CARA-VT: a Dosimetric in Silico Study (CARA-VT)

Non-invasive CArdiac RAdioablation for Ventricular Tachycardia: a Feasibility Dosimetric in Silico Study Based on a Prospective Cohort of Patients to Compare Photon to Proton and to Carbon Ion Radiotherapy

Ventricular tachycardia (VT) is a potentially deadly condition, common in patients with structural heart disease or dilated cardiomyopathy. VTpatients are currently treated with anti-arrhythmic drugs, implanted cardioverter defibrillators or invasive catheter ablation (CA) but the overall success rate of this techniqueis still suboptimal.

One of the main reasons is an anatomically inaccessible location of VT's origin (within the mid-wall of the myocardium, on the epicardial site or adjacent to critical structures). Moreover, repeated invasive ablation, technical difficulties or patient comorbidities can lead to non-eligibility for CA. Accordingly, a rationale exists to adopt more effective and less invasive therapies.

A promising novel non-invasive treatment option for refractory VT is stereotactic arrhythmia radio-ablation (STAR), originally born for cancer treatment, which consists in the application of high-energy photons in a single 25 Gy dose to limited areas of the ventricles, also to those inaccessible for CA, recognized through non-invasive surface ECG-mapping as the origin of VT. Preliminary small case series described good tolerance and improved VT burden during follow-up.

Due to the encouraging physical and biological characteristics of protons and carbon ions, the dose to surrounding healthy tissues could potentially be better spared in comparison with photons. Especially, the cardiac healthy sub-structures might benefit from the use of particle beams instead of photons. On the other hand, due to range uncertainties affecting particle beams, delivering an ideal radiation treatment with heavy ions to fast-moving targets such as the heart, is more complex. So far, the feasibility and the safety of cardiac radiotherapy with protons and heavy ions have only been evaluated in animal models and recently in the first in man case managed by the collaboration between CNAO and San Matteo Cardiology Department in a patient treated with compassionate aim.

To date, feasibility and safety data showing potential advantages of particles over photon therapy in dose distributions are missing.

Therefore, we propose a study aimed to compare different radiation therapy treatment modalities (photons vs. particle therapy: protons and carbon ions) simulating the RT treatment of ventricular arrhythmias on real patients candidates to invasive catheter ablation treatment.

STAR with photons was first reported in 2013 and an increasingly number of case reports and case series have been published ever since, showing an acceptable safety profile and promising efficacy.

Decreasing the dose to the surrounding healthy heart tissues is expected to be very advantageous for patients.

Particle therapy based on its dosimetric physical selectivity compared to SBRT (Stereotactic Body Radiotherapy) with photons might have the potential to both lower off-target doses and lower risk of possible side effects.

Study Overview

• Status: Completed
• Conditions: Ventricular Tachycardia; Ventricular Arrhythmias

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

Study Locations

• Italy
  • Pavia
    • Pavia, Pavia, Italy, 27100
      • SC Cardiologia, Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Thirty patients suffering recurrent VT with clinical indication to receive invasive catheter ablation will be included in the study

Description

Inclusion Criteria:

• Recurrent VT with clinical indication to receive catheter ablation
• Written informed consent
• Patient's ability to understand the characteristics and consequences of the clinical study
• Invasive mapping data

Exclusion Criteria:

• Allergy to iodinated contrast media
• Pregnancy and breastfeeding
• Younger than 18 years

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Photons (control group); "Stereotactic arrhythmia radioablation" (STAR) based on the delivery of a high, single dose (25 Gy) of photons to selected cardiac tissue (to limited areas of the ventricles), also to those inaccessible for CA, recognized through non-invasive surface ECG-mapping as the origin of VT.
Particle therapy with Protons and Carbon ions (Intervention group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of particle therapy (protons and carbon ions)	To verify the feasibility of particle therapy plans in patients with refractory VT. Plans will be considered feasible whether the dosimetric criteria outlined will be achieved in no fewer than 90% of enrolled patients (30 enrolled patients).	up to 3 years
Dose sparing on surrounding non-target tissues with particle therapy (protons and carbon ions)	To compare simulated RT plans with protons, carbon ions and photons, and quantify the differences in terms of dose released to surrounding cardiac and non-cardiac healthy tissues. Comparison of simulated RT plans, with protons, carbon ions and photons, by using cardiac motion management, optimizing the treatment plan on different cardiac phases at ECG-gated CT scan and ECG-gated radiotherapy beams delivery, for the same cardiac targets, will be done in terms of planned target coverage (target conformity index) and dose-volume histograms (DVH).	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Integration of ECGi Mapping into Planning CT for Target Contouring	To collect preliminary data of non-invasive electrocardiographic mapping (ECGi) usage for target definition in the setting of STAR, including the possibility of directly incorporating ECGi non-invasive mapping data into the planning CT to minimize potential mistakes in contouring the target.	up to 3 years
Feasibility and interferences of Ultrasound Probe on RT treatment planning	To verify the feasibility and possible interferences with simulated RT treatment planning of the use of an ultrasound probe (for online cardiac localization during beam delivery), positioned on the chest wall of patients during the imaging phase. The feasibility will not be achieved in case the limited beam angles due to the probe position do not allow to achieve the dosimetric plan criteria outlined in table 1 in more than 10% of the enrolled patients.	up to 3 years
Development of Automatic Image Alignment	To develop and assess techniques for the automatic alignment of different images including CT and electroanatomic maps (EAM), to compose a single multimodal ventricular image where ablation planning can be more easily performed.	up to 3 years
Optimizing Arrhythmogenic Site Detection with Advanced Signal Processing Tools	To develop and assess techniques for the advanced simulation of the patient's ventricle by electrophysiological modelling customized on the EAM and the associated electrical information, to allow an in-silico test of the planned ablation strategy on a digital twin. Optimal identification of arrhythmogenic sites will also be pursued by the adoption of novel signal and information processing tools that have already demonstrated to be effective in the local identification of abnormal ventricular potentials.	up to 3 years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
• Collaborators: CNAO National Center of Oncological Hadrontherapy, Pavia, Italy

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: radiotherapy; non-invasive; radiation therapy; SBRT; Ventricular Arrhythmias; Ventricular tachycardia; carbon ions; VT; Stereotactic Body Radiotherapy; radioablation; particle therapy; STAR; Stereotactic arrhythmia radioablation; photons; RT treatment; invasive catheter ablation
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Tachycardia; Pathological Conditions, Signs and Symptoms; Tachycardia, Ventricular
• Other Study ID Numbers: CARA-VT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No