Research Spotlight

Roberts, W. C., P. A. Grayburn, S. R. Lander, D. M. Meyer and S. A. Hall (2019). “Effect of Progressive Left Ventricular Dilatation on Degree of Mitral Regurgitation Secondary to Mitral Valve Prolapse.” Am J Cardiol 123(11): 1887-1888.

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Described herein is a 71-year-old man who at age 61 was found by echocardiogram to have severe mitral regurgitation (MR) from mitral valve prolapse. During the subsequent 9 years the MR progressively lessened as his left ventricular cavity dilated and his ejection fraction progressively fell such that just before orthotopic heart transplantation the degree of MR was no longer severe, and the prolapse of the mitral leaflets had disappeared. This report describes this unique patient.

Raoof, T. J., D. Hooper, A. Moore, M. Zaiac, T. Sullivan, L. Kircik, E. Lain, J. Jankicevic and I. Stuart (2019). “Efficacy and Safety of a Novel Topical Minocycline Foam for the Treatment of Moderate-to-Severe Acne Vulgaris: A Phase 3 Study.” J Am Acad Dermatol Jun 1. [Epub ahead of print].

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BACKGROUND: FMX101 4% topical minocycline foam, has been demonstrated as an effective and safe treatment for acne vulgaris. OBJECTIVE: Further evaluate the efficacy and safety of FMX101 4% in treating moderate-to-severe AV. METHODS: A 12-week, multicenter, randomized (1:1), double-blind, vehicle-controlled study was conducted. Co-primary end points were the absolute change in inflammatory lesion count from baseline and the rate of treatment success (IGA score: 0 or 1 with a greater-than-or-equal-to 2-grade improvement). RESULTS: 1488 subjects were in the intent-to-treat population. FMX101 4% group had significantly greater reductions in the number of inflammatory lesions from baseline (P<.0001) and a greater rate of IGA treatment success (P<.0001) vs foam vehicle group at week 12. FMX101 4% was generally safe and well-tolerated. LIMITATIONS: Efficacy and safety of FMX101 4% was not characterized in subjects with mild AV. CONCLUSION: FMX101 4% topical minocycline foam was effective and safe for the treatment of moderate-to-severe AV.

Que, J., K. S. Garman, R. F. Souza and S. J. Spechler (2019). “Pathogenesis and Cells of Origin of Barrett’s Esophagus.” Gastroenterology May 10. [Epub ahead of print].

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In patients with Barrett’s esophagus (BE), metaplastic columnar mucosa, containing epithelial cells with gastric and intestinal features, replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophago-gastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.

Qamer, S. Z., A. Malik, E. Bayoumi, P. H. Lam, S. Singh, M. Packer, I. E. Kanonidis, C. J. Morgan, A. Abdelmawgoud, R. M. Allman, G. C. Fonarow and A. Ahmed (2019). “Digoxin Use and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.” Am J Med May 28. [Epub ahead of print].

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BACKGROUND: Heart failure is a leading cause for hospital readmission. Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking. METHODS: Of the 11,900 patients with HFrEF (ejection fraction less-than-or-equal-to 45%) in Medicare-linked OPTIMIZE-HF, 8401 were not on digoxin, of whom 1571 received discharge prescriptions for digoxin. We matched 1531 of these patients with 1531 not receiving digoxin by propensity scores for digoxin use. The matched cohort (n=3062; mean age, 76years; 44% women; 14% African American) was balanced on 52 baseline characteristics. We assembled a second matched cohort of 2850 patients after excluding those with estimated glomerular filtration rate<15ml/min/1.73m(2) and heart rate<60 beats/min. Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin-associated outcomes were estimated in the matched cohorts. RESULTS: Among the 3062 matched patients, digoxin use was associated with a significantly lower risk of heart failure readmission at 30days (HR, 0.74; 95% CI, 0.59-0.93), 1year (HR, 0.81; 95% CI, 0.72-0.92) and 6years (HR, 0.90; 95% CI 0.81-0.99). The association with all-cause readmission was significant at 1 and 6years but not 30days. There was no association with mortality. Similar associations were observed among the 2850 matched patients without bradycardia or renal insufficiency. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, digoxin use is associated with a lower risk of hospital readmission, but not all-cause mortality.

Piffaretti, G., V. Grassi, C. Lomazzi, W. T. Brinkman, T. P. Navarro, M. P. Jenkins and S. Trimarchi (2019). “Thoracic endovascular stent graft repair for ascending aortic diseases.” J Vasc Surg May 21. [Epub ahead of print].

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OBJECTIVES: We describe the preliminary results of thoracic endovascular aortic repair (TEVAR) in a group of patients with ascending aortic disease from the Global Registry for Endovascular Aortic Treatment (GREAT). METHODS: We identified TEVAR performed for diseases truly originating from the ascending aorta. Between July 2011 and May 2015, 5014 patients were enrolled; six (0.12%) were identified and included in the analysis. One further patient was withdrawn from the study due to lack of a signed consent form. Patients having a “zone 0” proximal landing zone reported for their TEVAR without the presence of an ascending aortic disease were not included. Reinterventions of previous open and endovascular repair were also excluded. RESULTS: Three males and three females were treated. Mean age was 69 years +/- 10 years (range, 58-83 years). Indication for TEVAR was atherosclerotic aneurysm (n = 4; ruptured, n = 1), complicated type A dissection (n = 1, rupture), and pseudoaneurysm (n = 1). Mean maximum aortic lesion diameter was 60 mm 14 (range, 39-77 mm). Urgent intervention was performed in three (50%) cases. Primary clinical success was 100%. There was no TEVAR-related in-hospital mortality. Open conversion was never required. Complication such as cerebrovascular accidents, valve impairment, or myocardial infarction did not occur. All patients were discharged home alive. No patient was lost at a median follow-up of 26 months (range, 16-72 months). During the follow-up, no patient died and ongoing primary clinical success was maintained in all patients. Reintervention was never required; endoleaks, migrations, fractures, or ruptures were not observed. CONCLUSIONS: Preliminary “real-world” experience of ascending TEVAR shows satisfactory outcomes at short-term follow-up. Although concerns remain for “off-label” use of standard devices, TEVAR-related complications were not observed. Longer follow-up data are expected to confirm durability of these results.