Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Research in Cardiology
Published in: Clinical Research in Cardiology 11/2020

Open Access 01-11-2020 | Cardiac Arrhythmia | Trial Design

Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA)

Authors: Oliver Blanck, Daniel Buergy, Maren Vens, Lina Eidinger, Adrian Zaman, David Krug, Boris Rudic, Judit Boda-Heggemann, Frank A. Giordano, Leif-Hendrik Boldt, Felix Mehrhof, Volker Budach, Achim Schweikard, Denise Olbrich, Inke R. König, Frank-Andre Siebert, Reinhard Vonthein, Jürgen Dunst, Hendrik Bonnemeier

Published in: Clinical Research in Cardiology | Issue 11/2020

Login to get access

Abstract

Background

Single-session high-dose stereotactic radiotherapy (radiosurgery) is a new treatment option for otherwise untreatable patients suffering from refractory ventricular tachycardia (VT). In the initial single-center case studies and feasibility trials, cardiac radiosurgery has led to significant reductions of VT burden with limited toxicities. However, the full safety profile remains largely unknown.

Methods/design

In this multi-center, multi-platform clinical feasibility trial which we plan is to assess the initial safety profile of radiosurgery for ventricular tachycardia (RAVENTA). High-precision image-guided single-session radiosurgery with 25 Gy will be delivered to the VT substrate determined by high-definition endocardial electrophysiological mapping. The primary endpoint is safety in terms of successful dose delivery without severe treatment-related side effects in the first 30 days after radiosurgery. Secondary endpoints are the assessment of VT burden, reduction of implantable cardioverter defibrillator (ICD) interventions [shock, anti-tachycardia pacing (ATP)], mid-term side effects and quality-of-life (QoL) in the first year after radiosurgery. The planned sample size is 20 patients with the goal of demonstrating safety and feasibility of cardiac radiosurgery in ≥ 70% of the patients. Quality assurance is provided by initial contouring and planning benchmark studies, joint multi-center treatment decisions, sequential patient safety evaluations, interim analyses, independent monitoring, and a dedicated data and safety monitoring board.

Discussion

RAVENTA will be the first study to provide the initial robust multi-center multi-platform prospective data on the therapeutic value of cardiac radiosurgery for ventricular tachycardia.

Trial registration number

NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. The study was initiated on November 18th, 2019, and is currently recruiting patients.

