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Background Natriuretic peptides and diastolic dysfunction have prognostic value in asymptomatic subjects at risk for heart failure. Their integration might further refine the risk stratification process in this setting. Aim of this paper was to explore the possibility to predict heart failure and death combining diastolic dysfunction and natriuretic peptides in an asymptomatic population at risk for heart failure. Methods Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for heart failure. Baseline evaluation included electrocardiogram, echocardiogram, and natriuretic peptides collection. Based on diastolic dysfunction and natriuretic peptides, subjects were classified in four groups: control group (no diastolic dysfunction/normal natriuretic peptides, 57%), no diastolic dysfunction/high natriuretic peptides (9%), diastolic dysfunction/normal natriuretic peptides (24%), and diastolic dysfunction/high natriuretic peptides (11%). We applied Cox multivariable and Classification and Regression Tree analyses. Results The mean age of the population was 69 ± 7 years, 44% were women, mean left ventricular ejection fraction was 61%, and 35% had diastolic dysfunction. During a median follow-up of 5.7 years, 95 heart failure/death events occurred. Overall, diastolic dysfunction and natriuretic peptides were predictive of adverse events (respectively, hazard ratio 1.91, confidence interval 1.19–3.05, padjusted = 0.007, and hazard ratio 2.25, confidence interval 1.35–3.74, padjusted = 0.002) with Cox analysis. However, considering the four study subgroups, only the group with diastolic dysfunction/high natriuretic peptides had a significantly worse prognosis compared to the control group (hazard ratio 4.48, confidence interval 2.31–8.70, padjusted Conclusions The DAVID-Berg data suggest that we look for the quite common combination of diastolic dysfunction/high natriuretic peptides to correctly identify asymptomatic subjects at greater risk for incident heart failure/death, thus more suitable for preventive interventions.

BACKGROUND Mild asymptomatic left ventricular systolic dysfunction (ALVSD) may be associated with incident heart failure (HF). However, this gray zone group needs incremental risk refinement. We hypothesized that diastolic dysfunction (DD) may refine HF and death risk prediction in mild ALVSD. METHODS AND RESULTS Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, N-terminal pro B-type natriuretic peptide, and echocardiogram. Based on left ventricular ejection fraction (LVEF) and DD, subjects were classified as: control group (normal LVEF, n = 459, 76%), mild ALVSD (LVEF ≥40%/

Aims Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters. Methods and results Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/functional ones, associated with higher risk of HF/death [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.84–0.95, Padjusted < 0.001]. The risk of HF/death related to clinical data and NT-proBNP (baseline model) was reclassified by echocardiography only when MWFS was included into the model (baseline C-statistics 0.761; adding conventional structural/functional echocardiographic data 0.776, P = 0.09; adding MWFS 0.791, P = 0.007). Compared to subjects with normal LVEF and MWFS, only subjects with combined systolic dysfunction (11% of the population) were at higher risk (P = 0.001 for both abnormal; P > 0.24 for either LVEF or MWFS abnormal). Conclusion DAVID-Berg data suggest to include MWFS assessment in clinical practice, a simple and reliable echocardiographic parameter able to improve risk stratification in subjects at high risk for HF.

Background: Despite the burden of pre-clinical heart failure (HF) among diabetes mellitus (DM) patients, routine screening echocardiography is not currently recommended. We prospectively assessed risk prediction for HF/death of a screening strategy combining clinical data, electrocardiogram, NTproBNP, and echocardiogram, aiming to identify DM patients more suitable for selective echocardiography. Methods: Among 4047 screened subjects aged. ≥. 55/≤80. years, the DAVID-Berg Study prospectively enrolled 623 outpatients with DM, or hypertension, or known cardiovascular disease but with no HF history/symptoms. The present analysis focuses on data obtained during a longitudinal follow-up of the 219 patients with DM. Results: Mean age was 68. years, 61% were men, and median DM duration was 4.9. years. During a median follow-up of 5.2. years, 50 subjects developed HF or died. A predictive model using clinical data demonstrated moderate predictive power, which significantly improved by adding electrocardiogram (C-statistic 0.75 versus 0.70; p

