Abstract
Background: Cardiac rupture (CR), encompassing both free wall and ventricular septal ruptures, is a serious complication of ST-segment elevation myocardial infarction (STEMI). In this study, we aimed to investigate the incidence, characteristics, and clinical outcomes of CR in patients with STEMI.
Methods and Results: The Japan Acute Myocardial Infarction Registry (JAMIR) is a multicenter prospective study. Of the 3,411 patients hospitalized with acute MI between 2015 and 2017, data from 2,626 patients with STEMI (612 women [23.3%]; median age, 68 years) were analyzed. CR occurred in 34 patients (1.3%), comprising free wall rupture in 25 cases (73.5%), ventricular septal rupture in 8 cases (23.5%), and both in 1 case (2.9%). Compared to those without CR, the cumulative incidence of the primary endpoints (cardiovascular death, non-fatal MI, or non-fatal stroke) at 1 year was significantly higher in the CR group (64.7% vs. 7.9%, log-rank P<0.001). Factors independently associated with CR included older age, anterior wall infarction, and prolonged onset-to-admission time. Notably, the incidence of CR increased with longer onset-to-admission times (0–3 h, 0.6%; 3–6 h, 1.7%; 6–12 h, 1.7%; ≥12 h, 3.6%; P for trend <0.001), but was not associated with door-to-device times (≤90 min, 0.7% vs. >90 min, 1.4%; P=0.156).
Conclusions: CR following STEMI is associated with delayed onset-to-admission time and poor clinical outcomes.
Central Figure
Cardiac rupture (CR), encompassing both free wall and ventricular septal ruptures, remains a catastrophic and often fatal complication of ST-segment elevation myocardial infarction (STEMI).1–3 Although CR is relatively uncommon, it occurs more frequently in particular populations, including older individuals, patients experiencing MI for the first time, those with anterior wall infarction, and female patients.1–4 The introduction of reperfusion therapies has significantly improved STEMI management, notably reducing both deaths and CR incidence.1,3,4 However, current evidence on CR is derived from studies conducted before the widespread adoption of primary percutaneous coronary intervention (PCI) and the routine use of modern antiplatelet agents, such as prasugrel and clopidogrel, in STEMI treatment.2–5 Furthermore, prior research has predominantly focused on in-hospital outcomes, with limited data available on longer-term outcomes, including 1-year mortality rates after CR.2–5
In this study, we aimed to assess the incidence, clinical characteristics, and 1-year outcomes of CR in patients with STEMI, within the context of contemporary clinical practice, as a subanalysis of the Japan Acute Myocardial Infarction Registry (JAMIR).6–10
Methods
Study Population
JAMIR is a prospective, observational, multicenter study. Detailed protocols for the JAMIR study have been published previously.6–10 Briefly, 3,411 consecutive patients with type 1 or type 2 MI within 24 h of symptom onset were enrolled at 50 institutions across Japan between December 2015 and May 2017. Acute MI (AMI) was diagnosed using the universal definition, with the addition of the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) criteria when applicable to institutional settings.6,11–14 Notably, 99% of enrolled patients met the universal definition of AMI.6 STEMI was defined by the presence of ST-segment elevation ≥0.1 mV in ≥2 contiguous leads, new left bundle branch block, newly developed Q waves associated with chest pain, or elevated cardiac biomarker levels.10,11,13,15 Next, 785 patients with non-STEMI (NSTEMI) were excluded, so the final study cohort comprised 2,626 patients with STEMI (Figure 1).
Follow-up data were collected by investigators, clinical research coordinators, or local data managers at each participating site between 9 and 15 months after AMI onset. The median follow-up duration was 350 days (interquartile range [IQR], 269–395 days).
The JAMIR subanalysis followed the ethical principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Tohoku University Hospital (2024-1-321). The requirement for informed consent was waived due to the observational design of the study. However, study details were disseminated via a website and at study sites, allowing participants the opportunity to opt out of inclusion in the registry.
Definition of CR and Study Endpoints
CR was defined as either a free wall or ventricular septal rupture. The diagnosis was determined based on clinical, echocardiographic, and anatomical findings (postmortem or surgical) assessed by the investigators.1,3,4 Free wall rupture was classified into oozing or blow-out types. Papillary muscle rupture was not included in this study due to the unavailability of relevant data. The primary endpoint was a composite outcome comprising cardiovascular death, non-fatal MI, or non-fatal stroke. The secondary endpoint was all-cause death.
