Tricuspid Annular Plane Systolic Excursion in Acute Decompensated Heart Failure: Relevance for Risk Stratification.

BACKGROUND: Although the prognostic value of right ventricular dysfunction in chronic heart failure (HF) has been studied extensively, it remains insufficiently characterized in the setting of acute decompensated HF (ADHF). We sought to assess whether measurement of tricuspid annular plane systolic excursion (TAPSE) or TAPSE-to-estimated pulmonary arterial systolic pressure (ePASP) ratio allows improvement of risk prediction in ADHF. METHODS: Four hundred ninety-nine patients with ADHF were studied. Cox regression analyses were used to analyze the association of TAPSE and TAPSE-to-ePASP ratio with 1-year mortality and logistic regression analyses to analyze the association of the 2 variables of interest with adverse in-hospital outcome (AiHO) (in-hospital death plus worsening HF). RESULTS: During the 365-day follow-up, 143 patients (28.7%) died. At univariable analysis, both TAPSE (P = 0.026) and TAPSE-to-ePASP ratio (P < 0.0001) were significantly associated with 1-year mortality. At multivariable Cox analysis, age (P = 0.0270), ischemic heart disease (P = 0.020), systolic blood pressure (P = 0.006), log N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < 0.0001), serum sodium levels (P = 0.001), and hemoglobin levels (P = 0.001) at admission were independently associated with 1-year mortality. Adjusting for these covariates, neither TAPSE (P = 0.314) nor TAPSE-to-ePASP ratio (P = 0.237) remained independently associated with 1-year mortality. Eighty-three patients (16.6%) had an AiHO. At multivariable logistic regression analysis, the TAPSE-to-ePASP ratio was independently associated with an AiHO (P = 0.024). The association of TAPSE alone or ePASP alone was not statistically significant. CONCLUSIONS: Our data strongly suggest that early assessment of TAPSE or TAPSE-to-ePASP ratio does not improve prediction of 1-year mortality over other key risk markers in ADHF. Nonetheless, the TAPSE-to-ePASP ratio did appear to be independently associated with AiHO.

EaRly-start ExerciSe training afTer acute hemodynAmic decompensation in patients with chRonic hearT failure (RE-START). A multicenter, randomized, controlled trial on short-term feasibility and impact on functional capacity, symptoms and neurohumoral activation .

RE-START is a multicenter, randomized, prospective, open, controlled trial aiming to evaluate the feasibility and the short- and medium-term effects of an early-start AET program on functional capacity, symptoms and neurohormonal activation in chronic heart failure (CHF) patients with recent acute hemodynamic decompensation. Study endpoints will be: 1) safety of and compliance to AET; 2) effects of AET on i) functional capacity, ii) patient-reported symptoms and iii) AET-induced changes in beta-adrenergic receptor signaling and circulating angiogenetic and inflammatory markers. Two-hundred patients, randomized 1:1 to training (TR) or control (C), will be enrolled. Inclusion criteria: 1) history of systolic CHF for at least 6 months, with ongoing acute decompensation with need of intravenous diuretic and/or vasodilator therapy; 2) proBNP > 1000 pg/mI at admission. Exclusion criteria: 1) ongoing cardiogenic shock; 2) need of intravenous inotropic therapy; 3) creatinine > 2.5 mg/dl at admission. After a 72-hour run-in period, TR will undergo the following 12-day early-start AET protocol: days 1-2: active/passive mobilization (2 sessions/day, each 30 minutes duration); days 3-4: as days 1-2 + unloaded bedside cycle ergometer (3 sessions/day, each 5-10 minutes duration); days 5-8: as days 1-2 + unloaded bedside cycle ergometer (3 sessions/day, each 15-20 minutes duration); days 9-12: as days 1-2 + bedside cycle ergometer at 10-20 W (3 sessions/day, each 15-20 minutes duration). During the same period, C will undergo the same activity protocol as in days 1-2 for TR. All patients will undergo a 6-min WT at day 1, 6, 12 and 30 and echocardiogram, patient-reported symptoms on 7-point Likert scale and measurement of lymphocyte G protein coupled receptor kinase, VEGF, angiopoietin, TNF alfa, IL-1, IL-6 and eNOS levels at day 1, 12 and 30.

Independent role of left ventricular global longitudinal strain in predicting prognosis of chronic heart failure patients.