This study sought to develop a novel echocardiogram outflow ramp test to detect device malfunctions in centrifugal-flow left ventricular assist devices (LVADs). This new ramp pump test is based on the direct analyses of systolic and diastolic ratio (S/D) Doppler velocity in the outflow cannula in the HeartWare LVAD during progressive increases in speed. The results showed that in patients with normal pump function, the Doppler velocity S/D ratio gradually decreased during LVAD speed increases. This test is easily performed and seems promising to detect normal pump function in patients assisted by a centrifugal flow LVAD.

Background The assessment of pulmonary hypertension in patients with heart failure is of great clinical importance not only for diagnostic purposes but also for prognostication. The present study was undertaken on a consecutive basis with a group of patients with chronic heart failure. Patients were evaluated for their suitability for heart transplantation: (1) to explore the diagnostic accuracy of several echo Doppler parameters of pulmonary hemodynamics in predicting the presence of elevated pulmonary artery pressure (defined as pulmonary artery systolic pressure ≥35 mm Hg and mean pulmonary artery pressure >20 mm Hg); (2) to assess the diagnostic ability of the same parameters to identify patients with elevated pulmonary vascular resistance; and (3) to evaluate the influence of right ventricular function and degree of tricuspid regurgitation in modifying diagnostic accuracy. Methods Echo Doppler examination and right heart catheterization were performed consecutively within 24 hours in 86 patients. The optimal cut-off value for a series of echo Doppler parameters capable of identifying patients with pulmonary hypertension was obtained by dividing the entire sample into 2 groups; the optimal threshold (highest sensitivity and specificity) of the echo and Doppler parameters used to classify patients with and without pulmonary hypertension was determined in 67% of cases by means of the receiver operating characteristic (ROC) curve: this was the testing sample. The proportion of cases classified correctly according to the selected cut-off was computed. The remaining 33% of cases represented the validation sample: sensitivity, specificity and predictive values (and their 95% confidence intervals [CIs]) for identifying pulmonary hypertension were calculated from the proposed cut-offs in this second sample. Finally, the overall performance of the echo Doppler parameters was assessed over the whole sample by considering the extent of the area under the ROC curve (A-ROC) and its 95% CI, for the dichotomic measurement. Results On right heart catheterization, a pulmonary artery systolic (PAPs) pressure ≥35 mm Hg plus a mean pressure (mean PAP) >20 mm Hg was documented in 49 of 86 cases (57%), for whom mean values were 56 ± 17 and 38 ± 11 mm Hg, respectively. The proportion of cases identified correctly as having pulmonary hypertension was highest for PAPs (88%) and mean PAP (85%) in addition to acceleration time of pulmonary artery systolic flow (ACT) (79%) and pulmonary artery diastolic pressure obtained utilizing the early phase of the tricuspid regurgitation spectral flow (PAPd/TR) (75%). PAPd/TR performed better in the validating sample in terms of diagnostic ability, with high sensitivity and specificity (100% and 60%) and positive and negative predictive values (PPV 80%, NPV 100%). PAPs, mean PAP, ACT and PAPd/TR confirmed their prevailing diagnostic ability (A-ROC from 0.74 to 0.86) in identifying pulmonary hypertension with fair to high feasibility (67% to 91%) and an odds ratio (OR) indicative of strong association. ACT and PAPd/TR, the 2 parameters with the highest feasibility, allowed us to identify 46 of 49 (94%) hypertensive cases. The same parameters did not perform well in identifying patients with increased vascular resistance, with A-ROC ranging from 0.55 to 0.69. Heterogeneity of effect, due to right ventricular function or tricuspid regurgitation degree, could not be demonstrated in the ability of the echo Doppler measurements to identify pulmonary hypertension. Conclusions ACT, PAPd/TR, PAPs and mean PAP have been shown to accurately classify patients with chronic heart failure with or without pulmonary hypertension. In particular, ACT and PAPd/TR alone allowed reliable and accurate definition of pulmonary hypertension in 94% of patients, regardless of right ventricular function or degree of tricuspid regurgitation. Non-invasive pulmonary pressure assessment by the referred method might be useful in the evaluation of heart transplant candidates.

biopsies performed, only 42 cases of MPMNs were identified in allograft lungs. Because of their small size and the need to recut paraffin blocks to perform chimerism studies, only 2 of our 6 gender-mismatched recipients were available for study, but they provided convincing evidence that this cellular proliferation arises from the donated graft. This observation confirms earlier studies published in this journal that utilized primarily clinical data to arrive at this conclusion.

