The short and long-term characteristics and outcomes of patients with grade 1 myocardial uptake on cardiac scintigraphy.

AIMS: This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) requiring further invasive investigation with tissue biopsy. METHODS AND RESULTS: We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR-CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re-evaluation for ATTR-CA at long term. Of the 132 ATTR-CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light-chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR-CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow-up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re-evaluated at a median follow-up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long-term scintigraphy. CONCLUSIONS: Patients with suspected ATTR-CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long-term follow-up. Larger studies should define the optimal evaluation strategy in this population.

Transcatheter Interventions for Atrioventricular Dysfunction in Patients with Adult Congenital Heart Disease: An International Case Series.

INTRODUCTION: A substantial proportion of patients with adult congenital heart disease (ACHD) suffer from worsening valvular dysfunction in adulthood. Transcatheter valve interventions can offer a therapeutic alternative to surgery for those at high surgical risk. There is emerging but limited data on transcatheter interventions for atrioventricular (AV) valve dysfunction in patients with ACHD. METHODS: We compiled an international collaborative multi-center registry focusing on adult patients with congenital heart disease undergoing transcatheter AV valve interventions (repair or replacement). Included were patients from three international centers who underwent procedures between 2016 and 2022. Demographic, clinical, and procedural data were compiled. RESULTS: Nine patients with ACHD underwent AV valve interventions. The median age was 48 years (IQR (37; 56), 55% women). At baseline, seven patients (78%) were in NYHA functional class III and two (22%) were in NYHA functional class II. The diagnosis of ACHD varied. Three valve interventions were performed on the subpulmonary AV valve and six on the systemic AV valve. The primary valvular pathology was regurgitation (six patients, 78%). Five procedures were valve-in-valve interventions, and four procedures were transcatheter edge-to-edge repair procedures. There were no major complications or peri-procedural complications or peri-procedural mortality. One patient developed a suspected non-obstructive thrombus on the valve that was medically treated. One patient did not improve clinically following the procedure and underwent a heart transplant, one patient died 6 months following the procedure due to a cardiovascular implantable electronic device infection. At one year, six patients were in NYHA functional class I, and one patient was in NYHA functional class III. In conclusion, transcatheter AV heart valve interventions are feasible and safe procedures in carefully selected ACHD patients. These procedures can offer an effective treatment option in these younger patients with high surgical risk.

Fragmentation of Different Calcification Growth Patterns in Bicuspid Valves During Balloon Valvuloplasty Procedure.

This study focuses on the calcification development and routes of type-1 bicuspid aortic valves based on CT scans and the effect of the unique geometrical shapes of calcium deposits on their fragmentation under balloon valvuloplasty procedures. Towards this goal, the novel Reverse Calcification Technique (RCT), which can predict the calcification progression leading to the current state based on CT scans, is utilized for n = 26 bicuspid aortic valves patients. Two main calcification patterns of type-1 bicuspid aortic valves were identified; asymmetric and symmetric with either partial or full arcs and circles. Subsequently, a calcification fragmentation biomechanical model was introduced to study the balloon valvuloplasty procedure prior to transcatheter aortic valve replacement implantation that allows better device expansion. To achieve this goal, six representative stenotic bicuspid aortic valves of different calcification patterns were investigated. It was found that the distinct geometrical shape of the calcium deposits had a significant effect on the cracks' initiations. Full or partial circle deposits had stronger resistance to fragmentation and mainly remained intact, yet, arc-shaped pattern deposits resulted in multiple cracks in bottleneck regions. The proposed biomechanical computational models could help assess calcification fragmentation patterns toward improving treatment approaches in stenotic bicuspid aortic valve patients, particularly for the off-label use of transcatheter aortic valve replacement.

Anti-immunoglobulin-like transcript 3 induced acute myocarditis-A case report.

