Paolo Fontanive

Prognostic Value of N-Terminal Pro–Type-B Natriuretic Peptide and Doppler Left Ventricular Diastolic Variables in Patients With Chronic Systolic Heart Failure Stabilized by Therapy

Prognostication of patients with chronic heart failure (HF) stabilized by therapy may be difficult. Therefore, the aim was to evaluate whether combined assessment of plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) and Doppler left ventricular (LV) diastolic variables was relevant to the prognosis of patients with stable HF. Outpatients with LV systolic HF (ejection fraction < or =45%), classified using clinical criteria as decompensated (n = 94) and stable HF (n = 219), underwent a complete Doppler echocardiographic study. NT-pro-BNP was measured together with mitral wave velocities, E wave deceleration time, and tissue Doppler early septal annular velocity. Median follow-up was 22 months. Freedom from all-cause mortality or HF hospitalization at 24 months was worst (44%) in patients with decompensated HF, intermediate (58%) in patients with stable HF with NT-pro-BNP higher than the median (>1,129 pg/ml), and best (92%) in patients with lower NT-pro-BNP (log-rank p <0.0001). In patients with stable HF, NT-pro-BNP >1,129 pg/ml (hazard ratio [HR] 2.84, p = 0.003), E wave deceleration time <150 ms (HR 2.31, p = 0.004), and tissue Doppler early septal annular velocity <8 cm/s (HR 2.18, p = 0.01) were predictors of the end point at multivariate analysis. The addition of Doppler LV diastolic variables and NT-pro-BNP significantly improved the chi-square test for outcome prediction (from 14.4 to 46.4). In conclusion, NT-pro-BNP and spectral and tissue Doppler variables of LV diastolic dysfunction added independent and incremental contributions to prognostic stratification of patients with stable HF.

Patterns of left ventricular remodeling in chronic heart failure: prevalence and prognostic implications.

BACKGROUND AND AIM Many descriptors of left ventricular (LV) remodeling have important prognostic implications in patients with chronic systolic heart failure (HF). We sought to assess the prognostic value of the combination of increased LV mass with a disproportion between wall thickness and internal diameter. METHODS AND PATIENTS Patients (n = 536) with chronic HF, ejection fraction <50% and LV end-diastolic volume index >91 mL/m(2), classified according to LV mass index and relative wall thickness (RWT), were followed up for 33 ± 21 months. Ventricular mass was determined using a standard M-mode echocardiographic method. Relative wall thickness was defined as the ratio of (sum of interventricular septum thickness in diastole + posterior wall thickness in diastole)/LV end-diastolic diameter. RESULTS Prevalence of the pattern of increased LV mass index, defined as LV mass index >148 g/m(2) in men and >122 g/m(2) in women, and decreased RWT (<0.34) was 29%. Multivariable predictors of all-cause mortality were age >70 years (P < .0001), New York Heart Association class >2 (P < .0001), increased LV mass index, and decreased RWT (P = .003), E wave deceleration time ≤140 ms (P = .005), and male gender (P = .025). Patients with increased LV mass index and decreased RWT had a worse survival (33%) than patients with less LV mass index and normal to reduced RWT (log-rank 23.92; P < .0001). Comparisons of Cox models showed that the combination of increased mass index and decreased RWT added prognostic value to a model that included ejection fraction and end-systolic volume index. CONCLUSION In patients with systolic HF, an independent and incremental risk of adverse outcome was associated with increased mass index and decreased RWT.

Prognostic significance of tricuspid annular motion and plasma NT-proBNP in patients with heart failure and moderate-to-severe functional mitral regurgitation

The role of the right ventricle has been relatively neglected proportionate to its importance. We sought to evaluate the impact of right ventricular (RV) and NT‐proBNP on the outcome of patients with heart failure (HF) and functional mitral regurgitation (MR).

Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure

BACKGROUND A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF). AIM To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF. METHODS Patients (n=107; age 68±12 years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF)<45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model. RESULTS Follow-up period was 37±18 months. Multivariate predictors of events were T-IVT≥12.3% s/min, mean E/Em ratio≥10, log NT-pro-BNP levels≥2.47 pg/ml and LV EF≤32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/Em ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001). CONCLUSIONS Prolonged T-IVT added to the prognostic stratification of patients with systolic HF.

