[T-TEER: description of a development process]. / T-TEER: Beschreibung eines Entwicklungsprozesses.

Tricuspid valve regurgitation (TR) is becoming increasingly more clinically important. While considered as an accompanying symptom of left heart pathologies in the past, TR is now seen as an independent and clinically significant condition. TR can lead to volume overload of the right ventricle, resulting in dilatation of the tricuspid valve annulus and worsening of the regurgitation. Undetected or untreated severe TR can lead to recurrent cardiac decompensation with hospitalization, reduced quality of life and death. Previous treatment options were limited to cardiac surgery and associated with high complication and mortality rates, especially in isolated TR. Therefore, many patients are considered inoperable so that the new interventional treatment measures nowadays often represent the only treatment option. Interventional treatment options such as the edge-to-edge procedure (T-TEER) with TriClip™ or the PASCAL™ system are very safe interventions that have already shown promising results, including reduction of TR, improvement in heart failure symptoms and the quality of life. The influence on the mortality and the necessity for hospitalization due to heart failure are currently being investigated in several randomized studies. Patient selection and timing of the intervention are crucial. Cardiovascular imaging plays a decisive role in selecting the appropriate method and timing of the intervention. The prognosis depends on factors, such as the severity of TR, right ventricular dysfunction, and pulmonary arterial hypertension. Overall, interventional TR treatment is a promising advancement in treatment from which many patients can benefit in the future.

Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps.

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

Left and right ventricular dysfunction in patients with COVID-19-associated myocardial injury.

PURPOSE: SARS-COV-2 infection can develop into a multi-organ disease. Although pathophysiological mechanisms of COVID-19-associated myocardial injury have been studied throughout the pandemic course in 2019, its morphological characterisation is still unclear. With this study, we aimed to characterise echocardiographic patterns of ventricular function in patients with COVID-19-associated myocardial injury. METHODS: We prospectively assessed 32 patients hospitalised with COVID-19 and presence or absence of elevated high sensitive troponin T (hsTNT+ vs. hsTNT-) by comprehensive three-dimensional (3D) and strain echocardiography. RESULTS: A minority (34.3%) of patients had normal ventricular function, whereas 65.7% had left and/or right ventricular dysfunction defined by impaired left and/or right ventricular ejection fraction and strain measurements. Concomitant biventricular dysfunction was common in hsTNT+ patients. We observed impaired left ventricular (LV) global longitudinal strain (GLS) in patients with myocardial injury (-13.9% vs. -17.7% for hsTNT+ vs. hsTNT-, p = 0.005) but preserved LV ejection fraction (52% vs. 59%, p = 0.074). Further, in these patients, right ventricular (RV) systolic function was impaired with lower RV ejection fraction (40% vs. 49%, p = 0.001) and reduced RV free wall strain (-18.5% vs. -28.3%, p = 0.003). Myocardial dysfunction partially recovered in hsTNT + patients after 52 days of follow-up. In particular, LV-GLS and RV-FWS significantly improved from baseline to follow-up (LV-GLS: -13.9% to -16.5%, p = 0.013; RV-FWS: -18.5% to -22.3%, p = 0.037). CONCLUSION: In patients with COVID-19-associated myocardial injury, comprehensive 3D and strain echocardiography revealed LV dysfunction by GLS and RV dysfunction, which partially resolved at 2-month follow-up. TRIAL REGISTRATION: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Myosin 1f is specifically required for neutrophil migration in 3D environments during acute inflammation.

Neutrophil extravasation and interstitial migration are important steps during the recruitment of neutrophils to sites of inflammation. In the present study, we addressed the functional importance of the unconventional class I myosin 1f (Myo1f) for neutrophil trafficking during acute inflammation. In contrast to leukocyte rolling and adhesion, the genetic absence of Myo1f severely compromised neutrophil extravasation into the inflamed mouse cremaster tissue when compared with Myo1f+/+ mice as studied by intravital microscopy. Similar results were obtained in experimental models of acute peritonitis and acute lung injury. In contrast to 2-dimensional migration, which occurred independently of Myo1f, Myo1f was indispensable for neutrophil migration in 3-dimensional (3D) environments, that is, transmigration and migration in collagen networks as it regulated squeezing and dynamic deformation of the neutrophil nucleus during migration through physical barriers. Thus, we provide evidence for an important role of Myo1f in neutrophil trafficking during inflammation by specifically regulating neutrophil extravasation and migration in 3D environments.

