Contribution of First Contact With a Cardiologist to the Door-to-Cardiac Catheterization Laboratory Time in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock　― Data From K-ACTIVE ―

Abstract

Background: Current guidelines recommend early revascularization in patients with cardiogenic shock (CS) following acute myocardial infarction (AMI). However, guideline-recommended first medical contact-to-device times is reportedly achieved in only 40% of patients.

Methods and Results: We retrospectively analyzed 369 patients with AMI complicated by CS from the Kanagawa-Acute Cardiovascular Registry to evaluate factors influencing delays in treatment and their effect on in-hospital mortality. Patients were stratified into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time (≤39 or >39 min). In the group with D2C time ≤39 min, the first-contact physician was more frequently a cardiologist (71.9% vs. 47.0%; P<0.001) and significantly more patients had chest pain as the chief complaint (70.3% vs. 47.4%; P<0.001). Although pre- and post-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow was similar between the 2 groups, in-hospital mortality was significantly lower in the D2C time ≤39 min group (18.8% vs. 37.6%; P<0.001). Multivariate logistic regression analysis revealed that D2C time >39 min was independently associated with a non-cardiologist being the first-contact physician, the absence of chest pain, a higher heart rate, and elevated creatinine levels.

Conclusions: D2C time ≤39 min is correlated with reduced mortality in AMI patients with CS. Implementing systems to ensure cardiologists are the initial responders and optimizing in-hospital workflows could reduce the D2C time and improve outcomes.

Cardiogenic shock (CS) following acute myocardial infarction (AMI) is associated with high mortality, ranging from 40% to 50%, even in the era of revascularization.¹ The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated that an early revascularization strategy in patients with CS resulted in a significant decline in 1-year mortality.² Current European Society of Cardiology clinical guidelines recommend that patients with AMI complicated by CS should be transferred to a tertiary care center for invasive coronary angiography as soon as possible, regardless of the mode of presentation (i.e., the presence or absence of ST-segment elevation or equivalent electrocardiogram [ECG] patterns).³ Furthermore, the latest expert consensus statement on CS also recommends that patients who experience CS following an acute coronary syndrome are transferred to a percutaneous coronary intervention (PCI)-capable hospital.⁴ However, one study reported that guideline-recommended first medical contact-to-device (FMC2D) times were achieved in less than 40% of patients with ST-elevation myocardial infarction (STEMI) accompanied by CS.⁵ Furthermore, according to an analysis of door-to-balloon (D2B) times and 1-year outcomes from the J-PCI OUTCOME registry, the incidence of CS was higher in the group whose D2B time exceeded 90 min.⁶ It is imperative that clinicians focus not only on restoring coronary blood flow as quickly as possible but also on identifying other measures that may be beneficial.

Editorial p 1738

The FMC2D and D2B times have already been established as predictors of prognosis. Thus, in the present study, we focused on the time from presentation until transfer to the cardiac catheterization laboratory (i.e., door-to-cardiac catheterization laboratory [D2C] time) to investigate factors contributing to delays in the treatment of patients with AMI complicated by CS using data from the Kanagawa-Acute Cardiovascular Registry (K-ACTIVE).

Methods

Study Design

This retrospective observational study used data from K-ACTIVE, a multicenter observational prospective registry of AMI. K-ACTIVE has been enrolling patients from 52 primary PCI-capable hospitals in Kanagawa Prefecture, Japan, since October 2015, encompassing large and small, urban and rural, and teaching and non-teaching hospitals. The registry was approved by the local institutional review board and registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry in October 2015 (UMIN000019156).

All patients with AMI who presented to hospital within 24 h of symptom onset were registered in K-ACTIVE. AMI was diagnosed based on the third universal definition of myocardial infarction consensus document.⁷ Each participating hospital was required to submit the data of consecutive patients to an online database. During the present study period, all patients with AMI were treated according to the Japanese Circulation Society guidelines (Figure).⁸

Figure.

Study flow chart. Patients were divided into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time: shorter (D2C ≤39 min) or longer (D2C >39 min). AMI, acute myocardial infarction.

