Nationwide Analysis of Spontaneous Coronary Artery Dissection-Related Acute Myocardial Infarction in Japanese Patients Aged ≤60 Years Using the Administrative JROAD-DPC Database

Keima Wayama; Yu Kataoka; Koshiro Kanaoka; Michikazu Nakai; Yoshitaka Iwanaga; Yoko Sumita; Yoshihiro Miyamoto; Satoshi Yasuda; Teruo Noguchi

doi:10.1253/circrep.CR-25-0202

Abstract

Background: Spontaneous coronary artery dissection (SCAD) causes acute myocardial infarction (AMI). Clinical characteristics of SCAD patients remain insufficiently understood.

Methods and Results: We analyzed AMI patients aged ≤60 years using the nationwide Japanese Registry of All Cardiac and Vascular Diseases–Diagnosis Procedure Combination database (2012.04.01–2022.03.31). SCAD was defined by International Classification of Diseases, 10th revision code I24.8 and the presence of keyword ‘coronary artery dissection’. The primary outcome was in-hospital all-cause mortality. Among 96,304 eligible patients, 330 (0.34%) had SCAD. SCAD patients were younger (P<0.001), more often female (P<0.001), and had fewer atherogenic risk factors. They less frequently received aspirin (P<0.001), angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (P<0.001), statins (P<0.001), and percutaneous coronary intervention (PCI; P<0.001). After propensity score matching, in-hospital all-cause mortality did not differ between SCAD and non-SCAD patients (1.0% vs. 2.9%; P=0.142). The subgroup analysis revealed that the use of aspirin was associated with a lower adjusted in-hospital all-cause mortality (P=0.002), whereas primary PCI (P=0.223), β-blocker (P=0.646), and statin (P=0.608) were not. Of note, older SCAD patients were more likely to exhibit inferior MI (P=0.036 for trend) with shorter duration of hospitalization (P=0.025 for trend).

Conclusions: Short-term outcomes in SCAD patients are comparable with those of atherosclerotic AMI. While aspirin lowered in-hospital mortality, PCI, β-blocker, and statin did not. Our findings suggest the need for physicians to select appropriate therapeutic management in SCAD patients to achieve better outcomes.

Central Figure

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome (ACS), accounting for approximately 1% of acute myocardial infarction (AMI) cases overall and up to 20% of AMI cases among women aged <50 years.¹^–⁴ SCAD arises from unique pathophysiological mechanisms, including intramural hemorrhage and intimal disruption.¹^,⁵^–⁷ Invasive coronary angiography is commonly used for the diagnosis of SCAD. However, visualization of dissection is still challenging, and no standardized diagnostic criteria have been established. Given these limitations, detailed data on SCAD remain scarce, highlighting the need for further investigation into its presentation, clinical course, and optimal management strategies.

The Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database is a nationwide administrative claims registry covering over 1,000 cardiovascular training hospitals in Japan. These large data enable the potential to investigate Japanese patients with AMI attributable to SCAD. Using this resource, we sought to clarify the demographic profile, therapeutic practices, and early outcomes of SCAD-related AMI, and compare with atherosclerotic AMI among relatively young patients.

Methods

Data Source

This study utilized data from the JROAD-DPC database, which integrates the Japanese Registry of All Cardiac and Vascular Diseases (JROAD) with the Diagnosis Procedure Combination (DPC) system.⁸^–¹³ The JROAD-DPC provides nationwide, hospital-based information on cardiovascular hospitalizations in Japan and includes detailed patient-level data such as demographics, clinical characteristics, procedures, and diagnoses.¹⁴^,¹⁵ Diagnoses are recorded using the International Classification of Diseases, 10th revision (ICD-10) codes, supplemented by physician-entered clinical information. The accuracy of acute myocardial infarction (AMI) diagnoses in the JROAD-DPC has been validated and reported to be reliable in previous studies.¹⁶^–¹⁸

