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Brain & Heart Hypochloremia in refractory heart failure

US$53.1 billion by 2030. One study reported that, in 2006, hypochloremia, electrolytes, mortality, and certain Boolean
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Pakistan had 2.8 million subjects with HF. 3 searches. The authors investigated PubMed, Google Scholar,
HF is a severe and resource-intensive condition EBSCO, and Biomed Central databases from August
that leads to early mortality, high morbidity, impaired 02, 2022, to August 06, 2022. We searched for studies
functional status, low quality of life, and polypharmacy. HF published in the past 10 years in the English language only,
is characterized by symptoms such as shortness of breath, including randomized controlled trials, systematic reviews,
orthopnea, pedal edema, and signs such as elevated jugular meta-analyses, observational studies, and review articles.
venous pressure and pulmonary edema. Most guidelines Cross-references from relevant studies were employed. We
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refer to HF as chronic established HF, which can be graded identified a minimal number of studies from all sources.
according to the functional classification of the New York The search for articles using the Medical Subject Headings
Heart Association. To date, patients with HF are usually (MeSH) terms “Heart Failure,” “Electrolytes,” “Sodium
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categorized into those with reduced ejection fraction (EF) iodide,” and “Mortality” yielded no results in PubMed.
(HF with reduced EF [HFrEF]; EF < 40%), moderately 3. Serum Cl and the pathophysiology of HF
reduced (EF < 40 – 49%), and preserved (EF > 50%).
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Many population-based cohorts have described the factors Cl is usually tested in combination with other electrolytes
that commonly predispose individuals to HF, of which in cases of cardiac failure. Although there is no agreement
coronary artery disease, hypertension, diabetes mellitus, regarding the normal serum Cl level ranges, hypochloremia
obesity, and smoking are notable. HF with preserved EF and hyperchloremia are often defined as <96 mmol/L and
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(HFpEF) represents approximately 50% of all HF in most >105 mmol/L, respectively. Electrolytes are essential for
cases. The studies that reported long-term follow-up intracellular signaling in cardiac myocytes and contribute
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data and standardized criteria show that mortality in HF to cellular action potentials in the cardiovascular system.
is high. More recent studies have reported nearly 50% at Cl channels in the heart affect the membrane potential
5 years. The 1-year mortality rate after an HF incident in and action potential duration in the sinoatrial node, which
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the UK population was reported to be as high as 32%, of can cause arrhythmias. This arrhythmogenesis results
which 43% was attributed to CVDs. 7 from abnormal Cl levels, which are partly mediated by
There are many well-known independent predictors dysregulated myocyte intracellular pH and potassium (K)
of prognosis in HF. The outcome of HF remains poor levels, and can lead to sudden cardiac death. 12
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in terms of mortality, frequent hospitalizations, and Patients with HF demonstrate a more than 50% decrease
worsening of HF, comparable to that of many malignancies. in the presence of a Cl transfer regulator called the cystic
Advanced age, previous hospitalization, edema, lower fibrosis transmembrane conductance regulator in an adaptive
blood pressure, high blood urea nitrogen, high N-terminal mechanism during the HF progression. Consequently,
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pro-brain natriuretic peptide, anemia, and lack of beta- this may lead to instability in repolarization and a higher
blocker prescription are independently associated with tendency for cardiac arrhythmias. Moreover, this electrolyte
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mortality and re-hospitalization. Fluid and electrolyte imbalance causes dysregulation of myocyte intracellular
hemostasis are integral components of HF. Serum sodium pH, which carries the risk of arrhythmias. The adaptive
(Na) is the focus of discussion as a recognized marker of remodeling of Cl channels can contribute to the progression
adverse outcomes in patients with HF. However, this long- of myocardial hypertrophy and subsequent HF. 12-14
debated pro-Na view has been challenged by many recent
research studies. Recently, it has been observed that low 4. Studies of Cl abnormalities in HF
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serum chloride (Cl) levels (hypochloremia) on admission In a Chinese retrospective study comprising large amounts
can predict mortality risk in HF. Surprisingly, survival
analysis studies using Na and Cl have proposed a stronger of data from two registries (N = 4,762 and N = 3,481),
prognostic value for serum Cl levels. 10,11 hypochloremia was present in 10.2% and 20.1% of the
study population, respectively. Further, after adjusting for
In this SANRA-compliant review, we reviewed the role confounders, hypochloremia was associated with mortality
of serum Cl as a potential prognostic marker of HF. We also in HF (90-day mortality: Adjusted hazard ratio [aHR]: 1.69;
explored the possible mechanisms of the Cl interactions in 95% CI: 1.27 – 2.25; P < 0.001 in one population, and 1.36
HF and their impact on the outcome. [1.17 – 1.59]; P < 0.001 in the second population). The same
study also found hypochloremia as a predictor of long-
2. Search methods term mortality (aHR: 1.26; 95% CI: 1.06 – 1.50; P = 0.009,

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We carried out a comprehensive review of the literature and 1.48 [1.32 – 1.66]; P < 0.001), respectively. A study of
electronically. The keywords used were HF, serum Cl, patients with acute decompensated HF (ADHF) admitted

Volume 2 Issue 1 (2024) 2 https://doi.org/10.36922/bh.2257