prostacyclin Endothelin Aldosterone Angiotensin II Vasopressin Norepinephrine Vasodilation Vasoconstriction Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2

  4. Possible evidence of low perfusion • Narrow pulse pressure • Sleepy/obtunded • Low serum sodium • Cool extremities • Hypotension with ACE inhibitor • Renal dysfunction (one cause) Hemodynamic Profile Assessment Congestion at Rest No Yes • Signs/symptoms • of congestion • Orthopnea/PND • JVD • Ascites • Edema • Rales (rare in HF) Warm & Dry Warm & Wet No Low Perfusion at Rest Cold & Dry Cold & Wet Yes Stevenson LW. Eur J Heart Fail. 1999;1:251

  5. Patient Selection and Treatment Congestion at Rest No Yes Warm & Dry PCWP normal CI normal (compensated) Warm & Wet PCWP elevated CI normal Natriuretic Peptide Nesiritide or No Low Perfusion at Rest Vasodilators Nitroprusside Nitroglycerin Cold & Dry PCWP low/normal CI decreased Cold & Wet PCWP elevated CI decreased Yes Normal SVR High SVR Inotropic Drugs Dobutamine Milrinone Calcium Sensitizers Stevenson LW. Eur J Heart Fail. 1999;1:251

  6. Proven Outcomes for Heart Failure Therapies • Improve Survival • ACE inhibitor • ARB • Beta blocker • Aldosterone receptor antagonist • Hydralazine/long-acting nitrates • Reduce Hospitalization • ACE inhibitor • ARB • Beta blocker • Aldosterone receptor antagonist • Hydralazine/long-acting nitrates • Digoxin

  7. Intravenous Agents for Heart Failure Young JB. Rev Cardiovasc Med .2001;2(suppl 2):S19

  8. Ventricular Remodeling Ventricular Remodeling After Acute Infarction Global remodeling(days to months) Initial infarct Expansion of infarct(hours to days) Ventricular Remodeling in Diastolic and Systolic HF Normal heart Dilated heart(systolic HF) Hypertrophied heart(diastolic HF) Jessup M et al. N Engl J Med. 2003;348:2007

  9. Pharmacologies in Heart Failure Management • Hemodynamic • (balanced vasodilation) • Veins • Arteries • Coronary arteries • Neurohormonal •  aldosterone •  endothelin •  norepinephrine • Renal •  sodium and water excretion • Cardiac • Lusitropic • Antifibrotic • Antiremodeling Abraham WT et al. J Card Fail. 1998;4:37 Clemens LE et al. J Pharmacol Exp Ther. 1998;287:67 Marcus LS et al. Circulation. 1996;94:3184 Tamura N et al. Proc Natl Acad Sci U S A. 2000;97:4239Zellner C et al. Am J Physiol. 1999;276(3 pt 2):H1049

  10. Sites of Action for HF Therapies Beta blockers Heart Digoxin,inotropes Cardiac- resynchronization therapy PeripheralArteries ACE inhibitors,angiotensin receptor blockers,aldosterone antagonists Diuretics, aldosteroneantagonists, nesiritide Kidney ACE inhibitors,angiotensin receptor blockers,vasodilators, alpha blockade,nesiritide, exercise Jessup M, Brozena S. N Engl J Med. 2003;348:2007

  11. Current Heart Failure Strategies • “Primum non nacere” (First, do no harm) • Factors predicting quality outcomes • Correct diagnosis • Appropriate management strategies • Timing is everything • Utilization of available resources thoughtfully • Learn from the adult literature…

  12. Management of End-Stage Heart Failure Jessup et al. Circulation 2009;119:1977-2016.

  13. Management of End-Stage Heart Failure Jessup et al. Circulation 2009;119:1977-2016.

  14. Management of End-Stage Heart Failure Jessup et al. Circulation 2009;119:1977-2016.

  15. Patients with Reduced Left Ventricular Function Jessup et al. Circulation 2009;119:1977-2016.

  16. Ventricular Assist DevicesThe Next Frontier

  17. Ultrafiltration • Ultrafiltration (UF) is a potentially attractive treatment strategy for patients with volume overload with CRS • UF has no effect on serum electrolytes • Results are rapid • Volume removed is easily controlled and predictable • Does not stimulate the neurohormonal system • Restores responsiveness to diuretics in patients with diuretic resistance

  18. Costanzo et al. Semin Nephrol 2012;32:100-111.

  19. Ultrafiltration Costanzo et al. J Am Coll Cardiol 2007;49:675-683

  20. Costanzo et al. J Am Coll Cardiol 2007;49:675-683.

  21. Costanzo et al. Semin Nephrol 2012;32:100-111

  22. Bart et al. J Card Fail 2012;18:176-182.

  23. Vasopressin Antagonists • Arginine vasopressin (AVP) levels are often elevated in heart failure • Leads to water retention, hyponatremia, vasoconstriction, and myocardial fibrosis • AVP antagonists (Conivaptan and Tolvaptan) are available in the US • Enhance free water clearance without electrolyte loss • No effect on renal function

  24. Udelson et al. J Cardiac Fail 2011;17:973-981.

  25. Udelson et al. J Cardiac Fail 2011;17:973-981.

  26. Conclusions • Current treatment of decompensated heart failure involves multiple possible therapeutic strategies • Many of these are harmful to the kidney and may worsen AKI • Newer technologies may favorably impact markers of AKI and result in less long-term morbidity and mortality

  27. Conclusions • The treatment of acute decompensated heart failure requires recognition that HF is a syndrome involving complex interactions • Preservation of kidney function is critical to avoidance of readmission and survival • Consultation with Cardiologists that have recognized expertise in the management of HF is strongly recommended

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