Statistical Analysis
Categorical variables are expressed as numbers and percentages, while continuous variables are summarized as medians with IQRs. Categorical variables were analyzed using the chi-squared test or Fisher’s exact test, as appropriate. The frequency trends of CR based on the time from symptom onset to hospital admission were evaluated using the Cochran-Armitage trend test. Continuous variables were compared using the t-test or Wilcoxon rank sum test, according to the data distribution.
The Kaplan-Meier method was applied to estimate the cumulative incidence of endpoints, with group differences assessed using the log-rank test. Multivariate Cox proportional hazards models were used to compare outcomes between groups, adjusting for clinically relevant variables, including age, sex, hypertension, diabetes mellitus, dyslipidemia, estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), peak creatine phosphokinase (CPK), Killip class ≥2, onset-to-admission time, primary PCI, anterior wall infarction, final Thrombolysis in MI (TIMI) flow grade 3, dual antiplatelet therapy (DAPT), and oral anticoagulant use. Results are reported as hazard ratios (HRs) with 95% confidence intervals (CIs).
Three multivariate logistic regression models were constructed to identify CR predictors. Model 1 was adjusted for clinically relevant variables, including age, sex, eGFR, anterior wall infarction, primary PCI, final TIMI flow grade, DAPT, oral anticoagulant use, and onset-to-admission time. Model 2 included sex and variables with a P value <0.05 in the unadjusted analyses, excluding emergency coronary angiography (CAG). Model 3 was adjusted for clinically relevant variables, including age, sex, eGFR, anterior wall infarction, emergency CAG, and onset-to-admission time. Results are presented as odds ratios (ORs) with 95% CIs.
Statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA). All tests were two-sided, and statistical significance was set at P<0.05.
Results
Baseline Characteristics
The baseline characteristics of the 2,626 patients with STEMI are presented in Table 1. The overall median age was 68 years (58–78 years), 612 (23.3%) patients were female, and 1,329 (50.6%) patients had anterior wall infarction. The rate of primary PCI performed was 95.9%, and 2,502 (95.3%) patients received DAPT during hospitalization. Of the 2,626 patients with STEMI, 2,569 (97.8%) patients were prescribed aspirin, 2,231 (85.0%) prasugrel, and 399 (15.2%) clopidogrel.
Table 1.
Patients’ Characteristics
| |
Overall
(n=2,626) |
Cardiac rupture
(n=34 [1.3%]) |
Non-cardiac rupture
(n=2,592 [98.7%]) |
P value |
| Baseline characteristics |
| Age, years |
68 (58–78) |
75.5 (66.5–85) |
68 (58–78) |
<0.001 |
| ≥75 years |
874 (33.3) |
19 (55.9) |
855 (33.0) |
0.005 |
| Female sex |
612 (23.3) |
12 (35.3) |
600 (23.2) |
0.096 |
| BMI, kg/m2 |
23.6 (21.4–26.0) |
22.0 (19.8–24.6) |
23.6 (21.4–26.0) |
0.068 |
| Hypertension |
1,841 (70.1) |
20 (58.8) |
1,821 (70.3) |
0.148 |
| Diabetes mellitus |
885 (33.7) |
8 (23.5) |
