Attilio Di Benedetto

Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial.

OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy. BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure (HF), but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking. METHODS A total of 114 dialysis patients with dilated cardiomyopathy were randomized to receive either carvedilol or placebo in addition to standard therapy. A first analysis was performed at one year and was followed by an additional follow-up period of 12 months. RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling, with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group. At two years, 51.7% of the patients died in the carvedilol group, compared with 73.2% in the placebo group (p < 0.01). Furthermore, there were significantly fewer cardiovascular deaths (29.3%) and hospital admissions (34.5%) among patients receiving carvedilol than among those receiving a placebo (67.9% and 58.9%, respectively; p < 0.00001). The exploratory analyses revealed that fatal myocardial infarctions, fatal strokes, and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group. A reduction in sudden deaths and pump-failure deaths was also observed, though it did not reach statistical significance. CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy. These data suggest the use of carvedilol in all dialysis patients with chronic HF.

Clinical researchCarvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: A prospective, placebo-controlled trial

OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy. BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure (HF), but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking. METHODS A total of 114 dialysis patients with dilated cardiomyopathy were randomized to receive either carvedilol or placebo in addition to standard therapy. A first analysis was performed at one year and was followed by an additional follow-up period of 12 months. RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling, with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group. At two years, 51.7% of the patients died in the carvedilol group, compared with 73.2% in the placebo group (p < 0.01). Furthermore, there were significantly fewer cardiovascular deaths (29.3%) and hospital admissions (34.5%) among patients receiving carvedilol than among those receiving a placebo (67.9% and 58.9%, respectively; p < 0.00001). The exploratory analyses revealed that fatal myocardial infarctions, fatal strokes, and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group. A reduction in sudden deaths and pump-failure deaths was also observed, though it did not reach statistical significance. CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy. These data suggest the use of carvedilol in all dialysis patients with chronic HF.

Dilated Cardiomyopathy in Dialysis Patients— Beneficial Effects of Carvedilol: A Double-Blind, Placebo-Controlled Trial

OBJECTIVES The aim of this study was to investigate in dialysis patients with symptomatic heart failure New York Heart Association (NYHA) functional class II or III whether the addition of carvedilol to conventional therapy is associated with beneficial effects on cardiac architecture, function and clinical status. BACKGROUND Congestive heart failure (CHF) in chronic hemodialyzed patients, particularly when associated with dilated cardiomyopathy, represents an ominous complication and is an independent risk factor for cardiac mortality. METHODS We enrolled 114 dialysis patients with dilated cardiomyopathy. All patients were treated with carvedilol for 12 months in a double-blind, placebo-controlled, randomized trial. The patients underwent M-mode and two-dimensional echocardiography at baseline, 1, 6 and 12 months after the randomization. Each patients clinical status was assessed using an NYHA functional classification that was determined after 6 and 12 months of treatment. RESULTS Carvedilol treatment improved left ventricular (LV) function. In the active-treatment group, the increase in LV ejection fraction (from 26.3% to 34.8%, p < 0.05 vs. basal and placebo group) and the reduction of both LV end-diastolic volume (from 100 ml/m2 to 94 ml/m2, p < 0.05 vs. basal and placebo group) and end-systolic volume (from 74 ml/m2 to 62 ml/m2, p < 0.05 vs. basal and placebo group) reached statistical significance after six months of therapy, compared with baseline and corresponding placebo values, and they remained constant at one year of treatment (p < 0.05 vs. basal and placebo group). The clinical status of patients, assessed by NYHA functional classification, improved during the treatment period. Moreover, at the end of the trial, there were no patients in NYHA functional class IV in the carvedilol group, compared with 5.9% of the patients in the placebo arm. CONCLUSIONS One year of therapy with carvedilol in dialysis patients with CHF and dilated cardiomyopathy reduces LV volumes and improves LV function and clinical status.

Effects of Telmisartan Added to Angiotensin-Converting Enzyme Inhibitors on Mortality and Morbidity in Hemodialysis Patients With Chronic Heart Failure : A Double-Blind, Placebo-Controlled Trial

