Temporal trends in anticoagulation management for US active duty personnel with atrial fibrillation.

ObjectivesThis study aims to investigate US active duty (AD) military members diagnosed with atrial fibrillation (AF) and the temporal trends of systemic anticoagulation (AC). Our secondary objective is to study the AC prescriptions in AD military members diagnosed with AF and associated military dispositions and deployment rates. DESIGN AND SETTING: A retrospective investigation of Tricare pharmacy AC prescriptions within the San Antonio Military Health System from January 2004 to July 2019 for AD individuals diagnosed with AF was performed. PARTICIPANTS: 386 AD personnel with non-valvular AF were analysed (mean age 35.0±9.4 years; mean body mass index, 28.3±4.3 kg/m2; 93% male; 57% Caucasian, 94% paroxysmal AF). OUTCOMES: The temporal trends of systemic AC prescriptions were the primary outcome measures. The association between AC prescriptions and military dispositions and deployments were secondary outcomes of interest. STATISTICAL ANALYSIS: The association between AC management, future deployments and military disposition was analysed using χ2 and Fisher's exact test for categorical variables. The t-test was used for comparison of continuous variables. RESULTS: CHA2DS2-VASc and HAS-BLED scores were low (0.39±0.65 and 0.86±0.63, respectively). 127 (33%) members received warfarin and 58 (15%) received direct oral anticoagulants (DOACs). Rates of military retention were not different between AC histories (no AC (64%) vs warfarin (75%) vs DOAC (65%); p=0.425). There was a significant trend of more recent utilisation of DOACs compared with warfarin (p<0.0001). When adjusted for temporal changes in deployment rates, there was no significant difference in deployment between AC groups (no AC (39%) vs warfarin (49%) vs DOAC (27%); p=0.9472). CONCLUSIONS: This is the first report describing AC utilisation in US AD military members with AF. Young AD personnel with low stroke and bleeding risks do not commonly receive AC prescriptions. DOAC prescription rates are increasing and predominate over warfarin for AC indications.

Characteristics of United States military pilots with atrial fibrillation and deployment and retention rates.

INTRODUCTION: Atrial fibrillation (AF) is an arrhythmia that impacts deployment and retention rates for United States military pilots. This study aims to characterize United States active duty (AD) pilots with AF and review deployment and retention rates associated with medical and ablative therapies. METHODS: An observational analysis was performed to assess AD pilots diagnosed with AF in the largest military regional healthcare system from 2004 to 2019. Baseline characteristics and AF management were reviewed. RESULTS: 27 AD pilots (mean age, 37.3 ± 7.9 years; mean BMI, 27.3 ± 3.1 kg/m2; 100% male sex) were diagnosed with AF during the study dates. 17 (63%) were Air Force branch pilots with hypertension as the most common risk factor (26%). There were overall low CHA2DS2-VASc scores (mean 0.29 ± 0.47). 22 (82%) pilots were equally treated with medical rate and rhythm strategies (41% and 41%, respectively). 16 (59%) underwent pulmonary vein isolation (PVI) with zero complications. 11 (41%) pilots received warfarin and 5 (19%) received a direct oral anticoagulant for stroke prevention. After diagnosis, 12 (44%) pilots deployed and 25 (93%) were retained in military. PVI was not associated with a change in subsequent deployments rates (PVI, 38% vs no PVI, 55%; p = 0.3809) or retention rates (PVI, 94% vs no PVI, 91%; p = 0.7835). CONCLUSIONS: United States military pilots diagnosed with AF are younger patients with few traditional AF risk factors and  they receive medical rate and rhythm strategies equally. Many pilots maintain deployment eligibility and most remain on AD status after diagnosis. PVI is not associated with differences in retention or deployment rates. Further prospective study is needed to further evaluate these findings.

SGLT2 inhibitors: a narrative review of efficacy and safety.

Type 2 diabetes mellitus (T2DM) is a cardio-renal-metabolic condition that is frequently associated with multiple comorbidities, including atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). The sodium-glucose co-transporter-2 (SGLT2) inhibitors, which lower glycated hemoglobin, fasting and postprandial plasma glucose levels, body weight, and blood pressure, as well as reduce the risk of a range of cardiovascular and renal outcomes without increasing hypoglycaemic risk, have heralded a paradigm shift in the management of T2DM. These drugs are compatible with most other glucose-lowering agents and can be used in patients with a wide range of comorbid conditions, including ASCVD, HF, and CKD, and in those with estimated glomerular filtration rates as low as 30 mL/min/1.73 m2. However, there are misunderstandings surrounding the clinical implications of SGLT2 inhibitors' mechanism of action and concerns about the key adverse events with which this class of drugs has been associated. This narrative review summarizes the data that support the efficacy of SGLT2 inhibitors in reducing the risks of cardiovascular and renal outcomes in patients with T2DM and comorbid conditions and clarifies information relating to SGLT2 inhibitor-related adverse events.

