Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), historically linked to pregnancy but increasingly associated with emotional and physical stressors. The prognostic impact of these precipitating factors remains unclear. This study aimed to evaluate their clinical and prognostic relevance in a large, nationwide prospective SCAD cohort. The prospective Spanish SCAD Registry (RN-DCE) included 388 patients from 34 centers since 2015. Coronary angiograms were centrally reviewed, and patients were categorized based on the presence and type of precipitating factor (emotional or physical). Major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, reinfarction, unplanned revascularization, recurrent SCAD, and stroke, were centrally adjudicated. Cox regression models were used to assess associations with in-hospital and long-term outcomes. Precipitating factors were identified in 40% of patients, with emotional triggers more common than physical (26% vs 15%). Patients with triggers were younger (52 (±11.3) vs 55 (±11.8) years, p = 0.046) and had higher rates of depression and anxiety (24% vs 18%, p = 0.078 and 25% vs 13%, p <0.004). Emotional triggers were more frequent among women and strongly associated with psychiatric history. The overall presence of a trigger was not associated with increased MACCE risk (Adjusted HR: 0.90 (0.39–2.10), p = 0.794). However, SCAD events related to the peripartum period or to Valsalva maneuvers were associated with worse short- and long-term outcomes. In conclusion, in this large national cohort, most precipitating factors were not linked to worse prognosis. However, peripartum-related SCAD and events triggered by Valsalva-like maneuvers may indicate higher-risk presentations and warrant closer clinical attention.
Graphical abstract
Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute coronary syndrome (ACS), characterized by separation of the coronary artery wall into 2 lumens or the presence of an intramural hematoma. While historically linked to pregnancy especially the peripartum period as a pathophysiological trigger, current data suggest that pregnancy-related SCAD accounts for fewer than 5% of cases. Recent focus has shifted to other precipitating factors, such as acute emotional or physical stressors, which may act as immediate triggers. Since the first reported case in 1931 involving fatal vomiting-induced SCAD, various triggers like intense emotional stress, strenuous exercise, hormonal therapy, and Valsalva-like maneuvers have been implicated. ,, Although the interplay between predisposing and precipitating factors likely underlies SCAD pathophysiology, the prognostic value of such triggers remains uncertain. Prior research has explored predisposing factors, but data on the clinical and prognostic relevance of emotional and physical triggers remain very limited. ,,, Therefore, this study aimed to assess these aspects in a large, nationwide, prospective SCAD cohort.
Methods
Study design and clinical information
The prospective Spanish Registry on SCAD (RN-DCE) included patients from 34 university hospitals since 2015. Consecutive patients with angiographic diagnosis of SCAD were enrolled and baseline admission data, along with patients’ demographic and clinical characteristics, and triggers, were prospectively captured. Clinical follow-ups were scheduled at 6 months and then annually for up to 5 years after the initial event. The study protocol conforms to the International Conference on Harmonization/Good Clinical Practice standards and the Declaration of Helsinki and the protocol was approved by the local Medical Ethics Review Committees. All patients provided informed consent.
Procedural details and event adjudication
All coronary angiograms were jointly reviewed by two interventional cardiologists experts on SCAD at the coordinating center’s core lab. If, after reviewing the angiograms and associated clinical data, there were significant doubts about a diagnosis of SCAD, the patient was excluded from the study. A dedicated angiographic analysis notebook was used to systematically document angiographic features including lesion location, morphology, treatment approaches, and outcomes for cases requiring percutaneous coronary intervention (PCI). An independent, blinded Clinical Events Committee reviewed all anonymized clinical reports and angiograms to adjudicate events, which were classified by consensus.
Definitions
The classification of angiographic patterns of SCAD followed the system previously described by Saw et al as follows: Type 1 lesions were characterized by the presence of a double-lumen appearance and/or contrast staining of the vessel wall. Type 2 lesions were defined by diffuse arterial narrowing extending over a segment longer than 20 mm without evidence of a double-lumen image. These were further subclassified into type 2a, where the vessel caliber normalized distal to the lesion, and type 2b, in which the narrowing extended to the distal end of the vessel. Type 3 lesions presented as focal stenoses less than 20 mm in length. Additionally, a fourth category, type 4, was used to describe lesions where the initial angiographic finding was an abrupt vessel occlusion without a visible proximal lesion.
Details on the psychiatric history were captured during the hospitalization from the clinical history of the patients and included depression and anxiety disorders, as defined according to the current DSM-5 criteria.
With regards to precipitating factors (this term being used interchangeably with “triggers” in this manuscript) of SCAD, an emotional trigger was defined as experiencing significant emotional stress within 48 hours before SCAD presentation. Physical triggers were classified into three categories: (1) engagement in strenuous physical exertion within the preceding 48 hours; (2) Valsalva-like maneuvers, including coughing and vomiting; and (3) the postpartum period, defined as the first 12 weeks following childbirth.
