Faculty Bibliography

BACKGROUND:Catheter ablation of sustained monomorphic ventricular tachycardia (SMVT) guided by the identification of slowly conducting anatomical isthmuses (SCAIs) has been proposed to mitigate the risk of ventricular tachycardia in tetralogy of Fallot (TOF). However, the prevalence and clinical significance of SCAI remain uncertain. OBJECTIVES/OBJECTIVE:This study aimed to assess the association between SCAI and SMVT inducibility in patients with TOF. METHODS:A multicenter international cohort with retrospective (2017-2021) and prospective (commencing 2021) components enrolled patients with TOF referred for electrophysiological study before transcatheter pulmonary valve replacement. The proportion with SCAI and its association with SMVT inducibility were analyzed. RESULTS:A total of 162 patients (mean age 39.5 ± 14.2 years; 57.4% male) were included. SMVT was induced in 42 (25.9%) patients, and ≥1 SCAI was present in 76 (46.9%) patients. The prevalence of SCAI was higher in patients with inducible SMVT (78.6% vs 31.1%; P < 0.001). However, 21.4% of patients with inducible SMVT had normally conducting anatomical isthmus (14.3%) or a non-anatomical isthmus substrate (7.1%). The area under the curve of SCAI in predicting SMVT inducibility was 0.71 (sensitivity 78.6%; specificity 64.2%). Although SCAI was independently associated with SMVT (OR: 6.4; 95% CI: 2.6-18.2), the association with other clinical parameters improved prediction of SMVT inducibility. CONCLUSIONS:SCAI is highly prevalent in patients with TOF and is associated with inducible SMVT. However, the proportion of SCAI in noninducible patients is substantial, and some inducible patients have no SCAI. These findings suggest that SCAI alone is insufficient for arrhythmia management decisions, highlighting the need for an integrative approach combining electrophysiological study with other clinical parameters.

OBJECTIVE:To determine the optimal iodine concentration (IC) to differentiate enhancing from nonenhancing renal lesions at venous phase photon-counting CT (PCCT). MATERIALS AND METHODS/METHODS:Sixty-seven patients [41 males, mean (SD) age: 68 (13) y] who underwent contrast-enhanced venous phase abdominal PCCT and contrast-enhanced MRI were retrospectively identified. MRI characterization of renal lesions as simple cysts, hemorrhagic/proteinaceous cysts or masses was the reference standard. Two radiologists, blinded to MRI characterization, independently drew region-of-interests (ROI) within each renal lesion and the aorta to determine IC, iodine concentration normalized to aortic enhancement (NIC), postcontrast and virtual noncontrast attenuation. These variables were compared using nonparametric tests, and intraclass correlation coefficient was assessed. ROC analysis for IC, NIC, and attenuation difference was performed using mean measurements. RESULTS:Median (IQR) IC was 0.015 (0.00 to 0.20) mg/mL for cysts (n = 41) and 3.00 (1.59 to 4.10) mg/mL for masses (n = 26; P < 0.001). NIC was 2 (-1 to 4)% for cysts and 58 (33 to 81)% for masses (P < 0.001). For differentiating cysts from masses, 0.6 mg/mL IC had 100% sensitivity and 95% specificity [AUC = 1.00 (0.99, 1.00)] and 14.1%. NIC had 100% sensitivity and 98% specificity [AUC = 1.00 (0.99, 1.00)]. For differentiating cysts from enhancing masses, a 20 HU attenuation change from VNC to postcontrast images demonstrated a sensitivity of 96% and specificity of 95% [AUC = 1.00 (0.99, 1.00)]. IC was 0.13 (-0.11 to 0.20) mg/mL for hemorrhagic cysts (n = 16) and 1.63 (1.31 to 1.89) mg/mL for papillary neoplasms (n = 8; P < 0.001). NIC was 2 (-1 to 5)% and 32 (22 to 40)%, respectively (P < 0.001). For differentiating hemorrhagic cysts from papillary neoplasms, 0.53 mg/mL IC had 100% sensitivity and 88% specificity [AUC = 0.98 (0.93, 1.00)] and 14.1% NIC had 100% sensitivity and 94% specificity [AUC = 0.98 (0.95, 1.00)]. A 20 HU change had 88% sensitivity and specificity. For differentiating hemorrhagic cysts from papillary neoplasms, a 20 HU attenuation change had 88% sensitivity and 88% specificity [AUC = 0.98 (0.93, 1.00)]. CONCLUSIONS:PCCT iodine concentration showed outstanding diagnostic performance to differentiate renal cysts from neoplasms. A 20 HU change in attenuation from VNC to postcontrast imaging on PCCT remains a reliable threshold for enhancing lesion, similar to conventional CT. Iodine concentration demonstrated superior sensitivity and specificity compared with 20 HU change when identifying renal cysts versus masses.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Surgery in NF2-related schwannomatosis (NF2-SWN) vestibular schwannoma (VS) carries a higher risk of facial nerve damage, hearing loss, and partial resection, than in sporadic cases. Radiosurgery is also associated with higher failure compared with sporadic schwannomas. Nowadays, bevacizumab (BEV) is frequently considered in the NF2-SWN population. However, some patients experience progression despite treatment. Among other surgical risks, in BEV-treated patients, hemorrhage and impaired healing are specific considerations. These concerns have led manufacturers to recommend stopping BEV 6 to 8 weeks preoperatively. The aim of our multicentric study was to assess the perioperative bleeding risk and postoperative outcomes in NF2-SWN patients undergoing VS surgery after preoperative BEV treatment. METHODS:Our retrospective analysis included medical and surgical records along with imaging reviews from 4 high-volume tertiary academic referral centers for NF2-SWN and VS. RESULTS:A total of 21 patients met the inclusion criteria. VS had a mean volume of 13.2 ±7.6 cm3 corresponding to 1 KOOS III and 20 KOOS IV. BEV was stopped at a mean of 5.8 ± 4.0 months before surgery with a total mean treatment duration of 33.7 ± 20.7 months and a monthly dose of 10.2 ± 4.1 mg/kg. Intraoperatively, the tumor was assessed to be bloody by the operating surgeons in 7 patients. Late BEV discontinuation and high cumulative dose independently predicted perioperative bleeding and longer surgery duration. No other complication such as wound dehiscence was reported. CONCLUSION/CONCLUSIONS:Our findings suggest that a higher cumulative BEV dose (∼600 mg/kg) and a longer interval between BEV discontinuation and surgery (∼8 months) are associated with a modest but statistically significant increase in intraoperative bleeding risk. Based on these observations, a BEV-free window between 6 weeks and 6 months (depending on the clinical scenario) before tumor resection seems optimal, particularly for patients with high cumulative exposure.

