Adverse events after spontaneous coronary artery dissection

Spontaneous coronary artery dissection (SCAD) is an infrequent but increasingly recognised cause of acute coronary syndrome (ACS) that predominantly affects relatively young women aged 45–52 years and may even occur in association with pregnancy, where it is the most common cause of a myocardial infarction. 2 In contrast to ACS due to atherosclerotic disease, SCAD sufferers have few traditional risk factors apart from hypertension, and the pathophysiology involves impaired coronary flow, not due to plaque rupture, plaque erosion or thrombus formation associated with a calcific nodule, as is the case for atherosclerotic disease, but to the spontaneous formation of an intramural haematoma (IMH) that causes dissection of the vessel wall medial layer. The IHM is likely due to vasa vasorum rupture with or without an intimal tear. As the IMH expands, it compresses the ipsilateral coronary artery wall against the contralateral wall, thereby occluding the coronary lumen and results in ischaemia or infarction of the subtended myocardium. While much has been learnt about the clinical presentation and sequelae of SCAD from studies of retrospective and ambispective registries, metaanalyses and prospective cohorts, major gaps in our understanding of disease mechanisms, management and outcomes persist, with little prospective data from large cohorts and lack of data from randomised control studies. GarciaGuimaraes and colleagues report on the treatment and clinical outcomes of SCAD determined in a cohort of 389 patients assembled from The Spanish Registry on SCAD involving subjects from 34 hospitals. Although the study uses a nonrandomised observational design, particular strengths are its prospective nature, the reasonably large size of the cohort assembled, its careful documentation of SCAD diagnosis by a central angiography reading group and the use of an independent clinical events committee to evaluate adverse outcomes. Moreover, although the study has limitations, as duly acknowledged by the authors, and sheds little new light on the optimal management of SCAD, it does yield important new hypothesisgenerating findings that warranted confirmation in future controlled studies. The study confirms that for those patients who survive to hospital admission, the overall prognosis is favourable, with a survival at discharge of 98%, and 6% suffering a major inhospital adverse cardiovascular event (MAE), mainly driven by reinfarction or unplanned revascularisation and 13% developing a major adverse cardiovascular or cerebrovascular event (MACCE) over a median followup of 2 years. Of course, the outcomes of SCAD sufferers prior to hospitalisation remains unknown, and undoubtedly, some succumb to the disorder. Although the inhospital outcomes reported by GarciaGuimaraes et al are confirmatory, if not better than those reported by others, the MAEs and MACCEs reported did not include the considerable psychosocial burden associated with SCAD, including insomnia, anxiety, depression and even posttraumatic stress disorder, stemming from the lack of precise knowledge of disease pathophysiology and the considerable concerns experience by many SCAD sufferers of the possibility of recurrences. Of interest in this regard, GarciaGuimaraes and colleagues reported a SCAD recurrence rate of only 2% over a median followup of over 2 years, which is markedly lower than the 17% over a median followup of 3.9 years and 29.4% over 10 years reported by the Mayo Clinic Group, and 22% reported by Nakashima et al over a median followup of 2.8 years. This low incidence of recurrences is attributed by the authors possibly to the high use of therapies aimed at reducing vessel wall shear stress (β-blockers) and at stabilising the vessel wall (statins), although evidence for the latter is meagre, and in fact, statin usage has been reported not to be associated with reduced SCAD recurrences, and their usage is not recommended in the absence of atherosclerotic disease or diabetes mellitus. In keeping with previous reports, the incidence of chronic inflammatory disorders (~5%) and of connective tissue diseases (0.5%) was low, whereas the incidence of triggers, particularly acute stress within 48 hours of the index SCAD event, was high in the Spanish cohort, although, in terms of the latter, it would have been of interest to know more about the type and severity of the stress event. Of interest, GarciaGuimaraes et al found that on multivariable analysis involvement of proximal coronary artery segments, a type 2 IMH on angiography, a previous history of hypothyroidism and prescription of dual antiplatelet drugs were independently associated with a higher incidence of MACCEs at followup. The involvement of proximal coronary artery segments is perhaps not surprising given the predicted larger area of myocardium at risk and is confirmatory of a previous cardiac MRI study of SCAD showing that proximal involvement is associated with larger infarct size and with an autopsy study of patients who succumbed to SCAD versus angiography findings in SCAD survivors, which found a much higher incidence of proximal lesions in the former. Similarly, the association of type 2 IMH lesions with increased MACCEs confirms the findings of a previous study that evaluated predictors of SCAD progression, although, given that type 2 SCAD lesions account for the majority (~70%) of all angiographic types, and given that the association was lost in the fourth year of followup (GarciaGuimaraes et al; figure 3D), it will be of interest to see if it persists in larger prospective studies. Perhaps more surprising is the association of a history of hypothyroidism with MACCEs, given that one would anticipate that vessel wall shear stress would be reduced in the presence of hypothyroidism, so intuitively, one might expect a lower incidence of SCAD in such patients. In the study of GarciaGuimaraes et al, 40% of those with a history of hypothyroidism had subclinical disease, and only 4% were overtly hypothyroid at the time of their index SCAD event but, unfortunately, their thyroid function at the time of their MACCE was not available. Given that both hypothyroidism and SCAD show a female preponderance, it is unclear if this association is causal or merely fortuitous. However, hypothyroidism has previously been associated with arterial dissections in noncoronary arteries, as well as with increased vessel wall stiffness. Thus, it is possible, as the authors speculate, that hypothyroidism leads to chronic structural changes in the coronary artery wall that predispose to vessel wall dissection, a notion Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia Department of Cardiology, St Vincent’s Hospital, Sydney, New South Wales, Australia University of New South Wales, Sydney, New South Wales, Australia John Hunter Hospital, New Lambton Heights, New South Wales, Autralia