Testosterone supplementation increases red blood cell susceptibility to oxidative stress, decreases membrane deformability, and decreases survival after cold storage and transfusion.

BACKGROUND: Blood collection from donors on testosterone therapy (TT) is restricted to red blood cell (RBC) concentrates to avoid patient exposure to supraphysiological testosterone (T). The objective of this study was to identify TT-related changes in RBC characteristics relevant to transfusion effectiveness in patients. STUDY DESIGN: This was a two-part study with cohorts of patients and blood donors on TT. In part 1, we conducted longitudinal evaluation of RBCs collected before and at three time points after initiation of T. RBC assays included storage and oxidative hemolysis, membrane deformability (elongation index), and oximetry. In part 2, we evaluated the fate of transfused RBCs from TT donors in immunodeficient mice and by retrospective analyses of NIH's vein-to-vein databases. RESULTS: TT increased oxidative hemolysis (1.45-fold change) and decreased RBC membrane deformability. Plasma free testosterone was positively correlated with oxidative hemolysis (r = .552) and negatively correlated with the elongation index (r = -.472). Stored and gamma-irradiated RBCs from TT donors had lower posttransfusion recovery in mice compared to controls (41.6 ± 12 vs. 55.3 ± 20.5%). Recipients of RBCs from male donors taking T had 25% lower hemoglobin increments compared to recipients of RBCs from non-TT male donors, and had increased incidence (OR, 1.80) of requiring additional RBC transfusions within 48 h of the index transfusion event. CONCLUSIONS: TT is associated with altered RBC characteristics and transfusion effectiveness. These results suggest that clinical utilization of TT RBCs may be less effective in recipients who benefit from longer RBC survival, such as chronically transfused patients.

Safety and effects of volume loading during transesophageal echocardiography in the pre-procedural work-up for left atrial appendage closure.

BACKGROUND: In patients undergoing left atrial appendage (LAA) closure, an accurate sizing of the LAA is key to optimize device sizing, procedural success and reduce complications. Previous studies have shown that intraprocedural volume loading increases LAA dimensions and improves device sizing. However, the safety and effects on LAA and device sizing of administering a fluid bolus during pre-procedural transesophageal echocardiography (TEE) are unknown. The aim of this study was to determine the safety and impact on LAA dimensions and device sizing of an intravenous (IV) fluid bolus administered during TEE in the setting of the pre-procedural work-up for LAA closure. METHODS: The study included a total of 72 patients who underwent TEE to assess suitability for LAAC and received a 500 ml IV bolus of normal saline. The LAA landing zone (LZ) and depth were measured by TEE before and after volume loading, and these measurements were used to predict the device size implanted during a subsequent percutaneous LAAC procedure. RESULTS: There were no complications associated with volume loading. The baseline mean LZ was 19.6 ± 3.6 mm at 90o, and 20.2 ± 4.1 mm at 135o. Following fluid bolus, the maximum diameter increased 1.5 ± 1.0 mm at 90o (p<0.001), and 1.3 ± 1.0 mm at 135o (p<0.001). The baseline mean depth of the LAA was 26.5 ± 5.5 mm at 90o, and 23.9 ± 5.8 mm at 135o. After fluid bolus, the mean depth increased by 1.5 ± 1.8 mm (p<0.001) and 1.6 ± 2.0 (p<0.001), at 90o and 135o, respectively. Sizing based on post-bolus measurements of the LZ significantly improved the agreement with the final device size selection during the procedure in 71.0% of cases (vs. 42.0% with pre-bolus measurements). CONCLUSIONS: Volume loading during ambulatory TEE as part of the pre-procedural work-up of LAAC is safe and significantly increases LAA dimensions. This strategy may become the new standard, particularly in centers performing LAAC with no TEE guidance, as it improves LAA sizing and more accurately predicts the final device size.

Prognosis of functional mitral regurgitation after aortic valve replacement for pure severe aortic stenosis.

