Research Spotlight

Roberts, W. C., S. Haque and S. A. Hall (2019). “Total 12-Lead QRS Voltage in Patients Having Orthotopic Heart Transplantation for Heart Failure Caused by Adriamycin-Induced Cardiomyopathy.” Cardiology 141(3): 172-175.

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OBJECTIVE: Although several studies have described the effects of adriamycin on the heart, electrocardiographic total 12-lead QRS voltage (distance in millimeters from the peak of the R wave to the nadir of either the Q or S wave, whichever was deeper, with 10 mm [1 mV] being standard) both before and after orthotopic heart transplantation (OHT) has not been reported. This study describes the total 12-lead QRS voltage in 8 patients studied at Baylor University Medical Center at Dallas, from 1994 to June 2018, who underwent OHT for severe heart failure caused by anthracycline-induced cardiomyopathy. METHOD: Prior to OHT, the total 12-lead non-paced QRS voltages ranged from 86 to 189 mm (mean 125 +/- 56) and for paced QRS voltages from 82 to 113 mm (mean 97 +/- 15). The total 12-lead QRS voltages post-OHT ranged from 100 to 190 mm (mean 130 +/- 30). Total 12-lead QRS voltages were lower in patients with a pacemaker than without. RESULTS/CONCLUSION: These low voltages are like those found in patients with carcinoid syndrome, severe cardiac adiposity, cardiac amyloidosis, and cardiac sarcoidosis.

Ott, P. A., A. C. Pavlick, D. B. Johnson, L. L. Hart, J. R. Infante, J. J. Luke, J. Lutzky, N. E. Rothschild, L. E. Spitler, C. L. Cowey, A. R. Alizadeh, A. K. Salama, Y. He, T. R. Hawthorne, R. G. Bagley, J. Zhang, C. D. Turner and O. Hamid (2019). “A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma.” Cancer Jan 28. [Epub ahead of print].

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BACKGROUND: Glembatumumab vedotin is an antibody-drug conjugate that produced preliminary clinical activity against advanced melanoma in a phase 1 dose-escalation trial. The objective of the current study was to investigate further the antitumor activity of glembatumumab vedotin at the recommended phase 2 dose in heavily pretreated patients with melanoma. METHODS: This single-arm, phase 2 study enrolled patients with stage IV melanoma who were refractory to checkpoint inhibition and to B-raf proto-oncogene, serine/threonine kinase (BRAF)/mitogen-activated protein kinase kinase (MEK) inhibition (in the presence of a BRAF valine mutation at codon 600). Patients received 1.9 mg/kg glembatumumab vedotin intravenously every 3 weeks until they developed disease progression or intolerance. The primary endpoint was objective response rate (ORR), which was determined according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival (OS), safety, and clinical efficacy versus tumor glycoprotein NMB (gpNMB) expression. Tumor expression of gpNMB was assessed using immunohistochemistry. RESULTS: In total, 62 patients received treatment. The ORR was 11% and the median response duration was 6.0 months (95% confidence interval [CI], 4.1 months to not reached). The median PFS was 4.4 months (95% CI, 2.6-5.5 months), and the median OS was 9.0 months (95% CI, 6.1-11.7 months). For patients who developed rash during the first cycle versus those who did not, the ORR was 21% versus 7%, respectively, and there was an overall improvement in PFS (hazard ratio, 0.43; P = .013) and OS (hazard ratio, 0.43; P = .017). The most frequent adverse events were alopecia, neuropathy, rash, fatigue, and neutropenia. With one exception, all evaluable tumors were positive for gpNMB, and 46 of 59 tumors (76%) had 100% gpNMB-positive epithelial cells. CONCLUSIONS: Glembatumumab vedotin had modest activity and an acceptable safety profile in patients with advanced melanoma who were refractory to checkpoint inhibitors and MEK/BRAF inhibition. Treatment-related rash may be associated with response.

Mont, M. A., W. B. Beaver, S. H. Dysart, J. W. Barrington and D. J. Del Gaizo (2019). “Corrigendum to “Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial” [Journal of Arthroplasty 33 (2018) 90-96].” J Arthroplasty 34(2): 399-400.

