EAL

HESI: Congestive Heart Failure Population (2014)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To verify the effects of this combination on hospitalization time, re-admissions and mortality in patients in the New York Heart Association (NYHA) class III study.

Inclusion Criteria:

Decompensated HF, shown by chronic ischemic or non-ischemic cardiomyopathy
Older than18 years
Uncompensated HF (dyspnea, weakness and lower limb edema , according to HF definition and Framingham criteria for HF
In NYHA III functional class
Unresponsive to treatment, for at least four weeks before the study and before hospitalization, with:
- High doses of oral furosemide, up to 250mg per day
- Spironolactone
- Angiotensin-converting enzyme (ACE) inhibitors,
- Digitalis
- Nitrates.
Judged unresponsive when they showed, during treatment and despite the increase of furosemide:
- A reduction of urine volume
- A constant increase of body weight (BW)
- An impairment of clinical HF.
A left ventricular ejection fraction (EF), despite established treatments, showing:
- Serum creatinine (40%): 2.5mg per dL
- Blood urea nitrogen (BUN): 60mg per dL
- Reduced urinary volume: 800ml per day.

Exclusion Criteria:

Patients with NYHA class III or III on admission or with NYHA class III at discharge, with concomitant main comorbidities such as:
- Cerebral vascular disease
- Dementia
- Cancer
- Uncompensated diabetes
- Severe hepatic disease.
Inability to give informed consent
Required pacemaker implantation
Alcohol habit
Declined to take part in the study protocol
Side effects for ACE inhibitor treatment (cough), even if given angiotensin 2-receptor blockers to obtain treatments as homogeneous as possible
Unwilling or unable to follow the assigned treatment
Did not attend the scheduled clinical visits
Did not adhere to prescribed diet and the fluid intake of 1,000ml per day
Had a reduction or discontinuation of prescribed treatments during follow-up.

Description of Study Protocol:

Recruitment

From September 2000 to August 2007, 4,728 patients with worsening HF were consecutively admitted to Emergency Medicine and Cardiology Departments of Palermo University; Division of Cardiology, G.F. Ingrassia Hospital, Palermo; Division of Cardiology, Buccheri La Ferla Hospital, Palermo; and to Second Naples University, Italy.

Design

RCT.

Blinding Used

Patients were blinded.

Intervention

The recruited patients were divided into two groups (single-blind fashion; the patients were blinded on the administered treatments):
- Group 1: Received an intravenous 30-minute 250mg infusion of furosemide plus HSS (150ml of 1.4% to 4.6% NaCl) twice a day, with a moderate sodium restriction (120mmol)
- Group 2: Received an intravenous 250mg infusion of furosemide as bolus twice a day, without HSS, and a low-sodium diet (80mmol)
- Both groups received a fluid intake of 1,000ml per day.
In the first group, the dose of HSS was determined in each patient according to these schedules:
- Serum Na values 125mEq per L: HSS concentration was 4.6%
- Serum Na values between 126mEq and 135mEq per L: HSS concentration was 3.5%
- Serum Na values 135mEq per L: HSS concentration varied between 1.4% and 2.4%
- Intravenous KCl (20mEq to 40mEq) also was administered to prevent hypokalemia.
During the study period, the patients received ACE inhibitors, digitalis and nitrates. During hospitalization, when the patients reached a compensate state (dry status), the first group (HSS group) received the daily dietary sodium of 120mmol with a fluid intake of 1,000ml per day and oral KCl supplementation. The treatment was continued after discharge.
The patients receiving conventional treatment (without HSS) received and continued a reduced daily dietary sodium intake (80mmol) and the same fluid intake as HSS group and KCl supplementation
An accurate assessment of BW (in the morning before breakfast) and a measurement of 24-hour urinary volume were performed every day. Serum and urinary laboratory parameters were measured daily until a clinically compensated state was reached; this was considered as a change in NYHA functional class to at least II on clinical judgment and the accomplishment of ideal BW, as calculated by the Lorenz formula 16 and detected by bioimpedance vector analysis.
Once the clinically compensated state was reached, the intravenous administration of furosemide (both groups) and HSS (Group 1) was stopped and was replaced with oral furosemide administration (50mg to 125mg twice daily) and oral KCl supplementation. The best therapy, obtained during hospitalization, was also continued without changes after discharge.
During follow-up, the two groups continued the treatments according to randomization:
- Group 1: Continued to receive a moderate sodium restriction (120mmol per day) associated with a fluid restriction (1,000ml per day) and the furosemide dose as during hospitalization
- Group 2: Continued to receive a low-sodium diet (80mmol per day) associated with a restricted fluid intake (1,000ml per day) and the furosemide dose as during hospitalization, along with the best standard therapy (ACE inhibitors, beta blockers, digitalis and nitrates).
Furosemide doses used were 50mg to 125mg twice daily because these doses allowed maintenance of BW and water balance during hospitalization
Follow-up was performed on patients enrolled from September 2000 to August 2007, with a minimum period of observation of 31 months (from March 2010). In this period, we analyzed the incidence of re-admissions for worsening HF and mortality from all causes (sudden death, progressive left ventricular failure and non-cardiac causes).