OBJECTIVE: Whether patients with severe aortic stenosis (AS) and significant functional mitral regurgitation (MR) should undergo isolated aortic (aortic valve replacement [AVR]) or double aortic-mitral valve procedure (DVP) remains controversial. We sought to determine outcomes of such patients undergoing surgical (surgical aortic valve replacement [SAVR]) and transcatheter AVR (TAVR) or DVP, identify echocardiographic parameters predictive of significant residual MR after isolated AVR, and determine its impact on long-term survival. METHODS: Data prospectively collected from 736 consecutive patients with severe AS and significant MR undergoing AVR or DVP were retrospectively analyzed. Exclusion of organic MR, other valve diseases and concomitant CABG yielded a final population of 74 patients with significant functional MR (32 TAVR, 23 SAVR, 19 DVP). Demographics, postoperative complications and age-adjusted survival were compared. Echocardiographic predictors of significant residual MR and its impact on survival were analyzed for patients undergoing isolated AVR. RESULTS: In the isolated AVR group, MR improvement occurred in 60% of patients and was associated with a significant increase in survival compared to persistence of significant MR (p = .03). Patients with improved MR had significantly greater preoperative left ventricular dilatation (LVEDD: 49 vs. 43 mm, p = .001; LVESD: 35 vs. 29 mm, p = .03; LVEDV: 101 vs. 71 ml, p = .0003; LVESV: 57 vs. 33 ml, p = .002). There was no significant difference in perioperative mortality (5.3 vs. 4.4 vs. 9.4%, p = .85) or age-adjusted long-term survival between isolated AVR and DVP groups (76.3 vs. 84.2% survival at 2-year follow-up, p = .26), or between SAVR, TAVR and DVP groups (78.2 vs. 75.0 vs. 84.2% survival at 2-year follow-up, p = .13). CONCLUSIONS: After isolated AVR, MR improvement occurs in 60% of patients. It is predicted by greater ventricular dimensions and associated with significantly better long-term survival. Whether a staged approach with transcatheter correction of MR should be considered in patients with significant residual MR following AVR remains undetermined.

Transesophageal echocardiography complications associated with interventional cardiology procedures.

BACKGROUND: Although there have been several reports documenting complications related with transesophageal echocardiography (TEE) manipulation following cardiac surgery, there is a paucity of data regarding the safety of TEE used to guide catheter-based interventions. The aim of this study was to determine the prevalence, types and risk factors of complications associated with procedures requiring active TEE guidance. METHODS: This study included 1249 consecutive patients undergoing either transcatheter aortic valve implantation (TAVI), Mitraclip, left atrial appendage occlusion (LAAO) or paravalvular leak closure (PVLC). Patients were divided into 2 cohorts based on the degree of probe manipulation required to guide the procedure and the risk of developing a TEE-related complication: low-risk (TAVI, n = 1037) and high-risk (Mitraclip, LAAO and PVLC, n = 212). Patients were further analyzed according to the occurrence of major and minor TEE-related complications. RESULTS: The overall incidence of TEE-related complications was 0.9% in the TAVI group and 6.1% in the rest of the cohort (P < .001). Patients in the high-risk cohort had also a higher incidence of major-complications (2.8% vs 0.6%, P = .008), and factors associated with an increased risk were being underweight, having a prior history of gastrointestinal bleeding and the use of chronic steroids/immunosuppressive medications. Procedural time under TEE-manipulation was longer in patients exhibiting complications and was an independent predictor of major complications (OR = 1.13, 95% CI 1.01-1.25, for each 10 minutes increments in imaging time). Patients with major complications undergoing Mitraclip had the longest median time under TEE-manipulation (297 minutes) and a risk of developing a major-complication that was 10.64 times higher than the rest of the cohort (95% CI 3.30-34.29, P < .001). CONCLUSION: The prevalence of TEE-related complications associated with interventional procedures is higher than previously reported. Undergoing a prolonged procedure, particularly in the setting of Mitraclip, was the main factor linked to TEE-related complications.

Survival of aging CD264+ and CD264- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

In vivo mesenchymal stem cell (MSC) survival is relevant to therapeutic applications requiring engraftment and potentially to nonengraftment applications as well. MSCs are a mixture of progenitors at different stages of cellular aging, but the contribution of this heterogeneity to the survival of MSC implants is unknown. Here, we employ a biomarker of cellular aging, the decoy TRAIL receptor CD264, to compare the survival kinetics of two cell populations in human bone marrow MSC (hBM-MSC) cultures. Sorted CD264+ hBM-MSCs from two age-matched donors have elevated ß-galactosidase activity, decreased differentiation potential and form in vitro colonies inefficiently relative to CD264- hBM-MSCs. Counterintuitive to their aging phenotype, CD264+ hBM-MSCs exhibited comparable survival to matched CD264- hBM-MSCs from the same culture during in vitro colony formation and in vivo when implanted ectopically in immunodeficient NIH III mice. In vitro and in vivo survival of these two cell populations were independent of colony-forming efficiency. These findings have ramifications for the preparation of hBM-MSC therapies given the prevalence of aging CD264+ cells in hBM-MSC cultures and the popularity of colony-forming efficiency as a quality control metric in preclinical and clinical studies with MSCs.

Infective endocarditis following transcatheter edge-to-edge mitral valve repair: A systematic review.

OBJECTIVES: To assess the clinical characteristics, management, and outcomes of patients diagnosed with infective endocarditis (IE) after edge-to-edge mitral valve repair with the MitraClip device. BACKGROUND: Transcatheter edge-to-edge mitral valve repair has emerged as an alternative to surgery in high-risk patients. However, few data exist on IE following transcatheter mitral procedures. METHODS: Four electronic databases (PubMed, Google Scholar, Embase, and Cochrane Library) were searched for original published studies on IE after edge-to-edge transcatheter mitral valve repair from 2003 to 2017. RESULTS: A total of 10 publications describing 12 patients with definitive IE (median age 76 years, 55% men) were found. The mean logistic EuroSCORE/EuroSCORE II were 41% and 45%, respectively. The IE episode occurred early (within 12 months post-procedure) in nine patients (75%; within the first month in five patients). Staphylococcus aureus was the most frequent (60%) causal microorganism, and severe mitral regurgitation was present in all cases but one. Surgical mitral valve replacement (SMVR) was performed in most (67%) patients, and the mortality associated with the IE episode was high (42%). CONCLUSIONS: IE following transcatheter edge-to-edge mitral valve repair is a rare but life-threatening complication, usually necessitating SMVR despite the high-risk profile of the patients. These results highlight the importance of adequate preventive measures and a prompt diagnosis and treatment of this serious complication.

Left atrial appendage closure: Initial experience with the ultraseal device.

OBJECTIVES: We report the initial experience of percutaneous left atrial appendage (LAA) closure with the Ultraseal device. BACKGROUND: LAA closure is an alternative to oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) and high risk of bleeding. The Ultraseal device is a new LAA closure prosthesis that consists of a distal soft bulb and a proximal sail attached by an articulating joint that allows a high degree of device conformability to the different variations of the LAA anatomy. METHODS: We included 12 consecutive patients with NVAF who underwent LAA closure with the Ultraseal device between January and December 2015 in our center. Patients had clinical and transesophageal echocardiography (TEE) examinations at baseline and at 45 days following LAA closure. RESULTS: The device was successfully implanted in all patients, with no periprocedural complications. There were no episodes of bleeding, stroke, pericardial effusion, or device embolization at 45-day follow-up. No cases with residual leaks >5 mm were observed at TEE. One patient presented a device related thrombus without clinical consequences. CONCLUSIONS: This initial experience with the Ultraseal LAA closure device demonstrates preliminary safety and feasibility. Further larger studies with longer follow-up are warranted. © 2016 Wiley Periodicals, Inc.

Amount of Sleep, Daytime Sleepiness, Hazardous Driving, and Quality of Life of Second Year Medical Students.

OBJECTIVE: The authors describe the sleep habits of second year medical students and look for associations between reported sleep duration and depression, burnout, overall quality of life, self-reported academic success, and falling asleep while driving. METHODS: The authors conducted a cross-sectional descriptive study of two consecutive cohorts of second year medical students at a large public university in the USA. Participants completed an anonymous survey about their sleep habits, daytime sleepiness (Epworth sleepiness scale), burnout (Maslach burnout inventory), depression (PRIME MD), and perceived stress (perceived stress scale). Categorical and continuous variables were compared using chi square tests and t tests, respectively. RESULTS: Sixty-eight percent of the students responded. Many (34.3%) reported fewer than 7 h of sleep on typical weeknights, including 6.5% who typically sleep less than 6 h. Twenty-five students (8.4%) reported nodding off while driving during the current academic year. Low typical weeknight sleep (fewer than 6 h vs 6-6.9 h vs 7 or more hours) was associated with (1) higher Epworth sleepiness scale scores, (2) nodding off while driving, (3) symptoms of burnout or depression, (4) decreased satisfaction with quality of life, and (5) lower perceived academic success (all p values ≤0.01). Students reporting under 6 h of sleep were four times more likely to nod off while driving than those reporting 7 h or more. CONCLUSION: Educational, behavioral, and curricular interventions should be explored to help pre-clinical medical students obtain at least 7 h of sleep most on weeknights.

Clinical Presentation and Value of Echocardiography in the Diagnosis of Freestyle Aortic Bioprosthesis Leaflet Tears: A Retrospective Study.

BACKGROUND: The unique design of the Freestyle stentless aortic bioprosthesis has led to different mechanisms of failure, particularly leaflet tearing. The aim of this retrospective study was to review the clinical presentation and echocardiographic data of symptomatic patients with leaflet tears and significant aortic regurgitation (AR) following implantation of the Freestyle bioprosthesis. METHODS: Between January 1993 and May 2011, a total of 430 consecutive patients was identified at the authors' institution who had undergone primary aortic valve replacement with a Freestyle stentless aortic bioprosthesis. Clinical and echocardiographic data were collected prospectively for all patients. Structural valve deterioration was the major cause of bioprosthetic valve failure. RESULTS: Twenty symptomatic patients presented with significant AR due to leaflet tears in the absence of more than mild valvular calcification. At presentation, all patients complained of dyspnea. Some 50% of patients (n = 10) presented with acute pulmonary edema, and 10% (n = 2) with cardiogenic shock. A leaflet tear was initially diagnosed using transthoracic echocardiography in five cases (25%), using transesophageal echocardiography (TEE) in eight cases (40%), or at surgery in seven cases (35%). An appropriate diagnosis of leaflet tearing was recognized at surgery in more than one-third of patients. Consequently, clinicians must be aware of the variety of clinical presentations and should have a high degree of suspicion regarding leaflet tears in patients who have received a Freestyle stentless aortic bioprosthesis and present with moderate to severe AR. CONCLUSIONS: For the optimal management of patients with Freestyle stentless aortic bioprosthesis and new moderate to severe AR, TEE should be considered in all patients.