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The authors would like to inform the readership that during recent discussions with the US Food and Drug Administration (FDA) related to the registration trials for the label expansion of liposomal bupivacaine (LB; EXPAREL®, bupivacaine liposome injectable suspension; Pacira Pharmaceuticals, Inc., Parsippany, NJ), opioid conversion factors used in the statistical analyses were updated to reflect current knowledge of their relative potencies used in medical practice. The updates were approved by the FDA, as there is no current standard for opioid conversions. To maintain consistency with the FDA registration trials and the trials that will be registered with the European Medicines Agency (EMA; the European equivalent of the FDA), the conversion factors used in the PILLAR study were also updated. In place of intravenous morphine equivalent dose (MED), opioid consumption has been converted to oral MED using an updated set of conversion factors. These updates do not alter the original study conclusions. The changes affected both study arms equally and did not alter the findings or conclusions. (Excerpt from this correction, p. 399, to the study referenced in the title.)E

Michelson, E., J. S. Huff, J. Garrett and R. Naunheim (2019). “Triage of Mild Head-Injured Intoxicated Patients Could Be Aided by Use of an Electroencephalogram-Based Biomarker.” J Neurosci Nurs Jan 14. [Epub ahead of print].

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OBJECTIVE: Drug and alcohol (DA)-related emergency department (ED) visits represent an increasing fraction the head-injured population seen in the ED. Such patients present a challenge to the evaluation of head injury and determination of need for computed tomographic (CT) scan and further clinical path. This effort examined whether an electroencephalogram (EEG)-based biomarker could aid in reducing unnecessary CT scans in the intoxicated ED population. METHOD: This is a retrospective secondary study of an independent prospective US Food and Drug Administration validation trial that demonstrated the efficacy of (1) an automatic Structural Injury Classifier for the likelihood of injury visible on a CT (CT+) and (2) an EEG-based Brain Function Index to assess functional impairment in minimally impaired, head-injured adults presenting within 3 days of injury. Impact on the biomarker performance in patients who presented with or without DA was studied. RESULTS: Structural Injury Classifier sensitivity was not significantly impacted by the presence of DA. Although specificity decreased, it remained several times higher than obtained using standard CT decision rules. Furthermore, the potential to reduce the number of unnecessary scans by approximately 30% was demonstrated when the Structural Injury Classifier was integrated into CT clinical triage. The Brain Function Index was demonstrated to be independent of the presence of DA. CONCLUSION: This EEG-based assessment technology used to identify the likelihood of structural or functional brain injury in mildly head-injured patients represents an objective way to aid in triage patients with DA on presentation, with the potential to decrease overscanning while not sacrificing sensitivity to injuries visible on CT.

Messika-Zeitoun, D., G. Nickenig, A. Latib, K. H. Kuck, S. Baldus, R. Schueler, G. La Canna, E. Agricola, F. Kreidel, M. Huntgeburth, M. Zuber, P. Verta, P. Grayburn, A. Vahanian and F. Maisano (2019). “Transcatheter mitral valve repair for functional mitral regurgitation using the Cardioband system: 1 year outcomes.” Eur Heart J 40(5): 466-472.

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Aims: The Cardioband (Edwards Lifesciences) is a transcatheter implant designed to reduce mitral annulus size and mitral regurgitation (MR) severity. We report the 1-year outcomes of consecutive patients who underwent the Cardioband procedure between 2013 and 2016. Methods and results: Sixty patients with moderate or severe secondary MR (72 +/- 7 years, 60% ischaemic origin) on guideline-recommended medical therapy were treated and analyzed at 11 European institutions. There were two in-hospital deaths (none device-related), one stroke, two coronary artery complications, and one tamponade. Anchor disengagement, observed in 10 patients (all but one in the first half of the population), resulted in device inefficacy in five patients and led to device modification half way through the study to mitigate this issue. Technical, device, and procedural successes, assessed based on Mitral Valve Academic Research Consortium (MVARC) criteria, were 97% (58/60), 72% (43/60), and 68% (41/60), respectively. At 1-year, overall survival, survival free of readmission for heart failure, and survival free of reintervention (performed in seven patients) were 87%, 66%, and 78%, respectively. In the overall population, MR grade at 12 months was moderate or less 61% and moderate or less in 95% of the 39 patients who underwent a transthoracic echocardiography at 1-year [but worsened by at least one grade in 11 patients (22%)]. Functional status (79% vs. 14% in New York Heart Association Class I/II), quality of life (-19 points on the Minnesota Living with Heart Failure Questionnaire score), and exercise capacity (+58 m by 6MWT) improved significantly (all P < 0.01). Conclusion: In this multicentre trial, the Cardioband mitral system demonstrated reasonable performance and safety. At 1 year, most patients had moderate or less MR and experienced significant functional improvements. A randomized controlled trial is underway to demonstrate the impact of Cardioband in patients on guideline-directed medical therapy.