Research Spotlight

Huntley, G. D., K. M. Tecson, S. Sodhi, J. Saef, K. S. White, P. A. Ludbrook, A. M. Cedars and J. M. Ko (2019). “Cardiac Denial and Expectations Associated With Depression in Adults With Congenital Heart Disease.” Am J Cardiol 123(12): 2002-2005.

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Depression in adults with congenital heart disease is highly prevalent and strongly associated with adverse prognosis. Better management of risk factors for depression may improve clinical outcomes in this population. We conducted a single-site, cross-sectional study of 78 adults with congenital heart disease followed at Washington University School of Medicine. Data considered in the analyses included retrospectively obtained clinical information and patients’ self-assessed psychosocial functioning and health status. To identify the clinical and psychosocial variables associated with depression, we built a stepwise multivariate model to measure the relative contribution of these variables to depression status. The prevalence of depression in our sample was 26%. Our model accounted for approximately 67% of the variability in depression scores. The final model consisted of the Cardiac Denial of Impact Scale, expectations domain of Barriers to Care, and the energy and social domains of the Rand 36-Item Short Form Health Survey. Clinical variables did not predict variability in depression scores. In conclusion, greater cardiac denial and negative expectations of the healthcare team were associated with increased depression symptoms in ACHD.

Hughes, D. A., K. Nicholls, G. Sunder-Plassmann, A. Jovanovic, U. Feldt-Rasmussen, R. Schiffmann, R. Giugliani, V. Jain, C. Viereck, J. P. Castelli, N. Skuban, J. A. Barth and D. G. Bichet (2019). “Safety of switching to Migalastat from enzyme replacement therapy in Fabry disease: Experience from the Phase 3 ATTRACT study.” Am J Med Genet A 179(6): 1069-1073.

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Migalastat is the only oral treatment for Fabry disease, which provides a suitable alternative to once‐every‐2‐weeks intravenous ERT in patients with amenable mutations who are ERT‐experienced and can also be utilized as a first‐line therapy in ERT‐naive patients. Although there has not yet been a consensus among physicians who treat patients with Fabry disease on when to choose migalastat over ERT, we have developed some criteria in our clinical practices, which include: age 16 years and older (18 years and older in the United States and Canada), a confirmed amenable mutation, an eGFR > 30 mL/min/1.73 m2, compliance with every‐other‐day oral administration, and no intention by female patients to become pregnant. Patients’ preference and hypersensitivity to ERT are also factors in considering the best treatment option for patients. We suggest having a comprehensive counseling session with the patient to discuss the mechanism of action, clinical data, and approved indication for migalastat, as well as schedule of administration. For patients switching from ERT, migalastat is commonly initiated ~2 weeks after the last dose of ERT based on the infusion interval; however, other practical considerations may influence the exact duration between the last ERT infusion and first dose of migalastat. Migalastat may be safely initiated within days of the last ERT infusion. In conclusion, patients with amenable mutations who have been receiving ERT infusions can be safely switched to migalastat 150 mg QOD, and no special procedure is needed for the switch. (Excerpt from text, p. 1071-1072; no abstract available.)

House, A. A., C. Wanner, M. J. Sarnak, I. L. Pina, C. W. McIntyre, P. Komenda, B. L. Kasiske, A. Deswal, C. R. deFilippi, J. G. F. Cleland, S. D. Anker, C. A. Herzog, M. Cheung, D. C. Wheeler, W. C. Winkelmayer and P. A. McCullough (2019). “Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.” Kidney Int 95(6): 1304-1317.

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The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here.

Hong, S., R. Banchereau, B. L. Maslow, M. M. Guerra, J. Cardenas, J. Baisch, D. W. Branch, T. F. Porter, A. Sawitzke, C. A. Laskin, J. P. Buyon, J. Merrill, L. R. Sammaritano, M. Petri, E. Gatewood, A. M. Cepika, M. Ohouo, G. Obermoser, E. Anguiano, T. W. Kim, J. Nulsen, D. Nehar-Belaid, D. Blankenship, J. Turner, J. Banchereau, J. E. Salmon and V. Pascual (2019). “Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy.” J Exp Med 216(5): 1154-1169.

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Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4(+) T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes.

Gupta, A. K., R. P. Love, W. Abramovits and K. D. Vincent (2019). “Dupixent(R) (Dupilumab): A Newly Approved Interleukin-4 Receptor Antagonist for the Treatment of Atopic Dermatitis in Pediatric Patients.” Skinmed 17(2): 107-109.

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