Infarct-related chronic total coronary occlusion and the risk of ventricular tachyarrhythmic events in out-of-hospital cardiac arrest survivors

The present study is a post hoc analysis of the COACT (Coronary Angiography after Cardiac Arrest) trial, a multicentre randomised controlled trial that was conducted in 19 Dutch hospitals [12, 13]. Patients were included in the period between January 2015 and July 2018. Overall, 552 OHCA patients without ST-segment elevation were included, who were randomly assigned to undergo immediate coronary angiography or coronary angiography after neurological recovery. The COACT trial demonstrated that a strategy of immediate angiography was not superior to a strategy of delayed angiography with respect to survival at 90 days [13]. The 11 centres with the highest enrolment rates were approached, of which 10 centres participated in this study. Our study population included patients who survived their index hospitalisation and displayed coronary artery disease on their coronary angiogram.

In this study, a CTO was defined as a total coronary occlusion in a major epicardial coronary artery with Thrombolysis in Myocardial Infarction (TIMI) 0 flow and an estimated occlusion duration of ≥ 3 months [9]. Previously chronic occluded vessels that were surgically or percutaneous revascularised were not defined as CTO in this study. An IRA-CTO was defined as a CTO associated with a previous myocardial infarction in the territory of the coronary artery. Previous myocardial infarction had to be documented by Q waves on electrocardiography (ECG) and/or evidence of scar on imaging, such as regional wall motion abnormalities on echocardiography or late gadolinium enhancement on cardiac magnetic resonance imaging.

Patients were followed during 1 year after inclusion or until date of death, whichever occurred first. The primary endpoint was defined as the occurrence of a ventricular tachyarrhythmic event (VTE) after hospital discharge. A VTE was defined as appropriate ICD therapy (antitachycardia pacing and/or shock for ventricular tachyarrhythmia), sudden cardiac death (SCD) presumably due to ventricular tachyarrhythmia or documented sustained ventricular tachycardia or ventricular fibrillation during follow-up. Secondary endpoints were all-cause mortality and cardiac mortality.

Continuous variables are presented as mean ± standard deviation or median (interquartile range). Categorical variables are presented as frequencies with percentages. Continuous variables were compared between groups using the Student t-test or the Mann-Whitney U test. Categorical variables were compared using the chi-squared test or the Fisher exact test. The cumulative incidence rate for VTEs was calculated and compared between groups using Kaplan-Meier survival analysis. Time zero was the date of the cardiac arrest. To evaluate whether an IRA-CTO is independently associated with the occurrence of a VTE, multivariable Cox regression analysis was used. IRA-CTO and any variable with a p-value < 0.10 in the univariable analysis were entered in a multivariable regression model. Unless otherwise specified, a significance level of α = 0.05 was used. Statistical analysis was performed using SPSS version 25.0 (IBM Corporation, Armonk, NY, USA).

The presence of a CTO is common in patients with coronary artery disease. In the overall COACT population, thus survivors of OHCA without ST-segment elevation, a CTO was present in 36% in patients who underwent CAG [13]. In the present study, including only patients with coronary artery disease, 49% of patients had a CTO in at least one main vessel. This prevalence is comparable to previously reported prevalence rates of CTO in patients with coronary artery disease [6, 11, 13, 14]. In 71% of patients with a CTO, at least one CTO could be identified as an IRA-CTO based on ECG or cardiac imaging. While there are limited data concerning the prevalence of IRA-CTOs, this percentage is consistent with previous studies in which 56–74% of CTOs were located in an IRA [10, 15]. Several ICD studies have shown that the presence of CTO is an independent predictor for ventricular arrhythmias [6‐11]. However, the study by Raja et al. did not demonstrate this relationship [16]. Recent studies showed that this discrepancy may be explained by the presence of a CTO in an IRA or a non-IRA [9, 10, 17]. There are different pathophysiological mechanisms for the increased risk of VTEs in patients with an IRA-CTO, but the most prevailing theory is that the presence of scar with areas of activation delay is a prerequisite for the induction and maintenance of reentry tachycardias [18, 19]. Furthermore, the myocardium supplied by the CTO is a chronically hibernating myocardium which is associated with proarrhythmic properties despite the presence of a well-developed collateral system [20]. The present study demonstrates that patients with an IRA-CTO have an increased risk of a VTE in the 1st year after the index event. This increased VTE risk seems to be related to a higher proportion of patients with severe LV dysfunction in the IRA-CTO group (i.e. collinearity). Severe LV dysfunction was the only independent factor associated with a higher VTE risk. LV dysfunction is a well-known risk factor for recurrent ventricular arrhythmias in survivors of cardiac arrest [6, 11]. The discrepancy in the prognostic role of a CTO between our study and previous studies may be explained by the relative short follow-up period, smaller sample size and lower proportion of ICD carriers in our study population [6, 10, 11]. Despite these limitations of our study, we can conclude that severe LV dysfunction is a stronger predictor of VTE than the presence of an IRA-CTO.

Observational studies have shown that CTO PCI may be associated with LV reverse remodelling and improvement of various electrocardiographic parameters (e.g. QT dispersion, late potentials) that are associated with ventricular arrhythmias and SCD [4, 21]. Randomised trials, however, only demonstrated improvement in regional LV function and not in global LV function [22, 23]. The number of patients who underwent a CTO PCI in our study population was too small to perform solid statistical analysis. Thus, it is not known whether CTO PCI in the specific subset of OHCA survivors without ST-segment elevation is beneficial.

Finally, the current guidelines recommend not to implant an ICD in OHCA survivors when there is a reversible factor, such as cardiac ischaemia [24]. The majority of our study population underwent revascularisation and only 61% received an ICD. Small increases in troponin levels may present a challenge for clinicians, as it is difficult to determine whether this elevation is due to ventricular tachyarrhythmia and resuscitation or due to ischaemia causing the ventricular tachyarrhythmia. In the first case, an ICD is warranted; in the second case revascularisation seems to be sufficient. Data from the current study are reassuring, as no patient without an ICD died suddenly in the 1st year.

Several limitations of this study should be considered. First, the small sample size, limited number of events and the short follow-up period hamper the power of our study to detect a potentially clinically significant relationship between IRA-CTOs and the occurrence of VTEs. Second, only 61% of the study population received an ICD, which may lead to underestimation of the true incidence of VTEs. However, patients without an ICD were deemed to be at low risk for a VTE by the treating physician. On the other hand, our study population is unique, as prior studies investigating IRA-CTOs as a potential risk factor for VTEs were limited to an ICD population [6‐11].