Study Population

From April 1, 2012, to March 31, 2022, a total of 474,674 patients diagnosed with AMI were identified in the JROAD-DPC database across 1,122 hospitals. AMI was defined as an ICD-10 code I21.x recorded in any of the diagnosis fields, including ‘main diagnosis’ or ‘admission-precipitating diagnosis’. In addition, acute coronary syndrome (ACS) was defined as ICD-10 code I24.8 recorded in the ‘main diagnosis’, ‘admission-precipitating diagnosis’, or ‘coexisting comorbidities on admission’. Of these, we included the following patients: (1) those with ICD-10 code I21.x listed as either the main or admission-precipitating diagnosis; (2) those who were emergently hospitalized; and (3) those who received coronary angiography after admission. The current analysis excluded patients with iatrogenic coronary artery dissection. According to a published paper,¹⁹ this was defined as the presence of I24.8 along with the keyword ‘dissection’ in the complication diagnosis field (n=235). Patients without any information on age were excluded too (n=858). As a consequence, the remaining 393,248 patients were included in the current analysis. As it was necessary to exclude patients with AMI attributable to atherosclerotic causes, the primary analysis was conducted in those aged ≤60 years (n=96,304).²⁰ Patients were stratified into 2 groups based on the presence or absence of SCAD (Figure 1).

Figure 1.

Patients’ disposition. AMI, acute myocardial infarction; CAG, coronary angiography; DPC, diagnosis procedure combination; JROAD, Japanese Registry of all Cardiac and Vascular Diseases; SCAD, spontaneous coronary artery dissection.

Outcome Measure

The primary outcome was in-hospital all-cause mortality, defined as death during the index hospitalization.

Validation of SCAD Patients

A total of 50 SCAD patients were randomly selected. In these cases, coronary angiographic images were reviewed by 2 independent physicians (K.W. and Y.K.). The presence or absence of coronary angiography dissection was evaluated according to published studies.²¹^,²² Coronary angiography data were collected by the ongoing multi-center SCAD registry (jRCT1050240244).

Statistical Analysis

In AMI patients aged ≤60 years (n=96,304), baseline characteristics and treatments were compared between patients with and without SCAD. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate, and continuous variables were compared using the Student’s t-test or the Wilcoxon rank-sum test, depending on distribution. To compare in-hospital mortality, age- and sex-matched cohorts were generated using 1 : 1 matching. In addition, to address potential baseline differences between patients with and without SCAD, 1 : 1 propensity score matching was performed. The propensity score was estimated using a logistic regression model with covariates including age, sex, body mass index, hypertension, dyslipidemia, and diabetes, as listed in the Supplementary Table 1. Nearest-neighbor matching was conducted on the logit of the propensity score using a caliper width of 0.2 times the pooled standard deviation of the logit of the propensity scores. In SCAD patients, analysis of covariance was conducted to compare in-hospital mortality among a variety of subgroups (dual antiplatelet therapy [DAPT], percutaneous coronary intervention [PCI], aspirin, β-blocker, and statin). Clinical characteristics, location of myocardial infarction (anterior/inferior), and duration of hospitalization were compared in SCAD patients stratified according to their ages (≤35, 36–40, 41–45, 46–50, 51–55, and 56–60 years) using analysis of variance. In the entire 393,428 AMI patients, clinical characteristics and in-hospital all-cause mortality were similarly compared between those with and without SCAD. All statistical analyses were conducted using SPSS software. Two-sided P values <0.05 were considered statistically significant.

Ethics Statement

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki and was approved by the institutional review board of the National Cerebral and Cardiovascular Center (approval no. R21016-4). Given the retrospective and observational nature of the study, the requirement for written informed consent was waived.

Results

Clinical Demographics

Among the 96,304 patients included in the current analysis, 330 (0.34%) were diagnosed with SCAD. Table 1 summarizes the clinical characteristics of patients with and without SCAD. Patients with SCAD were younger (47.6±6.9 vs. 51.5±6.6 years; P<0.001) and more frequently female (82.7% vs. 10.0%; P<0.001) compared with those without SCAD. They also had a lower prevalence of cardiovascular risk factors, including lower body mass index (23.0±4.3 vs. 26.1±4.3 kg/m²; P<0.001), hypertension (58.5% vs. 67.3%; P<0.001), dyslipidemia (51.5% vs. 73.4%; P<0.001), and type 2 diabetes (5.5% vs. 30.4%; P<0.001). With regard to the severity of AMI, the Killip class at presentation was less severe among patients with SCAD (P=0.006). A lower frequency of inferior AMI was observed in patients with SCAD (26.9 vs. 33.1%; P=0.006). Additionally, patients with SCAD required a shorter hospital stay (13.0±9.0 vs. 14.0±11.0 days; P=0.040) compared with those without SCAD (Table 1).

