Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.
Action Potentials
Aged
Aged, 80 and over
Anti-Arrhythmia Agents
/ therapeutic use
Electrophysiologic Techniques, Cardiac
Female
Heart Ventricles
/ physiopathology
Humans
Male
Middle Aged
Missouri
Predictive Value of Tests
Prospective Studies
Quality of Life
Radiofrequency Ablation
/ adverse effects
Radiosurgery
/ adverse effects
Recurrence
Risk Factors
Surveys and Questionnaires
Tachycardia, Ventricular
/ diagnosis
Time Factors
Treatment Outcome
Ventricular Premature Complexes
/ diagnosis
noninvasive
stereotactic radiotherapy
ventricular tachycardia
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
pubmed:
28
12
2018
medline:
29
10
2019
entrez:
28
12
2018
Statut:
ppublish
Résumé
Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.
Sections du résumé
BACKGROUND
Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking.
METHODS
We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire.
RESULTS
Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months.
CONCLUSIONS
Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.
Identifiants
pubmed: 30586734
doi: 10.1161/CIRCULATIONAHA.118.038261
pmc: PMC6331281
mid: NIHMS1510552
doi:
Substances chimiques
Anti-Arrhythmia Agents
0
Banques de données
ClinicalTrials.gov
['NCT02919618']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
313-321Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL033343
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Références
J Am Coll Cardiol. 2017 Dec 12;70(23):2924-2941
pubmed: 29216988
Sci Rep. 2016 Dec 20;6:38895
pubmed: 27996023
J Thorac Dis. 2018 Apr;10(4):2346-2356
pubmed: 29850140
Heart Rhythm. 2018 May;15(5):734-740
pubmed: 29277687
Heart Rhythm. 2010 Jun;7(6):802-10
pubmed: 20156591
Comput Biol Med. 2018 Nov 1;102:376-380
pubmed: 30126615
Pacing Clin Electrophysiol. 2016 Aug;39(8):781-91
pubmed: 27197804
J Am Coll Cardiol. 2017 May 2;69(17):2105-2115
pubmed: 28449770
J Am Coll Cardiol. 2011 Oct 25;58(18):1893-902
pubmed: 22018301
J Am Heart Assoc. 2017 Oct 27;6(11):
pubmed: 29079566
Front Cardiovasc Med. 2018 Jul 09;5:83
pubmed: 30038908
J Thorac Oncol. 2018 Nov;13(11):1727-1732
pubmed: 30056162
Radiother Oncol. 2018 Aug;128(2):189-191
pubmed: 29753550
N Engl J Med. 2016 Jul 14;375(2):111-21
pubmed: 27149033
Heart Rhythm. 2015 Sep;12(9):1997-2007
pubmed: 26031376
N Engl J Med. 2017 Dec 14;377(24):2325-2336
pubmed: 29236642
CA Cancer J Clin. 2016 Jul;66(4):309-25
pubmed: 26919165
Circulation. 2008 Dec 16;118(25):2773-82
pubmed: 19064682
Sci Transl Med. 2011 Aug 31;3(98):98ra84
pubmed: 21885406
Nat Med. 2004 Apr;10(4):422-8
pubmed: 15034569
Med Phys. 2010 Aug;37(8):4078-101
pubmed: 20879569
Circ Arrhythm Electrophysiol. 2015 Jun;8(3):748-50
pubmed: 26082532
Circulation. 2018 Sep 25;138(13):e272-e391
pubmed: 29084731