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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.

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.

Objective B-type natriuretic peptide (BNP) has favourable effects on left ventricular remodelling, including antifibrotic and antiapoptotic properties. We tested the hypothesis that infusion of BNP after an acute myocardial infarction would reduce left ventricular systolic and diastolic volumes and improve left ventricular ejection fraction compared with placebo. Methods A total of 58 patients who underwent successful revascularisation for an acute ST elevation anterior myocardial infarction were randomised to receive 72-hour infusion of BNP at 0.006 µg/kg/min or placebo. Left ventricular end diastolic and systolic volumes and left ventricular ejection fraction were measured at baseline and at 30 days by multigated acquisition scan. Left ventricular infarction size was measured by cardiac MRI. Results BNP infusion led to significantly higher BNP levels and plasma cyclic guanosine monophosphate at 72 hours. No significant difference in change of left ventricular volumes or ejection fraction from baseline to 30 days was observed between groups. Although left ventricular infarction size measured by cardiac MRI was not significantly different between BNP infusion versus placebo (p=0.39), there was a trend towards reduced infarction size in patients with a baseline ejection fraction of <40% (p=0.14). Conclusions Infusion of BNP in patients with an anterior myocardial infarction did not affect parameters of left ventricular remodelling. Patients treated with BNP who had a baseline left ventricular ejection fraction of <40% had a trend towards reduced left ventricular infarction size compared with placebo. These results do not support the use of intravenous BNP in patients after recent myocardial infarction. Trial registration number NCT00573144.

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non‐traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016. Seventy‐four patients in this cohort presented with non‐traumatic ICH. Medical records including imaging data were reviewed to identify those with CAA and record baseline variables and outcomes of interest; 38 of our 74 patients (51.4%) (mean age 81.5 years) met Modified Boston Criteria for possible or probable CAA. Twenty‐six of 74 patients (35%) died during the first 30 days while 56 of the 74 (76%) patients died by 10 years follow‐up after index ICH. Overall mortality was not significantly different between the CAA and non‐CAA groups at any point of time during follow‐up ( P =0.89) even amongst patients restarted on anticoagulation +/− antiplatelet (n=19) ( P =0.46) or those patients restarted only on antiplatelet therapy (n=22) ( P =0.66). Three of the 41 patients who restarted on antithrombotic therapy had a recurrent ICH; these 3 patients met criteria for possible or probable CAA. Conclusions Although more than half of our patients with atrial fibrillation on antithrombotic therapy and non‐traumatic ICH met Modified Boston Criteria for CAA, CAA did not significantly influence the high mortality seen in this cohort.

AbstractIntroductionThe best management strategy for patients with atrial fibrillation (AF) with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) is unknown.Methods and ResultsThis cohort study was conducted in Olmsted County, Minnesota, with resources of the Rochester Epidemiology Project. Patients with incident AF occurring between 2000 and 2014 with a prior or concurrent HF were included. Patients with LVEF ≥ 50% were designated as HF and preserved ejection fraction (HFpEF) and those with LVEF < 50% were designated as HF and reduced ejection fraction (HFrEF). Rhythm control in the first year after AF diagnosis was defined as prescriptions for an antiarrhythmic drug, catheter ablation, or maze procedure. The primary endpoint was all‐cause mortality. The secondary endpoints were cardiovascular death, cardiovascular hospitalization, and stroke or transient ischemic attack. Of 859 patients (age, 77.2 ± 12.1 years; 49.2%, female), 447 had HFpEF‐AF, and 412 had HFrEF‐AF. There was no difference in all‐cause mortality (10‐year mortality, 83% vs 79%; p = .54) or secondary endpoints between the HFpEF‐AF and HFrEF‐AF, respectively. Compared with the rate control strategy, rhythm control in HFpEF‐AF patients (n = 40, 15.9%) offered no survival benefits (adjusted HR, 0.70; 95% CI, 0.42–1.16; p = .16), whereas rhythm control in HFrEF‐AF patients (n = 52, 22.5%) decrease cardiovascular mortality (HR, 0.38; 95% CI, 0.17–0.86; p = .02).ConclusionsPatients with HFpEF‐AF and HFrEF‐AF had similar poor prognoses. Rhythm control strategy was seldom adopted in community care in patients with HF and AF. A rhythm control strategy may provide survival benefit for patients with HFrEF‐AF and the benefit of rhythm control in patients with HFpEF‐AF warrants further study.