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

Not Applicable
Completed
Conditions
Ischemic Cardiomyopathy
Ventricular Tachycardia
Interventions
Procedure: Catheter ablation of ventricular tachycardia
Drug: Optimal medical treatment
Registration Number
NCT03421834
Lead Sponsor
University Medical Centre Ljubljana
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Prophylactic VT ablation prior to ICD implantationCatheter ablation of ventricular tachycardia-
Prophylactic VT ablation prior to ICD implantationOptimal medical treatment-
ICD implantation and optimal medical treatmentOptimal medical treatmentICD implantation and optimal medical care until at least 2 appropriate ICD shock occurs or an arrhythmic storm and catheter ablation thereafter.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Incidence of appropriate ICD therapyAt 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 electrical stormAt 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.

Time to appropriate ICD therapyAt least 24 months after enrolment

Appropriate ICD therapy defined as shock or ATP therapy.

Time to unplanned cardiac hospital admissionAt least 24 months after enrolment
Cardio-vascular mortalityAt least 24 months after enrolment
Changes in quality of life using the EQ-5D questionnaireAt 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.

Trial Locations

Locations (5)

Klinički bolnički centar Sestre Milosrdnice

🇭🇷

Zagreb, Croatia

General Hospital Celje

🇸🇮

Celje, Slovenia

General Hospital Izola

🇸🇮

Izola, Slovenia

University Medical Centre Ljubljana - Cardiovascular surgery department

🇸🇮

Ljubljana, Slovenia

University Medical Centre Ljubljana - Cardiology department

🇸🇮

Ljubljana, Slovenia

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