Our study found, based on patient medical histories and characteristics, that the most significant factor related to a longer SNT was gender. A possible cause and explanation of longer SNTs in women may be the more frequent occurrence of atypical symptoms, resulting in significant delays from symptom onset to contacting the emergency system [18,19]. Women often have no chest pain [20] or consider the pain to be insignificant or not life-threatening [21]. In the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), only half of patients < 55 years of age presenting with an acute myocardial infarction considered themselves at risk for heart disease before their event, despite having several cardiac risk factors [19]. Women were less likely than men to be told by their physician that they were at risk of cardiovascular disease or to have conversations about risk reduction.
Significantly longer SNTs were found in patients treated for arterial hypertension and in obese females, but not males. These findings are consistent with previous studies [22-24].
A negative trend toward longer delays (thus not statistically significant) was observed in patients with a history of CABG, and in diabetic patients while a trend toward shorter delay was seen in patients with a history of prior MI. Prolongation of time delay in diabetic patients has been consistently reported across studies, and related to atypical signs and symptoms of MI in this population [25–27] . Studies investigating pre-hospital delay in patients with prior CABG or MI reported conflicting results of whether patients with these comorbidities present earlier or not. In The Worcester Heart Attack Study, the researchers found that previous MI was associated with longer delays [27], other investigators [25,26,28,29] reported significantly shorter pre-hospital delays in these patients. In a prospective cohort study performed by Coventry et al. the patients with previous MI had shorter time delay than patients without previous MI or CABG, but patients with previous MI and CABG compared with previous MI alone had longer time delays [30]. The probable reason for these findings is that some patients perceive seriousness of the disease and potential threat after the first event while others think it is not likely to have a second MI after a successful CABG operation. Moreover, socio-demographic factors (e.g. marital status), cognitive (higher educational level [28,31]) and behavioral factors play a role when deciding to call emergency system or come to a hospital to seek help [32]. There is limited evidence that community media-based MI-awareness campaigns lead to shortening time delays [30,33], therefore a face-to-face educational intervention in selected high-risk patients (post MI/CABG, with diabetes) was proposed to be more beneficial. Despite the fact that a randomized trial conducted by Dracup et al [34] failed to prove this concept, the MEDEA study demonstrated that patients with a knowledge of MI symptoms and treatment presented with shorter time delays [35]. Thus, continuous efforts need to be taken to educate high risk patients to further reduce pre-hospital delay.
In the patients with longer SNTs, there was a higher incidence of post-PCI suboptimal TIMI flow in the culprit vessel despite the fact, that all patients were given appropriate combined antithrombotic therapy including prasugrel or ticagrelor at a cathlab prior to revascularization. Our results are consistent with previous reports that found a positive correlation between shorter time delays and more favorable postprocedural findings on the infarct-related artery [36,37]. In the ATLANTIC (Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery) study, early (pre-hospital) compared to in-hospital administration of ticagrelor in STEMI patients did not result in more frequent TIMI 3 flow prior to and post-PCI but reduced stent thrombosis rates, irrespective of initial TIMI risk score of the patients [38]. To sum up, the data suggest that affecting time delay is of higher importance than timing of the first (loading) dose of a potent P2Y12 inhibitor, as long as given prior to PCI.
The study found only a borderline relationship between longer SNTs (i.e., above the median value) and the occurrence of the composite ischemic endpoint when no risk stratification was applied. Despite a low incidence of endpoints both at 30 days and 1 year, the present data demonstrated that stratification of patients at admission, relative to ischemic risk using the TIMI Risk Score (including hemodynamic parameters, disease-specific patient medical history, and age) is still the most important act the attending clinician must perform, and in high-risk patients to subsequently take actions in order to maximally shorten time delay to reperfusion. Such approach, together with the use of potent antiplatelet therapy including prasugrel or ticagrelor, resulted in a better survival and less ischemic events. In patients with a low-risk profile at admission, with the same antiplatelet therapy applied, the prognostic effect of short time delay was not pronounced.
Similarly to previous publications [39,40], the majority of cardiogenic shock patients enrolled in our study arrived early (SNT ≤ 1 hour) after the onset of symptoms but still having the worst prognosis. These patients arrived in very poor condition, had been resuscitated, and on hemodynamic or ventilator support. The poor outcomes in these cases were likely determined before the patient ever reached a Cath lab and were independent of elapsed SNT.