Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear. Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls. Design, Setting, and Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA. Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year). Main Outcome and Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index). Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events. Conclusions and Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.

A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.

BACKGROUND: The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. METHODS: To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. RESULTS: We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. CONCLUSIONS: After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).

Spontaneous coronary artery dissection in old patients: clinical features, angiographic findings, management and outcome.

AIMS: Spontaneous coronary artery dissection (SCAD) is a relatively rare but well-known cause of acute coronary syndrome. Clinical features, angiographic findings, management and outcomes of SCAD in old patients (>65 years of age) remain unknown. METHODS AND RESULTS: The Spanish multicentre prospective SCAD registry (NCT03607981), included 318 consecutive patients with SCAD. Data were collected between June 2015 and April 2019. All angiograms were analysed in a centralized corelab. For the purposes of this study, patients were classified according to age in two groups <65 and ≥65 years old and in-hospital outcomes were analysed. Fifty-five patients (17%) were ≥65 years old (95% women). Older patients had more often hypertension (76% vs. 29%, P < 0.01) and dyslipidaemia (56% vs. 30%, P < 0.01), and less previous (4% vs. 18%, P < 0.001) or current smoking habit (4% vs. 33%, P < 0.001). An identifiable trigger was less often present in old patients (27% vs. 43%, P = 0.028). They also had more often severe coronary tortuosity (36% vs. 11%, P = 0.036) and showed more frequently coronary ectasia (24% vs. 9%, P < 0.01). Older patients were more often managed conservatively (89% vs. 75%, P = 0.025), with no significant differences in major adverse cardiac events during index admission (7% vs. 8%, P = 0.858). There were no differences between groups in terms of in-hospital stay, new acute myocardial infarction, unplanned coronary angiography or heart failure. CONCLUSION: Older patients with SCAD show different clinical and angiographic characteristics compared with younger patients. Initial treatment strategy was different between groups, though in-hospital outcomes do not significantly differ (NCT03607981).

Spontaneous Coronary Artery Dissection: Mechanisms, Diagnosis and Management.

Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome that usually affects young to middle-aged women. Mainly because of its low prevalence, until recently, most of the evidence on this condition was derived from case reports and small series. Over the last 5 years, more robust evidence has become available from larger retrospective and prospective cohorts of patients with SCAD. The increase in knowledge and recognition of this entity has led to the publication of expert consensus on both sides of the Atlantic. However, new data are continuously accumulating from larger cohorts of patients with SCAD, bringing new light to this little-understood condition. The aim of this article is to update the knowledge on SCAD, including new information from recent studies published since the consensus documents from the European Society of Cardiology and the American Heart Association.

Spontaneous coronary artery dissection: from expert consensus statements to evidence-based medicine.

Spontaneous coronary artery dissection (SCAD) represents an increasingly recognized cause of acute coronary syndrome (ACS), especially in young females. Novel diagnostic insights obtained from intracoronary imaging and the frequent association with fibromuscular dysplasia (FMD), have recently enriched our understanding of this unique clinical entity. Recently, two scientific statements from both sides of the Atlantic, summarizing the available information on SCAD, have been simultaneously published. These should help to guide the clinical management of these challenging patients. Major collaborative research efforts are required to move from expert-based recommendations to evidence-based [corrected] medicine.

Current management of spontaneous coronary artery dissection.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) remains an infrequent and elusive clinical entity of unknown etiology. However, our knowledge of SCAD has been significantly enriched in recent years. Large and prospective contemporary series have increased the interest in this disease with fewer patients misdiagnosed and a growing number of cases recognized in daily clinical practice. Classically, SCAD was thought to present mainly in young women without traditional atherosclerotic risk factors but, actually, most patients are middle-aged and are not free from coronary risk factors. A high number of associated conditions have been reported. Of these, fibromuscular dysplasia emerges as a major association with intriguing pathophysiological implications. Areas covered: This review aims to present a contemporary update on SCAD. We concentrate on the clinical scenario, related conditions, practical management and treatment strategies. Expert commentary: Recognition of SCAD is currently much more frequent and accurate as a result of increased clinical awareness and the widespread use of intravascular imaging techniques. Hopefully, in the near future an improvement in the management of SCAD patients will come not only from empirical evidence but also from dedicated clinical trials.

Diagnostic accuracy of a hybrid approach of instantaneous wave-free ratio and fractional flow reserve using high-dose intracoronary adenosine to characterize intermediate coronary lesions: Results of the PALS (Practical Assessment of Lesion Severity) prospective study.