Aims The study aimed at evaluating the prevalence of interventricular and intraventricular contractile dyssynchrony in heart failure patients with either normal or prolonged QRS duration. Methods and results Echocardiography and tissue Doppler imaging (TDI) were performed in 158 consecutive patients with advanced left ventricular dysfunction (LVEF

Heart transplantation (HTx) in patients with complex congenital heart disease (CHD) is a challenge because of structural anomalies and multiple previous procedures. We analysed our results in adult and paediatric patients to evaluate outcome and assess risk factors affecting mortality.Between 1985 and 2011, among 839 patients who underwent HTx, 85 received transplantation for end-stage CHD. Patients were divided into four age subgroups:1 year (8 patients, Group I), 1-10 years (20 patients, Group II), 11-18 years (24 patients, Group III) and18 years (33 patients, Group IV) and into two time periods: 1985-2000 (47 patients) and 2001-2011 (38 patients). Anatomical diagnoses were single-ventricle defect in 37 patients (44%) and two-ventricle defect in 48 patients (56%). Seventy-three patients (86%) had undergone one or more cardiac surgical procedures prior to HTx (mean 2.4 ± 0.9). Twenty-two of them were suffering from Fontan failure. Mean pulmonary artery pressure was 25.2 ± 14.2 mmHg. Mean transpulmonary gradient was 9.4 ± 6.9 mmHg.Mean follow-up after HTx was 7.8 ± 6.8 years. Survival at 1 month was 37.7% in Group I, 85.8% in Group II, 96.8% in Group II and 98.4% in Group IV and was significantly worse in younger recipients. Overall 30-day mortality was 17.6%. Currently 56 patients (65.8%) are alive. Overall survival at 1, 5, 10 and 15 years is 83-, 73-, 67- and 58%, respectively. There were 14 late deaths. Univariate analysis found that risk factors for early and late death were those related to recipient illness, such as pre-transplant creatinine, intravenous inotropic drugs, intravenous diuretics, mechanical ventilation and presence of protein-losing enteropathy (PLE). Multivariate analysis for all events (early and late deaths) identified preoperative mechanical ventilation as an independent risk factor for mortality. Number of previous procedures did not influence survival. Previous Fontan procedure did not increase mortality. We documented the reversibility of PLE in survivors.We demonstrated that heart transplantation for patients with CHD can be performed with the expectation of excellent results. Previous procedures, including the Fontan operation, do not reduce survival. Mortality is related to preoperative patient condition. We advocate early referral of complex CHD patients for transplant assessment and for inclusion in waiting lists before the detrimental effects of end-stage failure manifest themselves.

Patient survival after heart transplantation has improved dramatically since the availability of calcineurine inhibitor (CNIs); the number of long-term patients is progressively increasing. However, in these patients, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction. Since impaired renal function is an important issue that reduces long-term patient survival, it is important to develop strategies to improve renal function while maintaining immunologic safety to preserve graft function. Everolimus is an mTOR inhibitor sirolimus analogue, that has proved, to be highly efficacious to prevent acute myocardial rejection and reduce the severity of cardiac allograft vasculopathy in de novo HTx patients. There is reasonable evidence that, in long term heart transplanted patients, renal function may improve when everolimus is administered associated with a progressive reduction of CNIs. So far there is no evidence to identify which patient may benefit from this therapeutic approach. Indeed everolimus alone may be equally effective to prevent rejection and improve renal function when CNIs are completely discontinued, but data are still lacking on the risks, dosages and side effects of this type of immunosuppression. Ongoing clinical studies will provide further guidance about the possibility to halt or reduce the progression of renal impairment in long term heart transplant patients.