Graphic abstract

Literature
1.
Shivkumar K (2019) Catheter ablation of ventricular arrhythmias. N Engl J Med 380:1555–1564PubMed
2.
Al-Khatib SM, Stevenson WG, Ackerman MJ et al (2018) 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 15(10):e190–e252PubMed
3.
Dukkipati SR, Koruth JS, Choudry S et al (2017) Catheter ablation of ventricular tachycardia in structural heart disease: indications, strategies, and outcomes—part II. J Am Coll Cardiol 70(23):2924–2941PubMed
4.
Sapp JL, Wells GA, Parkash R et al (2016) Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med 375(2):111–121PubMed
5.
Tokuda M, Kojodjojo P, Tung S et al (2013) Acute failure of catheter ablation for ventricular tachycardia due to structural heart disease: causes and significance. J Am Heart Assoc 2(3):e000072PubMedCentralPubMed
6.
Santangeli P, Frankel DS, Tung R et al (2017) Early mortality after catheter ablation of ventricular tachycardia in patients with structural heart disease. J Am Coll Cardiol 69(17):2105–2115PubMed
7.
Gianni C, Mohanty S, Trivedi C et al (2017) Alternative approaches for ablation of resistant ventricular tachycardia. Card Electrophysiol Clin 9(1):93–98PubMed
8.
Rauschenberg R, Bruns J, Brütting J et al (2019) Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases. Eur J Cancer 110:11–20PubMed
9.
Wagner F, Gandalini M, Hakim A et al (2018) Radiosurgery of vestibular schwannoma: prognostic factors for hearing outcome using 3D-constructive interference in steady state (3D-CISS). Strahlenther Onkol 194(12):1132–1143PubMed
10.
Koca S, Distel L, Lubgan D et al (2019) Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia-a prospective observational study. Strahlenther Onkol 195(8):745–755PubMed
11.
Timmerman RD, Paulus R, Pass HI et al (2018) Stereotactic body radiation therapy for operable early-stage lung cancer: findings from the NRG Oncology RTOG 0618 trial. JAMA Oncol 4(9):1263–1266PubMedCentralPubMed
12.
Gkika E, Bettinger D, Krafft L et al (2018) The role of albumin-bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy. Strahlenther Onkol 194(5):403–413PubMed
13.
Widmark A, Gunnlaugsson A, Beckman L et al (2019) Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 394:385–395PubMed
14.
Rieber J, Streblow J, Uhlmann L et al (2016) Stereotactic body radiotherapy (SBRT) for lung metastases—a pooled analysis of the German working group “stereotactic radiotherapy”. Lung Cancer 97:51–58PubMed
15.
Andratschke N, Alheid H, Allgäuer M et al (2018) The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases. BMC Cancer 18:283PubMedCentralPubMed
16.
Palma DA, Olson RA, Harrow S et al (2018) Stereotactic ablative radiation therapy for the comprehensive treatment of oligometastatic tumors (SABR-COMET): results of a randomized trial. Int J Radiat Oncol Biol Phys 102(S3):S3–S4
17.
Pankratov M, Benetti F, Vivian J (2003) Method for non-invasive heart treatment. US Patent US6889695B2
18.
Sharma A, Wong D, Weidlich G et al (2010) Noninvasive stereotactic radiosurgery (CyberHeart) for creation of ablation lesions in the atrium. Heart Rhythm 7:802–810PubMed
19.
Loo BW Jr, Soltys SG, Wang L et al (2015) Stereotactic ablative radiotherapy for the treatment of refractory cardiac ventricular arrhythmia. Circ Arrhythm Electrophysiol 8(3):748–750PubMed
20.
Monroy E, Azpiri J, De La Pena C et al (2016) Late gadolinium enhancement cardiac magnetic resonance imaging post-robotic radiosurgical pulmonary vein isolation (RRPVI): first case in the world. Cureus 8(8):e738PubMedCentralPubMed
21.
22.
Robinson CG, Samson PP, Moore KMS et al (2019) Phase I/II trial of electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia. Circulation 139(3):313–321PubMedCentralPubMed
23.
