Meschia, James F.

Background Effective leadership is critical to the success of complex multidisciplinary healthcare organisations. As the organisation emerged from the global pandemic, Mayo Clinic recognised a need to transform its traditional, linear care model into a dynamic, platform-based approach to support its strategy. This required a new leadership model that could support and equip leaders with the skills needed to drive patient-centred healthcare transformation from within. Objective To develop and validate a new leadership competency framework capable of supporting future-ready leadership. Methods A multiphase, evidence-based approach was employed: (1) a visionary interview, goal setting and literature review; (2) focus groups with 23 leaders from across the organisation; (3) iterative competency framework development; and (4) a validation study involving a stratified sample of 129 physician leaders who rated competencies on importance and differentiation, and a qualitative verification by key stakeholders. Results Five core competencies with 23 behaviours were identified. The validation analysis established all behaviours as important for differentiating leadership performance. Stakeholder review confirmed the competencies were actionable and applicable across leadership roles at all levels. Conclusion The Leads Self, Leads Others, Inspires Others, Forward Thinking and Engages Others (abbreviated LLIFE) competency model positions a healthcare organisation to advance leadership excellence in a rapidly evolving healthcare environment that requires comprehensive transformation. It aligns with strategic goals, embeds values-based behaviours and supports continuous development, establishing a model that other healthcare institutions may learn from and adapt.

Objectives: This study aims to identify retinal biomarkers of NOTCH3 mutation carriers using optical coherence tomography (OCT) data from the UK Biobank. Methods: We conducted a cross-sectional, matched case-control study of individuals with or without NOTCH3 mutation from the UK Biobank between 2006 and 2010. All participants had macular OCT scan and cognitive assessment. Cases were identified based on pathogenic/likely pathogenic NOTCH3 mutations and 1:1 matched with controls based on age, sex, hypertension, diabetes mellitus, and cigarette smoking status. Baseline characteristics and cognitive test scores were compared using χ 2 or Mann-Whitney U test appropriately. Macular thickness at central, inner, and outer subfields and at each retinal layer was compared using Wilcoxon signed-rank test. Results: Our analysis included 134 participants (67 cases, 67 controls) with a mean age of 54 ± 9 years. NOCTH3 mutation carriers performed worse in prospective memory ( P =0.043), verbal and numerical reasoning ( P =0.178), visual memory ( P =0.227), and processing speed ( P =0.101) than matched controls. There were no differences in visual acuity between the 2 groups. NOTCH3 mutation carriers had significantly thinner macular inner subfield at the superior ( P =0.006), temporal ( P =0.008), and nasal ( P =0.034) quadrants, and significantly thinner macular RNFL ( P =0.008) compared with age-, sex-, and vascular risk factor-matched controls. Conclusion: The presence of NOTCH3 mutation is associated with reduced thickness in the inner macular subfield and macular RFNL. These retinal changes may reflect early pericyte dysfunction and microvascular ischemia. Longitudinal studies are needed to assess the temporal relationship between these retinal changes, cerebrovascular disease progression, and clinical severity of disease.

