Prognostic impact of serum chloride concentrations in acute heart failure patients: A systematic Rreview and meta-analysis.

Acute heart failure (AHF) is a common disease in the emergency departments. Its occurrence is often accompanied by electrolyte disorders, but little attention is paid to chloride ion. Recent studies have shown that hypochloremia was associated with poor prognosis of AHF. Therefore, this meta-analysis aimed to assess the incidence of hypochloremia and the impact of the reduction of serum chloride on the prognosis of AHF patients. We searched Cochrane Library, Web of science, PubMed, Embase databases and searched the relevant studies on chloride ion and AHF prognosis. The search time is from the establishment of the database to December 29, 2021. Two researchers screened the literature and extracted data independently. The quality of the included literature was evaluated using Newcastle-Ottawa Scale (NOS) scale. The effect amount is expressed as hazard ratio (HR) or relative risk (RR) and 95% confidence interval (CI). Review Manager 5.4.1 software for was used to perform the meta-analysis. Seven studies involving 6787 AHF patients were included in meta-analysis. Meta-analysis revealed that the incidence of hypochloremia in AHF patients at admission was 17% (95% CI: 0.11-0.22); One mmol /L decrease in serum chloride at admission was associated with 6% increased risk of all-cause death of AHF patients (HR = 1.06, 95% CI: 1.04-1.08, P < 0.00001); Compared with the non-hypochloremia group, the risk of all-cause death in the hypochloremia group increased by 1.71 times (RR = 1.71, 95% CI: 1.45-2.02, P < 0.00001), the risk of all-cause death in the progressive hypochloremia(development of hypochloremia after admission) group increased by 2.24 times (HR = 2.24, 95% CI: 1.72-2.92, P < 0.00001), and the risk of all-cause death in the persistent hypochloremia (hypochloremia both on admission and at discharge) group increased by 2.80 times (HR = 2.80, 95% CI: 2.10-3.72, P < 0.00001). The available evidence shows that the decrease of chloride ion at admission is associated with poor prognosis of AHF patients, and the prognosis of persistent hypochloremia is worse.Some outcome indicators(progressive hypochloremia, persistent hypochloremia, and composite of death + HF hospitalization)are as few as 2 studies in the literature, and the results should be interpreted carefully.

Wu F ，Lan Q ，Yan L 《-》

Trajectory of serum chloride levels during decongestive therapy in acute heart failure.

Hypochloremia is a risk factor for poor outcomes in patients with acute heart failure (AHF). However, the changes in serum chloride levels during decongestion therapy and their impact on prognosis remain unknown. In total, 2798 patients with AHF were retrospectively studied and divided into four groups according to their admission and discharge serum chloride levels: (1) normochloremia (n=2,192, 78%); (2) treatment-associated hypochloremia, defined as admission normochloremia with a subsequent decrease (<98 mEq/L) during hospitalization (n=335, 12%); (3) resolved hypochloremia, defined as admission hypochloremia that disappeared at discharge (n=128, 5%); (4) persistent hypochloremia, defined as chloride <98 mEq/L at admission and discharge (n = 143, 5%). The primary outcome was all-cause death, and the secondary outcomes were cardiovascular death and a composite of cardiovascular death and rehospitalization for heart failure after discharge. The mean age was 76 ± 12 years and 1584 (57%) patients were men. The mean left ventricular ejection fraction was 46 ± 16%. During a median follow-up period of 365 days, persistent hypochloremia was associated with an increased risk of all-cause death (adjusted hazard ratio [95% confidence interval]: 2.27 [1.53-3.37], p < 0.001), cardiovascular death (2.38 [1.46-3.87], p < 0.001), and a composite of cardiovascular death and heart failure rehospitalization (1.47 [1.06-2.06], p = 0.022). However, the outcomes were comparable between patients with resolved hypochloremia and normochloremia. Persistent hypochloremia was associated with worse clinical outcomes, while resolved hypochloremia and normochloremia showed a comparable prognosis. Changes in serum chloride levels can help identify patients with poor prognoses and can be used to determine subsequent treatment strategies.

Kurashima S ，Kitai T ，Matsue Y ，Nogi K ，Kagiyama N ，Oishi S ，Akiyama E ，Suzuki S ，Yamamoto M ，Kida K ，Okumura T ，Nogi M ，Ishihara S ，Ueda T ，Kawakami R ，Furukawa Y ，Saito Y ，Izumi C ... -  《-》

Prevalence and prognostic role of hypochloremia in patients with acute heart failure in Ethiopia: A single-center retrospective analysis.

