Author + information
- Pier D. Lambiase, MD, PhD∗ ()
- Institute of Cardiovascular Science, University College London & Barts Heart Centre, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Pier D. Lambiase, Institute of Cardiovascular Science, UCL & Barts Heart Centre, Cardiology Department, St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, United Kingdom.
- advanced cardiac life support
- cardiopulmonary resuscitation
- coronary artery disease
- out-of-hospital cardiac arrest
- percutaneous coronary intervention
Out-of-hospital cardiac arrest affects 235,000 to 325,000 people in the United States and 275,000 in Europe each year. However, the survival rate after out-of-hospital cardiac arrest, especially without neurological impairment, remains low (1–4). Every minute without cardiopulmonary resuscitation (CPR) and defibrillation reduces the chances of survival by 7% to 10%. Isovolumic left ventricular developed pressure falls by more than 50% within 30 s of the onset of total global ischemia, reaching zero by 5 min, necessitating effective defibrillation to be delivered within 5 min to significantly affect outcomes (5). To address this scenario, the American Heart Association recommended a “chain of survival” concept, consisting of the following 5 links: 1) early access to emergency medical care; 2) early CPR; 3) early defibrillation; 4) early advanced cardiac life support; and 5) expert post-resuscitation medical care (3). These links must be seamless, but there is huge variation in delivery. The emergence of public access automatic defibrillators (PADs) has made a significant impact on the first 3 links in the chain.
A recent study in Japan found that the proportion of PADs in use significantly increased from 0.0% in 2005 to 41.2% in 2011 at railway stations and from 0.0% to 56.5% at sports facilities (6). Mean time from collapse to shock was 5 min among those who received shocks with PADs. Twenty-eight percent had a favorable neurological outcome at railway stations, 51.6% at sports facilities, 23.3% in public buildings, and 41.9% in schools. In multivariate analysis, early defibrillation, irrespective of bystander or emergency medical service (EMS) personnel, was significantly associated with good functional outcome (adjusted odds ratio for 1-min increment: 0.89).
Rapid use of PADs could therefore have a major clinical and socioeconomic impact on out-of-hospital cardiac arrest outcomes before one engages the more sophisticated and resource-intensive processes required in the fifth link. This topic is the subject of the article by Yannopoulos et al. (7) in this issue of the Journal. The early resuscitation approach requires not only deployment of PAD universally in public areas and easy accessibility but training the general public in basic CPR and PAD use to ensure immediate shock deployment. Numerous strategies are being explored, including use of smart phone apps to localize PADs and even drones to deliver them more immediately (8). However, 80% of cardiac arrests occur at home in lone individuals, meaning that “wearables” and smart clothing to monitor physiology (e.g., Fitbit watches [Fitbit, Inc., San Francisco, California]) have the potential to issue an emergency call in the event of cardiac arrest. This scenario demands highly reliable detection of hemodynamically compromising arrhythmias with technology to verify hemodynamic collapse (positional information, tissue perfusion) and wearer interaction to prevent devices “crying wolf” and overwhelming emergency services.
Yannopoulos et al. (7) have concentrated on the fifth link in the chain: the rare but potentially reversible scenario of refractory ventricular fibrillation (VF), occurring in 0.9% of all cardiac arrests (9). The study required impressive engagement of EMS and specialized cardiac and intensive care unit teams to ensure a highly choreographed delivery of continuous external automated mechanical CPR, extracorporeal life support (ECLS), and coronary intervention achieving phenomenal 6-min door-to-ECLS-initiation and 12-min door-to-balloon times. The investigators and medical teams involved are to be applauded for this unprecedented achievement. The strategy resulted in 42% of patients leaving the hospital with a high level of neurological function versus 15.3% of historical control subjects. These outcomes compare favorably with the SAVE-J (Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan) and CHEER (Mechanical CPR, Hypothermia, ECMO and Early Reperfusion) trials, with 29% and 45% survival to hospital discharge, respectively—these trials also used ECLS and coronary intervention in resistant ventricular tachycardia/VF (10,11). To put these figures in context, a Japanese study focusing on return of spontaneous circulation (ROSC)-triaged cases transferred to tertiary centers for therapeutic hypothermia and coronary intervention only achieved a 1-month neurologically intact survival of 3.0% versus 0.5% in historical control subjects, highlighting the potential benefit of very early coronary intervention (12).
