Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Clinical Trial.

Importance: Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy. Objective: To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid ß-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. Design, Setting, and Participants: This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018. Interventions: Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months. Main Outcomes and Measures: The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro-brain natriuretic peptide level, and troponin T level. Results: Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, -2.58 to -0.11 mL/kg per minute; P = .03) in the intervention group after 3 months. Conclusions and Relevance: In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696370.

Reliability of a telephone-based Glasgow Outcome Scale assessment using a structured interview in a heterogenous population of patients and examiners.

A reliable telephone-based Glasgow Outcome Scale (GOS) assessment would be advantageous to both patients and investigators. Using a previously published structured GOS interview and scoring system, the aim of this study was to assess the reliability of telephone-based GOS scores compared to those obtained face-to-face in a heterogenous population of patients and examiners. Sixty-six patients hospitalized for a variety of acute neurological injuries underwent two GOS interviews approximately 90 days after injury. From a pool of six examiners, structured interviews were conducted using a standardized data form containing nine yes/no questions. One interview was conducted face-to-face and the other interview was conducted by telephone, the order being randomly selected. A different examiner conducted the second interview, and was unaware of the findings of the first interview. From this data, a separate investigator assigned GOS scores using standardized criteria. Concordant GOS scores were obtained in 71% (47/66) of patients and discordant scores in 29% (19/66); kappa = 0.56 +/- 0.08 (SE) (95% CI kappa = 0.40-0.73). Patient-, examiner-, and interview-related characteristics had no significant associations with GOS concordance, although patient sex had a significant association with discrepant responses to one specific question (work at previous capacity). When used by multiple examiners to assess patients with diverse neurological conditions, use of a structured GOS examination does not guarantee a reliable telephone-based GOS score. Determination of whether patient sex influences the validity of the structured face-to-face GOS interview is worthy of future study.

Clinically relevant issues related to preheating composites.

STATEMENT OF THE PROBLEM: Issues regarding the use of composite preheating need to be investigated so that the clinician will better understand the variables associated with this method. PURPOSE: To examine the multiple aspects of use of a commercial composite preheating device (Calset, AdDent Inc., Danbury, CT, USA). MATERIALS AND METHODS: Temperature values of three heating units and composite compules were obtained using a K-type thermocouple and were recorded digitally in real time. The following parameters were measured: maximum heater and composite temperature and its stability upon storage, composite temperature change when removed from the heater and injected, the effect of delivery system on ejected composite temperature, and the effect of repeated and extended preheating on composite monomer conversion (using infrared spectroscopy). Monomer conversion was measured after repeated composite cycling (from room temperature [RT] to 60 degrees C, 10x) or extended preheating (24 hours at 60 degrees C), and values were compared with composite maintained at RT (control group). Among test parameters, data (N=5 for each parameter) were analyzed using Student's t-test, analysis of variance, and the Tukey-Kramer post-hoc test where appropriate (alpha=0.05). RESULTS/CONCLUSIONS: Two of the three tested units achieved the stated preset temperatures. Composite attained temperature values close to the heating unit. Composite temperature drop upon removal from the heater was dramatic: within 2 minutes a 50% temperature drop was noted. Heating the compule while preloaded in the syringe provided higher delivery temperatures than heating the compule separately (p < 0.00). Optimum results were achieved when preheated composite was dispensed and used as quickly as possible. Neither repeated nor extended preheating of composite significantly affected monomer conversion. CLINICAL SIGNIFICANCE: Preheating composite has potential benefits, but should be used with knowledge of its limitations. Reheating of unused composite does not affect its degree of conversion, thus decreasing material waste. Heating of the composite preloaded in the delivery syringe enhances the temperature of extruded composite.