Troponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur)

doi:10.1016/j.ahj.2012.05.025

American Heart Journal

Volume 164, Issue 3, September 2012, Pages 351-357

https://doi.org/10.1016/j.ahj.2012.05.025 Get rights and content

Background

High values of cardiac troponin in acute decompensated congestive heart failure (ADHF) identify patients at higher risk and worsened prognosis. A cardiac troponin increase during therapy indicates the need for more appropriate intervention, aimed at compensating cardiac disease and effectively minimizing myocardial wall stress and subsequent cytolysis. This study evaluated the effects of an intravenous high dose of furosemide with (group A) or without small volume hypertonic saline solution (HSS) (group B) on myocardial cytolysis in patients with ADHF.

Methods

A total of 248 consecutive patients with ADHF (148 men, mean age 74.9 ± 10.9 years) were randomly assigned to group A or B. Plasma levels of cardiac troponin-I, brain natriuretic peptide, glomerular filtration rate by Modification of Diet in Renal Disease formula, bioelectrical impedance analysis measurements, and delta pressure/delta time (dP/dt) rate were observed on admission and discharge for all patients.

Results

We observed a significant reduction of cardiac troponin in both groups and a significant improvement in renal function, hydration state, pulmonary capillary wedge pressure (P < .0001), end diastolic volume (P < .01), ejection fraction (P < .01), and dP/dt (P < .004) in group A. We also observed a significant reduction in body weight (64.4 vs 75.8 kg) (P < .001), cardiac troponin I (0.02 vs 0.31 ng/mL) (P < .0001) and brain natriuretic peptide (542 vs 1,284 pg/mL) (P < .0001), and hospitalization time (6.25 vs 10.2 days) (P < .0001) in the HSS group.

Conclusions

These data demonstrate that intravenous high doses of furosemide do not increase myocardial injury and, in addition, when associated to HSS, significantly reduce cardiac troponin I release. This behavior is mirrored by the achievement of improved hemodynamic compensation at echocardiography and body hydration normalization.

Section snippets

Methods

This double-blind study included 248 consecutive patients with a diagnosis of ADHF (148 men, mean age 74.9 ± 10.9 years, between 36 and 91 years), according to the American Heart Association/European Society of Cardiology guidelines,14, 15 and who met the following criteria on hospital admission:

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signs/symptoms of HF;
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New York Heart Association (NYHA) functional class III or IV on admission due to an exacerbation of symptoms with at least 1 class deterioration;
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evidence of systolic dysfunction on

Results

The results of this study are summarized in the tables below; Table I, Table II, Table III lists clinical and instrumental parameters, respectively. Our data demonstrated a substantial improvement in clinical status in both groups at discharge. A significant increase was observed in daily diuresis in both groups. Serum K was decreased significantly, but the value remained in the reference range in both groups. Body weight was reduced, and the reduction was proportional to increased urinary

Discussion

The purpose of this study was to investigate the cardiac effects of 2 different strategies of diuretic treatment based on high doses of furosemide in patients with ADHF who were unresponsive to oral treatment, with particular regard to myocardial damage (cTnI plasma levels), BNP levels, and echocardiographic parameters of cardiac compensation (dP/dt).

High doses of diuretics administered during hospitalization, are associated with increased mortality and poor 6-month outcomes.19, 20 Other

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Cited by (22)

