Abstract
Background
The relationship between changes in serum sodium with clinical events in acute heart failure patients using different decongestive events has not been investigated. This study aimed to describe changes in serum sodium levels during decongestion therapy in patients receiving stepped pharmacologic therapy versus ultrafiltration.
Methods and Results
We studied 188 patients who were enrolled in the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS) trial. Treatment-induced hyponatremia (TIH) was defined as admission normonatremia (≥135 mEq/L) with a subsequent decrease (<135 mEq/L) during hospitalization. Patients treated with ultrafiltration had significantly lower sodium levels than those with conventional treatment at days 1, 4 and 7 (all P<0.01), while those at day-30 were similar between the groups. Changes in sodium levels in patients with ultrafiltration were negatively correlated to those in serum creatinine and plasma renin activity. The incidence of TIH was significantly higher in the ultrafiltration group than those receiving conventional treatment (P=0.002). Although patients with discharge hyponatremia had a higher risk for composite endpoint of all-cause death, re-hospitalization or unscheduled hospital visit in comparison to those without (adjusted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.03–2.65; P=0.037), the risk was comparable between patients with TIH and those who did not experience any hyponatremia (adjusted HR, 0.93; 95%CI, 0.57–1.51; P=0.76).
Conclusion
Fluid removal by ultrafiltration was associated with a decrease in serum sodium levels compared to diuretic treatment, but returned to baseline levels at day-30. Discharge hyponatremia but not TIH was associated with worse clinical outcomes.
Keywords: Acute Heart failure, Cardiorenal syndrome, Hyponatremia, Ultrafiltration
Treatment for acute decompensated heart failure (ADHF) is often complicated by electrolyte abnormalities, which have commonly been considered side effects of diuretic therapy rather than limiting the efficacy of decongestion.1 The natriuretic effect of conventional diuretic therapy contributes to neurohumoral activation,2 which can cause an imbalance between water retention and excretion and leads to hyponatremia.3, 4 Hyponatremia in the setting of heart failure (HF) has been known as a marker of increased disease severity and a predictor of short- and long-term morbidity and mortality in patients with impaired or unimpaired left ventricular systolic function.5, 6
Ultrafiltration has been used as an effective alternative approach to reduce volume overload in ADHF patients resistant to conventional diuretic treatment.7–9 Theoretically, isotonic plasma water removal by ultrafiltration preserves intravascular volume without activation of the neurohumoral axis, leading to fewer electrolyte imbalances than diuretics.10, 11 However, data are limited regarding changes in serum sodium levels between ultrafiltration and a more conventional treatment strategy in ADHF patients. Accordingly, we aimed to describe serum sodium levels at baseline and discharge, as well as changes in serum sodium during decongestion therapy. We also investigated the relationship between these values with outcomes in patients who developed worsening renal function despite persistent congestion following ADHF who received stepped pharmacologic therapy versus ultrafiltration.
METHODS
Study Population
The study design and primary results of the CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) trial have been reported in detail.12, 13 Briefly, the CARRESS-HF trial was a prospective, randomized, controlled trial that assessed the effects of ultrafiltration compared with a stepped pharmacological therapy strategy in patients hospitalized with ADHF and evidence of cardiorenal syndrome with persistent congestion. The trial was conducted from June 2008 to January 2012 at 22 sites and included 188 patients. Patients were eligible if they were admitted with a primary diagnosis of ADHF regardless of left ventricular ejection fraction (LVEF). Patients also were required to have had worsening renal function (defined as an increase in serum creatinine concentration of at least 0.3 mg/dl within 12 weeks before or 10 days after ADHF admission) and persistent congestion. Patients were excluded who had a serum creatinine concentration >3.5 mg/dl at admission or who required vasoactive medications. Ultrafiltration was performed at a fluid removal rate of 200 ml/h, and intravenous diuretic therapy was placed on a urine output-guided stepped pharmacologic approach to provide a comparable measure of fluid removal to ultrafiltration, 3 to 5 L/day.14 This study was approved by the Heart Failure Network Steering, Protocol Review, and Data Safety Monitoring Committees and was approved by each participating site’s institutional review board. All patients provided written informed consent.
