Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction.

BACKGROUND: We assessed the prognostic significance of absolute and percentage change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients hospitalised for acute decompensated heart failure with preservedejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF). METHODS: Patients with left ventricular ejection fraction ≥50% were categorised as HFpEF (n=283), while those with <40% as were categorised as HFrEF (n=776). Prognostic values of absolute and percentage change in NT-proBNP levels for 6 months all-cause mortality after discharge were assessed separately in patients with HFpEF and HFrEF by multivariable adjusted Cox regression analysis. Comorbidities were compared between heart failure groups. RESULTS: Discharge NT-proBNP levels predicted outcome similarly in HFpEF and HFrEF: for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Mortality prediction was equally possible for NT-proBNP reduction of ≤30% (HR 4.60, 95% CI 1.47 to 14.40 and HR 3.36, 95% CI 1.93 to 5.85 for HFpEF and HFrEF, respectively) and for >30%-60% (HR 3.28, 95% CI 1.07 to 10.12 and HR 1.79, 95% CI 0.99 to 3.26, respectively), compared with mortality in the reference groups of >60% reductions in NT-proBNP levels. Prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF in low (≤3000 pg/mL) but not in high (>3000 pg/mL) NT-proBNP discharge categories. CONCLUSIONS: Our study highlights-after demonstrating that NT-proBNP levels confer the same relative risk information in HFpEF as in HFrEF-the possibility that comorbidities contribute relatively more to prognosis in patients with HFpEF with lower NT-proBNP levels than in patients with HFrEF.

Spontaneous dissection of the celiac artery in the young: a case report and systematic review of the literature.

INTRODUCTION: The spontaneous isolated celiac artery dissection (siCAD) represents a challenging cause of abdominal pain and complete information regarding incidence, etiology and risk factors in the young is still lacking. In this study, we report a case of siCAD occurred in a young woman and we systematically searched for information on siCADs in literature databases. METHODS: PubMed/Embase and Cochrane were searched for, using the following terms: Isolated celiac trunk dissection, isolated celiac artery dissection, celiac artery dissection, celiac trunk dissection, spontaneous isolated visceral artery dissection, spontaneous isolated dissection of visceral arteries, isolated celiac artery dissection in the young, isolated celiac trunk dissection in the young. Patients were included if they were younger than 50 years, if they had a spontaneous etiology and a selective involvement of the celiac artery (with or without involvement of its branches). RESULTS: 180 studies were found, and 18 remained after screening. Twenty-one patients (male = 19, female = 2) with siCADs were included. Mean age was 44.71 ± 3.61 years. Hypertension was the most prevalent comorbidity. All patients presented with abdominal pain, more often located in the epigastrium (n = 11). Almost all patients underwent CT to confirm the diagnosis. A conservative treatment was adopted in 13 patients while an invasive approach was adopted in 8 patients (endovascular approach in 7). DISCUSSION: siCADs represent a rare but important cause of vascular dissection in the young. Uncomplicated cases can be safely treated with conservative strategies. The surgical or endovascular repair is indicated when dissections complicate or symptoms persist despite an adequate conservative treatment.

Targeting N-Terminal Pro-Brain Natriuretic Peptide in Older Versus Younger Acute Decompensated Heart Failure Patients.

OBJECTIVES: The aim of this study was to analyze the prognostic value and attainability of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in young and elderly acute decompensated heart failure (ADHF) patients. BACKGROUND: Less-effective NT-proBNP-guided therapy in chronic heart failure (HF) has been reported in elderly patients. Whether this can be attributed to differences in prognostic value of NT-proBNP or to differences in attaining a prognostic value is unclear. The authors studied this question in ADHF patients. METHODS: Our study population comprised 7 ADHF cohorts. We defined absolute (<1,500 ng/l, <3,000 ng/l, <5,000 ng/l, and <15,000 ng/l) and relative NT-proBNP discharge cut-off levels (>30%, >50%, and >70%). Six-month all-cause mortality after discharge was studied for each level in Cox regression analyses, and compared between elderly (age >75 years) and young patients (age ≤75 years). Thereafter, we compared percentages of elderly and young patients attaining NT-proBNP levels (= attainability). RESULTS: A total of 1,235 patients (59% male, 45% >75 years of age) was studied. Admission levels of NT-proBNP were significantly higher in elderly versus younger patients. The prognostic value of absolute and relative NT-proBNP levels was similar in elderly and young patients. Attainability was significantly lower in elderly patients for all absolute levels and a >50% relative reduction, but not for >30% and >70%. For absolute levels, attainability differences between age groups were decreased to a large extent after correction for admission NT-proBNP and anemia at discharge. For relative levels, attainability differences disappeared after correction for HF etiology and anemia at discharge. CONCLUSIONS: In young and elderly ADHF patients, it is not the prognostic value of absolute and relative NT-proBNP levels that is different, but the attainability of these levels that is lower in the elderly. This can largely be attributed to factors other than age.