877 (33.8) |
0.207 |
| Dyslipidemia |
1,810 (68.9) |
19 (55.9) |
1,791 (69.1) |
0.098 |
| Atrial fibrillation |
167 (6.4) |
2 (5.9) |
165 (6.4) |
1.000 |
| Prior myocardial infarction |
204 (7.8) |
0 (0) |
204 (7.9) |
0.107 |
| Prior stroke |
246 (9.4) |
4 (11.8) |
242 (9.3) |
0.554 |
| eGFR, mL/min/1.73 m2
|
65.5 (51.1–80.0) |
48.8 (29.8–65.5) |
65.7 (51.3–80.1) |
<0.001 |
| LVEF, % (n=2,031) |
51 (43–60) |
47 (41–54) |
51 (43–60) |
0.101 |
| Peak CPK, IU/L |
1,963 (897–3,817) |
2,699 (1,185–6,378) |
1,960 (889–3,793) |
0.123 |
| Peak CK-MB, IU/L (n=2,255) |
190 (81–365) |
214 (124–549) |
189 (81–364) |
0.078 |
| Presentation |
| Anterior wall infarction |
1,329 (50.6) |
21 (61.8) |
1,308 (50.5) |
0.190 |
| Killip class ≥2 |
653 (24.9) |
20 (58.8) |
633 (24.4) |
<0.001 |
| Heart rate, beats/min |
77 (63–90) |
96 (72–107) |
76 (63–90) |
<0.001 |
| SBP, mmHg |
138 (115–158) |
117 (96–144) |
138 (115–158) |
0.020 |
| Onset-to-admission time, min (n=2,500) |
125 (60–275) |
276 (145–585) |
125 (60–270) |
0.009 |
| Angiographic and procedural characteristics |
| Emergency CAG |
2,593 (98.4) |
28 (82.4) |
2,565 (99.0) |
<0.001 |
| Primary PCI (n=2,593) |
2,486/2,593 (95.9) |
22/28 (78.6) |
2,464/2,565 (96.1) |
<0.001 |
| IABP or ECMO use |
387 (14.7) |
17 (50.0) |
370 (14.3) |
<0.001 |
| IABP use |
379 (14.4) |
15 (44.1) |
364 (14.0) |
<0.001 |
| ECMO use |
61 (2.3) |
6 (17.7) |
55 (2.1) |
<0.001 |
| Infarct-related artery location |
| Right coronary artery |
1,030 (39.2) |
5 (14.7) |
1,025 (39.5) |
0.002 |
| Left main coronary artery |
44 (1.7) |
0 (0) |
44 (1.7) |
1.000 |
| Left anterior descending artery |
1,293 (49.2) |
21 (61.8) |
1,272 (49.1) |
0.141 |
| Left circumflex |
283 (10.8) |
2 (5.9) |
281 (10.8) |
0.575 |
| Unknown |
17 (0.7) |
2 (5.9) |
15 (0.6) |
0.020 |
| Multivessel disease (n=2,593) |
1,081/2,593 (41.7) |
16/28 (57.1) |
1,065/2,565 (41.5) |
0.095 |
| Stent use (n=2,486) |
2,286/2,486 (92.0) |
17/22 (77.3) |
2,269/2,464 (92.1) |
0.027 |
| Final TIMI flow grade 3 (n=2,593) |
2,330/2,593 (89.9) |
18/28 (64.3) |
2,312/2,565 (90.1) |
<0.001 |
| Onset-to-device time, min (n=2,367) |
205 (135–376) |
447 (223–837) |
204 (135–375) |
0.024 |
| Door-to-device time, min (n=2,486) |
66 (50–89) |
78 (55–98) |
66 (50–89) |
0.660 |
| Drugs during hospitalization |
| Dual antiplatelet therapy |
2,502 (95.3) |
20 (58.8) |
2,482 (95.8) |
<0.001 |
| Aspirin |
2,569 (97.8) |
28 (82.4) |
2,541 (98.0) |
<0.001 |
| Prasugrel |
2,231 (85.0) |
16 (47.1) |
2,215 (85.5) |
<0.001 |
| Clopidogrel |
399 (15.2) |
7 (20.6) |
392 (15.1) |
0.378 |
| Oral anticoagulant use |
358 (13.6) |
10 (29.4) |
348 (13.4) |
0.007 |
Data are expressed as n (%) or median (interquartile range). BMI, body mass index; CAG, coronary angiography; CK-MB, creatine kinase-myocardial band; CPK, creatine phosphokinase; ECMO, extracorporeal membrane oxygenation; eGFR, estimated glomerular filtration rate; IABP, intra-aortic balloon pump; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; TIMI, Thrombolysis in Myocardial Infarction.
