Curr Heart Fail Rep
DOI 10.1007/s11897-016-0295-7
BIOMARKERS OF HEART FAILURE (W H W TANG, SECTION EDITOR)
Pharmacologic Approaches to Electrolyte Abnormalities
in Heart Failure
Justin L. Grodin 1
# Springer Science+Business Media New York 2016
Abstract Electrolyte abnormalities are common in heart fail-
ure and can arise from a variety of etiologies. Neurohormonal
activation from ventricular dysfunction, renal dysfunction,
and heart failure medications can perturb electrolyte homeo-
stasis which impact both heart failure-related morbidity and
mortality. These include disturbances in serum sodium, chlo-
ride, acid-base, and potassium homeostasis. Pharmacological
treatments differ for each electrolyte abnormality and vary
from older, established treatments like the vaptans or acetazol-
amide, to experimental or theoretical treatments like hyperton-
ic saline or urea, or to newer, novel agents like the potassium
binders: patiromer and zirconium cyclosilicate.
Pharmacologic approaches range from limiting electrolyte in-
take or directly repleting the electrolyte, to blocking or pro-
moting their resorption, and to neurohormonal antagonism.
Because of the prevalence and clinical impact of electrolyte
abnormalities, understanding both the older and newer thera-
peutic options is and will continue to be necessity for the
management of heart failure.
Keywords Electrolytes . Heart failure . Treatment .
Hyponatremia . Hypochloremia . Metabolic alkalosis .
Hyperkalemia
This article is part of the Topical Collection on Biomarkers of Heart
Failure
* Justin L. Grodin
grodinj@ccf.org
1
Department of Cardiovascular Medicine, Heart and Vascular
Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4,
Cleveland, OH 44195, USA
Introduction
In heart failure, cardiac hemodynamic abnormalities and their
treatments can have a broad range of effects on the human
body. One of these downstream effects is electrolyte distur-
bance which can occur in both chronic stable patients or in
those hospitalized with acute heart failure (AHF). Commonly
encountered electrolyte disturbances include abnormalities in
sodium, chloride, acid-base (bicarbonate), and potassium
homeostasis.
These electrolyte abnormalities may be multifactorial and
interrelated resulting from neurohormonal activation, renal
dysfunction, and medication use. They are clinically impor-
tant with their strong association with heart failure treatments
[1–6] and impact on adverse clinical events [7–14]. It is there-
fore not surprising that checking electrolytes is currently high-
ly recommended by both the American College of
Cardiology/American Heart Association and European
Society of Cardiology heart failure treatment guidelines [15,
16]. Because of the frequency at which they are encountered
and their clinical relevance, therapies have been developed to
manage electrolyte abnormalities in patients with heart failure.
Herein, both older and newer pharmacological approaches to
disturbances in serum sodium, chloride, bicarbonate, and po-
tassium in heart failure will be reviewed.
Treatment for Abnormalities in Serum Sodium
Hypernatremia (Na ≥ 145 mEq/L) in heart failure is rare and
associated with adverse clinical events but is commonly treat-
ed by giving enteral or parenteral free water [17].
Hyponatremia (commonly Na < 134 mEq/L), on the other
hand, is one of the most well-recognized electrolyte distur-
bances in both chronic and acute heart failure, and it is a

popular marker of increased risk for adverse events [7, 8, 18,
19]. When present on admission, or when acquired in the
hospital, hyponatremia is associated with increased length of
stay, discharge to acute-care facilities, and mortality [20]. The
prevalence of hyponatremia upon hospitalization for acute
heart failure has been estimated to be approximately 20 %
[21]. In those that present with normal sodium levels,
hyponatremia may develop in approximately 15–25 % of pa-
tients treated for acute heart failure and may even be transient
[22–24].
The generation of hyponatremia in heart failure may be
multifactorial. Maladaptive neurohormonal responses can
lead to dysregulation of arginine vasopressin-mediated free
water absorption and thirst activation [25–27]. As a result,
the plasma concentration of sodium becomes diluted.
Sodium can also be lowered by chronic loop and thiazide
diuretic use. These therapies inhibit the electrolyte reabsorp-
tion in the thick ascending limb of Henle’s loop and the distal
convoluted tubules [28, 29]. In addition, as diuretics limit the
kidney’s ability to excrete maximally dilute urine through re-
nal sodium wasting, their chronic use may lead to sodium
depletion [30].