Table 1.

Baseline Clinical Demographics

	SCAD (−; n=95,974)	SCAD (+; n=330)	P value
Age (years)	51.5±6.6	47.6±6.9	<0.001
Sex, female	9,608 (10.0)	273 (82.7)	<0.001
BMI (kg/m²)	26.1±4.3	23.0±4.3	<0.001
Hypertension	64,564 (67.3)	193 (58.5)	<0.001
Diabetes	29,198 (30.4)	18 (5.5)	<0.001
Dyslipidemia	70,428 (73.4)	170 (51.5)	<0.001
Hyperuricemia	5,289 (5.5)	6 (1.8)	0.003
Smoking	72,940 (75.9)	132 (40.0)	<0.001
CKD	2,780 (2.9)	2 (0.6)	0.007
History of heart failure	315 (0.3)	0 (0.0)	0.632
History of MI	1,281 (1.3)	2 (0.6)	0.337
Severity of AMI
Killip I	53,646 (57.6)	215 (66.0)	0.006
Killip II	21,660 (23.2)	56 (17.2)
Killip III	5,248 (5.6)	12 (3.7)
Killip IV	8,974 (9.6)	25 (7.7)
Infarcted myocardium regions
Anterior	43,850 (45.7)	147 (44.5)	0.339
Inferior	31,786 (33.1)	89 (26.9)	0.006
Duration of hospital stay (days)	14.0±11.0	13.0±9.0	0.040

Data are presented as n (%), or mean±SD. AMI, acute myocardial infarction; BMI, body mass index; CKD, chronic kidney disease; MI, myocardial infarction; SCAD, spontaneous coronary artery dissection.

Therapeutic Management

Table 2 presents the comparison of in-hospital therapeutic management between patients with and without SCAD. After hospitalization, primary PCI (53.0% vs. 91.1%; P<0.001) and stent implantation (27.3% vs. 80.5%; P<0.001) were less frequently conducted among patients with SCAD. Moreover, the use of intravascular ultrasound was lower in those with SCAD (61.5 vs. 77.2%; P<0.001). Coronary artery bypass grafting was performed in 0.3% of patients with SCAD and 1.3% of those without SCAD (P=0.141). Patients with SCAD were less likely to receive intra-aortic balloon pumping (IABP; 9.4% vs. 12.8%), but this comparison did not meet statistical significance (P=0.073).

Table 2.

Therapeutic Management

	SCAD (−; n=95,974)	SCAD (+; n=330)	P value
Coronary revascularization
Primary PCI	87,398 (91.1)	175 (53.0)	<0.001
Stent implantation	77,283 (80.5)	90 (27.3)	<0.001
CABG	1,273 (1.3)	1 (0.3)	0.141
Intravascular Imaging
IVUS	74,068 (77.2)	203 (61.5)	<0.001
OCT	8,148 (8.5)	34 (10.3)	0.234
Mechanical circulatory support
IABP	12,320 (12.8)	31 (9.4)	0.073
ECMO	3,068 (3.2)	6 (1.8)	0.206
VAD	21 (0.1)	0 (0)	1.000
CRT/ICD	272 (0.3)	0 (0)	1.000
Medication use at discharge
β-blocker	61,952 (64.6)	205 (62.1)	0.357
ACEI/ARB	66,545 (69.3)	177 (53.6)	<0.001
Calcium channel antagonist	14,562 (15.2)	126 (38.2)	<0.001
Statin	79,666 (83.0)	178 (53.9)	<0.001
Cardiac rehabilitation	59,914 (62.4)	203 (61.5)	0.735
Anti-platelet therapy
Aspirin	81,797 (85.2)	251 (76.1)	<0.001
P2Y₁₂ inhibitor	79,284 (82.6)	117 (35.5)	<0.001
DAPT	75,943 (79.1)	107 (32.4)	<0.001
Patients with AMI who received PCI (n=87,573)	SCAD (−; n=87,398)	SCAD (+; n=175)
Aspirin	78,134 (89.4)	151 (86.3)	0.182
P2Y₁₂ inhibitor	78,309 (89.6)	111 (63.4)	<0.001
DAPT	75,250 (86.1)	103 (58.9)	<0.001
Patients with AMI who did not receive PCI (n=8,731)	SCAD (−; n=8,576)	SCAD (+; n=155)
Aspirin	3,662 (42.7)	100 (64.5)	<0.001
P2Y₁₂ inhibitor	952 (11.1)	6 (3.9)	0.004
DAPT	695 (8.1)	4 (2.6)	0.012

