Spontaneous coronary artery dissection (SCAD) is defined as an epicardial coronary artery dissection that is not associated with atherosclerosis or trauma and not iatrogenic [1]. The proposed mechanism of SCAD is coronary artery obstruction caused by formation of an intramural hematoma (most frequent form of SCAD) or intimal disruption [2]. This disease process is more common in younger women, particularly with pregnancy [3]. To date, fibromuscular dysplasia is now not considered as a SCAD risk factor but an associated pathology with probable common genetic background. SCAD poses a difficult challenge in management, as decisions regarding revascularization and medical management seem to be tailored to the individual patient; in general, a conservative strategy seems to be the mainstay of treatment with revascularization dictated by the clinical status of the patient [4, 5]. Cardiogenic shock (CS) incidence varies between 1–16% in patients with SCAD and the outcomes as well as management of these patients still remains a challenge considering rare occurrence. Therefore, we evaluated and compared outcomes (such as mortality, readmission rates, and complications) based on CS in patients with SCAD utilizing Nationwide Readmissions Database (NRD) between January 1, 2016, to December 30, 2020.

We analyzed the NRD from 2016–2019. Drawing data from Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), the NRD used verified patient linkage numbers to track entrants across hospitals within a state. The NRD contains unweighted data from about 18 million discharges each year in the United States and weighted, it estimates approximately 36 million discharges. Patients with the principal diagnosis or primary discharge diagnosis of SCAD with and without CS were identified, defined as ICD-CM 10 codes of I25.42 and R570. We excluded patients for various factors: missing critical demographic information, such as age; missing data for mortality; index admissions in the month of December because 30-day readmission outcomes would not be feasible; age 18; and concomitant iatrogenic puncture or laceration of the coronary vessels (ICD-10-CM code of I97.51). We followed the methodological standards recommended by the Agency for Healthcare Research and Quality.

We evaluated demographics (e.g., age, gender), conventional risk factors, comorbidities present on the index admission, and in-hospital outcomes using their specific ICD-10-CM codes as seen in Table 1. Aggregated Charlson comorbidity score was also calculated [6]. Complications included death, cardiac arrest, mechanical circulatory support (Intra-aortic balloon pump (IABP), impella, extracorporeal membrane oxygenation (ECMO)), cardiovascular implantable electronic device (CIED) use, sepsis, pressor support, stroke, acute kidney injury (AKI), dialysis, acute heart failure (HF), bleeding, and need for blood transfusions. In accordance with the HCUP Data Use Agreement, we excluded any number or variables containing small numbers of observations ($\le$10) that could potentially pose the risk for identification of persons or data privacy violation.

The primary outcomes were in-hospital mortality and 30-day readmission, and the secondary outcome was to compare the complications in SCAD patient with CS compared to those without CS. The weighting of patient-level observations was implemented to obtain national estimates. Multivariate regression analysis models were built by including all confounders significantly associated with the outcome on univariable analysis with a cutoff p-value of 0.2. Variables deemed important determinants of the outcomes based on literature were forced into the models. Binary outcomes such as index hospitalization mortality and complications were compared by logistic regression. For readmission comparison, we used the time-to-event Cox regression analysis. Propensity matching was done by the Greedy method. Proportions were compared using the Mantel-Haenszel Chi-square test or Fisher exact test, and continuous variables were compared using the Student t-test. All p values were two-sided, with 0.05 as the threshold for statistical significance. Percentages and means were computed for categorical and continuous variables, respectively. Odds/hazard ratios and their 95% confidence intervals are used to report the regression analysis results. All statistical analyses were performed using STATA (Version 16, Stata Statistical Software, College Station, TX, USA).

We analyzed 2473 individuals with SCAD, 2199 of these individuals did not have cardiogenic shock whereas 274 of these individuals did have cardiogenic shock. As seen in Table 1, the average age of the SCAD without cardiogenic shock group was slightly lower at 53 years compared to the average age of the SCAD with cardiogenic shock group being 60 years. The prevalence of men was higher in the cardiogenic shock group as compared to the non-cardiogenic shock group. The cardiogenic shock group was more likely to have Medicare for their insurance compared to private insurance for the non-cardiogenic shock group. Chronic comorbidities that were more likely to be found in the cardiogenic shock group included pulmonary hypertension, hypertension, peripheral vascular disease, congestive heart failure, diabetes mellitus, coagulation abnormalities, electrolyte imbalances, and coronary artery disease and equivalents (CADAE).

As seen in Table 2, when comparing SCAD with cardiogenic shock to SCAD without cardiogenic shock, there was a statistically significant increased OR for death (propensity matched OR 24.93 (7.49–83.05), use of mechanical circulatory support (propensity matched OR 15.30 (6.87–34.04), ventricular tachycardia (propensity matched OR 4.45 (1.92–10.34), utilization of blood transfusions (propensity matched OR 3.82 (1.86–7.87), acute kidney injury (propensity matched OR 4.02 (1.45–11.13), need for mechanical ventilation (propensity matched OR 8.87 (3.53–22.31), and respiratory failure (propensity matched OR 4.95 (1.83–13.41)))))))). There was no statistically significant difference in 30-day readmission rates between the two groups (Table 3).

