Hodge, David O.

Precis: In this population-based study of 509 open-angle glaucoma (OAG) patients over a 36-year period, we identified a decreased rate of developing dementia compared with the rate in the general population. Purpose: The aim was to determine the incidence of dementia and Alzheimer disease (AD) among patients with OAG. Patients and Methods: Retrospective, population-based cohort study. All residents of Olmsted County, Minnesota (≥40 y) who were diagnosed with OAG between January 1, 1965 and December 31, 2000, were eligible for inclusion in this study. A total of 509 patients were included over the 36-year period. The cumulative probability of developing dementia was calculated and compared with the population risk of dementia. Results: Of the 509 patients included, 300 (58.9%) were female, the median age was 67.5 years, and 278 patients (54.6%) had primary OAG. Other subgroups were pseudoexfoliation in 15.1%, treated ocular hypertension in 14.1%, normal tension glaucoma in 10.6%, and pigmentary glaucoma in 5.5% of the patients. Respectively, 118 (23.0%) and 99 (19.4%) patients developed dementia and AD. The 10-year cumulative probability of developing dementia and AD was 12.0% and 9.9%, with a 95% confidence interval of 9.3%-15.3% and 7.5%-13%, respectively. The observed 10-year incidence of dementia and AD were significantly lower than the expected population incidence (19.0% and 19.0%; P<0.001). Older age at diagnosis of glaucoma was a strong predictor for the development of dementia by multivariate analysis (hazard ratio: 3.31, 95% confidence interval: 2.61-4.20, P<0.001). Conclusion: The risk of developing dementia or AD was decreased in OAG patients compared with the general population. OAG with onset at a later age may present as a different etiopathogenetic entity compared with onset at a younger age, and represent the optic nerve findings of generalized neurodegenerative processes.

Précis: Kaplan-Meier analysis was used to compare the rate of corneal grafting after glaucoma drainage device (GDD) placement in pediatric and adult patients. Adults were at an increased risk of receiving a corneal graft after device placement. Purpose: The goal of this study was to compare the rate of corneal graft implantation after GDD placement in pediatric and adult patients. Patients: Patients receiving a GDD between January 1, 1985 and December 31, 2017 were selected from the medical records. Patients receiving their first device while <18 years of age were considered children for the extent of the study. Methods: We compared the rate of receiving a corneal graft after GDD implantation using Kaplan-Meier analysis. Baseline patient characteristics and surgical characteristics were compared using a generalized estimating equation. Results: Corneal grafting occurred in 8.6% of adults and 4.7% of children from the original cohort. The rate of receiving a corneal graft at 5, 10, and 15 years was 9.4%, 16.8%, 39.4% and 1.6%, 1.6%, 12.5% for adults and children, respectively. However, certain characteristics were different between the 2 groups. Conclusion: Adult patients were more likely to receive a corneal graft after GDD placement. However, pediatric and adult patients differed in the prevalence of preexisting corneal disease, glaucoma type, GDD type used, and types of previous surgeries. Elucidation of the impact of these factors on corneal graft rate requires a larger cohort size.

Introduction: Patients with D-TGA palliated with atrial switch operations have the morphologic right ventricle in the systemic position. There is increased risk of atrial arrhythmias and systemic right ventricle (SRV) failure. We sought to analyze the long term outcomes of these patients. Methods: All patients with D-TGA and SRV followed in the Adult Congenital Heart Disease Clinic of a large tertiary care institution were reviewed. A comprehensive retrospective analysis of the medical record was performed, including consult notes, ECGs, echocardiograms and electrophysiology reports. Results: A total of 154 patients (63% male) aged 29±11 years were followed for a mean of 10±9 years (range 0-51). During follow-up, 3 patients underwent cardiac transplantation and 15 died; 5 had sudden death, 2 had cardiogenic shock, 5 had non-cardiac death (i.e., infective endocarditis, sepsis) and 3 had unknown causes of death. Heart failure symptoms were present in 53(34%) patients. Severe SRV systolic dysfunction occurred in 37(24%) patients, with a mean EF of 23±5.5%; moderate SRV dysfunction occurred in 67(44%) patients, mean EF 35±4%. Sinus node dysfunction was present in 75(49%) patients, complete AV block in 9(5%) patients, and a pacemaker placed in 60(39%) patients, with cardiac resynchronization therapy in 5. Atrial arrhythmias occurred in 94(61%) patients and ablations were performed in 47(31%) patients. An ICD was implanted in 37 patients; 5 patients had appropriate shocks, but 7 had inappropriate shocks due to atrial arrhythmias. Age (HR 1.07, p=001), heart failure symptoms (HR 4.9, p= 0.007), severe SRV enlargement (HR 3.7, p=0.03), severe systolic dysfunction (HR 5.4, p=0.003), severe systemic AV valve regurgitation (HR 5.2, p=0.002) and a QRS duration> 122ms (HR 3.7, p=0.02) were significant predictors of mortality. The 15 year probability of sudden death was 3.2%(95% CI 0-6.9%). Conclusions: Atrial arrhythmias are common after atrial switch operations secondary to atriotomy scars. Further studies will need to determine whether restoration of sinus rhythm or cardiac synchrony may prevent further deterioration of the systemic right ventricle. Severe SRV dysfunction and prolonged QRS duration >122ms were significantly correlated with mortality.