To the best of our knowledge, this is the first published report of anti-immunoglobulin-like transcript 3 (ILT3)-induced myocarditis. A 48-year old female patient with refractory acute myeloid leukemia who was given a single dose of anti-ILT3 monotherapy presented with fever, hypotension, chest pain, and elevated cardiac biomarkers. Systolic bi-ventricular function was in normal limits. The patient was promptly treated with pulse dose steroids with a rapid hemodynamic and clinical improvement and declining levels of cardiac biomarkers. The diagnosis of acute myocarditis was confirmed using cardiac magnetic resonance imaging applying the revised Lake Lewis criteria. While larger-scale data are needed in order to assess the incidence, management and prognosis of anti-ILT-3 induced myocarditis, we believe a high level of suspicion for adverse non-target cardiac effects is required in patients receiving this novel class of drugs.

An unusual case report of transcatheter aortic valve implantation-related actinomycosis endocarditis.

Background: Actinomycosis is a chronic invasive infection caused by Actinomyces species. Actinomycosis endocarditis has been described, yet considered rare. We present the first reported transcatheter aortic valve implantation (TAVI)-related actinomycosis endocarditis. Case summary: A 70-year-old female patient, presented 4 months after TAVI with malaise and vocal-cord paralysis. She underwent computed tomography angiography which demonstrated a 28 mm pseudoaneurysm of the ascending aorta, which compressed the laryngeal nerves. Her condition rapidly deteriorated with cardiogenic shock and required an emergent surgery, which reviled a tamponade with active bleeding, due to an ascending aortic dissection. She underwent aortic valve and ascending aorta replacement. A 2 cm vegetation was found on the TAVI prosthetic valve and sent for cultures, which later revealed an Actinomyces neuii infection. Long-term intravenous ampicillin treatment was given. Discussion: This case describes a patient with endocarditis on TAVI prosthetic valve, with an unusual clinical presentation and rapid deterioration to an emergency intervention. This unique presentation of tumour-like tissue invasion is characteristic of actinomycosis, and should be suspected especially following valve replacement.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

BACKGROUND: Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. METHODS: We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. RESULTS: Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. CONCLUSION: Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Heartmate 3 as a bridge to heart transplantation in a patient with congenitally corrected transposition of the great arteries: a case report.

BACKGROUND: We report the first use of Heartmate 3 (HM3) in a Congenitally corrected Transposition of the Great Arteries (ccTGA) as a Systemic Ventricular Assist Device (SVAD) to treat HF. CASE PRESENTATION: A 55 years old man with a Congenitally corrected Transposition of the Great Arteries (ccTGA) a rare condition in which Heart Failure (HF) is a common presentation in adult life and survival without heart transplantation is hardly an option. Systemic Ventricular Assist Device (SVAD) can be an option if an organ does not become available. We present the first ever implantation of HM3 LVAD (Abbott Inc, Chicago IL) implanted to this patient as a bridge to transplantation, demonstrating the safety and feasibility of the procedure. Due to the unique mediastinal configuration, 3D cardiac CT reconstruction should be used for planning the procedure-intra ventricular placement of the inflow as well as mediastinal placemat of the outflow and pump. CONCLUSIONS: This successful first use of HM3 as a SVAD for ccTGA patients, opens a novel treatment option for these patients as a bridge for heart transplant or as definitive treatment.

The Effect of Tafamidis on Circulating Endothelial Progenitor Cells in Patients with Transthyretin Cardiac Amyloidosis.

AIMS: Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs. METHODS AND RESULTS: Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34(+)/VEGFR-2(+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133(+)/VEGFR-2(+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (from 0.12 (IQR 0.03, 0.16) to 0.30 (IQR 0.18, 0.33), p < 0.001). VEGF levels increased following treatment (from 54 (IQR 52, 72) to 107 (IQR 62, 129) pg/ml, p = 0.039). CONCLUSIONS: Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.

Diffused coronary involvement in Takayasu arteritis with concomitant malignancy.

Large vessel vasculitis (LVV) is composed of conditions in which inflammation of blood vessel walls affects mainly large arteries, such as the aorta and its main branches, and in some cases the coronary arteries. Coronary artery involvement in systemic vasculitis is associated with significant morbidity and mortality. We present a case of a young patient diagnosed with extensive coronary disease diagnosed as Takayasu arteritis, when whom a concomitant diagnosis of Hodgkin's lymphoma was made. The literature review revealed ten cases of malignancies associated with Takayasu arteritis. We discuss the complexity of the management of concurrent hematological malignancy with TAK and extensive coronary arteritis. This complicated and cross-disciplinary case also represents the pivotal importance of multi-disciplinary team decision in order to achieve the best clinical outcome of both disorders.

Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations.

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85 m s-1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.

Increased Rate of New-onset Left Bundle Branch Block in Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation (From a National Registry).

There is a growing interest in transcutaneous aortic valve implantation (TAVI) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVI, and new-onset permanent LBBB (NOP-LBBB) post-TAVI may be a marker of worse outcomes. We aimed to evaluate the rate of NOP-LBBB following TAVI among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVI Registry were reviewed and compared with patients with TAV. Patients with previous aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVI. A total of 387 patients (66 with BAV, 321 with TAV), age 80.3 ± 7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV versus TAV (29.2% vs 16.9%, p = 0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs 12.5%; respectively, p = 0.62). In BAV and TAV groups, 1-year mortality (6.1% vs 7.2%; respectively, p = 0.75) and stroke rates (6.1% vs 3.5%; respectively, p = 0.30) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (AdjOR = 2.7, 95%CI 1.3 to 5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (AdjOR = 3.2, 95%CI: 1.5 to 6.7). In conclusion, patients with BAV undergoing TAVI have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies.

Differences in the characteristics and contemporary cardiac outcomes of patients with light-chain versus transthyretin cardiac amyloidosis.

AIMS: To compare the baseline cardiovascular characteristics of immunoglobulin light-chain (AL) and amyloid transthyretin (ATTR) cardiac amyloidosis (CA) and to investigate patients' contemporary cardiac outcomes. METHODS: Single-center analysis of clinical, laboratory, echocardiographic and cardiac magnetic resonance imaging (CMRi) characteristics of AL and ATTR-CA patients' cohort (years 2013-2020). RESULTS: Included were 67 CA patients of whom 31 (46%) had AL-CA and 36 (54%) had ATTR-CA. Patients with ATTR-CA versus AL-CA were older (80 (IQR 70, 85) years versus 65 (IQR 60, 71) years, respectively, p<0.001) with male predominance (p = 0.038). Co-morbidities in ATTR-CA patients more frequently included diabetes mellitus (19% versus 3.0%, respectively, p = 0.060) and coronary artery disease (39% versus 10%, respectively, p = 0.010). By echocardiography, patients with ATTR-CA versus AL-CA had a trend to worse left ventricular (LV) ejection function (50 (IQR 40, 55)% versus 60 (IQR 45, 60)%, respectively, p = 0.051), yet comparable LV diastolic function. By CMRi, left atrial area (31 (IQR 27, 36)cm2 vs. 27 (IQR 23, 30)cm2, respectively, p = 0.015) and LV mass index (109 (IQR 96, 130)grams/m2 vs. 82 (IQR 72, 98)grams/m2, respectively, p = 0.011) were increased in patients with ATTR-CA versus AL-CA. Nevertheless, during follow-up (median 20 (IQR 10, 38) months), patients with AL-CA were more frequently admitted with heart failure exacerbations (HR 2.87 (95% CI 1.42, 5.81), p = 0.003) and demonstrated increased mortality (HR 2.51 (95%CI 1.19, 5.28), p = 0.015). CONCLUSION: Despite the various similarities of AL-CA and ATTR-CA, these diseases have distinct baseline cardiovascular profiles and different heart failure course, thus merit tailored-cardiac management.

Epicardial fat and the risk of atrial tachy-arrhythmia recurrence post pulmonary vein isolation: a computed tomography study.