OBJECTIVES the aim of this study was to determine whether telmisartan decreases all-cause and cardiovascular mortality and morbidity in hemodialysis patients with chronic heart failure (CHF) and impaired left ventricular ejection fraction (LVEF) when added to standard therapies with angiotensin-converting enzyme inhibitors. BACKGROUND in hemodialysis patients, CHF is responsible for a high mortality rate, but presently very few data are available with regard to this population. METHODS A 3-year randomized, double-blind, placebo-controlled, multicenter trial was performed involving 30 Italian clinics. Hemodialysis patients with CHF (New York Heart Association functional class II to III; LVEF ≤ 40%) were randomized to telmisartan or placebo in addition to angiotensin-converting enzyme inhibitor therapy. A total of 332 patients were enrolled (165 telmisartan, 167 placebo). Drug dosage was titrated to a target dose of telmisartan of 80 mg or placebo. Mean follow-up period was 35.5 ± 8.5 months (median: 36 months; range: 2 to 40 months). Primary outcomes were: 1) all-cause mortality; 2) cardiovascular mortality; and 3) CHF hospital stay. RESULTS at 3 years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission for CHF (33.9% vs. 55.1%; p < 0.0001). With Cox proportional hazards analysis, telmisartan was an independent determinant of all-cause mortality (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51; p < 0.0001). Adverse effects, mainly hypotension, occurred in 16.3% of the telmisartan group versus 10.7% in the placebo group. CONCLUSIONS addition of telmisartan to standard therapies significantly reduces all-cause mortality, cardiovascular death, and heart failure hospital stays in hemodialysis patients with CHF and LVEF ≤ 40%. (Effects Of Telmisartan Added To Angiotensin Converting Enzyme Inhibitors On Mortality And Morbidity In Haemodialysed Patients With Chronic Heart Failure: A Double-Blind Placebo-Controlled Trial; NCT00490958).

Longitudinal Changes in Body Composition in Patients After Initiation of Hemodialysis Therapy: Results From an International Cohort

OBJECTIVE In patients with advanced kidney disease, metabolic and nutritional derangements induced by uremia interact and reinforce each other in a deleterious vicious circle. Literature addressing the effect of dialysis initiation on changes in body composition (BC) is limited and contradictory. The aim of this study was to evaluate changes in BC in a large international cohort of incident hemodialysis patients. METHODS A total of 8,227 incident adult end-stage renal disease patients with BC evaluation within the initial first 6 months of baseline, defined as 6 months after renal replacement therapy initiation, were considered. BC, including fat tissue index (FTI) and lean tissue index (LTI), were evaluated by Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany). Exclusion criteria at baseline were lack of a BCM measurement before or after baseline, body mass index (BMI) < 18.5 kg/m(2), presence of metastatic solid tumors, treatment with a catheter, and prescription of less or more than 3 treatments per week. Maximum follow-up was 2 years. Descriptive analysis was performed comparing current values with the baseline in each interval (delta analysis). Linear mixed models considering the correlation structure of the repeated measurements were used to evaluate factors associated with different trends in FTI and LTI. RESULTS BMI increased about 0.6 kg/m(2) over 24 months from baseline. This was associated with increase in FTI of about 0.95 kg/m(2) and a decrease in LTI of about 0.4 kg/m(2). Female gender, diabetic status, and low baseline FTI were associated with a significant greater increase of FTI. Age > 67 years, diabetes, male gender, high baseline LTI, and low baseline FTI were associated with a significant greater decrease of LTI. CONCLUSIONS With the transition to hemodialysis, end-stage renal disease patients presented with distinctive changes in BC. These were mainly associated with gender, older age, presence of diabetes, low baseline FTI, and high baseline LTI. BMI increases did not fully represent the changes in BC.

Modifiable factors associated with achievement of high-volume post-dilution hemodiafiltration: results from an international study.

Background The aim was to investigate factors associated with the successful achievement of ≥21 l/session of substitution fluid volume in patients on post-dilution hemodiafiltration. Methods 3315 patients treated in 6 European countries with the Fresenius 5008 CorDiax machine including the AutoSub Plus feature were considered. Variables that showed a relationship with convection volume were entered in a multivariable logistic regression model. Results Mean blood flow was 379 ± 68 ml/min. Median substitution volume was 24.7 L (IQR 22.0–27.4 L). Mean filtration fraction was 28.3 ± 4.1%. 81.5% of sessions qualified as high-volume HDF (substitution volumes ≥21 L). Higher age, dialyzer surface area, blood flow and treatment time were positively associated with the achievement of ≥21 L substitution volume; higher body mass index, male gender, higher hematocrit, graft or catheter vs. fistula, and start of week vs. mid-week were negatively associated. Conclusions Dialysis center policy in terms of blood flow, treatment time, filter size, and perhaps even hemoglobin targets plays a key role in achieving high-volume HDF. All of these are modifiable factors that can help in prescribing an optimal combination of dialyzer size, achievable blood flows, and treatment times.

