Research Spotlight

O’Hair, D. P., T. K. Bajwa, S. J. Chetcuti, G. M. Deeb, R. C. Stoler, R. F. Hebeler, B. Maini, M. Mumtaz, N. S. Kleiman, M. J. Reardon, S. Li, D. H. Adams, D. R. Watson, S. J. Yakubov, J. J. Popma and G. Petrossian (2017). “One-year outcomes of transcatheter aortic valve replacement in patients with end-stage renal disease.” Ann Thorac Surg: 2017 Feb [Epub ahead of print].

Full text of this article.

BACKGROUND: End-stage renal disease (ESRD) poses unique challenges in the treatment of patients with severe aortic stenosis. Although surgical valve replacement in ESRD patients has been associated with increased mortality, the outcomes from transcatheter aortic valve replacement (TAVR) are not clearly defined. METHODS: The CoreValve US Expanded Use Study is a prospective, nonrandomized study of TAVR in extreme-risk patients with comorbidities excluding them from the Pivotal Trial. We report on patients with ESRD. The primary endpoint was a composite of all-cause mortality or major stroke at 1 year. RESULTS: Ninety-six patients with ESRD underwent TAVR with the CoreValve (Medtronic, Minneapolis, MN) and have reached 1-year follow-up. Mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 16.2% +/- 8.4%. The rate of all-cause mortality or major stroke at 1 year was 30.3%. The all-cause mortality rate was 5.3% at 30 days and 30.3% at 1 year. The rate at 1 year of any stroke or transient ischemic attack was 2.1%; major vascular injury was 5.2%; and new permanent pacemaker was 26.8%. Valve performance improved postprocedure and remained improved at 1 year (effective orifice area 1.71 cm2, mean gradient 9.33 mm Hg) CONCLUSIONS: Early mortality in patients with ESRD is comparable to previously published data on extreme-risk patients without ESRD, but our data suggest a higher mortality rate at 1 year for ESRD patients, likely due to comorbid conditions. Stroke and major vascular injury are infrequent, and improved valve hemodynamics are maintained at 1 year.

Martin, H. D. (2017). “Corr insights(r): The femoro-epiphyseal acetabular roof (fear) index: A new measurement associated with instability in borderline hip dysplasia?” Clin Orthop Relat Res 475(3): 870-871.

Full text of this article.

Wyatt and colleagues compared the novel Femoro-Epiphyseal Acetabular Roof (FEAR) Index, which uses principles of bone growth to create a new radiographic parameter [2, 3, 4, 5], with the LCEA and acetabular index. The FEAR Index was shown to have excellent reliability and it enhanced the authors’ ability to distinguish unstable hips from stable hips with borderline dysplasia.

Lichliter, A. and M. Cura (2017). “Uterine artery embolization in a patient undergoing extracorporeal membrane oxygenation: Overcoming the challenge of retrograde arterial flow at the aortoiliac bifurcation.” J Vasc Interv Radiol 28(3): 472-475.

Full text of this article.

Extracorporeal membrane oxygenation (ECMO), a modified cardiopulmonary bypass mechanism of life support, has seen extended use and increasing applications over the last 2 decades (1). There are 2 types of ECMO circuits: venoarterial (VA) and venovenous. In VA-ECMO, venous blood is withdrawn from the right atrium or a central vein, pumped through the oxygenator, and returned to the arterial circulation. When oxygenated blood is returned via the femoral artery in VA-ECMO, aortic blood flow is reversed, creating a technical challenge of retrograde flow at the aortoiliac bifurcation (1).

Lansky, A. J., S. R. Messe, A. M. Brickman, M. Dwyer, H. B. van der Worp, R. M. Lazar, C. G. Pietras, K. J. Abrams, E. McFadden, N. H. Petersen, J. Browndyke, B. Prendergast, V. G. Ng, D. E. Cutlip, S. Kapadia, M. W. Krucoff, A. Linke, C. S. Moy, J. Schofer, G. A. van Es, R. Virmani, J. Popma, M. K. Parides, S. Kodali, M. Bilello, R. Zivadinov, J. Akar, K. L. Furie, D. Gress, S. Voros, J. Moses, D. Greer, J. K. Forrest, D. Holmes, A. P. Kappetein, M. Mack and A. Baumbach (2017). “Proposed standardized neurological endpoints for cardiovascular clinical trials: An academic research consortium initiative.” J Am Coll Cardiol 69(6): 679-691.

Full text of this article.

Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.

Kanak, M. A., R. Shahbazov, G. Yoshimatsu, M. F. Levy, M. C. Lawrence and B. Naziruddin (2017). “A small molecule inhibitor of nfkappab blocks er stress and the nlrp3 inflammasome and prevents progression of pancreatitis.” J Gastroenterol 52(3): 352-365.

Full text of this article.

BACKGROUND: The underlying molecular mechanism that leads to development of chronic pancreatitis remains elusive. The aim of this study is to understand the downstream inflammatory signaling involved in progression of chronic pancreatitis, and to use withaferin A (WA), a small molecule inhibitor of nuclear factor kappaB (NFkappaB), to prevent progression of chronic pancreatitis. METHODS: Two different protocols were used to induce pancreatitis in mice: standard and stringent administration of cerulein. The severity of pancreatitis was assessed by means of pancreatic histology and serum amylase levels. Immunohistochemistry and flow-cytometric analysis was performed to visualize immune cell infiltration into the pancreas. Real-time PCR and Western blot were used to analyze the downstream signaling mechanism involved in the development of chronic pancreatitis. RESULTS: The severity of cerulein-induced pancreatitis was reduced significantly by WA, used as either preventive or curative treatment…NLRP3 inflammasome activation in cerulein-induced pancreatitis was identified, and this was also potently blocked by WA. The human pancreatitis tissue gene signature correlated with the mouse model. CONCLUSIONS: Our data provide evidence for the role of NFkappaB in the pathogenesis of chronic pancreatitis, and strongly suggest that WA could be used as a potential therapeutic drug to alleviate some forms of chronic pancreatitis.