Hypertonic Saline
The use of hypertonic saline solution (HSS) has classically
been studied for volume resuscitation in conditions with im-
paired regional organ blood flow or severe, symptomatic
hyponatremia [31]. The hemodynamic benefits of HSS ad-
ministration are likely a result of increased intravascular vol-
ume, peripheral arterial vasodilation (likely mediated by plas-
ma volume and hyperosmolality), reduction of tissue edema,
reduction in sympathetic tone, and an increase renal blood
flow [31, 32]. Because these physiologic changes are hemo-
dynamically favorable for a failing ventricle, HSS may be
useful in heart failure, especially in those with hyponatremia
and refractory congestion.
To date, there are no randomized, double-blinded data
supporting the use of HSS in heart failure. However, there
remains compelling data supporting its use. An early pilot
study by Paterna et al. comprised patients with acute heart
failure (AHF) and a left ventricular ejection fraction (LVEF)
of <35 % sought to determine the impact of HSS (1.4–4.6 %
normal saline, N = 30) as an adjunct to high-dose furosemide
(250-1000 mg/twice daily) in comparison to high-dose furo-
semide alone (N = 30) in patients with diuretic-refractory con-
gestion in a single-blinded, randomized fashion [33]. Their
provocative results suggested that HSS use increased urine
output and natriuresis without renal compromise in compari-
son to furosemide alone. In a very similar AHF patient popu-
lation (N = 53 with HSS and furosemide vs N = 54 with furo-
semide alone) receiving the same treatment, HSS was associ-
ated with a reduction in readmissions and improved survival
Curr Heart Fail Rep
[34]. Results from a similar small, blinded, randomized cohort
(N = 94) suggest that diuresis complimented with HSS was
associated more rapid decongestion, increased drop in B-
type natriuretic peptide (BNP) level, increased thoracic im-
pedance (a marker of decongestion), and similarly lower
readmissions in comparison to those that did not receive
HSS [35]. Comparable findings have been seen in other stud-
ies showing greater reductions in BNP, reductions echocardio-
graphic estimates of filling pressure, and reductions in cardiac
troponin levels during treatment with HSS [36–38].
In addition to greater decongestive efficacy, HSS use may
also preserve renal function during diuresis. Previous cohorts
have suggested a lower incidence of worsening renal function
during treatment for AHF [39–41]. Further, a meta-analysis of
nine studies of patients receiving HSS as an adjunct to loop
diuretic therapy in AHD revealed a consistent trend in the
renoprotective effects of HSS use [42].
Urea
Urea is a natural by-product of the urea cycle formed from
ammonia and carbon dioxide. In animals, it is an abundant
nitrogen containing compound. It has a neutral pH and is
highly soluble in water. Although it has many physiological
roles, its most notable role is nitrogen excretion.
Urea-containing skin products are commonly used for skin
rehydration. However, urea can also be used as a diuretic. The
ability of urea to diurese patients with congestion in heart failure
has been known for some time [43]. In the setting of refractory
congestion, the addition of oral urea causes increased urine
volume and urea excretion parallels volume excretion with
the unique ability to inhibit natriuresis. However, these effects
are tempered by several challenges of administering urea. It can
cause nausea and must be taken with food and has a metallic
taste. Although it is relatively well tolerated at higher levels
(e.g., 32–50 mmol/L), symptomatic uremia can also occur,
but its effects resolve with treatment cessation [44].
Urea causes an osmotic diuresis and has classically been
studied in cases of elevated cerebrospinal pressure [44, 45].
Because of this, early reports suggested immediate and
sustained improvement in hyponatremia (via negative free wa-
ter balance and positive sodium balance) with improvement in
neurological symptoms for the management of the syndrome of
inappropriate secretion of antidiuretic hormone (SIADH) [46,
47]. In fact, similar results suggest that long-term urea therapy
was surprisingly well-tolerated and led to a sustained resolution
of hyponatremia in patients with SIADH [48].
The osmotic diuresis caused by urea administration is
sustained, even in cases of diuretic-refractory congestion. In
particular, urea has been associated with increased deconges-
tion and reversal of hyponatremia in patients with cirrhosis
[49]. Although there have been no large, randomized con-
trolled clinical trials comparing the efficacy of urea to standard
Curr Heart Fail Rep
therapy, it may be an ideal therapy to treat congestion in the
setting of heart failure. As ventricular dysfunction progresses,
there is increased antidiuretic hormone (ADH)-mediated free
water absorption and increased thirst activation which drives
sodium concentrations downwards through dilution [25–27].