Epicardial and Pericardia fat have been hypothesized to exert local and systemic pathogenic effects on nearby cardiac structures. The present study aimed to evaluate the impact of epicardial and pericardial fat volumes on the outcome of patients that underwent a first pulmonary vein isolation (PVI) with cryoablation. We included 130 consecutive patients with atrial fibrillation (AF) that underwent contrast enhanced ECG-gated cardiac computed tomography (CCT) before a PVI. The control group included 50 patients in normal sinus rhythm that underwent ECG-gated CT to rule out coronary artery disease. Epicardial and pericardial fat volumes were quantified with CCT. Patients with AF compared to patients with normal sinus rhythm (control group) had significantly larger epicardial (140.3 ± 58.1 vs. 55.9 ± 17.7 ml; respectively, P < 0.001) and pericardial (77.0 ± 35.5 ml vs. 27.2 ± 9.5 ml; respectively, P < 0.001) fat volumes. Among patients that underwent PVIs, those with AF recurrence had a greater epicardial (175.0 ± 54.4 ml vs. 130.7 ± SD 54.2 ml; respectively, P < 0.001) and pericardial (93.7 ± SD 42.8 vs. 72.5 ± SD 31.9 ml; respectively, P < 0.001) fat volumes, compared to patients with no AF recurrence. Multivariate analyses revealed that epicardial fat was an independent predictor of recurrence post-ablation (HR = 1.08, 95% CI 1.02-1.16 per 10-ml increase in volume; P = 0.009). Pericardial fat was associated with 7% increase in risk of recurrent AF (HR = 1.07, 95% CI 0.98-1.18; P = 0.117). Epicardial fat, assessed with contrast enhanced CCT, is an independent predictor of AF recurrence after PVI ablation.

Natural History and Disease Progression of Early Cardiac Amyloidosis Evaluated by Echocardiography.

Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Preamyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain [AL] or amyloid transthyretin [ATTR]). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 [interquartile range {IQR} 1.0, 1.5] cm) ≥3 years before the diagnosis of CA and relative wall thickness was increased (0.47 [IQR 0.41, 0.50]) ≥7 years prediagnosis. One to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction ≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased relative wall thickness (0.74 [IQR 0.62, 0.92] versus 0.62 [IQR 0.54, 0.76], p = 0.004) and LV mass index (144 [IQR 129, 191] versus 115 [IQR 105, 146] g/m2, p = 0.020) and reduced LV ejection fraction (50 [IQR 44, 58] versus (60 [IQR 53, 60]%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography.

Biomechanical modeling of transcatheter aortic valve replacement in a stenotic bicuspid aortic valve: deployments and paravalvular leakage.

Calcific aortic valve disease (CAVD) is characterized by stiffened aortic valve leaflets. Bicuspid aortic valve (BAV) is the most common congenital heart disease. Transcatheter aortic valve replacement (TAVR) is a treatment approach for CAVD where a stent with mounted bioprosthetic valve is deployed on the stenotic valve. Performing TAVR in calcified BAV patients may be associated with post-procedural complications due to the BAV asymmetrical structure. This study aims to develop refined computational models simulating the deployments of Evolut R and PRO TAVR devices in a representative calcified BAV. The paravalvular leakage (PVL) was also calculated by computational fluid dynamics simulations. Computed tomography scan of severely stenotic BAV patient was acquired. The 3D calcium deposits were generated and embedded inside a parametric model of the BAV. Deployments of the Evolut R and PRO inside the calcified BAV were simulated in five bioprosthesis leaflet orientations. The hypothesis of asymmetric and elliptic stent deployment was confirmed. Positioning the bioprosthesis commissures aligned with the native commissures yielded the lowest PVL (15.7 vs. 29.5 mL/beat). The Evolut PRO reduced the PVL in half compared with the Evolut R (15.7 vs. 28.7 mL/beat). The proposed biomechanical computational model could optimize future TAVR treatment in BAV patients. Graphical abstract.

A New Growth Model for Aortic Valve Calcification.

Calcific aortic valve disease (CAVD) is a progressive disease in which minerals accumulate in the tissue of the aortic valve cusps, stiffening them and preventing valve opening and closing. The process of valve calcification was found to be similar to that of bone formation including cell differentiation to osteoblast-like cells. Studies have shown the contribution of high strains to calcification initiation and growth process acceleration. In this paper, a new strain-based calcification growth model is proposed. The model aims to explain the unique shape of the calcification and other disease characteristics. The calcification process was divided into two stages: Calcification initiation and calcification growth. The initiation locations were based on previously published findings and a reverse calcification technique (RCT), which uses computed tomography (CT) scans of patients to reveal the calcification initiation point. The calcification growth process was simulated by a finite element model of one aortic valve cusp loaded with cyclic loading. Similar to Wolff's law, describing bone response to stress, our model uses strains to drive calcification formation. The simulation grows calcification from its initiation point to its full typical stenotic shape. Study results showed that the model was able to reproduce the typical calcification growth pattern and shape, suggesting that strain is the main driving force behind calcification progression. The simulation also sheds light on other disease characteristics, such as calcification growth acceleration as the disease progresses, as well as sensitivity to hypertension.

Reconnoitering the linkage between cardiovascular disease mortality and long-term exposures to outdoor environmental factors in the USA using remotely-sensed data.

This ecological study aimed to assess the association between long-term exposures to outdoor environmental factors and mortality rate from cardiovascular disease (CVD) in a diverse and spatially distributed population from 3,094 counties within the U.S. (n > 3,780,000 CVD deaths) using satellite-derived data of PM2.5 concentrations, sunlight, and maximum heat index. Multivariable logistic regression analyses were conducted to determine whether PM2.5, sunlight and maximum heat index were related to the odds of the total CVD death rate based on gender, race, and age taking into consideration the confounding risk factors of diabetes, obesity, leisure- time physical inactivity, smoking and socioeconomic status. The study has shown that elevated levels of PM2.5, sunlight and heat long-term exposures are significantly associated with an increase in the odds ratio of the total CVD mortality. The results suggest a 9.8% (95% CI = 6.3% - 13.4%), 0.9% (95% CI = 0.5% - 1.2%), and 0.7% (95% CI = 0.5% - 11.2%) increase in total CVD mortality associated with 10 µg/m3 increase in PM2.5 concentrations, 1,000 kJ/m2 increases in sunlight, and 1 oF increase in heat index, respectively. The odds ratios for the CVD death rate due to long-term exposures of PM2.5, sunlight, and heat index were significantly greater than 1.0 for all categories except for Asians, Hispanics, and American Indians, indicating that the effect of long-term exposures to particulate matter, sunlight radiation, and maximum heat on CVD mortality is trivial for Asians, Hispanics, and American Indians. Among the categories of age, the group of 65 years and older had the highest odds ratios, suggesting that the age group of 65 years and older are the most vulnerable group to the environmental exposures of PM2.5 (OR = 1.179, 95% CI = 1.124 - 1.237), sunlight (OR = 1.047, 95% CI = 1.041 - 1.053), and maximum heat (OR = 1.014, 95% CI = 1.011 - 1.016). The odds ratios of CVD mortality due to the environmental exposures were higher for Blacks than those for Whites. The odds ratios for all categories were attenuated with the inclusion of diabetes, obesity, leisure-time physical inactivity, smoking, and income covariates, reflecting the effect of other medical conditions, lifestyle, behavioral and socioeconomic factors on the CVD death rate besides the environmental factors.

Investigating the effects of environmental factors on autism spectrum disorder in the USA using remotely sensed data.

This study aimed to assess the association between exposures to outdoor environmental factors and autism spectrum disorder (ASD) prevalence in a diverse and spatially distributed population of 8-year-old children from the USA (n = 2,097,188) using the air quality index (AQI) of the US Environmental Protection Agency as well as satellite-derived data of PM2.5 concentrations, sunlight, and maximum heat index. Multivariable logistic regression analyses were performed to determine whether the unhealthy AQI, PM2.5, sunlight, and maximum heat index were related to the odds of ASD prevalence based on gender and race and taking into consideration the confounding factors of smoking and socioeconomic status. The logistic regression odds ratios for ASD per 10% increase in the unhealthy AQI were greater than 1 for all categories, indicating that unhealthy AQI is related to the odds of ASD prevalence. The odds ratio of ASD due to the exposure to the unhealthy AQI was higher for Asians (OR = 2.96, 95% CI = 1.11-7.88) than that for Hispanics (OR = 1.308, 95% CI = 0.607-2.820), and it was higher for Blacks (OR = 1.398, 95% CI = 0.827-2.364) than that for Whites (OR = 1.219, 95% CI = 0.760-1.954). The odds ratio of ASD due to the unhealthy AQI was slightly higher for males (OR = 1.123, 95% CI = 0.771-1.635) than that for females (OR = 1.117, 95% CI = 0.789-1.581). The effects of the unhealthy environmental exposures on the odds ratios of ASD of this study were inconclusive (i.e., statically insignificant; p value > 0.05) for all categories except for Asians. The odds ratios of ASD for Asians were increased by 5, 12, and 14% with increased levels of the environmental exposures of 10 µg/m3 of PM2.5, 1000 kJ/m2 of sunlight, and 1 °F of maximum heat index, respectively. The odds ratios of ASD prevalence for all categories, except for Asians, were increased with the inclusion of the smoking covariate, reflecting the effect of smoking on ASD prevalence besides the unhealthy environmental factors.

