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

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

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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)

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Hyponatremia in Heart Failure: why it is important and what should we do about it?

Richard G. Kiel, M.D. Associate Clinical Professor of Medicine, UCSF Director, Advanced Heart Failure and Mechanical Circulator Support, UCSF-Fresno MEP

  • Pathophysiology of sodium and water retention in

heart failure

  • Hyponatremia in heart failure (mechanism and

prognostic importance)

  • How to treat volume overload in heart failure
  • Aquaresis vs. diuresis in treating volume overload

in patients with heart failure and hyponatremia

Objectives Pathophysiology of Heart Failure

Schrier RW. J Am Coll Cardiol. 2006; 47: 1-8.

Vicious Circle of Water Retention

Schrier RW. J Am Coll Cardiol. 2006; 47: 1-8.

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Pathophysiology of hyponatremia in acute decompensated heart failure

Dilutional Hyponatremia

  • Increased sensitivity of
  • smotic AVP release

lower osmo-checkpoint

  • Increased nonosmotic AVP

release

  • Impaired AVP degradation
  • Increased thirst
  • Decreased distal nephron

flow Mechanism of action

  • Baroreceptor

activation/angtiotensin II

  • Baroreceptor

activation/angtiotensin II

  • Liver/kidney dysfunction
  • Baroreceptor

activation/angtiotensin II

  • Impaired glomerular

filtration/increase reabsorption in proximal tubes

Verbrugge et al. J Am Coll Cardiol. 2015; 65: 480-492.

Pathophysiology of hyponatremia in acute decompensated heart failure

Depletional Hyponatremia

  • Low sodium intake
  • Exaggerated nonurinary

sodium loss

  • Exagerated natriuresis
  • Sodium shift toward the

intracellular compartment Mechanism of action

  • Salt-restricted diet
  • Diarrhea, ascites
  • Diuretics, osmotic diuresis
  • Potassium and/or

magnesium deficiency

Verbrugge et al. J Am Coll Cardiol. 2015; 65: 480-492.

Differentiate dilutional verus depletion

  • If volume overload you can assume at least a

component of dilutional

  • Urine osmolality should be depressed (<100

mOsm/L) in depletional but not dilutional hyponatremia.

  • Low urinary sodium (<50mEq/L) is a strong

argument for electrolyte depletion

Plasma hypotonicity

  • Confirm plasma hypotonicity (<285 mOsm/L)

– Pseudohyponatrmia: Elevated triglycerides, immunoglobulins, monoclonal gammanopathies can cause falsely low Na concentrations – Presence of effective osmoles (e.g. hyperglycemia) can falsely increase serum Na concentrations

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Role of Vasopressin in Heart Failure

Verbrugge FH. J Am Coll Cardiol. 2015; 65: 480-492.

Dilutional hyponatremia, high BUN

Free Water Excretion in Patients Without Heart Failure

Verbrugge FH. J Am Coll Cardiol. 2015; 65: 480- 492.

Free Water Excretion is Impaired in Heart Failure

Verbrugge FH. J Am Coll Cardiol. 2015; 65: 480- 492.

Hyponatremia in patients hospitalized for heart failure

Gheorghiade M et al. Eur Heart J. 2007; 28: 980-988.

20% with Na < 135 mmol/L

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Sodium and Survival in Heart Failure

Klein L et al. Circulation 2005; 111: 2454-2460.

BUN and Survival in Heart Failure

Klein L et al. Circ Heart Fail. 2008; 1: 25-33.

  • Diuretics

– Loop; thiazide; acetazolamide

  • Aquaretics (vaptans)

– Tolvaptan

  • Inotropic agents

– Dopamine; dobutamine

  • Vasodilators

– Nesiretide, nitroglycerin, nitroprusside

  • Ultrafiltration

– Continuous; intermittent

Volume Management in Heart Failure

  • Need combination (due to “braking” and

tolerance)

– Loop + Thiazide + Acetazolamide

  • Potency and protein binding

– Bumetanide > Torsemide > Furosemide

  • High vs. Low dose

– High dose better (DOSE - HF trial)

  • IV Bolus vs. IV Drip

– No difference (DOSE - HF trial)

  • High dose vs. Low dose + Dopamine

– Dopamine improves renal blood flow and size of renal arteries

Diuretic Strategies

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  • Tolvaptan is the most studied

– V2 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

Aquaretics (Vaptans)

Schrier RW et al. N Engl J Med. 2006; 355: 2099-2112; Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545; Lehrich RW et al. J Am Soc Nephrol. 2008; 19: 1054-1058.

Hemodynamics Effects of Tolvaptan

Slightly better reduction in filling pressures with tolvaptan

Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545.

Effects of Tolvaptan on PCWP

Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545.

Sustained reduction in filling pressures with tolvaptan Better diuresis with single dose tolvaptan No changes in renal function and electrolytes

Effects of Tolvaptan on Urine Output

Udelson JE et al. J Am Coll Cardiol. 2008; 52: 1540-1545.

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Renal Effects of Tolvaptan

  • TLV compared to

furosemide:

  • Similar urine
  • utput
  • No changes in

electrolytes

  • No changes in
  • smolality
  • Preserved renal

blood flow

* p < 0.05

Costello-Boerrigter et al. Am J Physiol Renal Physiol 2006; 290: F273-278

Effects of Tolvaptan vs. Furosemide

Udelson JE et al. J Card Fail. 2011; 17: 973-981.

TLV produced sustained decrease in body weight, increased urine volume, transient sodium increase (within normal range) and no change in potassium

Change in Global Clinical Status During Hospitalization in EVEREST

Gheorghiade M et al. JAMA. 2007; 297: 1332-1343.

Dyspnea in Hospitalized Patients with Hyponatremia in EVEREST

Hauptman PJ et al. J Card Fail. 2013; 19: 390-397.

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Diuretics in Hospitalized Patients with Hyponatremia in EVEREST

Hauptman PJ et al. J Card Fail. 2013; 19: 390-397.

* p < 0.05

Body Weight and Sodium in EVEREST

Konstam MA et al. JAMA. 2007; 297: 1319-1331.

* p < 0.001 * p < 0.001

(in pts. with Na < 134 mmol/L)

Body Weight and Sodium in EVEREST

Konstam MA et al. JAMA. 2007; 297: 1319-1331.

All-Cause Mortality in EVEREST

Konstam MA et al. JAMA. 2007; 297: 1319-1331.

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Event Analysis in EVEREST

Hauptman PJ et al. J Card Fail. 2013; 19: 390-397.

Managing Volume Overload in Heart 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

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