Between October 2015 and June 2024, 369 patients with AMI complicated by CS were registered in the K-ACTIVE database. CS was defined as hypotension (systolic blood pressure [SBP] <90 mmHg) at admission and classified as Killip IV. Patients with missing data pertaining to SBP, Killip classification, ECG changes, FMC2D time, D2B time, and D2C time were excluded. First medical contact (FMC) was defined as the point at which ambulance staff arrived to assist the patient. Door time was defined as the point at which the patient arrived at hospital. Cardiac catheterization laboratory time was defined as the point at which the patient arrived at the cardiac catheterization laboratory. Device time was defined as the point at which the first device was inserted into the coronary artery.⁹ In K-ACTIVE, the first physician to contact the patient at admission is listed as either a cardiologist or non-cardiologist. Thus, first contact with a cardiologist under any circumstances was deemed as the “presence of first contact by a cardiologist.”

Comparison Cohorts

In this study, patients were divided into 2 groups based on a median D2C time of 39 min (i.e. D2C time ≤39 min [n=155] and D2C time >39 min [n=155]). Demographic characteristics, comorbidities, laboratory data, angiographic findings, treatment details, and mortality were compared between these 2 groups.

Statistical Analysis

The normality of data distribution was examined using the Shapiro-Wilk test. Continuous variables are expressed as the mean±SD or median with interquartile range (IQR), as appropriate. Categorical variables are expressed as percentages. Continuous variables with a normal distribution were compared using Student’s t-test, whereas those with a skewed distribution were compared using Wilcoxon’s test. Categorical variables were analyzed using Fisher’s exact test or the Chi-squared test, as appropriate.

Associations of clinical parameters and laboratory data with D2C time were evaluated using univariate and multivariate logistic regression analyses, which yielded hazard ratios with 95% confidence intervals. The variables included in the multivariate logistic regression analysis were derived from the Global Registry of Acute Coronary Events (GRACE) risk score¹⁰ analysis of the National Registry of Myocardial Infarction (NRMI),¹¹ as well as results of univariate logistic regression conducted in this study. Stepwise multiple linear regression analysis was also performed to identify factors influencing D2C time.

Results were considered statistically significant at 2-sided P<0.05. Statistical analyses were performed using the SPSS version 27 (IBM Corp., Armonk, NY, USA).

Results

Patient Characteristics

Patient characteristics of the D2C ≤39 and >39 min groups are presented in Table 1. Patient age was similar between the D2C ≤39 and >39 min groups (73.1±11.2 vs. 74.4±12.3 years, respectively; P=0.338), as was the proportion of men in each group (72.9% vs. 74.0%, respectively; P=0.823). There was no significant difference in body mass index between the D2C ≤39 and >39 min groups (23.2±3.7 vs. 22.8±4.1, respectively; P=0.505). There were no significant differences in the prevalence of coronary risk factors, such as hypertension, diabetes, dyslipidemia and maintenance hemodialysis, history of atrial fibrillation (AF) (including paroxysmal AF), and past history of myocardial infarction between the 2 groups.

Table 1.

Baseline Characteristics

	D2C time ≤39 min (n=155)	D2C time >39 min (n=155)	P value
Age (years)	73.1±11.2	74.4±12.3	0.338
Male sex (%)	72.9	74.0	0.823
BMI (kg/m2)	23.2±3.7	22.8±4.1	0.505
Comorbidities (%)
Hypertension	67.5	74.0	0.224
Diabetes	36.6	37.6	0.860
Dyslipidemia	46.4	47.9	0.790
Hemodialysis	1.6	5.8	0.095
(Paroxysmal) AF	14.3	23.0	0.079
Prior MI	10.1	9.4	0.845

Unless indicated otherwise, data are given as the mean±SD. Patients were divided into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time: ≤39 and >39 min. AF, atrial fibrillation; BMI, body mass index; MI, myocardial infarction.

Temporal Parameters

The median FMC2D time was 103.5 min (IQR 76.5–142.5 min). Guideline-recommended FMC2D times (≤90 min) were achieved in only 34.6% of patients in this study. The median D2B time was 80.5 min (IQR 56.0–120.0 min). Both FMC2D time and D2B time were correlated with D2C time (r=780 [P<0.001] and r=0.841 [P<0.001], respectively). All temporal parameters (i.e., FMC2D time, D2B time, and D2C time) were longer in patients who died in hospital (Table 2).

Table 2.