Sodium Measurements and Study Endpoints
Patients in the trial had serial laboratory measurements measured at the study sites. The serum sodium concentrations and serum creatinine were measured at baseline, at day 1, 2, 3, 4 and 7 during hospitalization, and day 30 and 60 after discharge. Plasma renin activity was measured at baseline, and 4, 7 and 60 days after randomization. Treatment-induced hyponatremia (TIH) was defined as admission normonatremia (≥135 mEq/L) with a subsequent decrease (<135 mEq/L) during hospitalization. Decompensation hyponatremia was defined as admission hyponatremia (<135 mEq/L) that disappeared with decongestive treatment at discharge. Discharge hyponatremia was defined as hyponatremia (<135 mEq/L) at discharge or day-7. The post-discharge composite endpoint included all-cause mortality, re-hospitalization and unscheduled clinic and emergency department visits.12
Statistical Analysis
Categorical variables are shown as numbers and percentages and were compared using the chi-square test or the Fisher’s exact test, as appropriate. Continuous variables are expressed as mean and standard deviation or median and interquartile range (IQR) where appropriate. Based on their distribution, continuous variables were compared using the Student’s t test or Wilcoxon rank sum test. Two-sided p-values <0.05 were considered statistically significant. Mixed effects modeling with unstructured covariance was used to compare the association of pharmacological therapy or ultrafiltration with serum sodium levels over time. The Kaplan–Meier method was used to estimate cumulative event-free survival and differences in the survival curves were compared via the log-rank test. A multivariable Cox proportional hazards model was constructed to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Candidate variables for the multivariable model were selected when their p-values in univariable analysis were <0.10 or based on their clinical relevance. These included age, gender, ischemic etiology, LVEF, hypertension, diabetes mellitus, hyperlipidemia, creatinine, hemoglobin, albumin and plasma renin activity. All statistical analyses were performed with the statistical software program JMP Pro 10.0.0 (SAS Institute Inc., Cary, NC) and Stata 13.1 (StataCorp, College Station, TX).
RESULTS
Patient characteristics
The mean patient age was 68±13 years, 75% were male, and the mean LVEF was 37±18 %. A total of 47 (25%) patients had hyponatremia at admission, while 141 (75%) patients had normonatremia at admission (Figure 1). Among 141 patients who had normonatremia at admission, 46 (33%) patients had TIH during their hospital stay. Among 47 patients with hyponatremia at admission, 18 patients had normonatremia at discharge while 29 patients had persisting hyponatremia at discharge. Baseline characteristics that were stratified by the admission hyponatremia and the patterns of changes in sodium levels during decongestion therapy are shown in Table 1. The prevalence of TIH was significantly higher in the ultrafiltration group than in those in the pharmacological therapy group (47% vs. 22%, P=0.002, Supplemental Figure 1). Table 2 shows the comparison of baseline characteristics between patients with and without discharge hyponatremia. Patients with discharge hyponatremia had significantly lower plasma osmolarity than those without discharge hyponatremia. There were no significant differences in use of thiazide diuretics among the groups.
Figure 1.
Study patient flow. Treatment-induced hyponatremia (TIH) was defined as admission normonatremia with a subsequent decrease during hospitalization. Decompensation hyponatremia was defined as admission hyponatremia that disappeared with decongestive treatment at discharge.
Table 1.
