Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White and Texas A&M College of Dentistry communities. Each newly published article features the researcher, the abstract, and link to the full text. For information on including your own research, please contact John Fullinwider, john.fullinwider@BSWHealth.org for BSWH or Sudha Ramakrishnan, sudharamakrishnan@tamu.edu, for COD.


Posted February 15th 2020

A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

Michael J. Mack M.D.
Michael J. Mack M.D.

Dangas, G. D., J. G. P. Tijssen, J. Wohrle, L. Sondergaard, M. Gilard, H. Mollmann, R. R. Makkar, H. C. Herrmann, G. Giustino, S. Baldus, O. De Backer, A. H. C. Guimaraes, L. Gullestad, A. Kini, D. von Lewinski, M. Mack, R. Moreno, U. Schafer, J. Seeger, D. Tchetche, K. Thomitzek, M. Valgimigli, P. Vranckx, R. C. Welsh, P. Wildgoose, A. A. Volkl, A. Zazula, R. G. M. van Amsterdam, R. Mehran and S. Windecker (2020). “A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.” New England Journal of Medicine 382(2): 120-129.

Full text of this article.

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).


Posted February 15th 2020

Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.

David L. Brown M.D.
David L. Brown M.D.

Makkar, R. R., V. H. Thourani, M. J. Mack, S. K. Kodali, S. Kapadia, J. G. Webb, S. H. Yoon, A. Trento, L. G. Svensson, H. C. Herrmann, W. Y. Szeto, D. C. Miller, L. Satler, D. J. Cohen, T. M. Dewey, V. Babaliaros, M. R. Williams, D. J. Kereiakes, A. Zajarias, K. L. Greason, B. K. Whisenant, R. W. Hodson, D. L. Brown, W. F. Fearon, M. J. Russo, P. Pibarot, R. T. Hahn, W. A. Jaber, E. Rogers, K. Xu, J. Wheeler, M. C. Alu, C. R. Smith and M. B. Leon (2020). “Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.” New England Journal of Medicine 382(9): 1-11.

Full text of this article.

BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke. RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery. CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).


Posted February 15th 2020

Medical versus Surgical Treatment for Refractory Heartburn. Reply.

Stuart Spechler M.D.
Stuart Spechler M.D.

Spechler, S. J. (2020). “Medical versus Surgical Treatment for Refractory Heartburn. Reply.”
New England Journal of Medicine 382(3): 297-298.

Full text of this article.

Our trial, sponsored by the Department of Veterans Affairs, spanned more than a decade from planning to publication and presented numerous challenges that threatened its successful completion. We agree with Yadlapati and Pandolfino that future RCTs that compare interventional therapies for patients with GERD will encounter similarly daunting obstacles. A rigid requirement for such difficult and expensive RCTs to validate new endosurgical techniques will delay their implementation and may well discourage investigators and their industry partners from developing new devices. On the other hand, there is considerable potential for harm in using invasive treatments whose efficacy is substantiated only by low-quality evidence. Pragmatic yet valid alternatives to RCTs are highly desirable and would facilitate the introduction of sorely needed new treatments for GERD. We also agree with Nicolaides et al. that ensuring patient compliance with PPI dosing is a simple clinical maneuver that works in a substantial minority of patients with PPI-refractory heartburn. Since PPIs bind only to gastric proton pumps that are actively secreting acid, patients should take PPIs 30 to 60 minutes before meals to ensure that the drugs are in the bloodstream when the greatest number of proton pumps are activated by food. Switching PPIs may also be effective, since PPI potencies vary widely, and individual patients can exhibit considerable variability in response to different PPIs. These simple maneuvers can spare many patients the expense, inconvenience, and risk of invasive tests and alternative treatments. Patients in our medical treatment groups were given instructions to avoid lying down for 3 hours after meals and to avoid bedtime snacks. We did not specifically mandate other lifestyle modifications intended to address reflux, such as weight loss, avoidance of foods that may induce heartburn, elevation of the head of the bed, and smoking cessation. The body-mass index (the weight in kilograms divided by the square of the height in meters) in 86% of our patients with reflux-related heartburn was greater than 25, and we agree with Gardner that there are high-quality data showing that weight loss can ameliorate GERD symptoms in obese persons. However, evidence supporting the efficacy of the other lifestyle modifications for patients with GERD is far less robust, and none (including weight loss) have been shown to be effective in patients with heartburn that is refractory to twice-daily PPI therapy, the subject of our trial. The health benefits of smoking cessation and weight loss for obese persons go far beyond any reduction in GERD symptoms, and we certainly support those recommendations. However, our trial was designed specifically to compare the effectiveness of antireflux surgery with that of medications for PPI-refractory heartburn. (Text of author’s reply to commentators on: Spechler SJ, Hunter JG, Jones KM, et al. Randomized trial of medical versus surgical treatment for refractory heartburn. N Engl J Med 2019;381:1513-1523.)


Posted February 15th 2020

Rate Response Pacing in Left Ventricular Assist Device Patients.