In patients with heart failure (HF), multiple electrolyte disorders are common, and recent studies have shown that chloride disorders play a significant role in the prognosis of HF. Data about the prevalence and prognostic role of hypochloremia in patients with acute HF (AHF) are scarce in African nations, including Ethiopia. Hence, this study aimed to assess the prevalence, associated factors, and prognostic role of hypochloremia in patients with AHF in Ethiopia. This was a single-center retrospective analysis of AHF patients, aged ≥15 years, with chloride determination upon admission to the medical wards and medical ICU of Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia, from July 1, 2022, to July 1, 2023. Statistical Package for Social Sciences, version 26, was used to enter and analyze the data. Descriptive analysis was used to summarize clinical profiles, laboratory data, and outcomes of AHF patients stratified by the presence and absence of hypochloremia. Logistic regression analysis was used to determine the factors associated with hypochloremia and to assess the association of hypochloremia and other factors with in-hospital mortality in patients with AHF. A two-tailed P value <0.05 was regarded as statistically significant. A total of 267 AHF patients who had chloride determination on admission were included in this study; the mean age was 56.7 years (standard deviation: 18.6), and the gender-based distribution of the patients was nearly equal. The prevalence of hypochloremia was 36.7%. Diastolic blood pressure <60 mm Hg [adjusted odds ratio (AOR) = 3.63, 95% confidence interval (CI), 1.04, 12.72] and hyponatremia (AOR = 29.20, 95% CI, 13.21, 64.56) were significantly associated with hypochloremia. The in-hospital mortality rate was higher in AHF patients with hypochloremia (16.3%) compared to those without hypochloremia (4.7%). The odds of in-hospital mortality among AHF patients with hypochloremia were 2.8 times higher compared to patients without hypochloremia (AOR = 2.82, 95% CI: 1.08, 7.04) after adjusting for ICU admission, systolic blood pressure < 120 mm Hg and diastolic blood pressure < 60 mm Hg. This study revealed a high prevalence of hypochloremia among patients with AHF. Low diastolic blood pressure and hyponatremia were significantly associated with the development of hypochloremia. Most importantly, AHF patients with hypochloremia had a higher in-hospital mortality rate compared to those without hypochloremia. Hence, hypochloremia on admission should be considered a potential prognostic factor in patients with AHF, and further research with a larger sample size is needed to support the findings of this study.

Solela G 《PLoS One》

Serial Change in Serum Chloride During Hospitalization Could Predict Heart Failure Death in Acute Decompensated Heart Failure Patients.

Kondo T ，Yamada T ，Tamaki S ，Morita T ，Furukawa Y ，Iwasaki Y ，Kawasaki M ，Kikuchi A ，Ozaki T ，Sato Y ，Seo M ，Ikeda I ，Fukuhara E ，Abe M ，Nakamura J ，Sakata Y ，Fukunami M ... -  《-》

Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure.

Chloride plays a role in renal salt sensing, neurohormonal activation, and regulation of diuretic targets, and hypochloremia predicts mortality in acute heart failure (AHF). AHF therapies, such as diuretics, alter chloride homeostasis. We studied the association between (changes in) chloride levels and diuretic responsiveness, decongestion, and mortality in patients with AHF. Patients hospitalized for AHF in the PROTECT trial (n=2033) with serum chloride levels within 24 hours of admission and 14 days later were studied (n=1960). Hypochloremia was defined as serum chloride <96 mEq/L. Mean baseline chloride was 100.8±5.0 mEq/L. Low baseline chloride was associated with high bicarbonate, poor diuretic response, less hemoconcentration, and worsening heart failure (all P<0.01). Newly developed hypochloremia at day 14 was common and associated with a decline in renal function and an increase in blood urea nitrogen (P<0.01). In multivariable analyses, chloride measured at day 14, but not baseline chloride, was strongly and independently associated with mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03-1.10]; P<0.001). In comparison, sodium was not significantly associated with mortality after multivariable adjustment at any time point. Hypochloremia at baseline that resolved was not associated with mortality (P=0.55), but new or persistent hypochloremia at day 14 was associated with increased mortality (hazard ratio: 3.11 [2.17-4.46]; P<0.001). Low serum chloride at AHF hospital admission was strongly associated with impaired decongestion. New or persistent hypochloremia 14 days later was independently associated with reduced survival, whereas hypochloremia that resolved by day 14 was not. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354458.

Ter Maaten JM ，Damman K ，Hanberg JS ，Givertz MM ，Metra M ，O'Connor CM ，Teerlink JR ，Ponikowski P ，Cotter G ，Davison B ，Cleland JG ，Bloomfield DM ，Hillege HL ，van Veldhuisen DJ ，Voors AA ，Testani JM ... -  《-》