Fluid-Structure Interaction Models of Bicuspid Aortic Valves: The Effects of Nonfused Cusp Angles.

Bicuspid aortic valve (BAV) is the most common type of congenital heart disease, occurring in 0.5-2% of the population, where the valve has only two rather than the three normal cusps. Valvular pathologies, such as aortic regurgitation and aortic stenosis, are associated with BAVs, thereby increasing the need for a better understanding of BAV kinematics and geometrical characteristics. The aim of this study is to investigate the influence of the nonfused cusp (NFC) angle in BAV type-1 configuration on the valve's structural and hemodynamic performance. Toward that goal, a parametric fluid-structure interaction (FSI) modeling approach of BAVs is presented. Four FSI models were generated with varying NFC angles between 120 deg and 180 deg. The FSI simulations were based on fully coupled structural and fluid dynamic solvers and corresponded to physiologic values, including the anisotropic hyper-elastic behavior of the tissue. The simulated angles led to different mechanical behavior, such as eccentric jet flow direction with a wider opening shape that was found for the smaller NFC angles, while a narrower opening orifice followed by increased jet flow velocity was observed for the larger NFC angles. Smaller NFC angles led to higher concentrated flow shear stress (FSS) on the NFC during peak systole, while higher maximal principal stresses were found in the raphe region during diastole. The proposed biomechanical models could explain the early failure of BAVs with decreased NFC angles, and suggests that a larger NFC angle is preferable in suture annuloplasty BAV repair surgery.

The association of remotely sensed outdoor fine particulate matter with cancer incidence of respiratory system in the USA.

This study aimed to assess the association between exposure to fine particulate matter (PM2.5) and respiratory system cancer incidence in the US population (n = 295,404,580) using a satellite-derived estimate of PM2.5 concentrations. Linear and logistic regression analyses were performed to determine whether PM2.5 was related to the odds of respiratory system cancer (RSC) incidence based on gender and race. Positive linear regressions were found between PM2.5 concentrations and the age-adjusted RSC incidence rates for all groups (Males, Females, Whites, and Blacks) except for Asians and American Indians. The linear relationships between PM2.5 and RSC incidence rate per 1 µg/m3 PM2.5 increase for Males, Females, Whites, Blacks, and all categories combined had slopes of, respectively, 7.02 (R2 = 0.36), 2.14 (R2 = 0.14), 3.92 (R2 = 0.23), 5.02 (R2 = 0.21), and 4.15 (R2 = 0.28). Similarly, the logistic regression odds ratios per 10 µg/m3 increase of PM2.5 were greater than one for all categories except for Asians and American Indians, indicating that PM2.5 is related to the odds of RSC incidence. The age-adjusted odds ratio for males (OR = 2.16, 95% CI = 1.56-3.01) was higher than that for females (OR = 1.50, 95% CI = 1.09-2.06), and it was higher for Blacks (OR = 2.12, 95% CI = 1.43-3.14) than for Whites (OR = 1.72, 95% CI = 1.23-2.42). The odds ratios for all categories were attenuated with the inclusion of the smoking covariate, reflecting the effect of smoking on RSC incidence besides PM2.5.