Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction

ObjectivesThis study hypothesized that microvolt T-wave alternans (MTWA) improves selection of patients for implantable cardioverter-defibrillator (ICD) prophylaxis, especially by identifying patients who are not likely to benefit.BackgroundMany patients with left ventricular dysfunction are now eligible for prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has been proposed to improve patient selection.MethodsOur study was conducted at 11 clinical centers in the U.S. Patients were eligible if they had a left ventricular ejection fraction (LVEF) ≤0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association functional class IV heart failure. Participants underwent an MTWA test and then were followed for about two years. The primary outcome was all-cause mortality or non-fatal sustained ventricular arrhythmias.ResultsIschemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 ± 6 months of follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at two years (95% confidence interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was 97.5% at two years. The strong association between MTWA and the primary end point was similar in all subgroups tested.ConclusionsAmong patients with heart disease and LVEF ≤0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis

An assessment of the reliability of three methods used in evaluating the status of multiple sclerosis patients

The reliability of three different evaluation methods used in a cooperative clinical trial of the efficacy of ACTH in multiple sclerosis patients was evaluated in a uniformity study that used an efficient statistical design requiring only 10 patients and 5 examiners. The methods were the standard neurologic examination, a scoring system for functional grades and disability status, and a 7-day symptom score. Each patient was examined only 3 times at the beginning of the study and 3 more times 6 days later. No significant differences among the 5 examiners were observed on 82 of the 87 items used to measure neurologic function. With the exception of 1 variable, there were no significant differences among the average values of the sequence of the 3 examinations, nor among the average increments of change in the numerical scores between the first and second trials.In an additional examination in which all 5 examiners simultaneously evaluated 3 patients 1 at a time, it was found that the 5 examiners observed uniformly in all of the neurologic tests.The results of this study indicate that, by and large, the three evaluation methods appear to be reliable in the evaluation of neurologic status when used in a cooperative clinical trial where several investigators contribute data. Furthermore, investigations of reliability in cooperative studies can be performed with the use of efficient statistical designs such as the incomplete Latin-square design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32998/1/0000382.pd

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Cytotoxicity of Root Perforation Repair Biomaterials Using Periodontal Stem Cells

Objective. This study was intended to evaluate in vitro cytotoxicity of six common types of root perforation repair biomaterials on human periodontal stem cells (hPSCs). Background. An endodontic perforation is as an artificial communication between the root canal system and the external tooth surface, there are new materials that show better biocompatibility and results in direct contact with periodontal tissues. Methods. HPSCs (NIDCR, Bethesda, MD) were grown to confluence. Materials were packed into tubing to create 1mm by 1mm samples. The test biomaterials (n = 60 samples) were; A MTA (White ProRoot MTA, Dentsply, Tulsa, OK.); a calcium hydroxide material (USP, Henry Schein, Melville, NY.); a Zinc oxide-eugenol cement (IRM, Dentsply, Milford, DE.); a glass ionomer (Geristore, DenMat, St Maria, CA.); a composite (Resilon, Pentron, CT.), and amalgam (Dispersalloy, Dentsply Milford, DE.). The biomaterials were set for 48 hours in a 37oC incubator. The biomaterials were placed in contact with hPSCs for 24 hours. The cytotoxicity of the biomaterials was measured using a lactate dehydrogenase membrane integrity assay (CytoTox-ONE, Promega, Medison, WI). Results. The most to the least cytotoxic biomaterials were; Zinc oxide eugenol (96%), glass ionomer (49%), Amalgam (35%), mineral trioxide aggregate (30%), Composite (17%) and calcium hydroxide (8%). Conclusion. Root perforations should be repaired with calcium hydroxide, composite or MTA to limit the death of adjacent periodontal cells. Grants. This study was supported by the AAE Foundation and NSU HPD grants