The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular resilience as a dynamic and multifaceted concept spanning molecular, cellular and systemic levels across an individual's lifespan. The workshop emphasized the need to expand the focus from solely understanding whether and how sleep and circadian rhythm disturbances contribute to disease, to also exploring how healthy sleep and aligned circadian rhythms can increase cardiovascular resilience. To develop a Roadmap towards this goal, workshop participants identified key knowledge gaps and research opportunities, including the need to integrate biological, behavioural, environmental and societal factors in sleep and circadian health with cardiovascular research to identify therapeutic targets. Proposed interventions encompass behavioural therapies, chronotherapy, lifestyle changes, organizational policies and public health initiatives aimed at improving sleep and circadian health for better cardiovascular outcomes. Future cross-disciplinary research and translation of discoveries into public health strategies and clinical practices could improve cardiovascular resilience across the lifespan in all populations.

Liver transplant (LT) recipients experience a wide range of comorbidities, leading to frequent healthcare encounters. Until now, national registries, which have limited exposures and outcomes, and laborious small cohort studies have been the main data sources for LT research. Cosmos database offers electronic health record (EHR)-based insights into LT recipients at the national level with granular data. We evaluated if Cosmos data is representative of the entire US LT recipient population. Using Cosmos (N=20,235) and the national Scientific Registry of Transplant Recipients (SRTR) (N=51,281), we identified adult, first-time LT recipients between 7/2016-12/2022. We compared demographics, clinical data, and mortality across datasets, calculating Kaplan-Meier survival estimates and multi-variable Cox regressions. Recipient characteristics were highly comparable (e.g., female: Cosmos=36.5% vs. SRTR=36.4%, Black: 6.8% vs. 7.2%; BMI: 28.5 kg/m2 [24.8-32.9] vs. 28.2 [24.6-32.4]). Lab values were similar across cohorts, including MELD (24 [17-30] vs. 23 [16-30]). Transplant indications, donor characteristics, and 5-year survival (Cosmos 83.1% [82.3-83.8) vs. SRTR 80.9% [80.4-81.3]) were similar. The associations of clinical factors with survival were similar across both groups. Cosmos database demonstrated acceptable generalizability to the general US LT recipient population, which may advance LT research through a better understanding about LT recipients' experiences and outcomes.

