Reperfusion delay in patients with high-risk ST-segment elevation myocardial infarction: every minute counts, much more than suspected

This editorial refers to ‘Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial’†, by K.H. Scholz et al., on page 1065. Study director Karl H. Scholz, corresponding author Thomas Meyer, and their co-authors are publishing very important findings on the impact of treatment delays on mortality in ST-segement elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI) in the environment of a fully developed Emergency Medical Service (EMS).1 The data have been collected in the context of the ongoing FITT-STEMI trial (NCT 00794001) in Germany, a prospective, observational, registry-based study involving a consortium of nearly 50 hospital systems committing to enrol prospectively all STEMI patients presenting within <24 h after onset of symptoms. The study started in October 2007 and is planned to continue until December 2021 after enrolment of 50 000+ patients. Key strategies for reducing door to balloon (D2B) time2 and standard quality indicators3 were endorsed by all participating hospitals. Phase I evaluates whether formal data collection and regular feedback can improve first medical contact (FMC) to PCI treatment delays. Phase II investigates whether survival can be improved by behavioural changes triggered by quarterly feedback data analysis with cardiology, emergency department, and EMS staff. Outcome measures are the contact to balloon (C2B) time and mortality at various time intervals up to 1 year (NCT 00794001). As many as 12 675 patients with treatment delays of <360 min were included in the present analysis, out of all 20 130 patients presenting within 24 h. The main reasons for exclusion were as follows: interhospital transfer from a non-PCI centre (n = 3.025), self-transportation (n = 2.077), and STEMI during hospital admission (n = 483). All patients with the following conditions were included: pre-hospital resuscitation for out of hospital cardiac arrest (OHCA = 9.5%), cardiogenic shock (CS = 5.5%), and fibrinolysis (1.1%). Patients with brain damage were included, and global in-hospital mortality was 8%. The external validity of the findings was verified with the use of independent surveys from insurance reimbursement files and German hospital quality reports. Of note, this investigator group serves a population of 10 million (12% of the population of Germany), with currently 5.500 STEMI cases per year, consistent with the global incidence of hospital-treated STEMI cases in the entire country. Statistical analyses included logistic regression modelling to identify predictors of in-hospital mortality with FMC to balloon time as the independent variable, after adjustment for potential confounders. In patients treated within 60–180 min from FMC, there is a linear relationship between mortality and treatment delay. Patients stratified by haemodynamic instability in four groups showed increasing mortality rates (P < 0.0001): 3% in patients in a stable condition (n = 10.776), 16% after OHCA but in a stable condition (n = 369), 39% in patients with CS (n = 699), and 45% in patients with OHCA and CS (n = 831). In the two patient groups with haemodynamic instability, there was a steep increase in mortality with prolonged treatment delays, as shown in their figure 2.1 This strong association between mortality and treatment delays can be summarized by a number of memorable quotes (Table 1). Adjusted models show that treatment delay remains a significant independent predictor of survival, after accounting for clinical and procedural confounders, including disease severity assessed by TIMI risk score. The particular importance of implementing and monitoring best practices is nicely demonstrated by the driver analysis reported in their table 21 showing that C2B delays are shorter with pre-hospital ECG recording (– 5.4 min), pre-announcement of patient arrival (–17.5 min), or direct transfer to the catheterization laboratory (– 33.2 min). Of note, high-risk conditions per se are associated with longer delays: + 6.9 min in patients with CS and + 17.3 min in patients with OHCA, stressing the need for continued optimization of the care pathway in these subsets, representing 15% of all patients admitted with STEMI. Impact of reperfusion delay in high-risk STEMI patients: memorable quotes from the FITT-STEMI trial C2B, contact to balloon; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction. Impact of reperfusion delay in high-risk STEMI patients: memorable quotes from the FITT-STEMI trial C2B, contact to balloon; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction. As mentioned by the authors, the main limitation of the study design is the following: one cannot exclude that ‘late arrival of very sick patients could be the consequence of their poor condition, rather than the cause of increased mortality’. However, results of the regression analyses and the fact that both C2B time and TIMI risk score did confer independent prognostic significance are reassuring. It should be mentioned that these results were obtained in the context of a fully developed primary PCI (PPCI) programme engaging all stakeholders. High performance EMS was available, with trained physicians on board during transportation. The effect of a number of additional confounders on individual outcomes cannot be measured, such as the quality of resuscitation, the effect of hypothermia, or the use of balloon pump, extracorporeal membrane oxygenation (ECMO), or assist devices. The German prospective, multicentre FITT-STEMI trial is ongoing. With increasing sample size, the investigators will be able to evaluate whether feedback-driven quality control management of timely reperfusion has a positive causal effect on survival. By comparing temporal changes in outcomes, the relationship between gain in survival and decreased C2B time will become assessable. Lastly, data on longer term mortality outcomes are eagerly awaited. The importance of this work cannot be overemphasized. The most recent ESC Guidelines have insisted that the maximum expected delay between FMC and PPCI should be considered as the essential time target for clinical decision and the quality metric for care delivery, and not just the in-hospital D2B time.3 While the D2B time has been used extensively as a quality measure of the in-hospital processes, few data were available thus far on the components of pre-hospital delay and their impact on outcomes. The current study supports the recommendation to keep the FMC to treatment delay as short as possible, in any case below 120 min. In addition, the study by Scholz et al.1 provides, for the first time, impressive data on the strong impact of C2B time on in-hospital mortality in patients with CS and/or OHCA, and shows that 90 min should be the appropriate time target in high-risk cases. Guideline implementation programmes such as ‘Stent – Save a Life’ powered by the European Association of Percutaneous Cardiovascular Interventions4 and the PCR Interventional community worldwide (https://www.stentsavealife.com/#) should follow the outstanding ‘best practice’ example given by this consortium of hospital teams. The present work demonstrates that time matters even more than we used to think, especially in high-risk patients who still have poor outcomes, and that there are ways to expedite the process. Simply offering PPCI and reperfusion therapies is necessary, but not sufficient: the efficiency of the care pathway in expediting each step of the process matters tremendously, beyond what we suspected. The present data call for immediate action. D2B is part of the problem, but C2B is the main time target. Reducing treatment delays as much as possible in all patients, but especially in patients with CS and/or OHCA, should be our immediate next objective. Conflict of interest: The authors have no specific conflict of interest in relation to this manuscript. Both W.W. and C.K.N. are members of the Executive Committee of the ‘Stent – Save a Life’ initiative (https://www.stentsavealife.com/#).