Khibar Salah

A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ÉLAN-HF Score

Background Models to stratify risk for patients hospitalised for acute decompensated heart failure (ADHF) do not include the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels during hospitalisation. Objective The aim of our study was to develop a simple yet robust discharge prognostication score including NT-proBNP for this notorious high-risk population. Design Individual patient data meta-analyses of prospective cohort studies. Setting Seven prospective cohorts with in total 1301 patients. Patients Our study population was assembled from the seven studies by selecting those patients admitted because of clinically validated ADHF, discharged alive, and NT-proBNP measurements available at admission and at discharge. Main outcome measures The endpoints studied were all-cause mortality and a composite of all-cause mortality and/or first readmission for cardiovascular reason within 180 days after discharge. Results The model that incorporated NT-proBNP levels at discharge as well as the changes in NT-proBNP during hospitalisation in addition to age ≥75 years, peripheral oedema, systolic blood pressure ≤115 mm Hg, hyponatremia at admission, serum urea of ≥15 mmol/L and New York Heart Association (NYHA) class at discharge, yielded the best C-statistic (area under the curve, 0.78, 95% CI 0.74 to 0.82). The addition of NT-proBNP to a reference model significantly improved prediction of mortality as shown by the net reclassification improvement (62%, p<0.001). A simplified model was obtained from the final Cox regression model by assigning weights to individual risk markers proportional to their relative risks. The risk score we designed identified four clinically significant subgroups. The pattern of increasing event rates with increasing score was confirmed in the validation group (BOT-AcuteHF, n=325, p<0.001). Conclusions In patients hospitalised for ADHF, the addition of the discharge NT-proBNP values as well as the change in NT-proBNP to known risk markers, generates a relatively simple yet robust discharge risk score that importantly improves the prediction of adverse events.

Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes

BACKGROUND Hospital admissions for acute decompensated heart failure (ADHF) are frequent and are accompanied by high percentages of mortality and readmissions. Brain natriuretic peptide (BNP) and the inactive N-terminal fragment of its precursor proBNP (NT-proBNP) are currently the best predictors of prognosis in heart failure (HF) patients. In the setting of chronic HF, studies that performed guidance of therapy by NT-proBNP have had only limited success. For patients with ADHF, retrospective studies have shown that a reduction in NT-proBNP of ≤30% during admission is a significant predictor of HF readmissions and mortality. These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions. STUDY DESIGN The PRIMA II is an investigator-initiated, multicenter, randomized, controlled, prospective 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target (>30% reduction during admission) on the reduction of readmission and mortality rates within 180 days. Consenting ADHF patients with NT-proBNP levels of >1,700 ng/L are eligible. After achieving clinical stability, a total of 340 patients are randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point is dual, that is, a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days. Secondary end points are readmissions and/or mortality in 180 days, cost effectiveness of hospitalization days in 180 days, readmissions and mortality in 90 days, and quality of life. CONCLUSION The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP-guided therapy compared with conventional treatment in patients admitted for ADHF.

Competing Risk of Cardiac Status and Renal Function During Hospitalization for Acute Decompensated Heart Failure

OBJECTIVES The aim of this study was to analyze the dynamic changes in renal function in combination with dynamic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). BACKGROUND Treatment of ADHF improves cardiac parameters, as reflected by lower levels of NT-proBNP. However this often comes at the cost of worsening renal parameters (e.g., serum creatinine, estimated glomerular filtration rate [eGFR], or serum urea). Both the cardiac and renal markers are validated indicators of prognosis, but it is not yet clear whether the benefits of lowering NT-proBNP are outweighed by the concomitant worsening of renal parameters. METHODS This study was an individual patient data analysis assembled from 6 prospective cohorts consisting of 1,232 patients hospitalized for ADHF. Endpoints were all-cause mortality and the composite of all-cause mortality and/or readmission for a cardiovascular reason within 180 days after discharge. RESULTS A significant reduction in NT-proBNP was not associated with worsening of renal function (WRF) or severe WRF (sWRF). A reduction of NT-proBNP of more than 30% during hospitalization determined prognosis (all-cause mortality hazard ratio [HR]: 1.81; 95% confidence Interval [CI]: 1.32 to 2.50; composite endpoint: HR: 1.36, 95% CI: 1.13 to 1.64), regardless of changes in renal function and other clinical variables. CONCLUSIONS When we defined prognosis, NT-proBNP changes during hospitalization for treatment of ADHF prevailed over parameters for worsening renal function. Severe WRF is a measure of prognosis, but is of lesser value than, and independent of the prognostic changes induced by adequate NT-proBNP reduction. This suggests that in ADHF patients it may be warranted to strive for an optimal decrease in NT-proBNP, even if this induces WRF.

Challenging the two concepts in determining the appropriate pre-discharge N-terminal pro-brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?

NT‐proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT‐proBNP levels should be used as pre discharge treatment target.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

BACKGROUND Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. METHODS Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. RESULTS A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). CONCLUSIONS A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients.

