Table 1.

Current Knowledge, Gaps, and Research Priorities in SCAD

Domain	Current Knowledge	Knowledge Gaps	Research Priorities
Pathophysiology and disease mechanisms	Female, various genetic associations and different triggering events are now linked to SCAD Imaging studies have shown that a primary intramural hematoma is likely the predominant mechanism in SCAD	We do not yet understand how these predisposing factors lead to SCAD and what exactly happens at the levels of the arterial wall (eg, why does an intramural hematoma occur?) What is the prevalence and relationship between post-SCAD chest pain and coronary microvascular dysfunction (CMD)?	Deeper understanding of genetic mechanisms, including how known SCAD gene associations are causal Develop animal and cell-based model systems for SCAD and FMD Continued human imaging and other studies to delineate precise pathobiological mechanisms
Fibromuscular dysplasia	A high proportion of patients with SCAD also have FMD, with possible shared genetic mechanisms	How do SCAD and FMD relate, and does FMD alter the clinical trajectory of SCAD? Which FMD patients are at risk for SCAD?	Further genetic study into the mechanisms relating FMD and SCAD
Medical therapy	Beta-blockers associated with reduction in recurrent SCAD7 DAPT is associated with increased MACE among conservatively managed SCAD37	Efficacy and optimal duration of SAPT vs DAPT for conservatively managed SCAD Beta-blockers use and optimal duration post-SCAD Novel, disease-specific therapies are lacking	Randomized controlled trials of differing medical therapy strategies to assess short- and long-term clinical outcomes Further basic and translational research into pathophysiologic mechanisms of disease to enable development of disease-specific therapeutics
Angiography for diagnosis	Yip Saw SCAD Angiographic Classification29 Isolated intramural hematoma may have higher risk of progression4	Optimal diagnostic technique (invasive vs noninvasive) for initial diagnosis vs follow-up	Optimal invasive strategies for management of unstable patients with high-risk anatomy
Percutaneous coronary intervention	High rates of SCAD PCI complications32	Optimal intervention techniques	Comparative evaluation of suggested techniques to limit PCI complications Improved risk-prediction models to identify patients at high risk for failure of medical therapy
Coronary artery bypass surgery	Higher than expected early short-term mortality and poor graft patency long-term30	Optimal bypass techniques; indications for bypass	Comparative evaluation of PCI vs CABG for certain lesions considered high risk (LMCA)
Psychosocial Health	Acute emotional stress is a commonly identified SCAD trigger, particularly among women43 SCAD events are potentially traumatic experiences that can lead to depression, anxiety, and PTSD symptoms44,45	Mechanisms linking experiences of acute emotional stress with SCAD onset are unknown. Whether and how pre-SCAD mental health is relevant to SCAD onset is unclear. How depression, anxiety, and PTSD symptoms manifest over time after SCAD and whether they predict course of illness and event recurrence is unknown. Psychosocial treatments to address mental health outcomes IN SCAD ARE lacking.	Longitudinal studies of mental health outcomes after SCAD and how they relate to course of illness Evaluating psychosocial interventions specifically for addressing mental health in patients with SCAD Developing models for screening and treating SCAD-related mental health consequences in specialized cardiology care clinics
Reproductive health considerations	∼40% of pregnancy-associated MI are due to SCAD8 Pregnancy-associated SCAD is associated with higher-risk presentations as compared with nonpregnancy related SCAD (left main or multivessel coronary involvement, greater risk of left ventricular systolic dysfunction, cardiogenic shock)	Clearer understanding of pathophysiology of SCAD, to include role of estrogen, progesterone, and prolactin in the pathogenesis of SCAD A clearer understanding of relative contribution of predisposing factors, including hypertensive disorders of pregnancy, as they relate to better risk personalization for patients desiring pregnancy after SCAD	Patient level data of dose/temporal exposure of hormonal exposure as it relates to SCAD presentation including changes throughout the reproductive lifespan (eg, onset of premature menopause, diagnosis of cervical incompetence, uterine ablation, tubal ligation, and/or caesarean section) and impact of exogenous hormone use (including contraception, hormone replacement therapy, and hormone-based breast cancer therapy). Further risk stratification of patients desiring future pregnancy
Exercise	Repetitive Valsalva can increase intravascular pressure with theoretical increased risk for vascular dissection	How and to what degree is high-intensity exercise and/or repetitive Valsalva causal in the pathogenesis of SCAD.	Evidence-based guidance to give individual-level exercise recommendations to patients following SCAD to avoid overly restrictive recommendations that may have downstream negative physical and mental health consequences

CABG = coronary artery bypass grafting; DAPT = dual antiplatelet therapy; FMD = fibromuscular dysplasia; LMCA = left main coronary artery; PCI = percutaneous coronary intervention; SCAD = spontaneous coronary artery dissection.