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ELECTROLYTE DYSBALANCE
IN CHF: PROGNOSIS &
MANAGEMENT
Dr. Arindam Pande, MD, DM
Associate Consultant, Cardiology
Apollo Gl...
PATHOPHYSIOLOGY OF CHF
 Chronic activation of
Renin-angiotensin-aldosterone system (RAAS)
Sympathetic nervous system
A...
PATHOPHYSIOLOGY OF CHF
 Chronic activation leads to
Excessive ventricular preload & afterload
Adverse ventricular remod...
The heart disease is the primum movens, but the
kidney is the end organ responsible for increased
tubular reabsorption of ...
SODIUM
Sodium Homeostasis
 Sodium - dominant cation of extracellular fluid
 Principal determinant of extracellular osmolality.
...
Hyponatremia- Diagnosis
Cause of Hyponatremia by Urine Specimen
Cause Urine Na Urine
Volume
Osmolarity Specific
Gravity
Hy...
HYPONATREMIA IN CHF
 Excessive / inappropriate AVP secretion in
response to nonosmotic stimuli
 Solute losses from diure...
creatinine, and serum sodium were
related to progressive heart failure
death….serum potassium were
related to sudden cardi...
Multivariate analysis identified three
variables that were statistically significant
and independent predictors of outcome...
By regression analysis, pretreatment serum sodium
concentration was the most powerful predictor of cardiovascular
mortalit...
Therapy for
hyponatremia
is not as
straight
forward as the
picture by
simply
replenishing
sodium by
means of extra
salt…
 The failure to treat hyponatremia promptly, as
well as too rapid correction can lead to adverse
outcome
 The presence o...
Correction of Hyponatremia
Although the therapeutic distinction between
symptomatic and asymptomatic
hyponatremia is clear at the extremes of
symptom...
Therapeutic Options for Hyponatremia
Due to Congestive Heart Failure
LIMITATIONS OF EXISTING THERAPY
 variable efficacy,
 slow onset of action,
 compliance issues, and
 toxicities.
AVP IN CHF
 In many studies, it has been shown that AVP levels are higher
in presence of CHF
 AVP values typically are n...
Unfortunately….
AVP RECEPTOR BLOCKERS
(aquaretics)
Apart from reduction in body weight and increased urine
output, patients with hyponatremia had increases in
serum sodium l...
Post hoc analysis of ACTIVE in CHF
Total mortality was lower in the tolvaptan groups
combined compared with placebo in pat...
Serum sodium concentrations increased more in the
tolvaptan group than in the placebo group during the
first 4 days (P<0.0...
Tolvaptan significantly improved secondary end
points of day 1 patient-assessed dyspnea, day 1
body weight, and day 7 edem...
CONIVAPTAN
Development of the oral formulation was discontinued to
limit the potential for drug interactions resulting fro...
142 patients…single intravenous dose of conivaptan or placebo…
Conivaptan 20 mg and 40 mg significantly reduced pulmonary
...
 Nesiritide, the synthetic BNP
 A1-adenosine antagonists, which increase
natriuresis and diuresis
 Corticosteroids, whi...
POTASSIUM
Potassium Homeostasis
 Most potassium is intracellular
 Distribution of between the intra- and extracellular compartment...
Homeostasis- controlled by EXCRETION
Kidney plays the most important role
 90% is of K+ is resorbed before the distal tub...
Hypokalemia in CHF
Causes:
 Medication
 Increased losses: extrarenal and renal
 Transcellular shifts
 Decreased intake...
Initial serum potassium
concentration and
treadmill exercise time
carried weak but
independent prognostic
information.
The...
Treatment- Hypokalemia
Severe, symptomatic hypokalemia requires aggressive treatment
Because of the risk of hyperkalemia, ...
Hyperkalemia in CHF
“One of the few things one can die from
without any symptoms…”
Causes
Medications
Spurious
Increased I...
Hyperkalemia- Treatment
K+ level, the ECG, and the risk determine the aggressiveness of
therapy.