Cesar Y. Guerrero-Miranda, M.D.
Cesar Y. Guerrero-Miranda, M.D.

Alvarez Villela, M., C. Y. Guerrero-Miranda, T. Chinnadurai, S. R. Patel and U. P. Jorde (2020). “Rate Response Pacing in Left Ventricular Assist Device Patients.” ASAIO J 66(2): e29-e30.

Full text of this article.

Chronotropic incompetence (CI) is common in advanced heart failure and is associated with worse functional capacity. This impaired heart rate (HR) response during exercise is ameliorated but persists after left ventricular assist device (LVAD) implantation. Patients with continuous flow LVAD (CF-LVAD) suffer from significant exercise limitation despite restoration of resting cardiac output. Whether CI contributes to exercise limitation in this setting is unknown. We examined the role of CI and the effect of rate response pacing (RRP) on functional capacity in a group of stable patients with LVAD . . . Our findings demonstrate the association between CI and poor functional capacity in patients with advanced heart failure and CF-LVAD, in line with one small prior study. Findings in this cohort point out the inadequacy of current RRP technologies for sensing signals other than atrial rate during different types of physical activity. When RRP increased the HR promptly and in a sustained manner, replicating the activity of the sinus node, the effect on aerobic capacity was substantial, but this occurred in only a minority of patients. In contrast to the heterogeneous effect of RRP during treadmill-based CPX, its effect on 6 MWD was more homogeneous. This could represent a difference in CIED sensing efficacy since all of the employed devices in this study have an accelerometer-based RRP system. Ambulation, producing linear displacement of the body during 6 MWT could be more easily sensed by accelerometer-based systems than the more static motion during treadmill exercise. (Excerpt from text, p. e29; no abstract available.)


Posted February 15th 2020

Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial.

Joyce O'Shaughnessy M.D.
Joyce O’Shaughnessy M.D.

Golshan, M., S. Loibl, S. M. Wong, J. B. Houber, J. O’Shaughnessy, H. S. Rugo, N. Wolmark, M. D. McKee, D. Maag, D. M. Sullivan, O. Metzger-Filho, G. Von Minckwitz, C. E. Geyer, Jr., W. M. Sikov and M. Untch (2020). “Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial.” JAMA Surg Jan 8. [Epub ahead of print].

Full text of this article.

Importance: Neoadjuvant systemic therapy (NST) is often administered to enable breast-conserving therapy (BCT) in stages II to III breast cancer. Objectives: To prospectively evaluate the role of NST in conversion from BCT ineligibility to BCT eligibility and to assess the association of response to NST, germline BRCA (gBRCA) status, and region of treatment with surgical choice in women with triple-negative breast cancer (TNBC). Design, Setting, and Participants: This prespecified secondary analysis of a multicentered, phase 3, double-blind, randomized clinical trial (BrighTNess) enrolled 634 eligible women across 145 centers in 15 countries in North America, Europe, and Asia. Women with operable, clinical stages II to III TNBC who underwent gBRCA mutation testing before initiating NST were eligible to participate. Data were collected from April 1, 2014, to December 8, 2016. This preplanned analysis was performed from January 5, 2018, to October 28, 2019. Interventions: Study participants were randomized to receive 12 weeks of weekly paclitaxel alone or with the addition of carboplatin and/or veliparib, followed by 4 cycles of doxorubicin hydrochloride and cyclophosphamide. Main Outcomes and Measures: Surgeons assessed BCT candidacy by clinical and radiographic criteria before and after NST. Surgical choices and whether BCT eligibility was associated with the likelihood of pathologic complete response were then analyzed. Results: Among the 634 randomized patients (median age, 51 [range, 22-78] years), pre- and post-NST assessments were available for 604 patients. Of 141 patients deemed BCT ineligible at baseline, 75 (53.2%) converted to BCT eligible. Overall, 342 (68.1%) of 502 patients deemed BCT eligible after NST underwent BCT, including 42 (56.0%) of the 75 who converted to BCT eligible. Patients treated in Europe and Asia were more likely to undergo BCT (odds ratio, 2.66; 95% CI, 1.84-3.84) compared with those treated in North America. Among patients without gBRCA mutation undergoing mastectomy, those treated in North America were more likely to undergo contralateral prophylactic mastectomy (57 of 81 [70.4%] vs 6 of 30 [20.0%]; P < .001). Rates of pathologic complete response were similar between patients deemed BCT eligible at baseline and those who were BCT ineligible but converted to BCT eligibility after NST (55.3 [235 of 425] vs 49.3% [37 of 75]; P = .38). Conclusions and Relevance: This prospective analysis of NST and BCT eligibility in TNBC demonstrates a conversion from BCT ineligibility to BCT eligibility of 53.2%. Lower BCT rates among eligible patients and higher bilateral mastectomy rates among patients without gBRCA mutation in North America merit investigation. Trial Registration: ClinicalTrials.gov identifier: NCT02032277.