We analyzed DTB time in STEMI patients consecutively registered in a contemporary multicenter Japanese database, and found that, currently, half of the patients had DTB time >90 min. The predictors for DTB time delay was multifactorial, but there were significant variables suitable for intervention including PAD and off-hour arrival. Overall institutional volume was also associated with DTB time: high-volume institutions achieved shorter DTB times compared with low-volume institutions, and the trend was pronounced in recent years. It is important to determine the clinical characteristics and profiles of patients who undergo PCI in different regions, because such data are necessary to evaluate whether patients are being managed appropriately and in line with the available clinical guidelines and evidence-based medicine. This analysis supports the notion that regional (and individual) efforts are needed to improve DTB time, which is regarded globally as an important quality indicator of STEMI care.
Previous Studies and Implications for DTB Time in Japan
The present data imply that DTB time for Japanese STEMI patients is unsatisfactory in a considerable proportion of patients: 46.2% of the present patients received PCI after the recommended 90 min. More importantly, DTB time has remained unchanged during the study period (September 2008–December 2013), in contrast to that in Western countries.19
Internationally, DTB time has been a major focus in quality assessment for primary PCI for the past decade,9
and Western DTB time has been found to decrease in recent years. For example, the national registry of PCI in the US (NCDR) showed that the median DTB time was 86 min (IQR, 65–109 min) in 2005, but was shortened to 63 min (IQR, 47–80 min) by 2011.4
In contrast, the median DTB time in a multicenter registry conducted between January 2005 and December 2007 in Japan (CREDO-Kyoto) was 90 min (IQR, 60–132 min).15
The present study has noted similar results in the more contemporary era of PCI, and highlights the need for progress in this area. Another study from a Japanese multicenter registry (J-AMI registry) noted a better result than the present one, in that median DTB time was 42 min (IQR, 28–66 min) for May–October 2011.21
Those participants, however, were enrolled from only registered institutions of the Japanese Association of Cardiovascular Intervention and Therapeutics and not from all institutions, hence that registry has a potential selection bias, and therefore those findings must be interpreted with caution.
Since 2008, the Japanese Circulation Society guidelines for STEMI management have incorporated a DTB time recommendation.22
The recommendation has been further emphasized in more recent guidelines: when the guideline was revised in 2013, DTB time <90 min was recommended (class I) in all STEMI patients presenting ≤12 h of symptom onset. Moreover, in April 2014, the reimbursement rules for primary PCI were altered. When DTB time ≤90 min is not achieved, the reimbursement rate for each procedure is cut by 29%.23
Such pay for performance (P4P) initiatives (to a smaller extent) have improved the quality of care for STEMI patients in the USA,24,25
but its effect on the actual clinical outcome remains controversial. Further studies are needed to assess the implication of P4P in DTB time in Japan.
Clinical Predictors of Delay in DTB Time
Most of the baseline characteristics of the present STEMI patients were similar to previously published data, although the Japanese patients were generally older and had a lower burden of predisposing cardiac risk factors or comorbidities: a smaller percentage of patients had PAD or previous revascularization procedures.16
Despite these differences, predictors of prolonged DTB time were not substantially different from those in Western countries.11–13,26
Comorbid conditions would lead to complexity of the infarct or non-infarct related artery. In addition, difficulties in obtaining vascular access in these patients, particularly in those with PAD, or additional time required to stabilize respiratory status and/or hemodynamic derangement may all lead to prolonged DTB time. The latter is reflected in the proportion of patients with congestive heart failure or those requiring mechanical device support (e.g., VA-ECMO or IABP).27
These conditions are not currently indications for intervention, and it is likely that these will continue to predispose to prolonged DTB times, given the aging population in Japan, but caregivers should at least be made aware that these conditions would likely delay reperfusion. Further, rigorous adjustment or even separate classification of these high-risk patients may be necessary to justify DTB time assessment as a quality indicator.
