Impact of recurrent mitral regurgitation after mitral valve repair for functional mitral regurgitation: long-term analysis of competing outcomes.

AIMS: Recurrent mitral regurgitation (MR) has been reported after mitral valve repair for functional MR. However, the impact of recurrent MR on long-term survival remains poorly defined. In the present study, mortality-adjusted recurrent MR rates, the clinical impact of recurrent MR and its determinants were studied in patients after mitral valve repair with revascularization for functional MR in the setting of ischaemic heart disease. METHODS AND RESULTS: Long-term clinical and echocardiographic outcome was evaluated in 261 consecutive patients after restrictive mitral annuloplasty and revascularization for moderate to severe functional MR, between 2000 and 2014. The cumulative incidence of recurrent MR ≥ Grade 2, assessed by competing risk analysis, was 9.6 ± 1.8% at 1-year, 20.3 ± 2.5% at 5-year, and 27.6 ± 2.9% at 10-year follow-up. Cumulative survival was 85.8% [95% confidence interval (CI) 81.0-90.0] at 1-year, 67.3% (95% CI 61.1-72.6%) at 5-year, and 46.1% (95% CI 39.4-52.6%) at 10-year follow-up. Age, preoperative New York Heart Association Class III or IV, a history of renal failure, and recurrence of MR expressed as a time-dependent variable [HR 3.28 (1.87-5.75), P < 0.001], were independently associated with an increased mortality risk. Female gender, a history of ST-elevation myocardial infarction, a preoperative QRS duration ≥120 ms, a higher preoperative MR grade, and a higher indexed left ventricular end-systolic volume were independently associated with an increased likelihood of recurrent MR. CONCLUSION: Mitral valve repair for functional ischaemic MR resulted in a low incidence of recurrent MR with favourable clinical outcome up to 10 years after surgery. Presence of recurrent MR at any moment after surgery proved to be independently associated with an increased risk for mortality.

Grain versus AIN: Common rodent diets differentially affect health outcomes in adult C57BL/6j mice.

Semi-synthetic and grain-based diets are common rodent diets for biomedical research. Both diet types are considered nutritionally adequate to support breeding, growth, and long life, yet there are fundamental differences between them that may affect metabolic processes. We have characterized the effects of diet type on breeding outcomes, metabolic phenotype, and microbiota profile in adult mice. Healthy 8-week-old female and male C57BL/6J mice were fed a semi-synthetic or a grain-based diet for 12 weeks and changes in body weight and body composition were monitored. Breeding outcomes were determined. Body fat accumulation of female mice was lower on the semi-synthetic diet than on the grain-based diet. Pregnancy rate and newborn pup survival appeared to be lower in mice exposed to semi-synthetic diet compared to grain-based diet. Both female and male mice showed a profound change in fecal microbiota alpha and beta diversity depending on diet type. Our study shows that type of rodent diet may affect breeding outcomes whilst influencing metabolism and health of female laboratory mice. These factors have the potential to influence other experimental outcomes and the results suggest that semi-synthetic and grain-based diets are not interchangeable in research using rodent models. Careful consideration and increased understanding of the consequences of diet choice would lead to improvements in experimental design and reproducibility of study results.

Increased PXR and Suppressed T-Cell Signaling Are Associated With Malignant Degeneration of Barrett's Esophagus.

Background and Aims: Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC). To detect EAC in early stage, patients with BE undergo endoscopic surveillance. Surveillance cohorts largely consist of nondysplastic BE (NDBE) patients with a low annual progression risk (<0.5%). Predictive biomarkers for malignant progression of NDBE could improve efficacy of surveillance. Biomarker research has mostly focused on aberrant protein expression on BE epithelial cells. Moreover, insight in cell signaling driving malignant transformation is unknown. This study uses a data-driven approach to analyze tumor-stroma interaction in NDBE which progressed to high-grade dysplasia or EAC. Methods: In this case-control study, we performed RNA sequencing analysis on index NDBE biopsies from 6 patients who, during long-term follow-up, progressed and 7 who did not progress to high-grade dysplasia/EAC. For control samples, squamous and duodenum tissues from BE patients were analyzed. For validation, we used quantitative PCR. Results: Significant differences in BE transcriptomic profiles between progressors and nonprogressors were found by principal component and differential expression analyses. Ingenuity pathway analysis indicated that 8 cell signaling pathways were significantly upregulated in the progressors, and 14 pathways were significantly downregulated. The most interesting finding was the upregulation of the xenobiotic metabolism pregnane X receptor signaling pathway in the progressor cohort, while of the downregulated pathways in progressors, several were related to the immune system. Conclusion: These novel transcriptomic insights are fundamental for developing (chemo-)preventive therapies. These could be therapies, which protect against toxins, including biles, responsible for pregnane X receptor activation or which enhance protective immune mechanisms. The identified RNA markers are promising biomarkers for improving risk stratification in surveillance programs.

Prognostic value of left ventricular reverse remodelling and recurrent mitral regurgitation after personalized surgical treatment of patients with non-ischaemic cardiomyopathy and functional mitral regurgitation.

OBJECTIVES: The aim of this study was to determine the prevalence of left ventricular reverse remodelling (LVRR) and recurrent mitral regurgitation (MR) at mid-term follow-up (1-2 years after surgery) in patients after personalized surgical treatment of heart failure and functional MR due to non-ischaemic cardiomyopathy and to assess their prognostic impact on long-term clinical outcomes. METHODS: Consecutive patients with refractory heart failure and non-ischaemic MR, who underwent mitral valve surgery with or without additional procedures, were identified. Patients with complete preoperative and mid-term echocardiographic data were included. LVRR (≥15% decrease in indexed left ventricular end-systolic volume) and recurrent MR (≥ Grade 2) were echocardiographically assessed at mid-term follow-up, and the primary end point was a composite of all-cause mortality and heart transplantation (HTx-free survival). RESULTS: The prevalence of LVRR was 38%, and the prevalence of recurrent MR was 20% at mid-term follow-up. The absence of LVRR and the presence of recurrent MR-which were highly correlated-were significantly associated with worse HTx-free survival. HTx-free survival 1 and 3 years after mid-term follow-up were 100% and 88 ± 6% in patients with LVRR (n = 29), 82 ± 7% and 68 ± 8% in patients without LVRR and without recurrent MR (n = 34), and 49 ± 14% and 33 ± 13% in patients without LVRR and with recurrent MR (n = 14). CONCLUSIONS: Patients with LVRR at mid-term follow-up showed favourable HTx-free survival, whereas HTx-free survival was significantly worse in patients without LVRR and without recurrent MR and extremely poor in patients without LVRR and with recurrent MR. Close echocardiographic monitoring is warranted for timely identification of this latter subgroup of patients, in order to re-evaluate additional treatment options and improve their prognosis.