A number of caveats to the study by Yannopoulos et al. (7) should be pointed out. As an observational study, there are confounding biases of subject selection and comparison with historical control subjects in whom inclusion criteria promoting greater probability of survival could not have been as strictly applied. However, it is interesting to note that in this historical control group, ROSC on arrival was more than 4 times as common (approximately 38% vs. 9% [Figure 3 in Yannopoulos et al.]), indicating that these patients were in a better condition and yet had worse survival. Important critical differences were lack of ECLS and coronary intervention, although the patients were not matched for burden of coronary disease, comorbidities, and baseline ejection fraction. Furthermore, key significant determinants of survival in the treated group were only a 3-min difference in first response arrival (4.1 min vs. 7.1 min), again highlighting the time criticality of effective CPR. The presence of intermittent ROSC before arrival and the presence of coronary artery disease as survival predictors identify the prevalence and importance of a treatable, reversible cause, with 84% receiving percutaneous coronary intervention (PCI).
A significant source of complications was ECLS: 13% of patients had vascular complications, including retroperitoneal bleeding and leg ischemia (7). This finding is in line with the most recent meta-analysis of extracorporeal membrane oxygen: 27% major bleeding, 8% thromboembolic events–limb ischemia, circuit-related clotting, and stroke (13). Optimization of circulatory support requires new approaches to avoid full anticoagulation (e.g., antithrombotic circuit materials) and cannula redesign to prevent vascular complications.
Despite >40 years of work in the field of cardioprotection, only the re-establishment of perfusion has been shown to significantly influence survival in acute coronary occlusion (14). Indeed, during the first few minutes of refractory VF, profound ischemia-induced electrophysiological changes occur that can only be corrected by reperfusion. No drugs to date improve reversion rates, and amiodarone (our most effective antiarrhythmic agent) is suboptimal in this circumstance. This is especially important in the >80% of this study in whom ischemia will persist without PCI, despite CPR. Pharmacological pre-conditioning agents to reduce infarct size have not reached the burden of proof to enter clinical practice and have to be delivered before the initiation of infarction to enable protection, and thus are not applicable to reperfusion. This situation has led to post-conditioning (interruption of reperfusion with short periods of ischemia) or remote post-conditioning (e.g., using limb ischemia with a blood pressure cuff as the stimulus) strategies to diminish the effects of metabolic and ionic changes and activate myocyte survival pathways believed to operate mainly by inhibiting the opening of the mitochondrial permeability pore. However, the recent ERICCA (Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery) randomized controlled trial using remote pre-conditioning in cardiac surgery failed to show any benefit in a combined primary endpoint of major adverse cardiac and cerebral events within 12 months (15). Remote post-conditioning is currently being evaluated in ST-segment elevation myocardial infarction cases (RIC-STEMI [Remote Ischemic Conditioning in ST-elevation Myocardial Infarction as Adjuvant to Primary Angioplasty; NCT02313961]) and primary PCI (Remote Ischemic Preconditioning in Primary PCI [NCT00435266], unreported, despite completion in 2009, on ClinicalTrials.gov).
Although Yannopoulos et al. (7) are to be congratulated, from a practical perspective, the greatest gains will currently be from investment in ensuring immediate CPR and defibrillation in <5 min for the >0.5 million cardiac arrests per annum in Europe and the United States, where the numbers saved will be the greatest (approximately 50,000 vs. 450 lives with ECLS and PCI for refractory VF, assuming only 20% are witnessed). Inevitably, as immediate resuscitation improves, demand for optimizing the fifth link will increase, but the current priority should be links 1 to 3. Our challenge is to ensure that every dollar is spent to save the maximum number of lives when literally every minute counts.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Lambiase has received research grants and speaker fees from Medtronic and Boston Scientific; educational grants from Abbott; and is supported by UCLH Biomedicine NIHR.
- 2017 American College of Cardiology Foundation
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