A Fundamental Role of Myh9 for Neutrophil Migration in Innate Immunity.

Neutrophils are the first leukocytes to arrive at sites of injury during the acute inflammatory response. To maintain the polarized morphology during migration, nonmuscle myosins class II are essential, but studies using genetic models to investigate the role of Myh9 for neutrophil migration were missing. In this study, we analyzed the functional role of Myh9 on neutrophil trafficking using genetic downregulation of Myh9 in Vav-iCre+/Myh9wt/fl mice because the complete knockout of Myh9 in the hematopoietic system was lethal. Migration velocity and Euclidean distance were significantly diminished during mechanotactic migration of Vav-iCre+/Myh9wt/fl neutrophils compared with Vav-iCre-/Myh9wt/fl control neutrophils. Similar results were obtained for transmigration and migration in confined three-dimensional environments. Stimulated emission depletion nanoscopy revealed that a certain threshold of Myh9 was required to maintain proper F-actin dynamics in the front of the migrating cell. In laser-induced skin injury and in acute peritonitis, reduced Myh9 expression in the hematopoietic system resulted in significantly diminished neutrophil extravasation. Investigation of bone marrow chimeric mice in the peritonitis model revealed that the migration defect was cell intrinsic. Expression of Myh9-EGFP rescued the Myh9-related defects in two-dimensional and three-dimensional migration of Hoxb8-SCF cell-derived neutrophils generated from fetal liver cells with a Myh9 knockdown. Live cell imaging provided evidence that Myh9 was localized in branching lamellipodia and in the uropod where it may enable fast neutrophil migration. In summary, the severe migration defects indicate an essential and fundamental role of Myh9 for neutrophil trafficking in innate immunity.

Coronin 1A, a novel player in integrin biology, controls neutrophil trafficking in innate immunity.

Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the ß2 integrins lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) and macrophage-1 antigen (CD11b/CD18). Here, we identify coronin 1A (Coro1A) as a novel regulator of ß2 integrins that interacts with the cytoplasmic tail of CD18 and is crucial for induction of PMN adhesion and postadhesion events, including adhesion strengthening, spreading, and migration under flow conditions. Transition of PMN rolling to firm adhesion critically depends on Coro1A by regulating the accumulation of high-affinity LFA-1 in focal zones of adherent cells. Defective integrin affinity regulation in the genetic absence of Coro1A impairs leukocyte adhesion and extravasation in inflamed cremaster muscle venules in comparison with control animals. In a Helicobacter pylori mouse infection model, PMN infiltration into the gastric mucosa is dramatically reduced in Coro1A-/- mice, resulting in an attenuated gastric inflammation. Thus, Coro1A represents an important novel player in integrin biology, with key functions in PMN trafficking during innate immunity.

Save the children by treating their mothers (PriVileG-M-study) - study protocol: a sequentially randomized controlled trial of individualized psychotherapy and telemedicine to reduce mental stress in pregnant women and young mothers and to improve Child's health.

