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Abstract Background Dobutamine stress echocardiography (DSE) is recommended to distinguish between true-severe and pseudo-severe aortic stenosis (AS) in patients with low flow low-gradients and left ventricular ejection fraction (LVEF) <50%. However, DSE has mostly been tested in the setting of LVEF<35%. Purpose The purpose of this study was to examine the diagnostic accuracy of DSE according to aortic valve calcification (AVC) score, in patents with low-flow, low-gradient AS across a wide range of LVEF. Methods Patients with aortic mean gradient <40 mmHg, aortic valve area (AVA) <1.0 cm2, and stroke volume index (SVi) ≤35 mL/m2 undergoing DSE were identified from three prospectively collected patient cohorts, and stratified according to LVEF; <35%, 35-50% and >50%. Severe AS was defined as AVC score ≥2000 AU among men, and ≥1200 AU for women. Recommendation for severe AS according to DSE, are an AVA <1.0 cm2 combined with an aortic mean gradient ≥40 mmHg or peak velocity ≥4 m/s. Receiver operating characteristic curves for DSE-derived AVA, mean gradient and Vmax were used to identify optimal cut-off points for each LVEF subgroup. Results Of the 221 patients included in the study, 78 (35%) presented with LVEF <35%, 67 (30%) with LVEF 35-50%, and 76 (34%) with LVEF >50%. Baseline characteristics are presented in the table. Based on AVC, severe AS was present in 102 (46%) of patients. Using recommended thresholds for severe AS for AVC and DSE, led to a sensitivity of 49%, a specificity of 84% and an accuracy of 67% for DSE for all patients with LVEF <50%, but with significant heterogeneity between groups figure. AVA performed rather uniformly across LVEF subgroups; (AUC =0.68 vs 0.62 vs 0.54, p=0.36) LVEF<35%, LVEF 35-50%, LVEF>50% respectively and displayed a rather uniform optimal cut-off (1.0 cm2 vs 0.9 cm2 vs 0.8 cm2). However, mean gradient and Vmax during DSE, both showed significantly diagnostic heterogeneity across LVEF groups (AUC= 0.90 vs 0.67 vs 0.65, p=<0.001 and AUC= 0.90 vs 0.66 vs 0.60, p=<0.001) with different optimal thresholds (30 mmHg & 3.8 m/s, 45 mmHg & 4.3 m/s and 37mmHg & 4 m/s, LVEF<35%, LVEF 35-50%, LVEF>50%, respectively). Conclusion Our study shows, that the association between DSE gradients and AS severity assessed by AVC demonstrates important heterogeneity depending on LVEF. While DSE had the highest accuracy in patients with LVEF<35% both patients with LVEF 35-50%, and patients with LVEF>50% showed significantly less concordance between DSE and AVC.

Abstract Background Cardiomyopathy is a leading cause of pregnancy-related mortality and represents the number one cause of death in the late postpartum period. Purpose The goal of this study was to prospectively evaluate the effectiveness of an artificial intelligence-based electrocardiogram (AI-ECG) and a point-of-care artificial intelligence-enhanced digital stethoscope for cardiomyopathy screening among pregnant and postpartum women. Methods We conducted a single-arm prospective study of pregnant and postpartum women (up to 12 months following delivery) enrolled at three sites between October 2021 and October 2022. Study participants completed a standard 12-lead ECG, ECG + phonocardiogram recordings with a digital stethoscope, a demographic questionnaire, and a transthoracic echocardiogram (TTE) within a 24-hour period. Diagnostic performance of the AI-ECG and digital stethoscope for cardiomyopathy detection, defined as left ventricular ejection fraction (LVEF) < 45%, was evaluated using the area under the curve (AUC) and standard measures of diagnostic performance. Results We included 100 consecutive pregnant and postpartum women who provided informed consent and had at least one ECG recorded, completed the questionnaire, and had an echocardiogram performed. All participants self-identified as female, and 41% were recruited from a federally qualified health center. The median age of participants was 31 years (Q1: 27, Q3: 34). Thirty-eight percent identified as non-Hispanic White, 32% as non-Hispanic Black, 21% as Hispanic or Latino, 6% as Asian, and 3% as Other (1 Native Hawaiian and 2 multiracial). Five percent (5/100) had LVEF <45%. The 12-lead AI-ECG model demonstrated close to perfect discrimination (accuracy 99%; AUC 1.00, sensitivity 100%) for detection of cardiomyopathy with 1 false positive screen (LVEF 49%), Figure 1A. The digital stethoscope (angled position) had an AUC of 0.99 (95% CI: 0.97, 1.00) for detection of LVEF <45%. Sensitivity, specificity, positive predictive value, and negative predictive value for the digital stethoscope were 60%, 98%, 60% and 98%, respectively for detection of LVEF <45% (Figure 1B & 1C). Conclusions In this small prospective study, we found that 5% of pregnant and postpartum women had cardiomyopathy, a potentially life-threatening condition, and that a rapid, inexpensive, ubiquitous, massively scalable point-of-care test - the ECG - showed promising results, identifying it with an AUC > 0.98 with the application of artificial intelligence.Figure 1

