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Cardiac sarcoidosis is associated with a high mortality rate. Given multiple barriers to obtaining cardiac PET imaging, we suspect individuals with access to this imaging modality are not representative of the Sarcoid patient population, which in the United States are predominantly Black females.To evaluate the demographics of patients with cardiac PET access and the cost-effectiveness of cardiac PET/MR imaging relative to standard of care.This is a retrospective, observational study. The demographic information of patients with suspected cardiac sarcoidosis and cardiac PET/CT imaging within a national registry of sarcoidosis were reviewed (n = 4561). An individual-level, continuous, time-state transition model was used for the evaluation of long-term cost-effectiveness for the combined cardiac PET/MR compared to standard of care cardiac MR followed by cardiac PET/CT.Patients who underwent cardiac PET in the national registry had 88.35% higher odds of being male (p 0.001) and 43.82% higher odds of being White (p = 0.003) than their counterparts who did not have cardiac PET imaging. Combined cardiac PET/MR had overall lower total lifetime costs ($8761 vs $10,777) and overall improved expected quality of life-years compared to the standard of care (0.77 vs 0.69).The findings suggest that patients with access to cardiac PET/CT are not representative of the patient population most likely to have cardiac sarcoidosis in this limited study evaluation. Universal insurance coverage should be considered for Cardiac PET imaging as same day cardiac PET and MR imaging has potential long-term cost and quality of life benefit.

Background Presentation of life-threatening arrhythmias concomitantly with a new-onset non-ischaemic cardiomyopathy raises concern for an inflammatory cardiomyopathy such as cardiac sarcoidosis or cardiac manifestations of connective tissue disease. Comprehensive workup for specific aetiologies may be unrevealing except for signs of myocardial inflammation identified on cardiac positron emission tomography (PET). Here, we present five cases of such subjects and their clinical course. Case summary We collected clinical, imaging, pathological, and follow-up data of five subjects presenting with arrhythmias and unexplained new-onset cardiomyopathy. Mean age was 56.2 ± 5.8 years. Three subjects presented with ventricular tachycardia and two with atrial arrhythmias. Echocardiography showed a mean left ventricular ejection fraction of 37 ± 9%. Significant coronary artery disease was ruled out in all cases as the cause of the cardiomyopathy. All patients underwent cardiac magnetic resonance imaging (MRI) and PET scan at presentation and follow-up. In all patients, cardiac MRI revealed hyperenhancement in epicardial and mid-myocardial pattern in a non-coronary distribution, while PET scan revealed fluorodeoxyglucose (FDG) mismatch defects in multiple foci in a non-coronary distribution. Right ventricular biopsy was obtained in all patients and revealed interstitial fibrosis and cardiomyocyte hypertrophy. On median follow-up of 210 days, all subjects had improvement in both heart failure symptoms and arrhythmias and repeat PET in four out of five patients showed decreased inflammation. Discussion A high level of suspicion for inflammatory cardiomyopathy is needed in patients presenting with new unexplained cardiomyopathy and arrhythmias. A cardiac FDG-PET should be considered for diagnosis if cardiac inflammation is in the differential. This can inform further decisions regarding targeted immunomodulation therapy that may be helpful in this cohort.

Introduction: Dyslipidemia is characterized by high levels of total cholesterol (TC), LDL cholesterol (LDL-C), triglycerides (TG), or low levels of HDL cholesterol (HDL-C) and is an established risk factor for subclinical and clinical cardiovascular disease (CVD) among adults. Although several investigations exist in older American Indian (AI) adults, the data on AI adolescents and young adults are scarce. Hypothesis: Dyslipidemia will be prevalent, and the incidence of subclinical and clinical CVD will be higher in young AI with than without baseline dyslipidemia. Methods: We evaluated AI participants from the SHFS, who were 14-39 years old at the baseline examination, 2001-2003 (n=1,436). To measure lipids, we drew blood after a 12-hour fast and defined dyslipidemia as any of the following: TC ≥ 200 mg/dL, LDL-C ≥ 100 mg/dL, TG ≥ 150 mg/dL, HDL-C < 40 mg/dL for men, HDL-C < 50mg/dL for women, non-HDL-C ≥ 130 mg/dL or taking lipid lowering medication. We used carotid ultrasound to detect atherosclerotic plaque at baseline and at the follow-up examination, 2006-2009. We identified CVD events through 2019 with a median follow-up of 17.8 years. We used log-rank tests to determine if the incidence of plaque or CVD events differed according to different categories of dyslipidemia. Results: Prevalence of dyslipidemia was 42%, 65%, and 73% for participants Conclusions: AI adolescents and young adults have an unexpectedly high prevalence of dyslipidemia, which leads to higher incident plaque and CVD events later in life. These data provide evidence for the benefits of lipid screening and intervention among this population.

Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality.We evaluated AI participants from the Strong Heart Family Study (SHFS), who were40 years old and CVD free at the baseline examination, 2001-2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates. Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02-3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07-3.89, p = 0.0291).Among young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Introduction: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Subclinical atherosclerosis is typically detected later in life and may develop into clinical CVD. Although investigators have established the association in older adults, the burden of subclinical atherosclerosis and its relation to CVD risk among AI youth is unclear. Hypothesis: Subclinical atherosclerosis will be prevalent and the risk of CVD will be higher in AI with atherosclerotic plaque in adolescence and early adulthood. Methods: We evaluated AI participants from the SHFS, who were 14-39 years old, CVD free, and had a carotid ultrasound at the baseline examination, 2001-2003 (n=1,376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified fatal and/or non-fatal CVD events through the end of 2019 with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between subclinical atherosclerosis and time to CVD events, while controlling for covariates. Results: Among 1,376 participants, 71 (5.2%) had atherosclerotic plaque at baseline. During follow-up, 120 (8.7%) participants had a fatal or non-fatal CVD event. CVD incidence was higher in participants with baseline plaque (13.51/1,000 person-years) than in those without (4.95/1,000 person-years, p=0.0003, Figure 1). Risk of CVD was higher in participants with baseline plaque compared to those without, while controlling for age and obesity (CVD HR=1.85, 95% CI=1.02-3.37, p=0.0420). Conclusions: AI adolescents and young adults have an unexpectedly high prevalence of atherosclerotic plaque, which is independently associated with incident CVD later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.

Background: Prior work has shown that fibrinogen, a well-known inflammatory marker, is associated with cardiovascular (CV) events. While it is known that physical activity (PA) imparts CV health benefits, there remains a knowledge gap on the interactions of PA with systemic inflammation on risk of CV death among American Indians. Hypothesis: To investigate the relationship between PA, inflammation, and CV death, we tested the hypotheses that: (i) PA is associated with lower risk of CV death, and (ii) the CV benefit of PA is mediated via an inflammatory pathway. Methods: We examined the association between PA (leisure-time plus occupational as METs[Metabolic Equivalent of Task]-hours per week via a validated questionnaire) and CV death among 3,135 adults (mean age 56 ± 8) without baseline CV disease in Strong Heart Study (1989-1991), a longitudinal study among American Indians. Preacher and Hayes bootstrap method was used for the model assessing mediation by fibrinogen. Results: During 26 years (mean 17.3 ± 8 years) of follow-up, there were 378 CV deaths. Compared to participants with minimal activity, subjects with higher levels of PA had a lower risk of CV death. Odds ratios were 0.91 (95% confidence interval [CI]: 0.65-1.21), 0.69 (95% CI: 0.51-0.92), and 0.56 (95% CI: 0.39-0.71) (p-trend=0.003), for increasing quartile of activity compared to the lowest, after adjustment for age, sex, study site, education, smoking, diabetes, hypertension, BMI, LDL cholesterol, and urine albumin-creatinine ratio. Mediation analysis showed the effect of PA on CV death was fully mediated via fibrinogen level (correlation coefficient: 0.998, 95% CI 0.995-0.999; Sobel test z= -3.11, p=0.03) (Figure). Conclusion: In a population-based study of American Indians, PA compared to inactivity, was associated with lower risk of CV death. This study highlights that PA is associated with improved CV outcomes and this effect is largely driven by inflammation.

Patients with aortic disease should have regular imaging surveillance. The goal of this review is to provide an overview of the etiologies of aortic disease as well as provide information on available imaging modalities including ones that are under investigation. As routine imaging is required for surveillance of aortic disease, many concerns come up including cumulative radiation and contrast exposure, as well as limitations, availability, and cost of imaging modalities. Novel hybrid imaging modalities hold promise for the prediction of complications related to aortic disease. A variety of etiologies can lead to aortic disease which can cause fatal complications if not monitored regularly and intervened when appropriate. Therefore, routine imaging surveillance is critical in patients with aortic disease, especially in high-risk groups. Understanding of advantages and limitations of each imaging technique is important in choosing the right modality.

The optimal treatment of the calcaneal fracture is a controversial topic. Many patients get a very good result with open reduction and internal fixation using extensile lateral approach. But there are many patients who do not qualify this category. This is the reason why many of them are either denied any surgical intervention or are put at a significant risk of developing major complications because of the open surgical intervention. The height, width, length and shape of the hind foot can be restored using Minimally invasive reduction and fixation (MIRF) and also the orientation of the posterior facet of calcaneus (Bohler’s angle) can be restored. In this paper we present a series of 23 patients treated with minimally invasive reduction and fixation using Steinmann as a treatment method for the patients not suitable for open reduction and internal fixation. The use of Steinmann pin in the MIRF technique proved out to be very effective. As per our experience the time of the surgery is short and it can be easily performed even in the presence of extensive soft tissue swelling in the period immediate after the injury. The risk of infection is low also the morphology of the calcaneus was improved and properly maintained in the term of Bohler’s angle. This technique is very suitable for the patients with medical co-morbidities such as smokers, diabetics and is also very effective for the patients who are not suitable foe extensile approach and internal fixation.