Temporal Parameters According to In-Hospital Mortality

	In-hospital death		P value
	No	Yes
FMC2D time (min)	95.9 (70.0–128.5)	131.0 (102.0–176.0)	<0.001
D2B time (min)	74.0 (51.5–105.5)	110.0 (69.5–146.5)	<0.001
D2C time (min)	36.0 (24.0–60.0)	50.5 (29.0–75.0)	0.001

Unless indicated otherwise, data are given as the median (interquartile range). D2B, door-to-balloon; D2C, door-to-cardiac catheterization laboratory; FMC2D, first medical contact-to-device.

Patient Characteristics at the First Visit and Laboratory Data

Patient characteristics in the D2C ≤39 and >39 min groups at the first visit are presented in Table 3. Although there were no significant differences between the 2 groups in SBP and diastolic blood pressure at the first visit, heart rate was significantly higher in the D2C >39 than ≤39 min group (72.0 vs. 58.5 beats/min, respectively; P=0.002). In the D2C ≤39 min group, having a cardiologist as the first-contact physician was significantly more frequent (71.9% vs. 47.0%; P<0.001). The frequency of STEMI was similar between the D2C ≤39 and >39 min groups (91.6% vs. 88.2%, respectively; P=0.315). Although a higher proportion of patients presented with a chief complaint of chest pain in the D2C ≤39 than >39 min group compared (70.3% vs. 47.4%, respectively; P<0.001), the proportion of patients whose chief complaint was dyspnea was lower in the D2C ≤39 min group (7.1% vs. 17.5%; P=0.005). The proportions of patients presenting with other chief complaints (e.g., digestive symptoms and loss of consciousness) were similar between the 2 groups. There was no significant difference between the D2C ≤39 and >39 min groups in the proportion of patients transported for out-of-hospital cardiac arrest (OHCA; 8.5% vs. 13.3%, respectively; P=0.177). Peak creatinine phosphokinase and creatinine kinase MB levels, which are indicators of myocardial infarct size, were similar between the 2 groups. Creatinine levels were higher in the D2C >39 than ≤39 min group (1.17 vs. 1.23 mg/dL, respectively; P=0.008). In addition, the D2C >39 min group had lower low-density lipoprotein cholesterol (110.4±42.8 vs. 96.3±40.3 mg/dL; P=0.010) and albumin (3.7 vs. 3.58 g/dL; P=0.011 concentrations than the D2C ≤39 min group.

Table 3.

Characteristics at the First Visit and Laboratory Data

	D2C time ≤39 min (n=155)	D2C time >39 min (n=155)	P value
SBP at admission (mmHg)	72.0 (62.5–81.0)	76.0 (68.0–82.0)	0.085
DBP at admission (mmHg)	46.0 (39.0–53.0)	46.0 (40.0–57.0)	0.228
HR at admission (beats/min)	58.5 (42.0–86.0)	72.0 (48.5–103.5)	0.002
First contact: cardiologist (%)	71.9	47.0	<0.001
STEMI (%)	91.6	88.2	0.315
Symptoms (%)
Chest pain	70.3	47.4	<0.001
Dyspnea	7.1	17.5	0.005
Nausea and vomiting	13.5	12.3	0.751
LOC	28.4	35.1	0.207
OHCA	8.5	13.3	0.177
Irregular rhythm	28.3	33.3	0.357
Laboratory data
Maximum CPK (IU/L)	2,987.0 (1,400.5–7,164.5)	3,039.0 (1,288.5–6,725.0)	0.947
Maximum CK-MB (IU/L)	317.0 (164.0–608.5)	253.0 (87.0–628.5)	0.116
Cr (mg/dL)	1.17 (0.99–1.39)	1.23 (1.01–1.90)	0.008
HDL-C (mg/dL)	45.5±14.1	48.0±14.8	0.185
LDL-C (mg/dL)	110.4±42.8	96.3±40.3	0.010
HbA1c (%)	5.9 (5.6–6.6)	6.0 (5.7–6.5)	0.735
Albumin (g/dL)	3.7 (3.4–3.9)	3.6 (3.2–3.8)	0.011

Unless indicated otherwise, data are given as the mean±SD or median (interquartile range). Patients were divided into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time: ≤39 and >39 min. CK-MB, creatinine kinase MB; CPK, creatinine phosphokinase; Cr, creatinine; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; HR, heart rate; LDL-C, low-density lipoprotein cholesterol; LOC, loss of consciousness; OHCA, out-of-hospital cardiac arrest; SBP, systolic blood pressure; STEMI, ST-elevation myocardial infarction.