CR occurred in 34 (1.3%) patients, comprising 25 (73.5%) with free wall rupture, 8 (23.5%) with ventricular septal rupture, and 1 (2.9%) patient with both types of rupture (Figure 1, Table 1). Compared to patients without CR, those with CR were older, had a higher rate of Killip class ≥2, and had a lower eGFR. They also had a higher heart rate and lower systolic blood pressure. Regarding procedures, the CR group had significantly lower rates of emergency CAG, primary PCI, stent use, and right coronary artery culprit lesions than the non-CR group. In addition, the rates of intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) use were higher, and the final TIMI flow grade 3 rate was lower in the CR group. Aspirin and prasugrel were prescribed at lower rates during hospitalization, resulting in a significantly lower rate of DAPT. Conversely, the rate of oral anticoagulant use was significantly higher in the CR group than in the non-CR group (Table 1).
In this study, onset-to-admission time, onset-to-device time, and door-to-device time data were available for 2,500, 2,367, and 2,486 patients, respectively. Compared to the non-CR group, the onset-to-admission time (CR, 276 min [145–585 min] vs. non-CR, 125 min [60–270 min]; P=0.009) and onset-to-device time (CR, 447 min [223–837 min] vs. non-CR, 204 min [135–375 min]; P=0.024) were significantly longer in the CR group; however, the door-to-device time did not differ between groups (CR, 78 min [55–98 min] vs. non-CR, 66 min [50–89 min]; P=0.660) (Table 1).
Endpoints
The cumulative 1-year incidences of the primary and secondary endpoints were 64.7% and 64.7% in patients with CR and 7.9% and 7.8% in those without CR, respectively. Kaplan-Meier analysis demonstrated that the cumulative incidence of the primary and secondary endpoints was significantly higher in the CR group compared to the non-CR group (both, log-rank P<0.001) (Figure 2A,B). Furthermore, landmark analyses using the 30-day time point demonstrated that the CR group had higher rates of both the primary and secondary endpoints during the periods before and after 30 days, compared with the non-CR group (both, log-rank P<0.05) (Figure 2C,D).
Multivariate Cox proportional hazards analysis showed that CR was independently associated with both primary (adjusted HR, 9.0; 95% CI, 3.8–21.7) and secondary (adjusted HR, 9.9; 95% CI, 4.1–24.1) endpoints (Table 2).
Table 2.
Cox Proportional Hazards Analyses for the Primary Endpoint (Cardiovascular Death, Non-Fatal Myocardial Infarction, or Non-Fatal Stroke) and All-Cause Death in Patients With STEMI
| |
Unadjusted analysis |
Adjusted analysisA |
| HR (95% CI) |
P value |
HR (95% CI) |
P value |
| Primary endpoint |
| Cardiac rupture (vs. non-cardiac rupture) |
13.9 (8.9–21.6) |
<0.001 |
9.0 (3.8–21.7) |
<0.001 |
| Secondary endpoint (all-cause death) |
| Cardiac rupture (vs. non-cardiac rupture) |
13.9 (8.9–21.6) |
<0.001 |
9.9 (4.1–24.1) |
<0.001 |
AAdjusted for variables: age, sex, hypertension, diabetes mellitus, dyslipidemia, eGFR <30 mL/min/1.73 m2, LVEF, peak CPK, Killip class ≥2, onset-to-admission time, primary PCI, anterior wall infarction, final TIMI flow grade 3, dual antiplatelet therapy, and oral anticoagulant use. CI, confidence interval; HR, hazard ratio; STEMI, ST-segment elevation myocardial infarction. Other abbreviations as in Table 1.
Outcomes According to Type of CR
We also assessed outcomes based on the type of CR. As only 1 patient exhibited both blow-out and ventricular septal ruptures, that patient was categorized under the blow-out type group for analyses. Cumulative incidence rates of the primary and secondary endpoints according to the type of CR are shown in Figure 3. Primary and secondary endpoints occurred significantly more frequently in the blow-out type, followed by the ventricular septal rupture type and then the oozing type (both, log-rank P<0.001) (Figure 3A,B).
