1. ELECTROLYTE DYSBALANCE
IN CHF: PROGNOSIS &
MANAGEMENT
Dr. Arindam Pande, MD, DM
Associate Consultant, Cardiology
Apollo Gleneagles Hospital, Kolkata

2. PATHOPHYSIOLOGY OF CHF
 Chronic activation of
Renin-angiotensin-aldosterone system (RAAS)
Sympathetic nervous system
Antidiuretic hormone arginine vasopressin (AVP)

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. 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. SODIUM

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. 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. 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.

10. creatinine, and serum sodium were
related to progressive heart failure
death….serum potassium were
related to sudden cardiac death

12. 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.

14. 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.

15. Therapy for
hyponatremia
is not as
straight
forward as the
picture by
simply
replenishing
sodium by
means of extra
salt…

16.  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:

17. Correction of Hyponatremia

19. 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.

20. Therapeutic Options for Hyponatremia
Due to Congestive Heart Failure

21. LIMITATIONS OF EXISTING THERAPY
 variable efficacy,
 slow onset of action,
 compliance issues, and
 toxicities.

22. 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.

23. Unfortunately….

24. AVP RECEPTOR BLOCKERS
(aquaretics)

26. 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.

27. 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)

29. 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.

31. 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.

32. 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.

34. 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.

35.  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…

36. POTASSIUM

37. 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.

38. 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

39. Hypokalemia in CHF
Causes:
 Medication
 Increased losses: extrarenal and renal
 Transcellular shifts
 Decreased intake
 *Lab error- spurious

41. 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.

42. 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

43. Hyperkalemia in CHF
“One of the few things one can die from
without any symptoms…”
Causes
Medications
Spurious
Increased Intake
Decreased Excretion
Transcellular shifts

44. 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

45. 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+

46. MAGNESIUM

47. Hypomagnesemia (<1.4mEq/L)
 Contributing factors:
Malnutrition
Starvation
Diuretics
Aminoglcoside antibiotics
Hyperglycemia
Insulin administration

48.  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

50. 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.

51. Hypermagnesemia (>2.0mEq/L)
 Contributing factors:
Increased Mag intake
Decreased renal excretion

53. 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.

54. Hypomagnesemia (<1.4mEq/L)
 Interventions:
Eliminate contributing drugs
Diet Therapy
IV MgSO4
Assess DTR’s hourly with MgSO4

55. Hypermagnesemia (>2.0mg/dL)
 Interventions
Eliminate contributing drugs
Administer diuretic
Calcium gluconate reverses cardiac effects
Diet restrictions

56. CONCLUSION

57. 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

58. 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.