Background: Mast cells are prevalent in the shoulder of unstable atheromas; cardiac mast cells secrete proteases capable of activating matrix metalloproteinases. Histamine is essential in the inflammatory cascade of the unstable plaque. Ascorbate depletion has been correlated with histaminemia which has been shown to impair endothelial‐dependent vasodilation. This study evaluates whether oxidative stress as measured by isoprostanes (PGF2α) coupled with an inflammatory state characterized by histaminemia predisposes patients to acute coronary syndrome (ACS). Methods: Whole blood histamine, serum vitamin C, and serum PGF2α levels were drawn on 50 patients with ACS as determined by standard diagnostic criteria, 50 patients with stable coronary artery disease (SCAD), and 50 age and sex matched normal controls (C). Results: Data were analyzed by stepwise discriminant and Spearman's rank correlation coefficient. A significant relationship exists between histamine and PGF2α. As PGF2α rises above 60 pg/mL, an increase in histamine occurs in both the ACS and SCAD groups. A significant inverse relationship exists between ascorbate and histamine in the ACS versus C groups (P < 0.01) and the SCAD versus C groups (P < 0.01). Conclusion: Histamine and isoprostane levels increase in SCAD and ACS patients. Mast cell activation and lipid oxidation generated during atherosclerosis manifest this inflammatory response. Accelerated isoprostane formation and depleted ascorbate paired with histaminemia is active in CAD and predispose patients to acute coronary syndrome. Blood histamine alone may be a better risk factor for coronary events, and a better prognostic indicator than CRP even when combined with lipid indexes.

Esophageal echocardiography has been developed for use in patients with chronic obstructive pulmonary disease and is a safe diagnostic procedure which provides high resolution mirror image echoes of many cardiac structures. Conventional anterior and esophageal echocardiograms were performed in 38 subjects. Esophageal echoes were of diagnostic quality in all 38 subjects, anterior echoes were of diagnostic quality in only 18. Measurements from anterior and esophageal echocardiograms correlated well for aortic valve diameter (r = 0.87), left atrium diameter (r = 0.96), mitral valve EF slope (r = 0.97) and less well for aortic root diameter (r = 0.69).

Background: Oral factor XIa (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without significantly increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6–2 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on factor XIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% were women, 51% had ST-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10, 20, 50 mg, and placebo (pooled asundexian vs. placebo: HR 0.98, 90% CI 0.71–1.35). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10, 20, 50 mg, and placebo (pooled asundexian 20 and 50 mg vs. placebo: HR 1.05, 90% CI 0.69–1.61). Conclusions: : In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients following acute MI.

IMPORTANCE Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low.OBJECTIVE To track LDL-C treatment patterns in the US over 2 years. DESIGN, SETTING, AND PARTICIPANTS GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020. MAIN OUTCOMES AND MEASURESThe primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years.RESULTS A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels Ն100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardi...

To determine whether rotational blood flow or chiral asymmetry exists in the human descending thoracic aorta, we established the ability of color Doppler ultrasound to detect rotational flow in a tornado tube model of a vortex descending fluid column. In a model of the human aortic arch with a pulse duplicator, color Doppler was then used to demonstrate that rotational flow occurs first in the transverse arch and then in the proximal descending thoracic aorta. With the use of color Doppler esophageal echocardiography, 53 patients (age range, 25-78 years; mean age, 56.4 years) were prospectively examined for rotational flow in the descending thoracic aorta. At 10 cm superior to retro-left ventricular position, 22 of 38 patients (58%) revealed rotational flow with obvious diastolic counterclockwise rotation but less obvious systolic clockwise rotation. At 5 cm superior to retro-left ventricular position, 29 of 46 patients (63%) revealed rotational flow with a tendency toward systolic clockwise and diastolic counterclockwise rotation. At the retro-left ventricular position, 47 of 53 patients (89%) revealed rotational flow, usually of a clockwise direction, occurring in systole. Our data suggest that aortic flow is not purely pulsatile and axial but has a rotational component. Rotational flow begins in the aortic arch and is carried through to the descending thoracic aorta, where flow is chirally asymmetric with systolic clockwise and diastolic counterclockwise components. These data demonstrate an aortic rotational flow component that may have physiological implications for organ perfusion. (Circulation 1990;82:1985-1994 Be ecause most objects in nature are not symmetrical, handedness, or chirality, exists.' Although humans demonstrate structural chirality (e.g., the heart is to the left of center and the liver is to the right), the existence of functional chirality and its relation to blood flow have not been elucidated.The parabolic nature of blood flow in the descending thoracic aorta characterized by a higher velocity in the center of the aorta during peak systole has long been recognized2 and recently confirmed by videodensitometric methods3 and magnetic resonance imaging.4 In the aortic arch, blood flow has been shown to be more complex, and research by Yearwood and