In contrast, specific interventions to decrease DTB time should be targeted. For example, the time interval between activation of the cardiac on-call team and commencement of the procedure accounts for a substantial proportion of the delay in primary PCI for STEMI patients. In the present analysis, this was reflected in the longer DTB time during night-time and weekend presentation. This may be improved by increasing the efficiency of on-call cardiac catheterization.28
We also found that high-volume centers were more likely to achieve shorter DTB times compared with low-volume centers. The reason for this is not entirely clear, but previous studies in both medical and surgical settings have demonstrated that a lower patient load can impair efficiency in patient care.29,30
Traditionally, Japan has a higher number of PCI-capable hospitals compared with Western countries due to the coverage of social health insurance.17
Transportation of patients to primary PCI centers by emergency medical service is free and highly accessible,31
but, as a trade-off, primary PCI volume has diverged, and the number of primary PCI performed in each hospital is relatively small. Importantly, several studies have linked higher hospital PCI volume and greater adherence to evidence-based medicine to better outcomes.32,33
This inverse association between primary PCI volume and in-hospital mortality has been reported for other Japanese cohorts.34
The present results indicate that the balancing of the number of PCI-capable facilities and maintenance of performance indicators such as DTB time may be challenging. Further studies to delineate these relationships could facilitate the international standardization of health-care delivery.35
DTB Time and In-Hospital Mortality: Current Status
Improving both in-hospital and post-discharge care remain key targets for enhancing long-term outcomes after STEMI. Recent studies have suggested increased risk in patients undergoing primary PCI owing to increased complexity of comorbidities presenting with acute MI.9
Consistent with these studies, the present data suggest a correlation between aging patients and multiple comorbidities with prolonged DTB time. These patients are typically more likely to have delayed hospital arrival time,36
and are less likely to be treated with evidence-based medical therapy (e.g., β-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and statins).37
Still, Nallamothu et al showed that shorter patient-specific DTB time was strongly and consistently associated with lower risk-adjusted in-hospital and 6-month mortality.4
Importantly, the present study showed that DTB time tends to be prolonged in patients with comorbidities such as CKD or concomitant vascular disease (e.g., PAD or previous revascularization). Debate persists as to whether the shortening of DTB time in high-risk patients improves outcome.19,24
A solution may involve the detailed consideration of medical resource allocation, system improvement, and disease management, but this warrants further discussion.
There were several limitations in the present study. First, the study had the inherent limitations of any non-randomized observational research: it is possible that unmeasured confounders could have contributed to prolonged DTB time, even after rigorous measurement and recording of key clinical variables. As quoted, the present registry was developed in accordance with NCDR version 4.1, and did not record non-quantifiable parameters (e.g., presence of dementia or physical frailty) or out-of-hospital variables such as arrival time at the initial satellite clinic, method of transportation to the initial hospital, use of prehospital 12-lead electrocardiography, or treatment within emergency medical systems. Specifically, the use of IABP included patients who required IABP during the procedure. We could not define whether IABP was used before or after first device use for the culprit artery. Moreover, we did not record key clinical variables that might have contributed to differences between high- and low-volume centers. For instance, parameters surrounding the emergency department (ED) or catheterization laboratory, especially door-to-electrocardiogram time, patient load in ED (i.e., average number of patients treated by each physician), the number of interventional cardiologists or other medical staff members who were on call, the interval between time of page and arrival of staff at the catheterization laboratory, or whether timely data feedback and analysis were provided to members of the STEMI care team. A multivariable-adjusted logistic regression model was used to investigate differences in high- and low-volume centers in the present dataset (Figure S2). Subgroup analysis in high-volume centers demonstrated a similar tendency with the overall model. In low-volume centers, there was no predictive value for DTB time delay due to PAD, prior revascularizations, age >75 years, heart failure at arrival, use of IABP/VA-ECMO, or LAD lesion. This study may be statistically underpowered because of the small population size, but patients who arrived at low-volume centers in off-hours were more likely to have prolonged DTB time (OR, 2.22; 95% CI: 1.32–3.74; P=0.003).
shows the annual trends of median DTB time in the high- and low-volume centers. In 2010, the median DTB time was 88 min (IQR, 69–108 min) in the high-volume centers and 90 min (IQR, 60–117 min) in the low-volume centers (P=0.78). It seems that the median DTB time worsened in the low-volume centers after 2011, which may be due to the inclusion of different hospitals each year (e.g., the number of participating hospitals and the mean percentage of achievement of DTB time <90 min in the low-volume centers differed with year). Second, onset time of the event was collected in only a limited number of patients (2012–2013). Despite this limitation, we assessed the total ischemic time in 13.4% of the patients (n=305). Overall median symptom onset-to-balloon time was 235 min (IQR, 153.5–357.5 min). There was no difference in onset-to-balloon time between high- (228 min: IQR, 165–325 min) and low-volume centers (236 min: IQR, 153–364 min). Hence, it is unlikely that difference in DTB times is attributed to time interval differences in the field. Rather, the difference in DTB time with institution volume seemed to have been due to institutional factors (e.g., management within the hospital). Third, the present numbers are relatively small, particularly for the analysis of in-hospital mortality, therefore the clinical outcomes must be interpreted with caution. It is still unknown whether increasing the percentage of patients with DTB time ≤90 min would actually contribute significantly to improve STEMI outcome. Fourth, several key variables (e.g., ejection fraction or maximum creatinine kinase after primary PCI) that are considered predictors of in-hospital death were not measured in the current registry. Last, the present cases of suspected STEMI were based on cardiologist review. Other studies have used different criteria such as emergency physician decision without cardiologist review, which may result in a higher STEMI rate.