Prognostic impact of vasopressor test in transcatheter edge-to-edge repair of secondary mitral regurgitation: The PETIT study.

BACKGROUND: Vasopressor test (VPT) might be useful in patients with functional mitral regurgitation (MR) and left ventricular dysfunction (MITRA-FR-like patients) during transcatheter edge-to-edge repair (TEER). AIMS: We aimed to evaluate the prognostic impact of VPT. METHODS: MR treated with TEER were included in a multicenter prospective registry. VPT was used intraprocedurally in patients with left ventricular dysfunction and/or hypotension. The 1-year echocardiographic and clinical outcomes were compared according to the use of VPT. The primary endpoint was a combination of mortality + heart failure (HF) readmission at 1-year. RESULTS: A total of 1115 patients were included, mean age was 72.8 ± 10.5 years and 30.4% were women. VPT was performed in 128 subjects (11.5%), more often in critically ill patients with biventricular dysfunction. Postprocedurally the VPT group had greater rate of MR ≥ 2+ (46.9% vs. 31.7%, p = 0.003) despite greater number of devices (≥2 clips, 52% vs. 40.6 p = 0.008) and device repositioning or new clip in 12.5%. At 1-year, the primary endpoint occurred more often in the VPT group (27.3% vs. 16.9%, p = 0.002) as well as all-cause mortality (21.9% vs. 8.1%, p ≤ 0.001) but no differences existed in HF readmission rate (14.8% vs. 13.2%, p = 0.610), cardiovascular mortality (4.4% vs. 3.9%, p = 0.713) or residual MR ≥ 2+ (51.1% vs 51.7%, p = 0.371). CONCLUSIONS: Dynamic evaluation of MR during TEER procedure through VPT was performed in patients with worse baseline risk who also presented higher all-cause mortality at 1-year follow-up. However, 1-year residual MR, cardiovascular mortality and HF readmission rate remained comparable suggesting that VPT might help in the management of MITRA-FR-like patients.

Procedural Tools and Technics for Transcatheter Paravalvular Leak Closure: Lessons from a Decade of Experience.

Prosthetic paravalvular leaks (PVLs) are associated with congestive heart failure and hemolysis. Surgical PVL closure carries high risks. Transcatheter implantation of occluding devices in PVL is a lower risk but challenging procedure. Of the available devices, only two have been specifically approved in Europe for transcatheter PVL closure (tPVLc): the Occlutech® Paravalvular Leak Device (PLD) and Amplatzer™ ParaValvular Plug 3 (AVP 3). Here, we review the various tools and devices used for tPVLc, based on three observational registries including 748 tPVLc procedures performed in 2005-2021 at 33 centres in 11 countries. In this case, 12 registry investigators with over 20 tPVLc procedures each described their practical tips and tricks regarding imaging, approaches, delivery systems, and devices. They considered three-dimensional echocardiography to be the cornerstone of PVL assessment and procedure guidance. Anterograde trans-septal mitral valve and retrograde aortic approaches were used in most centres, although some investigators preferred the transapical approach. Hydrophilic-coated low-profile sheaths were used most often for device deployment. The AVP 3 and PLD devices were chosen for 89.0% of procedures. Further advances in design and materials are awaited. These complex procedures require considerable expertise, and experience accumulated over a decade has no doubt contributed to improve practices.

Linking In Vitro Models of Endothelial Dysfunction with Cell Senescence.

Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction-associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in ß-galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p < 0.0001), and a significant increase in oxidative stress (p < 0.0001). Furthermore, HUVECs subjected to 96 h of starvation, or exposed to concentrations of H2O2 of 400 to 1000 µM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds.

Feasibility of Left Atrial Appendage Occlusion in Left Atrial Appendage Thrombus: A Systematic Review.

OBJECTIVES: This study aimed to investigate the feasibility and safety of left atrial appendage occlusion (LAAO) procedures in patients with persistent left atrial appendage (LAA) thrombus. BACKGROUND: The left atrial appendage (LAA) is the most common site of thrombus formation in patients with nonvalvular atrial fibrillation (AF). Oral anticoagulation (OAC) is used to prevent and treat AF-related thrombus. However, a significant proportion of patients may not be eligible for long-term OAC therapy. In many cases, OAC may fail to resolve the thrombus. Left atrial appendage occlusion (LAAO) may be a potential option in such cases. Major LAAO studies have excluded patients with LAA thrombus, and it is not known whether LAAO procedures in the presence of LAA thrombus is feasible and safe. METHODS: This was a systematic review of patient-level data of all published cases of LAAO in the presence of LAA thrombus. RESULTS: There was a total of 58 patients included in the study. Most of the patients had a distally located thrombus in the LAA. All cases underwent successful implantation of LAAO devices with some procedural modifications. Amulet was the most commonly used device (50%). A cerebral protection device was used in 17 (29%) patients, and procedural transesophageal echocardiography was used in most of the cases. One stroke (1.7%) and 2 (3.4%) device-related thromboses were noted during the mean follow-up of 3.4 ± 7 months. CONCLUSIONS: Percutaneous LAAO procedures appear to be feasible in patients with a distally located persistent LAA thrombus when performed by experienced operators with some technical modifications. Further studies are required to determine the long-term safety and efficacy of this approach.