Knutson NC, Samson P, Hugo G et al (2019) Radiotherapy workflow and dosimetric analysis from a phase I/II trial of noninvasive cardiac radioablation for ventricular tachycardia. Int J Radiat Oncol Biol Phys 104(5):1114–1123PubMed
24.
Cuculich PS, Schill MR, Kashani R et al (2017) Noninvasive cardiac radiation for ablation of ventricular tachycardia. N Engl J Med 377(24):2325–2336PubMedCentralPubMed
25.
Neuwirth R, Cvek J, Knybel L et al (2019) Stereotactic radiosurgery for ablation of ventricular tachycardia. Europace 21:1088–1095PubMed
26.
Cvek J, Neuwirth R, Knybel L et al (2014) Cardiac radiosurgery for malignant ventricular tachycardia. Cureus 6(7):e190
27.
Jumeau R, Ozsahin M, Schwitter J et al (2018) Rescue procedure for an electrical storm using robotic non-invasive cardiac radio-ablation. Radiother Oncol 128(2):189–191PubMed
28.
Haskova J, Peichl P, Pirk J et al (2018) Stereotactic radiosurgery as a treatment for recurrent ventricular tachycardia associated with cardiac fibroma. Heart Rhythm Case Rep 5(1):44–47
29.
Zeng LJ, Huang LH, Tan H et al (2019) Stereotactic body radiation therapy for refractory ventricular tachycardia secondary to cardiac lipoma: a case report. Pacing Clin Electrophysiol. 42:1276–1279PubMed
30.
Scholz EP, Seidensaal K, Naumann P et al (2019) Risen from the dead: cardiac stereotactic ablative radiotherapy as last rescue in a patient with refractory ventricular fibrillation storm. Heart Rhythm Case Rep 5(6):329–332
31.
Krug D, Blanck O, Demming T et al (2020) Stereotactic body radiotherapy for ventricular tachycardia (cardiac radiosurgery): first-in-patient treatment in Germany. Strahlenther Onkol 196(1):23–30PubMed
32.
Maguire PJ, Gardner E, Jack AB et al (2011) Cardiac radiosurgery (CyberHeart) for treatment of arrhythmia: physiologic and histopathologic correlation in the porcine model. Cureus 3(8):e32
33.
Gardner EA, Sumanaweera TS, Blanck O et al (2012) In vivo dose measurement using TLDs and MOSFET dosimeters for cardiac radiosurgery. J Appl Clin Med Phys 13(3):3745PubMed
34.
Blanck O, Bode F, Gebhard M et al (2014) Dose-escalation study for cardiac radiosurgery in a porcine model. Int J Radiat Oncol Biol Phys 89(3):590–598PubMed
35.
Lehmann HI, Richter D, Prokesch H et al (2015) Atrioventricular node ablation in Langendorff-perfused porcine hearts using carbon ion particle therapy: methods and an in vivo feasibility investigation for catheter-free ablation of cardiac arrhythmias. Circ Arrhythm Electrophysiol 8(2):429–438PubMed
36.
Bode F, Blanck O, Gebhard M et al (2015) Pulmonary vein isolation by radiosurgery: implications for non-invasive treatment of atrial fibrillation. Europace 17(12):1868–1874PubMed
37.
Zei PC, Wong D, Gardner E et al (2018) Safety and efficacy of stereotactic radioablation targeting pulmonary vein tissues in an experimental model. Heart Rhythm 15(9):1420–1427PubMed
38.
Hohmann S, Deisher AJ, Suzuki A et al (2019) Left ventricular function after noninvasive cardiac ablation using proton beam therapy in a porcine model. Heart Rhythm 16:1710–1719PubMed
39.
Rapp F, Simoniello P, Wiedemann J et al (2019) Biological cardiac tissue effects of high-energy heavy ions—investigation for myocardial ablation. Sci Rep 9(1):5000PubMedCentralPubMed
40.
Ernst F, Bruder R, Schlaefer A et al (2011) Forecasting pulsatory motion for non-invasive cardiac radiosurgery: an analysis of algorithms from respiratory motion prediction. Int J Comput Assist Radiol Surg 6(1):93–101PubMed
41.
Ipsen S, Blanck O, Oborn B et al (2014) Radiotherapy beyond cancer: target localization in real-time MRI and treatment planning for cardiac radiosurgery. Med Phys 41(12):120702PubMed
42.
Constantinescu A, Lehmann HI, Packer DL et al (2016) Treatment planning studies in patient data with scanned carbon ion beams for catheter-free ablation of atrial fibrillation. J Cardiovasc Electrophysiol 27(3):335–344PubMed