Data surrounding SCAD have broadened in recent years, however data for SCAD-CS are less robust. The present study is among the largest to evaluate real-world clinical experience of SCAD with comparative evaluation of those with SCAD-CS in both men and women of all ages. In this NRD study, 11% of identified SCAD hospitalizations had cardiogenic shock, which is considerably higher than previous estimates of 2–6% with SCAD-shock [7, 8]. Additionally, SCAD-CS patients were older, less likely to be female, and had higher prevalence of comorbid hypertension (HTN), diabetes mellitus (DM), congestive heart failure (CHF), or existing atherosclerotic cardiovascular disease, a departure from previous findings [8, 9]. Mortality for SCAD-CS was high in our study, as has been described previously with in-hospital mortality rates between 8–30% [8, 9]. Nonetheless, SCAD-CS mortality is likely lower than atherosclerotic MI-related CS [10]. Pharmacologic and mechanical circulatory support were necessary for 17% and 40% of SCAD-CS cases, respectively, and mechanical circulatory support (MCS) strategies included IABP, Impella, and ECMO support.

The reason behind this study’s differing epidemiologic findings is unclear but likely multifactorial. Prior SCAD studies typically compared SCAD populations with non-SCAD (i.e., atherosclerotic) MI populations who represent inherently higher-risk population, or specifically assessed SCAD in women with MI. Our sample included all recorded US hospitalizations for SCAD in the NRD. Further, in our sample those who developed CS were more likely to have high-risk characteristics, which may explain a certain predilection for higher-acuity presentation. Due to limitations of the NRD data and our study, we could not control for potential confounders such as dissection anatomy, thrombolysis in myocardial infarction (TIMI) flow grade, pre-admission medication use (i.e., antiplatelet or anticoagulation therapy), or even misclassification bias (i.e., atherosclerosis-related dissection) that may explain the differences between the SCAD-CS and non-CS groups. Lastly, the variation and potential biases associated with NRD analysis increase the risk of type I error and may account for the differing findings.

Clinical practice recommendations for management of SCAD and in particular SCAD-CS are based on understanding and experience with atherosclerotic coronary disease, which represents an inherently different pathophysiologic phenomenon. Studies have demonstrated spontaneous “healing” of the native coronary vessels after presentation [11, 12], as well as increased technical complexity with PCI for SCAD, which informs the current preference for conservative management. Nonetheless, our experience and understanding are broadening. In a recent observational study of a SCAD population, those treated with PCI at index hospitalization had similar 3-year outcomes compared to those managed medically [13]. Those with high-risk presentation or SCAD-CS are more likely to be treated with revascularization [8]. Additionally, MCS use has been described previously, though largely in case report or case series. Critically ill patients undergo management as deemed medically necessary, and in the largest study of SCAD-CS, 14 patients managed with IABP did not experience IABP-related complications [2]. However, in light of the angiographic course of SCAD, the theoretical risk of iatrogenic vascular injury and/or false lumen propagation that may be associated with MCS strategies require further evaluation. Further data are not available to assess MCS use in SCAD-CS nor to compare supportive strategies utilizing inotropic support alone. Finally, optimal management strategies in cases of recurrent SCAD are even more elusive.

It can be argued that the greater complications seen in SCAD with cardiogenic shock is secondary to both the acute clinical instability of the patient, in addition to these patient’s having significant comorbidities in greater frequency, such as hypertension, congestive heart failure, diabetes mellitus, and peripheral vascular disease, when compared to SCAD without cardiogenic shock. More research needs to be conducted to elucidate other reasons for the greater rate of complications as other factors, such as hospital capabilities and physician experience can also factor in.

The present study contains several limitations, including those noted above. First, the inherent pitfalls of retrospective, non-randomized database analysis cannot be avoided. We performed multivariate regression analysis which was further balanced by propensity matching to adjust for confounding variables, but other confounding factors may be present and unaccounted for. Second, the NRD data are based on ICD-10 codes which are subject to errors or variation in coding practice that cannot be adjusted for. Third, we included patient with SCAD as primary diagnosis for admission, which represents ultimate outcome but does not adequately provide information surrounding initial presentation severity nor clinical progression throughout the stay as data are finalized at the time of discharge. Fourth, the NRD dataset is limited as it includes only hospitalization information rather than individual-level data, without longitudinal follow-up data to allow for longer-term outcome assessment. Fifth, Procedure-level data, such as angiographic and intravascular imaging findings, and detailed management-related information are also not provided. Despite the limitations, our data provide novel findings of the clinical characteristics of SCAD-CS. However, these findings require further assessment through robust prospective study, if feasible. Additionally, management strategies should be evaluated to improve in-hospital and long-term outcomes in this population.

SCAD is a unique condition that can lead to many complications. In our analysis, we showed that SCAD associated with cardiogenic shock compared to SCAD not associated with cardiogenic shock results in greater odds of complications including death, use of mechanical circulatory support, need for blood transfusions, ventricular tachycardia, acute kidney injury, use of mechanical ventilation, and respiratory failure. It can be argued that the greater complications seen in SCAD with cardiogenic shock is secondary to both the acute clinical instability of the patient, in addition to these patient’s having significant comorbidities in greater frequency, such as hypertension, congestive heart failure, diabetes mellitus, and peripheral vascular disease, when compared to SCAD without cardiogenic shock. Regardless, SCAD with cardiogenic shock represents a significantly critical clinical scenario that requires a multi-disciplinary approach to prevent the many potential complications associated with this disease process.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

CK designed the research study and drafted the manuscript. DB and NP performed analyses and drafted the manuscript. CK and ZW provided help and advice on analysis. CK and ZW cross-validated the results. NP, YQ, NM, MA, SS, ZW and HJ authors reviewed, edited, and interpreted data for the work and substantially contributed to the conception of the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

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This research received no external funding.

The authors declare no conflict of interest. Hani Jneid is serving as one of the Editorial Board members of this journal. We declare that Hani Jneid had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Lloyd W. Klein, Karim Bendjelid and Ahmed Zaky.