Patient Characteristics Stratified by Patterns of Changes in Sodium Levels during Decongestion Therapy
| Variable | No hyponatremia (N=95) |
Treatment induced hyponatremia (N=46) |
Decompensation hyponatremia (N=18) |
Persistent hyponatremia (N=29) |
P |
|---|---|---|---|---|---|
| Clinical characteristics | |||||
| Age, years | 68 ± 14 | 68 ± 13 | 68 ± 14 | 67 ± 10 | 0.96 |
| Male | 68 (72) | 36 (78) | 15 (83) | 22 (76) | 0.67 |
| Body weight, lb | 240.7 ± 77.5 | 232.1 ± 71.0 | 216.3 ± 50.5 | 223.6 ± 73.4 | 0.48 |
| Ischemic etiology | 39 (41) | 15 (33) | 8 (44) | 12 (41) | 0.74 |
| Ejection fraction, % | 39.5 ± 18.0 | 37.8 ± 16.9 | 30.9 ± 13.4 | 34.2 ± 18.8 | 0.19 |
| Hypertension | 85 (89) | 39 (85) | 11 (61) | 24 (83) | 0.02 |
| Diabetes mellitus | 64 (67) | 28 (61) | 11 (61) | 21 (72) | 0.72 |
| Hyperlipidemia | 81 (85) | 34 (74) | 11 (61) | 18 (62) | 0.02 |
| Ultrafiltration | 33 (35) | 29 (63) | 10 (56) | 22 (76) | <0.001 |
| Baseline laboratory measures | |||||
| Sodium, mEq/l | 139.8 ± 2.7 | 137.3 ± 1.9 | 132.5 ± 1.7 | 131.2 ± 2.9 | <0.001 |
| Potassium, mEq/l | 4.2 ± 0.6 | 4.1 ± 0.5 | 4.1 ± 0.5 | 4.2 ± 0.6 | 0.77 |
| Blood urea nitrogen, mg/dl | 51.0 ± 19.8 | 58.3 ± 26.7 | 50.6 ± 22.1 | 62.7 ± 27.8 | 0.06 |
| Creatinine, mg/dl | 2.24 ± 0.56 | 2.24 ± 0.58 | 2.15 ± 0.53 | 2.10 ± 0.58 | 0.67 |
| Hemoglobin, g/dl | 10.9 ± 1.7 | 10.9 ± 1.8 | 11.1 ± 2.1 | 11.3 ± 1.9 | 0.79 |
| Albumin, g/dl | 3.3 ± 0.5 | 3.6 ± 0.5 | 3.3 ± 0.7 | 3.3 ± 0.5 | 0.06 |
| Plasma renin activity, ng/ml/hr |
8.1 ± 11.0 | 15.0 ± 20.0 | 25.0 ± 45.7 | 21.9 ± 30.0 | 0.003 |
| Plasma osmolarity, mOsm/l | 303.8 ± 7.1 | 300.2 ± 5.5 | 289.6 ± 6.9 | 289.7 ± 6.7 | <0.001 |
| Baseline medication | |||||
| ACE inhibitor or ARB | 42 (44) | 18 (39) | 6 (33) | 14 (48) | 0.72 |
| Beta-blockers | 75 (79) | 37 (80) | 13 (72) | 22 (76) | 0.89 |
| Thiazide | 20 (21) | 10 (22) | 5 (28) | 9 (31) | 0.68 |
Values are n (%), or mean ± SD.
ACE = angiotensin converting enzyme; ARB = angiotensin receptor antagonist.
Table 2.
Patient Characteristics and Clinical Outcomes: Patients With versus Without Discharge hyponatremia
| Variable | Discharge hyponatremia (+) (N=46) |
Discharge hyponatremia (−) (N=88) |
P Value |
|---|---|---|---|
| Age, years | 68 ± 11 | 66 ± 14 | 0.30 |
| Male | 36 (78) | 64 (73) | 0.48 |
| Ischemic etiology | 28 (61) | 48 (55) | 0.48 |
| Left ventricular ejection fraction, % | 39.1 ± 18.5 | 36.3 ± 16.9 | 0.37 |
| Ultrafiltration | 29 (63) | 33 (35) | 0.002 |
| Hypertension | 39 (85) | 76 (86) | 0.80 |
| Diabetes mellitus | 33 (71) | 58 (66) | 0.49 |
| Dyslipidemia | 31 (67) | 68 (77) | 0.22 |
| Baseline laboratory measures | |||
| Sodium, mEq/l | 134.1 ± 3.8 | 138.4 ± 3.8 | <0.001 |
| Creatinine, mg/dl | 2.24 ± 0.58 | 2.24 ± 0.56 | 0.98 |
| Blood urea nitrogen, mg/dl | 60.8 ± 24.6 | 52.3 ± 23.0 | 0.05 |
| Plasma renin activity, ng/ml/hr | 18.9 ± 26.3 | 10.3 ± 14.4 | 0.02 |
| Plasma osmolarity, mOsm/l | 295.2 ± 7.5 | 300.8 ± 9.1 | <0.001 |
| Primary outcomes | |||
| All cause mortality | 11 (24) | 7 (8) | 0.01 |
| Rehospitalization | 23 (52) | 36 (41) | 0.22 |
| Unscheduled hospital visit | 7 (16) | 12 (14) | 0.73 |
Values are n (%), or mean ± SD
Changes in Serum Sodium Concentration: Pharmacological Therapy versus Ultrafiltration