Because free water excretion is limited without increased na-
triuresis, decongestion with urea may be attractive. Adding to
this, the correction of hyponatremia with urea in heart failure
may be a safer alternative to other therapies. Murine models of
hyponatremia suggest that urea does not hyperionize (increase
sodium and chloride) and therefore its use is less prone to
cause demyelination [50]. Despite these favorable effects,
the correction of hyponatremia in heart failure with urea re-
mains theoretical and merits further study.
Vaptans
The neurohormone vasopressin (or ADH) exerts a potent va-
soconstrictive effect via the cardiac V1A and induces water
retention via the renal V2 receptors. The first in the class of
vaptans, conivaptan—an orally active, non-peptide, V1A and
V2 receptor antagonist—increases free water clearance in heart
failure [51, 52]. The vaptans inhibit renal water resorption by
antagonizing the V2 receptors and therefore leading to free
water loss and a secondary increase in serum sodium levels.
Therefore, vaptans are appealing decongestive therapies in
heart failure—especially those with hyponatremia. In fact,
conivaptan has a dose-dependent relationship in pulmonary
capillary wedge pressure reduction and increase in serum so-
dium [53]. Similarly effective is another vaptan, tolvaptan,
which is V2 receptor specific and increases sodium levels in
patients with hyponatremia, and is more effective in doing so
than fluid restriction alone in patients with heart failure [54,
55].
In AHF, the vaptans are additionally effective in reducing
congestion and improving heart failure symptoms when added
to standard diuretic regiments [56–59]. Despite these promis-
ing findings, however, results from the Efficacy of
Vasopressin Antagonism in Heart Failure Outcome Study
With Tolvaptan (EVEREST, N = 4,133) show that, despite
improvement of hyponatremia and short-term clinical im-
provement, the use of tolvaptan in patients with heart failure
does not effect long-term clinical outcomes.
In response to EVEREST, others have tried to identify sub-
groups of heart failure patients that may have a more favorable
clinical response. For example, a sub-analysis form
EVEREST attempting to determine if there were an interac-
tion between ADH levels and tolvaptan suggested no added
clinical benefit [60]. However, in subjects with hyponatremia
(Na < 135 mEq/L), tolvaptan was associated with greater
weight reduction at day 1 and discharge and dyspnea relief
in comparison to placebo [61]. In a minority of these patients
(n/N = 92/4133) with more profound hyponatremia
(Na < 130 mEq/L), there was a trend towards a reduction in
all long-term endpoints including mortality, cardiovascular
mortality, and heart failure or cardiovascular hospitalizations.
However, the clinical benefits of correcting serum sodium with
tolvaptan remain uncertain.
As a result of the EVEREST trial, the use of vaptans for the
management of hyponatremia in heart failure is not strongly
endorsed by the ACC/AHA or ESC heart failure treatment
guidelines and that it is mainly reserved for patients with
treatment-resistant hyponatremia [15, 16]. Yet, unanswered
questions remain regarding the use of vasopressin antagonists
for other short-term outcomes in acute heart failure. For in-
stance, the vaptans may be used in Bdiuretic sparing^ or
Bdiuretic dose reduced^ decongestive strategies in heart fail-
ure [62, 63]. For example, the Acute and Chronic Therapeutic
Impact of a Vasopressin Antagonist in Congestive Heart
Failure (ACTIV-CHF) trial sought to determine the affect of
tolvaptan versus placebo through 60 days in addition to di-
uretic therapy in 319 patients [64]. Interestingly, by 24 h, the
tolvaptan arm had a greater weight reduction without
compromising renal function. These findings are consistent
with a prior physiologic study showing that V2 antagonism
increases renal free water clearance without affecting renal
hemodynamics [65]. Two ongoing clinical trials will attempt
to inform more evidenced-based clinical decision making re-
garding the use of oral tolvaptan in AHF: the Targeting Acute
Congestion With Tolvaptan in Congestive Heart Failure Study
(TACTICS) and Study to Evaluate Challenging Responses to
Therapy in Congestive Heart Failure (SECRET of CHF) trials
[66].