Background: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) can be misdiagnosed as multiple sclerosis (MS). This study aims to contrast demographic, clinical, neuroimaging, and genetic features of CADASIL patients with vs. without prior MS misdiagnosis. Methods: We conducted a retrospective cohort study to compare genetically or histopathologically confirmed CADASIL patients with and without a prior MS misdiagnosis across Mayo Clinic. Patients were classified into high-, medium-, low-, or unknown-risk by location of NOTCH3 mutation. Disease severity was assessed using NOTCH3 Small-Vessel Disease (N3SVD) scale. Between-group comparisons used independent t-test for age, chi-square or Fisher’s exact test for categorical variables, and Mann–Whitney U test for quantitative variables. Within the misdiagnosed subgroup, neuroimaging changes between MS to CADASIL diagnosis were assessed using Wilcoxon signed-rank test for quantitative data and Stuart–Maxwell test for categorical data. Significance was set at p<0.05 (two-sided). Results: Among 107 patients (mean age 57.5±13.4 yrs) with CADASIL, 12 (11.2%) had a prior MS misdiagnosis (Table 1). Compared to patients without misdiagnosis (n=95), those misdiagnosed were younger, more frequently Asian, more likely to undergo lumbar puncture (83.3% vs 26.3%, p <0.001), and less likely to have had stroke (33.3% vs 65.3%, p =0.031). There were no significant differences in deep white matter hyperintensity scores or lacune counts. However, the misdiagnosed group had a higher median modified Rankin Scale ( p =0.008) and a different distribution of N3SVD stages ( p =0.017), with a higher proportion in stage 3A (33.3% vs 5.3%). There was no significant difference in genetic risk categories (Figure), but 5 of 12 misdiagnosed cases clustered in the medium risk EGFR 13, 13.5, and 14 domains. Among the misdiagnosed, 41.7% received MS-specific treatment during a median of 10.2 months (range 0.4–138.1) before diagnostic correction (Table 2). Over this period, there were no significant changes in DWMH score, lacune count, mRS, or N3SVD stage (all p >0.05). Conclusions: About one in nine CADASIL patients had a prior MS diagnosis. Atypical presentations in younger individuals without a clear stroke history may prompt consideration of MS over CADASIL, leading to diagnostic delays and unnecessary treatments. EGFR domain risk category did not correlate with misdiagnosis.

Introduction: Studies suggest that stroke and hypoperfusion from heart failure (HF) may contribute to cognitive decline. However, the relationship between the HF subtypes and cognition remains poorly described in real-world populations. Hypothesis: We hypothesized that HF subtypes are differentially associated with cognitive impairment and that lower left ventricular ejection fraction (LVEF) correlates with poorer cognitive performance. Methods: We conducted a cross-sectional study of patients aged ≥18 years seen at a Heath System in 2022 who underwent both echocardiogram and cognitive assessment within one year. HF was classified into four groups based on 2022 American Heart Association HF guideline: No heart failure, HFpEF (HF with preserved LVEF), HFmrEF (HF with mid-range LVEF), and HFrEF (HF with reduced LVEF). Cognitive impairment was categorized using the Montreal Cognitive Assessment (MOCA) as normal (≥26), mild (18–25), moderate (10–17), and severe (<10). Multivariable linear regression assessed the correlation between EF and MoCA, and logistic regression evaluated the association between HF subtypes and severity of cognitive loss, adjusting for age, sex, race, hypertension, diabetes, dyslipidemia, chronic kidney disease, stroke. Results: A total of 1,695 patients were included in the study (mean age, 75.3±14 years; 48.3% female). 82.0% had HFpEF; 7.1%, HFmrEF; 7.9%, HFrEF, and 3.0% no HF. LVEF was positively associated with MoCA score (β=0.028, p=0.032). Patients with LVEF ≤40% had lower MoCA scores (17.7 ± 6.2 vs. 19.1 ± 5.9, p=0.008) and higher adjusted odds of moderate/severe cognitive impairment (aOR 2.49, 95%CI 1.20-5.15, p=0.014), compared to those with LVEF >40%. Adjusted odds of moderate to severe cognitive impairment were 1.14 for HFpEF, 0.99 for HFmrEF, and 2.81 for HFrEF compared to patients with no heart failure (trend-P=0.031, Table). Conclusions: Lower LVEF was independently associated with worse cognitive performance. Patients with HFrEF had a 2.5-fold higher risk of moderate to severe cognitive impairment. This association was not observed in patients with HFpEF or HFmrEF, suggesting differential cognitive effects across HF subtypes. Further studies are warranted to confirm these findings and evaluate the impact of interventions targeting EF and HF subtypes on cognitive outcomes.