 Stop all sources of add...
Hyperkalemia- Treatment
Remove potassium from the body.
 Loop diuretic increases renal excretion of K+- only if
making ur...
MAGNESIUM
Hypomagnesemia (<1.4mEq/L)
 Contributing factors:
Malnutrition
Starvation
Diuretics
Aminoglcoside antibiotics
Hyperg...
 Magnesium deficit is not infrequently
observed in CHF patients but its
pathophysiology remains less well-studied
 There...
Hypomagnesemia was found in 17.4% of
hospitalized CHF patients… Inappropriate
magnesiuria (fractional excretion of
magnesi...
Hypermagnesemia (>2.0mEq/L)
 Contributing factors:
Increased Mag intake
Decreased renal excretion
Serum magnesium does not appear to be an independent
risk factor for either sudden death or death due to all causes
in pat...
Hypomagnesemia (<1.4mEq/L)
 Interventions:
Eliminate contributing drugs
Diet Therapy
IV MgSO4
Assess DTR’s hourly wit...
Hypermagnesemia (>2.0mg/dL)
 Interventions
Eliminate contributing drugs
Administer diuretic
Calcium gluconate reverses...
CONCLUSION
PROGNOSIS
 Hyponatremia is an independent predictor
of morbidity & mortality in CHF
 Hypokalemia is an independent predi...
MANAGEMENT
 The use of hypertonic saline solution for the treatment of acute
and chronic symptomatic hyponatremia involve...
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
Electrolyte dysbalance  in chf – prognosis & management
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Electrolyte dysbalance in chf – prognosis & management

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Electrolyte dysbalance in chf – prognosis & management

  1. 1. ELECTROLYTE DYSBALANCE IN CHF: PROGNOSIS & MANAGEMENT Dr. Arindam Pande, MD, DM Associate Consultant, Cardiology Apollo Gleneagles Hospital, Kolkata
  2. 2. PATHOPHYSIOLOGY OF CHF  Chronic activation of Renin-angiotensin-aldosterone system (RAAS) Sympathetic nervous system Antidiuretic hormone arginine vasopressin (AVP)
  3. 3. PATHOPHYSIOLOGY OF CHF  Chronic activation leads to Excessive ventricular preload & afterload Adverse ventricular remodelling Pulmonary and systemic congestion Electrolyte abnormalities, such as hyponatremia
  4. 4. The heart disease is the primum movens, but the kidney is the end organ responsible for increased tubular reabsorption of sodium and water. Over time, a gradually falling glomerular filtration rate, due to CHF progression, medications or chronic kidney injury due to comorbidities, becomes more critical in sodium/water imbalance.
  5. 5. SODIUM
  6. 6. Sodium Homeostasis  Sodium - dominant cation of extracellular fluid  Principal determinant of extracellular osmolality.  The low intracellular sodium concentration, approximately 10 mEq/L, is maintained by Na+ K+-ATPase, which exchanges Na+ for K+  Sodium is necessary for the maintenance of intravascular volume.  Sodium excretion occurs in stool and sweat, but the kidney regulates sodium balance and is the principal site of sodium excretion.  Plasma VOLUME- not osmolality determines the excretion of sodium by the kidney  renin-angiotensin-aldosterone system  In hyponatremia or hypernatremia, the underlying pathophysiology determines urinary Na+, not the serum sodium concentration  When extracellular sodium ↑’s→ plasma tonicity ↑→water efflux from cells →cellular dehydration (↓ cell volume) (to maintain equal osmolality inside and outside the cell)  Also ADH is released- renal conservation of water Sodium is unique among electrolytes… because water balance, not sodium balance, usually determines its concentration.