“Pouring Salt in the Wound”: Sodium Restriction in Acute Heart Failure
2023, Journal of Cardiac Failure
A normal sodium diet preserves serum sodium levels during treatment of acute decompensated heart failure: A prospective, blind and randomized trial
2019, Clinical Nutrition ESPEN
Citation Excerpt :
Sample size was calculated using the OpenEpi software, version 3.01, available at www.openepi.com. The primary outcome for the calculation of sample size was considered to be a difference in serum sodium ≥3 mmol/L, with an estimated standard deviation of ±3.5 [24], a 95% confidence interval and 80% test power. On this basis, the sample size was defined as 22 patients per study group.
We tested the hypothesis that a normal sodium diet could be associated with preservation of serum sodium during treatment of acute decompensated heart failure (ADHF).
Forty-four patients hospitalized for ADHF were blindly randomized by using block method to a low sodium diet (LS: 3 g/day of dietary sodium chloride; n = 22, 59.5 ± 11.9 y.o., 50% males. LVEF = 30.0 ± 13.6%); and a normal sodium diet (NS: 7 g/day; n = 22, 56.4 ± 10.3 y.o., 68% males; LVEF = 27.8 ± 11.7%), and both groups were submitted to fluid restriction of 1.000 mL/day. At the 7th day of intervention 16 patients of LS group and 15 patients of NS group were assessed for difference in serum sodium. Both groups had equivalent decongestion, reflected by similar percent reduction of body weight (LS: −5.0 ± 4.7% vs NS: −4.5 ± 5.2%. p = 0.41). Reduction of the N terminal fragment of type B natriuretic peptide (NT-proBNP) was significant only in the NS (−1497.0 [−18843.0 − 1191.0]. p = 0.04). The LS group showed lower levels of serum sodium (135.4 ± 3.5 mmol/L) compared to the NS group (137.5 ± 1.9 mmol/L; p = 0.04). Four cases of hyponatremia were observed only in the LS group (22%). The NS group exhibited higher mean blood pressure values (79.4 ± 2.4 mmHg vs 75.5 ± 3.0 mmHg. p = 0.03), and lower heart rate (73.2 ± 1.6 bpm vs 75.5 ± 2.1 bpm. p = 0.02).
These results suggest that a normal sodium diet, when compared to a low sodium diet, is associated with similar degrees of decongestion, but with higher levels of natremia, blood pressure and lower neurohormonal activation during ADHF treatment.
clinicaltrials.gov Identifier no. NCT03722069.
Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study
2017, Journal of Veterinary Cardiology
Citation Excerpt :
Although total urine production was greater for CRI compared to bolus furosemide administration in healthy dogs and horses, urine output declined after 3–4 h of the CRI, possibly due to volume contraction and reduced drug delivery to the nephron [7,8]. Other studies in human beings have shown diuretic superiority and added renal safety when small volumes of hypertonic saline were administered concurrently with furosemide CRI [12–23]. The benefits to this approach included restored urine production with protection of renal function, reduction of neurohormonal activation, and reduction of myocardial injury [19–21,24].
The goal of this study was to investigate the short-term safety and diuretic efficacy of furosemide constant rate infusion (CRI) diluted with 5% dextrose in water (D5W) compared to dilution with 2.4% hypertonic saline in healthy dogs.
Six healthy dogs.
Dogs were studied in a randomized, blinded, crossover manner. Furosemide 3.3mg/kg was diluted to 2.2mg/mL with either 1.5mL/kg D5W for the DEX method or with 1.0mL/kg D5W and 0.5mL/kg of 7.2% hypertonic saline for the H-SAL method. After a 0.66mg/kg furosemide IV bolus, the infusion rate was 0.3 mL/kg/hr for 5 h such that both methods delivered 0.66 mg/kg/hr (total 3.3mg/kg) furosemide in equal volume for the study duration. Urine output, water intake, central venous pressure (CVP), physical parameters, furosemide concentrations, blood and urine electrolytes, and urine aldosterone to creatinine ratio (UAldo:C) were evaluated.
Measured variables were not different between methods but showed changes over time consistent with diuresis. Mean CVP decreased over time similarly for both methods. Plasma furosemide and urine concentrations were stable and not different between methods. Both furosemide CRI methods showed an increase in the UAldo:C, however, the rise was greater for DEX than for H-SAL.
Diuresis was similar for both furosemide CRI methods; however, the H-SAL method induced less renin-angiotensin-aldosterone system activation than the DEX method. The absence of intravascular volume expansion based on CVP suggests that dilution of a furosemide CRI with 2.4% hypertonic saline may be well tolerated in heart failure.
Echocardiography in Acute Heart Failure: Current Perspectives
2016, Journal of Cardiac Failure