BACKGROUND AND AIMS/OBJECTIVE:There is limited information regarding performance of fecal immunochemical test (FIT) in post-polypectomy surveillance, or for screening individuals with a family history of CRC . We conducted a systematic review to assess current evidence regarding diagnostic performance of one time FIT in increased risk populations. METHODS:A comprehensive search of multiple databases was conducted to assess studies reporting performance of a one-time FIT as screening or surveillance tool in individuals at increased risk of CRC. RESULTS:We identified three studies reporting on 8817 individuals with personal history of polyps who underwent FIT testing. For CRC detection, one time FIT showed sensitivity ranging from 27.6% to 100.0% and specificity ranging from 55.9% to 94.1% with variable test thresholds and index polyp histology. We identified 12 studies reporting on 5525 individuals with family history of CRC. One time FIT showed a sensitivity ranging from 25.0% to 100.0% and specificity ranging from 83.1% to 92.0% , with variable test thresholds and family history characteristics. CONCLUSION/CONCLUSIONS:Current evidence is limited to adequately assess diagnostic performance of FIT in individuals with family history of CRC, or as follow up after polypectomy.

PURPOSE/OBJECTIVE:There is a lack of safety and efficacy data for newer biologic agents among adults ≥ 60 years old with inflammatory bowel disease (IBD) given their limited inclusion in clinical trials. We conducted a retrospective cohort study comparing the safety and efficacy of ustekinumab (UST) or vedolizumab (VDZ) use in older adults as compared to younger adults with IBD. METHODS:This single-center retrospective study compared individuals 18 to 59 years old to individuals ≥ 60 years old with a confirmed diagnosis of IBD who began VDZ or UST treatment between 2014 and 2022. The primary efficacy and safety outcomes were endoscopic remission and serious infection, respectively. Secondary outcomes included endoscopic response, clinical remission, and non-severe adverse events. Multivariable regression was used to identify factors independently associated with safety and efficacy. RESULTS:Overall, 948 individuals were included, with 779 (82.2%) < 60 years-old. In total, 548 (57.8%) had Crohn's disease, 367 (38.7%) had ulcerative colitis, 33 (3.5%) had indeterminate colitis, and a total of 403 individuals (42.5%) initiated VDZ whereas 545 (57.5%) initiated UST. When assessing efficacy, younger and older individuals had comparable rates of endoscopic remission (< 60 years-old 27.5% vs 29.0% ≥ 60 years-old, p = 0.69) as well as clinical remission (< 60 years-old 26.4% vs 26.6% ≥ 60 years-old, p = 0.96). When assessing safety, serious infection rates (< 60 years-old 8.9% vs 8.9% ≥ 60 years-old, p  = 0.99) and non-severe adverse event rates (< 60 years-old 12.3% vs 8.9% ≥ 60 years-old, p = 0.21) were not significantly different. On multivariable analysis, measures of disease severity (prior advanced therapy use, prior corticosteroid use, severe disease) significantly decreased the odds of endoscopic and clinical remission. Additionally, prior advanced therapy use and the presence of comorbidities increased the odds of serious infections. CONCLUSION/CONCLUSIONS:The use of UST and VDZ had similar efficacy and safety outcomes in older adults as compared to younger individuals with IBD. Decisions to utilize these biologics should be driven by overall disease burden and comorbidities, and not be deferred due to advanced chronological age alone.

PURPOSE/OBJECTIVE:The long scan times of quantitative MRI techniques make them vulnerable to motion artifacts. For MR-Fingerprinting-like approaches, this problem can be addressed with self-navigated retrospective motion correction based on reconstructions in a singular value decomposition (SVD) subspace. However, the SVD promotes high signal intensity in all tissues, which limits the contrast between tissue types and ultimately reduces the accuracy of registration. The purpose of this paper is to rotate the subspace for maximum contrast between two types of tissue and improve the accuracy of motion estimates. METHODS:A subspace is derived that promotes contrasts between brain parenchyma and CSF, achieved through the generalized eigendecomposition of mean autocorrelation matrices, followed by a Gram-Schmidt process to maintain orthogonality. We tested our motion correction method on 85 scans with varying motion levels, acquired with a 3D hybrid-state sequence optimized for quantitative magnetization transfer imaging. RESULTS:A comparative analysis shows that the contrast-optimized basis significantly improves the parenchyma-CSF contrast, leading to more accurate motion estimates and reduced artifacts in the quantitative maps. CONCLUSION/CONCLUSIONS:The proposed contrast-optimized subspace improves the accuracy of the motion estimation.