Background It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. Methods We studied 26 patients (21 males and five females) with a mean age of 58 ± 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. Results The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. Conclusions Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile.

Background Noninvasive estimation of pulmonary artery systolic and diastolic pressures usually requires the investigation of both tricuspid and pulmonary regurgitant jets and an estimate of right atrial pressure. A new, noninvasive method to obtain pulmonary diastolic pressure (based on the hemodynamic demonstration that right ventricular systolic pressure and pulmonary artery diastolic pressure are equal at the time of pulmonary valve opening) from the analysis of tricuspid regurgitation alone has been described in a small cohort of patients. We sought to verify the accuracy of this method in a large population of patients with heart failure. Methods An estimate of pulmonary artery diastolic pressure was obtained by transposing the pulmonary opening time (from the onset of the R wave on the electrocardiographic tracing to the beginning of pulmonic forward flow on Doppler examination) onto the tricuspid regurgitant velocity curve and calculating the pulmonary artery diastolic pressure value as the pressure gradient between the right ventricle and right atrium at this time. The study group included 86 consecutive patients (64 men, aged 52 ± 11 years) with heart failure (New York Heart Association class ≥II, 94%) who were in stable clinical condition with a chiefly idiopathic (57%), ischemic (24%), or other form (13%) of dilated cardiomyopathy. Noninvasive, right-sided pressures were compared with invasive measurements obtained during right heart catheterization performed within 24 hours. The Bland and Altman graphic method was used together with the calculation of the Lin concordance correlation coefficient and its 95% CI to assess the agreement between hemodynamic and echocardiographic measurements. Results Catheter-derived pulmonary artery systolic pressure ranged from 8 to 119 mm Hg (mean 42 ± 21 mm Hg), pulmonary artery diastolic pressure from 1 to 59 mm Hg (mean 20 ± 11 mm Hg), and right atrial pressure from −5 to 20 mm Hg (mean 6 ± 5 mm Hg). Tricuspid regurgitation was detected in 75 of 86 patients (87%). Pulmonary artery systolic pressure ranged from 13 to 110 mm Hg (mean 44 ± 21 mm Hg); the pressure gradient between the right ventricle and right atrium at time t of the pulmonary valve opening on the tricuspid regurgitation velocity curve was measurable in 70 of 75 (93%) cases and ranged from 3.5 to 64 mm Hg (mean 22 ± 11 mm Hg). Good agreement was observed not only for pulmonary artery systolic pressure but also for pulmonary artery diastolic pressure, based on the analysis of the tricuspid regurgitation velocity jet, with a slight difference between measurements (−1.8 and 0.1, respectively), no evident pattern of point scattering, and a high concordance correlation coefficient that was elicited by the virtually total overlapping of lines on the graph. Overall results were not significantly different whether patients with depressed right ventricular function (right ventricular ejection fraction ≤35%), with a tricuspid regurgitation grade ≥2 and atrial fibrillation were included in the analysis. Conclusions The narrow paired difference for the estimate of pulmonary artery systolic pressure and the even better difference for pulmonary artery diastolic pressure using the tricuspid regurgitation velocity curve analysis indicates that this new method reliably estimates invasive right-sided pressures over a wide range of pressure values in patients with heart failure. The overall good correlation with invasive values indicates that Doppler examination of tricuspid regurgitation alone may provide a simple and comprehensive new method for the noninvasive evaluation of right ventricular and pulmonary hemodynamics in patients with heart failure. (Am Heart J 2002;144:1087-94.)

common in the SR group than the EV group (see table). Drop out rate from drug was lower in the EV vs. SR group (5% vs. 31%, p 0.001). Conclusions: Everolimus appeared to have less AEs compared to sirolimus. This is especially significant since everolimus patients were treated earlier, immediately after transplant when AEs are more common, compared to the sirolimus group. A head-to-head comparison trial is warranted.