43.
Wang L, Fahimian B, Soltys SG et al (2016) Stereotactic arrhythmia radioablation (STAR) of ventricular tachycardia: a treatment planning study. Cureus 8(7):e694PubMedCentralPubMed
44.
Xia P, Kotecha R, Sharma N et al (2016) A treatment planning study of stereotactic body radiotherapy for atrial fibrillation. Cureus 8(7):e678PubMedCentralPubMed
45.
Blanck O, Ipsen S, Chan MK et al (2016) Treatment planning considerations for robotic guided cardiac radiosurgery for atrial fibrillation. Cureus 8(7):e705PubMedCentralPubMed
46.
Gardner EA, Weidlich GA (2016) Analysis of dose distribution in the heart for radiosurgical ablation of atrial fibrillation. Cureus 8(7):e703PubMedCentralPubMed
47.
Bahig H, de Guise J, Vu T et al (2016) Analysis of pulmonary vein antrums motion with cardiac contraction using dual-source computed tomography. Cureus 8(7):e712PubMedCentralPubMed
48.
Ipsen S, Blanck O, Lowther NJ et al (2016) Towards real-time MRI-guided 3D localization of deforming targets for non-invasive cardiac radiosurgery. Phys Med Biol 61(22):7848–7863PubMed
49.
Lowther N, Ipsen S, Marsh S et al (2018) Investigation of the XCAT phantom as a validation tool in cardiac MRI tracking algorithms. Phys Med 45:44–51PubMed
50.
John RM, Shinohara ET, Price M et al (2018) Radiotherapy for ablation of ventricular tachycardia: assessing collateral dosing. Comput Biol Med 102:376–380PubMed
51.
Lydiard S, Caillet V, Ipsen S et al (2018) Investigating multi-leaf collimator tracking in stereotactic arrhythmic radioablation (STAR) treatments for atrial fibrillation. Phys Med Biol 63(19):195008PubMed
52.
Weidlich GA, Hacker F, Bellezza D et al (2018) Ventricular tachycardia: a treatment comparison study of the cyberknife with conventional linear accelerators. Cureus 10(10):e3445PubMedCentralPubMed
53.
Teo BK, Dieterich S, Blanck O et al (2009) Effect of cardiac motion on the cyberknife synchrony tracking system for radiosurgical cardiac ablation. Med Phys 36(6):2653
54.
Sullivan RM, Mazur A (2010) Stereotactic robotic radiosurgery (CyberHeart): a cyber revolution in cardiac ablation? Heart Rhythm 7(6):811–812PubMed
55.
Bert C, Engenhart-Cabillic R, Durante M (2012) Particle therapy for noncancer diseases. Med Phys 39(4):1716–1727PubMed
56.
Bhatt N, Turakhia M, Fogarty TJ (2016) Cost-effectiveness of cardiac radiosurgery for atrial fibrillation: implications for reducing health care morbidity, utilization, and costs. Cureus 8(8):e720PubMedCentralPubMed
57.
Zei PC, Soltys S (2017) Ablative radiotherapy as a noninvasive alternative to catheter ablation for cardiac arrhythmias. Curr Cardiol Rep 19(9):79PubMedCentralPubMed
58.
Kim EJ, Davogustto G, Stevenson WG et al (2018) Non-invasive cardiac radiation for ablation of ventricular tachycardia: a new therapeutic paradigm in electrophysiology. Arrhythm Electrophysiol Rev 7(1):8–10PubMedCentralPubMed
59.
Graeff C, Bert C (2018) Noninvasive cardiac arrhythmia ablation with particle beams. Med Phys 45(11):e1024–e1035PubMed
60.
Refaat MM, Zakka P, Youssef B et al (2019) Noninvasive cardioablation. Card Electrophysiol Clin 11(3):481–485PubMed
61.
Ector J, De Buck S, Loeckx D et al (2008) Changes in left atrial anatomy due to respiration: impact on three-dimensional image integration during atrial fibrillation ablation. J Cardiovasc Electrophysiol 19(8):828–834PubMed
62.
Keall PJ, Mageras GS, Balter JM et al (2006) The management of respiratory motion in radiation oncology report of AAPM Task Group 76. Med Phys 33(10):3874–3900PubMed
63.
Ipsen S, Bruder R, O'Brien R, Keall PJ, Schweikard A, Poulsen PR (2016) Online 4D ultrasound guidance for real-time motion compensation by MLC tracking. Med Phys 43(10):5695PubMed
64.
Boda-Heggemann J, Knopf AC, Simeonova-Chergou A et al (2016) Deep inspiration breath hold-based radiation therapy: a clinical review. Int J Radiat Oncol Biol Phys 94(3):478–492PubMed
