PREVENTIVE VT: Impact of PREVENTIVE Substrate Ablation of Coronary Chronic Total Occlusion on Implantable cardioVerTer-Defibrillator Interventions

Sponsor

University Medical Centre Ljubljana (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03421834

Collaborator

(none)

Enrollment

Locations

Arms

72.3

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to assess whether preventive substrate ablation of chronic total occlusion infarct-related artery (CTO-IRA) area in heart failure (HF) patients correlates with lower appropriate implantable cardiac defibrillator (ICD) therapies. In addition, the purpose of the study is to determine whether prophylactic substrate ablation at the time of primary ICD implantation in high-risk ischemic patients affects unplanned hospitalization, HF progression, and quality of life.

Condition or Disease	Intervention/Treatment	Phase
Ventricular Tachycardia Ischemic Cardiomyopathy	Procedure: Catheter ablation of ventricular tachycardia Drug: Optimal medical treatment	N/A

Detailed Description

Implantable cardioverter-defibrillators (ICDs) improve survival among patients with ischemic heart failure (HF) who have not previously had a sustained ventricular arrhythmia. However, ICD shocks that terminate ventricular tachycardia (VT) are associated with higher mortality, which may be a reflection of ICD shocks being a marker of more advanced disease versus shocks causing a worse prognosis. In addition, ICD shocks are associated with decreased functional status and quality of life. Antiarrhythmic medications (AAD) reduce ICD shocks but have high rates of side effects and lack of compliance within 1 year of initiation. Some randomized, controlled clinical trials have shown that catheter ablation (CA) of VT can decrease the number of episodes of VT and ICD shocks which could translate to an improvement in patient outcomes.

Regarding the approach to CA of VT, several controversies and gaps of knowledge can be found in the literature. Some authors target predominantly "clinical VTs" (activation and entrainment mapping), while others focus on the substrate causing VTs without focusing on VT morphologies (elimination of local abnormal ventricular activities and late potentials). In addition, data on timing of the CA procedure is inconsistent. However, early CA strategy seems feasible as end-stage cardiovascular disease increases procedural risk and is associated with arrhythmias that may be less amenable to successful treatment with ablation.

The current focus on risk stratifying patients with ischemic cardiomyopathy who could benefit from a primary prevention ICD solely on basis of ejection fraction and NYHA class is far from ideal. In patients with ischemic HF, the presence of the coronary chronic total occlusion (CTO) is related to worse long-term prognosis. Moreover, in a subgroup of ischemic patients, CTO associated with a previous infarction in its territory was an independent predictor of ventricular arrhythmias. Recent studies reported that primary prevention patients with CTO of an infarct-related artery (CTO-IRA) have a very high risk of appropriate ICD therapies due to fast VTs. As post-myocardial infarction scar is a well-recognized substrate of VTs, these patients might benefit from prophylactic substrate ablation at the time of primary ICD implantation.

Eligible and consenting patients on optimal medical HF treatment with confirmed CTO-IRA will be equally randomized to receive either a primary prevention ICD or a CA procedure and an ICD. Catheter ablation with a uniform procedural endpoint and definition of acute procedural success was to be performed before ICD implantation. ICD programming will be standardized for all subjects according to primary prevention settings.

Subjects will be seen at baseline randomization, then 1 month after ICD implantation and every 6 months thereafter until the end of the study. Subjects will be followed up for a minimum of 24 months. Quality of life questionnaires will be done at each visit.

The aim of this study is to assess whether preventive substrate ablation of CTO-IRA area in HF patients correlates with lower appropriate ICD therapies. In addition, the purpose of the study is to determine whether prophylactic substrate ablation at the time of primary ICD implantation in high-risk ischemic patients affects unplanned hospitalization, HF progression, and quality of life.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact of PREVENTIVE Substrate Catheter Ablation on Implantable cardioVerter-defibrillaTor Interventions in Patients With Ischaemic Cardiomyopathy and Infarct-related Coronary Chronic Total Occlusion

Actual Study Start Date :

Feb 6, 2018

Anticipated Primary Completion Date :

Feb 17, 2024

Anticipated Study Completion Date :

Feb 17, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prophylactic VT ablation prior to ICD implantation	Procedure: Catheter ablation of ventricular tachycardia Catheter ablation with a uniform mapping system, procedural endpoint, and definition of acute procedural success. Drug: Optimal medical treatment Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. Antiarrhythmics will be avoided if possible in the ablation group.
Active Comparator: ICD implantation and optimal medical treatment ICD implantation and optimal medical care until at least 2 appropriate ICD shock occurs or an arrhythmic storm and catheter ablation thereafter.	Drug: Optimal medical treatment Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. Antiarrhythmics will be avoided if possible in the ablation group.

Arm

Intervention/Treatment

Experimental: Prophylactic VT ablation prior to ICD implantation

Procedure: Catheter ablation of ventricular tachycardia

Catheter ablation with a uniform mapping system, procedural endpoint, and definition of acute procedural success.

Drug: Optimal medical treatment

Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. Antiarrhythmics will be avoided if possible in the ablation group.

Active Comparator: ICD implantation and optimal medical treatment

ICD implantation and optimal medical care until at least 2 appropriate ICD shock occurs or an arrhythmic storm and catheter ablation thereafter.

Drug: Optimal medical treatment

Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. Antiarrhythmics will be avoided if possible in the ablation group.

Outcome Measures

Primary Outcome Measures

Time to first event comprising appropriate ICD therapy and unplanned hospital admission for symptomatic ventricular tachycardia (VT)/ ventricular fibrillation (VF) [From randomization until official study end or drop-out, patients will be followed and assessed at least 24 months.]
Appropriate ICD therapy defined as shock or ATP therapy.

Secondary Outcome Measures

Time to appropriate ICD therapy [At least 24 months after enrolment]
Appropriate ICD therapy defined as shock or ATP therapy.
Incidence of appropriate ICD therapy [At least 24 months after enrolment]
Time to unplanned hospital admission for symptomatic ventricular tachycardia (VT)/ ventricular fibrillation (VF) [At least 24 months after enrolment]
Time to unplanned cardiac hospital admission [At least 24 months after enrolment]
Time to electrical storm [At least 24 months after enrolment]
Electrical storm defined by 3 or more sustained episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), or appropriate ICD therapy within 24 hours.
Cardio-vascular mortality [At least 24 months after enrolment]
Changes in quality of life using the EQ-5D questionnaire [At least 24 months after enrolment]
EQ-5D is a standardised measure of health status consisting of 2 pages - the EQ-5D descriptive system (descriptive system with 3 levels) and the EQ visual analogue scale ranging from 0 (worst state) to 100 (best state).
Psychometric evaluation of ICD shock-related anxiety using The Florida Shock Anxiety Scale (FSAS) [At least 24 months after enrolment]
Questions were designed to capture patient opinion on perceptions of current health status, as well as a subjective opinion of how the ICD has affected them in specific areas, including anxiety levels. A higher score indicates an positive response and a lower score indicates a negative response.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ischemic cardiomyopathy with reduced ejection fraction (EF ≤ 40%) estimated by cardiac MRI or echocardiography within 30 days before enrollment
Coronary Chronic Total Occlusion (CTO) associated with a previous MI confirmed by coronary angiography and late gadolinium enhancement MRI or myocardial perfusion imaging within 30 days before enrollment
Implantable cardioverter-defibrillator (ICD) indication for primary prevention
Patient has provided written informed consent

Exclusion Criteria:

Age < 18 years or > 85 years
Documented sustained ventricular tachycardia before enrollment
Class IV New York Heart Association (NYHA) heart failure
CTOs not associated with a prior infarction in their territory
Acute myocardial infarction (MI) or acute coronary syndrome
Subjects with active ischemia that are eligible for revascularization
Documented history of MI less than 6 months before enrollment
Patients requiring chronic renal dialysis
Thrombocytopenia or coagulopathy
Pre-existing implantable cardioverter-defibrillator (ICD)
Pregnancy or breastfeeding women
Acute illness or active systemic infection
Life expectancy less than 12 months
Unwillingness to participate or lack of availability for follow-up
Valvular heart disease or mechanical heart valve precluding access to the left ventricle

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Klinički bolnički centar Sestre Milosrdnice	Zagreb	Croatia	HR-10000
2	General Hospital Celje	Celje	Slovenia	3000
3	General Hospital Izola	Izola	Slovenia	6310
4	University Medical Centre Ljubljana - Cardiology department	Ljubljana	Slovenia	1000
5	University Medical Centre Ljubljana - Cardiovascular surgery department	Ljubljana	Slovenia	1000

Sponsors and Collaborators

University Medical Centre Ljubljana

Investigators

Study Chair: Matjaz Sinkovec, Prof., University Medical Centre Ljubljana (Slovenia)
Study Chair: Andrej Pernat, Prof., University Medical Centre Ljubljana (Slovenia)
Principal Investigator: David Zizek, Assist. Prof., University Medical Centre Ljubljana (Slovenia)