BACKGROUND: As early as pregnancy, maternal mental stress impinges on the child's development and health. Thus, this may cause enhanced risk for premature birth, lowered fetal growth, and lower fetal birth weight as well as enhanced levels of the stress hormone cortisol and lowered levels of the bonding hormone oxytocin. Maternal stress further reduces maternal sensitivity for the child's needs which impairs the mother-child-interaction and bonding. Therefore, prevention and intervention studies on mental stress are necessary, beginning prenatally and applying rigorous research methodology, such as randomized controlled trials, to ensure high validity. METHODS: A randomized controlled trial is used to assess the impact of psychotherapy and telemedicine on maternal mental stress and the child's mental and physical health. Mentally stressed pregnant women are randomized to an intervention (IG) and a not intervened control group. The IG receives an individualized psychotherapy starting prenatal and lasting for 10 months. Afterwards, a second randomization is used to investigate whether the use of telemedicine can stabilize the therapeutic effects. Using ecological momentary assessments and video recordings, the transfer into daily life, maternal sensitivity and mother-child-bonding are assessed. Psycho-biologically, the synchronicity of cortisol and oxytocin levels between mother and child are assessed as well as the peptidome of the colostrum and breast milk, which are assumed to be essential for the adaptation to the extra-uterine environment. All assessments are compared to an additional control group of healthy women. Finally, the results of the study will lead to the development of a qualification measure for health professionals to detect mental stress, to treat it with low-level interventions and to refer those women with high stress levels to mental health professionals. DISCUSSION: The study aims to prevent the transgenerational transfer of psychiatric and somatic disorders from the mother to her child. The effects of the psychotherapy will be stabilized through telemedicine and long-term impacts on the child's and mothers' mental health are enhanced. The combination of psychotherapy, telemedicine and methodologies of ecological momentary assessment, video recording and bio banking are new in content-related and methodological manner. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017065. Registered 02 May 2019. World Health Organization, Universal Trial Number: U1111-1230-9826. Registered 01 April 2019.

Self-reported influenza vaccination rates and attitudes towards vaccination among health care workers: results of a survey in a German university hospital.

OBJECTIVES: The objective of this survey was to analyse vaccination rates and attitudes towards vaccination among health care workers (HCWs). The period prevalence of self-reported acute respiratory infections in the influenza season 2014/2015 was examined. STUDY DESIGN: A cross-sectional study was conducted among HCWs of a German university hospital using an anonymised questionnaire. Recruitment was performed by providing all medical and nursing staff a paper questionnaire with an invitation to participate. METHODS: Descriptive aggregated data were generated from digitalised questionnaires for all variables. Differences in categorical variables were analysed by Chi-squared test. Textual data were analysed by an iterative process based on the grounded theory by Glaser and Strauss. RESULTS: The response rate was 31% (677/2186). Probable influenza was described by 9% (64/677) of the participants. The overall self-reported vaccination rate was 55% (366/666). Self-reported vaccination rate was higher in physicians (172/239, 72%) than in nursing staff (188/418, 45%). HCWs in paediatrics (103/148, 70%) more likely received vaccines than HCWs in surgery (31/84, 37%). Most vaccinations were provided by medical staff on the wards (164/368, 45%). Self-reported lost work-time due to adverse events after vaccination was low (6/336, 2%). Eight categories for vaccine refusal were identified, whereof doubts about effectiveness and indication of the vaccine was most frequently mentioned (72/202, 36%). CONCLUSIONS: Efforts to promote vaccination should focus on nursing staff and should provide scientific evidence on effectiveness, adverse effects, and the benefits of health care workers' vaccination for patients. Administering vaccines at the workplace proved to be a successful strategy in our setting. Studies are needed to assess the frequency of influenza causing disease in HCWs.

The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation.

Mechanical forces in blood circulation such as shear stress play a predominant role in many physiological and pathophysiological processes related to vascular responses or vessel remodeling. Arteriogenesis, defined as the growth of pre-existing arterioles into functional collateral arteries compensating for stenosed or occluded arteries, is such a process. Midkine, a pleiotropic protein and growth factor, has originally been identified to orchestrate embryonic development. In the adult organism its expression is restricted to distinct tissues (including tumors), whereby midkine is strongly expressed in inflamed tissue and has been shown to promote inflammation. Recent investigations conferred midkine an important function in vascular remodeling and growth. In this review, we introduce the midkine gene and protein along with its cognate receptors, and highlight its role in inflammation and the vascular system with special emphasis on arteriogenesis, particularly focusing on shear stress-mediated vascular cell proliferation and vasodilatation.

The cytokine midkine supports neutrophil trafficking during acute inflammation by promoting adhesion via ß2 integrins (CD11/CD18).

