Cryoballoon pulmonary vein isolation-mediated rise of sinus rate in patients with paroxysmal atrial fibrillation

Background!#!Modulation of the cardiac autonomic nervous system by pulmonary vein isolation (PVI) influences the sinoatrial nodal rate. Little is known about the causes, maintenance and prognostic value of this phenomenon. We set out to explore the effects of cryoballoon PVI (cryo-PVI) on sinus rate and its significance for clinical outcome.!##!Methods and results!#!We evaluated 110 patients with paroxysmal atrial fibrillation (AF), who underwent PVI using a second-generation 28 mm cryoballoon by pre-, peri- and postprocedural heart rate acquisition and analysis of clinical outcome. Ninety-one patients could be included in postinterventional follow-up, indicating that cryo-PVI resulted in a significant rise of sinus rate by 16.5% (+ 9.8 ± 0.9 beats/min, p < 0.001) 1 day post procedure compared to preprocedural acquisition. This effect was more pronounced in patients with initial sinus bradycardia (< 60 beats/min.) compared to patients with faster heart rate. Increase of rate was primarily driven by ablation of the right superior pulmonary vein and for a subset of patients, in whom this could be assessed, persisted ≥ 1 year after the procedure. AF recurrence was neither predicted by the magnitude of the initial rate, nor by the extent of rate change, but postprocedural sinus bradycardia was associated with higher recurrence of AF in the year post PVI.!##!Conclusions!#!Cryo-PVI causes a significant rise of sinus rate that is more pronounced in subjects with previous sinus bradycardia. Patient follow-up indicates persistence of this effect and suggests an increased risk of AF recurrence in patients with postprocedural bradycardia

Biological Cardiac Tissue Effects of High-Energy Heavy Ions – Investigation for Myocardial Ablation

Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects

Immobilization for carbon ion beam ablation of cardiac structures in a porcine model

Introduction Whereas hadron therapy of static targets is clinically established, treatment of moving organs remains a challenge. One strategy is to minimize motion of surrounding tissue mechanically and to mitigate residual motion with an appropriate irradiation technique. In this technical note, we present and characterize such an immobilization technique for a novel noncancerous application: the irradiation of small targets in hearts with scanned carbon ion beams in a porcine model for elimination of arrhythmias. Material and methods A device for immobilization was custom-built. Both for the treatment planning 4D-CT scan and for irradiation, breath-hold at end-exhale was enforced using a remotely-controlled respirator. Target motion was thus reduced to heartbeat only. Positioning was verified by orthogonal X-rays followed by couch shift if necessary. Reproducibility of bony anatomy, diaphragm, and heart position after repositioning and between repeated breath-hold maneuvers was evaluated on X-rays and cardiac-gated 4D-CTs. Treatment was post hoc simulated on sequential 4D-CTs for a subset of animals, after immediate repositioning and after a delay of one week, similar to the delay between imaging and irradiation. Results Breath-hold without repositioning was highly reproducible with an RMS deviation of at most one millimeter. 4D-CTs showed larger deformations in soft tissue, but treatment simulation on sequential images resulted in full target coverage (V95 >95%). Conclusion The method of immobilization permitted reproducible positioning of mobile, thoracic targets for range-sensitive particle therapy. The presented immobilization strategy could be a reasonable approach for future animal investigations with the ultimate goal of translation to therapy in men

Biological Cardiac Tissue Effects of High-Energy Heavy Ions – Investigation for Myocardial Ablation

Abstract Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects