Background-Nonatherosclerotic spontaneous coronary artery dissection (NA-SCAD) is underdiagnosed and an important cause of myocardial infarction in young women. The frequency of predisposing and precipitating conditions and cardiovascular outcomes remains poorly described. Methods and Results-Patients with NA-SCAD prospectively evaluated (retrospectively or prospectively identified) at Vancouver General Hospital were included. Angiographic SCAD diagnosis was confirmed by 2 experienced interventional cardiologists and categorized as type 1 (multiple lumen), 2 (diffuse stenosis), or 3 (mimic atherosclerosis). Fibromuscular dysplasia screening of renal, iliac, and cerebrovascular arteries were performed with angiography or computed tomographic angiography/MR angiography. Baseline, predisposing and precipitating conditions, angiographic, revascularization, inhospital, and long-term events were recorded. We prospectively evaluated 168 patients with NA-SCAD. Average age was 52.1±9.2 years, 92.3% were women (62.3% postmenopausal). All presented with myocardial infarction. ECG showed ST-segment elevation in 26.1%, and 3.6% had ventricular tachycardia/ventricular fibrillation arrest. Fibromuscular dysplasia was diagnosed in 72.0%. Precipitating emotional or physical stress was reported in 56.5%. Majority had type 2 angiographic SCAD (67.0%), only 29.1% had type 1, and 3.9% had type 3. The majority (134/168) were initially treated conservatively. Overall, 6 of 168 patients had coronary artery bypass surgery and 33 of 168 had percutaneous coronary intervention in-hospital. Of those treated conservatively (n=134), 3 required revascularization for SCAD extension, and all 79 who had repeat angiogram ≥26 days later had spontaneous healing. Two-year major adverse cardiac events were 16.9% (retrospectively identified group) and 10.4% (prospectively identified group). Recurrent SCAD occurred in 13.1%. Conclusions-Majority of patients with NA-SCAD had fibromuscular dysplasia and type 2 angiographic SCAD. Conservative therapy was associated with spontaneous healing. NA-SCAD survivors are at risk for recurrent cardiovascular events, including recurrent SCAD. (Circ Cardiovasc Interv. 2014;7:645-655.)

Abstract-Endothelin-1 (ET-1) is a potent vasoconstrictor. Its effect on arterial wave reflections and central pressure augmentation is unknown. We studied whether ET-1, in plasma concentrations present in disease, increases pulse wave velocity (PWV) and augmentation index (AIx) and therefore compromises cardiac output, and whether the ET-1 receptor blocker VML-588 (previously AXV-034343 and Ro 61-1790) prevents such effects. Nine healthy men received a 2-hour infusion with ET-1 (2.5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1) superimposed on vehicle or VML-588 (0.05, 0.20, or 0.40 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 ) (randomized order). Arterial tonometry and pulse wave contour analysis were used to assess aortic PWV and central aortic pressures and impedance cardiography for cardiac output. ET-1 slightly increased mean arterial pressure and peripheral resistance but had no significant effect on systolic blood pressure and pulse pressure. PWV increased from 5.4Ϯ0.2 to 5.7Ϯ0.3 m/s (PϽ0.05), AIx from 9.9Ϯ3.3 to 17.2Ϯ3.8 (PϽ0.05), central systolic blood pressure by 8.7Ϯ1.7 mm Hg (PϽ0.05), and central pulse pressure by 5.1Ϯ1.9 mm Hg (PϽ0.05). This was associated with a fall in cardiac output by Ϸ18% (PϽ0.05). VML-588 caused a slight decrease in brachial mean arterial pressure, PWV, and AIx, and prevented the effects of ET-1 on central hemodynamics without a clear dose-response effect. In summary, ET-1 in plasma concentrations as found in renal failure and heart failure accelerates PWV, causes a disproportionate increase in central aortic systolic blood pressure and pulse pressure, and decreases cardiac output. These effects can be prevented with an ET-1 receptor blocker such as VML-588. This makes it worthwhile to focus on endothelin as a target to prevent ventricular hypertrophy and to maintain cardiac function in diseases associated with high ET-1. Key Words: endothelin Ⅲ vasoconstriction Ⅲ pressure Ⅲ cardiac output E ndothelin (ET)-1 is a potent vasoconstrictor. The effects in the kidney are particularly strong and include vasoconstriction and sodium retention. 1,2 Although ET-1 has a positive inotropic effect on the heart, 3 it decreases cardiac output, 4 -6 probably by increasing systemic vascular resistance and afterload, and coronary vasoconstriction. 5-7 Theoretically, vasoconstriction by ET-1 could also lead to decreased arterial compliance and, subsequently, enhanced arterial pulse wave reflection and central pressure augmentation, such as was shown recently for caffeine. 8 This would further compromise cardiac function. Nonselective ET receptor blockade induces a mild decrease in blood pressure, suggesting resting ET-1 activity contributes modestly to circulatory control. 9 However, in pathological conditions such as renal failure, 10,11 heart failure, 12,13 and saltsensitive hypertension, 14 ET-1 levels are elevated. In such conditions, ET-1 may suppress cardiac function, and ET receptor blockers may be valuable.Most studies on the effects of ET in humans have been focused on kidney and peripheral circulation, but little is known on the effect...