Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Echocardiographic and Clinical Outcomes in Symptomatic Patients With Less Than Severe Aortic Stenosis After Supra-Annular Self-Expanding Transcatheter Aortic Valve Replacement.

Optimal timing for aortic valve replacement in symptomatic patients with less than severe aortic stenosis (AS) is not well defined. There is limited information on the benefit of valve replacement in these patients. Symptomatic patients with less than severe AS, defined as a mean aortic gradient ≥20 and <40 mm Hg, peak aortic velocity >3 and <4 m/s, and aortic valve area >1.0 and <1.5 cm2, enrolled in the Society for Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry and who underwent attempted supra-annular, self-expanding transcatheter aortic valve replacement (TAVR) were reviewed. Site-reported valve hemodynamics, clinical events, and quality of life metrics were analyzed at 30 days and 1 year after the procedure. A total of 1,067 patients with attempted TAVR (mean age 78.4 ± 8.4 years; Society for Thoracic Surgery score 4.7 ± 3.4%) were found to have symptoms but less than severe AS. From baseline to postprocedure, mean gradient decreased (29.9 ± 4.9 vs 8.4 ± 4.8 mm Hg, p <0.001), and aortic valve area increased (1.2 ± 0.1 vs 2.2 ± 0.7 cm2, p <0.001). Clinical events included 30-day and 1-year all-cause mortality (1.5% and 9.6%), stroke (2.2% and 3.3%), and new pacemaker implantation (18.1% and 20.9%). There were statistically significant improvements in the New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire at 30 days and 1 year. In conclusion, patients with symptomatic but less than severe AS who underwent supra-annular, self-expanding TAVR experienced improved valve hemodynamics and quality of life measures 1 year after the procedure. Randomized studies of TAVR versus a control arm in symptomatic patients with less than severe AS are ongoing.

Modulating T-cell activation with antisense oligonucleotides targeting lymphocyte cytosolic protein 2.

Dysregulated T-cell activation is a hallmark of several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The lymphocyte cytosolic protein 2 (LCP2), also known as SLP-76, is essential for the development and activation of T cells. Despite the critical role of LCP2 in T-cell activation and the need for developing drugs that modify T-cell activation, no LCP2 inhibitors have been developed. This can be explained by the "undruggable" nature of LCP2, lacking a structure permissive to standard small molecule inhibitor modalities. Here, we explored an alternative drug modality, developing antisense oligonucleotides (ASOs) targeting LCP2 mRNAs, and evaluated its activity in modulating T-cell activation. We identified a set of 3' UTR targeting LCP2 ASOs, which knocked down LCP2 in a human T-cell line and primary human T cells and found that these suppressed T-cell receptor mediated activation. We also found that the ASOs suppressed FcεR1-mediated mast cell activation, in line with the role of LCP2 in mast cells. Taken together, our data provide examples of how immunomodulatory ASOs that interfere with undruggable targets can be developed and propose that such drug modalities can be used to treat autoimmune diseases.

The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR.

Individuals expressing HLA-DR4 bearing the shared susceptibility epitope (SE) have an increased risk of developing rheumatoid arthritis (RA). Posttranslational modification of self-proteins via citrullination leads to the formation of neoantigens that can be presented by HLA-DR4 SE allomorphs. However, in T cell-mediated autoimmunity, the interplay between the HLA molecule, posttranslationally modified epitope(s), and the responding T cell repertoire remains unclear. In HLA-DR4 transgenic mice, we show that immunization with a Fibß-74cit69-81 peptide led to a population of HLA-DR4Fibß-74cit69-81 tetramer+ T cells that exhibited biased T cell receptor (TCR) ß chain usage, which was attributable to selective clonal expansion from the preimmune repertoire. Crystal structures of pre- and postimmune TCRs showed that the SE of HLA-DR4 represented a main TCR contact zone. Immunization with a double citrullinated epitope (Fibß-72,74cit69-81) altered the responding HLA-DR4 tetramer+ T cell repertoire, which was due to the P2-citrulline residue interacting with the TCR itself. We show that the SE of HLA-DR4 has dual functionality, namely, presentation and a direct TCR recognition determinant. Analogous biased TCR ß chain usage toward the Fibß-74cit69-81 peptide was observed in healthy HLA-DR4+ individuals and patients with HLA-DR4+ RA, thereby suggesting a link to human RA.

