Research Spotlight

Squiers, J., H. Baumgarten, G. Filardo, D. Sass, B. Pollock, J. Edgerton, R. Marcel, J. M. DiMaio and R. L. Smith (2019). “Prospective Evaluation of a Blood Transfusion Protocol for Patients Undergoing Cardiac Surgery.” Ann Thorac Surg Nov 23. [Epub ahead of print].

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BACKGROUND: The Society of Thoracic Surgeons clinical practice guidelines recommend the creation of an interdisciplinary blood management team to implement protocols for improved blood transfusion practices. We report our center’s prospective evaluation of a blood transfusion protocol. METHODS: An interdisciplinary blood management team developed protocols for transfusion of packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate. The protocols were prospectively evaluated by tracking transfusions administered to consecutive patients undergoing cardiac surgery, and the primary outcome of interest was the mean number of adjusted units of blood product transfused per patient. Protocol implementation phases were separated by washout phases to control for a potential Hawthorne effect associated with protocol implementation. Protocol compliance was also assessed. RESULTS: A total of 1441 patients underwent cardiac surgery during the 16-month study period. Although there was no statistically significant reduction in transfusions with an unadjusted analysis, there was a significant trend towards reduction of mean adjusted total units transfused per patient over the course of the study period (p<0.001). The mean adjusted total units transfused per patient were significantly less during the second washout phase (2.8 units, 95%CI 2.3-3.3) and second protocol phase (2.8 units, 95%CI 2.32-3.27) as compared to the initial baseline survey phase (3.6 units, 95%CI 3.1-4.1; p<0.05 for both comparisons). Only 55.2% of all units were transfused in compliance to the implemented protocols: platelets (46.8%), cryoprecipitate (32.1%), packed red blood cells (60.7%), and fresh frozen plasma (53.6%). CONCLUSIONS: During a prospective evaluation of blood transfusion protocols, a risk-adjusted analysis demonstrated a reduction in transfusions despite poor protocol compliance.

Solomon, S. D., M. Vaduganathan, B. L. Claggett, M. Packer, M. Zile, K. Swedberg, J. Rouleau, M. A. Pfeffer, A. Desai, L. H. Lund, L. Koeber, I. Anand, N. K. Sweitzer, G. Linssen, B. Merkely, J. L. Arango, D. Vinereanu, C. H. Chen, M. Senni, A. Sibulo, S. Boytsov, V. Shi, A. Rizkala, M. Lefkowitz and J. J. V. McMurray (2019). “Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure.” Circulation Nov 17. [Epub ahead of print].

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Background: While disease modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin- system (RAS) inhibitor alone in two similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF. Methods: We combined data from PARADIGM-HF (LVEF eligibility/=45%; n=4,796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories:22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality and non-cardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF. Results: Among 13,195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of non-cardiovascular death, among patients in the highest vs. lowest groups. Overall sacubitril/valsartan was superior to RAS inhibition for first cardiovascular death or heart failure hospitalization (HR 0.84, 95% CI 0.78, 0.90), cardiovascular death (HR 0.84, 95% CI 0.76, 0.92), heart failure hospitalization (HR 0.84, 95% CI 0.77, 0.91), and all-cause mortality (HR 0.88, 95% CI 0.81, 0.96). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction p=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions. Conclusions:The therapeutic effects of sacubitril/valsartan, compared with a RAS inhibitor alone, vary by LVEF, with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men. Clinical Trial Registration: NCT01920711. PARADIGM-HF Unique Identifier: NCT01035255.

Smith, M. S., B. Cash, V. Konda, A. J. Trindade, S. Gordon, S. DeMeester, V. Joshi, D. Diehl, E. Ganguly, H. Mashimo, S. Singh, B. Jobe, M. McKinley, M. Wallace, Y. Komatsu, S. Thakkar, F. Schnoll-Sussman, R. Sharaiha, M. Kahaleh, P. Tarnasky, H. Wolfsen, R. Hawes, J. Lipham, H. Khara, D. Pleskow, U. Navaneethan, P. Kedia, M. Hasan, A. Sethi, J. Samarasena, U. D. Siddiqui, F. Gress, R. Rodriguez, C. Lee, T. Gonda, I. Waxman, S. Hyder, J. Poneros, K. Sharzehi, J. A. Di Palma, D. V. Sejpal, D. Oh, J. Hagen, R. Rothstein, M. Sawhney, T. Berzin, Z. Malik and K. Chang (2019). “Volumetric laser endomicroscopy and its application to Barrett’s esophagus: results from a 1,000 patient registry.” Dis Esophagus 32(9): 1-8.

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Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett’s esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Rolfes, M. A., B. Flannery, J. R. Chung, A. O’Halloran, S. Garg, E. A. Belongia, M. Gaglani, R. K. Zimmerman, M. L. Jackson, A. S. Monto, N. B. Alden, E. Anderson, N. M. Bennett, L. Billing, S. Eckel, P. D. Kirley, R. Lynfield, M. L. Monroe, M. Spencer, N. Spina, H. K. Talbot, A. Thomas, S. M. Torres, K. Yousey-Hindes, J. A. Singleton, M. Patel, C. Reed and A. M. Fry (2019). “Effects of Influenza Vaccination in the United States During the 2017-2018 Influenza Season.” Clin Infect Dis 69(11): 1845-1853.

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BACKGROUND: The severity of the 2017-2018 influenza season in the United States was high, with influenza A(H3N2) viruses predominating. Here, we report influenza vaccine effectiveness (VE) and estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the 2017-2018 influenza season. METHODS: We used national age-specific estimates of 2017-2018 influenza vaccine coverage and disease burden. We estimated VE against medically attended reverse-transcription polymerase chain reaction-confirmed influenza virus infection in the ambulatory setting using a test-negative design. We used a compartmental model to estimate numbers of influenza-associated outcomes prevented by vaccination. RESULTS: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. We estimated that influenza vaccination prevented 7.1 million (95% CrI, 5.4 million-9.3 million) illnesses, 3.7 million (95% CrI, 2.8 million-4.9 million) medical visits, 109 000 (95% CrI, 39 000-231 000) hospitalizations, and 8000 (95% credible interval [CrI], 1100-21 000) deaths. Vaccination prevented 10% of expected hospitalizations overall and 41% among young children (6 months-4 years). CONCLUSIONS: Despite 38% VE, influenza vaccination reduced a substantial burden of influenza-associated illness, medical visits, hospitalizations, and deaths in the United States during the 2017-2018 season. Our results demonstrate the benefit of current influenza vaccination and the need for improved vaccines.

Roberts, C. S., Y. M. Salam, A. J. Moore and W. C. Roberts (2019). “Pseudoaneurysm of the Ascending Aorta at the Cannulation Site Diagnosed More Than Four Decades After Repair of Ventricular Septal Defect.” Am J Cardiol 124(12): 1962-1965.

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Described herein is a 69-year-old woman who developed a large saccular aortic aneurysm at a previous cannulation site for repair of a ventricular septal defect at age 25 years. The aneurysm was resected and proved histologically to be a false one. The long interval between operations (44 years) exceeds those reported previously.