Background Left atrial thrombus (LAT) and dense spontaneous echocardiographic contrast (SEC) detected by transesophageal echocardiography (TEE) in patients on continuous direct oral anticoagulants (DOAC) therapy before catheter ablation of atrial fibrillation (AF) or atrial flutter (AFL) have been described. Objective We sought to compare rates of TEE-detected LAT and dense SEC among patients taking different DOACs. Methods We evaluated 609 consecutive patients from 3 tertiary hospitals (median age 65 years; interquartile range 58–71 years; 436 (72%) men) who were on ≥4 weeks of continuous DOAC therapy (dabigatran, n=166 [27%]; rivaroxaban, n=257 [42%]; or apixaban, n=186 [31%]) undergoing TEE before catheter ablation of AF/AFL. Demographic, clinical, and TEE data were collected for each patient. Results Despite ≥4 weeks of continuous DOAC therapy, 17 patients (2.8%) had LAT and 15 patients (2.5%) had dense SEC detected by TEE. The rates of LAT were 3.0%, 3.5%, and 1.6% for patients on dabigatran, rivaroxaban, and apixaban, respectively ( P = .482). The rates of dense SEC were 1.2%, 3.5%, and 2.2% for patients on dabigatran, rivaroxaban, and apixaban, respectively ( P = .299). Congestive heart failure (odds ratio 4.4; 95% confidence interval 1.6–12; P = .003) and moderate/severe left atrial enlargement (odds ratio 3.1; 95% confidence interval 1.1–8.6; P = .026) were independent predictors of LAT. Conclusion In this study, ∼3% of patients on continuous DOAC therapy had LAT detected before catheter ablation of AF/AFL. Specific DOAC therapy did not significantly affect the rates of LAT detection.

Aortic aneurysms (AA) are often asymptomatic before the occurrence of acute, potentially fatal complications including dissection and/or rupture. Beyond aortic size, the ability to assess aortic wall characteristics and processes contributing to aneurysm development may allow improved selection of patients who may benefit from prophylactic surgical intervention. Current risk stratification for aneurysms relies upon routine noninvasive imaging of aortic size without assessing the underlying pathophysiologic processes, including features such as inflammation, which may be associated with aneurysm development and progression. The use of molecular imaging modalities with positron emission tomographic (PET) scan allows characterization of aortic wall inflammatory activity. Elevated uptake of Fuorine-2-deoxy-D-glucose (FDG), a radiotracer with elevated avidity in highly-metabolic cells, has been correlated with the development and progression of both abdominal and thoracic AA in a number of animal models and clinical studies. Other novel PET radiotracers targeting matrix metalloproteinases (MMPs), mitochondrial translocator proteins (TSPO) and endothelial cell adhesion molecules are being investigated for clinical utility in identifying progression of disease in AA. By further defining the activation of molecular pathways in assessing aortic regions at risk for dilatation, this imaging modality can be integrated into future clinical decision-making models.

Objectives The purpose of this study is to determine whether patients on ≥4 weeks of continuous non–vitamin K antagonist oral anticoagulant (NOAC) therapy require transesophageal echocardiography (TEE) before catheter ablation of atrial fibrillation (AF) or atrial flutter and to compare rates of left atrial (LA) thrombus and dense spontaneous echocardiographic contrast (SEC) in patients on NOAC versus warfarin therapy. Background The impact of NOAC therapy on the rates of LA thrombus detection by TEE in patients undergoing catheter ablation of AF is unknown. Methods Initial TEEs for 388 patients (median age, 65 years; 74% male) on ≥4 weeks of continuous NOAC (n = 183) or warfarin therapy (n = 205) undergoing catheter ablation of AF and flutter were reviewed. Results After ≥4 weeks of therapy, the prevalence of LA thrombus and LA thrombus/dense SEC among patients on NOACs was 4.4% and 6.0%, respectively, which was comparable with that of patients on warfarin. LA thrombus rates among patients on dabigatran, rivaroxaban, and apixaban were 5.4%, 4.8%, and 0%, respectively (p = 0.46). Predictors of LA thrombus were congestive heart failure (odds ratio [OR]: 5.38; 95% confidence interval [CI]: 1.79 to 16.2; p = 0.003); and persistent AF (OR: 3.27; 95% CI: 1.06 to 10.2; p = 0.040). Conclusions Despite ≥4 weeks of anticoagulation, the rate of LA thrombus in patients on NOACs before catheter ablation of AF or atrial flutter was 4.4%. This suggests that continuous NOAC therapy does not eliminate the need for TEE before catheter ablation of AF.

Left atrial thrombus (LAT) may be detected by transesophageal echocardiography (TEE) in patients with atrial fibrillation (AF) or flutter (AFL) despite continuous anticoagulation therapy. We sought to examine the rates and timing of LAT resolution in response to changes in anticoagulation regimen. A retrospective study of 1517 consecutive patients on ≥ 4 weeks continuous oral anticoagulation (OAC) undergoing TEE prior to either direct current cardioversion or catheter ablation for AF or AFL was performed. Patients who had LAT on index TEE imaging and had follow-up TEEs were analyzed. Despite ≥ 4 weeks of continuous anticoagulation therapy, 63 (4.2%) patients had LAT. Forty-four patients (median age 67 [IQR 58, 74]; 33 [75%] male; 25 [57%] on direct oral anticoagulant [DOAC]) had follow-up TEEs performed. Upon detection of LAT on index TEE, 8 patients switched from warfarin to a DOAC, 21 patients switched from a DOAC to warfarin or another DOAC, and 15 patients remained on the same OAC. Over median 4.2 months (IQR 2.9, 6.6), LAT resolution was seen in 25 (57%) patients. Of the 25 patients who had LAT resolution, 7 (28%) required TEE imaging > 6 months after index TEE to show clearance of thrombus. Rates of LAT resolution were similar between patients who had alterations in OAC and those who did not (52 vs. 60%; P = 0.601). After initial detection of left atrial thrombus despite uninterrupted anticoagulation for atrial fibrillation or flutter, > 40% patients have persistent clot despite additional extended anticoagulation.

Objectives This study sought to determine whether splenic activation after acute coronary syndrome (ACS) is linked to leukocyte proinflammatory remodeling and whether splenic activity independently predicts the risk of cardiovascular disease (CVD) events. Background Pre-clinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the spleen) results in liberation of proinflammatory leukocytes and accelerated atherosclerotic inflammation. However, it is presently unknown whether a cardiosplenic axis exists in humans and whether splenic activation relates to CVD risk. Methods 18F-fluorodeoxyglucose (18FDG)–positron emission tomography (PET) imaging was performed in 508 individuals across 2 studies. In the first study, we performed FDG-PET imaging in 22 patients with recent ACS and 22 control subjects. FDG uptake was measured in spleen and arterial wall, whereas proinflammatory gene expression of circulating leukocytes was assessed by quantitative real-time polymerase chain reaction. In a second study, we examined the relationship between splenic tissue FDG uptake with subsequent CVD events during follow-up (median 4 years) in 464 patients who previously had undergone FDG-PET imaging. Results Splenic activity increased after ACS and was significantly associated with multiple indices of inflammation: 1) up-regulated gene expression of proinflammatory leukocytes; 2) increased C-reactive protein; and 3) increased arterial wall inflammation (FDG uptake). Moreover, in the second study, splenic activity (greater than or equal to the median) was associated with an increased risk of CVD events (hazard ratio [HR]: 3.3; 95% confidence interval [CI]: 1.5 to 7.3; p = 0.003), which remained significant after adjustment for CVD risk factors (HR: 2.26; 95% CI: 1.01 to 5.06; p = 0.04) and for arterial FDG uptake (HR: 2.68; 95% CI: 1.5 to 7.4; p = 0.02). Conclusions Our findings demonstrate increased splenic metabolic activity after ACS and its association with proinflammatory remodeling of circulating leukocytes. Moreover, we observed that metabolic activity of the spleen independently predicted risk of subsequent CVD events. Collectively, these findings provide evidence of a cardiosplenic axis in humans similar to that shown in pre-clinical studies.

Background Fluorine-18–sodium fluoride (18F-NaF) uptake is a marker of active vascular calcification associated with high-risk atherosclerotic plaque. Objectives In patients with abdominal aortic aneurysm (AAA), the authors assessed whether 18F-NaF positron emission tomography (PET) and computed tomography (CT) predicts AAA growth and clinical outcomes. Methods In prospective case-control (n = 20 per group) and longitudinal cohort (n = 72) studies, patients with AAA (aortic diameter >40 mm) and control subjects (aortic diameter, Central Illustration

Early identification of atherosclerosis and at-risk lesions plays a critical role in reducing the burden of cardiovascular disease. While invasive coronary angiography serves as the gold standard for diagnosing coronary artery disease, non-invasive imaging techniques provide visualization of both anatomical and functional atherosclerotic processes prior to clinical presentation. The development of cardiac positron emission tomography (PET) has greatly enhanced our capability to diagnose and treat patients with early stages of atherosclerosis. Cardiac PET is a powerful, versatile non-invasive diagnostic tool with utility in the identification of high-risk plaques, myocardial perfusion defects, and viable myocardial tissue. Cardiac PET allows for comparisons of myocardial function both at time of rest and stress, providing accurate assessments of both myocardial perfusion and viability. Furthermore, novel PET techniques with unique radiotracers yield clinically relevant data on high-risk plaques in active progressive atherosclerosis. While PET exercise stress tests were previously difficult to perform given short radiotracer half-life, the development of the novel radiotracer Flurpiridaz F-18 provides a promising future for PET exercise stress imaging. In addition, hybrid imaging with computed tomography angiography (CTA) and cardiac magnetic resonance (CMR) provides integration of cardiac function and structure. In this review article, we discuss the principles of cardiac PET, the clinical applications of PET in diagnosing and prognosticating patients at risk for future cardiovascular events, compare PET with other non-invasive cardiac imaging modalities, and discuss future applications of PET in CVD evaluation and management.

Standard cine-cardiac magnetic resonance (CMR) imaging is commonly used to evaluate cardiac structure, geometry and function. Prior studies have shown that automated segmentation via partial voxel interpolation (PVI) accurately quantifies phantom-based cardiac chamber volumes and necropsy left ventricular myocardial mass. Despite this, the applicability and usefulness of PVI in the determination of physiologic parameters of the aorta such as aortic stiffness has yet to be investigated.Routine CMR was conducted with a 1.5T (GE) scanner with pulse sequences similar to that of standard CMR (parameters: TR 3.4 msec, TE 1.14 msec, flip angle 60°, temporal resolution ~30-40 msec). Views were obtained in standard cardiac-oriented longitudinal or axial views (2, 3 and 4 chambers). Within non-dilated regions of the descending thoracic aorta, aortic area was quantified via a novel PVI automated process (LV-METRIC), which discerns relative amounts of blood pool in each voxel. Aortic stiffness, as calculated from brachial artery pulse pressure and aortic area at maximal and minimal dimensions, was evaluated in 60 total segments (one segment per patient). All segments were in the descending aorta and were not aneurysmal.Sixty patients in total were studied, including 50 that had genetically-related aortic disorder [35 bicuspid aortic valve (BAV), 15 Marfan syndrome (MFS)]. Ten normal controls without aortic disease were included for comparison purposes. All patients (n=60) had evaluable CMR images for assessment of the descending aorta with use of automated segmentation. Patients with BAV and MFS were similar to controls in age, systolic blood pressure, brachial artery pulse pressure, smoking status or hypercholesterolemia (all P=NS). There were more women (P0.001), lower body mass index (P=0.008), and greater height (P0.001) in the MFS cohort compared to BAV and controls. Descending aortic area in either systole (maximal) or diastole (minimal) was similar among all three cohorts. However, change in aortic area (ΔArea) throughout the cardiac cycle was substantially lower in MFS than control subjects (P0.001). In contrast, change in aortic area throughout the cardiac cycle was not significantly different between BAVThe application of PVI to standard CMR imaging can assess abnormal descending aorta functional indices in normal caliber segments in MFS subjects. Future prospective studies with larger subject populations are warranted to further determine the overall utility of automated aortic segmentation as a possible early biomarker of aortic dysfunction before overt dilatation.

Objectives The purpose of this study was to test whether high-dose statin treatment would result in a reduction in periodontal inflammation as assessed by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT). Background Periodontal disease (PD) is an independent risk factor for atherosclerosis. Methods Eighty-three adults with risk factors or with established atherosclerosis and who were not taking high-dose statins were randomized to atorvastatin 80 mg vs. 10 mg in a multicenter, double-blind trial to evaluate the impact of atorvastatin on arterial inflammation. Subjects were evaluated using FDG-PET/CT at baseline and at 4 and 12 weeks. Arterial and periodontal tracer activity was assessed while blinded to treatment allocation, clinical characteristics, and temporal sequence. Periodontal bone loss (an index of PD severity) was evaluated using contrast-enhanced CT images while blinded to clinical and imaging data. Results Seventy-one subjects completed the study, and 59 provided periodontal images for analysis. At baseline, areas of severe PD had higher target-to-background ratio (TBR) compared with areas without severe PD (mean TBR: 3.83 [95% confidence interval (CI): 3.36 to 4.30] vs. 3.18 [95% CI: 2.91 to 3.44], p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 mg vs. 10 mg (ΔTBR 80 mg vs. 10 mg group: mean −0.43 [95% CI: −0.83 to −0.02], p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (mean −0.74 [95% CI: −1.29 to −0.19], p = 0.01) and in patients with severe bone loss at baseline (−0.61 [95% CI: −1.16 to −0.054], p = 0.03). Furthermore, the changes in periodontal inflammation correlated with changes in carotid inflammation (R = 0.61, p Conclusions High-dose atorvastatin reduces periodontal inflammation, suggesting a newly recognized effect of statins. Given the concomitant changes observed in periodontal and arterial inflammation, these data raise the possibility that a portion of that beneficial impact of statins on atherosclerosis relate to reductions in extra-arterial inflammation, for example, periodontitis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )

Bronchial asthma is a chronic inflammatory condition associated with increased cardiovascular (CV) events. Here, we assess arterial inflammation, using 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging (FDG-PET/CT), in patients with bronchial asthma and low to intermediate Framingham risk scores (FRS). A total of 102 patients underwent FDG-PET/CT imaging for clinical indications. Thirty-four patients (mean age 54.9 ± 16.1) with mild asthma and no known atherosclerotic disease were compared to 2 non-asthmatic groups. The first control group (n = 34) were matched by age, gender, and FRS. The second control group (n = 34) had clinical atherosclerosis and were matched by gender. Thereafter, arterial FDG uptake on PET images was determined, while blinded to patient identifiers. Target-to-background-ratio (TBR) in the aorta was higher in asthmatics vs non-asthmatic FRS-matched controls (1.96 ± 0.26 vs 1.76 ± 0.20; P

Background: It has been previously shown that physical activity lowers the risk of incident diabetes in American Indians. However, in this population at high risk for cardiovascular (CV) events, it remains to be fully explored whether physical activity reduces CV death in subjects with diabetes and whether this effect is equal between genders. Objectives: To determine the inter-relationship between activity, diabetes, gender and CV death, we tested the hypotheses that, (i) activity lowers CV death in diabetes, and (ii) the CV benefit of activity is similar across genders. Methods: We examined the association between activity (leisure-time plus occupational) and CV death among 1,896 diabetic adults (mean age 56.9 ± 8) in phase I of Strong Heart Study (1989-1991. Of these, 1,254 were female (mean age 57.4 ± 8) and 642 were male (mean age 55.9 ± 8). Activity was measured as METS-hours per week on a validated survey. Regression models were used to assess for the prespecified associations and adjust for traditional CV risk factors. Kaplan-Meir analysis was used to plot survival based on activity. Results: After 14 years of follow-up (1989-1999), there were 222 CV deaths. Compared to diabetic subjects with minimal activity (quartile 1), those with higher activity levels had a lower risk of CV death (p=0.001, Fig 1A). Odds ratios were 0.60 (95% CI: 0.40-0.90; p=0.014), and 0.63 (0.41-0.95; p=0.027) for increasing activity (3rd and 4th quartiles), after adjustment for age and traditional CV risk factors. Moreover, in a subgroup analysis of female subjects with diabetes, increasing physical activity levels was significantly associated with less CV death compared to male subjects with diabetes (Fig. 1B), independent of conventional CV risk factors (p=0.003). Conclusion: In a large population study of American Indians, physical activity lowered CV death in subjects with diabetes, a finding most pronounced in females. Additional studies are needed to further investigate the pathophysiologic basis of the disparate gender response to activity.

A simple, flexible and very low cost hardware plus software framework for developing computer-interfaced science experiments is presented. It can be used for developing computer-interfaced science experiments without getting into the details of electronics or computer programming. For developing experiments this is a middle path between push-button systems and the develop-from-scratch approach. Emphasis is on leveraging the power of personal computers for experiment control, data acquisition and the mathematical analysis of data. The language 'Python' is chosen for data acquisition and analysis. This article explains the architecture of Phoenix (Physics with Home-made Equipment and Innovative Experiments) along with some sample experiments. The hardware design is open and the project is totally based on free software.

F-FDG accumulates in glycolytically active tissues and is known to concentrate in tissues that are rich in activated macrophages. In this study, we tested the hypotheses that human granulocyte-macrophage colony-stimulating factor (GM-CSF), a clinically used cytokine, increases macrophage glycolysis and deoxyglucose uptake in vitro and acutely enhances F-FDG uptake within inflamed tissues such as atherosclerotic plaques in vivo. Methods: In vitro experiments were conducted on human macrophages whereby inflammatory activation and uptake of radiolabeled 2-deoxyglucose was assessed before and after GM-CSF exposure. In vivo studies were performed on mice and New Zealand White rabbits to assess the effect of GM-CSF on F-FDG uptake in normal versus inflamed arteries, using PET. Results: Incubation of human macrophages with GM-CSF resulted in increased glycolysis and increased 2-deoxyglucose uptake (P , 0.05). This effect was attenuated by neutralizing antibodies against tumor necrosis factor-α or after silencing or inhibition of 6-phosphofructo- 2-kinase. In vivo, in mice and in rabbits, intravenous GM-CSF administration resulted in a 70% and 73% increase (P , 0.01 for both), respectively, in arterial F-FDG uptake in atherosclerotic animals but not in nonatherosclerotic controls. Histopathologic analysis demonstrated a significant correlation between in vivo F-FDG uptake and macrophage staining (R 5 0.75, P , 0.01). Conclusion: GM-CSF substantially augments glycolytic flux in vitro (via a mechanism dependent on ubiquitous type 6-phosphofructo-2-kinase and tumor necrosis factor-α) and increases F-FDG uptake within inflamed atheroma in vivo. These findings demonstrate that GM-CSF can be used to enhance detection of inflammation. Further studies should explore the role of GM-CSF stimulation to enhance the detection of inflammatory foci in other disease states., James H.F. Rudd is in part supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and HEFCE. Zahi A. Fayad is supported by NIH/NHLBI R01 HL071021, R01 HL078667, NIH/NBIB R01 EB009638, and the NIH/NHLBI Program of Excellence in Nanotechnology (PEN) Award, contract HHSN268201000045C. Parmanand Singh was supported by a grant from the NHLBI (5T32 HL076136) and is funded by the Marfan Foundation. Lisardo Boscá was supported by SAF2014-52492R, RTC2015-3741 from MINECO, and RD12/0042/0019. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas is funded by the Instituto de Salud Carlos III and S2010/BMD-2378 from Comunidad de Madrid. Ahmed Tawakol is supported by NIH/NHLBI R01 HL122177.

Offers a thorough assessment of vascular disease burden by yielding incremental data to SPECT on the presence of disease within the coronary microcirculation.

Nonobstructive coronary plaques manifesting high-risk morphology (HRM) associate with an increased risk of adverse clinical cardiovascular events. We sought to test the hypothesis that statins have a greater anti-inflammatory effect within coronary plaques containing HRM.In this prospective multicenter study, 55 subjects with or at high risk for atherosclerosis underwentIn this first study to evaluate the impact of statins on coronary inflammation, we observed that the anti-inflammatory impact of statins is substantially greater within coronary plaques that contain HRM features. These findings suggest an additional mechanism by which statins disproportionately benefit individuals with more advanced atherosclerotic disease.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00703261.

The purpose of this study is to determine whether patients on ≥4 weeks of continuous non-vitamin K antagonist oral anticoagulant (NOAC) therapy require transesophageal echocardiography (TEE) before catheter ablation of atrial fibrillation (AF) or atrial flutter and to compare rates of left atrial (LA) thrombus and dense spontaneous echocardiographic contrast (SEC) in patients on NOAC versus warfarin therapy.The impact of NOAC therapy on the rates of LA thrombus detection by TEE in patients undergoing catheter ablation of AF is unknown.Initial TEEs for 388 patients (median age, 65 years; 74% male) on ≥4 weeks of continuous NOAC (n = 183) or warfarin therapy (n = 205) undergoing catheter ablation of AF and flutter were reviewed.After ≥4 weeks of therapy, the prevalence of LA thrombus and LA thrombus/dense SEC among patients on NOACs was 4.4% and 6.0%, respectively, which was comparable with that of patients on warfarin. LA thrombus rates among patients on dabigatran, rivaroxaban, and apixaban were 5.4%, 4.8%, and 0%, respectively (p = 0.46). Predictors of LA thrombus were congestive heart failure (odds ratio [OR]: 5.38; 95% confidence interval [CI]: 1.79 to 16.2; p = 0.003); and persistent AF (OR: 3.27; 95% CI: 1.06 to 10.2; p = 0.040).Despite ≥4 weeks of anticoagulation, the rate of LA thrombus in patients on NOACs before catheter ablation of AF or atrial flutter was 4.4%. This suggests that continuous NOAC therapy does not eliminate the need for TEE before catheter ablation of AF.

To the Editor: Previous reports have demonstrated that lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzymatic inflammatory biomarker, is associated with increased risk of cardiovascular events [(1)][1]. Lp-PLA2 mediates formation of bioactive mediators (lysophosphatidyl choline and

Narayana's Treatment of Magic Squares

PMCID: PMC4441599.-- et al., [Objective]: Although it is accepted that macrophage glycolysis is upregulated under hypoxic conditions, it is not known whether this is linked to a similar increase in macrophage proinflammatory activation and whether specific energy demands regulate cell viability in the atheromatous plaque. [Approach and Results]: We studied the interplay between macrophage energy metabolism, polarization, and viability in the context of atherosclerosis. Cultured human and murine macrophages and an in vivo murine model of atherosclerosis were used to evaluate the mechanisms underlying metabolic and inflammatory activity of macrophages in the different atherosclerotic conditions analyzed. We observed that macrophage energetics and inflammatory activation are closely and linearly related, resulting in dynamic calibration of glycolysis to keep pace with inflammatory activity. In addition, we show that macrophage glycolysis and proinflammatory activation mainly depend on hypoxia-inducible factor and on its impact on glucose uptake, and on the expression of hexokinase II and ubiquitous 6-phosphofructo-2-kinase. As a consequence, hypoxia potentiates inflammation and glycolysis mainly via these pathways. Moreover, when macrophages' ability to increase glycolysis through 6-phosphofructo-2-kinase is experimentally attenuated, cell viability is reduced if subjected to proinflammatory or hypoxic conditions, but unaffected under control conditions. In addition to this, granulocyte-macrophage colony-stimulating factor enhances anerobic glycolysis while exerting a mild proinflammatory activation. [Conclusions]: These findings, in human and murine cells and in an animal model, show that hypoxia potentiates macrophage glycolytic flux in concert with a proportional upregulation of proinflammatory activity, in a manner that is dependent on both hypoxia-inducible factor -1α and 6-phosphofructo-2-kinase.

Previous studies have demonstrated that patients with rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). Although a prior study has reported an increase in atherosclerotic plaque inflammation in RA patients [(1)][1], the relationship between joint inflammation and

In this paper, a compact analytical model for sub onset current, the current before the onset of Band-to-Band tunneling, is presented for tunnel field-effect transistor. Shockley-Reed-Hall (SRH) generation and recombination is used to explain the sub-onset current at the two reverse biased source/channel and channel/drain junctions. 2-D numerical simulations are used to understand the device physics and importance of SRH generation in the drain current. The same model can be used to understand the I-V characteristics of p-type TFET. The dependency of drain current on key parameters i.e. effective tunneling mass (m*) and recombination lifetime (τ) is presented.

