Research Spotlight

Posted September 15th 2017

CT-Defined Prosthesis-Patient Mismatch Downgrades Frequency and Severity, and Demonstrates No Association With Adverse Outcomes After Transcatheter Aortic Valve Replacement.

Michael J. Mack M.D.

Michael J. Mack M.D.

Mooney, J., S. L. Sellers, P. Blanke, P. Pibarot, R. T. Hahn, D. Dvir, P. S. Douglas, N. J. Weissman, S. K. Kodali, V. H. Thourani, H. Jilaihawi, O. Khalique, C. R. Smith, S. H. Kueh, M. Ohana, R. Grover, C. Naoum, A. Crowley, W. A. Jaber, M. C. Alu, R. Parvataneni, M. Mack, J. G. Webb, M. B. Leon and J. A. Leipsic (2017). “Ct-defined prosthesis-patient mismatch downgrades frequency and severity, and demonstrates no association with adverse outcomes after transcatheter aortic valve replacement.” JACC Cardiovasc Interv 10(15): 1578-1587.

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OBJECTIVES: This study sought to determine if indexed effective orifice area (EOAi), using left ventricular outflow tract measured from computed tomography (EOAiCT), reclassified prosthesis-patient mismatch (PPM) compared with conventional echocardiogram-defined measurements (EOAiTTE). BACKGROUND: PPM does not predict mortality following transcatheter aortic valve replacement (TAVR). However, it is unknown if the EOAiCT of the left ventricular outflow tract improves risk stratification. METHODS: A total of 765 TAVR patients from the PARTNER II (Placement of Aortic Transcatheter Valves II) trial S3i cohort were evaluated. EOAi was calculated using the continuity equation, and the left ventricular outflow tract area was derived from baseline computed tomography. Traditional echocardiographic categories defined PPM: absent (>0.85 cm2/m2), moderate (>/=0.65 and


Posted September 15th 2017

Multicenter analysis of the use of transjugular intrahepatic portosystemic shunt for management of MPN-associated portal hypertension.

Ranjeeta Bahirwani M.D.

Ranjeeta Bahirwani M.D.

Reilly, C. R., D. V. Babushok, K. Martin, J. L. Spivak, M. Streiff, R. Bahirwani, J. Mondschein, B. Stein, A. Moliterno and E. O. Hexner (2017). “Multicenter analysis of the use of transjugular intrahepatic portosystemic shunt for management of mpn-associated portal hypertension.” Am J Hematol 92(9): 909-914.

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BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7-18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known. In order to assess the efficacy and long-term outcomes of TIPS in MPN-associated pHTN, we performed a retrospective analysis of 29 MPN patients who underwent TIPS at three academic medical centers between 1997 and 2016. The majority of patients experienced complete clinical resolution of pHTN and its clinical sequelae following TIPS. One, two, three, and four-year overall survival post-TIPS was 96.4%, 92.3%, 84.6%, and 71.4%, respectively. However, despite therapeutic anticoagulation, in-stent thrombosis occurred in 31.0% of patients after TIPS, necessitating additional interventions. In conclusion, TIPS can be an effective intervention for MPN-associated pHTN regardless of etiology. However, TIPS thrombosis is a frequent complication in the MPN population and indefinite anticoagulation post-TIPS should be considered.


Posted September 15th 2017

Impact of Accurate 30-Day Status on Operative Mortality: Wanted Dead or Alive, Not Unknown.

James R. Edgerton M.D.

James R. Edgerton M.D.

Ring, W. S., J. R. Edgerton, M. Herbert, S. Prince, C. Knoff, K. M. Jenkins, M. E. Jessen and B. L. Hamman (2017). “Impact of accurate 30-day status on operative mortality: Wanted dead or alive, not unknown.” Ann Thorac Surg: 2017 Aug [Epub ahead of print].

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BACKGROUND: Risk-adjusted operative mortality is the most important quality metric in cardiac surgery for determining The Society of Thoracic Surgeons (STS) Composite Score for star ratings. Accurate 30-day status is required to determine STS operative mortality. The goal of this study was to determine the effect of unknown or missing 30-day status on risk-adjusted operative mortality in a regional STS Adult Cardiac Surgery Database cooperative and demonstrate the ability to correct these deficiencies by matching with an administrative database. METHODS: STS Adult Cardiac Surgery Database data were submitted by 27 hospitals from five hospital systems to the Texas Quality Initiative (TQI), a regional quality collaborative. TQI data were matched with a regional hospital claims database to resolve unknown 30-day status. The risk-adjusted operative mortality observed-to-expected (O/E) ratio was determined before and after matching to determine the effect of unknown status on the operative mortality O/E. RESULTS: TQI found an excessive (22%) unknown 30-day status for STS isolated coronary artery bypass grafting cases. Matching the TQI data to the administrative claims database reduced the unknowns to 7%. The STS process of imputing unknown 30-day status as alive underestimates the true operative mortality O/E (1.27 before vs 1.30 after match), while excluding unknowns overestimates the operative mortality O/E (1.57 before vs 1.37 after match) for isolated coronary artery bypass grafting. CONCLUSIONS: The current STS algorithm of imputing unknown 30-day status as alive and a strategy of excluding cases with unknown 30-day status both result in erroneous calculation of operative mortality and operative mortality O/E. However, external validation by matching with an administrative database can improve the accuracy of clinical databases such as the STS Adult Cardiac Surgery Database.


Posted September 15th 2017

A leadless pacemaker in the real-world setting: The Micra Transcatheter Pacing System Post-Approval Registry.

Robert C. Kowal M.D.

Robert C. Kowal M.D.

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.


Posted September 15th 2017

Health-related quality of life results from the phase III CheckMate 067 study.

Charles L. Cowey M.D.

Charles L. Cowey M.D.

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.