Statistical Analysis

The analysis of hospital re-admission for worsening HF and mortality (the primary end point) included all patients, according to the intention-to-treat principle and according to relative risk reduction; the number needed to treat to prevent one event was calculated
The Kaplan–Meier method was used to construct cumulative survival curves for the two groups
The primary comparison between the two groups was based on a log-rank test
For analyses of mortality or re-admissions (first re-admission), data were censored at the time of loss to follow-up or at the time of first readmissions
Data were analyzed using a two-tailed Student T-test to identify differences between groups and analysis of variance for repeated measures with Bonferroni post-hoc test correction for intragroup data
Nominal data were analyzed by the two-test significance of P<0.05
The sample size was calculated on the basis of the estimated reduction in re-admissions for worsening HF of 50% on the basis of our previous study
The power of the study to detect a difference between treatment groups was set at 95% (with a two-tailed level of 0.05). Therefore, the sample size obtained was 231 for each group, and this number was assumed as a minimum for this study.

Data Collection Summary:

Timing of Measurements

After discharge (baseline), patients were observed as outpatients, with clinical and laboratory evaluations, every week for the first month, every month for the next six months and thereafter every three months
Follow-up was a minimum of 31 months, with a mean of 57 months.

Dependent Variables

Mortality
Hospitalization time
Re-admission for worsening CHF.

Independent Variables

A total of 1,771 patients (881 in the intervention group and 890 in the control group)
Intervention group was allowed 1,840mg per day of Na while the control group was allowed 2,760mg per day of Na
Intervention diets contained 1,840mg Na compared to the control intervention group diet and 920mg per day of Na (each group was allowed the same amount of saturated fat, fruit, and so on)
Diaries recorded fluid intake and diet variations.

Description of Actual Data Sample:

Initial N: A total of 1,927 patients (1,213 males, 714 females)
Attrition (final N): A total of 1,771 patients completed the study and were analyzed (881 from Group 1 and 890 from Group 2)
Age: Ranged from 57 to 84 years, with NYHA class III HF of different etiologies
Ethnicity: Italian
Location: Palermo University and Naples University, Italy.

Summary of Results:

Findings

Intervention group vs. control group had significant reduction in:

Hospitalization time: 3.5 vs.5.5 days, P≤ 0.0001
Re-admission rates: 18.5% vs. 34.2%, P<0.0001
Mortality: 12.9% vs. 23.8%, P<0.0001.

	Furosemide with HSS			Furosemide without HSS
	Entry	Discharged	P-value	Entry	Discharged	P-value
Urinary Na (mEq per 24 hours)	73.7±11.4	119±13	0.0001	79.1±10	76± 5	0.0001
Serum creatinine (mg per dL)	1.65±0.05	1.45±0.05	0.0001	1.61±0.05	1.91±0.1	0.0001

Author Conclusion:

This study suggests that in-hospital HSS administration combined with moderate Na restriction reduces hospitalization time and that a moderate sodium diet restriction determines long-term benefit in patients with NYHA class III HF.

Funding Source:

Reviewer Comments:

No funding source was mentioned.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		No
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???