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?

AIMS: 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. METHODS AND RESULTS: Our study population was assembled from seven ADHF cohorts. We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT-proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (∼60-70%) was observed for <1500 or >70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets. CONCLUSION: In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target.

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: ELAN-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.

[Continuity of care in heart failure: pilot study of the Tuscany region]. / Continuità assistenziale nello scompenso cardiaco: studio pilota della regione Toscana.

BACKGROUND: Heart failure (HF) is one of the leading causes of hospitalization and medical expenditure, especially in elderly patients. Cooperation between specialists and general practitioners may improve outcomes. A 1-year hospital-territory disease management program was designed in collaboration with the Tuscany Region and the Ministry of Health involving specialists, general practitioners and nurses to investigate the impact of our model on healthcare organization and hospitalization rates in patients with HF. METHODS: The program used a web-based clinical report form, and monitoring of patients from specialists and nurses was coordinated by the general practitioners. We enrolled 106 patients (78.3% male, mean age 74.6 years), with a mean left ventricular ejection fraction 49% and mean Charlson index 2.2. RESULTS: A statistically significant reduction was observed in the number of hospitalizations and emergency calls compared with the previous year. HF severity did not substantially changed in 69.8% of patients, whereas it improved in 17.0% and worsened in 13.2% (NYHA class). CONCLUSIONS: Our preliminary data suggest that cooperation between hospitals and medical systems in the territory by means of a web-based clinical report may result in better management of healthcare interventions in the territory with subsequent reduction of hospitalizations. An extension of this model is now ongoing for collecting data from different areas, both within and outside Tuscany.

Worsening renal function in patients hospitalized with acute heart failure: risk factors and prognostic significances.

Objectives. To determine the prevalence, the clinical predictors, and the prognostic significances of Worsening Renal Function (WRF) in hospitalized patients with Acute Heart Failure (AHF). Methods. 394 consecutively hospitalized patients with AHF were evaluated. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dL from baseline to discharge. Results. Nearly 11% of patients developed WRF. The independent predictors of WRF analyzed with a multivariable logistic regression were history of chronic kidney disease (P = .047), age >75 years (P = .049), and admission heart rates ≥100 bpm (P = .004). Mortality or rehospitalization rates at 1 month, 6 months, and 1year were not significantly different between patients with WRF and those without WRF. Conclusion. Different clinical predictors at hospital admission can be used to identify patients at increased risk for developing WRF. Patients with WRF compared with those without WRF experienced no significant differences in hospital length of stay, mortality, or rehospitalization rates.

S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure.

BACKGROUND: Prolongation of the action potential duration, whose major determinants are the delayed-rectifier potassium currents, is a hallmark of failing ventricular myocardium. Genetic variants in the KCNE1 gene, encoding for the beta-subunit (minK) of a slowly activated cardiac potassium channel (I(ks)), may impair myocardial repolarization. Experimental data demonstrated a higher KCNE1 expression in heart failure (HF). OBJECTIVE: The purpose of this study was to investigate the association between a KCNE1 S38G single-nucleotide polymorphism (SNP) and HF. METHODS: We genotyped 197 out of 323 previously investigated patients and 352 healthy controls comparable for age and sex. This study was replicated in 186 HF patients and in 200 healthy subjects comparable for age and sex and recruited from the Department of Cardiovascular Medicine of the National Research Council, Pisa, Italy. RESULTS: A significant difference in genotype distribution and allele frequency between patients and controls was observed for the KCNE1 S38G SNP (P = .002 and P = .0008, respectively). The KCNE1 38G variant was associated with a significant predisposition to HF under a dominant (odds ratio [OR] = 2.22 [1.23-3.28]; P = .008) and additive (OR = 2.13 [1.09-4.15]; P = .03) model, after adjustment for age, sex, and traditional cardiovascular risk factors. No difference in genotype distribution and allele frequency for the KCNE1 S38G SNP according to functional New York Heart Association class was found (P = .4 and P = .3, respectively). In the HF replication study, the KCNE1 38G allele frequency was significantly higher in comparison with that observed in the control population (38G = 0.59 vs. 0.49; P = .004). The 38G allele was associated with HF predisposition under the recessive (OR [95% confidence interval (CI)] = 2.49 [1.45-4.29]; P = .001) and additive models (OR [95% CI] = 2.63 [1.29-5.35]; P = .008), after adjustment for traditional risk factors. CONCLUSION: KCNE1 S38G SNP is associated with HF predisposition in two study populations. Nevertheless, further studies performed in larger populations and aimed to better define the role of this locus are required.

