Introduction

Recommendations for performing coronary angiography (CAG) in patients admitted after out-of-hospital cardiac arrest (OHCA) are limited to patients presenting with shockable rhythm, cardiogenic shock, or in patients with ST-segment elevation myocardial infarction (STEMI) on electrocardiography (ECG) after a return of spontaneous circulation (ROSC) (Table 1) [1–6]. As the majority of sudden cardiac arrests (CAs) are caused by non-shockable rhythms without underlying acute coronary lesion, they lack a clear indication for CAG [7, 8]. The 2021 update of European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) guidelines describe post-resuscitation care outlining emergent CAG strategy in the context of ST-elevation (STE) prevalence, as well as in patients without STE on the ECG but at a high probability of acute coronary occlusion [4]. The 2020 European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent STE recommend considering delayed, as opposed to immediate, CAG among hemodynamically stable patients without STE who were successfully resuscitated after OHCA [3]. The recommendations are to be altered by ongoing trials focusing on more detailed clinical settings to further define the possible benefit of an early invasive approach.

Etiology of OHCA

The timeline of OHCA management implies a number of pitfalls, and long-term clinical outcomes that are strictly determined by the promptness and quality of the measures undertaken during the initial period after CA. Sudden CA is characterized by a relatively low prevalence among the general population, challenging the development of an accurate individual risk prediction tool. It is particularly difficult among individuals without premonitory symptoms who remain at risk of sudden CAs as their first cardiac event [9–12]. Ischemic heart disease remains a dominant contributor to sudden CAs, albeit cardiomyopathies associated with myocardial fibrosis and left ventricular hypertrophy also significantly increases its prevalence [11]. Moreover, ischemic heart disease is less frequent among younger populations (where genetic structural disorders and cardiac channelopathies, myocarditis, and congenital heart disease are more widespread), but its prevalence increases with age which allows for the atherosclerotic burden to build up [13].

ST-elevation on ECG

Since the OHCA population is so diverse, it is necessary to implement a differential diagnosis as soon as possible after stabilizing the patient’s condition. This allows for the ROSC status to be reached or maintained and the patient’s prognosis to be improved. The simultaneous implementation of various diagnostic elements enables a comprehensive assessment of the patient’s condition and the determination of therapeutic priorities. One of the fastest, widely available, and cost-effective tools is the ECG, which is used in the initial stage of patient management before reaching ROSC. ECG is of additional importance in the context of high positive predictive value of STE for acute coronary lesions causing CA (85–96%), and OHCA being the first manifestation of coronary artery disease (CAD) [14–17]. International guidelines for decades gave strong recommendations on the timely management of patients presenting with STE on post-ROSC ECG. Urgent (≤ 2 h) angiography with primary percutaneous coronary intervention (PCI) was the strategy of choice in this population [1]. As a consequence, for over 12 years (2000 vs. 2012) CAG and PCI were performed more frequently in patients after post-ROSC STEMI of ventricular tachycardia or ventricular fibrillation (VT/VF) of OHCA origin (53.7% vs. 87.2% and 29.7% vs. 77.3%, respectively). Additionally, patient survival to discharge has also improved (59.2% vs. 74.3%) [18, 19] over this period.

Non-ST-elevation myocardial infarction

The potential benefit or harm of urgent CAG in patients without STE is still a subject of debate. A question on the proper selection of patients for early CAG strategy is particularly important. An advantage of CAG in OHCA patients could only be present in the group with significant stenosis in the coronary artery who received PCI for reversing ongoing ischemia [20]. Thus, it is conceivable that the potential benefit of emergency CAG in patients with post-ROSC depends heavily on the presence of significant stenosis in the coronary arteries.

While the observational and registry data suggest improved survival with early CAG [21–24], randomized studies showed no such benefit when comparing emergency CAG with a delayed strategy [8, 25]. This was confirmed by a recent meta-analysis showing no difference in early vs. non-early CAG in terms of mortality, neurological status, and rate of PCI during 30 days among patients with OHCA without STE [26].