The mean serum sodium concentration at baseline, day-1, 2, 3, 4, 7, 30 and 60 was 137.2±4.1, 137.3±4.1, 136.9±4.4, 136.4±4.4, 135.9±4.7, 135.6±4.4, 137.1±4.5 and 137.8±3.4 mEq/L, respectively. Figure 2 compares the changes in serum sodium concentrations between patients in the pharmacological therapy and those with ultrafiltration. The mean serum sodium levels were significantly lower in the ultrafiltration group than those in the pharmacological therapy group at baseline (137.8±4.2 vs. 136.6±4.0 mEq/L, P=0.03), day-1 (138.1±3.9 vs. 136.4±4.1 mEq/L, P=0.004), day-2 (138.3±4.1 vs. 135.5±4.3 mEq/L, P<0.001), day-3 (137.8±3.9 vs. 135.0±4.4 mEq/L, P<0.001), day-4 (137.7±3.7 vs. 134.1±4.8 mEq/L, P<0.001), and day-7 (137.1±3.6 vs. 134.2±4.6 mEq/L, P<0.001), respectively. However, there were no significant differences in sodium levels between the groups at day-30 (137.6±4.5 vs. 136.6±4.5 mEq/L, P=0.08) and day-60 (138.0±3.4 vs. 137.5±3.4 mEq/L, P=0.21). In comparison to pharmacological therapy, ultrafiltration significantly impacted sodium levels over time (P<0.001, Figure 2). There were no significant differences in weight changes from baseline to day 4 between the ultrafiltration and the pharmacological therapy (−12.6±8.6 vs −12.5±11.5 kg, P=0.99), nor among 4 groups stratified by patterns of sodium changes; normonatremia, −12.6±11.1 kg; TIH, −11.5±8.6 kg, decompensation hyponatremia, −15.3±11.4 kg; persistent hyponatremia, −12.2±8.7 kg, P=0.64).
Figure 2.
Comparison of changes in serum sodium levels between patients on pharmacological therapy versus ultrafiltration. * Denotes P<0.05 and † denotes P<0.01.
Correlation of Changes in Serum Sodium Levels with Other Biomarkers
The mean serum creatinine in patients with ultrafiltration at baseline, and days 1, 2, 3, 4, 7, 30 and 60 were 2.02±0.64, 2.07±0.70, 2.16±0.81, 2.29±1.00, 2.41±1.14, 2.10±1.21, 1.96±0.80 and 1.91±0.84 mg/dL, respectively. The mean plasma renin activity (PRA) in patients with ultrafiltration at baseline, day-4, day-7 and day-60 were 11.5±13.0, 23.6±35.2, 20.1±29.7 and 12.5±21.2 ng/ml/hr, respectively. Figure 3 illustrates changes in serum sodium, serum creatinine and PRA. In patients with ultrafiltration, both serum creatinine levels and PRA were increased along with decongestion therapy and peaked at day-4, then returned to baseline levels at day-30. These changes were negatively correlated with those in serum sodium levels (Figure 3A). In contrast, changes in serum sodium, creatinine and PRA were relatively stable in patients with conventional therapy (Figure 3B).
Figure 3.
Comparison of changes in serum sodium, creatinine, and plasma renin activity in patients receiving ultrafiltration (A) and those with pharmacological therapy (B). PRA = plasma renin activity.
Sodium Levels and Post-discharge Clinical Events
Overall, there were 29 (15.4%) deaths, 83 (44.1%) re-hospitalizations after discharge, and 32 (17.0%) unscheduled hospital visits without admission. The median follow-up was 58 (IQR, 51 to 63) days. There were 46 patients (24.4%) with hyponatremia at discharge. Patients with discharge hyponatremia had greater event rates than those without discharge hyponatremia (HR, 1.62; 95% CI, 1.02–2.58; P=0.042). Even after adjusting for confounders, the excess risk of patients with discharge hyponatremia relative to those without for the outcome remained significant (adjusted HR: 2.01, 95% CI: 1.09–3.70, P=0.041, Figure 4A). The risks for the outcomes were neutral between patients with and without admission hyponatremia (adjusted HR: 1.64, 95% CI: 0.96–2.80, P=0.07, Figure 4B). The adverse event rates in patients who developed TIH were comparable to those who did not experience any hyponatremia (adjusted HR: 0.99, 95% CI: 0.50–1.96, P=0.99, Figure 4C). Although there were no significant differences in mortality among the 4 groups (P=0.27, Figure 4D), patients with TIH had significantly lower mortality than patients with persistent hyponatremia (adjusted HR: 0.43, 95% CI: 0.19–0.97, P=0.041, Figure 4E). Although outcomes after discharge were comparable among TIH patients between ultrafiltration versus pharmacological therapy, patients with persistent hyponatremia in the ultrafiltration group had significantly worse outcomes than those in the pharmacological therapy group (P=0.024).
