Research Spotlight

McCullough, P. A., H. S. Mehta, C. M. Barker, D. P. Cork, C. Gunnarsson, M. P. Ryan, E. R. Baker, J. Van Houten, S. Mollenkopf and P. Verta (2019). “The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.” Am J Cardiol 124(8): 1226-1231.

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The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p=0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p=0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

Jupiter, D. C., F. Saenz, W. Mileski and N. Shibuya (2019). “Acute Deep Venous Thrombosis and Pulmonary Embolism in Foot and Ankle Trauma in the National Trauma Data Bank: An Update and Reanalysis.” J Foot Ankle Surg 58(6): 1152-1162.

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The data regarding rates of deep venous thrombosis and pulmonary embolism after foot and ankle trauma remain sparse. In this study of the National Trauma Data Bank Data set (2007-2009 and 2010-2016), these rates were reexamined and risk factors associated with these complications were assessed. Data quality is improved in the later data set; the incidence of deep venous thrombosis and pulmonary embolism was 0.28% and 0.21%, respectively, in the 2010-2016 data. Prophylaxis, male gender, treatment in a university hospital, open reduction, chronic obstructive pulmonary disease, and hypertension were notable significant risk factors for pulmonary embolism. For deep venous thrombosis, male gender, bleeding disorder, angina, and prophylaxis were risk factors. Careful, individualized assessment of the risk factors associated with deep venous thrombosis and pulmonary embolism is important, and the merits of routine prophylaxis remain in question.

Husain-Syed, F., H. W. Birk, C. Ronco, T. Schormann, K. Tello, M. J. Richter, J. Wilhelm, N. Sommer, E. Steyerberg, P. Bauer, H. D. Walmrath, W. Seeger, P. A. McCullough, H. Gall and H. A. Ghofrani (2019). “Doppler-Derived Renal Venous Stasis Index in the Prognosis of Right Heart Failure.” J Am Heart Assoc Nov 5;8(21). [Epub 2019 Oct 19].

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Background Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods and Results We enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra-abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH-related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH-specific therapy escalation) and all-cause mortality for 1-year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (P<0.0001) and was significantly associated with right heart and renal function, intra-abdominal pressure, and neurohormonal and hydration status. During follow-up, the morbidity/mortality end point occurred in 91 patients and was independently predicted by RVSI (RVSI in the third tertile versus referent: hazard ratio: 4.72 [95% CI, 2.10-10.59; P<0.0001]). Receiver operating characteristic curves suggested superiority of RVSI to individual intrarenal venous flow patterns in predicting outcome (areas under the curve: 0.789 and 0.761, respectively; P=0.038). Conclusions We propose RVSI as a conceptually new and integrative Doppler index of renal congestion. RVSI provides additional prognostic information to stratify PH for the propensity to develop right heart failure. Clinical Trial Registration Unique identifier: NCT03039959.

Hollander, P. A., J. Kiljanski, E. Spaepen and C. J. Harris (2019). “Risk of clinically relevant hypoglycaemia in patients with type 2 diabetes self-titrating insulin glargine U-100.” Diabetes Obes Metab 21(11): 2413-2421.

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AIMS: We evaluated risk factors for clinically relevant hypoglycaemia (blood glucose <3 mmol/L) in patients with type 2 diabetes during insulin glargine self-titration. Data were from two clinical trials in which patients were able to improve glycaemic control by self-titration of insulin glargine using a simple algorithm. MATERIALS AND METHODS: We performed post hoc analyses of pooled treatment groups from each of two Phase 3 studies comparing LY2963016 with LANTUS: ELEMENT-2 (double-blind) and ELEMENT-5 (open label). Clinically relevant hypoglycaemia was analysed by category of HbA1c (<7%, 7%-8.5%, >8.5%) at Week 12 (titration period) and at Week 24 (overall study), and by subgroups of age (<65, >/=65 years) and previous insulin use (naive or not). RESULTS: In the ELEMENT-2 study (N = 756), there were no overall differences in rate or incidence of hypoglycaemia among HbA1c categories. In the ELEMENT-5 study (N = 493), patients with HbA1c greater than 8.5% had a lower rate and incidence of hypoglycaemia throughout the study compared to those in the lower HbA1c categories. In both studies, patients 65 years of age or older, compared to those less than 65 years, had a higher rate and incidence of hypoglycaemia during the titration phase, had lower baseline HbA1c, and experienced smaller increases in dose, with no differences in HbA1c post baseline. The rate and incidence of hypoglycaemia was similar between naive patients and patients previously using basal insulin, across all levels of glycaemic control. With the exception of the older subgroup, hypoglycaemia rates were similar during titration and maintenance periods. CONCLUSION: Our results support broader use of self-titration algorithms for patients with type 2 diabetes.

Hasan, M. M., L. Thompson-Snipes, G. Klintmalm, A. J. Demetris, J. O’Leary, S. Oh and H. Joo (2019). “CD24(hi)CD38(hi) and CD24(hi)CD27(+) Human Regulatory B Cells Display Common and Distinct Functional Characteristics.” J Immunol 203(8): 2110-2120.

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Although IL-10-producing regulatory B cells (Bregs) play important roles in immune regulation, their surface phenotypes and functional characteristics have not been fully investigated. In this study, we report that the frequency of IL-10-producing Bregs in human peripheral blood, spleens, and tonsils is similar, but they display heterogenous surface phenotypes. Nonetheless, CD24(hi)CD38(hi) transitional B cells (TBs) and CD24(hi)CD27(+) B cells (human equivalent of murine B10 cells) are the major IL-10-producing B cells. They both suppress CD4(+) T cell proliferation as well as IFN-gamma/IL-17 expression. However, CD24(hi)CD27(+) B cells were more efficient than TBs at suppressing CD4(+) T cell proliferation and IFN-gamma/IL-17 expression, whereas they both coexpress IL-10 and TNF-alpha. TGF-beta1 and granzyme B expression were also enriched within CD24(hi)CD27(+) B cells, when compared with TBs. Additionally, CD24(hi)CD27(+) B cells expressed increased levels of surface integrins (CD11a, CD11b, alpha1, alpha4, and beta1) and CD39 (an ecto-ATPase), suggesting that the in vivo mechanisms of action of the two Breg subsets are not the same. Lastly, we also report that liver allograft recipients with plasma cell hepatitis had significant decreases of both Breg subsets.