Changes in Exercise Tolerance over Time in Patients with Transthyretin Amyloidosis Cardiomyopathy Treated with Tafamidis.

Tafamidis improves the prognosis of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM). Additionally, it delays the decline in exercise tolerance, as observed in the six-minute walking test. However, the changes in cardiopulmonary function over time based on cardiopulmonary exercise tests are unclear. Thus, this preliminary study investigated the changes in exercise tolerance after one year of tafamidis treatment using cardiopulmonary exercise testing. Eight patients with ATTR-CM (average age: 77 years; male: n = 7) underwent cardiopulmonary exercise testing at baseline and after one year of tafamidis treatment. All eight patients completed a one-year follow-up. At baseline, the anaerobic threshold oxygen uptake (AT VO2: 10.9 ± 1.5) and peak VO2 (14.3 ± 3.0 mL/kg/minute) indicated relatively favorable exercise capacity; however, the minute ventilation/carbon dioxide production (VE/VCO2 slope), which indicates effective ventilation, showed poor performance (33.7 ± 12.8). One year after tafamidis treatment, frailty, as assessed by the Clinical Frailty Scale, had progressed in seven of eight patients (88%) (P < 0.01), and AT VO2 and peak VO2 were significantly reduced (19.2% and 22.3%, respectively; P < 0.05). The VE/VCO2 slope and peak O2 pulse decreased nonsignificantly by approximately 20% (P = 0.47, and P = 0.16, respectively). Further, the structure of the ventricles and atrium and the left ventricle ejection fraction on echocardiography did not change. Thus, exercise tolerance in patients with ATTR-CM was reduced after one year despite tafamidis administration. Not only ATTR-CM progression, but also frailty progression may influence this decrease in exercise tolerance. A comprehensive approach, including tafamidis administration and cardiac rehabilitation, is required for further improvement in the exercise capacity of patients with ATTR-CM.

Early cardiac rehabilitation for acute decompensated heart failure safely improves physical function (PEARL study): a randomized controlled trial.

BACKGROUND: Improvements in the Short Physical Performance Battery (SPPB) rather than exercise tolerance reportedly led to favorable prognosis in elderly patients with acute decompensated heart failure (ADHF). However, about 50% of heart failure shows heart failure with preserved ejection fraction, safe and effective interventions to improve SPPB for these types remain unclear. In addition, although a standard cardiac rehabilitation (CR) program for heart failure is widely used in Japan, whether this is sufficient to improve SPPB in elderly patients with ADHF remains unclear. AIM: This study aimed to evaluate whether the addition of multidisciplinary physical interventions to the standard CR program would prove effective for improving SPPB among elderly patients with ADHF regardless types of heart failure. DESING: The design of this study was randomized, prospective study. SETTING: Patients admitted to our hospital due to ADHF in Japan. POPULATION: Elderly patients with ADHF between March 2019 and March 2020 were randomized to two groups, an Intervention group and a Control group. METHODS: The Control group performed standard CR. The Intervention group received balance training and resistance training and used a cycling ergometer in addition to the standard CR program. The primary outcome was the improvement in SPPB after CR. RESULTS: Seventy-five patients with ADHF were divided into the two groups (Intervention group, N.=36; Control group, N.=39). At baseline, both groups showed low physical performance and a high prevalence of frailty. Intervention size effect was an improvement in SPPB score of +2.2 (+3.7±1.1 vs. +1.5±1.7; P<0.001). Of the 3 components of SPPB, both gait speed and timed repeated chair rise were significantly improved in the Intervention group compared to the Control group, with intervention size effect of +0.76 and +0.94, respectively (P<0.001). Subgroup analysis of heart failure with preserved ejection fraction showed significant improvement in SPPB score in the Intervention group compared to the Control group (P<0.001). No adverse events were observed during the study period. CONCLUSIONS: A multi-faceted intervention in addition to standard CR improved physical performance among elderly patients with ADHF regardless types of heart failure. CLINICAL REHABILITATION IMPACT: We believe that use of a cycling ergometer and load-specific resistance training provide specific CR for patients with ADHF during acute hospitalization and highlight the need for active intervention.

Application of Microreactor to the Preparation of C-11-Labeled Compounds via O-[11C]Methylation with [11C]CH3I: Rapid Synthesis of [11C]Raclopride.

A new radiolabeling method using a microreactor was developed for the rapid synthesis of [(11)C]raclopride. A chip bearing a Y-shaped mixing junction with a 200 µm (width)×20 µm (depth)×250 mm (length) flow channel was designed, and the efficiency of O-[11C]methylation was evaluated. Dimethyl sulfoxide solutions containing the O-desmethyl precursor or [11C]CH3I were introduced into separate injection ports by infusion syringes, and the radiochemical yields were measured under various conditions. The decay-corrected radiochemical yield of microreactor-derived [11C]raclopride reached 12% in 20 s at 25 °C, which was observed to increase with increasing temperature. In contrast, batch synthesis at 25 °C produced a yield of 5%: this indicates that this device could effectively achieve O-[11C]methylation in a shorter period of time. The microreactor technique may facilitate simple and efficient routine production of 11C-labeled compounds via O-[11C]methylation with [11C]CH3I.

Synthesis and evaluation of (-)- and (+)-[¹¹C]galanthamine as PET tracers for cerebral acetylcholinesterase imaging.

Improved radiopharmaceuticals for imaging cerebral acetylcholinesterase (AChE) are needed for the diagnosis of Alzheimer's disease (AD). Thus, (11)C-labeled (-)-galanthamine and its enantiomers were synthesized as novel agents for imaging the localization and activity of AChE by positron emission tomography (PET). C-11 was incorporated into (-)- and (+)-[(11)C]galanthamine by N-methylation of norgalanthamines with [(11)C]methyl triflate. Simple accumulation of (11)C in the brain was measured in an in vivo biodistribution study using mice, whilst donepezil was used as a blocking agent in analogous in vivo blocking studies. In vitro autoradiography of rat brain tissue was performed to investigate the distribution of (-)-[(11)C]galanthamine, and confirmed the results of PET studies in mice. The radiochemical yields of N-methylation of (-)- and (+)-norgalanthamines were 13.7% and 14.4%, respectively. The highest level of accumulation of (11)C in the brains of mice was observed at 10 min after administration (2.1% ID/g). Intravenous pretreatment with donepezil resulted in a 30% decrease in accumulation of (-)-[(11)C]galanthamine in the striatum; however, levels in the cerebellum were unchanged. In contrast, use of (+)-[(11)C]galanthamine led to accumulation of radioactivity in the striatum equal to that in the cerebellum, and these levels were unaffected by pretreatment with donepezil. In in vitro autoradiography of regional radioactive signals of brain sections showed that pretreatment with either (-)-galanthamine or donepezil blocked the binding of (-)-[(11)C]galanthamine to the striatum, while sagittal PET imaging revealed accumulation of (-)-[(11)C]galanthamine in the brain. These results indicate that (-)-[(11)C]galanthamine showed specific binding to AChE, whereas (+)-[(11)C]-galanthamine accumulated in brain tissue by non-specific binding. Thus, optically pure (-)-[(11)C]galanthamine could be a useful PET tracer for imaging cerebral AChE.