Data are presented as n (%). ACEI, angiotensin-converting enzyme inhibitor; AMI, acute myocardial infarction; ARB, angiotensin II receptor blocker; CABG, coronary artery bypass grafting; CAG, coronary angiography; CRT, cardiac resynchronization therapy; DAPT, dual antiplatelet therapy; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pumping; ICD, implantable cardioverter defibrillator; IVUS, intravascular ultrasound; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; SCAD, spontaneous coronary artery dissection; VAD, ventricular assist device.

While the use of β-blockers was similar between the groups (62.1% vs. 64.6%; P=0.357), patients with SCAD were less likely to receive angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (53.6% vs. 69.3%; P<0.001) and statins (53.9% vs. 83.0%; P<0.001), accompanied by a greater frequency of calcium channel blocker use (38.2% vs. 15.2%; P<0.001; Table 2). Antiplatelet therapy was less frequently administered in patients with SCAD, including aspirin (76.1% vs. 85.2%; P<0.001), P2Y₁₂ inhibitors (35.5% vs. 82.6%; P<0.001), and DAPT (32.4% vs. 79.1%; P<0.001). In patients receiving PCI, lower frequencies of P2Y₁₂ inhibitor (63.4 vs. 89.6%; P<0.001) and DAPT (58.9 vs. 86.1%; P<0.001) were observed in SCAD patients (Table 2). In those who did not receive PCI, while SCAD patients more frequently received aspirin (64.5 vs. 42.7%; P<0.001), they were less likely treated with P2Y₁₂ inhibitor (P=0.004) and DAPT (2.6 vs. 8.1%; P=0.012); Table 2).

In-Hospital Outcomes

In-hospital all-cause mortality is summarized in Figure 2. Three (0.9%) out of 330 patients with SCAD died during their index hospitalization. In the unadjusted cohort, patients with SCAD showed a lower rate of in-hospital all-cause mortality compared with those without SCAD (0.9% vs. 3.1%; P=0.016). However, after matching for age and sex, this difference was no longer statistically significant (1.0% vs. 3.3%; P=0.089; Figure 2). Additional matching for age, sex, body mass index, hypertension, diabetes, and dyslipidemia similarly showed no significant difference in mortality between the groups (1.0% vs. 2.9%; P=0.142; Figure 2). Standard mean differences of covariates after propensity score matching are shown in Supplementary Table 1.

Figure 2.

Comparison of in-hospital all-cause mortality. BMI, body mass index; SCAD, spontaneous coronary artery dissection.

Subgroup Analyses of SCAD Patients

Further analysis was conducted to compare in-hospital all-cause mortality in a variety of subgroups (Table 3). The use of aspirin was associated with a lower adjusted in-hospital all-cause mortality (0.0 vs. 4.3%; P=0.002), whereas primary PCI (1.6 vs. 0.2%; P=0.223), and the use of β-blocker (0.0 vs. 1.6%; P=0.646) and statin (0.0 vs. 2.2%; P=0.608) did not lower in-hospital all-cause mortality (Table 3).

Table 3.