Emerging evidence suggests a role of the cytokine midkine (MK) in inflammation. In this study, its functional relevance for recruitment of polymorphonuclear neutrophils (PMNs) during acute inflammation was investigated. Intravital microscopy and histologic analysis of tumor necrosis factor-α-stimulated cremaster muscle venules revealed severely compromised leukocyte adhesion and extravasation in MK(-/-) mice compared with MK(+/+) animals. Systemic administration of recombinant MK completely rescued the adhesion defect in MK(-/-) mice. In a hind limb ischemia model, leukocyte accumulation in MK(-/-) mice was significantly diminished compared with MK(+/+) animals. However, MK did not lead to an inflammatory activation of PMNs or endothelial cells suggesting that it does not serve as classical proinflammatory cytokine. Unexpectedly, immobilized MK mediated PMN adhesion under static and flow conditions, whereas PMN-derived MK was dispensable for the induction of adhesion. Furthermore, adhesion strengthening remained unaffected by MK. Flow cytometry revealed that immobilized, but not soluble MK, significantly promoted the high affinity conformation of ß2 integrins of PMNs. Blocking studies of low-density lipoprotein receptor-related protein 1 (LRP1) suggested that LRP1 may act as a receptor for MK on PMNs. Thus, MK seems to support PMN adhesion by promoting the high affinity conformation of ß2 integrins, thereby facilitating PMN trafficking during acute inflammation.

The T-plasty: a modified YV-plasty for highly recurrent bladder neck contracture after transurethral surgery for benign hyperplasia of the prostate: clinical outcome and patient satisfaction.

OBJECTIVE: To describe a modified surgical technique for treatment of highly recurrent bladder neck contracture (BNC) after transurethral surgery for benign hyperplasia and to evaluate success rate and patient satisfaction of this novel technique. METHODS: Ten patients with highly recurrent BNC and multiple prior attempts of endoscopic treatment underwent the T-plasty. Perioperative complications were recorded and classified according to the Clavien classification. Patient reported functional outcomes were retrospectively analysed using a standardized questionnaire assessing recurrence of stenosis, incontinence, satisfaction and changes in quality of life (QoL). The questionnaires included validated IPSS and SF-8-health survey items. RESULTS: Mean age at the time of surgery was 69.2 years (range 61-79), and the mean follow-up was 26 months (range 3-46). No complications grade 3 or higher according to the Clavien classification occurred. Success rate was 100 %. No de novo stress incontinence occurred. Urinary stream was described as very strong to moderate by 80 % of the patients, mean post-operative IPSS-score was 11.3 (range 4-29), and mean post-operative IPSS-QoL was 2.4 (range 1-5). Patients satisfaction was very high or high in 90 %, and QoL improved in 90 %. The SF-8-health survey showed values comparable to the reference population. CONCLUSION: The T-plasty represents a safe and valuable option in treating highly recurrent BNC after surgery for benign hyperplasia. It offers multiple advantages compared to other techniques such as a single-staged approach and the opportunity for reconstruction of a reliable wide bladder neck by usage of two well-vascularized flaps. Success rate, low rate of complications and preservation of continence are highly encouraging.

Sedation during bronchoscopy: data from a nationwide sedation and monitoring survey.

BACKGROUND: There is limited knowledge on practice patterns in procedural sedation and analgesia (PSA), the use of propofol, and monitoring during flexible bronchoscopy (FB). The purpose of this study was to assess the current practice patterns of FBs and to focus on the use of propofol, the education of the proceduralist, and the involvement of anaesthesiologists during FB. METHODS: An anonymous questionnaire was sent to 299 pulmonologists. Only respondents who were active physicians in adult respiratory medicine performing FB were subsequently analysed. RESULTS: The response rate was 78 % and 27,149 FB in the previous 12 months were analysed. The overall sedation-related morbidity rate was 0.02 % and mortality was 7/100'000 FB. Sedation was used in 95 % of bronchoscopies. The main drugs used for PSA were propofol (77 %) and midazolam (46 %). In 84 % of PSAs propofol was used without the attendance of an anaesthesiologist. The use of propofol was associated with high volume bronchoscopists (p < 0.010) and career-young pulmonologists (p < 0.001). While monitoring vital parameters has become standard practice, pulmonologists reported a very low rate of systematic basic education and training in the field of PSA (50 %). CONCLUSIONS: In Switzerland, PSA during FB is mostly performed with propofol without the attendance of an anaesthesiologist and the use of this drug is expected to increase in the future. While monitoring standards are very high there is need for policies to improve education, systematic training, and support for pulmonologists for PSA during FB.