65.
Sihono DS, Vogel L, Weiß C et al (2017) A 4D ultrasound real-time tracking system for external beam radiotherapy of upper abdominal lesions under breath-hold. Strahlenther Onkol 193(3):213–220PubMed
66.
Moustakis C, Blanck O, Ebrahimi Tazehmahalleh F et al (2017) Planning benchmark study for SBRT of early stage NSCLC: results of the DEGRO Working Group Stereotactic Radiotherapy. Strahlenther Onkol 193(10):780–790PubMed
67.
Moustakis C, Chan MKH, Kim J et al (2018) Treatment planning for spinal radiosurgery: a competitive multiplatform benchmark challenge. Strahlenther Onkol 194(9):843–854PubMed
68.
Boda-Heggemann J, Jahnke A, Chan MKH et al (2019) In-vivo treatment accuracy analysis of active motion-compensated liver SBRT through registration of plan dose to post-therapeutic MRI-morphologic alterations. Radiother Oncol 134:158–165PubMed
69.
Seuntjens J, Lartigau EF, Cora S et al (2014) ICRU report 91. Prescribing, recording, and reporting of stereotactic treatments with small photon beams. J ICRU 14(2):1–160
70.
Wilke L, Andratschke N, Blanck O et al (2019) ICRU report 91 on prescribing, recording, and reporting of stereotactic treatments with small photon beams: statement from the DEGRO/DGMP working group stereotactic radiotherapy and radiosurgery. Strahlenther Onkol 195(3):193–198PubMed
71.
Grimm J, LaCouture T, Croce R et al (2011) Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J Appl Clin Med Phys 12(2):3368PubMed
72.
Gauter-Fleckenstein B, Israel CW, Dorenkamp M et al (2015) DEGRO/DGK guideline for radiotherapy in patients with cardiac implantable electronic devices. Strahlenther Onkol 191(5):393–404PubMed
73.
Steger F, Hautmann MG, Süß C et al (2019) Radiotherapy of patients with cardiac implantable electronic devices according to the DEGRO/DGK guideline-is the risk of relevant errors overestimated? Strahlenther Onkol 195:1086–1093PubMed
74.
Fowler JF, Welsh JS, Howard SP (2004) Loss of biological effect in prolonged fraction delivery. Int J Radiat Oncol Biol Phys 59(1):242–249PubMed
75.
Di Biase L, Burkhardt JD, Lakkireddy D et al (2015) Ablation of stable VTs versus substrate ablation in ischemic cardiomyopathy: the VISTA randomized multicenter trial. J Am Coll Cardiol 66(25):2872–2882PubMed
Metadata
Title
Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA)
Authors
Oliver Blanck
Daniel Buergy
Maren Vens
Lina Eidinger
Adrian Zaman
David Krug
Boris Rudic
Judit Boda-Heggemann
Frank A. Giordano
Leif-Hendrik Boldt
Felix Mehrhof
Volker Budach
Achim Schweikard
Denise Olbrich
Inke R. König
Frank-Andre Siebert
Reinhard Vonthein
Jürgen Dunst
Hendrik Bonnemeier
Publication date
01-11-2020
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 11/2020
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-020-01650-9

Other articles of this Issue 11/2020

Clinical Research in Cardiology 11/2020 Go to the issue

Original Paper

Optimizing diastolic pressure gradient assessment

Letter to the Editors

Successful endovascular treatment of multiple systemic aneurysms in a patient with vascular Ehlers–Danlos syndrome

Original Paper

Recurrent infective endocarditis versus first-time infective endocarditis after heart valve surgery

Original Paper

Left atrial appendage closure in patients with a reduced left ventricular ejection fraction: results from the multicenter German LAARGE registry

Original Paper

Iron deficiency is a common disorder in general population and independently predicts all-cause mortality: results from the Gutenberg Health Study

Letter to the Editors

Renal AA amyloidosis leading to early diagnosis and treatment of takayasu arteritis: a case report and review of the literature

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits