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

NCT ID: NCT03421834

Last Updated: 2024-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-06
• Study Completion Date: 2024-01-04

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.

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.

Conditions

Ventricular Tachycardia; Ischemic Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prophylactic VT ablation prior to ICD implantation

Group Type: EXPERIMENTAL

Catheter ablation of ventricular tachycardia

Intervention Type: PROCEDURE

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

Optimal medical treatment

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Optimal medical treatment

Intervention Type: DRUG

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

Interventions

Catheter ablation of ventricular tachycardia

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

Intervention Type: PROCEDURE

Optimal medical treatment

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Ischemic cardiomyopathy with reduced ejection fraction (EF ≤ 40%) estimated by cardiac MRI or echocardiography within 30 days before enrollment

2. 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

3. Implantable cardioverter-defibrillator (ICD) indication for primary prevention

4. Patient has provided written informed consent

Exclusion Criteria

1. Age < 18 years or > 85 years

2. Documented sustained ventricular tachycardia before enrollment

3. Class IV New York Heart Association (NYHA) heart failure

4. CTOs not associated with a prior infarction in their territory

5. Acute myocardial infarction (MI) or acute coronary syndrome

6. Subjects with active ischemia that are eligible for revascularization

7. Documented history of MI less than 6 months before enrollment

8. Patients requiring chronic renal dialysis

9. Thrombocytopenia or coagulopathy

10. Pre-existing implantable cardioverter-defibrillator (ICD)

11. Pregnancy or breastfeeding women

12. Acute illness or active systemic infection

13. Life expectancy less than 12 months

14. Unwillingness to participate or lack of availability for follow-up

15. Valvular heart disease or mechanical heart valve precluding access to the left ventricle

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

David Žižek, MD, PhD

Assistant Professor, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matjaz Sinkovec, Prof.

Role: STUDY_CHAIR

University Medical Centre Ljubljana (Slovenia)

Andrej Pernat, Prof.

Role: STUDY_CHAIR

University Medical Centre Ljubljana (Slovenia)

David Zizek, Assist. Prof.

Role: PRINCIPAL_INVESTIGATOR

University Medical Centre Ljubljana (Slovenia)

Locations

Klinički bolnički centar Sestre Milosrdnice

Zagreb, , Croatia

General Hospital Celje

Celje, , Slovenia

General Hospital Izola

Izola, , Slovenia

University Medical Centre Ljubljana - Cardiology department

Ljubljana, , Slovenia

University Medical Centre Ljubljana - Cardiovascular surgery department

Ljubljana, , Slovenia

Countries

Croatia; Slovenia

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Other Identifiers

PREVENTIVE VT

Identifier Type: -

Identifier Source: org_study_id