Figure 4.
The Comparison of Kaplan-Meier survival curves for freedom from the primary outcome measures between patients with and without discharge hyponatremia (A), those with and without admission hyponatremia (B), those with and without treatment induced hyponatremia (C), among patients stratified by patterns of sodium levels during decongestion therapy (D), and those with persistent hyponatremia versus treatment induced hyponatremia (E).
DISCUSSION
The current analysis of the CARRESS-HF trial investigated the changes in serum sodium levels during hospitalization and after discharge, and its association with treatment strategies (ultrafiltration versus stepped pharmacological therapy), in 188 patients hospitalized with ADHF, irrespective of LVEF, who had renal dysfunction and persistent signs of congestion. The major findings of this study were as follows: (1) Serum sodium levels in patients with ultrafiltration were decreased during decongestive therapy, but returned to baseline levels at 30 days after discharge. In contrast, changes in sodium levels in patients with pharmacological therapy were relatively stable; (2) changes in serum sodium levels during decongestive therapy inversely correlated with changes in serum creatinine and plasma renin activity; and (3) treatment-induced hyponatremia was observed in 24.5% of the patients, but TIH was not associated with excessive event rates, while discharge hyponatremia had a significant prognostic value for adverse events.
Hyponatremia in HF is a common electrolyte disorder, and is associated with an increased risk for short- and long-term mortality.5, 6 The pathophysiology of hyponatremia in HF has been thought to be dilutional in most cases and sodium depletion is relatively rare without loop or thiazide diuretics.15–17 However, it is difficult to differentiate these two categories, and overlap likely exists. In HF, decreased cardiac output leads to activation of baroreceptors, which in turn activates the sympathetic nervous system, the renin angiotensin aldosterone system, and the release of non-osmotic arginine vasopressin. These maladaptive responses limit solute and free water delivery to the distal segments of the nephron which ensures maximal free water absorption and leads to hyponatremia.18, 19 The natriuretic effect of conventional diuretic therapy also significantly contributes to the development of hyponatremia in HF.1, 2 In addition, hyponatremia was found to be more prevalent in ADHF patients with renal dysfunction.20 A decreased glomerular filtration rate results in diminution in the amount of fluid delivered to the distal tubule and limits the rate of renal water excretion.21
Ultrafiltration can remove isotonic fluid without affecting effective circulating volume, leading to decreased neurohumoral activity.7–9 Dilutional hyponatremia is a condition in which intravascular volume is increased and the total amount of sodium is not depleted. Therefore, inappropriate intravascular fluid retention leads to a low serum sodium concentration. If patients had pure dilutional hyponatremia, sodium levels increase along with fluid removal by decongestion therapy. In fact, tolvaptan, a vasopressin type 2 receptor antagonist, shows an increase in serum sodium levels in ADHF with hyponatremia.22 Ultrafiltration can remove a higher amount of sodium in addition to isotonic fluid in contrast to diuretics treatment which only removes hypotonic fluid. Theoretically, if patients had only dilutional hyponatremia, a more favorable water and salt balance can be achieved by ultrafiltration.9 However, we found that patients with ultrafiltration had a significant decrease in sodium levels during decongestion therapy compared to those with diuretic therapy. This unexpected result could be explained by patients having depletional, or mixed dilutional and depletional hyponatremia. Higher amount of sodium removal by ultrafiltration could worsen hyponatremia in those patients. Therefore, decreasing sodium levels during decongestion therapy may suggest co-existing sodium depletion even if patients had signs of residual congestion. It is, however, difficult to predict these sodium changes or diagnose underlying sodium depletion before decongestion therapy. In the current study, patients with admission hyponatremia were thought to have dilutional hyponatremia because those patients had signs of residual congestion and lower plasma osmolarity than those without. Another explanation for the decrease in sodium levels by ultrafiltration may be related to the fluid removal rate. If an isotonic fluid removal rate by ultrafiltration is too fast to refill intravascular sodium from extracellular interstitial space, this could lead to reducing circulating volume and sodium depletion. This phenomenon may be seen with other methods of fluid removal. Continuous ambulatory peritoneal dialysis is associated with higher sodium removal than automated peritoneal dialysis thought to be related to longer dwell times despite equal daily fluid removal. 23, 24 Our finding that serum creatinine levels and PRA were increased in parallel with the decreasing sodium levels supports this hypothesis. Of note, the baseline plasma osmolarity was similar between patients with pharmacologic therapy and ultrafiltration. Further studies are needed to diagnose or differentiate these two different, but often overlapped conditions of hyponatremia.