Coronary Angiographic Findings, Treatment, and In-Hospital Mortality

Table 4 presents coronary angiography findings, treatment, and in-hospital mortality. The prevalence of the right coronary artery as the infarct-related artery was significantly higher in the D2C ≤39 min group (P<0.001). Pre- and post-PCI Thrombolysis in Myocardial Infarction flow were similar between the 2 groups, as was the frequency of coronary artery bypass grafting. There were no significant differences in the frequency of intra-aortic balloon pump (IABP) or veno-arterial extracorporeal membrane oxygenation (ECMO) use between the 2 groups. It is of note that in-hospital mortality was significantly lower in the D2C ≤39 min group than in the D2C >39 min group (18.8% vs. 37.6%, respectively; P<0.001).

Table 4.

Coronary Angiography Findings and Mortality

	D2C time ≤39 min (n=155)	D2C time >39 min (n=155)	P value
Angiographic findings (%)
Culprit vessel			<0.001
RCA	56.9	42.4
LAD	29.2	36.8
LCX	9.2	10.4
LMT	10.0	13.6
Graft	0	0.8
Multivessel	63.1	60.3	0.619
Pre-TIMI flow 0	73.0	67.1	0.260
Post-TIMI flow ≤2	13.8	14.0	0.963
Treatment (%)
CABG	1.9	4.6	1.000
IABP	50.0	54.9	0.390
VA-ECMO	11.7	19.0	0.077
In-hospital mortality (%)	18.8	37.6	<0.001

Patients were divided into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time: ≤39 and >39 min. CABG, coronary artery bypass graft; IABP, intra-aortic balloon pump; LAD, left anterior descending artery; LCX, left circumflex artery; LMT, left main trunk; RCA, right coronary artery; TIMI, Thrombolysis in Myocardial Infarction; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.

Multivariate Logistic Regression Analysis for Predictors of Longer D2C Time

The results of multivariate logistic regression analysis of longer D2C time in patients with AMI complicated by CS are presented in Table 5. A non-cardiologist as the first-contact physician, a higher heart rate, the absence of chest pain as the chief complaint, and higher creatinine concentrations were independent predictors of a longer D2C time.

Table 5.

Logistic Regression Analyses of the Relationship Between Study Variables and D2C Time >39 min

	Univariate analysis		Multivariate analysis
	HR (95% CI)	P value	HR (95% CI)	P value
Age	1.009 (0.990–1.029)	0.337	1.015 (0.991–1.040)	0.221
Male sex	1.059 (0.639–1.756)	0.823	1.399 (0.744–2.629)	0.297
SBP	1.019 (0.999–1.040)	0.057	1.012 (0.989–1.035)	0.318
Heart rate	1.010 (1.003–1.018)	0.005	1.010 (1.002–1.019)	0.016
First contact: cardiologist	0.347 (0.216–0.558)	<0.001	0.360 (0.210–0.618)	<0.001
STEMI	0.682 (0.321–1.445)	0.317	0.907 (0.362–2.275)	0.835
OHCA	1.657 (0.792–3.465)	0.180	1.192 (0.466–3.045)	0.714
Chest pain	0.380 (0.238–0.607)	<0.001	0.377 (0.217–0.656)	<0.001
Dyspnea	2.783 (1.327–5.836)	0.007	1.762 (0.742–4.187)	0.199
Creatinine	1.393 (1.111–1.745)	0.004	1.352 (1.077–1.696)	0.009
Albumin	0.554 (0.326–0.940)	0.0029
LDL-C	0.992 (0.985–0.998)	0.012
RCA	0.557 (0.339–0.915)	0.021

CI, confidence interval; HR, hazard ratio. Other abbreviations as in Tables 3,4.

Multiple Linear Regression Analysis for Factors Affecting D2C Time

Age, male sex, STEMI, heart rate and SBP at admission, and first contact with a cardiologist were included in the multivariate analysis. The results of multiple linear regression analysis for D2C time are presented in Table 6. Multiple linear regression analysis revealed that first contact with a cardiologist (β=−26.260, P<0.001) and STEMI (β=−41.364, P=0.001) were factors influencing D2C time.

