Discussion
ventricular ectopies, syncope, fibrosis, cardiac arrhythmia, pericardial effusion, Atrial fibrillation, pericarditis, prolonged QT, oesophagitis, cardiac valvulopathy, myocardial inflammation
FIBROSIS, CARDIAC ARRHYTHMIA, MYOCARDIAL INFLAMMATION, EFFUSIONS, EVENTS, OESOPHAGITIS, CHRONIC PERICARDITIS, SIDE EFFECT, TYPICAL ATRIAL FLUTTER, PERICARDIAL EFFUSION, TORSADE DE POINTES, HYPERTENSIVE HEART DISEASE, OESOPHAGITIS, ADVERSE EVENTS, ATRIAL FIBRILLATION, PERICARDITIS, CARDIAC VALVULOPATHY, COMPLICATIONS, RECURRENCES, EVENT, SECONDARY
Atrial fibrillation is the most common cardiac arrhythmia with an increased risk of complications especially if a proper anticoagulation or a proper rhythm and rate control is lacking.Pulmonary vein isolation remains the cornerstone of AF ablations.As a result, there is ongoing interest in developing improved therapies for AF and non-invasive therapeutic alternatives are warranted. The STAR study was born from the desire to obtain PVI using a non-invasive method, suitable for older patients or those who cannot have or not desire an invasive procedure. The outpatient care setting allows for the treatment of a large number of patients without occupying hospital beds. This aspect is of great importance considering the large number of patients eligible for the procedure as opposed to the progressive reduction of hospital beds.The present phase II LINAC-STAR trial is the first worldwide study designed to evaluate the safety of this treatment. In terms of safety endpoint, the adverse events with a possible correlation to STAR were mild oesophagitis and mild pericardial effusion among which only one required pharmacological therapy.Oesophagitis is essentially due to the anatomical proximity of the oesophagus and the PVs, and we documented mild oesophagitis without the onset of fistulas in a longer follow-up. We performed a ‘simultaneous integrated protection’ dose for the oesophagus and bronchus, for reducing the risk of side effect. Moreover, STAR was delivered using IGRT and SGRT to increase precision of target position and organs at risk and the delivering treatment time was very short (3 min instead of 45–90 min for other technologies), reducing the risk of oesophagus displacement during a longer treatment.The patient’s anatomy is essential for structuring an optimal treatment plan and some unfavourable anatomies (mainly oesophagus, PVs, and left bronchus very close together) may not allow it. In our series, one patient was excluded due to the oesophagus located behind the left PVs and in one patient the oesophagus and left bronchus were located so close to the superior PV ostia that the STAR treatment was planned deeper in the veins to avoid their damage. In the last case, the ES after STAR documented a suboptimal PV isolation since the PV antral electrical activity was widely recorded.Finally, we highlighted mild pericarditis and asymptomatic effusions during follow-up. It is necessary to monitor these events over a long time for potential development of chronic pericarditis and, in addition, to understand a possible correlation with arrhythmic recurrences.For the ‘torsade de pointes’, it is not possible to determine if this event was due to STAR or to a chance because in the patient’s clinical history there are factors that can be associated with this type of event. In particular, the patient had a syncope about 5 years ago and mild prolonged QT interval on ECG (corrected QTc 480 ms) and was suffering from hypertensive heart disease (ventricular septum diameter 15 mm). His treating physician decided to resume the flecainide therapy 7 days before STAR due to daily symptomatic AF episodes. After 1 h from STAR, the patient had a torsade de pointes treated effectively by electrical cardioversion and he was admitted to the cardiology department. Coronary angiography, echocardiogram, serum electrolytes, and troponin were normal. The patient underwent cardiac ICD implantation. During his follow-up visits, very early ventricular ectopies (minimum coupling interval 290 ms) were documented and the ICD recorded only one atypical atrial flutter after 1 year from STAR. The patient is in good general condition with a significant improvement in the quality of life.Regarding the secondary endpoints, the efficacy data have several limits (small number of patients, the analysis of recurrences carried out only through ECG and 15 days ECG-Holter monitoring, and the absence of a control group). However, our data report a trend towards a strong reduction in arrhythmic events, a reduction in the intake of AAT, and an improvement in the patients’ quality of life. According to recent data,Three patients developed a form of persistent AF and refused the catheter ablation. These patients had a cardiac valvulopathy that predisposed them to an atrial arrhythmic substrate worsening, even if catheter ablation was performed.In terms of ES, we have demonstrated for the first time that STAR is effective in performing PVI even 12 months after treatment. Regarding pathophysiological mechanisms, previous studies reported that myocardial inflammation and structural changes can be induced within a month after STAR, while fibrosis develops after several months.In terms of treatment dosimetry, our treatment plan has been performed to minimize the radiation dose to heart and close organs, conforming dose to PVs. However, despite dose to healthy organs (including heart, lungs, bronchus, oesophagus, and all body) respected the radiation dose constrains, as previously reported,The main limitations of our treatment concern the anatomical characteristics of patients and the absence of a pre-treatment arrhythmic substrate analysis.Furthermore, due to a non-invasiveness design of the present trial, an electroanatomical map to analyse the arrhythmic substrate was not performed. However, the ablative target in patients with paroxysmal AF is PVI that was achieved with STAR.