N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Measurements Until a 30% Reduction Is Attained During Acute Decompensated Heart Failure Admissions and Comparison With Discharge NT-proBNP Levels: Implications for In-Hospital Guidance of Treatment

BACKGROUND A >30% N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction at discharge in acute decompensated heart failure (ADHF) predicts a favorable prognosis. To study the feasibility of guiding ADHF treatment by measuring NT-proBNP well before discharge, we assessed at which moment during hospitalization patients attain a NT-proBNP reduction of >30% (target) and whether this target is still attained at discharge. METHODS Twenty-five consecutive ADHF patients with NT-proBNP >1,700 ng/L were included (original cohort). NT-proBNP was measured daily until the target was attained, at clinical stability, and at discharge and was analyzed as percentages of patients on target. For comparison purposes, the same analysis was performed in individual patient data from 2 other ADHF cohorts (42 and 111 patients, respectively), in which NT-proBNP was measured from admission to day 3 and at discharge. RESULTS In the original cohort of 25 patients (median age 70 years, 40% male), the cumulative percentage of patients attaining the target increased gradually during admission to 22 patients (88%) in a median of 3 days (interquartile range 2-5). In the comparison cohorts, a similar course was observed in patients attaining the target before discharge. Compared with levels measured at days 2 and 3, rebound NT-proBNP increases to levels off-target at discharge were seen in up to 33% of patients in the original and comparison cohorts. CONCLUSION A target >30% NT-proBNP reduction is gradually attained before discharge, and rebound NT-proBNP increases to levels off-target occur in up to 33% of ADHF patients who initially attained target early during admission.

NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?)

Background: The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. Methods: We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. Results: Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P=0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (hazard ratio, 0.96; 95% confidence interval, 0.72–1.37; P=0.99) or the median number of days alive outside of the hospital (178 versus 179 days for NT-proBNP versus conventional patients, P=0.39). Guided therapy also did not significantly improve any of the secondary end points. Conclusions: The PRIMA II trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) demonstrates that the guidance of HF therapy to reach an NT-proBNP reduction of >30% after clinical stabilization did not improve 6-month outcomes. Clinical Trial Registration: URL: http://www.trialregister.nl. Unique identifier: NTR3279.Background —The concept of natriuretic peptide guidance has been extensively studied in chronic heart failure (HF) patients, with only limited success. The effect of NT-proBNP-guided therapy in acute decompensated HF (ADHF) patients using a relative NT-proBNP target has not been investigated. The aim of this study was to assess whether NT-proBNP-guided therapy of ADHF patients using a relative NT-proBNP target would lead to improved outcome compared with conventional therapy. Methods —We conducted a prospective randomized, controlled trial to study the impact of in-hospital guidance for ADHF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. ADHF patients with NT-proBNP levels of > 1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary endpoint was dual, i.e. a composite of all-cause mortality and HF readmissions in 180 days, and the number of days alive out of the hospital in 180 days. Secondary endpoints were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. Results —Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P =0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (HR for NT-proBNP-guided therapy, 0.96; 95% CI, 0.72 to 1.37; P=0.99), or the median number of days alive outside of the hospital (178 vs. 179 days for NT-proBNP vs. conventional patients, P =0.39). Guided therapy also did not significantly improve any of the secondary endpoints. Conclusions —The PRIMA II demonstrates that that guidance of HF therapy to reach an NT-proBNP reduction of >30% after clinical stabilization did not improve 6-months outcome. Clinical Trial Registration —URL: http://www.trialregister.nl Unique Identifier: NTR3279

SERUM LACTATE INCREASE DURING HOSPITALIZATION AFTER TEMPORARY CIRCULATORY SUPPORT WITH THE IMPELLA LP5.0 IS AN INDEPENDENT PREDICTOR OF 30-DAY MORTALITY FOR PATIENTS WITH ACUTE LEFT VENTRICULAR CARDIOGENIC SHOCK

Acute primary left heart failure (HF) or post-cardiotomy cardiogenic shock is associated with a high mortality rate and remains a therapeutic challenge even after mechanical support. In this study with the Impella LP5.0 we evaluated the relationship between serum lactate changes during

Reply: Worsening Renal Function in Acute Decompensated Heart Failure: The Puzzle is Still Incomplete

We thank Dr. Nunez and colleagues for their comments on our recent study on the competing risk between cardiac status and renal function during hospitalization for acute decompensated heart failure (HF) [(1)][1]. We agree that there are different mechanisms for worsening renal function (WRF)

ABSOLUTE DISCHARGE LEVEL OR RELATIVE REDUCTION IN NT-PROBNP DURING HOSPITALISATION FOR ACUTE DECOMPENSATED HEART FAILURE AS A TARGET TO REDUCE 6-MONTH MORTALITY?

NT-proBNP is a strong predictor for prognosis in acute decompensated heart failure (ADHF). Both NT-proBNP levels at discharge and relative reduction have been incorporated in risk models. It is still debated which NT-proBNP level (absolute or relative) should be used as treatment target in an ADHF