Tatsuhiko Hirao

BACKGROUND: Cardiac radioablation is emerging as a treatment modality for refractory ventricular tachycardia. This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam cardiac radioablation. METHODS: Eighteen swine underwent single-fraction 30 to 40 Gy pencil-beam scanning proton therapy targeting the left ventricle and were euthanized 12 to 40 weeks later. Treatment planning was performed without restricting the dose to the coronary arteries. The maximum point dose (D _max ) to the epicardial coronary arteries was calculated. In secondary analyses, the mean (D _mean ) and minimum dose received by the highest irradiated 0.01 cm ³ (D _0.01 ) of each coronary artery were also calculated. Coronary artery segments were harvested from the D _max sites for histological analysis, and the D _max was correlated with stenosis severity. RESULTS: Ninety-six coronary arteries were analyzed. No stenoses were observed by computed tomography imaging preirradiation. By histological analysis posteuthanasia, 25/96 (26%) coronaries sampled at their D _max sites had ≥75% stenosis. The median D _max was 4.7 Gy for the P max and stenosis ≥75% was 92.2%. A D _max value of 20.1 Gy best predicted stenosis ≥75%, with sensitivity 92.3% and specificity 87.1%. The AUC-ROCs for the associations of D _mean and D _0.01 with stenosis ≥75% were 84.8% and 91.6%, respectively. In histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D _max sites, and it was present in 61.5% of all arteries and in 93.9% of arteries with D _max ≥20 Gy. CONCLUSIONS: In this preclinical model of proton beam cardiac radioablation, coronary stenoses occurred in a dose-dependent manner, with D _max showing the closest correlation with stenosis ≥75%. These data provide for the first time a framework for dose constraint considerations for the coronary arteries during treatment planning for cardiac radioablation and thoracic malignancy radiation.

BACKGROUND: Power-controlled radiofrequency ablation with irrigated-tip catheters has been the norm for ventricular ablation for almost 2 decades. New catheter technology has recently integrated more accurate tissue temperature sensing enabling temperature-controlled irrigated ablation. We aimed to investigate the in vivo ablation parameters and lesion formation characteristics in ventricular myocardium using a novel temperature-controlled radiofrequency catheter. METHODS: Twenty canines were divided into 3 groups: 4 noninfarcted, acute (phase I); 8 noninfarcted, chronic (phase II); and 8 infarcted, chronic (phase III). Lesions were delivered with a temperature-controlled radiofrequency system utilizing a chemical vapor deposit diamond for efficient thermal diffusivity. In phase I, 17 ablation settings were tested (temperature set points, 50/60/70 °C; ablation duration, 15/30/60/90/120 s; and power limit, 30/50 W). Four and one of these sets of parameters were further tested in phases II and III, respectively. Lesions were assessed by ex vivo contrast-enhanced magnetic resonance imaging and gross pathology 5 weeks after ablation in phases II/III. RESULTS: Across all phases, 111 ablation lesions were delivered. Ablation with the power limit of 50 W, the temperature set point of 60 °C, and the duration of 60 s produced significantly larger and deeper lesions (mean, 569.2 mm ³ ; mean maximal depth, 9.8 mm) compared with 50 W/60 °C/30 s (mean, 340.4 mm ³ ; mean maximal depth, 8.3 mm) and 50 W/50 °C/60 s (mean, 227 mm ³ ; mean maximal depth, 6.9 mm), with P <0.05 for all pairwise comparisons. Ablation of infarcted myocardium in phase III (50 W/60 °C/30 s) resulted in smaller impedance and bipolar electrogram amplitude changes and lesion size compared with ablation in normal myocardium with the same settings. No steam pop, myocardial perforation, or char formation was observed in any of the 111 ablations across all phases. CONCLUSIONS: In vivo radiofrequency ablation in a canine model with a diamond-tip temperature-controlled catheter using a temperature set point of 60 °C and a power limit of 50 W created large lesions without steam pop risk in both normal and infarcted ventricular myocardia.

Introduction: Gastric hypomotility (GH) is a major complication of atrial fibrillation (AF) ablation. We aimed to clarify whether additional cryoballoon ablation (CBA) of the left atrial (LA) roof is associated with GH. Methods and Results: This study included 54 patients with non-paroxysmal AF who underwent CBA for pulmonary vein isolation and of the LA roof line. GH was defined according to the results of esophagogastroscopy performed 2 days after ablation. GH was observed in 10 patients. There were significant differences in LA diameter (LAD), right inferior pulmonary vein (RIPV) diameter, and the height of the LA roof from the point where the LA posterior wall and esophagus make contact between patients with (GH+) and without GH (GH–) (LAD: 41.0 [36.3–41.8] mm vs. 46.5 [42.8–50.0] mm, p<0.01; RIPV diameter: 19.7 [19.0–20.5] mm vs. 23.2 [21.2–24.9] mm, p<0.01; height of LA roof: 5.7 [5.1–6.1] mm vs. 8.8 [7.1–11.2] mm for, p<0.01, respectively). Multivariate analysis revealed that LA roof height was a predictor of GH. Moreover, Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) scores increased significantly 1 week after ablation (from 1.0 [0.0–2.8] to 5.0 [3.0–11.0], p=0.03) in patients with GH. Conclusion: The height of the LA roof may be a predictor of GH after CBA of the LA roof line. Additionally, GH-related symptoms may still appear 1 week after ablation.

Cardiac motion remains a challenge in the treatment of ventricular tachycardia with external beam ablation therapy. Current techniques involve expansion of the treatment area which can lead to unwanted collateral damage. Surrounding healthy tissue could be spared by gating the delivery of the beam to the cardiac cycle. In prior work, we assessed cardiac motion using in vivo fiducial markers and demonstrated that motion would be reduced if treatment were gated to half of the cardiac cycle, approximately corresponding to diastole. In the current work, we extend our prior analysis by quantitatively assessing the optimal gating window for motion reduction in the left ventricle. Motion was assessed in five porcine models with two fiducial clips per animal for a total of ten clips. The minimal cardiac motion occurred when the gating window started at 70% of the cardiac cycle. Without gating, three-dimensional cardiac motion was 7.0 ± 3.9 in x (left/right), 5.3 ± 2.5 in y (anterior/posterior), and 5.6 ± 2.3 in z (superior/inferior) mm. Using an optimal gating window, cardiac motion was 3.1 ± 1.8 in x (left/right), 2.5 ± 1.2 in y (anterior/posterior), and 3.1 ± 1.7 in z (superior/inferior) mm. The percentage reduction in motion with optimal gating was 51 ± 23 in x (left/right), 49 ± 21 in y (anterior/posterior), and 45 ± 24 % in z (superior/inferior). This work demonstrates that gating shows significant promise for reducing the effects of left ventricular motion when treating ventricular tachycardia with external beam ablation therapy.