Value of tissue Doppler imaging for risk stratification of patients with chronic systolic heart failure with or without restrictive mitral flow

AIMS The aim of this study was to assess the prognostic value of tissue Doppler imaging (TDI) in patients with chronic systolic heart failure (HF) with or without restrictive mitral flow (RMF). METHODS AND RESULTS Echocardiograms were obtained in 378 patients with chronic systolic HF [ejection fraction (EF) < or = 45%] in sinus rhythm. Restrictive mitral flow was defined by an E wave deceleration time (EDT) < or = 140 ms. Tissue Doppler imaging early (Em) diastolic and systolic (Sm) velocities were measured at the mitral annulus. Patients were followed-up for a median of 32 months. Endpoints were all-cause mortality and the combination of death or HF hospitalization. Mean left ventricular EF was 32 +/- 8%. Restrictive mitral flow and TDI annular velocities were all univariate predictors of the endpoints. Ejection fraction <25% was the only multivariate predictor of all-cause mortality. E wave deceleration time and Em < 8 cm/s were independently associated with the combined endpoint of death or HF hospitalization. At 48 months, survival was 61% in patients with RMF and 82% in patients with non-RMF (log-rank: 21.6; P < 0.0001). When patients were stratified according to Em at or above 8 cm/s or below 8 cm/s, those with RMF and Em < 8 cm/s exhibited the worst survival (log-rank: 27.16; P < 0.0001). Patients with Sm < or = 6 cm/s had a 58% survival rate, whereas it was 82% in patients with Sm > 6 cm/s (log-rank: 12.73; P = 0.0004). CONCLUSION Doppler annular velocities provided useful information for prognostication of patients with systolic HF. Particularly, categorization of patients according to Em velocities allowed us to further stratify patients with RMF and non-RMF.

Atrial fibrillation and amino-terminal pro-brain natriuretic peptide as independent predictors of prognosis in systolic heart failure.

BACKGROUND Survival of patients with systolic heart failure (HF) may be influenced by the presence of chronic atrial fibrillation (AF) and circulating concentrations of B-type natriuretic peptides. In this study, we sought to assess the prognostic value of chronic AF in comparison to those of amino-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels and of echocardiographic parameters among HF patients of the entire study population and in those with AF. METHODS Plasma NT-proBNP levels and echocardiography were prospectively assessed in 489 patients with chronic systolic HF (LV ejection fraction <or=45%) in sinus rhythm or AF (16%). Follow-up duration was 26+/-15 months. RESULTS Patients with AF were older (p<0.0001), had a worse NYHA class (p=0.002) and higher NT-proBNP levels (p<0.0001) than those in sinus rhythm. Presence of AF (HR [hazards ratio]: 2.01, p=0.013) and plasma NT-proBNP (HR: 3.05, p<0.0001) were the only independent predictors of all-cause mortality. At receiver operating characteristic analyses, the threshold level for outcome prediction of NT-proBNP was higher in patients with AF (3883 pg/ml) than in patients in sinus rhythm (1653 pg/ml). Multivariate analysis performed in patients with HF and AF showed that plasma NT-proBNP was the most important predictor of death after statistic adjustment for age. CONCLUSIONS Chronic AF and NT-proBNP independently predicted the outcome of patients with HF. The threshold level of NT-proBNP for outcome prediction was different in patients with AF with respect to those in sinus rhythm. NT-proBNP was the most important independent predictor of all-cause mortality in HF patients with AF.

Plasma N-terminal protype-B natriuretic peptide levels in risk assessment of patients with mitral regurgitation secondary to ischemic and nonischemic dilated cardiomyopathy