OBJECTIVES: We sought to investigate the diagnostic accuracy of instantaneous wave-free ratio (iFR) and high-dose intracoronary adenosine fractional flow reserve (IC-FFR) compared with classical intravenous adenosine fractional flow reserve (IV-FFR) to assess coronary stenosis severity. The usefulness of two hybrid strategies combining iFR and high-dose IC-FFR was also evaluated. BACKGROUND: Physiological assessment of intermediate coronary stenoses to guide revascularization is currently recommended. METHODS: Consecutive real-world patients with angiographically intermediate coronary stenosis (40-80% diameter stenosis) were prospectively included in the PALS (Practical Assessment of Lesion Severity) study. In every target lesion iFR, high-dose IC-FFR and IV-FFR were systematically measured to assess the accuracy of an hybrid sequential approach combining iFR and IC-FFR. RESULTS: A total of 106 patients with 121 intermediate coronary lesions were analyzed. Both, iFR and IC-FFR showed a significant correlation with IV-FFR (iFR: r = 0.60, 95%CI 0.48-0.70; IC-FFR: r = 0.88; 95%CI: 0.83-0.92). High-dose IC-FFR provided lower FFR values than IV-FFR (0.81 ± 0.08 vs. 0.82 ± 0.09, P = 0.25). Using a receiver-operating-characteristic curve an optimal iFR threshold of 0.91 for the screening test was identified. A sequential test strategy (initial iFR followed by IC-FFR only in lesions with iFR <0.91) yielded an excellent diagnostic accuracy (96.7%, 95%CI 96.7-99.1%) with a sensitivity, specificity, positive and negative predicted values of 100%, 94.7%, 91.8%, and 100%, respectively. A hybrid approach using the previously described iFR gray zone (0.85-0.94) also provided an excellent diagnostic accuracy (95%, 95%CI: 89.5-98.1%). CONCLUSIONS: In patients with intermediate coronary lesions a hybrid strategy by using a sequential approach of iFR and high-dose IC-FFR, provided a very good diagnostic performance to identify physiologically significant stenoses. © 2017 Wiley Periodicals, Inc.

Reliability of physiological assessment of coronary stenosis severity using intracoronary pressure techniques: a comprehensive analysis from a large cohort of consecutive intermediate coronary lesions.

AIMS: We sought to assess the reliability of the most frequently used intracoronary physiologic indices (including intravenous adenosine FFR [IV-FFR], intracoronary low-dose adenosine FFR [LD-IC-FFR], intracoronary high-dose adenosine FFR [HD-IC-FFR], Pd/Pa and iFR). We also sought to analyse factors affecting their reproducibility in a real-world patient population. METHODS AND RESULTS: A total of 91 lesions in 86 consecutive patients were included. Measurements of all physiological indices were repeated within a systematic standardised prospective protocol. All measured indices showed excellent test-retest reliability, with intraclass correlation coefficient (ICC) over 0.96. IV-FFR showed the highest coefficient of variation (CV) values among the studied measurements (Pd/Pa: 0.05; iFR: 0.10; LD-IC-FFR: 0.10; HD-IC-FFR: 0.08; IV-FFR: 0.12). Pd/Pa was significantly less variable than the other indices. On multivariate analysis, female gender, distal lesion location, history of hypertension or kidney failure, as well as presentation as an acute coronary syndrome, were associated with more variability in all physiological intracoronary measurements. CONCLUSIONS: The reliability of most frequently used intracoronary physiologic indices is high. Clinical and anatomic factors significantly influence the reliability of these physiologic indices.

Spontaneous coronary artery dissection: new insights into diagnosis and treatment.

Spontaneous coronary artery dissection (SCAD) remains an infrequent, elusive, and challenging clinical entity of unknown etiology eight decades after its initial description. Our understanding of the pathophysiology of SCAD, initially limited to information from early pathological studies, case reports, and very short series, has been enriched recently by relatively large contemporary series of patients studied prospectively. The typical presentation involves a young woman without coronary risk factors suffering an acute coronary syndrome but, actually, most patients are middle-aged and have coronary risk factors. A high number of conditions have been related to SCAD, but fibromuscular dysplasia has shown a major intriguing association with potential pathophysiological implications. SCAD may present (a) with an intimal tear and the classic angiographic 'flap' leading to the appearance of two lumens (true and false), or (b) without an intimal rupture, as an intramural hematoma. An increased clinical awareness together with new diagnostic tools have led to a major surge in the diagnosis of SCAD. High-resolution intracoronary techniques provide unique diagnostic insights into the underlying pathophysiology and facilitate identification of the disease in patients misdiagnosed previously. After the initial acute ischemic insult, most patients stabilize and have a benign clinical course and eventually experience spontaneous healing of the vessel wall during follow-up. However, recurrences may still occur in up to 10-20% of cases. Accordingly, a conservative medical management (watchful waiting strategy) has been recommended as the initial approach. Revascularization remains particularly challenging and may be associated with suboptimal results, acute complications, and poor long-term outcome. Nevertheless, in patients with ongoing or refractory ischemia and adequate anatomy, revascularization should be attempted. Some novel and attractive coronary interventions have been proposed in this uniquely challenging anatomic scenario. This review aims to present a comprehensive and contemporary update on this elusive and intriguing clinical entity.