Interim Report of a Japanese Phase II Trial for Cardiac Stereotactic Body Radiotherapy in Refractory Ventricular Tachycardia　- Focus on Target Determination.

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.

Ablation index-guided cavotricuspid isthmus ablation with contiguous lesions using fluoroscopy integrated 3D mapping in atrial flutter.

PURPOSE: The feasibility and safety of cavotricuspid isthmus (CTI) ablation with contiguous lesions using ablation index (AI) under the guidance of fluoroscopy integrated 3D mapping (CARTO UNIVU/CU) in typical atrial flutter (AFL) remains uncertain. This study aimed to determine the efficacy of AI-guided CTI ablation with contiguous lesions in patients with AFL. METHODS: In this single-center, prospective, non-randomized, single-arm, observational study, procedural outcomes were determined in 151 patients undergoing AI-guided CTI ablation (AI group) with a target AI value of 450 and an interlesion distance of ≤ 4 mm under CU guidance. These outcomes were compared with those of 30 patients undergoing non-AI-guided ablation (non-AI group). RESULTS: Among 151 patients, first-pass conduction block was achieved in 120 (80%) patients in the AI group (67% in the non-AI group, P = 0.152) with a shorter fluoroscopy time of 0.2 ± 0.4 min (1.7 ± 2.0 min in the non-AI group, P < 0.001). Conduction gaps were located at the atrial aspects near the inferior vena cava in 24 of 31 (78%) patients without first-pass conduction block. The AI group received 11 ± 5 (12 ± 4 in the non-AI group, P = 0.098) radiofrequency (RF) applications, and the RF time was 4.2 ± 2.4 (5.1 ± 2.5 min in the non-AI group, P = 0.011). Despite the occurrence of steam pop in 3 (2%) patients, none of them developed cardiac tamponade. No patients had recurrence within 6 months of follow-up. CONCLUSIONS: AI-guided CTI ablation in combination with CU was feasible and effective in reducing radiation exposure in patients with AFL.

Impact of exercise capacity on the long-term incidence of atrial arrhythmias in heart failure.

We sought to demonstrate the impact of improved peak exercise oxygen consumption (V̇O2) during maximal exercise testing after cardiac rehabilitation (CR) on the incidence of arrhythmias in patients with heart failure (HF). The present study comprised of 220 patients with HF, and peak V̇O2 was examined at 2 and 5 months after CR. Of the 220 patients, 110 (50%) had a low peak V̇O2 of < 14 mL/min/kg at 2 months. The peak V̇O2 improved in 86 of these 110 (78%) patients at 5 months after CR. During a median follow-up of 6 years, the patients with improvement in peak V̇O2, compared to those without peak V̇O2 improvement, had a lower rate of mortality (4% vs. 29%, log-rank, P < 0.001) and HF hospitalization (6 vs. 17%, log-rank, P = 0.044) and a lower incidence of new-onset atrial arrhythmias (9 vs. 27%, log-rank, P = 0.013), with no difference in the incidence of ventricular arrhythmias between groups (1 vs. 4%, log-rank, P = 0.309). The majority of deaths in the patients without an improved peak V̇O2 were because of cardiovascular events (73%), particularly progressive HF (55%). Early detection and management of atrial arrhythmias may improve outcomes in patients without peak V̇O2 improvement after CR.

Clinical Significance of the Head-Up Tilt Test in Improving Prognosis in Patients with Possible Neurally Mediated Syncope.

Syncope is commonly encountered in daily clinical practice. Depending on its etiology (benign or life-threatening conditions or environmental triggers), syncope can be neurally mediated (reflex), cardiac, or orthostatic. Furthermore, neurologic disease can cause symptoms that mimic syncope. However, there is limited research on neurally mediated syncope (NMS), which is considered a benign disorder, and close follow-ups are rarely performed. NMS can cause serious clinical events, including severe trauma and car accidents. The head-up tilt test (HUTT) is the gold standard for diagnosing NMS; however, its clinical significance remains unknown, and its relevance to NMS prognosis requires further research. This retrospective study aimed to assess the clinical significance of the HUTT for NMS. We reviewed the charts of 101 patients who underwent HUTT at Tokai University Hospital in Japan between January 2016 and March 2019. During the HUTT, 72 patients (69.2%) experienced syncope. Patients were followed up for 886.1 ± 457.7 days (interquartile range: 518-1293 days). The syncope recurrence rate was 16.9%; however, no significant difference was observed between the two groups (HUTT positive vs. negative) (13.8% vs. 18.1%, p = 0.772). Four of 29 (13.9%) and two of 72 (2.8%) patients in the negative and positive HUTT groups, respectively, experienced cardiac events (p = 0.019). Negative HUTT results may assist in anticipating unexpected clinical events within a few years. A negative HUTT result may allow us to reconsider the NMS diagnosis based on clinical information. Close outpatient follow-up of patients with negative HUTT results is warranted.