Elevated intraocular pressure (IOP) is the most prevalent risk factor for primary open-angle glaucoma. However, IOP alone does not fully describe a mechanical basis for disease in patients with normal tension glaucoma or primary open-angle glaucoma. The translaminar pressure difference (TLPD) theory proposes that the pressure gradient generated by the difference of IOP and cerebrospinal fluid pressure (CSFp) acting at the level of the optic nerve can lead to cupping and glaucoma when IOP is higher than normal and/or CSFp is lower than normal. The study results to date have generally supported the TLPD theory; however, varying methods, populations, and sample sizes make it difficult to compare results. To further assess whether there is an association between low CSFp and open-angle glaucoma, 30 years of clinical data that assess 96,543 lumbar punctures were analyzed. Patients with open-angle glaucoma showed a significantly lower CSFp than randomly selected normal control patients (9.9 ± 3 mm·Hg (n = 86) versus 12.1 ± 3.6 mm·Hg (n = 114), p < 0.001 ) following adjustment for age and sex. This retrospective study provides strong evidence for an association between open-angle glaucoma and low CSFp.

Background:There is limited published data on the association between malignancy and the location of venous thromboembolism (VTE) in the body. Aims:Assess the location of VTE in the body in patients with active cancer and compare these results in patients without malignancy. Methods:Consecutive patients enrolled in the Mayo Clinic VTE Registry between March 1, 2013 and November 30, 2019 for acute VTE were followed prospectively. Anatomical site of thrombosis and malignancy status were recorded. Patient outcomes were assessed in person, by mailed questionnaire, or by a scripted phone interview. Active cancer was defined as treatment for malignancy within the last six months or not yet in remission. Results:During the study period there were 2,798 patients with acute VTE (1256 with and 1542 without active cancer). Pulmonary emboli were more common in patients with active cancer compared to patients without cancer (49.5% vs. 39.7%, p&lt;0.001). Upper extremity deep vein thrombosis (11.4 % vs. 7.7%, p&lt;0.001), renal vein thrombi (1.4% vs. 0.2%, p&lt;0.001) and splanchnic vein thrombi (9.3% vs. 6.0%, p=0.001) were all more common in patients with active cancer compared to patients without cancer. Conclusion:Compared to those without malignancy, patients with active cancer were more likely to have pulmonary emboli, upper extremity deep vein thrombosis, renal vein thrombi, and splanchnic vein thrombi. Disclosures No relevant conflicts of interest to declare.

Objective: Vasopressin increases water permeability and activity of the epithelial sodium channel ENaC in the distal nephron of the kidney, favoring increased water and sodium retention. We hypothesized that genetically mediated differences in circulating vasopressin concentrations could contribute to features of hypertension that vary between non-Hispanic blacks and whites. To test this hypothesis we measured copeptin, a fragment of pre-pro arginine vasopressin with a prolonged half-life that is more easily quantified. Methods: The Genetic Epidemiology of Responses to Antihypertensives (GERA) I study was designed to identify predictors of response to diuretic therapy in non-Hispanic black and non-Hispanic white adults with essential hypertension. Blood samples were obtained after a 4 week washout of anti-hypertensive medication while on a sodium intake of 2 mmol/kg. Copeptin was measured from thawed EDTA plasma samples using the copeptin proAVP homogeneous automated immunofluorescent assay on the BRAHMS Kryptor Compact PLUS (Thermo Fisher). Results: Copeptin was significantly higher in blacks (median: 7.4 pmol/L, IQR: 4.4-10.2 pmol/L) than in whites (median: 5.4 pmol/L, IQR: 3.6-8.0 pmol/L) (p <0.001), while renin was lower (Table 1). Racial differences remained significant (p = 0.001) in multivariate models that included 24 hour urine sodium excretion and calculated plasma osmolality. Conclusions: Higher copeptin (vasopressin) concentrations in non-Hispanic blacks compared to whites may contribute to the distinct differences in the hypertensive phenotypes between these racial groups. The underlying mechanism(s) require further study.

Abstract Background Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear.Methods The study included 1,316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record. Results Of the study cohort, 350 patients (26.6%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7-6.2). Hypothyroidism was not associated with a higher risk of all-cause mortality in patients receiving CRT for heart failure. The risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid-stimulating hormone level in the entire cohort (hazard ratio, 1.23 per 5mIU/L increase; 95% CI, 1.01-1.5; P=0.04) as well as in the hypothyroid group (hazard ratio, 1.44 per 5mIU/L increase; 95% CI, 1.13-1.84; P=0.004). Conclusions CRT improves cardiac function in hypothyroid patients. The ventricular arrhythmic events requiring ICD therapies are associated with baseline TSH level, which might be considered as an important biomarker to stratify the risk of sudden death for patients with heart failure and hypothyroidism.

Abstract Background The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins. Methods Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016–August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared. Results Over the study period, there were 647 patients with calf DVT equally distributed between axial (n = 321) and muscular (n = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%; p = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%, p = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%; p = 0.0017) and PE (3.4% vs. 0.6%; p = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%; p = 0.029). Conclusion Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.