Subgroup Analyses of In-Hospital All-Cause Mortality

Variable	Adjusted in-hospital all-cause mortality (%)	P value
PCI
−	0.2	0.223^¶
+	1.6	0.223^¶
Aspirin
−	4.3	0.002^†
+	0.0	0.002^†
DAPT
−	1.5	0.192^†
+	0.0	0.192^†
β-blocker
−	1.6	0.646^‡
+	0.0	0.646^‡
Statin
−	2.2	0.608^§
+	0.0	0.608^§

The following clinical characteristics were adjusted: ^¶traditional risk factors+aspirin, β-blocker, and ACEI; ^†traditional risk factors+PCI; ^‡traditional risk factors+aspirin, statin, and ACEI; ^§traditional risk factors+aspirin (traditional risk factors include age, female, BMI, hypertension, dyslipidemia, diabetes, smoking, and CKD). Abbreviations as in Tables 1,2.

SCAD Patients’ Ages, Location of Infarcted Myocardium Regions and Duration of Hospital Stay

Infarcted myocardium regions and duration of hospital stay in patients with SCAD were further compared according to age. As shown in Figure 3, the frequency of inferior MI increased in association with the age of patients with SCAD (P=0.036 for trend; Figure 3A). There was a trend toward an increase in the proportion of anterior MI in younger patients with SCAD, but this comparison did not meet statistical significance (P=0.083 for trend; Figure 3A). Shorter duration of hospital stay was observed in older patients with SCAD (P=0.025 for trend; Figure 3B). Table 4 summarizes the clinical characteristics in each age category. There were significant differences in age and the use of aspirin across the groups (Table 4).

Figure 3.

Comparison about affected myocardium regions and duration of hospital stay in different age categories of spontaneous coronary artery dissection patients. (A) Infarcted myocardium regions. (B) Duration of hospitalization. MI, myocardial infarction.

Table 4.

Comparison of Clinical Characteristics in SCAD Patients Stratified According to Age

	Age (years)						P value
	≤35 (n=23)	36–40 (n=32)	41–45 (n=49)	46–50 (n=100)	51–55 (n=87)	56–60 (n=39)	P value
Female	15 (69.5)	25 (84.3)	38 (77.5)	93 (93.0)	70 (81.6)	28 (71.7)	0.012
BMI (kg/m²)	23.5±5.9	22.5±5.2	23.6±3.9	23.0±4.2	22.7±3.9	22.9±3.9	0.857
Hypertension	7 (30.4)	15 (50.0)	26 (53.1)	64 (64.0)	51 (59.8)	28 (71.8)	0.021
Dyslipidemia	10 (47.8)	12 (40.6)	21 (42.9)	52 (52.0)	48 (56.3)	24 (61.5)	0.361
Diabetes	0 (0.0)	2 (6.3)	0 (0.0)	5 (5.0)	6 (6.9)	5 (12.8)	0.122
Hyperuricemia	1 (4.3)	1 (3.1)	1 (2.0)	1 (1.0)	1 (1.1)	1 (2.6)	0.871
Smoking	9 (43.5)	17 (56.3)	19 (38.8)	37 (37.0)	33 (39.1)	14 (35.9)	0.505
CKD	0 (0.0)	0 (0.0)	1 (2.0)	0 (0.0)	1 (1.1)	0 (0.0)	0.661
Killip class ≥2	8 (36.3)	8 (26.6)	20 (40.8)	23 (23.0)	24 (27.9)	10 (25.6)	0.307
Therapeutic management
Primary PCI	9 (43.5)	16 (53.1)	28 (57.1)	54 (54.0)	43 (50.6)	22 (56.4)	0.903
IABP	4 (17.4)	3 (9.4)	3 (6.1)	8 (8.0)	9 (10.3)	4 (10.3)	0.750
ECMO	1 (4.3)	2 (6.3)	0 (0.0)	3 (3.0)	0 (0.0)	0 (0.0)	0.137
Aspirin	18 (82.6)	19 (62.5)	43 (87.8)	82 (82.0)	59 (69.0)	27 (69.2)	0.025
DAPT	7 (34.8)	9 (28.1)	15 (30.6)	35 (35.0)	26 (31.0)	13 (33.3)	0.978
β-blocker	10 (47.8)	10 (31.3)	24 (49.0)	31 (31.0)	27 (32.2)	18 (46.2)	0.134
ACEI/ARB	10 (47.8)	13 (43.7)	25 (51.0)	57 (57.0)	46 (54.0)	23 (58.9)	0.763
Calcium channel antagonist	9 (43.5)	16 (53.1)	19 (38.8)	37 (37.0)	32 (37.9)	10 (25.6)	0.312
Statin	9 (43.5)	13 (43.8)	27 (55.1)	54 (54.0)	45 (52.9)	27 (69.2)	0.300
Cardiac rehabilitation	10 (47.8)	19 (62.5)	30 (61.2)	68 (68.0)	52 (60.9)	21 (53.8)	0.472

Data are presented as n (%), or mean±SD. Abbreviations as in Tables 1,2.

