Clinical evidence
The published record
Two bodies of evidence, in date order. One where the heart is the target. One where it is the organ to protect. Both end at the same open problem. The heart moves
Target · sections 01 to 08
Heart as the target
Cardiac radioablation. Four eras, from the catheter tip to the gated proton beam. What each era settled, and what it left open.
Read the target recordProtect · section 09
Heart as the organ at risk
Thoracic radiotherapy for tumors next to the heart. The evidence that every gray to the heart has a price, with no threshold below which it is free.
Read the protect recordTargetFirst body of evidence
From a catheter tip inside the heart to a gated beam outside it. The record below is how the heart became a target you can hit without touching it.
Target02 / 1979–2019
The catheter era.
The therapy radioablation is measured against, and the patients it leaves behind.
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An accident
Vedel and colleagues report complete heart block after repeated DC cardioversion with a recording catheter at the bundle of His. Current ran down the catheter and destroyed conduction tissue. Nobody meant to ablate anything.
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First deliberate catheter ablation
Scheinman (UCSF) ablates the AV junction on purpose with high-energy DC shocks. First reported series: nine patients.
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Radiofrequency replaces DC
DC arcs and causes barotrauma. Borggrefe interrupts an accessory pathway with RF energy. The technique still used today.
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Ablation goes mainstream
Haïssaguerre finds the pulmonary-vein triggers of atrial fibrillation. Marchlinski (2000) maps and ablates ventricular scar substrate. Catheter ablation becomes routine cardiology.
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The randomised trials, and the ceiling
SMASH-VT, VTACH and VANISH show catheter ablation beats escalated drugs for ventricular tachycardia. Recurrence stays high. Patients with advanced heart failure tolerate the procedure worst.
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Consensus, and an admitted gap
HRS/EHRA/APHRS/LAHRS expert consensus on catheter ablation of ventricular arrhythmias. Refractory VT after failed ablation is named as an unmet need.
Target03 / 2010–2022
Proof in animals.
Can a beam do what a catheter tip does? Yes. The dose that does it was measured before any patient was treated.
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First noninvasive cardiac radiosurgery
Sharma isolates pulmonary veins in swine with a CyberKnife. Photons, no catheter, conduction block achieved.
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Carbon ions interrupt conduction
Lehmann irradiates the AV junction, PV junction and LV free wall in intact pigs at 25, 40 and 55 Gy, in forced breath-hold. 40–55 Gy slows, then interrupts, impulse propagation. Fibrosis is the mediator. First particle-beam cardiac ablation data.
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Immobilisation becomes its own problem
A dedicated porcine study on holding cardiac structures still enough for carbon-ion ablation. The beam is ready before the motion answer is.
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Catheter-free ablation with scanned protons
Lehmann shows pencil-beam scanned protons producing the same targeted lesions in pigs. The modality with a Bragg peak, so no exit dose.
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What the dose does electrically
Porcine work characterises the early electrophysiological effect of proton irradiation. Conduction changes before transmural fibrosis appears.
Target04 / 2012–2026
Photons, in patients.
STAR, stereotactic arrhythmia radioablation. One outpatient session, 25 Gy, no anesthesia. The clinical proof the field rests on.
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First human treated
Loo (Stanford) treats refractory VT with a CyberKnife at 25 Gy, tracking an implanted fiducial. Case report published three years later.
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The landmark: Cuculich, NEJM
Five patients. Single 25 Gy fraction on a standard linac, target defined by noninvasive ECG imaging. VT burden across the group fell by orders of magnitude. Motion handled by a free-breathing internal target volume. Margin, not tracking.
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ENCORE-VT, the first prospective trial
Robinson, Circulation. 19 patients, phase I/II, 25 Gy. Confirms the burden reduction and gives the field a reproducible protocol.
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It travels
Prague (Neuwirth), a US multicenter series (Lloyd) and single-center cohorts across Europe reproduce the effect outside the originating institution.
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STOPSTORM.eu: Europe standardises
A multidisciplinary consortium publishes a shared treatment and outcome platform, plus a survey of how differently STAR was being delivered.