Abstract Objective The primary aim of this paper is to review evidence and clinical implications related to lifestyle activities associated with promoting brain and cognitive health. Our review targets four key lifestyle factors: physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets. Method We conducted a critical review of the lifestyle factor literature in the four domains listed earlier. We contextualize this literature review by translating findings, when possible, into evidence-based recommendations to consider when providing neuropsychological services. Results There is significant current evidence supporting the role of physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets on positive brain and cognitive health outcomes. While some null findings are present in all four areas reviewed, the weight of the evidence supports the notion that engaging in these activities may promote brain and cognitive functioning. Conclusions Clinical neuropsychologists can have confidence in recommending engagement in physical activity, social activity, and cognitively stimulating activity, and adhering to a Mediterranean-style diet to promote brain and cognitive health. We discuss limitations in existing lifestyle factor research and future directions to enhance the existing evidence base, including additional research with historically underrepresented groups and individuals with neurological conditions.

ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P < .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

Summary: Lymphaticovenous anastomosis (LVA) surgery is an effective surgery for the treatment of lymphedema in the extremities. Indocyanine green lymphography is the reference standard for visualizing lymphatics for LVA surgery, but it has several limitations; most notably, superficial dermal congestion can mask deeper lymphatic vessels. To overcome the limitations, we add contrast-enhanced ultrasound (CEUS) lymphography. We have previously reported that CEUS lymphography can identify lymphatic vessels for LVA surgery that indocyanine green lymphography does not. Here, we describe how we perform CEUS lymphography, including workflow, technique, and documentation. Before informed consent, the patient must be screened for possible adverse reactions to microbubbles. The procedure involves multiple intradermal injections of the microbubble agent at various sites along the extremity. After each injection, imaging for microbubble uptake by lymphatic vessels is performed using an ultrasound scanner with contrast-specific software. We use sulfur hexafluoride lipid-type A microspheres (Lumason/SonoVue; Bracco Suisse SA), but we are investigating the performance of other Food & Drug Administration–approved microbubble agents for CEUS lymphography. Having a systematic approach to marking the skin can mitigate the hindrance of marking over ultrasound coupling gel. Another benefit of CEUS lymphography is the rapid identification of neighboring veins compatible in size and location for anastomosis. We hold regular scheduled multidisciplinary meetings for coordination of care, discussion of outcomes, quality assurance, and ongoing innovation.

Objectives Photon-counting detector (PCD) computed tomography (CT) offers improved spatial and contrast resolution, which can impact quantitative measurements. This work aims to determine in human subjects the effect of dual-source PCD-CT on the quantitation of coronary artery calcification (CAC) compared with dual-source energy-integrating detector (EID) CT in both 1- and 3-mm images. Methods This prospective study enrolled patients receiving a clinical EID-CT CAC examination to undergo a research PCD-CT CAC examination. Axial images were reconstructed with a 512 × 512 matrix, 200-mm field of view, 3-mm section thickness/1.5-mm interval using a quantitative kernel (Qr36). Sharper kernels (Qr56/QIR strength 4 for PCD and Qr49/ADMIRE strength 5 for EID) were used to reconstruct images with 1-mm section thickness/0.5-mm interval. Pooled analysis was performed for all calcifications with nonzero values, and volume and Agatston scores were compared between EID-CT and PCD-CT. A Wilcoxon signed-rank test was performed with P < 0.05 considered statistically significant. Results In 21 subjects (median age, 58 years; range, 50–75 years; 13 male [62%]) with a total of 42 calcified arteries detected at 3 mm and 46 calcified arteries at 1-mm images, EID-CT CAC volume and Agatston scores were significantly lower than those of PCD-CT (P ≤ 0.001). At 3-mm thickness, the mean (standard deviation) volume and Agatston score for EID-CT were 55.5 (63.4) mm3 and 63.8 (76.9), respectively, and 61.5 (69.4) mm3 and 70.4 (85.3) for PCD-CT (P = 0.0001 and P = 0.0013). At 1-mm thickness, the mean (standard deviation) volume and score for EID-CT were 50.0 (56.3) mm3 and 61.1 (69.3), respectively, and 59.5 (63.9) mm3 and 72.5 (79.9) for PCD-CT (P < 0.0001 for both). The applied radiation dose (volume CT dose index) for the PCD-CT scan was 2.1 ± 0.6 mGy, which was 13% lower than for the EID-CT scan (2.4 ± 0.7 mGy, P < 0.001). Conclusions Relative to EID-CT, PCD-CT demonstrated a small but significant increase in coronary artery calcium volume and Agatston score.