In contrast to chronic heart failure (HF), the use of echocardiography in acute HF (AHF) is less well defined, both in clinical practice and in clinical trials. Current guidelines recommend the utility of echocardiography as an adjunct diagnostic tool in the clinical setting of new-onset or decompensated HF. However, despite its unique advantages as the only practical imaging modality in AHF, echocardiography poses unique challenges in this setting. Data from early-phase clinical studies and trials provide evidence that echocardiographic end points can be clinically meaningful surrogate end points as a means to track response to treatment in AHF; however, the optimal timing and selection of echocardiographic measures is under active investigation. In addition, despite a number of studies indicating that certain echocardiographic measures of cardiac function are predictive of post-discharge prognosis, the role of echocardiography as a tool for patient classification and risk determination in AHF is less well defined. Importantly, it is unclear whether echocardiography can be used to phenotype and select AHF patients for interventions. In this article, we (1) appraise the current evidence for use of echocardiographic measures in AHF, (2) identify knowledge gaps regarding optimal use of echocardiography in AHF, and (3) assess the evidence for echocardiography as a prognosis determination and risk stratification tool in AHF.
Hypertonic saline with furosemide for the treatment of acute congestive heart failure: A systematic review and meta-analysis
2014, International Journal of Cardiology
Citation Excerpt :
Licata et al. had mean follow-up of 31 months, Paterna (2000) [23] followed up patients for 6–12 months, Paterna (2005) [11] used a 30-day double-blind follow-up period, and Paterna (2011) [24] used a mean follow-up of 57 months. Seven randomized control trials [8–11,22–24] that assessed hospitalization length of stay met inclusion criteria with 1392 patients treated with hypertonic saline and 1327 controls (Fig. 6). Mean difference in hospital length of stay between patients treated with hypertonic saline and controls was − 3.13 days (95% CI –(− 4.23)–(− 2.03), p < 0.00001).
Advanced congestive heart failure (CHF) therapies include intravenous inotropic agents, change in class of diuretics, and venous ultrafiltration or hemodialysis. These modalities have not been associated with improved prognosis and are limited by availability and cost. Compared to high-dose furosemide alone, concomitant hypertonic saline solution (HSS) administration has demonstrated improved clinical outcomes with good safety profile.
A literature search was conducted for randomized controlled trials that investigated the use of HSS in patients admitted to hospital with acute CHF.
1032 patients treated with HSS and 1032 controls, demonstrated decreased all-cause mortality in patients treat with HSS with RR of 0.56 (95% CI 0.41–0.76,p = 0.0003). 1012 patients treated with HSS and 1020 controls, demonstrated decreased heart failure hospital readmission with RR of 0.50 (95% CI 0.33–0.76,p = 0.001). Patients treated with HSS also demonstrated decreased hospital length of stay (p = 0.0002), greater weight loss (p < 0.00001), and preservation of renal function (p < 0.00001).
The results of this meta-analysis demonstrate that in patients with advanced CHF concomitant hypertonic saline administration improved weight loss, preserved renal function, and decreased length of hospitalization, mortality and heart failure rehospitalization. A future adequately powered, multi-centre, placebo controlled, randomized, double dummy, blinded trial is needed to assess the benefit of hypertonic saline in patients with renal dysfunction, in diverse patient populations, as well using a patient population on optimal current heart failure treatment. Pending further validation, there is promise for hypertonic saline as an advanced therapy for the management of acute advanced CHF.
Strategies to Prevent Postdischarge Adverse Events Among Hospitalized Patients with Heart Failure
2013, Heart Failure Clinics
Citation Excerpt :
Overall poor inpatient quality of care and lack of guideline-based therapy is associated with higher readmission rates.77 Patients with early decreased dyspnea or lower congestion scores at discharge have reduced organ damage, all-cause mortality, and readmission rates,6,71,78,79 although 45% of patients are discharged with persistent congestion.13 Patients with decreased markers of multiorgan damage also have improved outcomes.70,75,76

View all citing articles on Scopus

: ClinicalTrials.gov Identifier: NCT01419132.

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Clinical InvestigationCongestive Heart FailureTroponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur)

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

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Clinical Investigation
Congestive Heart Failure
Troponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur)