Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White community. 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@baylorhealth.edu. 214-828-8989.


Posted April 15th 2019

Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients.

Michael J. Mack M.D.

Michael J. Mack M.D.

Mack, M. J., M. B. Leon, V. H. Thourani, R. Makkar, S. K. Kodali, M. Russo, S. R. Kapadia, S. C. Malaisrie, D. J. Cohen, P. Pibarot, J. Leipsic, R. T. Hahn, P. Blanke, M. R. Williams, J. M. McCabe, D. L. Brown, V. Babaliaros, S. Goldman, W. Y. Szeto, P. Genereux, A. Pershad, S. J. Pocock, M. C. Alu, J. G. Webb and C. R. Smith (2019). “Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients.” N Engl J Med Mar 17. [Epub ahead of print].

Full text of this article.

BACKGROUND: Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk. METHODS: We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery. The primary end point was a composite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population. RESULTS: At 71 centers, 1000 patients underwent randomization. The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan-Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, -6.6 percentage points; 95% confidence interval [CI], -10.8 to -2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P = 0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P = 0.02) and in lower rates of death or stroke (P = 0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe paravalvular regurgitation. CONCLUSIONS: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).


Posted April 15th 2019

Procedural Volume and Outcomes for Transcatheter Aortic-Valve Replacement.

Michael J. Mack M.D.

Michael J. Mack M.D.

Vemulapalli, S., J. D. Carroll, M. J. Mack, Z. Li, D. Dai, A. S. Kosinski, D. J. Kumbhani, C. E. Ruiz, V. H. Thourani, G. Hanzel, T. G. Gleason, H. C. Herrmann, R. G. Brindis and J. E. Bavaria (2019). “Procedural Volume and Outcomes for Transcatheter Aortic-Valve Replacement.” N Engl J Med Apr 3. [Epub ahead of print].

Full text of this article.

BACKGROUND: During the introduction of transcatheter aortic-valve replacement (TAVR) in the United States, requirements regarding procedural volume were mandated by the Centers for Medicare and Medicaid Services as a condition of reimbursement. A better understanding of the relationship between hospital volume of TAVR procedures and patient outcomes could inform policy decisions. METHODS: We analyzed data from the Transcatheter Valve Therapy Registry regarding procedural volumes and outcomes from 2015 through 2017. The primary analyses examined the association between hospital procedural volume as a continuous variable and risk-adjusted mortality at 30 days after transfemoral TAVR. Secondary analysis included risk-adjusted mortality according to quartile of hospital procedural volume. A sensitivity analysis was performed after exclusion of the first 12 months of transfemoral TAVR procedures at each hospital. RESULTS: Of 113,662 TAVR procedures performed at 555 hospitals by 2960 operators, 96,256 (84.7%) involved a transfemoral approach. There was a significant inverse association between annualized volume of transfemoral TAVR procedures and mortality. Adjusted 30-day mortality was higher and more variable at hospitals in the lowest-volume quartile (3.19%; 95% confidence interval [CI], 2.78 to 3.67) than at hospitals in the highest-volume quartile (2.66%; 95% CI, 2.48 to 2.85) (odds ratio, 1.21; P = 0.02). The difference in adjusted mortality between a mean annualized volume of 27 procedures in the lowest-volume quartile and 143 procedures in the highest-volume quartile was a relative reduction of 19.45% (95% CI, 8.63 to 30.26). After the exclusion of the first 12 months of TAVR procedures at each hospital, 30-day mortality remained higher in the lowest-volume quartile than in the highest-volume quartile (3.10% vs. 2.61%; odds ratio, 1.19; 95% CI, 1.01 to 1.40). CONCLUSIONS: An inverse volume-mortality association was observed for transfemoral TAVR procedures from 2015 through 2017. Mortality at 30 days was higher and more variable at hospitals with a low procedural volume than at hospitals with a high procedural volume.


Posted April 15th 2019

Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial.

Donald E. Wesson M.D.

Donald E. Wesson M.D.

Wesson, D. E., V. Mathur, N. Tangri, Y. Stasiv, D. Parsell, E. Li, G. Klaerner and D. A. Bushinsky (2019). “Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial.” Lancet 393(10179):1417-1427. Epub 2019 Mar 8.

Full text of this article.