Predictors of CR in Patients With STEMI
Multivariate logistic regression results to identify independent predictors of CR in patients with STEMI are presented in Table 3. Prolonged onset-to-admission time (OR, 2.83; 95% CI, 1.10–7.26), age ≥75 years (OR, 2.51; 95% CI, 1.06–5.96), and anterior wall infarction (OR, 2.53; 95% CI, 1.02–6.28) were significantly associated with CR (model 1). Another multivariate analysis showed that prolonged onset-to-admission time (OR, 2.95; 95% CI, 1.05–8.31) and age ≥75 years (OR, 3.18; 95% CI, 1.20–8.40) correlated with an increased incidence of CR, whereas DAPT (OR, 0.21; 95% CI, 0.06–0.79) was associated with a reduced incidence of CR (model 2). Furthermore, in the multivariable model that included emergency CAG as a covariate, prolonged onset-to-admission time (OR, 3.83; 95% CI, 1.53–9.63), age ≥75 years (OR, 2.33; 95% CI, 1.04–5.24), eGFR <30 mL/min/1.73 m2
(OR, 2.71; 95% CI, 1.04–7.09), and anterior wall infarction (OR, 2.47; 95% CI, 1.01–6.00) were independently associated with a higher incidence of CR, whereas undergoing emergency CAG (OR, 0.03; 95% CI, 0.01–0.12) was independently associated with a lower incidence of CR (model 3).
Table 3.
Multivariate Predictors of Cardiac Rupture in Patients With STEMI
| |
Unadjusted analysis |
Adjusted analysis
(model 1)A |
Adjusted analysis
(model 2)B |
Adjusted analysis
(model 3)C |
| OR (95% CI) |
P value |
OR (95% CI) |
P value |
OR (95% CI) |
P value |
OR (95% CI) |
P value |
Longer onset-to-admission
time (>125 min)D |
4.09
(1.66–10.03) |
0.002 |
2.83
(1.10–7.26) |
0.031 |
2.95
(1.05–8.31) |
0.041 |
3.83
(1.53–9.63) |
0.004 |
| Age ≥75 years |
2.57
(1.30–5.09) |
0.007 |
2.51
(1.06–5.96) |
0.037 |
3.18
(1.20–8.40) |
0.020 |
2.33
(1.04–5.24) |
0.040 |
| Female sex |
1.81
(0.89–3.68) |
0.101 |
0.85
(0.33–2.19) |
0.740 |
0.94
(0.35–2.52) |
0.904 |
1.02
(0.44–2.38) |
0.959 |
| BMI, per 1-kg/m2 increase |
0.90
(0.81–1.01) |
0.062 |
|
|
|
|
|
|
| Diabetes mellitus |
0.60
(0.27–1.34) |
0.211 |
|
|
|
|
|
|
| eGFR <30 mL/min/1.73 m2 |
4.49
(2.06–9.74) |
<0.001 |
2.54
(0.87–7.38) |
0.088 |
1.98
(0.65–6.03) |
0.230 |
2.71
(1.04–7.09) |
0.042 |
Large infarct size
estimated using peak
CK-MB (>190 IL/L)E |
1.40
(0.68–2.86) |
0.364 |
|
|
|
|
|
|
SBP, per 10-mmHg
increase |
0.88
(0.78–0.98) |
0.020 |
|
|
0.91
(0.79–1.06) |
0.211 |
|
|
Heart rate, per 1-beat/min
increase |
1.02
(1.01–1.04) |
<0.001 |
|
|
1.01
(1.00–1.03) |
0.106 |
|
|
| Anterior wall infarction |
1.59
(0.79–3.18) |
0.194 |
2.53
(1.02–6.28) |
0.045 |
|
|
2.47
(1.01–6.00) |
0.047 |
| Killip class ≥2 |
4.42
(2.22–8.80) |
<0.001 |
|
|
2.00
(0.71–5.63) |
0.187 |
|
|
| Emergency CAG |
0.05
(0.02–0.13) |
<0.001 |
|
|
|
|
0.03
(0.01–0.12) |
<0.001 |
| Primary PCI |
0.15
(0.06–0.38) |
<0.001 |
0.39
(0.10–1.55) |
0.183 |
0.53
(0.11–2.71) |
0.448 |
|
|
| Final TIMI grade <3 flow |
0.20
(0.09–0.43) |
<0.001 |
0.58
(0.20–1.65) |
0.307 |
1.17
(0.31–4.51) |
0.816 |
|
|
| Dual antiplatelet therapy |
0.06
(0.03–0.13) |
<0.001 |
0.28
(0.08–1.00) |
0.050 |
0.21
(0.06–0.79) |
0.021 |
|
|
| Oral anticoagulant use |
2.69
(1.27–5.67) |
0.009 |
1.88
(0.74–4.77) |
0.185 |
1.18
(0.40–3.46) |
0.770 |
|
|
AAdjusted for clinically relevant variables: age, sex, eGFR <30 mL/min/1.73 m2, anterior wall infarction, primary PCI, final TIMI grade, dual antiplatelet therapy, oral anticoagulant use, and onset-to-admission time. BAdjusted for sex and variables with a P value <0.05 in unadjusted analyses, excluding emergency CAG. CAdjusted for clinically relevant variables: age, sex, eGFR <30 mL/min/1.73 m2, anterior wall infarction, emergency CAG, and onset-to-admission time. DLonger onset-to-admission time was defined as longer than the median time (>125 min). ELarge infarct size estimated by peak CK-MB was defined by peak CK-MB higher than the median peak CK-MB (>190 IU/L). OR, odds ratio. Other abbreviations as in Tables 1 and 2.
