Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement.

BACKGROUND: Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive. METHODS: This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1-1.5 cm2; mean gradient, 20-40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record. RESULTS: The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01-1.95]; P=0.048), diabetes (1.46 [95% CI, 1.08-1.96]; P=0.01), elevated averaged mitral valve E/e' ratio (hazard ratio, 1.57 [95% CI, 1.18-2.10]; P<0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15-2.91]; P=0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk. CONCLUSIONS: These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population.

Predicting the final clinical phenotype after the first attack of optic neuritis.

BACKGROUND AND OBJECTIVES: To evaluate the factors determining the final clinical phenotype after an initial isolated attack of optic neuritis (ON). ON could be an isolated event or the initial presentation of a chronic neuroimmunological condition. METHODS: This was a retrospective analysis of patients presenting to University Hospitals Cleveland Medical Center for an initial, isolated attack of ON. Final clinical phenotypes were idiopathic ON, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein associated disease (MOGAD), or secondary ON (e.g. neurosarcoidosis). Several potential predictors at the time of initial presentation were compared among the different phenotypes to determine early predictors. Categorical variables were compared using Pearson χ2 or Fisher's exact test, and continuous variables were compared using independent t-test. RESULTS: Sixty-four patients met criteria (average age 41.3 ± 13.3, 78.1% females). Average time to final diagnosis was 8.3 months, and average follow-up was 47 months. The final phenotypes were MS (22, 34%), idiopathic ON (14, 22%), MOGAD (11, 17%), NMOSD (10, 16%), and secondary ON (7, 11%). White race, unilateral ON, short segment hyperintensity on orbital MRI, classical demyelination on brain MRI, and not requiring PLEX were associated with MS. Older age, poor steroid responsiveness, and requiring PLEX were associated with NMOSD. African American race, bilateral ON, papillitis on fundoscopy, long segment hyperintensity on orbital MRI, and normal brain MRI were associated with MOGAD. Normal or thinned retinal nerve fiber layer on OCT, short segment hyperintensity on orbital MRI, and normal brain MRI were associated with idiopathic ON. CONCLUSION: The final clinical phenotype may be predictable at the time of initial ON presentation. This requires a careful evaluation of patient demographics, treatment response, funduscopic findings, OCT, and orbital and brain MRIs. Utilizing early predictors in clinical practice could better inform prognosis and management decisions.

Parkinsonism in multiple sclerosis patients: A prospective observational study.

BACKGROUND: Rare cases of coexisting multiple sclerosis and parkinsonism have been reported in the literature. However, the true prevalence, clinical characteristics, and causal relation between the two entities have not been systematically evaluated. OBJECTIVE: To evaluate the prevalence of parkinsonism in patients with multiple sclerosis and examine the causal relationship, if any. METHODS: Consecutive patients referred to the multiple sclerosis clinic were evaluated by a neurologist with double training in both neuroimmunology and movement disorders. All patients were specifically screened for movement disorders via a movement disorder survey and a focused exam. Video samples were independently rated by two blinded movement disorder raters. Pre-specified criteria were developed for five potential clinical scenarios: incidental idiopathic Parkinson's disease, incidental Parkinson-plus syndrome, drug-induced parkinsonism, acute symptomatic parkinsonism, and chronic symptomatic parkinsonism. RESULTS: From 2016 to 2021, 336 patients were evaluated. Of those, 12 patients (3.6%) had clinical parkinsonism (average age 68 years, 66% females). Nine patients (75%) were deemed to have incidental Parkinson's disease, 2 (17%) had drug-induced parkinsonism, and 1 (8.3%) was deemed to have demyelination-related chronic symptomatic parkinsonism. The latter presented with gradual and progressive parkinsonism without prodromal symptoms. Both blinded raters agreed with the parkinsonism phenomenology. In addition to typical enhancing and non-enhancing demyelinating lesions, the patient had lesions bilaterally in the basal ganglia. She had positive oligoclonal bands in the cerebrospinal fluid. DAT scan was normal. She was diagnosed with PPMS with activity and progression manifesting solely with secondary parkinsonism. Her disease stabilized with ocrelizumab. There were no cases of acute symptomatic parkinsonism or co-existing Parkinson-plus syndrome over the five-year duration of the study. Three of the incidental idiopathic Parkinson's disease cases had radiologically isolated syndrome. CONCLUSION: Parkinsonism in MS is rare and most cases are incidental. However, clinicians need to recognize the entity of demyelination-related chronic symptomatic parkinsonism in patients with progressive MS phenotypes and demyelinating lesions in the basal ganglia and/or upper midbrain. Parkinsonism may be the sole clinical presentation of progressive MS and the only indication for DMT initiation or escalation. There is an over-representation of radiologically isolated syndrome in patients with presumptive incidental demyelination and idiopathic Parkinson's disease. Prospective studies utilizing high-field MRI and longitudinal DAT scans are needed to better characterize the complex relationship between demyelination and parkinsonism.