The obstructive coronary atherosclerosis and acute thrombotic occlusions in the post-OHCA population are not uncommon but can vary between different subgroups. In the PROCAT registry [16], the reported prevalence of acute CAD was 58%, while in TOMAHAWK randomized trial [25], authors claimed a 40% prevalence of coronary culprit lesions. In the EMERGE trial [8], the latest published randomized study, significant CAD was found only in 49.7% of patients. The highest number of CAD post-OHCA, reaching 65%, was observed in COACT trial [27]; however, patients with non-shockable rhythm were excluded from randomization. Other studies conducted in patients with CA without STE who underwent CAG report approximately 25% acute occlusions and nearly 60% significant obstructive lesions [28]. Despite the high prevalence of CAD in OHCA patients without STE, a high burden of comorbidities, including intracranial bleeding, is present in this population [29, 30], suggesting that the cause of CA in this setting may be due to non-cardiac causes. Additionally, the ECG changes originating from a brain injury can be present and mimic myocardial ischemia (widespread giant T-wave inversions, QT prolongation, bradycardia, STE/ST-depression, increased U wave amplitude) [31, 32]. Therefore, before the final decision to perform CAG, unfavorable features that potentially affect the survival of complicated OHCA patients should be assessed, preferably after consultation by a multidisciplinary team. In this population, the outcomes are driven by neurological complications or multiorgan failure, resulting in a 10-fold higher mortality rate compared to non–CA patients with STE [33]. Faced with numerous features indicating multiorgan and irreversible ischemia, the incremental benefit of restoring coronary perfusion would be marginal and clinically insignificant.

To address some of these controversies, a number of studies were conducted on patients without STE in order to quantify the potential role of CAG and intervention (Table 2) [8, 25, 27, 34–37]. The COACT trial [25] showed no significant difference in clinical outcomes after 1-year follow-up in OHCA patients with a shockable rhythm in the absence of STE treated with both strategies. These results suggested that CAG can be delayed until neurologic recovery. The data from the TOMAHAWK trial [23] point toward the lack of benefit of early CAG in clinical outcomes such as survival, bleeding, stroke, or renal failure. Moreover, the authors noted a slight increase in the composite outcome of death and severe neurologic deficit in the group treated with immediate CAG. Additionally, the most recent randomized clinical trial showed that a strategy of emergency CAG was not better than a strategy of delayed CAG with respect to 180-day survival rate and neurologic sequelae [8]. Immediate CAG may be warranted for a specific subgroup of OHCA patients with no significant comorbidities who are hemodynamically unstable and have an unknown cause of arrest at the time of admission, but who are likely to regain consciousness. These patients were excluded from previous trials, but are still at a high likelihood of having underlying CAD.

The choice to perform emergency CAG post-ROSC should also consider issues related to poor neurological outcome. The clear-cut benefit of immediate CAG in other settings is still a matter of debate. Coronary angiography holds both potential risks and benefits that, could either improve a patient’s condition or result in a greater burden for complications. This would depend on the underlying cause of the OHCA and concomitant medical issues (Table 3). Urgent CAG may increase the risk of bleeding and procedural complications, especially in unstable and neurologically compromised patients after an extensive resuscitation, which can further decline chances of survival. On the other hand, primary revascularization of coronary occlusions increases myocardial viability, securing better cardiovascular and perfusion stability that might be of a paramount importance in patients with severe acute myocardial dysfunction. In cases where coronary revascularization is not feasible, the exclusion of underlying CAD can provide valuable insights into differential diagnosis of complicated OHCA cases and optimal pharmacological management. Some investigators believe that reorganization and facilitation of OHCA management could offer significant clinical benefit. The ongoing ARREST [34] trial assesses the impact of the facilitated organization of OHCA management (direct transfer to CA center) in patients without STE vs. the current standard of care. Notably, a consulting cardiologist should be aware of potential neurological compromise and questionable survival benefit when qualifying to CAG. As reported in the study by Laver et al. [38], regardless of initial rhythm or ECG findings, the main reason for death in patients with OHCA is due to anoxic brain injury and, secondly, due to a refractory post-arrest shock and multi-organ failure. It was also confirmed in the COACT trial [27], which demonstrated that neurological condition was the cause of death in more than 70% of cases.