  7. 7. Hyponatremia- Diagnosis Cause of Hyponatremia by Urine Specimen Cause Urine Na Urine Volume Osmolarity Specific Gravity Hypovolemic renal Na loss ↑ >20mEq/L ↑ ↓ ↓ Hypovolemic extrarenal loss ↓ ↓ ↑ ↑ Hypervolemic HypoNa- CHF,edema ↓<20mEq/L ↓ ↑ ↑ Hypervolemic HypoNa- Renal Failure varies ↓ varies varies SIADH-like syndrome ↑ >20mEq/L ↓ ↑ ↑ History can tell us most of the story Laboratory studies: Urine Na and Osm compared to Serum Na and Osm Calculate Osmolar Gap: Difference between measured & calculated osm Gap is high with mannitol, glycerol, lactate, methanol, EtOH, ethylene glycol Calc Osm= 2( Serum Na + serum K+) + (BUN/2.8) + (glucose/18)
  8. 8. HYPONATREMIA IN CHF  Excessive / inappropriate AVP secretion in response to nonosmotic stimuli  Solute losses from diuretic therapy Hyponatremia in CHF is not an isolated event, rather is a part of the syndrome.
  9. 9. creatinine, and serum sodium were related to progressive heart failure death….serum potassium were related to sudden cardiac death
  10. 10. Multivariate analysis identified three variables that were statistically significant and independent predictors of outcome… In order of importance these were plasma sodium level, left ventricular ejection fraction and peak oxygen consumption.
  11. 11. By regression analysis, pretreatment serum sodium concentration was the most powerful predictor of cardiovascular mortality, with hyponatremic patients having a substantially shorter median survival than did patients with a normal serum sodium concentration. The unfavorable prognosis for hyponatremic patients appeared to be related to the marked elevation of plasma renin activity, since hyponatremic patients fared significantly better when treated with angiotensin converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin 2 biosynthesis. In contrast, there was no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low.
  12. 12. Therapy for hyponatremia is not as straight forward as the picture by simply replenishing sodium by means of extra salt…
  13. 13.  The failure to treat hyponatremia promptly, as well as too rapid correction can lead to adverse outcome  The presence or absence of neurologic symptoms and signs must guide treatment  The rate at which sodium concentrations should be corrected depends on whether the sodium imbalance is acute or chronic THERAPY GUIDED BY 3 GENERAL PRINCIPLES:
  14. 14. Correction of Hyponatremia
  15. 15. Although the therapeutic distinction between symptomatic and asymptomatic hyponatremia is clear at the extremes of symptomatology, in reality many patients with hyponatremia are somewhere between these poles, with chronic hyponatremia and mild or subtle manifestations of neurologic symptoms. It is often difficult to ascertain whether symptoms are due to hyponatremia or to underlying comorbidities.
  16. 16. Therapeutic Options for Hyponatremia Due to Congestive Heart Failure
  17. 17. LIMITATIONS OF EXISTING THERAPY  variable efficacy,  slow onset of action,  compliance issues, and  toxicities.
  18. 18. AVP IN CHF  In many studies, it has been shown that AVP levels are higher in presence of CHF  AVP values typically are not suppressed appropriately with a water load in CHF patients  The elevated or ‘‘normal’’ levels of AVP in the presence of hyponatremia suggest that non-osmotic mechanisms for vasopressin release are essential factors in the hyponatremia which characterizes the complex heart failure syndrome  A more rational approach to the treatment of hyponatremia in CHF, therefore, would be to address the issue of excessive AVP secretion or its effects.
  19. 19. Unfortunately….
  20. 20. AVP RECEPTOR BLOCKERS (aquaretics)
  21. 21. Apart from reduction in body weight and increased urine output, patients with hyponatremia had increases in serum sodium levels that were maintained throughout the study... There were no significant differences in outpatient outcome of worsening CHF (defined as death, hospitalization, or unscheduled visits for CHF) at 60 days between the tolvaptan and placebo groups… Event-free survival tended to be longer for the tolvaptan groups combined when compared with placebo.