Table 6.

Multiple Linear Regression Analysis of Factors Affecting D2C Time

Variables	β	t	P value	95% CI
Age	0.470	1.377	0.170	−0.202, 1.143
Male sex	−1.466	−0.162	0.872	−19.298, 16.365
First contact: cardiologist	−26.260	−3.393	<0.001	−41.494, −11.027
STEMI	−41.364	−3.242	0.001	−66.477, −16.251
SBP at admission	0.314	0.932	0.352	−0.349, 0.978
Heart rate at admission	0.056	0.465	0.642	−0.181, 0.293

Abbreviations as in Tables 3,5.

Discussion

This study investigated factors affecting delays in treatment, represented by a longer D2C time, in patients with AMI complicated by CS. A non-cardiologist as the first-contact physician was an independent predictor of a longer D2C time. Furthermore, in-hospital mortality was lower in the group with a shorter (≤39 min) D2C time than in the group with a longer D2C time.

To the best of our knowledge, this is the first study to report on the contribution of the first contact being a cardiologist to a decrease in the D2C time in the treatment of patients with AMI complicated by CS.

Early revascularization has emerged as the most important treatment strategy for CS complicating AMI.¹² The latest expert consensus statement on CS emphasizes the importance of rapid reperfusion therapy, airway management, and early initiation of mechanical circulatory support (MCS) when necessary.⁴ In the present study, all temporal parameters were longer in patients who died in hospital. D2B time is an important modifiable factor affecting treatment delay, and various methods have been devised to shorten the D2B time. Sawano et al. analyzed the D2B time and 1-year outcomes using the J-PCI OUTCOME registry and reported that the incidence of CS was higher in the group whose D2B exceeded 90 min.⁶ In the present study, the guideline-recommended FMC2D time (≤90 min) was achieved in only 34.6% of patients. Shortening the treatment time is more difficult in patients with than without CS. The D2B time is divided into 3 intervals, namely door-to-ECG time, ECG-to-cardiac catheterization laboratory (E2C) time, and cardiac catheterization laboratory-to-balloon time. Previous studies have shown that the E2C time can contribute to major delays in implementing primary PCI.^13,14 In the present study, the D2C time was selected for analysis instead of the E2C time, because the timing of ECG acquisition was not available in the K-ACTIVE database. Furthermore, the effect of a shorter D2B time on survival was more pronounced in patients without an MCS device use than in those with an MCS device.¹⁵ Subsequently, we examined the association of D2C time with mortality by stratifying the cohort according to the median D2C time.

Various studies have investigated factors that can reduce the total ischemia time. Prehospital 12-lead ECG,^9,16,17 activation of the cardiac catheterization laboratory by emergency medical services,¹⁸ and a cardiologist as the first-contact physician^9,19 were associated with a shorter D2B time because they facilitated more rapid transfer to the cardiac catheterization laboratory. Primary PCI procedures that skip diagnostic catheterization and single-catheter PCI²⁰ reportedly reduce PCI procedural times after the patient enters the catheterization room. However, unlike in the present study, the previous studies mentioned above did not restrict their populations to patients with AMI complicated by CS. In general, patients with shock status are often transferred to the emergency medical care center instead of the cardiovascular intensive care unit. Patients with AMI who were transferred to the emergency medical care center instead of the cardiovascular intensive care unit reportedly had a more severe condition, longer door-to-reperfusion time, and worse in-hospital mortality.²¹ In the present study, although the infarct size, represented by the maximum creatinine phosphokinase level, was equivalent between the 2 groups, the group with the shorter D2C time (i.e., ≤39 min) may have included patients with lesser disease severity. This may be attributed to a lower heart rate at admission, a tendency towards a lower incidence of OHCA, significantly better renal function, lower frequency of veno-arterial ECMO use, and a lower incidence of culprit lesions in the left anterior descending artery. Jansky et al. reported that the treatment strategy for patients after OHCA was influenced by the presence of a cardiologist upon admission to the hospital, which increased the likelihood of an early diagnosis of acute coronary syndromes as the cause of the OHCA.²² Although there are limits to medical resources, even in cases of AMI with CS transferred to the emergency medical care center, if a non-cardiologist is the first-contact physician, seamless direct communication with a cardiologist is of paramount importance to immediately transfer the patient to the cardiac catheterization laboratory, as in the case of AMI, regardless of the presence or absence of CS.²³ Upon first contact with patients with CS, emergency physicians and cardiologists could contribute to shortening the D2C time.

