Most cited article - PubMed ID 34600851
Radiation-Induced Changes in Ventricular Myocardium After Stereotactic Body Radiotherapy for Recurrent Ventricular Tachycardia
Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering the pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including aetiology-specific aspects and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before the expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.
- Keywords
- Ablation, Radiotherapy, Stereotactic arrhythmia radioablation (STAR), Sudden death, Ventricular tachycardia,
- MeSH
- Action Potentials MeSH
- Cardiology * standards MeSH
- Tachycardia, Ventricular * physiopathology surgery diagnosis MeSH
- Consensus MeSH
- Humans MeSH
- Radiosurgery * adverse effects standards methods MeSH
- Risk Factors MeSH
- Patient Selection * MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Practice Guideline MeSH
- Geographicals
- Europe MeSH
We performed a histological and immunohistochemical analysis of myocardia from 3 patients who underwent radiosurgery and died for various reasons 3 months to 9 months after radiotherapy. In Case 1 (death 3 months after radiotherapy) we observed a sharp transition between relatively intact and irradiated regions. In the myolytic foci, only scattered cardiomyocytes were left and the area was infiltrated by immune cells. Using immunohistochemistry we detected numerous inflammatory cells including CD68+/CD11c+ macrophages, CD4+ and CD8+ T-lymphocytes and some scattered CD20+ B-lymphocytes. Mast cells were diminished in contrast to viable myocardium. In Case 2 and Case 3 (death 6 and 9 months after radiotherapy, respectively) we found mostly fibrosis, infiltration by adipose tissue and foci of calcification. Inflammatory infiltrates were less pronounced. Our observations are in accordance with animal experimental studies and confirm a progress from myolysis to fibrosis. In addition, we demonstrate a role of pro-inflammatory macrophages in the earlier stages of myocardial remodeling after stereotactic radioablation for ventricular tachycardia.
- Keywords
- apoptosis, arrhythmia, immunohistochemistry, inflammation, macrophage, radioablation,
- MeSH
- Fibrosis MeSH
- Tachycardia, Ventricular * etiology radiotherapy surgery MeSH
- Humans MeSH
- Radiosurgery * adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.
- Keywords
- Cardiac arrhythmias, Consortium, EU Horizon 2020, Stereotactic arrhythmia radioablation, Stereotactic body radiotherapy, Ventricular tachycardia,
- MeSH
- Catheter Ablation * adverse effects methods MeSH
- Tachycardia, Ventricular * MeSH
- Humans MeSH
- Prospective Studies MeSH
- Arrhythmias, Cardiac MeSH
- Heart Ventricles MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.
- Keywords
- STAR, radioablation, stereotactic body radiotherapy (SBRT), structural heart disease, ventricular tachycardia,
- Publication type
- Journal Article MeSH
Stereotactic body radiotherapy (SBRT) has been reported as an attractive option for cases of failed catheter ablation of ventricular tachycardia (VT) in structural heart disease. However, even this strategy can fail for various reasons. For the first time, this case series describes three re-do cases of SBRT which were indicated for three different reasons. The purpose in the first case was the inaccuracy of the determination of the treatment volume by indirect comparison of the electroanatomical map and CT scan. A newly developed strategy of co-registration of both images allowed precise targeting of the substrate. In this case, the second treatment volume overlapped by 60% with the first one. The second reason for the re-do of SBRT was an unusual character of the substrate-large cardiac fibroma associated with different morphologies of VT from two locations around the tumor. The planned treatment volumes did not overlap. The third reason for repeated SBRT was the large intramural substrate in the setting of advanced heart failure. The first treatment volume targeted arrhythmias originating in the basal inferoseptal region, while the second SBRT was focused on adjacent basal septum without significant overlapping. Our observations suggested that SBRT for VT could be safely repeated in case of later arrhythmia recurrences (i.e., after at least 6 weeks). No acute toxicity was observed and in two cases, no side effects were observed during 32 and 22 months, respectively. To avoid re-do SBRT due to inaccurate targeting, the precise and reproducible strategy of substrate identification and co-registration with CT image should be used.
- Keywords
- electroanatomical mapping, failed catheter ablation, safety, stereotactic body radiotherapy, ventricular tachycardia,
- Publication type
- Journal Article MeSH
- Case Reports MeSH