Research Spotlight

Posted October 15th 2021

Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial.

Milton Packer M.D.

Milton Packer M.D.

Januzzi, J. L., Jr., F. Zannad, S. D. Anker, J. Butler, G. Filippatos, S. J. Pocock, J. P. Ferreira, N. Sattar, S. Verma, O. Vedin, J. Schnee, T. Iwata, D. Cotton and M. Packer (2021). “Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial.” J Am Coll Cardiol 78(13): 1321-1332.

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BACKGROUND: The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported. OBJECTIVES: The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction). METHODS: Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP. RESULTS: Incidence rates for each study outcome were 4- to 6-fold higher among those in the highest versus lowest NT-proBNP quartiles (≥3,480 vs <1,115 pg/mL). Study participants with higher NT-proBNP had 2- to 3-fold total hospitalizations higher than the lowest NT-proBNP quartile. Empagliflozin reduced risk for major cardiorenal events without heterogeneity across NT-proBNP quartiles (primary endpoint P(interaction) = 0.94; renal composite endpoint P(interaction) = 0.71). Empagliflozin treatment significantly reduced NT-proBNP at all timepoints examined; by 52 weeks, the adjusted mean difference from placebo was 13% (P < 0.001). An NT-proBNP in the lowest quartile (<1,115 pg/mL) 12 weeks after randomization was associated with lower risk for subsequent cardiovascular death or heart failure hospitalization regardless of baseline concentration. Treatment with empagliflozin resulted in 27% higher adjusted odds of an NT-proBNP concentration of <1,115 pg/mL by 12 weeks compared with placebo (P = 0.01). CONCLUSIONS: In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration. The NT-proBNP concentration after treatment with empagliflozin better informs subsequent prognosis than pretreatment concentrations. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).


Posted October 15th 2021

Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure.

Milton Packer M.D.

Milton Packer M.D.

Böhm, M., S. D. Anker, J. Butler, G. Filippatos, J. P. Ferreira, S. J. Pocock, F. Mahfoud, M. Brueckmann, W. Jamal, A. P. Ofstad, E. Schüler, P. Ponikowski, C. Wanner, F. Zannad and M. Packer (2021). “Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure.” J Am Coll Cardiol 78(13): 1337-1348.

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BACKGROUND: Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with reduced ejection fraction. Its interplay with systolic blood pressure (SBP) is not known. OBJECTIVES: The goal of this study was to evaluate the interplay of SBP and the effects of empagliflozin in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction). METHODS: Study patients (N = 3,730) were randomly assigned to groups according to SBP at baseline (<110 mm Hg, n = 928; 110-130 mm Hg, n = 1,755; >130 mm Hg, n = 1,047). This study explored the influence of SBP on the effects of empagliflozin on cardiovascular death or HF hospitalization (primary outcome), as well as on total HF hospitalizations, rate of decline in estimated glomerular filtration rate, renal outcomes, and empagliflozin’s effects and significance on SBP. RESULTS: Over a median of 16 months considering only patients receiving placebo, baseline SBP and the risk of cardiovascular death or hospitalization for HF (P trend = 0.0015) were inversely related. Corrected for placebo, a slight early increase was observed in SBP at <110 mm Hg, no change at 110-130 mm Hg, and a slight reduction at >130 mm Hg. These between-group differences were of borderline significance (P for interaction trend = 0.05-0.10) after 4 and 12 weeks but were not significant later. SBP at baseline did not influence the effect of empagliflozin to reduce the risk of HF events or renal endpoints. When treated with empagliflozin, patients with SBP <110 mm Hg did not have an increased rate of symptomatic hypotension. CONCLUSIONS: Empagliflozin was effective and safe, with no meaningful interaction between SBP and the effects of empagliflozin in the EMPEROR-Reduced trial. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).


Posted October 15th 2021

Surveillance genome sequencing reveals multiple SARS-CoV-2 variants circulating in central Texas, USA, with a predominance of delta variant and review of vaccine breakthrough cases.

Manohar B. Mutnal, Ph.D.