Treatment algorithm for management of OHCA

While response time and quality of care in the “chain of survival” predominantly affect survival of OHCA patients, an access to certain specific treatments, such as early activation of emergency medical services and resuscitation or advanced post-admission care with a focus on treating the underlying cause of OHCA, improves chances of recovery [39–41]. Upon OHCA patient arrival to a hospital emergency department, rapid and detailed assessment is required to develop a tailored treatment plan to be implemented in the department specializing in intensive management (Central illustration) [28, 42, 43]. Notably, 80% of OHCA patients admitted alive to the hospital are unconscious [44, 45]. Considering the high frequency of CAD as a cause of OHCA, interventional cardiologists are consulted frequently to consider CAG. Although emergency CAG is recommended in post-resuscitation STEMI patients, there is a common belief among physicians about the alleged benefit of CAG in OHCA patients without STE, which is not supported by current evidence.

Central illustration. Proposed algorithm for coronary catheterization. Based on Rab et al. [28], Jentzer et al. [42], and Kelly et al. [43]; I. Exclude non-cardiac reasons for arrest = (acute respiratory failure, non-cardiogenic shock) by surgical management of trauma, neurosurgical or vascular patients, and/or brain and chest computed tomography--scans with subsequent thrombectomy of cerebral arteries, pneumothorax dressing, etc.; ACO — acute coronary occlusion; ALS — advanced life support; CABG — coronary artery bypass grafting; CAD — coronary artery disease; CICU — cardiac intensive care unit; CPR — cardiopulmonary resuscitation; ECG — electrocardiography; ECLS — extracorporal life support; ED — emergency department; ETCO2 — end tidal carbon dioxide; ICU — intensive care unit; LBBB — left bundle branch block; LV — left ventricle; OHCA — out-of-hospital cardiac arrest; PCI — percutaneous coronary intervention; ROSC — return of spontaneous circulation; STE — ST-elevation; TTM — targeted temperature management; VF — ventricular fibrillation; VT — ventricular tachycardia.

Timely introduction of post-ROSC care, including admission to cardiac intensive care unit (CICU) or intensive care unit (ICU), targeted temperature management, vital-organ support, and treatment of the underlying cause of the arrest improves neurological outcomes that are detrimental drivers of survival and quality of life after hospital discharge, with studies reporting the majority of non-survivors dying of neurologic complications after the CA [27, 38, 46–48]. Therefore, any procedures delaying the initiation of post-ROSC management should be accounting for the potential benefit-risk ratio of an individual patient. This, depends on the center’s organization and team leader approach for a specific clinical presentation, that usually takes one of two forms — ordering advanced imaging procedures, and consults from the level of the emergency department, prior to the admission to CICCU/ICU, or timely admission to CICU/ICU, where additional procedures are conducted after a period of initial stabilization of the condition and initiation of post-ROSC care. The clinical condition of the patient and OHCA presentation remains a significant driver for diverse steps of treatment management. Unclear presentation requires the execution of not only general post-ROSC care but also an introduction of differential diagnosis and personalized management. Any concomitant conditions that contributed to OHCA or has complicated its presentation require urgent medical attention and are commonly prioritized in treatment plan development. This includes, but is not limited to, the treatment of reversible arrest causes (acute respiratory failure, non-cardiogenic shock), surgical management of trauma, neurosurgical or vascular patients, coronary angiography and/or brain and chest computed tomography — scans with subsequent thrombectomy of cerebral arteries, pneumothorax dressing, etc. Despite delaying patient admission to the ICU, these procedures can provide vital clinical reserves for stabilizing and subsequently improving a patients’ condition and future outcomes.

Closing remarks

The facilitation and individualization of OHCA management remain a pivotal point of focus to assert improvement of clinical outcomes. With patients facing poor survival and requiring timely neurological- or cardiovascular-oriented management, there is an urgent need for data, especially in patients without STE who could benefit from either immediate or delayed angiography.

Conflict of interest: None declared