Cartilage boundary lubrication of ovine synovial fluid following anterior cruciate ligament transection: a longitudinal study.

OBJECTIVE: To assess ovine synovial fluid (oSF) from different post-injury time points for (1) proteoglycan-4 (PRG4) and hyaluronan (HA) concentration, (2) HA molecular weight (MW) distribution, (3) cartilage boundary lubrication function, and (4) lubricant composition-function relationships. The association between cartilage boundary lubrication and gross cartilage changes after injury was also examined. METHODS: oSF was collected 2, 4, 10, and 20 weeks post anterior cruciate ligament (ACL) transection in five skeletally mature sheep. PRG4 and HA concentrations were measured using sandwich enzyme-linked immunosorbent assay, and HA MW distribution by agarose gel electrophoresis. Cartilage boundary lubrication of oSF was assessed using a cartilage-cartilage friction test. Gross damage to articular cartilage was also quantified at 20 weeks using modified Drez scoring protocol. RESULTS: Early (2-4 weeks) after ACL injury, PRG4 concentrations were significantly higher (P = 0.045, P = 0.037), and HA concentrations were substantially lower (P = 0.005, P = 0.005) compared to 20 weeks. The HA MW distribution also shifted towards lower ranges in the early post-injury stage. The kinetic friction coefficients were significantly higher 2-4 weeks post injury (P = 0.008 and P = 0.049) compared to 20 weeks. Poor cartilage boundary lubricating ability early after injury was associated with cartilage damage at 20 weeks. CONCLUSION: Altered composition and diminished boundary lubrication of oSF early after ACL transection may pre-dispose the articular cartilage to degenerative changes and initiate osteoarthritis (OA). These observations also provide potential motivation for biotherapeutic interventions at earlier time points post injury.

The mammalian actin-binding protein 1 is critical for spreading and intraluminal crawling of neutrophils under flow conditions.

Recently, the mammalian actin-binding protein 1 (mAbp1; Hip-55, SH3P7, debrin-like protein) was identified as a novel component of the ß(2) integrin-mediated signaling cascade during complement-mediated phagocytosis and firm adhesion of polymorphonuclear neutrophils (PMN) under physiological shear stress conditions. In this study, we found that the genetic ablation of mAbp1 severely compromised not only the induction of adhesion, but also subsequent spreading of leukocytes to the endothelium as assessed by intravital microscopy of inflamed vessels of the cremaster muscle of mice. In vitro studies using murine PMN confirmed that mAbp1 was required for ß(2) integrin-mediated spreading under shear stress conditions, whereas mAbp1 was dispensable for spreading under static conditions. Upon ß(2) integrin-mediated adhesion and chemotactic migration of human neutrophil-like differentiated HL-60 cells, mAbp1 was enriched at the leading edge of the polarized cell. Total internal reflection fluorescence microscopy revealed that mAbp1 formed propagating waves toward the front of the lamellipodium, which are characteristic for dynamic reorganization of the cytoskeleton. Accordingly, binding of mAbp1 to actin was increased upon ß(2) integrin-mediated adhesion, as shown by coimmunoprecipitation experiments. However, chemotactic migration under static conditions was unaffected in the absence of mAbp1. In contrast, the downregulation of mAbp1 by RNA interference technique in neutrophil-like differentiated HL-60 cells or the genetic ablation of mAbp1 in leukocytes led to defective migration under flow conditions in vitro and in inflamed cremaster muscle venules in the situation in vivo. In conclusion, mAbp1 is of fundamental importance for spreading and migration under shear stress conditions, which are critical prerequisites for efficient PMN extravasation during inflammation.