Objectives: Cerebral hemodynamic impairment in patients with asymptomatic high-grade internal carotid artery (ICA) stenosis confers a risk of stroke and cognitive decline, but correlations between degree of stenosis and hemodynamic impairment are derived from small case series only. Using baseline data from 282 participants in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis – Hemodynamics (CREST-H) study, we hypothesized that degree of stenosis, measured by peak systolic velocity (PSV) and end diastolic velocity (EDV) in the ipsilateral ICA, would correlate with time-to-peak (TTP) delay using MR (n=275) or CT (n=7) perfusion scans, adjusting for demographic and cardiovascular risk variables. Methods: Using a 7-10MHz Doppler probe, ICA PSV and EDV were assessed. Doppler results were adjudicated centrally. Dynamic contrast perfusion imaging was standardized across 61 CREST-H sites, using sequential T2*-weighted time-sequence scanning (e.g. TR=1500, TE=25ms, flip angle=60deg, phase=128, slice thickness=5mm for GE 3T magnet). CTP was acquired with standard clinical protocols. TTP delay was calculated in the ipsilateral versus contralateral MCA/ACA territories using OLEA software. Linear regression used TTP delay as the outcome variable and PSV and EDV as predictor variables, adjusting for covariates.The 282 with complete data for all variables were included in the analysis. Results: Among 392 CREST-H participants, 63% were men, 7% Black, 3% Hispanic, 33% with less than college education. Tables 1a/b show the regression results for PSV and EDV as main predictor variables. PSV and EDV on the index side significantly correlated with TTP delay (p=0.004, p=0.002 respectively). Neither PSV nor EDV on the non-index side correlated with TTP delay (p=0.49, p=0.82). Compared with moderate exercise, vigorous exercise correlated with lower TTP delay in both models (p=0.05. p=0.04). Compared with college graduates, those with HS education had longer TTP delays in both models (p=0.03. p=0.02). Conclusions: In this large cohort of patients with high-grade asymptomatic carotid stenosis, higher flow velocities correlated with greater TTP delays, suggesting an increasing hemodynamic impairment with greater degree of stenosis above 70%. Our findings have implications for management of asymptomatic carotid stenosis which are being tested in the CREST-H and CREST-2 studies. Exercise and education may independently impact cerebral hemodynamics.

BACKGROUND: Cerebral hemodynamic impairment in patients with asymptomatic high-grade (>70%) internal carotid artery (ICA) stenosis is associated with risk of stroke and cognitive decline, but correlations between the degree of stenosis and hemodynamic impairment are derived from small case series. Using baseline data from 242 participants in the CREST-H study (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics), we hypothesized that the degree of stenosis in the ICA would correlate with time-to-peak (TTP) delay in ipsilateral cerebral blood flow using MR/CT perfusion scans, adjusting for demographic and cardiovascular risk variables. METHODS: From all participants, ICAs were insonated using a 7 to 10 MHz probe for peak systolic velocity (PSV) and end diastolic velocity. Dynamic contrast perfusion imaging was standardized across 61 CREST-H sites, using standard sequential T2*-weighted perfusion imaging. CT perfusion used standard clinical protocols. TTP delay was calculated in the ipsilateral versus contralateral hemispheres. In cross-sectional analysis, linear regression was used to model TTP delay as the outcome variable and PSV, end diastolic velocity, and PSV ICA/common carotid artery ratio on the index and nonindex side as primary predictor variables in 6 separate models, adjusting for covariates, followed by automated backward elimination model reduction. RESULTS: Among 392 CREST-H participants, the 242 with complete data for all variables were included in the regression analysis (age, 70±7.6; 62% M). End diastolic velocity on the index side correlated with TTP delay (β=0.003, P =0.005). PSV had a similar correlation but did not reach significance (β=0.001, P =0.099), nor did ICA/common carotid artery ratio (β=0.003, P =0.126). Nonindex side PSV, end diastolic velocity, and ICA/common carotid artery ratio showed no correlation with TTP delay ( P =0.268, P =0.495, P =0.380, respectively). Circle of Willis completeness did not correlate with TTP. CONCLUSIONS: In this large cohort of patients with high-grade asymptomatic carotid stenosis, higher end-diastolic flow velocities correlated with greater TTP delays, supporting a definition of hemodynamically significant stenosis. Our findings have implications for the management of asymptomatic carotid stenosis, which will be tested in the CREST-H study. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03121209.