Manohar B. Mutnal, Ph.D.

Mutnal, M. B., S. Johnson, N. Mohamed, R. Abddelgader, L. Morales, M. Volz, K. Walker, A. C. Arroliga and A. Rao (2021). “Surveillance genome sequencing reveals multiple SARS-CoV-2 variants circulating in central Texas, USA, with a predominance of delta variant and review of vaccine breakthrough cases.” J Med Virol.

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As surges in the COVID-19 pandemic have continued worldwide, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has mutated, spawning several new variants, and impacting, to various degrees, transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. Baylor Scott & White Health has implemented, along with laboratory diagnosis, SARS-CoV-2 sequencing to identify variants in its geographical service area. We analyzed virus sequencing results of specimens collected across Central Texas and found dramatic changes in variant distribution in the first half of 2021. The alpha variant (B 1.1.7) became predominant at week 13 and continued dominance until week 25. A growth rate of 1.20 (R(2)  = 0.92) for the first 15 weeks was noted and this growth gradually declined to -0.55 (R(2)  = 0.99) for the final 13 weeks. Currently, B.1.1.7 is being displaced with B.1.617.2 at a 0.58 growth rate (R(2)  = 0.97). We also investigated vaccine breakthrough cases (VBCs) within our healthcare system and present clinical data on 28 symptomatic patients.


Posted October 15th 2021

Pelvic fracture-related hypotension: A review of contemporary adjuncts for hemorrhage control.

Jennifer Mooney M.D.

Jennifer Mooney M.D.

DuBose, J. J., C. C. Burlew, B. Joseph, M. Keville, M. Harfouche, J. Morrison, C. J. Fox, J. Mooney, R. O’Toole, G. Slobogean, L. S. Marchand, D. Demetriades, N. L. Werner, E. Benjamin and T. Costantini (2021). “Pelvic fracture-related hypotension: A review of contemporary adjuncts for hemorrhage control.” J Trauma Acute Care Surg 91(4): e93-e103.

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ABSTRACT: Major pelvic hemorrhage remains a considerable challenge of modern trauma care associated with mortality in over a third of patients. Efforts to improve outcomes demand continued research into the optimal employment of both traditional and newer hemostatic adjuncts across the full spectrum of emergent care environments. The purpose of this review is to provide a concise description of the rationale for and effective use of currently available adjuncts for the control of pelvic hemorrhage. In addition, the challenges of defining the optimal order and algorithm for employment of these adjuncts will be outlined. LEVEL OF EVIDENCE: Review, level IV.


Posted October 15th 2021

Dynamics of risk: Recent changes in psychological inflexibility precede subsequent changes in returning US veterans’ posttraumatic stress.

Eric C. Meyer, Ph.D.

Eric C. Meyer, Ph.D.

Crabtree, M. A., W. J. Hale, E. C. Meyer, N. A. Kimbrel, B. B. DeBeer, S. B. Gulliver and S. B. Morissette (2021). “Dynamics of risk: Recent changes in psychological inflexibility precede subsequent changes in returning US veterans’ posttraumatic stress.” J Clin Psychol.

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OBJECTIVES: As a malleable risk-factor, psychological inflexibility is implicated in the development and maintenance of posttraumatic stress symptoms (PTS). Unfortunately, limited research has addressed whether changes in psychological inflexibility are antecedent to changes in PTS severity over time, or whether such changes are mutually dependent. METHODS: Utilizing bivariate latent difference score modeling, this longitudinal study sequenced intraindividual changes in psychological inflexibility and PTS severity within a sample of 305 returning US veterans. Veterans’ self-reported psychological inflexibility and PTS severity were assessed quarterly over 1 year. RESULTS: Results indicated that early reductions in psychological inflexibility potentiated later declines in veterans’ PTS severity, accounting for veterans’ prior levels of psychological inflexibility and PTS severity. CONCLUSIONS: These findings underscore the unique role of changes in psychological inflexibility as an important mechanism of change in PTS severity and provide empirical support for an antecedent model of the role of psychological inflexibility in PTS recovery.