Ten Future Challenges in the Field of Transcatheter Mitral Valve Edge-to-Edge Repair.

Mitral valve transcatheter edge-to-edge repair (M-TEER) and replacement (TMVR) have evolved as guideline-recommended treatment approaches for mitral regurgitation (MR). Even though they are supported by a growing body of evidence from either randomized trials or large registries, there are still several unsolved challenges in the field of interventional MR treatment. In the present review, we discuss the ten most important open questions regarding M-TEER and TMVR.

4-Year Follow-Up After Transcatheter Tricuspid Valve Replacement Using the EVOQUE System.

Transcatheter tricuspid valve replacement (TTVR) is an increasingly used treatment technique for patients with severe tricuspid regurgitation (TR). Currently, available data from international registries and randomized controlled trials provide outcome data until a maximum follow-up of 2 years after the procedure. This case report presents 4-year follow-up data for an 84-year-old woman who underwent TTVR for torrential TR in 2019. The patient experienced durable TR reduction, symptomatic improvement, right ventricular reverse remodeling, and substantial improvement in liver and kidney function.

Applying the TRILUMINATE Eligibility Criteria to Real-World Patients Receiving Tricuspid Valve Transcatheter Edge-to-Edge Repair.

BACKGROUND: According to the TRILUMINATE (Clinical Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System) trial, transcatheter tricuspid edge-to-edge repair (T-TEER) improves quality of life beyond medical treatment, while no effects on heart failure hospitalization (HFH) and survival were observed at 1 year. However, the generalizability of the TRILUMINATE trial to real-world conditions remains a subject of discussion. OBJECTIVES: The aim of this study was to apply the clinical TRILUMINATE inclusion and exclusion criteria to a real-world T-TEER patient group and evaluate symptomatic and survival outcome in TRILUMINATE-eligible and TRILUMINATE-ineligible patients. METHODS: Clinical TRILUMINATE inclusion and exclusion criteria were applied to a cohort of patients who underwent T-TEER at 5 European centers from 2016 to 2022. Study patients were compared regarding baseline characteristics, survival, HFH, and symptomatic outcomes as measured by NYHA functional class, a quality-of-life questionnaire and 6-minute walk distance. RESULTS: Of 962 patients, 54.8% were classified as TRILUMINATE eligible, presenting with superior left ventricular function and fewer comorbidities compared with the ineligible population. Tricuspid regurgitation reduction, improvement in NYHA functional class, quality of life, and exercise capacity were comparable in both groups. However, the 1-year survival and HFH rates significantly differed (tricuspid regurgitation ≤2+ at discharge, 82% vs 85%; survival, 85% vs 75%; HFH, 14% vs 22% for eligible vs ineligible patients). CONCLUSIONS: The observed differences in survival and HFH outcomes suggest a limited generalizability of TRILUMINATE to real-world conditions and indicate the need for additional studies evaluating the outcomes after T-TEER in less selected patient populations.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

Longitudinal In Vivo Monitoring of Atheroprogression in Hypercholesterolemic Mice Using Photoacoustic Imaging.

BACKGROUND AND AIM: The ability to recognize and monitor atherosclerotic lesion development using noninvasive imaging is crucial in preventive cardiology. The aim of the present study was to establish a protocol for longitudinal monitoring of plaque lipid, collagen, and macrophage burden as well as of endothelial permeability. METHODS AND RESULTS: Photoacoustic signals derived from endogenous or exogenous dyes assessed in vivo, in plaques of albino Apoe -/- mice, correlated with lesion characteristics obtained after histomorphometric and immunofluorescence analyses, thus supporting the validity of our protocol. Using models of atheroprogression and regression, we could apply our imaging protocol to the longitudinal observation of atherosclerotic lesion characteristics in mice. CONCLUSIONS: The present study shows an innovative approach to assess arterial inflammation in a non-invasive fashion, applicable to longitudinal analyses of changes of atherosclerotic lesion composition. Such approach could prove important in the preclinical testing of therapeutic interventions in mice carrying pre-established lesions.