Methods

We conducted a case-control study to assess mortality predictors in patients with acute HF. To assess prognostic predictors’ independence of admission natriuretic peptides, patients surviving and not surviving the 6-month period after discharge were matched for admission BNP.

During a 2-year period (January 2009 to December 2010), a registry of acute HF was conducted in the internal medicine department of Hospital São João, Porto, Portugal. All patients admitted with the primary diagnosis of acute HF were eligible for inclusion in the registry. The 2008 European Society of Cardiology guidelines were used for the diagnosis of HF. As part of the registry’s protocol, a complete physical examination at admission and discharge was performed; all patients were drawn a venous blood sample within the first 48 hours of hospitalization and in the discharge day; a 12-lead electrocardiogram was performed at admission; and an echocardiogram was performed during hospitalization. Demographic characteristics, medications in use before hospitalization, discharge medication, and co-morbidities were recorded. Plasma BNP was measured with a chemiluminescent immunoassays using an Architect i2000 automated analyzer (Abbott, Lisboa, Portugal). Serum sodium, creatinine, urea, uric acid, albumin, total cholesterol, cardiac troponin I, and C-reactive protein were measured using conventional methods with an Olympus AU5400 automated clinical chemistry analyzer (Beckman-Coulter, Izasa, Porto, Portugal). Prealbumin was assayed using particle-enhanced immunonephelometric assays on a BN II laser nephelometer (Siemens, Lisboa, Portugal). Hemoglobin was obtained using an automated blood counter Sysmex XE-5000 (Emilio de Azevedo Campos, Porto, Portugal). Heart images were obtained with a standard ultrasound machine (System 6; GE Vingmed, Horten, Norway) with a 2.5-MHz probe. The registry’s protocol conforms to the ethical guidelines of the Declaration of Helsinki, and it was approved by the local ethics committee. Patients provided informed consent. Physicians treating patients with acute HF were aware of the ongoing HF registry. Patients’ vital status at 6 months was ascertained by consulting hospital registries and by telephone contact with the patients or their relatives.

A total of 659 patients were included in the registry; from these, 627 survived the hospitalization, and 503 were still alive at 6 months. From this prospectively recruited population, we retrospectively selected a convenience sample of 224 patients (34% of the whole patient population). Cases were 112 patients not surviving the first 6 months after discharge; and controls were patients surviving the follow-up period. Controls and cases were 1:1 pair matched for age (±5 years), gender, and admission BNP. The concordance between BNP in cases and controls was of at least 80%: the ratio of cases to control BNP was between 0.80 and 1.20. Patients surviving and not surviving the 6-month period were compared: McNemar’s test for categorical variables, paired-samples t test for normally distributed continuous samples, and Wilcoxon test for non-normally distributed continuous variables. The 6-month all-cause mortality predictors were analyzed using a Cox regression analysis. Multivariate models were built. A model was built considering all variables associated with mortality in a univariate approach: atrial fibrillation, arterial hypertension history, admission heart rate and systolic blood pressure, hemoglobin, urea, albumin, and prognostic-modifying therapy. A second model was built also taking into consideration variables classically associated with outcome: systolic dysfunction, admission New York Heart Association class, and ischemic etiology. The p value considered for statistical significance was 0.05. Data were stored and analyzed using SPSS software, version 20.0 (IBM Corp., Armonk, New York).

Results

A total of 224 patients were analyzed: 112 surviving and 112 age-, gender-, and BNP matched not surviving a 6-month period post-hospitalization because of acute HF. Ninety-two percent of the patients had >85% admission BNP concordance. The median time to death in nonsurvivors was 69 days (interquartile range 30 to 112 days). Patients’ characteristics and comparison between matched cases and controls are listed in Table 1 . The 6-month survivors had higher admission heart rate, higher admission systolic blood pressure, higher hemoglobin, lower plasma urea, and more often had >30% decrease in BNP during hospitalization; they were also more often discharged on HF prognostic-modifying therapy.

Table 2 lists variables associated with mortality at 6 months. Mortality predictors in a univariate approach were atrial fibrillation, lower admission systolic blood pressure and heart rate, lower hemoglobin, lower albumin, and higher urea at admission. Hypertension history and prognostic-modifying therapy use had a protective effect. A >30% decrease in BNP during hospitalization also showed a protective effect. Tables 3 and 4 show 2 multivariate models built to study mortality predictors in our population of age-, gender-, and admission BNP–matched cases (6 months post-discharge nonsurvivors) and controls (alive at 6 months post-discharge). In model 1, variables used were all those associated with outcome in a univariate approach, and in model 2, variables classically associated with HF outcome–systolic dysfunction, New York Heart Association class, and ischemic etiology—also entered the model. In both multivariate models, no inflammatory, nutritional, or hemodynamic parameters predicted death. The only independent mortality predictor was BNP decrease. In model 1, a BNP decrease >30% during admission predicted a 45% decrease in mortality risk (95% confidence interval 15 to 64), and in model 2, the risk decrease was of 43% (95% confidence interval 11 to 63). If models were built without BNP variation, no variable was associated with mortality.

Table 3

Mortality predictors: multivariate analysis – model 1

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