As for clinical events, major adverse cardiovascular and cerebrovascular events (MACCE) encompassed all-cause mortality, nonfatal reinfarction, unplanned revascularization, recurrent SCAD, or stroke, occurring during hospitalization or follow-up. Reinfarction was defined according to the third universal definition in place at the time of the study protocol. SCAD recurrence was defined as a new, distinct dissection unrelated to the original lesion, accompanied by clinical evidence of recurrent myocardial ischemia.
Statistical analysis
Continuous variables were expressed as either mean ± standard deviation (SD) or median with interquartile range (IQR 25–75), depending on the data distribution, as assessed by Shapiro-Wilk and Kolmogorov-Smirnov test results. Comparisons were conducted using the independent two-sample t-test, Wilcoxon test, or Mann-Whitney U test, as appropriate. Categorical variables were reported as counts with corresponding percentages and analyzed using Pearson’s chi-square test or Fisher’s exact test. We used the Log-rank test to compare Kaplan–Meier curves. Univariate and multivariate Cox-regression models were generated in order to evaluate the prognostic value of precipitating factors for in-hospital and during follow-up MACCE. Multivariate regression models allowed inclusion of variables with p-value less than 0.10 in the univariate analysis or those of clinical significance. A total of 14 potential covariates were evaluated: These included systemic arterial hypertension, history of hypothyroidism, connective tissue disease, clinical presentation as sudden cardiac death or ventricular arrhythmia, type 2 IMH angiographic pattern, severe coronary tortuosity, proximal or multisegment involvement, lesion termination in a lateral branch, broken line morphology, treatment strategy (conservative management vs PCI), and prescription of beta-blockers, statins, and DAPT at discharge. Collinearity among variables was excluded based on correlation coefficient values. We ensured fulfillment of the proportionality of hazards criteria by visually assessing Kaplan–Meier survival graphs and respective log(-log) plots. A two-sided p-value less than 0.05 was considered significant. Adjustment of p-values for multiple comparisons of data was not performed. Statistical analysis was performed using MedCalc (version 22.005) and SPSS (version 25, IBM).
Results
Clinical characteristics and presentation
A total of 388 consecutive patients with a mean age of 54 years (±11.5) were enrolled in the study. The median clinical follow-up duration was 29 months (IQR 17–38), with no significant difference observed between patients with a precipitating factor and those without (29 months [IQR 14–36] vs 27 months [IQR 15–41], p = 0.382). Baseline clinical characteristics are summarized in Table 1 . The cohort was predominantly female (88%), and nearly three-quarters of patients had at least one cardiovascular risk factor. The most common clinical presentation was non–ST-segment elevation myocardial infarction (NSTEMI) (54%), followed by ST-segment elevation myocardial infarction (STEMI) (40%) ( Table 1 ).
Table 1
Clinical characteristics according to triggers
| Variable, n (%) | All patients, n = 388 | A: Trigger (any), n = 157 | B: No trigger, n = 231 | C: Physical trigger, n = 59 | D: Emotional trigger, n = 100 | p value (A vs B) | p value (C vs D) |
|---|---|---|---|---|---|---|---|
| Age | 54 (±11.5) | 52 (±11.3) | 55 (±11.8) | 56 (±11.3) | 53 (±10.9) | 0.046 | 0.532 |
| Sex (female) | 343 (88) | 141 (90) | 202 (87) | 47 (83) | 92 (94) | 0.293 | 0.030 |
| BMI | 26.5 (±5.3) | 26.5 (±5.4) | 27.1(±5.3) | 26 (±5.6) | 27 (±5.0) | 0.589 | 0.328 |
| Active smoker | 102 (26) | 42 (27) | 60 (26) | 16 (28) | 26 (27) | 0.162 | 0.961 |
| Arterial Hypertension | 139 (36) | 57 (36) | 82 (36) | 20 (35) | 36 (37) | 0.914 | 0.864 |
| Dyslipidemia | 128 (33) | 48 (31) | 80 (35) | 19 (33) | 29 (30) | 0.235 | 0.719 |