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RADIATE-VT, the pivotal randomised trial
Cardiac radioablation versus repeat catheter ablation, 1:1, in high-risk refractory VT with LVEF ≤ 49 %. Primary completion estimated May 2026, final 2030. The trial that decides whether beams enter the standard of care.
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Society backing
STOPSTORM publishes a systematic review and meta-analysis of the prospective trials. EHRA and HRS issue a clinical consensus statement on patient selection, substrate delineation and data transfer for STAR.
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Three-year outcomes
STAR versus repeat catheter ablation, safety and efficacy at three years. The first medium-term comparison against the incumbent.
Target05 / 2021–2026
Particle beams, in patients.
A proton beam stops. Nothing downstream of the target gets dose. Which is exactly why the target has to be where the plan said.
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First-in-man proton radiotherapy for VT
Dusi, Eur J Heart Fail. A single proton session at CNAO Pavia in advanced heart failure. Well tolerated. Near-immediate VT suppression, then a sustained fall in episodes.
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Protons versus photons, on paper
In-silico and dosimetric comparisons, including the Italian CARA-VT cohort, show protons cutting dose to lung, esophagus and healthy myocardium. They also flag interplay with cardiorespiratory motion as the catch. CNAO separately confirms early cardiac safety of carbon ions near the heart.
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First patients in a proton trial
Mayo Clinic (Rochester) announces the first patients treated in its early feasibility study of catheter-free proton cardiac radioablation.
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The proton result
Late-breaker at Heart Rhythm Society, published in Heart Rhythm. 7 patients, mean age 68, single fraction 30 Gy intensity-modulated proton therapy through 2–3 beams. VT events fell 7.24 → 1.52 per patient-month, a 79 % reduction, with no probable or definite treatment-related serious adverse events out to two years.
Delivered expiration-gated, through all phases of the cardiac cycle. Breathing was gated. The beating was not.
Target06 / 2014–2026
The motion thread.
The same story, told through one question: where is the target, right now? Highlighted rows are EBAMed's own steps.
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Motion named as the problem
Ipsen and Blanck, Med Phys: real-time MRI target localisation for cardiac radiosurgery. The first paper to treat cardiac motion as the thing standing between the beam and the substrate.
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Answer one: hold still
Forced breath-hold in the carbon-ion pig work. Dedicated immobilisation studies. Removes breathing. Does nothing about the heartbeat.
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Answer two: irradiate everywhere it goes
Cuculich's free-breathing ITV. Safe and simple. It also means healthy myocardium inside the margin takes the full ablative dose.
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EBAMed
Founded in Geneva
Adriano Garonna, technical director of the TERA Foundation from 2016 to 2018, co-founds EBAMed, External Beam Ablation, with Ugo Amaldi (CERN, founder of TERA and CNAO), Giovanni Leo and Douglas Packer (Mayo Clinic). The thesis: image the heart itself, in real time, and let the beam wait for it. A CHF 1.2 M seed round follows in 2019, then the Mayo Clinic Business Accelerator and a €2.4 M EIC Accelerator grant in 2020.
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Answer three: watch it, but not the heart
Mayinger performs the first MR-guided cardiac radioablation. The implanted defibrillator blanks the heart on cine-MRI, so gating tracks the liver dome instead. A respiratory surrogate, not the target.
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EBAMed
First patient enrolled
Prospective imaging study opens at Policlinico San Matteo, Pavia. Can transthoracic ultrasound see the beating heart well enough, in real VT patients, to steer a proton beam?
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EBAMed
Automatic acquisition and tracking
Front Cardiovasc Med: an automatic ultrasound acquisition system with an AI algorithm, monitoring cardiac motion in real time during radioablation. Paired with a treatment-planning case report showing transthoracic ultrasound guiding proton VT ablation.
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Both motions at once, on a bench
Akdag, Phys Med Biol: first experimental cardiorespiratory motion management for STAR on an MR-linac. The cardiac component gates the beam, the respiratory component drives MLC tracking.
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EBAMed
Demonstrator in the clinic
Prospective cardiac ultrasound imaging study with the demonstrator system (NCT05850741). The tracking hardware and algorithm, on patients, in the room.
