Clinical trial NCT03421834: Impact of PREVENTIVE Substrate Ablation of Coronary Chronic Total Occlusion on Implantable cardioVerTer-Defibrillator Interventions
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ventricular Tachycardia
Ischemic Cardiomyopathy
Keywords: Ventricular Tachycardia
Ischemic Cardiomyopathy
Primary prevention
Heart Failure
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to first event comprising appropriate ICD therapy and unplanned hospital admission for symptomatic ventricular tachycardia (VT)/ ventricular fibrillation (VF)
timeFrame: From randomization until official study end or drop-out, patients will be followed and assessed at least 24 months.
Secondary outcomes:
measure: Time to appropriate ICD therapy
timeFrame: At least 24 months after enrolment
measure: Incidence of appropriate ICD therapy
timeFrame: At least 24 months after enrolment
measure: Time to unplanned hospital admission for symptomatic ventricular tachycardia (VT)/ ventricular fibrillation (VF)
timeFrame: At least 24 months after enrolment
measure: Time to unplanned cardiac hospital admission
timeFrame: At least 24 months after enrolment
measure: Time to electrical storm
timeFrame: At least 24 months after enrolment
measure: Cardio-vascular mortality
timeFrame: At least 24 months after enrolment
measure: Changes in quality of life using the EQ-5D questionnaire
timeFrame: At least 24 months after enrolment
measure: Psychometric evaluation of ICD shock-related anxiety using The Florida Shock Anxiety Scale (FSAS)
timeFrame: At least 24 months after enrolment
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: Klinički bolnički centar Sestre Milosrdnice
city: Celje
country: Slovenia
facility: General Hospital Celje
city: Izola
country: Slovenia
facility: General Hospital Izola
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana - Cardiology department
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana - Cardiovascular surgery department
Study officials:
affiliation: University Medical Centre Ljubljana (Slovenia)
name: Matjaz Sinkovec, Prof.
role: STUDY_CHAIR
affiliation: University Medical Centre Ljubljana (Slovenia)
name: Andrej Pernat, Prof.
role: STUDY_CHAIR
affiliation: University Medical Centre Ljubljana (Slovenia)
name: David Zizek, Assist. Prof.
role: PRINCIPAL_INVESTIGATOR
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