BACKGROUND Functional mitral regurgitation (MR) is a factor affecting prognosis of patients with chronic left ventricular (LV) dysfunction. The aim of the study was to investigate whether the evaluation of plasma N-terminal protype-B natriuretic peptide (NT-proBNP) concentrations is useful for prognostic assessment of patients with functional MR due to either ischemic or nonischemic chronic LV dysfunction. METHODS Echocardiograms were obtained in 207 patients with chronic LV dysfunction (ejection fraction <or=45%) and secondary MR at color flow imaging. The NT-proBNP was measured at the time of the index echocardiogram. The MR was graded as mild when a small central jet <4 cm(2) or <20% of left atrial area or a vena contracta width <0.3 cm was present. It was considered moderate in the presence of signs of more-than-mild MR without criteria for severe MR. A vena contracta width >or=0.7 cm raised MR grade to severe. Median follow-up duration was 29 months. RESULTS The NT-proBNP levels increased significantly with MR severity. At multivariate analysis, NT-proBNP was an independent predictor of cardiac death (hazard ratio 2.17, CI 1.10-4.30, P = .026) and the most powerful predictor of cardiac death or heart failure-related hospitalization (hazard ratio 3.19, CI 1.89-5.37, P < .0001). A progressively worse outcome was apparent when patients were stratified by a graded increase in MR severity and by quartiles of NT-proBNP levels. Increased NT-proBNP concentrations and more-than-mild MR identified patients with the highest risk of cardiac mortality. CONCLUSION Assessment of plasma NT-proBNP allows for stratifying patients with functional MR regardless of their degree of valvular incompetence. Even in case of only mild or moderate MR, but increased NT-proBNP, patients have to face poor outcome.

Association of furosemide dose with clinical status, left ventricular dysfunction, natriuretic peptides, and outcome in clinically stable patients with chronic systolic heart failure.

In chronic heart failure (HF), high daily doses of furosemide have been associated with increased mortality. The authors sought to evaluate the relationships between orally administered furosemide doses, clinical status, left ventricular (LV) dysfunction, N-terminal proBNP (NT-proBNP), and outcome in 400 outpatients with chronic HF and LV ejection fraction (EF) ≤ 45%. Clinical status, NT-proBNP levels, and estimated glomerular filtration rate (eGFR) were evaluated. Median follow-up duration was 32 months. The median values of daily-dose furosemide and of furosemide dose normalized to body surface area were 25 mg (12.5-62.5 mg) and 15 mg/m(2) (13-34 mg/m(2)), respectively. A total of 32% of patients had decompensated HF according to Framingham score and criteria for congestion. In clinically stable patients, a multivariable Cox model, which included clinical and echocardiographic parameters plus NT-proBNP, hemoglobin, and eGFR, showed that normalized furosemide dose (P=.017), anemia (P=.060), age (P=.080), and New York Heart Association class (P=.080) were predictors of all cause-mortality. In patients with decompensated HF, LV end-systolic volume index (P=.018), NT-proBNP (P=.060), and reduced eGFR (P=.070) were independently related to the outcome. Normalized furosemide dose was a major determinant of prognosis in patients with chronic HF but without ongoing signs and symptoms, and this suggests a possible negative interaction of this drug in clinically stable patients.

Double-chambered left ventricle in an asymptomatic adult patient

This article shows a case of double-chambered left ventricle in asymptomatic 60-year-old man. This rare congenital entity is usually diagnosed in the neonatal or paediatric age, and it is characterized by the subdivision of the left ventricle in two chambers by an abnormal septum or muscle band. Differential diagnosis includes two other congenital left ventricular (LV) outpouching entities, such as diverticulum and aneurysm. As shown in our case, double-chambered left ventricle exhibits mixed features. A comprehensive cardiovascular magnetic imaging study is useful in the distinction of these closely related congenital diseases and, therefore, important for the correct final diagnosis.

Independent and Incremental Value of Severely Enlarged Left Atrium in Risk Stratification of Very Elderly Patients With Chronic Systolic Heart Failure

The authors sought to assess the impact on survival of demographic, clinical, and echo-Doppler parameters in patients with chronic heart failure due to left ventricular systolic dysfunction divided according to age groups. This study included 734 patients (age 69±11 years) who were classified into tertiles of age: I (22-66 years), II (67-76 years), and III (77-94 years). Severely enlarged left atrial size was defined as ≥52 mm in men and ≥47 mm in women. Multivariable analysis identified male sex (P=.018) and severely enlarged left atrium (P=.024) as significant correlates of all-cause mortality in the very elderly cohort, while restrictive filling pattern (RFP) (P=.004) and New York Heart Association class III or IV (P=.005) among patients of the first tertile and RFP (P=.028) among patients in the second tertile were independently associated with mortality after 30±21 months of follow-up. At the interactive stepwise model in the very elderly population, a severely enlarged left atrium, added to the model after clinical parameters and ejection fraction, moved the chi-square value from 20.7 to 25.8 (P=.048). RFP emerged as the single best predictor of all-cause mortality in the younger and intermediate ranges, whereas severely enlarged left atrium was the best predictor in the very elderly.