Heterotopic caval valve implantation for the management of severe tricuspid regurgitation: a case series.

BACKGROUND: Severe tricuspid regurgitation (TR) is a complex condition that can be difficult to treat medically, and often surgical intervention is prohibited due to the high morbidity and mortality associated with this intervention. In patients who have failed maximal medical therapy and have progressive symptoms related to their severe TR, heterotopic caval valve implantation (CAVI) offers potential for symptom relief for these patients. CASE SUMMARY: We present two cases of patients with severe TR with symptoms of heart failure that were refractory to medical therapy. Due to extensive comorbidities in these patient's surgical intervention was deemed unsuitable and the decision was made to proceed with heterotopic CAVI in order to try and control their symptoms. Both patients successfully underwent the procedure and had an Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) implanted in the inferior vena cava/right atrium junction. In both patients, there was improvement in the postoperative haemodynamics as measured by invasive and non-invasive methods. Successful discharge was achieved in both patients with improvement in their symptoms. DISCUSSION: Selective use of heterotopic CAVI to treat symptomatic severe TR that is refractory to medical therapy may be a viable option to improve symptoms in those patients that are unsuitable for surgical intervention.

CoreValve bioprosthesis dysfunction treated with a Sapien 3 valve-in-valve transcatheter aortic valve replacement and BASILICA technique.

Structural deterioration of transcatheter heart valve (THV) has been previously described. With the expansion of transcatheter aortic valve replacement (TAVR) indications toward treating lower risk patients with longer life expectancy, there will be increased necessity of managing the patients with THV dysfunction including those at risk for coronary obstruction or sinus sequestration. Coronary access also remains a challenge in such cases with THV dysfunction undergoing valve-in-transcatheter heart valve (ViTHV) TAVR. A unique and first reported case of THV deterioration treated with Sapien 3 ViTHV-TAVR inside a 31 mm CoreValve bioprosthesis along with left coronary leaflet laceration using the BASILICA technique has been presented.

Biased TCR gene usage in citrullinated Tenascin C specific T-cells in rheumatoid arthritis.

We aimed to search for common features in the autoreactive T cell receptor (TCR) repertoire in patients with rheumatoid arthritis (RA), focusing on the newly identified candidate antigen citrullinated Tenascin C (cit-TNC). Mononuclear cells from peripheral blood or synovial fluid of eight RA-patients positive for the RA-associated HLA-DRB1*04:01 allele were in-vitro cultured with recently identified citrullinated peptides from Tenascin C. Antigen-specific T cells were isolated using peptide-HLA tetramer staining and subsequently single-cell sequenced for paired alpha/beta TCR analyses by bioinformatic tools. TCRs were re-expressed for further studies of antigen-specificity and T cell responses. Autoreactive T cell lines could be grown out from both peripheral blood and synovial fluid. We demonstrate the feasibility of retrieving true autoreactive TCR sequences by validating antigen-specificity in T cell lines with re-expressed TCRs. One of the Tenascin C peptides, cit-TNC22, gave the most robust T cell responses including biased TCR gene usage patterns. The shared TCR-beta chain signature among the cit-TNC22-specific TCRs was evident in blood and synovial fluid of different patients. The identification of common elements in the autoreactive TCR repertoire gives promise to the possibility of both immune monitoring of the autoimmune components in RA and of future antigen- or TCR-targeted specific intervention in subsets of patients.

Lessons for Treating Structural Heart Patients during the COVID-19 Pandemic and Beyond.