Diagnosis and prevention of the vasodepressor type of neurally mediated syncope in Japanese patients.

We investigated circulatory dynamics in patients with vasodepressor type neurally mediated syncope (VT-NMS) by performing high-resolution Holter electrocardiography and a correlation analysis of changes in adenylate cyclase activity, blood pressure, and pulse during the head-up tilt test. Holter electrocardiography was performed for 30 patients. Adenylate cyclase activity was evaluated in lymphocytes from blood samples taken at rest and during the head-up tilt test. There was no change in autonomic nerve fluctuation during electrocardiography in VT-NMS patients, but our results showed a significant difference in blood pressure and adenylate cyclase activity between VT-NMS patients and healthy volunteers; the systolic blood pressure of VT-NMS patients decreased after 5 min, while at 10 min, the adenylate cyclase activity was the highest (0.53%) and the systolic blood pressure was the lowest (111.8 mm Hg). Pulse rates increased after 10 min. VT-NMS patients showed higher blood pressure, pulse rate, and adenylate cyclase activity during the tilt test than did healthy volunteers. In patients with syncope, standing for longer than 10 minutes may increase the risk of VT-NMS. From our results, we consider it likely that high systolic blood pressure and adenylate cyclase activity at rest cause fainting in VT-NMS patients. Our findings may be helpful for identifying individuals with a high risk of developing NMS in the healthy population.

Late-onset atrioventricular block after transcatheter aortic valve replacement.

BACKGROUND: Conduction disturbances leading to permanent pacemaker implantation (PPI) rarely occur late after transcatheter aortic valve replacement (TAVR). The clinical features of this phenomenon and its association with periprocedural conduction disturbances remain uncertain. OBJECTIVES: We aimed to determine the incidence and characteristics of late-onset atrioventricular block (AVB) after TAVR. METHODS: This single-center study included 246 patients undergoing TAVR. Late-onset AVB was defined as AVB ≥1 month after the TAVR. RESULTS: Periprocedural AVB (periAVB) occurred in 43 patients (17%). Patients with periAVB had a higher rate of right bundle branch block (47% vs 7%, P < .0001). Of the 43 patients with periAVB, 15 underwent PPI (35%) at a median duration of 6 days, whereas 1 of the remaining 203 patients without periAVB underwent PPI within 1 month (0.5%). During a median follow-up duration of 365 days, late-onset AVB occurred in 10 of 230 patients without PPI within 1 month (4%) at a median duration of 76 days. All 10 patients presented transient periprocedural atrioventricular conduction disturbances, including 8 patients with periAVB (80%), all of whom recovered within 1 month, and 9 patients underwent self-expanding valve implantation (90%). The mortality rate in patients with PPI within 1 month was higher than in those without, although the difference was not statistically significant (hazard ratio 2.68, 95% confidence interval 0.97-9.05, log-rank P = .09). CONCLUSION: Late-onset AVB occurred in a minority of patients undergoing TAVR. Greater vigilance is warranted, particularly in patients with transient conduction disturbances during the periprocedural period following self-expanding valve implantation.

Relation Between Autonomic Nervous Activity after Pulmonary Vein Isolation and Recurrence in Paroxysmal Atrial Fibrillation Patients.

OBJECTIVE: Pulmonary vein isolation (PVI) has been widely used for the treatments of paroxysmal atrial fibrillation (PAF); however, AF recurrence remains a significant challenge. We evaluated relation between autonomic nervous activity and AF recurrence using heart rate variability (HRV) and deceleration and acceleration capacity (DC/AC) analyses. METHODS: High-resolution Holter electrocardiogram was performed in 56 PAF patients pre- and 3 and 6 months post-PVI by cryoballoon. HRV and DC/AC analysis data were compared between the non-recurrence and recurrence groups. RESULTS: AF recurrence occurred in 10 cases. Total heart beats and maximum heart rate significantly decreased and minimum heart rate increased only in the non-recurrence group post-PVI. In HRV analysis, root mean square successive difference (RMSSD), low-frequency components (LF), high frequency components (HF) and LF/HF significantly decreased only in the non-recurrence group at both 3 and 6 months post-PVI; in contrast, significant decreases in RMSSD, LF and HF were observed in the recurrence group only at 6 months. In DC/AC analysis, DC significantly decreased in both groups post-PVI; in contrast, AC increased only in the non-recurrence group, resulting in significantly greater [AC]/DC ratio in the recurrence group at 3 months post-PVI. CONCLUSIONS: To prevent AF recurrence after PVI, it is important not only to reduce vagosympathetic overall activity but also to minimize imbalance between vagosympathetic reflex responses.