Several clinical studies have shown that hyponatremia is a predictor of re-hospitalization, and short- and long-term mortality in subjects hospitalized with HF.5, 6 Our findings are consistent with previous studies that have demonstrated patients with discharge hyponatremia were associated with poor outcomes.25 Recently, Verbrugge and colleagues investigated the temporal pattern of hyponatremia development during decongestion therapy. The authors reported that TIH was observed in 14.3% of the patients in ADHF.26 In the current study, TIH was observed in 24.5% of patients. Consistent with previous studies, patients with TIH had similar outcomes compared to those who did not experience any hyponatremia during the treatment.26 More advanced chronic kidney disease patients may explain a higher prevalence of TIH in our study. Development of TIH is not necessarily a bad sign unless hyponatremia persists after decongestion therapy; however, care is needed for their potential risks to persistent hyponatremia because patients who developed TIH may have co-existing sodium depletion. Further research is unquestionably needed to identify a sub-phenotype of HF patients with hyponatremia based on the physiologic response to decongestion therapy or sodium loading.
This study has several limitations inherent to its design. First, the number of patients studied and the trial duration may be insufficient to assess the relationships between sodium levels and post-discharge outcomes. However, CARRESS-HF trial was a unique study performed by a volume-targeted decongestion strategy which enabled us to investigate the relationships between intravascular volume and serum sodium levels across the decongestion strategies. Second, this was a post hoc analysis from a randomized clinical trial with the inherent associated limitations. Despite covariate adjustment, we cannot exclude the influence of other measured and unmeasured confounders. Third, plasma levels of vasopressin were not available in this study, which could be insightful to assess changes in effective arterial blood volume or volume depletion. Assessment of urine osmolality and sodium were not available in this study either, although these are important to know whether the hyponatremia is due to excess renal excretion of sodium relative to water. Finally, weight gain prior to hospitalization and blood pressure changes during the decongestion therapy were not available.
CONCLUSIONS
Fluid removal by ultrafiltration was associated with significant decrease in serum sodium levels compared to diuretic treatment, but return to baseline levels at day-30. Although discharge hyponatremia was associated with worse clinical outcomes, patients with TIH had similar outcomes to those without.
Supplementary Material
CLINICAL PERSPECTIVE.
Hyponatremia is a common electrolyte disorder and a therapeutic challenge in heart failure, and may be a side effect of diuretic therapy. On the other hand, ultrafiltration has been thought of as an effective alternative approach to mechanically reduce congestion which may be resistant to conventional diuretic treatment. In comparison to diuretic use, it has been thought to have less activation of the neurohormonal axis and fewer electrolyte imbalances. However, data are limited regarding changes in serum sodium levels between ultrafiltration and conventional diuretic therapy. In this post hoc analysis of the CARRESS trial, contrary to expectations, we observed a greater reduction in serum sodium with ultrafiltration versus pharmacological therapy, which was negatively correlated to corresponding serum creatinine and plasma renin activity. The prompt resolution of serum sodium levels after discharge may indicate the electrolyte depletion by ultrafiltration. Furthermore, although patients with discharge hyponatremia had a higher risk for composite endpoint of all-cause mortality, re-hospitalization or unscheduled hospital visits in comparison to those without, the risk was comparable between patients with treatment-induced hyponatremia and those who did not experience any hyponatremia. These findings highlight the need to differentiate two different conditions of hyponatremia, dilutional versus depletional, and to refine a slower ultrafiltration regimen to avoid over-aggressive mechanical removal of salt and water.
Acknowledgments
FUNDING
Dr. Tang has received funding support from the National Institutes of Health (R01HL103931). This article was prepared using public access research materials of CARRESS-HF obtained from the National Heart, Lung, and Blood Institute (NHLBI)’s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) and does not necessarily reflect the opinions or views of the CARRESS-HF study investigators or the NHLBI.
Footnotes
Clinical Trial Registration: URL: http://www.clinicaltrial.gov. Unique identifier: NCT00608491
DISCLOSURES. None.
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