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EBAMed
Cardiorespiratory-gated proton delivery
Clin Transl Radiat Oncol: cardiac proton radiotherapy gated on both breathing and heartbeat, using the ultrasound guidance system. The gate opens where diastole meets end-expiration.
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Cardiac-physiology gating, demonstrated
MR-linac gating driven by cardiac physiology rather than an external surrogate. Followed in 2025 by work quantifying how much implanted-device artifact costs on cine-MRI.
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EBAMed
Into the treatment plan
J Appl Clin Med Phys: ultrasound-guided motion management integrated into proton treatment plans for VT radioablation. The gate stops being an add-on and becomes part of the dose calculation. Large-animal gated proton ablation under CardioKit guidance, with Mayo Clinic, runs in parallel.
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Where the gap sits today
The first proton VT trial reports a 79 % reduction in events, delivered expiration-gated, across all cardiac phases. Breathing is solved in the clinic. The heartbeat, on a beam that stops inside the patient, is the open one. That is the gap CardioKit is built for.
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EBAMed
First-in-human
First-in-human trials at clinical partner centers, funded by the 2023 Series A. The full chain, ultrasound tracking, dual gate and proton beam, on patients.
Target07 / Other cardiac targets
Beyond arrhythmia.
Two more indications where the heart itself is the target, and the record is young.
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Cardiac and paracardiac tumors with carbon ions
CNAO reports early cardiac safety of carbon-ion radiotherapy for intra- and paracardiac tumors. A beam that stops inside the patient, on a target that moves with the heart wall.
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Septal reduction in obstructive hypertrophic cardiomyopathy
First reports of stereotactic radiation to the basal septum as a non-invasive alternative to surgical myectomy and alcohol septal ablation. The target sits millimetres from the conduction system. The case for tracking is the same as for VT.
Target08 / Where it stands
What the STAR literature says.
88studies published 2015–2025
7clinical trials in the 2026 pooled analysis
1outpatient session per patient
VT burden falls markedly in patients who had exhausted conventional therapy, and ejection fraction holds: no significant LVEF impairment on meta-analysis.
The population is a very sick one: pooled mortality is 16 % at six months, 33 % at twelve. An EHRA/HRS clinical consensus statement is in place.
ProtectSecond body of evidence
From here the heart is no longer the target. It sits next to one. The record below is what a dose to it costs.
Protect09 / Heart as the organ at risk
What heart dose costs.
Tumors next to the heart. This record put a price on every gray, and made sparing the heart a planning objective in its own right.
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QUANTEC puts numbers on the heart
The QUANTEC review collects dose-volume data for radiation-induced heart disease. Planners get their first consensus constraints for pericarditis and long-term cardiac mortality.
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Breast: 7.4 % per gray
Darby, NEJM. In women irradiated for breast cancer, major coronary events rise linearly with mean heart dose, by 7.4 % per gray. No threshold. The excess begins within the first five years.
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Lung: heart dose predicts survival
Bradley, Lancet Oncology. RTOG 0617 set out to test dose escalation in stage III lung cancer. The higher-dose arm did worse. Heart dose emerged as an independent predictor of overall survival.
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Esophagus: the heart in the field
Reviews of chemoradiation for esophageal cancer find cardiac toxicity, pericardial effusion above all, to be common and dose-related. They call for heart-sparing planning in a tumor that lies against the left atrium.
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Lymphoma: a lifetime of risk
van Nimwegen, J Clin Oncol. In Hodgkin lymphoma survivors, coronary heart disease risk rises with mean heart dose in the same linear way seen in breast cancer. It stays elevated for decades after cure.
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Breath-hold becomes the standard, for those who can
Deep inspiration breath-hold moves the heart down and away from breast and mediastinal fields, and becomes the cardiac-sparing standard. It depends on the patient holding, and holding the same way every time. The heartbeat itself is still covered by margin.
10 / Sources
Every link on this page.