AIMS: To evaluate the independent prognostic role of two-dimensional (2D) strain measures reflecting global longitudinal left ventricular (LV) systolic function in outpatients affected by chronic heart failure (CHF). METHODS AND RESULTS: Global longitudinal LV systolic strain (GLS) was assessed in 308 outpatients affected by CHF, by analyzing standard views with 2D speckle tracking technique. During a mean follow-up of 26 ± 13 months 37 patients died (29 due to cardiovascular causes), 10 patients underwent heart transplantation, and 75 patients experienced at least 1 episode of hospitalization due to acute decompensated heart failure (ADHF). Thirty-one patients without a history of major ventricular arrhythmic events experienced the occurrence of ventricular fibrillation and/or tachycardia or sudden death was observed. Multivariate Cox regression analysis showed that GLS was significantly associated with all-cause mortality (HR: 1.15; 95%CI: 1.02-1.30; P: 0.026), cardiovascular death (HR: 1.20; 95%CI: 1.04-1.39; P: 0.011), cardiovascular death or heart transplantation (HR: 1.24; 95%CI: 1.09-1.41; P: 0.001), ADHF-related hospitalizations (HR: 1.15; 95%CI: 1.05-1.25; P: 0.003), and arrhythmic events (HR: 1.17; 95%CI: 1.03-1.33; P: 0.018). CONCLUSIONS: Quantifying LV longitudinal systolic function in CHF outpatients on the basis of 2D speckle tracking analysis provides a new parameter that independently predicts patient outcome, thus, strengthening its possible role in current clinical practice.

Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score.

BACKGROUND: NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score. METHODS: This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score. RESULTS: One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798-0.880) and the Hosmer-Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711-0.817); the Hosmer-Lemeshow statistic was 2.76 (p=0.251), after recalibration. CONCLUSIONS: The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.

Association between conformity with performance measures and 1-year postdischarge survival in patients with acute decompensated heart failure.

Recognition of the treatment gap in patients with heart failure (HF) led to the development of a set of process-of-care measures to improve the quality of care. To assess the association of established and emerging process-of-care measures with 1-year postdischarge survival, 496 patients with acute decompensated HF were studied. After adjustment for established prognostic factors, the relative risk (RR) for mortality in patients eligible for treatment was as follows: 0.49 (P < .001) for discharge prescription of renin-angiotensin system inhibitors (RAS-Is), 0.59 (P = .015) for ß-blockers, 0.44 (P < .001) for combination therapy (ie, a ß-blocker and a RAS-I), 0.87 (P nonsignificant) for aldosterone antagonists, and 0.49 (P nonsignificant) for planned cardioverter-defibrillator implantation. After adjustment for propensity scores, the RR was 0.49 (P < .001) for RAS-Is, 0.67 (P = .04) for ß-blockers, and 0.57 (P < .001) for combination therapy. The data suggest that performance measures for RAS-Is, ß-blockers, and combination therapy are strongly associated with improved 1-year survival.

Amino-terminal pro-B-type natriuretic peptide for risk prediction in acute decompensated heart failure.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has been associated with prognosis in heart failure. The aim of this study was to assess whether NT-proBNP enhances risk prediction in acute decompensated heart failure (ADHF). The authors enrolled 453 patients hospitalized for ADHF. The primary outcome was 12-month mortality. Two separate multivariable predictive models were built by using standard variables-only and NT-proBNP concentrations. The models were internally validated using the bootstrapping method. Twelve-month mortality was 28.3%. There was no statistical evidence of overfit. Compared with the standard variables-only model, the NT-proBNP model had a better predictive performance as judged by the Nagelkerke R(2) (0.410 vs 0.374) and the Brier score (0.136 vs 0.141), which are measures of overall performance; the Akaike Information Criterion (399.2 vs 415.0), which is a tool for model selection; and the C index (0.844 vs 0.831), which is a measure of the discriminative ability. Both models were well calibrated, as judged by the Hosmer-Lemeshow chi-square test. Both models predicted 12-month mortality significantly better than the Enhanced Feedback for Effective Cardiology Treatment risk score. In conclusion, the NT-proBNP model improved risk prediction compared with the standard variables-only model.

Incidence and prevalence of hypothyroidism in patients affected by chronic heart failure: role of amiodarone.

BACKGROUND: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodine-containing antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. AIM OF THE STUDY: To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. RESULTS: Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17%and, as expected, it was significantly higher in females than males (33% vs 13%; p < 0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. CONCLUSIONS: Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

Inpatient cardiac rehabilitation soon after hospitalization for acute decompensated heart failure: a propensity score study.

