Research Spotlight

Roberts, P. R., N. Clementy, F. Al Samadi, C. Garweg, J. L. Martinez-Sande, S. Iacopino, J. B. Johansen, X. Vinolas Prat, R. C. Kowal, D. Klug, L. Mont, J. Steffel, S. Li, D. Van Osch and M. F. El-Chami (2017). “A leadless pacemaker in the real-world setting: The micra transcatheter pacing system post-approval registry.” Heart Rhythm 14(9): 1375-1379.

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BACKGROUND: First-in-man studies of leadless pacemakers have demonstrated high rates of implant success, and safety and efficacy objectives were achieved. Outside of the investigational setting, there are concerns, particularly over cardiac effusion and perforation, device dislodgement, infection, telemetry, and battery issues. OBJECTIVE: The acute performance of the Micra transcatheter pacemaker from a worldwide Post-Approval Registry is reported. METHODS: The registry is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of Micra in the post-approval setting. The safety end point was system- or procedure-related major complications at 30 days post implant. We compared the major complication rate with that of the 726 patients from the investigational study. Electrical performance was also characterized. RESULTS: The device was successfully implanted in 792 of 795 registry patients (99.6%) by 149 implanters at 96 centers in 20 countries. Through 30 days post implant, a total of 13 major complications occurred in 12 patients, for a major complication rate of 1.51% (95% confidence interval, 0.78%-2.62%). Major complications included cardiac effusion/perforation (1, 0.13%), device dislodgement (1, 0.13%), and sepsis (1, 0.13%). After adjusting for baseline differences, the rate of major complications in the registry trended lower than the investigational trial (odds ratio, 0.58, 95% confidence interval, 0.27-1.25; P = .16). Early pacing capture thresholds were low and stable. CONCLUSION: Performance of the Micra transcatheter pacemaker in a real-world setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%) of major complications through 30 days post implant. In particular, the rates of pericardial effusion, device dislodgement, and infection were low, reinforcing the positive results seen in the investigational study.

Schadendorf, D., J. Larkin, J. Wolchok, F. S. Hodi, V. Chiarion-Sileni, R. Gonzalez, P. Rutkowski, J. J. Grob, C. L. Cowey, C. Lao, J. Wagstaff, M. K. Callahan, M. A. Postow, M. Smylie, P. F. Ferrucci, R. Dummer, A. Hill, F. Taylor, J. Sabater, D. Walker, S. Kotapati, A. Abernethy and G. V. Long (2017). “Health-related quality of life results from the phase iii checkmate 067 study.” Eur J Cancer 82: 80-91.

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BACKGROUND: Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL). Here we report analyses of HRQoL for patients with advanced melanoma in clinical trial CheckMate 067. PATIENTS AND METHODS: HRQoL was assessed at weeks 1 and 5 per 6-week cycle for the first 6 months, once every 6 weeks thereafter, and at two follow-up visits using the European Organization for Research and Treatment of Care Core Quality of Life Questionnaire and the EuroQoL Five Dimensions Questionnaire. In addition to the randomised population, patient subgroups, including BRAF mutation status, partial or complete response, treatment-related AEs of grade 3/4, and those who discontinued due to any reason and due to an AE, were investigated. RESULTS: Nivolumab and ipilimumab combination and nivolumab alone both maintained HRQoL, and no clinically meaningful deterioration was observed over time compared with ipilimumab. In addition, similar results were observed across patient subgroups, and no clinically meaningful changes in HRQoL were observed during follow-up visits for patients who discontinued due to any cause. CONCLUSION: These results further support the clinical benefit of nivolumab monotherapy and nivolumab and ipilimumab combination therapy in patients with advanced melanoma. The finding that the difference in grade 3/4 AEs between the arms did not translate into clinically meaningful differences in the reported HRQoL may be relevant in the clinical setting.

Roberts, W. C. (2017). “Proceedings of the editorial board meeting of the american journal of cardiology on march 17, 2017.” Am J Cardiol 120(4): 718-719.