ACE insertion/deletion, but not -240A>T polymorphism, modulates the severity in heart failure.

OBJECTIVE: : ACE gene is reported to be a candidate gene in heart failure. The insertion/deletion (I/D) polymorphism has been observed to be a predictor of mortality in this disease, but no data are available concerning the role of ACE -240A>T polymorphism. In this study, we investigated the role of ACE I/D and -240A>T polymorphisms in influencing both severity and clinical outcomes in patients with heart failure, according to New York Heart Association (NYHA) class. PATIENTS: : We studied 323 patients with heart failure (258 men/65 women; age, 70.8 +/- 11.5 years) followed-up for 11.9 +/- 6.6 months. RESULTS: : The ACE D and -240T allele frequency significantly increased according to the NYHA functional class (P = 0.0002 and P < 0.0001, respectively).No significant difference in ACE polymorphism genotype distribution and allele frequency according to N-terminal pro-brain natriuretic peptide tertiles was observed. At multinomial regression analysis, ACE D but not -240T allele has been evidenced to be a significant and independent predictor of severity for both NYHA III and IV classes (P = 0.01 and P = 0.004, respectively). The ACE D allele prevalence was higher, even if not significantly in both death and rehospitalization groups in comparison with survivors and nonrehospitalized (P = 0.6 and P = 0.9, respectively). No difference in -240T allele frequency has been observed for the ACE -240A>T polymorphism, in relation to both death and rehospitalization (P = 0.1 and P = 0.6, respectively). CONCLUSIONS: : This study suggests that ACE I/D polymorphism might represent a predisposing factor to severe heart failure, independently of well-known prognostic markers.

NT-ProBNP reduction percentage during hospital stay predicts long-term mortality and readmission in heart failure patients.

We prospectively evaluated whether the N-terminal brain natriuretic peptide (NT-ProBNP) reduction percentage, during hospitalization for acutely decompensated heart failure (HF), has a prognostic significance in 6-month follow-up. In 120 patients consecutively admitted for acute HF to an internal medicine unit, plasma NT-ProBNP was measured on admission and at discharge. During a 6-month follow-up 52 (43.3%) patients had events: 9 (7.5%) died from cardiovascular causes, and 43 (35.8%) were readmitted for HF. In patients without events, the mean reduction percentage of NT-ProBNP was greater than in patients with events (39.5 +/- 7.4 versus 26.3 +/- 5.9%; P = 0.04). In receiver operating characteristic curve analysis, the mean area under the curve for NT-ProBNP reduction percentage was 0.63 (95% CI, 0.51-0.75; P = 0.04) for the composite end point (death or readmission), and 0.81 (95% CI, 0.65-0.97, P = 0.01) for cardiovascular mortality. NT-ProBNP reduction percentage less than 30% was the best cut-off for the identification of patients at risk of events. We suggest that in clinical practice the evaluation of change of NT-ProBNP levels during admission is probably more helpful than predischarge NT-ProBNP absolute value.

Heart failure with preserved systolic function: prevalence and clinical features in a cohort of patients admitted to internal medicine units. The study PRESYF-HF Tuscany.

BACKGROUND: There is uncertainty about the prevalence and clinical characteristics of heart failure (HF) patients with preserved systolic function (PRESYF). AIM: To analyze the prevalence and clinical characteristics of patients with PRESYF in an unselected cohort of subjects consecutively hospitalized for HF. METHODS: The study cohort included 338 patients consecutively admitted for HF at 24 Internal Medicine units homogeneously settled in Tuscany area (Italy). We did not have any criteria for exclusion. All patients had an echocardiographic measure of left ventricular ejection fraction (LVEF) within 72 hours from hospital admission. Patients with LVEF > or = 50% were considered to have PRESYF. RESULTS: The patients with PRESYF were 112 (33.1%), those with depressed systolic function (DESYF) 226 (66.9%). In the group PRESYF were prevalent female sex, hypertensive etiology, and elevated BMI. The distribution for classes of age shows a great frequency of PRESYF in the elderly. CONCLUSION: About one third of patients admitted for HF have a PRESYF. They are different compared to those with DESYF. A correct identification of this form of HF may be important in clinical practice for more targeted therapeutic options and for prognostic implications.