Analysis of Entire Patients With AMI

Of all patients with AMI (n=392,820), 0.1% (n=428) were defined as SCAD. Supplementary Table 2 describes the comparison of clinical characteristics, therapeutic management and in-hospital all-cause mortality between all patients with and without SCAD. The demographics of SCAD patients were almost similar to those in patients aged ≤60 years. The frequencies of IABP (11.0 vs. 14.8%; P=0.043) and CABG (0.2 vs. 1.7%; P=0.018) were significantly lower in patients with SCAD (Supplementary Table 2). With regard to the in-hospital outcome, a lower all-cause mortality was observed in patients with SCAD (3.7 vs. 6.8%; P=0.011). However, after adjusting for clinical characteristics, in-hospital all-cause mortality did not differ between the 2 groups (adjustments for age and gender: 7.7 vs. 6.8%, P=0.445; adjustments for age, gender, BMI, hypertension, diabetes and dyslipidemia: 4.5 vs. 5.7%, P=0.271; Supplementary Table 2).

Validation of SCAD

In 50 randomly selected SCAD cases, all exhibited angiographic coronary dissection. Of these, the type II SCAD pattern was observed in 72% (36/50). The type I and III pattern was exhibited in 8% and 20%, respectively. None of these were driven by iatrogenic causes. The comparison of clinical demographics between these 50 validated cases and the remaining 280 cases is shown in Supplementary Table 3. There were no significant differences in clinical characteristics between these 2 groups (Supplementary Table 3).

Discussion

In the present analysis using the nationwide JROAD-DPC database, SCAD was identified in 0.34% of 96,304 patients hospitalized for AMI in Japan. In SCAD patients, a greater frequency of inferior AMI and a shorter duration of hospital stay were observed in association with older age. Following adjustments of clinical characteristics, in-hospital outcomes in SCAD patients were comparable with those of patients with atherosclerotic AMI. Of note, subgroup analysis revealed a lower in-hospital mortality in SCAD patients receiving aspirin, whereas the use of β-blocker, statin, and primary PCI was not necessarily associated with lower in-hospital all-cause mortality. These findings provide insights into the clinical characteristics, outcomes, and therapeutic management in the setting of SCAD.

The diagnosis of SCAD using DPC data remains challenging. One recent DPC analysis from the United States excluded AMI patients without documentation of ‘coronary angiography’,³ while a Japanese study restricted the analysis to female AMI patients.¹⁶ Thus, a standardized DPC-based definition of SCAD has not yet been established. In the current analysis, given that most SCAD patients require emergent coronary angiography, ‘dissection’, ‘emergent hospitalization’, and ‘coronary angiographic evaluation’ were considered major key terms for identifying SCAD cases within the DPC framework. Furthermore, this analysis focused on patients aged <60 years because SCAD occurred in those with a younger age. As a consequence, the frequency of SCAD in the present study was 0.34%, comparable with that reported in other observational studies.¹⁹^,²³^,²⁴ The clinical profiles in our SCAD cohort characterized by younger age, female predominance, fewer traditional atherogenic risk factors, and lower frequencies of primary PCI and stent implantation are consistent with previous reports.³^,¹⁶^,²³ We conducted validation in 50 randomly selected cases, and all of these exhibited angiographic coronary dissections that were not attributable to iatrogenic causes. The diagnostic validity of cardiovascular conditions using the DPC data has been supported in prior studies.¹⁶^,¹⁷ Specifically, high diagnostic concordance rates have been reported for acute myocardial infarction, heart failure, and related cardiovascular procedures in Japanese administrative data, including those from the JROAD-DPC database.¹⁶^,¹⁷ These findings suggest that our DPC-based definition could be applicable for identifying and characterizing the clinical features and management patterns of SCAD.