Physical methods for evaluating the nutrition status of hemodialysis patients

This article aims to provide an overview of the different nutritional markers and the available methodologies for the physical assessment of nutrition status in hemodialysis patients, with special emphasis on early detection of protein energy wasting (PEW). Nutrition status assessment is made on the basis of anamnesis, physical examination, evaluation of nutrient intake, and on a selection of various screening/diagnostic methodologies. These methodologies can be subjective, e.g. the Subjective Global Assessment score (SGA), or objective in nature (e.g. bioimpedance analysis). In addition, certain biochemical tests may be employed (e.g. albumin, pre-albumin). The various subjective-based and objective methodologies provide different insights for the assessment of PEW, particularly regarding their propensity to differentiate between the important body composition compartments—fluid overload, fat mass and muscle mass. This review of currently available methods showed that no single approach and no single marker is able to detect alterations in nutrition status in a timely fashion and to follow such changes over time. The most clinically relevant approach presently appears to be the combination of the SGA method with the bioimpedance spectroscopy technique with physiological model and, additionally, laboratory tests for the detection of micro-nutrient deficiency.

Sustained-Release Diltiazem Reduces Myocardial Ischemic Episodes in End-Stage Renal Disease: A Double-Blind, Randomized, Crossover, Placebo-Controlled Trial

End-stage renal disease (ESRD) patients receiving maintenance hemodialysis and suffering from coronary artery disease (CAD) often receive doses of calcium channel antagonists that are too low. This may be the result of physicians desire to avoid adverse side effects during hemodialysis. The aim of this study was the assessment of the safety and efficacy of incremental doses of diltiazem for the treatment of myocardial ischemia in ERSD patients with CAD to identify the optimal dose of the drug. A total of 196 chronic hemodialysis patients were enrolled with CAD showing more than 5 min of transient myocardial ischemia during a 48-h Holter ECG monitoring. A double-blind, randomized, crossover, placebo-controlled trial design was used. Incremental doses of diltiazem (120 to 240 mg/d) were administered in 4 mo. With a dose of 120 and 180 mg/d, a significant reduction in the number and duration of total and symptomatic ischemic episodes was observed (P < 0.001), but the number and the duration of silent ischemic episodes were not reduced. Conversely, the efficacy on silent myocardial ischemia was obtained with a dosage of diltiazem of 240 mg/d (P < 0.001). In addition, with a sustained-release formulation (120 mg twice daily), the efficacy was similar to that obtained with four 60-mg tablets, but the safety was improved, especially during hemodialytic session. The circadian variations analysis of transient ischemic episodes showed a significant reduction in both ischemic peaks observed at baseline only with 240 mg/d of diltiazem. The findings emphasize that sustained-release diltiazem (120 mg twice daily) can be largely useful in uremic patients with CAD on maintenance dialysis. Diltiazem reduces the number and the duration of silent ischemic episodes, has a good tolerability, and positively modifies the circadian pattern of ischemic episodes.

A comparative study of the risk profile of hemodialysis patients in a for profit network and in two regional registries of the Italian Society of Nephrology

In 2013, the Italian Society of Nephrology joined forces with Nephrocare-Italy to create a clinical research cohort of patients on file in the data-rich clinical management system (EUCLID) of this organization for the performance of observational studies in the hemodialysis (HD) population. To see whether patients in EUCLID are representative of the HD population in Italy, we set out to compare the whole EUCLID population with patients included in the regional HD registries in Emilia-Romagna (Northern Italy) and in Calabria (Southern Italy), the sole regions in Italy which have systematically collected an enlarged clinical data set allowing comparison with the data-rich EUCLID system. An analysis of prevalent and incident patients in 2010 and 2011 showed that EUCLID patients had a lower prevalence of coronary heart disease, peripheral vascular disease, heart failure, valvular heart disease, liver disease, peptic ulcer and other comorbidities and risk factors and a higher fractional urea clearance (Kt/V) than those in the Emilia Romagna and Calabria registries. Accordingly, survival analysis showed a lower mortality risk in the EUCLID 2010 and 2011 cohorts than in the combined two regional registries in the corresponding years: for 2010, hazard ratio (HR) EUCLID vs. Regional registries: 0.80 [95% confidence interval: 0.71–0.90]; for 2011, HR: 0.76 [0.65–0.90]. However, this difference was nullified by statistical adjustment for the difference in comorbidities and risk factors, indicating that the longer survival in the EUCLID database was attributable to the lower risk profile of patients included in that database. This preliminary analysis sets the stage for future observational studies and indicates that appropriate adjustment for difference in comorbidities and risk factors is needed to generalize to the Italian HD population analyses based on the data-rich EUCLID database.