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The annual editorial board meeting of The American Journal of Cardiology ( AJC ) was held on March 17, 2017, at the time of the Annual Scientific Sessions of the American College of Cardiology. The major purpose of the meeting was to thank the editorial board members for their considerable help during the previous year in reviewing manuscripts and to seek their suggestions for improving the journal. Several changes occurred during 2016: there was a publisher change from Ms. Joan Anuels to Ms. Heather Luciano, and the Managing Editor in the Dallas office changed from Ms. Lynn Guillen to Ms. Jill Rutherford. In early 2017, the Journal Manager in St. Louis changed from Ms. Ashley Rodenberry to Mr. John Beckemeier. I think these changes will be advantageous for the journal.

Aguilar, P. R., B. C. Bemiss, C. Witt, D. E. Byers, D. Kreisel, V. Puri, B. Meyers, G. A. Patterson, A. S. Krupnick, R. D. Yusen, E. P. Trulock and R. R. Hachem (2017). “Impact of delayed chest closure on surgical site infection after lung transplantation.” Ann Thorac Surg: 2017 Aug [Epub ahead of print].

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BACKGROUND: Delayed chest closure is an increasingly used approach in the management of bleeding and hemodynamic instability after lung transplantation. We sought to evaluate the impact of delayed chest closure on surgical site infection. METHODS: We performed a single-center retrospective cohort study and included adult patients who received a lung transplant at our center between January 1, 2010, and July 31, 2014. We defined surgical site infection as a thoracotomy incision wound or pleural space infection. Follow-up was complete through 6 months after transplantation. We used logistic regression models to examine the impact of delayed chest closure on surgical site infection and to identify other potential risk factors. RESULTS: During the study period, 67 of the 232 transplant procedures (29%) required delayed chest closure, and surgical site infection developed in 22 recipients (9%). Among the patients with surgical site infection, 18 experienced a wound infection, and 8 experienced a pleural space infection; 4 experienced concomitant wound and pleural space infection. Among the 67 who underwent delayed chest closure, 13 patients (19%) experienced a surgical site infection compared with 9 of the 165 patients (5%) who underwent primary closure (p = 0.001). In multivariate analysis, delayed chest closure was an independent risk factor for surgical site infection. CONCLUSIONS: Although delayed chest closure may have an important role in the immediate management of recipients of a lung transplant, it is an independent risk factor for surgical site infection, and this is associated with increased morbidity.

Butler, J., C. E. Hamo, G. Filippatos, S. J. Pocock, R. A. Bernstein, M. Brueckmann, A. K. Cheung, J. T. George, J. B. Green, J. L. Januzzi, S. Kaul, C. S. P. Lam, G. Y. H. Lip, N. Marx, P. A. McCullough, C. R. Mehta, P. Ponikowski, J. Rosenstock, N. Sattar, A. Salsali, B. M. Scirica, S. J. Shah, H. Tsutsui, S. Verma, C. Wanner, H. J. Woerle, F. Zannad and S. D. Anker (2017). “The potential role and rationale for treatment of heart failure with sodium-glucose co-transporter 2 inhibitors.” Eur J Heart Fail: 2017 Aug [Epub ahead of print].

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Heart failure (HF) and type 2 diabetes mellitus (T2DM) are both growing public health concerns contributing to major medical and economic burdens to society. T2DM increases the risk of HF, frequently occurs concomitantly with HF, and worsens the prognosis of HF. Several anti-hyperglycaemic medications have been associated with a concern for worse HF outcomes. More recently, the results of the EMPA-REG OUTCOME trial showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin was associated with a pronounced and precocious 32% reduction in cardiovascular mortality in subjects with T2DM and established cardiovascular disease. These benefits were more related to a reduction in incident HF events rather than to ischaemic vascular endpoints. Several mechanisms have been put forward to explain these benefits, which also raise the possibility of using these drugs as therapies not only in the prevention of HF, but also for the treatment of patients with established HF regardless of the presence or absence of diabetes. Several large trials are currently exploring this postulate.