PURPOSE: Postdischarge management of acute decompensated heart failure (ADHF) remains an ongoing challenge. We sought to assess whether inpatient cardiac rehabilitation (CR) soon after hospitalization for ADHF improves outcome. METHODS: Patients (N = 275) hospitalized for ADHF were enrolled. The primary outcome was a composite of all-cause mortality and urgent heart transplantation (UHT) at 1 year. The followup started at the time of discharge from the acute care setting. Because of the observational nature of the study, a propensity score analysis was used to predict the likelihood of undergoing CR. A multivariable Cox regression analysis adjusted for propensity score was used to assess the effect of CR on the primary outcome. RESULTS: Of the 275 patients, 130 underwent CR. Among the baseline variables of the index hospitalization for ADHF, propensity score derivation identified male gender, New York Heart Association Class IV, refractory HF, moderate to severe mitral or tricuspid regurgitation, nonuse of renin-angiotensin-aldosterone system inhibitors, and daily dosage of furosemide, as being independently associated with the likelihood of undergoing CR. No patient was lost to followup. During the 12-month followup, 74 patients died and 3 underwent UHT. The overall incidence of the primary outcome was 28%. On propensity score-adjusted Cox multivariable analysis, the relative risk of the primary outcome for participants in CR compared with nonparticipants in CR was 0.58 (confidence interval [CI]: 0.34-0.99; P = .04). CONCLUSIONS: Results suggest that the strategy of inpatient CR soon after discharge from the acute care setting improves 1-year UHT-free survival of patients with ADHF.

Clinical utility of different estimates of renal function for predicting mortality in chronic heart failure.

BACKGROUND: The clinical utility of different renal function (RF) measures for risk stratification in chronic heart failure (CHF) and the incremental discriminative value of renal dysfunction have not been investigated thoroughly. METHODS: We studied 802 patients with systolic CHF. The primary outcome was all-cause mortality. The association of candidate variables and RF measures [serum creatinine (SCr), serum urea nitrogen (SUN), estimated creatinine clearance adjusted for body-surface area (eCrCl(BSA)), and estimated glomerular filtration rate (eGFR)] with mortality was evaluated using Cox proportional-hazards analyses. Recommended metrics of goodness-of-fit and discrimination were calculated. RESULTS: At follow-up (median: 1269days), there were 301 deaths. Age (p<0.001), ischemic etiology (p=0.009), NYHA class (p<0.001), anemia (p<0.001), and left ventricular ejection fraction (p<0.001) independently predicted mortality (reference risk model). On multivariable analysis incorporating one of the measures of RF at a time, each had an independent value for predicting mortality (p<0.001). The addition of each RF measures to the reference model significantly increased the likelihood-ratio χ(2) and the models incorporating eCrCl(BSA) or SUN demonstrated the highest probability of being the best. Although changes in C statistic and net reclassification were not significant, the Integrated Discrimination Index was significantly improved by the addition of eCrCl(BSA). Calibration was improved by all measures of RF expect SUN. The model incorporating eCrCl(BSA) demonstrated both the best goodness-of-fit and discrimination. CONCLUSIONS: Our data suggest that renal dysfunction significantly improves risk stratification in a context of established risk factors. eCrCl(BSA) appears to be the most performing measure of RF for this purpose.

The cardiorenal anaemia syndrome in systolic heart failure: prevalence, clinical correlates, and long-term survival.

AIMS: We sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes. METHODS AND RESULTS: We studied 951 patients with chronic heart failure (CHF) and systolic dysfunction. The primary outcome was all-cause mortality and urgent heart transplantation (UHT). Cox's regression analyses were used to assess the relation of the variables to the primary outcome. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. The prevalence of CRA syndrome was 21.1%. Age (P < 0.001), body mass index (P< 0.001), diabetes (P =< 0.001), ischaemic aetiology (P< 0.006), left ventricular ejection fraction (P= 0.018), and treatment with renin-angiotensin system inhibitors (P< 0.001) were independently related to CRA syndrome. During a median follow-up of 3.7 years, the primary outcome occurred in 404 patients (42.5%). Compared with patients with preserved renal function and normal haemoglobin (Hb) levels, those with CRA syndrome had a significantly increased risk for the primary outcome; the univariate and multivariate-adjusted HRs were 4.04 (CI: 3.11-5.24; P< 0.0001) and 2.22 (CI: 1.64-2.98; P< 0.0001), respectively. Three-year UHT-free survival was 86 and 47%, respectively. Among patients with renal dysfunction, the adjusted HR for the primary outcome increased by 17% (CI: 8-26; P= 0.0001) for each 1g/dL decrease below an Hb value of 13.0 g/dL. CONCLUSION: Heart failure, renal dysfunction, and anaemia are a fatal combination. Despite a relatively low prevalence, the CRA syndrome contributes to considerable mortality due to CHF.