Treatment for Abnormalities in Serum Chloride
Hyperchloremia (Cl > 107 mEq/L) in heart failure is rare and
likely treated similarly to hypernatremia [10]. The focus on
electrolyte abnormalities in heart failure has been primarily on
hyponatremia. However, several recent epidemiological stud-
ies have emphasized the importance of hypochloremia (Cl ≤
96 mEq/L) in heart failure [9, 10, 12]. Like sodium, serum
chloride levels are affected similarly by ADH. In that regard,
hypochloremia in heart failure can be dilutional in nature as a
result of increased renally mediated free water retention
through heightened stimulation of the V 2 receptors.
However, chloride levels are also tightly regulated by two
major mechanisms: (1) maintaining electroneutrality between
the intracellular and extracellular spaces, and (2) the ability of
the kidney to maintain serum chloride balance through reab-
sorption and excretion. This second is likely the major mech-
anism in heart failure commonly dysregulated by salt restric-
tion and loop diuretic usage. A reduction in dietary chloride
intake limits tubular delivery of chloride, and loop diuretics
limit chloride resorption via blockade of the sodium-

potassium-chloride transporter in the thick ascending limb
[28].
Chloride homeostasis may be maintained through volume
and chloride distribution in the intracellular and extracellular
spaces into the vasculature. This effect can be transiently
effected in the AHF setting with short-term courses of inten-
sive loop diuretic during AHF or more chronically perturbed
through escalating loop diuretic dosage over time in ambula-
tory heart failure patients. In that sense, loop-diuretic minimiz-
ing or sparing decongestive strategies in the acute or chronic
settings may preserve chloride homeostasis.
Indeed, therapies may directly or indirectly increase serum
chloride levels. For instance, lysine chloride (an orally admin-
istered organic chloride salt) or hypertonic saline may directly
increase serum chloride levels, but the pharmacological im-
pact of these therapies on serum chloride levels is not
completely known [67]. On the other hand, other approaches
that increase free water excretion, through similar mechanisms
to improving hyponatremia, may also increase serum chloride
levels. These include both the vaptans or even urea.
Regardless, whether these strategies effect short-term clinical
effects such as diuretic responsiveness or renal function im-
pact or long-term morbidity or mortality is unknown.
Treatment for Metabolic Acid-Base Abnormalities
Metabolic acidoses are not classically associated with heart
failure and can occur from other common causes including
uremia, metabolic abnormalities, toxins, secondary to a respi-
ratory alkalosis, or ketoacidosis. However, a metabolic acido-
sis (HCO3− <20 mEq/L) from impaired organ perfusion can
be seen in severe cardiogenic shock and can be reversed with
correction of the hemodynamic disarray. On the other hand,
the most well-recognized acid-base disturbance in heart fail-
ure is a contraction metabolic alkalosis (HCO3− >30 mEq/L),
typically in the setting of diuretic-mediated decongestion. It is
not uncommon and may be present in as many as ∼30–40 %
of patients with heart failure [68]. Interestingly, some esti-
mates suggest that the prevalence may be as high as 47 % in
AHF [6]. The mechanisms driving a contraction metabolic
alkalosis include chloride loss, decreased effective arterial
blood volume, activation of the renin-angiotensin-
aldosterone system, increased sodium delivery to the distal
nephron, and hypokalemia [69]. Although, animal models
suggest that hypochloremia may be the strongest mediator of
a contraction alkalsosis [70]. Data compiled from the Diuretic
Optimization Strategies Evaluation in Acute Heart Failure,
Renal Optimization Strategies Evaluation in Acute Heart
Failure, and the Cardiorenal Rescue Study in Acute
Decompensated Heart Failure clinical trials suggest that there
is no clear relationship between decongestive treatment and
the magnitude of increase in serum bicarbonate [6].
Curr Heart Fail Rep
Nevertheless, a metabolic alkalosis can be clinically
concerning. In severe cases, the metabolic alkalosis can de-
press the central respiratory drive by inhibiting brain chemo-
receptors and thereby leasing to a compensatory
hypoventilation to drive down pH [71, 72]. Alkaloses may
have detrimental effects on both the cardiovascular and central
nervous systems such as ventricular arrhythmia and decreased
cerebral blood flow. Symptoms from the latter vary in severity
from light-headedness, confusion, and syncope, to seizures. In
AHF, changing bicarbonate during admission may also iden-
tify patients at high risk for long-term adverse events [73].
Paradoxically, the opposite may be true for short-term events.
In an observational cohort of 1000 patients with AHF, the
evolution of a metabolic alkalosis was actually associated with
better inpatient survival and may be perhaps linked to the
ability to achieve adequate decongestion [14].
Unfortunately, the choices for correcting an elevated serum
bicarbonate or metabolic alkalosis in heart failure are limited.