Background: We sought to compare characteristics and outcomes of structural heart disease (SHD) patients treated during the regional peak of the Coronavirus Disease 2019 (COVID-19) pandemic ("COVID era") compared with historical controls. During the COVID era, elective SHD procedures at Beth Israel Deaconess Medical Center were canceled but urgent cases were still performed. We enacted several practice changes in an effort to minimize complications, prevent COVID transmission, and decrease hospital stay during the pandemic. Methods: Baseline characteristics and outcomes were collected on all patients who underwent SHD procedures during the COVID era and compared with patients treated during the same time period in 2019. Results: Compared with SHD patients treated during 2019 (N = 259), those treated during the COVID era (N = 26) had higher left ventricular end diastolic pressure (LVEDP; 28 vs. 21 mmHg, p = 0.001), and were more likely New York Heart Association class IV (26.9% vs. 10.0%, p = 0.019), but had a lower rate of bleeding/vascular complications (0% vs. 16.2%, p = 0.013), a lower rate of permanent pacemaker implantation (0% vs. 17.4%, p = 0.019), and a greater proportion of patients were discharged on post-operative day 1 (POD#1; 68.2% vs. 22.2%, p < 0.001). Conclusion: Practice changes employed for patients treated during the COVID era were associated with fewer vascular complications, a greater proportion of patients discharged on POD#1, and a lower rate of pacemaker implantation despite more severe illness. As a result, we plan to continue these practices in the post-COVID era.

Post hoc closure of large bore vascular access using the MANTA closure device.

Successful closure of large bore vascular access (≥12 Fr) is facilitated by the MANTA vascular closure device; however, it requires a critical first step of measuring "skin to arterial wall" depth of the access site using the depth locator before dilating the vessel above 8 Fr. It may be challenging at times to acquire the deployment depth at the onset of the procedure due to case urgency, delayed closure, or when large bore access is obtained at a different institution. We discuss a novel technique of measuring the deployment depth and successful delayed closure of large bore arterial access using the MANTA closure device.

References Values for Left Atrial Volumes, Emptying Fractions, Strains, and Strain Rates and Their Determinants by Age, Gender, and Ethnicity: The Multiethnic Study of Atherosclerosis (MESA).

RATIONALE AND OBJECTIVES: Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. MATERIALS AND METHODS: 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010-2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. RESULTS: The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45-65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (-1.4 ± 0.7 s-1), (-2.1 ± 1 s-1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (-1 ± 0.6 s-1), (-2.1 ± 1 s-1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. CONCLUSION: This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53-94 years evaluated by FTMRI.

Retino-choroidal changes in patients with acute pancreatitis: A prospective analysis of a novel biomarker.

BACKGROUND: There is paucity of data on ocular changes in acute Pancreatitis (AP). Moreover, subclinical alterations in retina & choroid have not been studied in AP. OBJECTIVE: To prospectively study retino-choroidal changes in AP. METHODS: Sixty patients (mean age 39.07 years; 41 males) with AP were followed up till recovery/death. Baseline slit-lamp examination, choroidal thickness (CT), retinal thickness (RT), choroidal vascularity index (CVI), retinal capillary density index (CDI) and arteriovenous ratio (AVR) were recorded. The patients were divided into two groups - mild (Group A; 5 patients) and moderately severe/severe (Group B; 55 patients) as per revised Atlanta classification. RESULTS: Fundus examination showed mild optic disc edema with retinal hemorrhages in 6 (10%) patients in group B as compared to none in group A (p = 1.00). None of the patients had Purtscher retinopathy. Mean CT (317 ± 56.29 µm) was increased as compared to normal subjects (278.90 ± 57.84 µm, p = 0.003). The mean CVI (0.62 ± 0.04) was decreased as compared to normal (0.66 ± 0.01, p < 0.0001) as was the mean AVR (0.67 ± 0.03 vs. 0.7 ± 0.02, p < 0.0001). However, the mean RT of subjects with AP (239.68 ± 33.76 µm) was not significantly different compared to the normal subjects 253.17 ± 33.67 µm (p=NS). The mean CDI of superficial and deep plexus were comparable between normal and patients with AP. CT, RT, CVI, AVR and CDI were comparable between group A and group B as well as survivors and non-survivors. CONCLUSIONS: Clinically significant ocular changes are seen infrequently in AP. However, subclinical changes in CT, CVI and AVR are observed in patients with AP compared to normal individuals.

Proteinase 3 Autoreactivity in Anti-Neutrophil Cytoplasmic Antibody-associated vasculitis-Immunological versus clinical features.