| Diabetes mellitus | 21 (5) | 9 (6) | 12 (5) | 2 (4) | 6 (6) | 0.581 | 0.711 |
| Inflammatory disease | 18 (5) | 5 (3) | 13 (6) | 2 (4) | 3 (3) | 0.330 | 0.608 |
| Stroke | 11 (3) | 4 (3) | 7 (3) | 2 (4) | 2 (2) | 0.520 | 0.569 |
| CCS | 20 (5) | 9 (6) | 11 (5) | 1 (2) | 8 (8) | 0.830 | 0.156 |
| Depression | 79 (20) | 38 (24) | 41 (18) | 9 (16) | 28 (29) | 0.078 | 0.052 |
| Anxiety | 69 (18) | 39 (25) | 30 (13) | 5 (9) | 34 (35) | 0.004 | <0.001 |
| Other psychiatric disease | 14 (4) | 6 (4) | 8 (4) | 4 (7) | 2 (2) | 0.530 | 0.193 |
| Alcohol | 12 (3) | 6 (4) | 6 (3) | 2 (4) | 4 (4) | 0.345 | 0.612 |
| Menopause | 192 (49) | 75 (48) | 117 (51) | 22 (38) | 53 (54) | 0.047 | 0.056 |
| Hypothyroidism | 47 (12) | 21 (13) | 26 (11) | 7 (12) | 14 (14) | 0.085 | 0.532 |
| STEMI | 155 (40) | 61 (39) | 94 (41) | 20 (35) | 41 (42) | 0.752 | 0.256 |
| NSTEMI | 211 (54) | 86 (55) | 125 (55) | 30 (53) | 54 (55) | 0.918 | 0.448 |
| Unstable angina | 6 (2) | 3 (2) | 3 (1) | 3 (5) | 0 (0) | 0.689 | 0.048 |
| Stable angina | 1 (0.3) | 0 (0) | 1 (0.4) | 0 (0) | 0 (0) | 0.595 | – |
| Atypical chest pain | 3 (1) | 0 (0) | 3 (1) | 0 (0) | 0 (0) | 0.275 | – |
| Ventricular arrhythmia | 8 (2) | 5 (3) | 3 (1) | 3 (5) | 2 (2) | 0.179 | 0.261 |
| SCD | 4 (1) | 1 (0.6) | 3 (1) | 0 (0) | 1 (1) | 0.650 | 0.632 |
| Syncope | 3 (0.8) | 1 (0.6) | 2 (1) | 0 (0) | 1 (1) | 0.642 | 0.652 |
BMI = body mass index; CCS = chronic coronary syndrome; NSTEMI = Non–ST-segment elevation myocardial infarction; SCD = sudden cardiac death; STEMI = ST-segment elevation myocardial infarction.
Angiographic details
Angiographic data are summarized in Table 2 . The left anterior descending artery (LAD) was the most commonly affected vessel (51%), with distal segments and side branches being the most frequently involved locations (54% and 34%, respectively). The majority of patients presented with an initial thrombolysis in myocardial infarction (TIMI) flow grade of 2 to 3 (73%), and in most cases, the angiographic appearance was consistent with a type 2 SCAD lesion (58%).
Table 2
Angiographic details according to triggers
| Variable, n (%) | All patients, n = 388 | A: Trigger (any), n = 157 | B: No trigger, n = 231 | C: Physical trigger, n = 59 | D: Emotional trigger, n = 100 | p value (A vs B) | p value (C vs D) |
|---|---|---|---|---|---|---|---|
| Coronary artery involved | |||||||
| LMCA | 13 (3) | 5 (3) | 8 (4) | 2 (4) | 3 (3) | 0.561 | 0.608 |
| LAD | 197 (51) | 84 (54) | 113 (49) | 28 (49) | 54 (55) | 0.498 | 0.507 |
| LCX | 138 (36) | 48 (31) | 90 (40) | 19 (33) | 39 (30) | 0.105 | 0.719 |
| RCA | 86 (22) | 40 (26) | 46 (20) | 16 (28) | 4 (25) | 0.214 | 0.704 |
| Multivessel disease | 36 (9) | 18 (12) | 18 (8) | 6 (11) | 12 (12) | 0.285 | 0.804 |
| Segment involved | |||||||
| Proximal | 58 (15) | 22 (14) | 36 (16) | 8 (14) | 14 (14) | 0.772 | 0.583 |
| Medial | 120 (31) | 44 (48) | 76 (33) | 14 (25) | 29 (30) | 0.317 | 0.579 |
| Distal | 174 (45) | 67 (42) | 107 (46) | 22 (38) | 43 (44) | 0.533 | 0.319 |
| Secondary branch | 147 (34) | 64 (41) | 83 (36) | 19 (41) | 37 (38) | 0.340 | 0.684 |
| Type of Dissection | |||||||
| Type 1 | 95 (25) | 45 (29) | 50 (22) | 16 (28) | 29 (30) | 0.107 | 0.417 |
| Type 2 | 226 (58) | 88 (56) | 138 (59) | 31 (54) | 55 (56) | 0.197 | 0.419 |
| Type 3 | 61 (16) | 21 (13) | 40 (17) | 7 (12) | 14 (14) | 0.163 | 0.401 |
| Initial TIMI flow | 0.173 | 0.857 | |||||
| 0 | 56 (14) | 23 (15) | 33 (14) | 7 (12) | 16 (16) | ||
| 1 | 42 (11) | 24 (15) | 18 (8) | 9 (16) | 15 (15) | ||
| 2 | 52 (13) | 22 (14) | 30 (13) | 9 (16) | 12 (12) | ||
| 3 | 34 (60) | 87 (55) | 147 (64) | 32 (56) | 54 (55) | ||
| Length of dissection (mm) | 30 (20–50) | 30 (20–50) | 30 (20–50) | 30 (30–50) | 30 (20–50) | 0.652 | 0.592 |
| Initial treatment | |||||||
| Conservative | 303 (78) | 125 (79) | 178 (77) | 50 (88) | 73 (74) | 0.707 | 0.064 |
| PCI | 84 (22) | 32 (20) | 52 (23) | 7 (12) | 25 (26) | 0.519 | 0.064 |
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