All-cause mortality is one of the most robust outcome measures available in the JROAD-DPC dataset. In the present study, after adjusting for clinical characteristics, no significant difference in in-hospital all-cause mortality was observed between patients with and without SCAD. This finding is consistent with observations from 2 other DPC-based studies in the United States.³^,²⁰ In particular, one of these is the largest nationwide analysis that included 2,654,087 patients with AMI who were aged <60 years.³ Similar to our analysis, both of these studies showed lower unadjusted in-hospital mortality in patients with SCAD. However, after propensity-matching analysis, this difference was not evident between SCAD and non-SCAD patients.³^,²⁰ These findings indicate that younger age, predominance of females, and fewer atherosclerotic risk factors may be potential contributors to lower in-hospital mortality in SCAD patients, and SCAD itself may not necessarily be associated with lower mortality.

A notable finding is that >50% of SCAD patients underwent primary PCI. While this rate was significantly lower than that in non-SCAD patients, it remains substantially higher than the 14.1% reported in the Canadian SCAD registry.²⁵ One explanation may lie in the angiographic characteristics of SCAD, such as diffuse arterial narrowing,²⁴^,²⁶ which can mimic atherosclerotic lesions and lead to underdiagnosis. As a result, primary PCI may be performed under the assumption of typical atherosclerotic AMI. To date, favourable effiacy of primary PCI has not been clearly demonstrated in SCAD patients.²⁷^,²⁸ In our subgroup analysis, primary PCI was not associated with lower in-hospital all-cause mortality in patients with SCAD. Given that risks of PCI-related complications are increased due to fragile vessel walls of SCAD,²⁷^,²⁸ clinical benefits of coronary revascularization may be diminished in the setting of SCAD.

Our findings provide clinical insights into therapeutic management of SCAD. One of the therapeutic concerns is that antiplatelet therapy may induce intramural bleeding and then cause recurrence of SCAD. We observed lower all-cause mortality in SCAD patients who received aspirin after hospitalization, whereas the use of dual-antiplatelet therapy did not necessarily improve all-cause mortality. These findings highlight single antiplatelet therapy as an appropriate management, as current statements from the American Heart Association and the European Society of Cardiology recommend.⁶^,⁷ In contrast, all-cause mortality did not differ between those with and without the use of β-blockers. While current statements recommend β-blockers in SCAD patients,⁶^,⁷ the efficacy of β-blockers on cardiac outcomes was inconsistent in observational studies.²⁹ Currently, a randomized controlled trial is ongoing to investigate the efficacy of β-blockers on major cardiovascular events in patients with SCAD.³⁰ It is expected that these studies will provide additional evidence about the benefit of β-blockers in the setting of SCAD.

The difference in the proportion of infarcted myocardium regions between patients with atherosclerotic-related and SCAD-related AMI has been reported in published studies.³¹^,³² In STEMI patients with SCAD, left main or left anterior descending coronary arteries were more frequently involved, accompanied by a lower frequency of right coronary artery.³¹ Our DPC analysis showed a smaller proportion of inferior MI, which was consistent with the aforementioned finding. Interestingly, in particular, myocardium regions attributable to SCAD varied according to age. A lower prevalence of inferior MI was observed in association with younger age in SCAD patients. In those aged ≤35 years, the frequency of inferior MI was 8.7%, and anterior MI occurred in 56.5% of those. The detailed mechanism behind these observations remains unknown. Whether age might affect the coronary segment, which more likely harbors fragile vessel walls and intramural bleeding, requires further investigation.

The JROAD-DPC data provides the duration of hospital stay, which is a potential measure to evaluate disease severity. We observed a shorter duration of hospital stay in SCAD patients compared with non-SCAD patients. This characteristic was more pertinent to aging. As mentioned above, considering that the proportion of inferior MI was greater in older SCAD patients, this may reflect a smaller size of MI, leading to a shorter duration of hospital stay. In contrast, younger SCAD patients required longer hospital stays. Numerically higher occurrence of anterior MI in younger SCAD patients might account for their longer duration of hospital stay. It could be argued that age might be another important clinical feature to stratify the disease severity of SCAD patients.