  22. 22. Post hoc analysis of ACTIVE in CHF Total mortality was lower in the tolvaptan groups combined compared with placebo in patients with ---elevated blood urea nitrogen levels (10.35 mmol/L [29 mg/dL]) and ---severe systemic congestion at randomization (defined as presence of dyspnea, jugular venous distention, and edema)
  23. 23. Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days (P<0.001) and after the full 30 days of therapy (P<0.001). The condition of patients with mild or marked hyponatremia improved (P<0.001 for all comparisons)… During the week after discontinuation of tolvaptan on day 30, hyponatremia recurred.
  24. 24. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased… Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups.
  25. 25. CONIVAPTAN Development of the oral formulation was discontinued to limit the potential for drug interactions resulting from cytochrome P-450 enzyme inhibition. Blockade of the V1a receptor causes vasodilation of vascular smooth muscle, leading to increased cardiac output and lower systemic vascular resistance. V1a receptor blockade may also prevent AVP-induced coronary artery vasoconstriction and a direct myocardial remodeling stimulus, all of which may be beneficial in patients with hyponatremia caused by CHF.
  26. 26. 142 patients…single intravenous dose of conivaptan or placebo… Conivaptan 20 mg and 40 mg significantly reduced pulmonary capillary wedge pressure at 3 to 6 hours, the primary end point….and the right atrial pressure at 3 to 6 hours, a secondary end point. Dose- dependent increases in urine output were observed during the first 4 hours...Changes in cardiac index, systemic and pulmonary resistance, blood pressure, and heart rate at 3 to 6 hours (all secondary end points) were not significantly different among groups… Hypotension and thirst were the only treatment emergent adverse events that were reported in 5% of patients.
  27. 27.  Nesiritide, the synthetic BNP  A1-adenosine antagonists, which increase natriuresis and diuresis  Corticosteroids, which improve natriuresis and diuresis induced by diuretics  Ultrafiltration, when the other treatment failed or is not available FUTURE DIRECTIONS…
  28. 28. POTASSIUM
  29. 29. Potassium Homeostasis  Most potassium is intracellular  Distribution of between the intra- and extracellular compartments alters serum levels  Na+, K+-ATPase maintains the high intracellular K+ concentration  Pumping Na+ out of the cell and K+ into the cell.  Insulin activates the Na+, K+-ATPase- drives K+ into the cell  Acidosis (high H+) drives potassium extracellularly; (H+ in for K+ out)  Alkalosis drives K+ into the cell  β-Adrenergic agonists stimulate the Na+, K+-ATPase, ↑cellular uptake of K+  α-Adrenergic agonists and exercise cause a net movement of K+ out.  Potassium is necessary for:  Electrical responsiveness of nerve and muscle cells  Contractility of cardiac, skeletal, and smooth muscle.
  30. 30. Homeostasis- controlled by EXCRETION Kidney plays the most important role  90% is of K+ is resorbed before the distal tubule and collecting duct-  In distal tubule and collecting duct- K+ absorbed and secreted  Tubular secretion that regulates the amount of K+ in the urine  Regulating hormone- aldosterone (↑in hyperkalemia)  Acts on cortical collecting duct  Moves sodium into cells  Creates a negative charge in the lumen → K+ excretion.  ↑ intracellular Na+ stimulates the basolateral Na+, K+-ATPase  Moves K+ into cells lining the cortical collecting duct from blood side.  Glucocorticoids, ADH, high urine flow, and high Na+ delivery to the distal nephron also ↑ urine K+.  Alkalosis -↑ urine K+.  Acidosis ↓ urine K+.  Excretion is decreased by insulin, catecholamines, and urine ammonia
  31. 31. Hypokalemia in CHF Causes:  Medication  Increased losses: extrarenal and renal  Transcellular shifts  Decreased intake  *Lab error- spurious
  32. 32. Initial serum potassium concentration and treadmill exercise time carried weak but independent prognostic information. There did, however, appear to be a reduction in the frequency of sudden death when angiotension converting enzyme inhibitors were given.