The present study demonstrated that in-hospital mortality was significantly lower in the group with the shorter than longer D2C time. In patients with AMI, earlier reperfusion therapy improves prognosis, regardless of the presence of CS,¹⁵ whereas early reperfusion for STEMI with CS also has the benefit of transfer to the cardiac catheterization laboratory, which allows timely insertion of MCS devices. The concept of “door-to-unload” has emerged recently, and it is thought that earlier unloading with Impella (Abiomed, Danvers, MA, USA) could limit damage to the left ventricle.²⁴ Basir et al. presented a regional shock protocol wherein early delivery of MCS (Impella) with invasive hemodynamic monitoring can achieve rapid door-to-support time and improve survival in patients with AMI complicated by CS.²⁵ Because the present study was conducted at a time when Impella was not available and the timing of MCS insertion was unknown, we could not analyze the door-to-unload time or door-to-MCS time. In the present study, the utilization rates of IABP and ECMO did not differ according to D2C time, although the use of ECMO tended to be higher in the group with a longer D2C time. However, the timing of IABP and ECMO introduction in the present study was unclear. According to the concept of “door-to-unload,” earlier transportation of the patient with AMI complicated by CS to the cardiac catheterization laboratory would facilitate early insertion of MCS devices such as the IABP and Impella.

Although early diagnosis of CS is important for the timely implementation of interventions (including reperfusion and MCS insertion) to achieve better outcomes, the diagnosis of CS is difficult because its severity varies from mild hypoperfusion to a pulseless state.²⁶ In the present study, we adopted SBP <90 mmHg as the inclusion criterion in accordance with the standardized definition for CS.²⁷ However, the latest expert consensus statement on CS lists signs of hemodynamic instability, including, in addition to SBP <90 mmHg, a mean blood pressure of <65 mmHg.⁴ Various signs other than blood pressure are also listed, and undertriage should be avoided.⁴

In the present study, the frequency of patients without chest pain was higher in the group with a longer D2C time. Previous studies reported that patients with myocardial infarction presenting without chest pain not only presented late to hospital but also had a lower likelihood of receiving a timely reperfusion strategy, resulting in poor outcomes.^28,29 Park et al. reported that a non-chest pain-based chief complaint was an independent predictor of longer D2B times in patients with STEMI.³⁰ The other predictors of D2B time delay reportedly include hospital transfer, non-daytime presentation, and treatment at low-volume centers.¹¹ Moreover, the D2C time was more delayed in patients with non-chest pain complaints than in patients complaining of chest pain, which may be ascribed to delays in performing ECGs and low triage scores.¹¹ In patients with CS, it is desirable to perform an ECG earlier to shorten the D2C time.

Study Limitations

This study has some limitations. Details of the emergency systems, including the methods of collaboration between the emergency physicians and cardiologists in each hospital participating in K-ACTIVE, were not available in this study. Moreover, information on the respiratory status necessitating intubation and the use of a ventilator, which are related to the time course of treatment, was not available in this registry.

Conclusions

In conclusion, in patients with AMI complicated by CS, in-hospital mortality was lower in those with shorter than longer D2C times. This implies that implementing systems to ensure cardiologists provide the initial response to patients with CS, optimizing in-hospital workflows that enable rapid responses to patients with CS who do not complain of chest pain, and improving physicians’ diagnostic ability could potentially shorten the D2C time.

Acknowledgments

The authors thank all the investigators, clinical research coordinators, and data managers involved in K-ACTIVE for their contributions.

Sources of Funding

None.

Disclosures

Y.A., J.A., Y.I., K.T., and K.K. are members of Circulation Journal’s Editorial Team. The remaining authors have no conflicts of interest to declare.

IRB Information

This study was approved by the Ethics Committee of Nippon Medical School Musashi-Kosugi Hospital (Reference no. 785-6-14).

Date Availability

The deidentified participant data will not be shared.

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