Acetazolamide—a diuretic used for decongestion prior to the
advent of loop diuretics—inhibits carbonic anhydrase. Via
inhibition of this enzyme in the proximal nephron, it inhibits
resorption of bicarbonate, sodium, and chloride [74, 75]. This
pharmacological action results in increased urinary bicarbon-
ate losses and subsequent acidification of the blood. The
added natriuresis from the sodium counterions to bicarbonate
leads to decongestion. Because of this, it is an attractive agent
for reducing serum bicarbonate in patients with heart failure—
especially when they are congested [76]. Furthermore, the
addition of acetazolamide to loop diuretics provides sequential
nephron blockade that may break diuretic-refractory conges-
tion [77]. Through its ability to modulate systemic acid-base
status, acetazolamide use may be additionally beneficial
through reducing affecting periodic breathing and apnea/
hypopnea episodes during sleep [78].
Despite these therapeutic benefits of acetazolamide, its ef-
ficacy in heart failure has not been rigorously tested.
Acetazolamide was shown in a largely outdated retrospective
cohort (N = 74) of AHF patients with a loop diuretic- and
spironolactone-induced metabolic alkalosis to reduce serum
bicarbonate levels with augmented diuresis [76]. In a small
prospective cohort of patients with AHF and daily urine col-
lection (N = 54), the addition of acetazolamide to bumetanide
amplified natriuretic response in comparison to loop diuretics
alone [79]. Regardless, the use of acetazolamide for treatment
of metabolic alkalosis in heart failure is an attractive option,
especially if there is lingering congestion with understanding
that its impact on clinical events is not completely understood.
Treatment for Serum Potassium Abnormalities
Abnormal potassium homeostasis is typically a result of phar-
macological treatment for heart failure. Loop and thiazide
Curr Heart Fail Rep
diuretics can cause hypokalemia (K < 3.5 mEq/L) which is
easily corrected by potassium salt supplementation, adding
potassium-sparing diuretics, or loop diuretic dose reduction
or cessation. On the other hand, hyperkalemia (K > 5.0
mEq/L) is more challenging. Drugs that antagonize the
renin-angiotensin system (RAS) such angiotensin converting
enzyme inhibitors or angiotensin receptor blockers, or miner-
alocorticoid receptor antagonists (MRA) have mild potassium
increasing properties. This is potentially problematic given
their clinical benefits. RAS blockade can cause hyperkalemia
as result of decreased aldosterone. Although this effect may be
mild or even insignificant in patients with normal renal func-
tion, in patients with renal impairment or who are already
taking potassium supplementation or an MRA, hyperkalemia
can occur [80].
Although rare, hyperkalemia does occur with concomitant
RAS blocker and MRA use [81–83]. Interestingly, the inci-
dence of hyperkalemia may mirror the release of clinical tri-
als for these pharmacotherapies as clinicians are likely
responding to their results [84]. Although estimates suggest
that the incidence of hyperkalemia in patients taking these
medications may be only 5–15 % [81–83], heart failure prev-
alence exceeds more than 5.8 million people in the united
states and may have an annual incidence of >550,000 new
case each year [85]. Therefore, a substantial population of
heart failure patients may be risk for hyperkalemia. In these
patients, continuing or increasing the offending therapies may
be difficult when the serum potassium is elevated out of con-
cern that it may rise to dangerous levels. Therein lies the
disconnect, however, as the long-term risk benefit of these
therapies, especially MRAs, persists without an excess risk
from hyperkalemia [3, 13].
Risk factors for hyperkalemia with the use of RAS blockers
and MRAs include older age, higher dose RAS blocker or
MRA, diabetes, increased heart failure clinical severity, higher
baseline serum potassium values, and renal function impair-
ment [4, 81, 83, 86, 87]. These can be common in heart failure
populations, and thus, there is a significant portion at risk for
hyperkalemia from RAS blockers and MRAs that would still
have clinical benefit from their use. Further, hyperkalemia for
these agents can result in lower than target or maximally tol-
erated doses of these medications, especially in patients with
chronic kidney disease.
