Hyponatremia in Heart Failure: why it Pathophysiology of sodium and - PDF document

9/30/16 Objectives Hyponatremia in Heart Failure: why it • Pathophysiology of sodium and water retention in is important and what should we do heart failure about it? • Hyponatremia in heart failure (mechanism and prognostic importance) • How to treat volume overload in heart failure Richard G. Kiel, M.D. Associate Clinical Professor of Medicine, UCSF Director, Advanced Heart Failure and Mechanical Circulator • Aquaresis vs. diuresis in treating volume overload Support, UCSF-Fresno MEP in patients with heart failure and hyponatremia Pathophysiology of Heart Failure Vicious Circle of Water Retention Schrier RW. J Am Coll Cardiol. 2006; 47: 1-8. Schrier RW. J Am Coll Cardiol. 2006; 47: 1-8. 1

9/30/16 Pathophysiology of hyponatremia in acute Pathophysiology of hyponatremia in acute decompensated heart failure decompensated heart failure Dilutional Hyponatremia Mechanism of action Depletional Hyponatremia Mechanism of action • Baroreceptor • Salt-restricted diet • Increased sensitivity of • Low sodium intake activation/angtiotensin II osmotic AVP release • Diarrhea, ascites • Exaggerated nonurinary lower osmo-checkpoint sodium loss • Baroreceptor • Increased nonosmotic AVP • Exagerated natriuresis • Diuretics, osmotic diuresis activation/angtiotensin II release • Sodium shift toward the • Potassium and/or • Liver/kidney dysfunction • Impaired AVP degradation intracellular compartment magnesium deficiency • Baroreceptor • Increased thirst activation/angtiotensin II • Impaired glomerular • Decreased distal nephron filtration/increase flow reabsorption in proximal tubes Verbrugge et al. J Am Coll Cardiol. 2015; 65: 480-492. Verbrugge et al. J Am Coll Cardiol. 2015; 65: 480-492. Differentiate dilutional verus Plasma hypotonicity depletion • If volume overload you can assume at least a • Confirm plasma hypotonicity (<285 mOsm/L) component of dilutional – Pseudohyponatrmia: Elevated triglycerides, immunoglobulins, monoclonal gammanopathies • Urine osmolality should be depressed (<100 can cause falsely low Na concentrations mOsm/L) in depletional but not dilutional – Presence of effective osmoles (e.g. hyperglycemia) hyponatremia. can falsely increase serum Na concentrations • Low urinary sodium (<50mEq/L) is a strong argument for electrolyte depletion 2

9/30/16 Role of Vasopressin in Heart Failure Free Water Excretion in Patients Without Heart Failure Dilutional hyponatremia, high BUN Verbrugge FH. J Am Coll Cardiol. 2015; 65: 480- Verbrugge FH. J Am Coll Cardiol. 2015; 65: 480-492. 492. Free Water Excretion is Impaired in Hyponatremia in patients hospitalized for heart failure Heart Failure 20% with Na < 135 mmol/L Verbrugge FH. J Am Coll Cardiol. 2015; 65: 480- Gheorghiade M et al. Eur Heart J. 2007; 28: 980-988. 492. 3

9/30/16 Sodium and Survival in Heart Failure BUN and Survival in Heart Failure Klein L et al. Circ Heart Fail. 2008; 1: 25-33. Klein L et al. Circulation 2005; 111: 2454-2460. Volume Management in Heart Failure Diuretic Strategies • Need combination (due to “braking” and • Diuretics tolerance) – Loop; thiazide; acetazolamide – Loop + Thiazide + Acetazolamide • Aquaretics (vaptans) • Potency and protein binding – Tolvaptan – Bumetanide > Torsemide > Furosemide • Inotropic agents • High vs. Low dose – Dopamine; dobutamine – High dose better (DOSE - HF trial) • Vasodilators • IV Bolus vs. IV Drip – Nesiretide, nitroglycerin, nitroprusside – No difference (DOSE - HF trial) • Ultrafiltration • High dose vs. Low dose + Dopamine – Continuous; intermittent – Dopamine improves renal blood flow and size of renal arteries 4

9/30/16 Aquaretics (Vaptans) Hemodynamics Effects of Tolvaptan • Tolvaptan is the most studied – V 2 antagonist – Studied in chronic heart failure, acute heart failure – Hemodynamic studies – Remodeling studies • Potential of improving volume status and serum sodium • No increases in short or long term mortality • No adverse effects on blood pressure, heart rate, renal function, electrolytes Slightly better reduction in filling pressures with tolvaptan Schrier RW et al. N Engl J Med. 2006; 355: 2099-2112; Udelson JE et al. J Am Coll Cardiol. 2008; Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545. 52: 1540-1545; Lehrich RW et al. J Am Soc Nephrol. 2008; 19: 1054-1058. Effects of Tolvaptan on PCWP Effects of Tolvaptan on Urine Output Better diuresis with single dose tolvaptan Sustained reduction in filling pressures with tolvaptan No changes in renal function and electrolytes Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545. Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545. 5

9/30/16 Renal Effects of Tolvaptan Effects of Tolvaptan vs. Furosemide * p < 0.05 • TLV compared to furosemide: • Similar urine output • No changes in electrolytes • No changes in osmolality • Preserved renal TLV produced sustained decrease in body weight, blood flow increased urine volume, transient sodium increase (within normal range) and no change in potassium Costello-Boerrigter et al. Am J Physiol Renal Physiol Udelson JE et al. J Card Fail. 2011; 17: 973-981. 2006; 290: F273-278 Change in Global Clinical Status Dyspnea in Hospitalized Patients with During Hospitalization in EVEREST Hyponatremia in EVEREST Gheorghiade M et al. JAMA. 2007; 297: 1332-1343. Hauptman PJ et al. J Card Fail. 2013; 19: 390-397. 6

9/30/16 Diuretics in Hospitalized Patients with Body Weight and Sodium in EVEREST Hyponatremia in EVEREST * p < 0.001 * p < 0.05 (in pts. with Na < 134 mmol/L) * p < 0.001 Hauptman PJ et al. J Card Fail. 2013; 19: 390-397. Konstam MA et al. JAMA. 2007; 297: 1319-1331. Body Weight and Sodium in EVEREST All-Cause Mortality in EVEREST Konstam MA et al. JAMA. 2007; 297: 1319-1331. Konstam MA et al. JAMA. 2007; 297: 1319-1331. 7

9/30/16 Managing Volume Overload in Heart Event Analysis in EVEREST Failure: Diuretics vs. Vaptans Vaptans Diuretics Urine Output ã ã Serum Sodium ã ä Serum Potassium No change ä Plasma Osmolality ã ä Blood Pressure No change ä BUN/Creatinine No change ã Renal Blood Flow ã ä GFR ã ä Renal vascular resistance ä ã Vasopressin level ã ã Norepinephrine level No change ã Plasma renin activity No change ã Aldosterone level No change ã Hauptman PJ et al. J Card Fail. 2013; 19: 390-397. Costello-Boerrigter et al. Am J Physiol Renal Physiol 2006; 290: F273-278 Conclusions • Volume overload is the main reason for hospitalizations in pts. with HF – Up to 20% of pts. develop dilutional hyponatremia • Volume control is paramount – Use diuretics, vaptans, inotropes, ultrafiltration • Diuretics can lead to worse neurohormonal activity, renal function and hyponatremia – Diuretic resistance leads to use of combination • Tolvaptan: better symptomatic relief than diuretics in HFrEF pts. with hyponatremia – No deleterious hemodynamic effects, preserves renal function and potassium, corrects hyponatremia 8