The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network.

The ability of red blood cells (RBC) to undergo a wide range of deformations while traversing the microvasculature is crucial for adequate perfusion. Interpretation of RBC deformability measurements performed in vitro in the context of microvascular perfusion has been notoriously difficult. This study compares the measurements of RBC deformability performed using micropore filtration and ektacytometry with the RBC ability to perfuse an artificial microvascular network (AMVN). Human RBCs were collected from healthy consenting volunteers, leukoreduced, washed and exposed to graded concentrations (0-0.08%) of glutaraldehyde (a non-specific protein cross-linker) and diamide (a spectrin-specific protein cross-linker) to impair the deformability of RBCs. Samples comprising cells with two different levels of deformability were created by adding non-deformable RBCs (hardened by exposure to 0.08% glutaraldehyde) to the sample of normal healthy RBCs. Ektacytometry indicated a nearly linear decline in RBC deformability with increasing glutaraldehyde concentration. Micropore filtration showed a significant reduction only for concentrations of glutaraldehyde higher than 0.04%. Neither micropore filtration nor ektacytometry measurements could accurately predict the AMVN perfusion. Treatment with diamide reduced RBC deformability as indicated by ektacytometry, but had no significant effect on either micropore filtration or the AMVN perfusion. Both micropore filtration and ektacytometry showed a linear decline in effective RBC deformability with increasing fraction of non-deformable RBCs in the sample. The corresponding decline in the AMVN perfusion plateaued above 50%, reflecting the innate ability of blood flow in the microvasculature to bypass occluded capillaries. Our results suggest that in vitro measurements of RBC deformability performed using either micropore filtration or ektacytometry may not represent the ability of same RBCs to perfuse microvascular networks. Further development of biomimetic tools for measuring RBC deformability (e.g. the AMVN) could enable a more functionally relevant testing of RBC mechanical properties.

Spontaneous oscillations of capillary blood flow in artificial microvascular networks.

Previous computational studies have suggested that the capillary blood flow oscillations frequently observed in vivo can originate spontaneously from the non-linear rheological properties of blood, without any regulatory input. Testing this hypothesis definitively in experiments involving real microvasculature has been difficult because in vivo the blood flow in capillaries is always actively controlled by the host. The objective of this study was to test the hypothesis experimentally and to investigate the relative contribution of different blood cells to the capillary blood flow dynamics under static boundary conditions and in complete isolation from the active regulatory mechanisms mediated by the blood vessels in vivo. To accomplish this objective, we passed whole blood and re-constituted blood samples (purified red blood cells suspended in buffer or in autologous plasma) through an artificial microvascular network (AMVN) comprising completely inert, microfabricated vessels with the architecture inspired by the real microvasculature. We found that the flow of blood in capillaries of the AMVN indeed oscillates with characteristic frequencies in the range of 0-0.6 Hz, which is in a very good agreement with previous computational studies and in vivo observations. We also found that the traffic of leukocytes through the network (typically neglected in computational modeling) plays an important role in generating the oscillations. This study represents the key piece of experimental evidence in support of the hypothesis that spontaneous, self-sustained oscillations of capillary blood flow can be generated solely by the non-linear rheological properties of blood flowing through microvascular networks, and provides an insight into the mechanism of this fundamentally important microcirculatory phenomenon.

Artificial microvascular network: a new tool for measuring rheologic properties of stored red blood cells.

BACKGROUND: The progressive deterioration of red blood cell (RBC) rheologic properties during refrigerated storage may reduce the clinical efficacy of transfusion of older units. STUDY DESIGN AND METHODS: This article describes the development of a microfluidic device designed to test the rheologic properties of stored RBCs by measuring their ability to perfuse an artificial microvascular network (AMVN) comprised of capillary-size microchannels arranged in a pattern inspired by the real microvasculature. In the AMVN device, the properties of RBCs are evaluated by passing a 40% hematocrit suspension of RBCs through the network and measuring the overall perfusion rate. RESULTS: The sensitivity of the AMVN device to the storage-induced change in rheologic properties of RBCs was tested using five prestorage leukoreduced RBC units stored in AS-1 for 41 days. The AMVN perfusion rate for stored RBCs was 26 ± 4% (19%-30%) lower than for fresh RBCs. Washing these stored RBCs in saline improved their performance by 41 ± 6% (the AMVN perfusion rate for washed stored RBCs was still 15 ± 2% lower than for fresh RBCs). CONCLUSIONS: The measurements performed using the AMVN device confirm a significant decline in the rheologic properties of RBCs in units nearing expiration and demonstrate the sensitivity of the device to these storage-induced changes. The AMVN device may be useful for testing the effect of new storage conditions, additive solutions, and rejuvenation strategies on the rheologic properties of stored RBCs in vitro.