The purpose of this study was to test whether high-dose statin treatment would result in a reduction in periodontal inflammation as assessed by (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT).Periodontal disease (PD) is an independent risk factor for atherosclerosis.Eighty-three adults with risk factors or with established atherosclerosis and who were not taking high-dose statins were randomized to atorvastatin 80 mg vs. 10 mg in a multicenter, double-blind trial to evaluate the impact of atorvastatin on arterial inflammation. Subjects were evaluated using FDG-PET/CT at baseline and at 4 and 12 weeks. Arterial and periodontal tracer activity was assessed while blinded to treatment allocation, clinical characteristics, and temporal sequence. Periodontal bone loss (an index of PD severity) was evaluated using contrast-enhanced CT images while blinded to clinical and imaging data.Seventy-one subjects completed the study, and 59 provided periodontal images for analysis. At baseline, areas of severe PD had higher target-to-background ratio (TBR) compared with areas without severe PD (mean TBR: 3.83 [95% confidence interval (CI): 3.36 to 4.30] vs. 3.18 [95% CI: 2.91 to 3.44], p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 mg vs. 10 mg (ΔTBR 80 mg vs. 10 mg group: mean -0.43 [95% CI: -0.83 to -0.02], p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (mean -0.74 [95% CI: -1.29 to -0.19], p = 0.01) and in patients with severe bone loss at baseline (-0.61 [95% CI: -1.16 to -0.054], p = 0.03). Furthermore, the changes in periodontal inflammation correlated with changes in carotid inflammation (R = 0.61, p 0.001).High-dose atorvastatin reduces periodontal inflammation, suggesting a newly recognized effect of statins. Given the concomitant changes observed in periodontal and arterial inflammation, these data raise the possibility that a portion of that beneficial impact of statins on atherosclerosis relate to reductions in extra-arterial inflammation, for example, periodontitis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261).

Background: Coronary artery disease (CAD) detected by coronary CT angiography (CCTA) independently predicts cardiovascular events. We assessed the potential of CCTA to tailor aspirin (ASA) and statin medical therapy in acute chest pain patients presenting to the emergency department. Methods: We included all patients from the Rule Out Myocardial Infarction Using Computer Assisted Tomography (ROMICAT) Trial. This prospective double-blinded observational cohort study included patients presenting with chest pain to the emergency department with low-intermediate risk for acute coronary syndrome (ACS). Patients underwent CCTA prior to admission, followed by standard evaluation. Caretakers were blinded to CCTA results. We assessed medical therapy at presentation and discharge, and determined concordance of CAD status by CCTA with medical therapy dictated by standard care. Results: Complete data on medical therapy was available in 358/368 patients (99%), (53±12 years, 61% men) of whom 7 had a contraindication to ASA and 11 to statin. Standard of care included stress testing in 71% of patients. Prescription of ASA and statins increased from admission to discharge (See Figure). At discharge, 33% of patients without CAD were on ASA and 14% were on statin. Conversely, 46% of patients with nonobstructive CAD by CCTA did not receive ASA and 59% did not receive statin at discharge. Only 66% of patients with obstructive CAD were on statin and ASA at discharge. Based on 2011 American College of Cardiology/American Heart Association secondary prevention guidelines, there was discordance between CAD status by CCTA and medical therapy in 51% of patients. Conclusions: CCTA has great potential to optimize adherence to secondary prevention guidelines in chest pain patients presenting to the emergency department.

This paper proposes an overall improvement in performance of Gate-Source/Drain underlap FinFET structure by introducing the concept of dual-k spacer between gate and source. By optimizing the underlap length, we demonstrate the sensitivity of dual-k spacer width. We analyze that the variation in width of high-k presents a noticeable improvements in On-Off current ratio (I on /I off ). The proposed structure is verified by TCAD simulations of underlap FinFET device with varying device physical parameters such as spacer width, spacer material etc. and optimizes the width of the high-k and low-k spacer. The proposed device architecture enhances gate control over channel and can be used to design low power digital circuits.

What are generally referred to as the Fibonacci numbers and the method for their formation were given by Virah a ṅka (between a.d. 600 and 800), Gop a la (prior to a.d. 1135) and Hemacandra (c. a.d. 1150), all prior to L. Fibonacci (c. a.d. 1202). N a r a ya n na Pa n d ita ( a.d. 1356) established a relation between his s m a sik a -paṅkti, which contains Fibonacci numbers as a particular case, and “the multinomial coefficients.”

The incidence of tuberculosis of ear, nose and throat is not rare as reported from developed countries. A thorough study ond observations of 500 cases of pulmonary tuberculosis have revealed 129 cases (nearly 25%) with involvement of ear, nose and larynx. Larynx alone has shown 23% involvement, ear 2% and nose 0.8%. The response to specific chemotherapy is equally good in ENT lesions. Some findings of academic interest have been noted in larynx and nose. Routine ENT examination of all cases of pulmonary tuberculosis and periodic review of these cases with positive findings in ENT appear desirable.

A case of unusual presentation of rhinolith has been reported and the salient features of the case have been discussed. Literature on rhinolith has been reviewed.

Skiagrams of the Maxillary sinus often show rounded shadows in the antrum and on antrum puncture a thin straw coloured fluid drips out. On opening up the antrum a thin walled bluish cyst is seen arising from the floor, such Maxillary sinus cysts seen in eight patients during the last 2 years are discussed.

Previous reports have demonstrated that oxidized low-density lipoprotein (oxLDL) is a key mediator in atherogenesis [(1)][1]. oxLDL increases endothelial cell adhesion molecules, recruitment of inflammatory cells into the vessel wall, and formation of foam cells, all hallmarks of atherosclerosis