  33. 33. Treatment- Hypokalemia Severe, symptomatic hypokalemia requires aggressive treatment Because of the risk of hyperkalemia, use IV potassium cautiously 0.5–1 mEq/kg, usually given over 1 hr. The adult maximum dose is 40 mEq. Oral potassium is safer. Potassium chloride is the usual choice for supplementation. Potassium acetate or potassium citrate for patients with acidosis and hypokalemia Potassium phosphate if hypophosphatemia is present Potassium-sparing diuretics- ACE – Inhibitors/ARB
  34. 34. Hyperkalemia in CHF “One of the few things one can die from without any symptoms…” Causes Medications Spurious Increased Intake Decreased Excretion Transcellular shifts
  35. 35. Hyperkalemia- Treatment K+ level, the ECG, and the risk determine the aggressiveness of therapy.  Stop all sources of additional potassium (oral, intravenous) and drugs  If K+ level is believable at >6.0 mEq/L, get ECG Stabilize the heart to prevent life-threatening arrhythmias  Calcium-stabilizes the cell membrane of heart cells Rapidly decrease serum K+ level (even if only temporary)  Bicarbonate- K+ to move intracellularly, lowering the plasma K+ level  Insulin- K+ to move intracellularly, give with glucose  Albuterol neb- stimulates β1-receptors→rapid movement of K+ into cells
  36. 36. Hyperkalemia- Treatment Remove potassium from the body.  Loop diuretic increases renal excretion of K+- only if making urine.  Kayexalate- exchange resin that is given either rectally or orally  Dialysis for acute potassium removal  necessary if severe renal failure or high rate of endogenous K+ release  Hemodialysis better than Peritoneal dialysis  Chronic management  reducing dietary intake and eliminating or reducing medications that cause hyperkalemia. May need meds to remove K+
  37. 37. MAGNESIUM
  38. 38. Hypomagnesemia (<1.4mEq/L)  Contributing factors: Malnutrition Starvation Diuretics Aminoglcoside antibiotics Hyperglycemia Insulin administration
  39. 39.  Magnesium deficit is not infrequently observed in CHF patients but its pathophysiology remains less well-studied  There is evidence that early detection and correction of magnesium abnormalities could obviate potentially deleterious arrhythmogenic effects
  40. 40. Hypomagnesemia was found in 17.4% of hospitalized CHF patients… Inappropriate magnesiuria (fractional excretion of magnesium > 4%) was evident in half of them... A variety of associated conditions, including poor dietary intake, also favored magnesium depletion.
  41. 41. Hypermagnesemia (>2.0mEq/L)  Contributing factors: Increased Mag intake Decreased renal excretion
  42. 42. Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure. Hypomagnesemia is associated with an increse in the frequency of certain forms of ventricular ectopic activity, but this is not associated with an incrase in clinical events. The higher mortality rate among the patients with hypermagnesemia is attributable to older age, more advanced heart failure and renal insufficiency.
  43. 43. Hypomagnesemia (<1.4mEq/L)  Interventions: Eliminate contributing drugs Diet Therapy IV MgSO4 Assess DTR’s hourly with MgSO4
  44. 44. Hypermagnesemia (>2.0mg/dL)  Interventions Eliminate contributing drugs Administer diuretic Calcium gluconate reverses cardiac effects Diet restrictions
  45. 45. CONCLUSION
  46. 46. PROGNOSIS  Hyponatremia is an independent predictor of morbidity & mortality in CHF  Hypokalemia is an independent predictor of sudden cardiac death  Serum magnesium is not an independent risk factor of death in patients with moderate to severe CHF
  47. 47. MANAGEMENT  The use of hypertonic saline solution for the treatment of acute and chronic symptomatic hyponatremia involves complex calculations and requires careful monitoring  Fluid restriction for the treatment of chronic asymptomatic hyponatremia is only moderately effective and presents serious therapeutic adherence issues for patients  Agents such as demeclocycline and lithium have potentially serious side effects  AVP receptor antagonists, the vaptans, are a promising new class of aquaretic agents that increase free-water excretion while maintaining levels of sodium and other essential electrolytes.

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