Association of Onset-to-Admission Time, Door-to-Device Time, and CR
The relationship between onset-to-admission time and door-to-device time with CR incidence was evaluated. CR incidence significantly increased with longer onset-to-admission times (0–3 h, 0.6%; 3–6 h, 1.7%; 6–12 h, 1.7%; ≥12 h, 3.6%; P for trend <0.001) (Figure 4A). In contrast, door-to-device time showed no significant association with CR incidence (≤90 min, 0.7% vs. >90 min, 1.4%; P=0.156) (Figure 4B).
Comparison of Patient Characteristics With and Without the Primary Endpoint in the CR Group
Among the patients with CR, clinical characteristics were compared between those with and without occurrence of the primary endpoint. Compared with patients without the primary endpoint occurrence, those with the primary endpoint occurrence were older, more likely to have the blow-out type of CR, and less likely to have the oozing type. There were no significant differences in the rates of primary PCI and emergency CAG, peak CPK levels, and onset-to-admission time (Supplementary Table).
Discussion
Our major findings were as follows. (1) CR occurred in 1.3% of patients with STEMI; (2) CR was significantly associated with the primary endpoint (composite of cardiovascular death, non-fatal MI, or non-fatal stroke) as well as all-cause death; (3) independent predictors of CR included older age, anterior wall infarction, and prolonged onset-to-admission time; and (4) CR incidence increased significantly with longer onset-to-admission times. This prospective nationwide registry offers comprehensive data on the incidence, clinical features, and outcomes of CR in the modern era of primary PCI in Japan.
Characteristics, Trends, and Prognosis of CR in STEMI
During the pre-reperfusion era, CR occurred in approximately 6% of transmural MI cases.3 Figueras et al. reported a decline in CR prevalence, decreasing from 6.2% before 1982 to 3.2% between 2001 and 2006.2 Similarly, Honda et al. documented a time-dependent reduction in CR incidence among Japanese AMI populations, with rates of 3.3% (1977–1989), 2.8% (1990–2000), and 1.7% (2001–2011), a decline that paralleled the increased adoption of reperfusion therapies.4 Additionally, Honda et al. reported a CR incidence in patients with STEMI between 2001 and 2011 (≈1%) that aligned with other multicenter registries, including the Global Registry of Acute Coronary Events (GRACE) study and the AMI-Kyoto Multi-Center Risk Study.3,4,16
Moreover, several studies on CR predate the use of contemporary antiplatelet agents, such as the potent P2Y12 inhibitor prasugrel, now a standard STEMI treatment. In this current study, primary PCI was performed in 95.9% of patients, and prasugrel was prescribed in 85.0%, reflecting the high utilization of modern STEMI treatments.17 The CR incidence in the JAMIR cohort was 1.3%, which is similar to that of prior studies.3,4,16,18,19 Notably, a lower proportion of patients with CR underwent DAPT comprising aspirin and prasugrel. As JAMIR is a real-world database rather than a randomized controlled trial, the reasons for not undergoing DAPT may include clinical factors, such as CR on admission or an elevated risk of significant bleeding.20
The results of this study highlight the characteristics and 1-year outcomes of patients with CR managed with modern STEMI treatments. Most previous studies of STEMI-related mechanical complications, including CR, focused on short-term outcomes such as in-hospital or 30-day mortality rates.2–5,16,18,19,21 However, in our study, a 1-year cardiovascular event rate of 64.7% was observed among patients with CR, predominantly driven by deaths. Furthermore, most adverse events occurred within 30 days of STEMI onset, emphasizing the acute phase as a critical period requiring intensive management. The landmark analyses in this study also revealed significant differences in event rates even beyond 30 days, indicating the importance of careful follow-up during the chronic phase in patients with CR.