BACKGROUND: Patients with advanced chronic kidney disease lose the capacity to fully excrete endogenous acid, resulting in chronic metabolic acidosis that increases the risk of disease progression and causes muscle catabolism and bone resorption. Veverimer, a non-absorbed, counterion-free, polymeric drug, selectively binds and removes hydrochloric acid from the gastrointestinal lumen, unlike current oral sodium bicarbonate therapy for metabolic acidosis that only neutralises accumulated acid. We assessed the efficacy and safety of veverimer as a treatment for metabolic acidosis in patients with chronic kidney disease. METHODS: We did a multicentre, parallel, randomised, double-blind, placebo-controlled study at 37 sites (hospitals and specialty clinics) in Bulgaria, Croatia, Georgia, Hungary, Serbia, Slovenia, Ukraine, and the USA. Eligible participants were patients aged 18-85 years with non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate of 20-40 mL/min per 1.73 m(2)) and metabolic acidosis (serum bicarbonate concentration of 12-20 mmol/L). Patients were randomly assigned (4:3) to veverimer 6 g/day or placebo for 12 weeks while they consumed their typical diet. Both drugs were taken as oral suspensions in water with lunch. Randomisation was done by study site personnel with a computer-generated randomisation code with balanced permuted blocks (block size of seven) and stratified by baseline bicarbonate (18 mmol/L). Patients and investigators were masked to treatment allocation; however, because the appearance of placebo differed from veverimer, a non-masked site staff member who had no other role in the study dispensed, prepared, and supervised dosing of the study drugs. The composite primary efficacy endpoint was the difference (veverimer-placebo) in the proportion of patients achieving at week 12 either an increase of 4 mmol/L or more from baseline in serum bicarbonate concentration or serum bicarbonate in the normal range of 22-29 mmol/L, assessed in the modified intention-to-treat population (all patients with a baseline and at least one post-baseline serum bicarbonate value). Patients fasted for at least 4 h (consuming only water) before measurements of bicarbonate. Safety was assessed in all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, number NCT03317444. FINDINGS: Between Sept 26, 2017, and Feb 9, 2018, we randomly assigned 124 participants to veverimer and 93 to placebo. The composite primary endpoint was met by 71 (59%) of 120 patients in the veverimer group versus 20 (22%) of 89 patients in the placebo group (a difference of 37%, 95% CI 23-49; p<0.0001). The most common body system in which adverse events in the veverimer group occurred was gastrointestinal; of these, non-treatment limiting diarrhoea was the most common event (11 [9%] vs three [3%] in the veverimer and placebo groups, respectively). The most common treatment-related adverse events were gastrointestinal (diarrhoea, flatulence, nausea, and constipation) occurring in 16 (13%) patients with veverimer and five (5%) patients with placebo. Two deaths occurred during the study, both in the placebo group (unstable angina and pneumonia). INTERPRETATION: Veverimer effectively and safely corrected metabolic acidosis. Longer-term studies are warranted to assess the effects of veverimer on physical functioning and to assess other deleterious consequences of metabolic acidosis including progression of chronic kidney disease and bone health. FUNDING: Tricida.


Posted April 15th 2019

Rational Dispersion for the Introduction of Transcatheter Mitral Valve Repair Into Clinical Practice: Lessons Learned From TAVR.

Michael J. Mack M.D.

Michael J. Mack M.D.

Holmes, D. R., Jr. and M. J. Mack (2019). “Rational Dispersion for the Introduction of Transcatheter Mitral Valve Repair Into Clinical Practice: Lessons Learned From TAVR.” JAMA 321(11): 1043-1044.

Full text of this article.

The introduction of new medical devices to address unmet clinical needs into the patient care arena, with little or no previous physician experience with the therapy, is a complex process with several important considerations. The questions regarding implementation of transcatheter mitral valve therapy are generally the same as the questions that occurred with TAVR, but with some important nuances. What are the safety and effectiveness profiles, the risk/benefit ratio, and cost-effectiveness of the new therapy compared with other available therapies? In the case of the transcatheter mitral valve repair device for functional mitral regurgitation, additional questions include the following: which specific patient populations may derive the maximal intended benefit of the device (responders), what are the characteristics and qualifications of the centers that care for these patients, what is the optimal geographic dispersion to facilitate patient access, and what specific training and qualifications will the operators need? Surgical and cardiovascular professional societies will need to work closely with the FDA, the Centers for Medicare & Medicaid Services, and device manufacturers to address these issues and develop appropriate methods for rational dispersion to help improve the outcome of patients treated with this new technology. (Excerpt from text, p. 1044; no abstract available.)


Posted April 15th 2019

Minimally Invasive Oncologic Surgery, Part II.

James W. Fleshman M.D.

James W. Fleshman M.D.

Conrad, C. and J. W. Fleshman, Jr. (2019). “Minimally Invasive Oncologic Surgery, Part II.” Surg Oncol Clin N Am 28(2): xv-xvii.

Full text of this article.

Minimally invasive techniques for the management of intra-abdominal cancer have become an accepted option for almost all solid tumors. Some of these approaches have been vetted with prospective trials, some even randomized, but it is unusual to find a discussion that encompasses all in one publication. It was this reason that led to these two-part Surgical Oncology Clinics of North America issues that contain discussions of almost every solid intra-abdominal tumor. The experts who have participated are experienced with both open and minimally invasive approaches, and they understand the issues that arise when making recommendations for treatment of curable cancer with new techniques. Dr Conrad and I are indebted to them for their truly authoritative contributions. The discussion around limitations of a technique is almost more important than the assumed possibilities and the recovery outcomes beyond cancer cure. As the advanced techniques are applied in institutions beyond academic institutions where clinical trials are underway, the most important consideration becomes whether generalization of the technique is possible or even appropriate. As one reads this compilation of articles, it is hoped that a balanced message will be apparent, and that the thoughtful application of surgical judgment will be enhanced by the contents herein. Each year brings more applications for minimally invasive surgery regardless of the specific technique. The current level of application of minimally invasive techniques to cancer shows that we have the opportunity to expand their use for even the most basic and appropriate indications. Educators involved in the continued education of surgical trainees and practicing surgeons should be able to use the articles within this issue to engage trainees in a thoughtful approach to expand their use of minimally invasive surgery for resection of cancer. (Excerpt from commentary on a special issue of the journal, p. xvi.)