Prophylactic Use of Implantable Cardioverter-Defibrillators in the Prevention of Sudden Cardiac Death in Dialysis Patients.

BACKGROUND: Patients with end-stage renal disease who are undergoing dialysis are reported to be at high risk of sudden cardiac death (SCD), and to date, no therapy has been shown to be effective in reducing this risk. The feasibility and value of prophylactic implantable cardioverter-defibrillator (ICD) implantation to prevent SCD is uncertain. METHODS: We conducted the ICD2 trial (Implantable Cardioverter-Defibrillator in Dialysis Patients), a prospective, randomized, controlled study investigating the value and safety of ICD implantation to prevent SCD in 200 patients on dialysis with a left ventricular ejection fraction ≥35%, after adequate screening and optimization of other treatments. The primary end point was SCD. Secondary end points were all-cause mortality and ICD-related complications. RESULTS: The trial was stopped as per the recommendation of the data and safety monitoring board for futility reasons after inclusion of 188 patients, 97 in the ICD group and 91 in the control group. The median duration of follow-up was 6.8 years (interquartile range, 3.8-8.8 years). SCD occurred in 19 of 188 cases (10.1%), 11 of 97 in the ICD group and 8 of 91 in the control group. The cumulative SCD incidence at 5 years was 9.7% (95% CI, 3.3%-16.2%) in the ICD group and 7.9% (95% CI, 1.7-14.0%) in the control group, resulting in a hazard ratio of 1.32 (95% CI, 0.53-3.29; P=0.55). Overall, 99 of 188 patients died (52.7%), 52 in the ICD group and 47 in the control group. Five-year survival probability was 50.6% (95% CI, 39.8%-61.5%) in the ICD group and 54.5% (95% CI, 43.0-66.0%) in the control group, resulting in a hazard ratio of 1.02 (95% CI, 0.69-1.52; P=0.92). Among 80 patients who received an ICD, 25 adverse events related to ICD implantation occurred. CONCLUSIONS: In a well-screened and well-treated population undergoing dialysis, prophylactic ICD therapy did not reduce the rate of SCD or all-cause mortality, which remained high. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com . Unique identifier: ISRCTN20479861.

Long-term effects of melatonin on quality of life and sleep in haemodialysis patients (Melody study): a randomized controlled trial.

AIM: The disturbed circadian rhythm in haemodialysis patients results in perturbed sleep. Short term melatonin supplementation has alleviated these sleep problems. Our aim was to investigate the effects of long-term melatonin supplementation on quality of life and sleep. METHODS: In this randomized double-blind placebo-controlled trial haemodialysis patients suffering from subjective sleep problems received melatonin 3 mg day(-1) vs. placebo during 12 months. The primary endpoint quality of life parameter 'vitality' was measured with Medical Outcomes Study Short Form-36. Secondary outcomes were improvement of three sleep parameters measured by actigraphy and nighttime salivary melatonin concentrations. RESULTS: Sixty-seven patients were randomized. Forty-two patients completed the trial. With melatonin, no beneficial effect on vitality was seen. Other quality of life parameters showed both advantageous and disadvantageous effects of melatonin. Considering sleep, at 3 months sleep efficiency and actual sleep time had improved with melatonin compared with placebo on haemodialysis days (difference 7.6%, 95% CI 0.77, 14.4 and 49 min, 95% CI 2.1, 95.9, respectively). At 12 months none of the sleep parameters differed significantly from placebo. Melatonin salivary concentrations at 6 months had significantly increased in the melatonin group compared with the placebo group. CONCLUSIONS: The high drop-out rate limits the strength of our conclusions. However, although a previous study reported beneficial short term effects of melatonin on sleep in haemodialysis patients, in this long-term study the positive effects disappeared during follow up (6-12 months). Also the quality of life parameter, vitality, did not improve. Efforts should be made to elucidate the mechanism responsible for the loss of effect with chronic use.

Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study - a randomized controlled trial.

BACKGROUND: Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. METHODS AND RESULTS: The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. CONCLUSIONS: The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturation.

Left ventricular diastolic dysfunction in dialysis patients assessed by novel speckle tracking strain rate analysis: prevalence and determinants.

Background. Diastolic dysfunction is common among dialysis patients and is associated with increased morbidity and mortality. Novel echocardiographic speckle tracking strain analysis permits accurate assessment of left ventricular diastolic function, independent of loading conditions and taking all myocardial segments into account. The aim of the study was to evaluate the prevalence of diastolic dysfunction in chronic dialysis patients using this novel technique, and to identify its determinants among clinical and echocardiographic variables. Methods. Patients currently enrolled in the ICD2 study protocol were included for this analysis. Next to conventional echo measurements diastolic function was also assessed by global diastolic strain rate during isovolumic relaxation (SRIVR). Results. A total of 77 patients were included (age 67 ± 8 years, 74% male). When defined as E/SRIVR ≥236, the prevalence of diastolic dysfunction was higher compared to more conventional measurements (48% versus 39%). Left ventricular mass (OR 1.02, 95% CI 1.00-1.04, P = 0.014) and pulse wave velocity (OR 1.34, 95% CI 1.07-1.68, P = 0.01) were independent determinants of diastolic dysfunction. Conclusion. Diastolic dysfunction is highly prevalent among dialysis patients and might be underestimated using conventional measurements. Left ventricular mass and pulse wave velocity were the only determinants of diastolic dysfunction in these patients.