ANCA-associated vasculitis (AAV) is a group of chronic inflammatory diseases of small- and medium-sized vessels, which are broadly subdivided based on organ manifestations and disease-specific autoantibodies. The so called anti-neutrophil cytoplasmic antibodies (ANCA) mostly target one of the enzymes, proteinase 3 (PR3) or myeloperoxidase (MPO). Accumulating genetic data demonstrates that these two autoantibodies discriminate two distinct disease entities, more so than the clinical subdivision which is mainly criteria-based. Treatment of AAV includes heavy immunosuppression and is guided by which organs that are involved. Generally, patients with PR3-ANCA display higher risk for disease relapse than patients with MPO-ANCA. In this review, we will focus on the autoimmune features of PR3+ AAV and our current understanding of its triggers and the potential translation into clinical practice.

Antidepressant effects of ketamine and ECT: A pilot comparison.

BACKGROUND: To compare the antidepressant effects and cognitive adverse effects of intravenous ketamine infusion and Electro-convulsive therapy (ECT) in persons with severe depressive episodes. METHODS: This assessor-blinded randomized control trial included 25 patients (either sex; 18-65 years) meeting ICD-10 criteria for severe depression (bipolar or unipolar). Patients received either ECT (n = 13) or intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min; n = 12) for six alternate day sessions over a period of two weeks. Severity of depression was assessed at baseline and on every alternate day of intervention using the Hamilton Depression Rating Scale (HDRS) and self-reported Beck Depression Inventory (BDI). RESULTS: Baseline socio-demographic and clinical variables including HDRS (ECT: 25.15±6.58; Ketamine: 23.33±4.05, p = 0.418) and BDI (ECT: 37.07±6.58; Ketamine: 33.33±9.29; p = 0.254) were comparable. Repeated-measures analysis of variance revealed that ECT patients showed significantly greater reduction in HDRS (group*time interaction effect; F = 4.79; p<0.001) and BDI scores (group*time interaction effect; F = 3.83; p<0.01). ECT patients had higher response rate than ketamine patients [HDRS: ECT- 13/13(100%) vs ketamine- 8/12 (66.70%); p = 0.04]. This was true for remission as well [ECT- 12/13(92.30%) vs ketamine- 6/12(50%), p = 0.030; both HDRS and BDI]. Performance on Digit Symbol Substitution Test (as part of the Battery for ECT-Related Cognitive Deficits scale) significantly improved in ketamine patients (p = 0.02) while that in ECT patients worsened non significantly (p = 0.30). LIMITATIONS: Relatively small sample size; higher proportion of dropouts in the Ketamine arm. CONCLUSION: This study favoured ECT over ketamine for a better efficacy over six treatment sessions in severe depression. The results need to be replicated in larger studies. TRIAL REGISTRATION: CTRI/2019/09/021184.

Clinical and morphological consequences of permanent indwelling transmural plastic stents in disconnected pancreatic duct syndrome.

BACKGROUND: Long-term indwelling transmural stents in patients with walled-off necrosis (WON) and disconnected pancreatic duct syndrome (DPDS) is an effective strategy to decrease risk of recurrence of pancreatic fluid collection (PFC). However, long-term studies on the safety and efficacy of this strategy are lacking. METHODS: Retrospective analysis of database of patients with WON treated with endoscopic transmural drainage over the past 8 years was done to identify patients with DPDS and indwelling transmural stents for >3 years. RESULTS: During the past 8 years, 56 patients with indwelling transmural stent for >3 years were identified and 67.85% of these patients had 10 Fr stents and 32.15% of patients had 7 Fr stents. On follow-up, 5 (8.9%) patients had pancreatic pain with one patient (1.78%) developing recurrence of PFC despite stent being in situ. Two (3.5%) patients had asymptomatic spontaneous external migration of the transmural stent. Fourteen (25%) patients developed diabetes. Two (3.5%) patients developed local complications due to indwelling stent (stent eroded into descending colon in one patient and stent-induced parenchymal calcification in the other). Forty-eight (85.7%) patients underwent EUS on follow-up and disconnected pancreas revealed ≥5 criteria for the diagnosis of chronic pancreatitis in 15 (31.25%) patients. CONCLUSIONS: Long-term indwelling transmural plastic stents in patients with WON and DPDS are safe and effective with minimal complications. Despite the presence of stents, disconnected pancreas develops morphological changes resembling chronic pancreatitis in one-third patients and clinical consequences of these changes need to be further evaluated.

Association of smoking and right ventricular function in middle age: CARDIA study.

Objective: To evaluate the association of cigarette smoking and right ventricular (RV) systolic and diastolic functions in a population-based cohort of individuals at middle age. Methods: This cross-sectional study included participants who answered the smoking questionnaire and underwent echocardiography at the Coronary Artery Risk Development in Young Adulthood year 25 examination. RV systolic function was assessed by echocardiographic-derived tricuspid annular plane systolic excursion (TAPSE) and by right ventricular peak systolic velocity (RVS'), while RV diastolic function was evaluated by early right ventricular tissue velocity (RVE'). Multivariable linear regression models assessed the relationship of smoking with RV function, adjusting for age, sex, race, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, diabetes mellitus, alcohol consumption, pulmonary function, left ventricular systolic and diastolic function and coronary artery calcium score. Results: A total of 3424 participants were included. The mean age was 50±4 years; 57% were female; and 53% were black. There were 2106 (61%) never smokers, 750 (22%) former smokers and 589 (17%) current smokers. In the multivariable analysis, current smokers had significantly lower TAPSE (ß=-0.082, SE=0.031, p=0.008), RVS' (ß=-0.343, SE=0.156, p=0.028) and RVE' (ß=-0.715, SE=0.195, p<0.001) compared with never smokers. Former smokers had a significantly lower RVE' compared with never smokers (ß=-0.414, SE=0.162, p=0.011), whereas no significant difference in RV systolic function was found between former smokers and never smokers. Conclusions: In a large multicenter community-based biracial cohort of middle-aged individuals, smoking was independently related to both worse RV systolic and diastolic functions.

Sleep-disordered breathing and left ventricular scar on cardiac magnetic resonance: results of the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: The objectives of this study were to evaluate the independent association between sleep-disordered breathing (SDB) using overnight polysomnography and left ventricular (LV) scar using cardiac magnetic resonance (CMR) with late-gadolinium enhancement in a community-based cohort of the Multi-Ethnic Study of Atherosclerosis. METHODS: Our analytical sample includes 934 participants from the fifth examination of the Multiethnic Study of Atherosclerosis who underwent both polysomnography and CMR. SDB was categorized as follows: no-SDB (apnea-hypopnea index [AHI] < 5 events/h), mild SDB (5 events/h ≤ AHI < 15 events/h), and moderate-severe SDB (AHI ≥ 15 events/h). LV scar was considered present if there was presence of scar on CMR (late-gadolinium enhancement > 0%). Logistic regression with multivariable adjustment for confounders (age, sex, race/ethnicity, body mass index, and cardiometabolic risk factors) was used to examine the independent association of SDB with LV scar. Confounders were identified using directed acyclic graphs. RESULTS: The mean age of our sample was 67.0 ± 8.5 years (SD), with 49% (n = 461) females and a prevalence of SDB (AHI ≥ 5 events/h) of 63% (n = 590). LV scar was more prevalent in individuals with SDB (9.5%) versus those without SDB (3.8%; P < .01), and 88% of all LV scars were clinically unrecognized. After multivariable adjustment, both mild SDB and moderate-severe SDB were independently associated with LV scar (odds ratio, 2.53; 95% confidence interval, 1.13-5.64 and odds ratio, 2.31; 95% confidence interval, 1.01-5.24, respectively). CONCLUSIONS: In a community-based cohort, SDB (including mild) is independently associated with a more than 2-fold increase in the odds of LV scar presence measured using CMR with late-gadolinium enhancement. Most LV scars were clinically unrecognized. The impact of SDB treatment on subclinical myocardial infarction needs to be investigated in future studies.

Percutaneous Management of a Contained Annular Rupture Occurring With Self-Expanding Transcatheter Aortic Valve Replacement.

Annular rupture is a rare catastrophic event during transcatheter aortic valve replacement, often life threatening and requiring emergent surgical repair. We describe, herein, a case of contained annular rupture successfully managed percutaneously with coiling and polymer injection. This is a novel technique to manage this complication. (Level of Difficulty: Advanced.).