While SCAD is still a challenging disease in clinical settings, its diagnosis and appropriate management are crucial. According to our observations, physicians have to recognize SCAD as a potential diagnosis in younger female patients presenting with AMI. In particular, in the case of female AMI patients who do not have atherogenic coronary risk factors, physicians should be more aware of SCAD. Meticulous evaluation of coronary angiography is an important approach to diagnosing SCAD. As shown in the validation data, the frequency of visible dissection is low. Given that diffuse narrowing is more frequently observed, physicians need to understand 3 types of angiographic coronary dissections and differentiate them from atherosclerotic diseases. With regard to therapeutic management, primary PCI is associated with an increased risk of procedural complications. As shown in the subgroup analysis, PCI did not necessarily lower in-hospital mortality. This finding supports conservative management in SCAD patients. With regard to medication use, the use of aspirin was associated with a lower in-hospital all-cause mortality. As such, prompt diagnosis and selection of appropriate medical therapies are needed to manage SCAD.

Study Limitations

Several limitations should be considered when interpreting the present findings. First, the DPC data offer limited clinical detail for accurately diagnosing SCAD, raising the possibility that some SCAD cases were misclassified as non-SCAD. Nonetheless, the SCAD patients identified in this study were predominantly female and had a lower prevalence of atherogenic risk factors, reflecting typical characteristics of clinically diagnosed SCAD. Second, despite the use of a nationwide large-scale dataset, the number of SCAD cases remained relatively small, potentially limiting statistical power. In particular, all-cause death occurred in only 3 SCAD cases. Due to this low frequency of all-cause death, the current study does not have enough statistical power to evaluate this difficult outcome in SCAD patients. Third, as with all observational studies, treatment decisions – including the choice of medical therapy and coronary revascularization – were made at the discretion of treating physicians rather than by random assignment. Although adjustments were made for clinical characteristics, unmeasured confounding and selection bias may persist. Fourth, the JROAD-DPC database captures only in-hospital all-cause mortality; therefore, differences in other cardiovascular outcomes between groups could not be assessed. Fifth, a coronary angiographic evaluation was conducted in 50 randomly selected cases of SCAD patients. While clinical demographics in the remaining 280 SCAD patients were similar to those in validated cases, their angiographic images were not reviewed. Sixth, the JROAD-DPC database does not have any data about sex hormones and vessel tortuosity, which are features of SCAD patients. In addition, none of the SCAD patients exhibited connective-tissue disorders. Therefore, whether these features affected our findings remains unknown. Seventh, since the current analysis did not have any data about the recurrence of SCAD, the clinical characteristics and factors associated with the recurrence of SCAD remain unknown. Last, the database records readmissions only when they occur at the same hospital as the index admission; rehospitalizations at other institutions are not captured, potentially leading to underestimation of readmission rates.

Conclusions

In this JROAD-DPC analysis, SCAD accounted for 0.34% of AMI cases among patients aged ≤60 years and was associated with fewer atherogenic risk factors and lower use of aspirin, β-blockers, and primary PCI. In SCAD patients, a greater frequency of inferior AMI and shorter duration of hospital stay were observed in association with older age. However, in-hospital all-cause mortality was similar to that of atherosclerotic AMI. Of note, subgroup analysis revealed a lower in-hospital mortality in SCAD patients receiving aspirin, whereas the use of β-blocker, statin, and primary PCI was not necessarily associated with lower in-hospital all-cause mortality, suggesting that SCAD carries a comparable clinical burden. Our observations highlight the need for physicians to manage SCAD patients with appropriate medical therapies.

Acknowledgments

We acknowledge Ms. Yuko Yoshioka and Ms. Emi Kanai for their excellent assistance.

Sources of Funding

This study was funded by the Japan Agency for Medical Research and Development (grant no. 22ek0109575h0002).

Disclosures

Y.M., S.Y. are members of Circulation Reports’ Editorial Team. Y.K. received research support from Kowa, Nipro, and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda, and Daiichi-Sankyo. The other authors have no relationships relevant to the contents of this paper.

IRB Information

This study was approved by the institutional ethics committee of the National Cerebral and Cardiovascular Center (R21016-4).

Data Availability

The deidentified participant data will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-25-0202

References

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