The current treatment for chronic hyperkalemia is limited
and commonly leads to cessation of RAS blocker or MRA use
[88]. Until recently, the pharmacological treatment for
hyperkalemia in heart failure was relegated to the use of sodi-
um polystyrene sulfate (or kayexalate) which is an ion ex-
change resin that binds potassium in the colon. This treatment
was approved by the US Food and Drug Administration in
1958. It may be useful if used infrequent doses. However, it
has poor tolerability (constipation and fecal impaction) and
recent concerns have been raised regarding rare cases of
colonic necrosis or other serious gastrointestinal adverse
events with concomitant use of sorbitol (a cathartic) and its
efficacy in reducing serum potassium levels [89]. In addition,
other adverse events including sodium loading, hypocalcemia,
and hypomagnesemia further add to its unsuitability for chron-
ic administration.
Patiromer
Two newer pharmacotherapies for hyperkalemia are coming
onto the horizon. Patiromer and sodium zirconium
cyclosilicate (ZS-9) are two newer therapies which demon-
strate both early and sustained maintenance of normokalemia
over weeks with good tolerability. Patiromer is a cationic
polymer that works by binding potassium in the colon thus
reducing the amount of potassium available for absorption
into the blood stream. Early studies demonstrated a proof-of-
concept in its ability to allow MRA uptitration without in-
creased potassium levels in comparison to placebo [90]. The
Efficacy and Safety of Patiromer for the Treatment of
Hyperkalemia (OPAL-HK) was a phase 3 study that sought
to determine the median change in serum potassium level over
4 weeks in patients with chronic kidney disease (estimated
glomerular filtration rate [eGFR] 15–60 ml/min per 1.73 m2
of body-surface area), with elevated serum potassium levels
(5.1–6.5 mmol/L) taking RAS blockers, MRAs, or both [91].
In this trial, patiromer was associated with a reduction in se-
rum potassium and a lower incidence of recurrent
hyperkalemia and was relatively well-tolerated with the most
common gastrointestinal side effect being constipation.
Comparable findings were seen in the Patiromer in the
Treatment of Hyperkalemia in Patients with Hypertension
and Diabetic Nephropathy (AMYTHYST-DN) clinical trial
[92].
Zirconium Cyclosilicate
In contrast to both sodium polystyrene sulfate and patiromer,
ZS-9 was engineered as a highly selective binder of potassium
(a monovalent cation, K+) over other divalent cations like
calcium (Ca2+) or magnesium (Mg2+). This property stems
from its high-capacity inorganic crystalline lattice structure.
Additionally, ZS-9 is completely insoluble in aqueous solu-
tions and is not systemically absorbed after oral ingestion [93].
Similar to patiromer, early results in patients with potassium
levels 5.0–6.0 mEq/L and stage 3 chronic kidney disease
(eGFR 30–60 ml/min per 1.73 m2 of body-surface area) dem-
onstrated efficacy in reducing serum potassium levels with
good tolerability. Results from the Safety & Efficacy of
Zirconium Silicate Dosed for 28 Days in Hyperkalemia
(HARMONIZE) clinical trial suggested that ZS-9 was effica-
cious in both lowering serum potassium levels into the normal
range (commonly ≤5.0 mEq/L) within 4 h [94]. There was a

dose-dependent lowering of potassium that was sustained to
28 days. In a larger, multinational, multicenter study which
randomized patients with serum potassium levels 5.0–
6.5 mmol/L, there was a similar dose-dependent decrease in
serum potassium levels and the drug was well tolerated with a
safety profile similar to placebo [95].
While both of these novel potassium-binding agents show
promising results, their clinical impact on heart failure patients
is unknown. Only a portion of the patients recruited to these
trials had heart failure. The utility of these drugs in heart fail-
ure remains to be seen but is dependent on the following
outcomes: (1) their ability to allow added RAS blockers or
MRAs, (2) their ability to permit increasing doses of RAS
blockers or MRAs to target or maximum tolerated dosing,
and (3) whether their use will sustain the long-term benefits
of RAS blocker or MRA use.
Conclusion
Electrolyte abnormalities are common in heart failure and are
multifactorial in nature. Hyponatremia and hyperkalemia are
both well-studied with an array of both historical and newer
novel treatments. Whether treatments such as urea or hyper-
tonic saline for hyponatremia or potassium binders for
hyperkalemia have a meaningful impact on clinical outcomes
in heart failure patients remains unclear. The electrolyte ab-
normalities hypochloremia and metabolic alkalosis are incom-
pletely studied and have less well-established therapies.
Because of their prevalence, understanding and treating elec-
trolyte abnormalities will continue to be a mainstay in the
management of heart failure.
Compliance with Ethical Standards
Conflict of Interest Justin L. Grodin has nothing to disclose.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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