Impact of right ventricular-to-pulmonary artery coupling on remodeling and outcome in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Right ventricular-to-pulmonary artery (RV-PA) coupling has recently been shown to be associated with outcome in valvular heart disease. However, longitudinal data on RV dysfunction and reverse cardiac remodeling in patients following transcatheter edge-to-edge mitral valve repair (M-TEER) are scarce. METHODS: Consecutive patients with primary as well as secondary mitral regurgitation (MR) were prospectively enrolled and had comprehensive echocardiographic and invasive hemodynamic assessment at baseline. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization and death. RESULTS: Between April 2018 and January 2021, 156 patients (median 78 y/o, 55% female, EuroSCORE II: 6.9%) underwent M-TEER. On presentation, 64% showed impaired RV-PA coupling defined as tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio < 0.36. Event-free survival rates at 2 years were significantly lower among patients with impaired coupling (57 vs. 82%, p < 0.001), both in patients with primary (64 vs. 91%, p = 0.009) and secondary MR (54 vs. 76%, p = 0.026). On multivariable Cox-regression analyses adjusted for baseline, imaging, hemodynamic, and procedural data, TAPSE/PASP ratio < 0.36 was independently associated with outcome (adj.HR 2.74, 95% CI 1.17-6.43, p = 0.021). At 1-year follow-up, RV-PA coupling improved (TAPSE: ∆ + 3 mm, PASP: ∆ - 10 mmHg, p for both < 0.001), alongside with a reduction in tricuspid regurgitation (TR) severity (grade ≥ II: 77-54%, p < 0.001). CONCLUSIONS: TAPSE/PASP ratio was associated with outcome in patients undergoing M-TEER for primary as well as secondary MR. RV-PA coupling, alongside with TR severity, improved after M-TEER and might thus provide prognostic information in addition to established markers of poor outcome.

A Real World 10-Year Experience With Vascular Closure Devices and Large-Bore Access in Patients Undergoing Transfemoral Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve replacement (TAVR) has established itself as a safe and efficient treatment option in patients with severe aortic valve stenosis, regardless of the underlying surgical risk. Widespread adoption of transfemoral procedures led to more patients than ever being eligible for TAVR. This increase in procedural volumes has also stimulated the use of vascular closure devices (VCDs) for improved access site management. In a single-center examination, we investigated 871 patients that underwent transfemoral TAVR from 2010 to 2020 and assessed vascular complications according to the Valve Academic Research Consortium (VARC) III recommendations. Patients were grouped by the VCD and both, vascular closure success and need for intervention were analyzed. In case of a vascular complication, the type of intervention was investigated for all VCDs. The Proglide VCD was the most frequently used device (n = 670), followed by the Prostar device (n = 112). Patients were old (median age 83 years) and patients suffered from high comorbidity burden (60% coronary artery disease, 30% type II diabetes, 40% atrial fibrillation). The overall rate of major complications amounted to 4.6%, it was highest in the Prostar group (9.6%) and lowest in the Manta VCD group (1.1% p = 0.019). The most frequent vascular complications were bleeding and hematoma (n = 110, 13%). In case a complication occurred, 72% of patients did not need any further intervention other than manual compression or pressure bandages. The rate of surgical intervention after complication was highest in the Prostar group (n = 15, 29%, p = 0.001). Temporal trends in VCD usage highlight the rapid adoption of the Proglide system after introduction at our institution. In recent years VCD alternatives, utilizing other closure techniques, such as the Manta device emerged and increased vascular access site management options. This 10-year single-center experience demonstrates high success rates for all VCDs. Despite successful closure, a significant number of patients does experience minor vascular complications, in particular bleeding and hematoma. However, most complications do not require surgical or endovascular intervention. Temporal trends display a marked increase in TAVR procedures and highlight the need for more refined vascular access management strategies.

Nanoscale analysis of clustered DNA damage after high-LET irradiation by quantitative electron microscopy--the heavy burden to repair.

Low- and high-linear energy transfer (LET) ionising radiation are effective cancer therapies, but produce structurally different forms of DNA damage. Isolated DNA damage is repaired efficiently; however, clustered lesions may be more difficult to repair, and are considered as significant biological endpoints. We investigated the formation and repair of DNA double-strand breaks (DSBs) and clustered lesions in human fibroblasts after exposure to sparsely (low-LET; delivered by photons) and densely (high-LET; delivered by carbon ions) ionising radiation. DNA repair factors (pKu70, 53BP1, γH2AX, and pXRCC1) were detected using immunogold-labelling and electron microscopy, and spatiotemporal DNA damage patterns were analysed within the nuclear ultrastructure at the nanoscale level. By labelling activated Ku-heterodimers (pKu70) the number of DSBs was determined in electron-lucent euchromatin and electron-dense heterochromatin. Directly after low-LET exposure (5 min post-irradiation), single pKu70 dimers, which reflect isolated DSBs, were randomly distributed throughout the entire nucleus with a linear dose correlation up to 30 Gy. Most euchromatic DSBs were sensed and repaired within 40 min, whereas heterochromatic DSBs were processed with slower kinetics. Essentially all DNA lesions induced by low-LET irradiation were efficiently rejoined within 24h post-irradiation. High-LET irradiation caused localised energy deposition within the particle tracks, and generated highly clustered DNA lesions with multiple DSBs in close proximity. The dimensions of these clustered lesions along the particle trajectories depended on the chromatin packing density, with huge DSB clusters predominantly localised in condensed heterochromatin. High-LET irradiation-induced clearly higher DSB yields than low-LET irradiation, with up to ∼ 500 DSBs per µm(3) track volume, and large fractions of these heterochromatic DSBs remained unrepaired. Hence, the spacing and quantity of DSBs in clustered lesions influence DNA repair efficiency, and may determine the radiobiological outcome.

Carboxy-methyl-cellulose hydrogel-filled breast implants - an ideal alternative? A report of five years' experience with this device.

The controversy over the potential health risks from exposure to silicone gel from breast implants has led to extensive research to improve the safety of silicone gel-filled implants. In addition, there has been simultaneous research directed toward the development of alternative filling materials, with the goal of a breast implant that would minimize health risks and maximize cosmetic attributes. In the present study, experience with a filler material that has textural characteristics similar to that of silicone gel, but which is biodegradable and can therefore be eliminated by the body in case of implant failure, is reported.Since February 2000, the authors have been monitoring carboxy-methyl-cellulose (CMC) hydrogel breast implants as participants in a prospective clinical trial. CMC hydrogel is a biodegradable, nontoxic, nonmutagenic and viscoelastic gel, which has been in clinical use since 1984 and has been available as the Monobloc breast implant since 1994. For the present study, 122 patients who underwent surgery between February 2000 and February 2005 were evaluated. It was determined that CMC hydrogel implants have a higher radiotranslucency than silicone gel, and the integrity of this device was easy to prove by clinical examination. In case of rupture, the implant can be replaced immediately; it is easily inserted and can be placed through a small incision because of its highly elastic shell. The complication rate was very low, and the patients were highly satisfied. In terms of safety, the implant is comparable with saline, and its consistency is comparable with that of silicone gel.