Catheter era
Preclinical: beams in animals
- Lehmann et al., 2016. Cardiac arrhythmia ablation with high-energy heavy ion beams · Sci Rep 6:38895
- Immobilization for carbon ion beam ablation of cardiac structures in a porcine model, 2017
- Catheter-free arrhythmia ablation using scanned proton beams, 2021 · Circ Arrhythm Electrophysiol
- Early impact of proton beam therapy on electrophysiological characteristics in a porcine model, 2022
Photon STAR: clinical
- Cuculich et al., 14 Dec 2017. Noninvasive cardiac radiation for ablation of VT · N Engl J Med 377:2325
- Robinson et al., 2019. ENCORE-VT phase I/II trial · Circulation 139:313
- STOPSTORM.eu consortium, 2023. Standardised platform and European practice survey · Europace 25:1284
- STAR systematic review and meta-analysis of prospective trials, 2024 · Heart Rhythm
- EHRA/HRS clinical consensus statement on STAR: patient selection, substrate delineation, data transfer
- RADIATE-VT (NCT05765175), pivotal randomised trial vs repeat catheter ablation
- STAR vs repeat catheter ablation, 3-year safety and efficacy outcomes · Int J Radiat Oncol Biol Phys
- Shah et al., 2026. STAR for refractory VT: pooled analysis of outcomes and delivery approaches · J Appl Clin Med Phys
- STAR for VT: clinical trials and the emerging role of imaging · J Radiat Res
Particle beams: clinical
- Dusi et al., 2021. First-in-man noninvasive proton radiotherapy for refractory VT · Eur J Heart Fail 23:195
- Mayo Clinic, Oct 2024. First patients treated with proton beam therapy for VT
- Early feasibility study of catheter-free proton cardiac radioablation, 2026 · Heart Rhythm
- HRS 2026 late-breaker, 26 Apr 2026. 79 % reduction in VT episodes, 7 patients
- Comparison of proton and photon therapy in STAR for ventricular tachycardia
- CNAO pilot. Early cardiac safety of carbon-ion radiotherapy for intra- and para-cardiac tumors, 2024
- Robustness evaluation of carbon ion radiotherapy for ventricular tachycardia, 2026
Motion management
- Mayinger et al., 2020. First MRI-guided cardiac radioablation of sustained VT · Radiother Oncol 152:203
- Akdag et al., 2022. First experimental real-time cardiorespiratory motion management for STAR on the MR-linac
- Real-time cardiac physiology-based radiotherapy gating on an MR-linac, 2024
- Impact of cardiac implantable electronic devices on cine-MRI for real-time adaptive cardiac radioablation, 2025 · Med Phys
Heart as the organ at risk
- Gagliardi et al., 2010. QUANTEC: radiation dose-volume effects in the heart · Int J Radiat Oncol Biol Phys
- Darby et al., 2013. Risk of ischemic heart disease in women after radiotherapy for breast cancer · N Engl J Med 368:987
- Bradley et al., 2015. RTOG 0617, standard-dose versus high-dose chemoradiotherapy in stage III NSCLC · Lancet Oncol 16:187
- Beukema et al., 2015. Is cardiac toxicity a relevant issue in the radiation treatment of esophageal cancer? · Cancer
- van Nimwegen et al., 2016. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma · J Clin Oncol 34:235
EBAMed's own studies
- Automatic ultrasonographic acquisition with an AI algorithm for real-time monitoring of cardiac motion during cardiac radio-ablation, 2022 · Front Cardiovasc Med
- Treatment planning study: transthoracic ultrasound guidance to facilitate VT ablation with protons, 2022
- Prospective cardiac ultrasound imaging study with demonstrator (NCT05850741)
- Cardiorespiratory-gated cardiac proton radiotherapy with a novel ultrasound guidance system · Clin Transl Radiat Oncol
- Large-animal study: cardiac-ultrasound guidance for gated proton ablation of VT targets
- Integration of ultrasound-guided motion management into proton therapy treatment plans for VT radioablation, 2025 · J Appl Clin Med Phys
Figures come from the literature above and from EBAMed program milestones. Dates are publication or event dates unless an entry says otherwise. CardioKit is an investigational device. Clinical-benefit claims are subject to ongoing studies and regulatory review.