Background: Cardiac radiotherapy using stereotactic body radiation therapy (SBRT) has attracted attention as a minimally invasive treatment for refractory ventricular tachycardia. However, a standardized protocol and software program for determining the irradiation target have not been established. Here, we report the first preclinical stereotactic radioregulation antiarrhythmic therapy trial in Japan, focused on the target-setting process.

Methods and Results: From 2019 onwards, 3 patients (age range 60–91 years) presenting with ischemic or non-ischemic cardiomyopathy were enrolled. Two patients were extremely serious and urgent, and were followed up for 6 and 30 months. To determine the irradiation targets, we aggregated electrophysiological, structural, and functional data and reflected them in an American Heart Association 17-segment model, as per the current recommendations. However, in all 3 patients, invasive electrophysiological study, phase-contrast computed tomography, and magnetic resonance imaging could not be performed; therefore, electrophysiological and structural information was limited. As alternatives, high-resolution ambulatory electrocardiography and nuclear medicine studies were useful in assessing arrhythmic substrates; however, concerns regarding test weighting and multiple scoring remain. Risks to surrounding organs were fully taken into account.

Conclusions: In patients requiring cardiac SBRT, the information needed for target planning is sometimes limited to minimally invasive tests. Although there are issues to be resolved, this is a promising option for the life-saving treatment of patients in critical situations.

Background: Off-label dosing of direct oral anticoagulants (DOAC) as a treatment for non-valvular atrial fibrillation (NVAF) is problematic. Here, we investigated the status of rivaroxaban and edoxaban dosing by monitoring plasma concentrations (PCs).

Methods and Results: We monitored drug PCs in 391 and 333 outpatients receiving rivaroxaban and edoxaban, respectively, for NVAF. Drug doses were adjusted if the PC was above the cut-off value (rivaroxaban: 404 ng/mL; edoxaban: 402 ng/mL), determined from receiver operating characteristic curves for predicting bleeding events. On-label standard dosing was reduced to off-label underdosing due to high PCs above the cut-off more often for rivaroxaban (28.1%) than edoxaban (12.6%; P<0.001). Over a median follow-up of 13 months for rivaroxaban and 10 months for edoxaban, the annual incidence of bleeding events was higher with rivaroxaban than with edoxaban (4.88 vs. 3.73 patient-years; P<0.05), although no thromboembolic events occurred in either group. Furthermore, for patients with creatinine clearance >50 mL/min and body weight ≤60 kg, there was a greater incidence of bleeding events with rivaroxaban on-label 15 mg dosing than with edoxaban on-label 30 mg dosing (22.2% vs 2.9%; P<0.01).

Conclusions: Monitoring the PCs of rivaroxaban and edoxaban in NVAF patients enables dose adjustments to reduce bleeding risk. The incidence of bleeding under drug PC monitoring was less in the edoxaban than rivaroxaban group.

Background: Clinical practice guidelines strongly recommend optimal medical therapy (OMT), including lifestyle modification, pharmacotherapy, and exercise-based cardiac rehabilitation (CR), in patients with stable ischemic heart disease (SIHD). However, the efficacy and safety of CR in patients with SIHD without revascularization remain unclear.

Methods and Results: The Prospective Registry of STable Angina RehabiliTation (Pre-START) study is a multicenter, prospective, single-arm, open-label pilot study to evaluate the efficacy and safety of CR on health-related quality of life (HRQL), exercise capacity, and clinical outcomes in Japanese patients with SIHD without revascularization. In this study, all patients will undergo guideline-based OMT and are encouraged to have 36 outpatient CR sessions within 5 months after enrollment. The primary endpoint is the change in the Seattle Angina Questionnaire-7 summary score between baseline and the 6-month visit; an improvement of ≥5 points will be defined as a clinically important change. Secondary endpoints include changes in other HRQL scores and exercise capacity between baseline and the 6-month visit, as well as clinical outcomes between enrollment and the 6-month visit.

Conclusions: The Pre-START study will provide valuable evidence to elucidate the efficacy and safety of CR in patients with SIHD and indispensable information for a subsequent randomized controlled trial. The study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000045415) on April 1, 2022.