Pre-discharge B-type natriuretic peptide predicts early recurrence of decompensated heart failure in patients admitted to a general medical unit.

BACKGROUND: B-type natriuretic peptide (BNP) represents a promising predictor of early (30 days) re-admission in patients with heart failure (HF) admitted to cardiology units. Whether BNP retains its predictive value in unselected patients admitted to general medical wards is unknown. METHODS: We determined BNP levels on admission and pre-discharge in 100 consecutive patients (71 male, mean age 78+/-10 years) admitted to a general medical unit due to decompensated HF. Follow-up after discharge was 30 days. RESULTS: Of the 100 patients, 86 had >/=1 comorbid conditions. Median BNP was 739 pg/ml on admission (25th-75th percentile 355-1333 pg/ml, respectively), and 414 pg/ml pre-discharge (25th-75th percentile 220-696 pg/ml). Seventeen patients were re-admitted or died within 30 days. Patients with pre-discharge BNP values >75th percentile (696 pg/ml) had greater risk of re-hospitalisation, as compared to values 75th percentile were associated with a 15.0 independent relative hazard (RH) of early re-admission or death (95% CI 4.2-53.8; p<0.0001). The other independent predictor was a NYHA class >/=III at discharge (RH 2.9; 95% CI 1.1-9.3; p<0.05). CONCLUSION: In a general medical unit, pre-discharge BNP levels were a strong independent predictor of early re-admission or death due to HF, irrespective of substantial comorbidity and advanced age.

In-hospital management and outcome in women with acute myocardial infarction (data from the AMI-Florence Registry).

Primary percutaneous coronary intervention proved to be superior to thrombolysis in reducing ST-segment elevation acute myocardial infarction (STEAMI) mortality. However, whether such benefit is similar in women and men remains unclear. The aim of the present analysis was to assess the independent effect of female gender on management and on early and 1-year mortality in Florence, Italy, where primary percutaneous coronary intervention is the preferred reperfusion strategy for STEAMI. The study included a cohort of 920 unselected patients with STEAMI (men = 627, women = 293) prospectively enrolled in the AMI-Florence, population-based registry over 12 months. Women were older (76 vs 68 years, p <0.001) and more frequently had Killip class >I heart failure than men. The median delay to hospital admission was marginally longer in women (160 vs 130 minutes, p = 0.09). Coronary reperfusion treatment was performed less often in women (49% vs 58%, p <0.013); primary percutaneous coronary intervention was performed more often in both genders (90% vs 91%) and with similar median door-to-balloon time (50 vs 45 minutes, p = 0.44). Both in-hospital (16% vs 8%, p <0.001) and 1-year mortality (25% vs 18%, p = 0.016) were higher in women. However, after adjusting for age and other baseline characteristics, reperfusion treatment (odds ratio 1.27, 95% confidence interval [CI] 0.78 to 2.08) and 1-year mortality (hazard ratio [HR] 0.91, 95% CI 0.67 to 1.24) were independent of female gender. Compared with conservative therapy, reperfusion treatment was associated with a similar reduction in 1-year mortality in women (HR 0.59, 95% CI 0.34 to 1.02) and men (HR 0.58, 95% CI 0.37 to 0.92). Our data suggest that older age and several age-related factors may largely account for the higher mortality of women after STEAMI. Even in the general population,improvement in prognosis associated with reperfusion treatment is independent of gender.

[Heart failure: preventing rehospitalizations by disease management programs]. / Scompenso cardiaco: prevenire le riospedalizzazioni applicando programmi di gestione.

Chronic heart failure is a growing public health problem for prevalence, morbidity and costs. The major proportion of costs is attributable to rehospitalizations and many of these readmissions may be preventable. Since 1990, some investigators have tested a variety of disease management programs designed to improve quality of life, functional status and decrease rehospitalizations rates. We identified these studies by a computerized search of the MEDLINE database. The programs described reflected a wide variety of methods and we categorized these programs recognizing the prevalent disease management approach. We reported the results of these trials about rehospitalizations and analysed a number of limitations that must be considered when determining their adoption into clinical practice.