Our findings underscore the challenges encountered in managing CR, necessitating multidisciplinary collaboration for rapid recognition, accurate diagnosis, hemodynamic stabilization, and decision-making support for definitive or palliative therapies. In addition, consistent with previous studies, independent predictors of CR included older age, elevated heart rate, anterior wall infarction, and prolonged onset-to-admission time.3,4,18,19 For patients exhibiting these characteristics, close monitoring of hemodynamics and echocardiographic findings is crucial to ensure timely surgical intervention when CR is detected.
Impact of Timing on CR Incidence and Prevention Strategies
One notable strength of this study was the availability of detailed timing data. We observed that the frequency of CR increased with prolonged onset-to-admission time, but no significant association was identified between door-to-device time and CR occurrence. In addition, onset-to-admission time was one of the strongest factors associated with CR. Findings from the Portuguese Registry on Acute Coronary Syndromes (ProACS), a prospective multicenter observational study, similarly demonstrated that a longer duration from symptom onset to hospitalization (≥6 h) was associated with an increased risk of mechanical complications.19 The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) AMI registry further showed that a shorter onset-to-balloon time was associated with better 3-year clinical outcomes in patients with STEMI undergoing primary PCI, although the benefit of shorter door-to-balloon time was limited to those presenting early.22 Early presentation to a healthcare facility following symptom onset not only enables timely primary PCI but also facilitates the early administration of β-blockers and angiotensin-converting enzyme inhibitors, both recognized as protective against CR.2,3,23 These findings, along with those from previous studies, underscore the importance of patient education and awareness campaigns aimed at reducing prehospital delays to enhance outcomes and mitigate CR risk in patients with STEMI.
Study Limitations
First, CR occurred in only 34 patients (1.3%), and the sample size may have been insufficient to draw definitive conclusions. Second, as an observational study rather than a randomized controlled trial, the findings are subject to selection bias and potential unmeasured confounders. Decision-making regarding PCI, surgical repair, and medication use was at the discretion of the attending physicians, which may have influenced the results. Third, data on specific treatments for CR, including surgical repair, were unavailable. Given the high mortality rate associated with CR, surgical intervention is a critical option that could impact the outcomes of STEMI patients with CR in this study.1,24,25 Finally, the timing of CR onset was not documented. Consequently, we could not differentiate between patients who presented with CR on admission and those who developed CR during hospitalization, limiting insights into the characteristics and outcomes of these subgroups. In this study, emergency CAG was associated with a lower frequency of CR. Patients who had already developed CR at the time of admission may not have been considered appropriate candidates for emergency CAG. Despite these limitations, this study provides valuable insights into the status of CR in patients with STEMI during the contemporary primary PCI era, characterized by the widespread use of prasugrel. Further research is needed to address these gaps and build on these findings.
Conclusions
This real-world study of JAMIR, assessing 1-year outcomes, showed that CR following STEMI is associated with delayed onset-to-admission time and poor clinical outcomes. These results emphasize the need for strategies to minimize delays in seeking medical care after symptom onset.
Acknowledgments
The JAMIR is a project planned by the Japan Cardiovascular Research Foundation and is funded by Daiichi Sankyo Co., Ltd.
The authors wish to thank all the investigators, clinical research coordinators, and data managers involved in the JAMIR study for their contributions.
