Month: April 2025

Front Cardiovasc Med. 2025 Feb 7;12:1512961. doi: 10.3389/fcvm.2025.1512961. eCollection 2025.

ABSTRACT

INTRODUCTION: Clinical evidence highlighting the efficacy and safety of transcatheter aortic valve replacement (TAVR) and the 2019 Food and Drug Administration (FDA) approval for TAVR in low-risk (younger) patients has created a demand for durable and long-lasting bioprosthetic heart valve (BHV) leaflet materials. Over the life of an implanted BHV mechanical stress, immunogenicity, calcification, and hemodynamic dysfunction lead to failure via structural valve deterioration (SVD). Consequently, the durability of the bioprosthetic materials selected for valve manufacture is of utmost importance.

TECHNOLOGY: The ADAPT™ tissue engineering process, an anti-calcification preparation that transforms xenograft tissue (bovine pericardium) into a durable valve bioscaffold, shows significant clinical benefits in mitigating the interrelated mechanisms leading to SVD. The novel acellular, biostable and non-calcifying biomaterial has recently been molded into a single-piece 3D biomimetic valve (DurAVR™) with excellent early clinical results and the potential to meet the growing demand of durable BHVs for the treatment of aortic stenosis.

DISCUSSION: The unique design of the DurAVR biomimetic valve in combination with the superior biostability of ADAPT tissue could advance the BHV space by providing superior performance and durability to aortic stenosis patients in need of TAVR.

PMID:39991635 | PMC:PMC11842446 | DOI:10.3389/fcvm.2025.1512961

Langenbecks Arch Surg. 2025 Apr 3;410(1):118. doi: 10.1007/s00423-025-03689-6.

ABSTRACT

PURPOSE: Extended pancreatic resections with venous reconstruction are increasingly performed for borderline resectable pancreatic cancer. Various venous reconstruction techniques have been described. At our center, reconstruction is performed using bovine pericardium patches. So far, few studies reported outcomes using this technique in the field of pancreatic surgery.

METHODS: Data of consecutive pancreatoduodenectomies between January 1st 2015 and December 31st 2023 were analyzed retrospectively. Postoperative complications were graded by the Clavien-Dindo Classification, Comprehensive Complication Index (CCI) and complications specific to pancreatic resections as recommended and published by the International Study Group of Pancreatic Surgery (ISGPS).

RESULTS: Pancreatoduodenectomy included portal vein resection (PVR) in 23 patients compared to 95 patients without PVR. Patient age and comorbidities were similarly distributed between groups. Pancreatic adenocarcinoma was more prevalent in the PVR-group compared to no-PVR (87% vs. 58%, p = 0.009). Operation time and blood loss were both increased with PVR (median: 416 min vs. 315 min and 300 ml vs. 150 ml, p < 0.001 for both comparisons). Within ISGPS defined complications, grade B delayed gastric emptying and grade A postoperative hemorrhage were increased with PVR (N = 22 vs. N = 1, p = 0.001 and N = 13 vs. N = 0, p = 0.007). All other ISGPS complications, overall complications, CCI, 30-day and 90-day mortality were similar between groups. Out of 23 patients with PVR, early and late thrombosis occurred in one patient each.

CONCLUSION: Portal vein reconstruction with bovine pericardium is feasible with comparable overall morbidity and mortality compared to pancreatoduodenectomy without PVR.

PMID:40178671 | DOI:10.1007/s00423-025-03689-6

Circulation. 2025 Feb 24. doi: 10.1161/CIRCULATIONAHA.124.071954. Online ahead of print.

ABSTRACT

BACKGROUND: To date, the only effective treatment of severe aortic stenosis is valve replacement. With the introduction of transcatheter aortic valve replacement and extending indications to younger patients, the use of bioprosthetic valves (BPVs) has considerably increased. The main inconvenience of BPVs is their limited durability because of mechanisms similar as the fibro-calcifying processes observed in native aortic stenosis. One of the major gaps of the field is to identify therapeutic targets to prevent or slow the fibro-calcifying process leading to severe and symptomatic aortic stenosis. The aim was to identify new targets for anticalcification drugs to prevent aortic and BPV calcification using an unbiased translational approach.

METHODS: Explanted valves were collected from patients and organ donor hearts. A comparative transcriptomic analysis was performed on valvular interstitial cells (VIC) obtained from calcified (bicuspid and tricuspid) versus control valves. The mechanisms and consequences of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) downregulation were analyzed in VIC cultures from control human aortic valves. ALDH1A1 was inhibited or silenced and its impact on osteogenic marker expression and calcification processes assessed in VIC. The effect of all-trans retinoic acid on calcification was tested on human VIC cultures and on 2 animal models: the model of subcutaneous implantation of bovine pericardium in rats and the model of xenograft aortic valve replacement in juvenile sheep.

RESULTS: Transcriptome analysis of human VIC identified ALDHA1 as the most downregulated gene in VIC from calcified versus control valves. In human VIC, ALDH1A1 expression is downregulated by TGF-β1 in a SMAD2/3-dependent manner. ALDH1A1 inhibition promotes an osteoblast-like VIC phenotype and increases calcium deposition through inhibition of retinoic acid receptor alpha signaling. Conversely, VIC treatment with retinoids decreases calcium deposition and attenuates VIC osteoblast activity. Last, all-trans retinoic acid inhibits calcification development of aortic BPV in both in vivo models and improves aortic valve echocardiographic parameters in the xenograft sheep model.

CONCLUSIONS: These results show that ALDH1A1 is downregulated in calcified valves, hence promoting VIC transition into an osteoblastic phenotype. Retinoic acid receptor alpha agonists, including all-trans retinoic acid through a drug repositioning strategy, represent a promising and innovative pharmacological approach to prevent calcification of native aortic valves and BPV.

PMID:39989358 | DOI:10.1161/CIRCULATIONAHA.124.071954