The JAMIR study group consists of the following institutions and members: Hokkaido Medical Center: Takashi Takenaka; Hirosaki University: Hirofumi Tomita, Hiroaki Yokoyama; Iwate Medical University: Tomonori Ito, Masaru Ishida, Yorihiko Koeda; Yamagata University: Masafumi Watanabe, Tetsu Watanabe, Taku Toshima; Tohoku University: Hiroaki Shimokawa, Yasuhiko Sakata, Jun Takahashi, Kiyotaka Hao; Sakakibara Heart Institute: Tetsuya Sumiyoshi, Morimasa Takayama; Yokohama City University Hospital: Kazuo Kimura, Masami Kosuge, Toshiaki Ebina; Showa Medical University Fujigaoka Hospital: Hiroshi Suzuki, Atsuo Maeda; Mie University Hospital: Masaaki Ito, Tairo Kurita, Jun Masuda; Matsuzaka Central General Hospital: Takashi Tanigawa; Ehime University Hospital: Jitsuo Higaki, Kazuhisa Nishimura; Oita University: Naohiko Takahashi, Hidefumi Akioka, Kyoko Kawano; Nagasaki University: Koji Maemura, Yuji Koide; Kumamoto University: Sunao Kojima, Kenichi Tsujita; National Cerebral and Cardiovascular Center: Hisao Ogawa, Satoshi Yasuda, Yasuhide Asaumi, Kensaku Nishihira, Yoshihiro Miyamoto, Misa Takegami, Satoshi Honda; Nagasaki Harbor Medical Center: Hiroshi Nakajima; Isahaya General Hospital: Kenji Yamaguchi; Sapporo City General Hospital: Takao Makino; Sapporo Cardiovascular Clinic: Daitarou Kanno; Teine Keijinkai Hospital: Yasuhiro Omoto; Hokkaido Cardiology Hospital: Daisuke Hotta; Sapporo Kosei General Hospital: Toshiya Sato; Nippon Medical School Musashi Kosugi Hospital: Naoki Sato, Arifumi Kikuchi, Michiko Sone, Koji Takagi; Ayase Heart Hospital: Imun Tei; Tokyo Metropolitan Hiroo General Hospital: Takashi Shibui, Sho Nagamine; Nippon Medical School Hospital: Wataru Shimizu, Takeshi Yamamoto; Tokyo Saiseikai Central Hospital: Toshiyuki Takahashi; Tokyo Medical Center: Yukihiko Momiyama; St. Luke’s International Hospital: Atsushi Mizuno; Edogawa Hospital: Hiroshi Ohira; Kyorin University Hospital: Hideaki Yoshino, Youhei Shigeta; Nihon University Itabashi Hospital: Atsushi Hirayama, Yasuo Okumura, Daisuke Fukamachi, Tadateru Takayama; Toho University Omori Medical Center: Hiroki Niikura, Hiroki Takenaka; Mitsui Memorial Hospital: Shuzo Tanimoto, Kazuyuki Yahagi; Tokyo Metropolitan Tama Medical Center: Hiroyuki Tanaka; Disaster Medical Center: Yasuhiro Sato, Ohno Masakazu; Musashino Red Cross Hospital: Takamichi Miyamoto, Nobuhiro Hara; NTT Medical Center: Mikio Kishi; Ome Municipal General Hospital: Shigeo Shimizu, Ken Kurihara; Ogikubo Hospital: Yasuhiro Ishii; Teikyo University Hospital: Ken Kozuma, Yusuke Watanabe; Fraternity Memorial Hospital: Yasuhiro Takahashi; Jikei University Hospital: Michihiro Yoshimura, Satoshi Morimoto; Tokyo Women’s Medical University Hospital: Nobuhisa Hagiwara, Yuichiro Minami; Tokyo Medical University Hospital: Jun Yamashita; Osaki Citizen Hospital: Kaoru Iwabuchi, Takeshi Yamauchi; Sendai Open Hospital: Atsushi Kato, Shigeto Namiuchi; Sendai Medical Center: Tsuyoshi Shinozaki, and Kesennuma City Hospital: Kazunori Ogata, Ryuji Tsuburaya.
Funding
The JAMIR project was planned by the Japan Cardiovascular Research Foundation and funded by Daiichi Sankyo Co., Ltd.
Disclosures
Y.S., S.Y. are members of Circulation Reports’ Editorial Team. S.Y. reports remuneration for lectures from Takeda, Daiichi Sankyo, and Bristol-Myers Squibb, and trust research/joint research funds from Takeda and Daiichi Sankyo; Morimasa Takayama reports lecture fees from Daiichi Sankyo; H.O. reports lecture fees and research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Pfizer and Sanofi. The remaining authors have no conflicts of interest.
IRB Information
Institutional Review Board of Tohoku University Hospital (2024-1-321).
Data Availability
The data underlying this article cannot be shared publicly due to ethical reasons.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circrep.CR-25-0196
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