Predictors and prognosis of early ischemic mitral regurgitation in the era of primary percutaneous coronary revascularisation.

BACKGROUND: Studies assessing ischemic mitral regurgitation (IMR) comprised of heterogeneous population and evaluated IMR in the subacute setting. The incidence of early IMR in the setting of primary PCI, its progression and clinical impact over time is still undetermined. We sought to determine the predictors and prognosis of early IMR after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). METHODS: Using our primary PCI database, we screened for patients who underwent ≥2 transthoracic echocardiograms early (1-3 days) and late (1 year) following primary PCI. The primary outcomes were: (1) major adverse events (MACE) including death, ischemic events, repeat hospitalization, re-vascularization and mitral repair or replacement (2) changes in quantitative echocardiographic assessments. RESULTS: From January 2006 to July 2012, we included 174 patients. Post-primary PCI IMR was absent in 95 patients (55%), mild in 60 (34%), and moderate to severe in 19 (11%). Early after primary PCI, IMR was independently predicted by an ischemic time > 540 min (OR: 2.92 [95% CI, 1.28 - 7.05]; p = 0.01), and female gender (OR: 3.06 [95% CI, 1.42 - 6.89]; p = 0.004). At a median follow-up of 366 days [34-582 days], IMR was documented in 44% of the entire cohort, with moderate to severe IMR accounting for 15%. During follow-up, MR regression (change ≥ 1 grade) was seen in 18% of patients. Moderate to severe IMR remained an independent predictor of MACE (HR: 2.58 [95% CI, 1.08 - 5.53]; p = 0.04). CONCLUSIONS: After primary PCI, IMR is a frequent finding. Regression of early IMR during long-term follow-up is uncommon. Since moderate to severe IMR post-primary PCI appears to be correlated with worse outcomes, close follow-up is required.

Outcomes following surgical correction of pure aortic regurgitation in presence or absence of significant functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (MR) can occur secondary to severe aortic regurgitation (AR). However, data on the overall impact of mitral surgical intervention after aortic valve replacement (AVR) are scarce. We sought to study the left ventricular (LV) remodeling process and determine predictors of clinical outcomes of patients with pure severe AR in presence or absence of significant functional MR. METHODS: Patients were categorized into AR-MR group (≤ mild MR; n = 51, 76%) and AR + MR group (≥ moderate MR; n = 16, 24%). All patients in the AR + MR group underwent AVR and MR correction. Serial echocardiographic measurements and clinical follow-up up to 5 years were obtained in all patients. RESULTS: Significant reverse LV remodeling occurred in both groups compared with baseline. No 30-day deaths occurred. Mortality and heart failure-related hospitalization rates, at follow-up, were significantly higher in the AR + MR group (19% vs. 2%, P = 0.04 and 38% vs. 12% P = 0.03, respectively), but a similar proportion of patients from both groups was in New York Heart Association class I or II (87% vs. 92%, P = 0.62). Preoperative indexed stroke volume (SV) <50 mL/m2 was the only independent predictor of death and/or rehospitalization after surgery (odds ratio: 61.1, [95% CI, 12.6­425.2]; P < 0.0001). CONCLUSION: Despite being a higher risk population, patients with moderate-to-severe functional MR secondary to severe AR experience similar postoperative mortality at the expense of a moderately higher 5-year overall mortality, rate of hospitalization for congestive heart failure, and medication use. Preoperative indexed SV < 50 mL/m2 may be helpful in predicting long-term outcomes.

Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin.

Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.

Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis.

BACKGROUND: Recent studies emphasized the usefulness of exercise stress echocardiography in asymptomatic patients with aortic stenosis. Nevertheless, the additive value of exercise pulmonary hypertension (Ex-PHT) in such patients remains unexplored. We therefore aimed to identify the determinants and to test the impact on outcome of Ex-PHT in asymptomatic patients with severe aortic stenosis. METHOD AND RESULTS: Asymptomatic patients with severe aortic stenosis (n=105; aortic valve area <0.6 cm(2)/m(2); age, 71±9 years; male, 59%) and preserved left ventricular systolic function (ejection fraction ≥55%) were prospectively submitted to exercise stress echocardiography. Resting PHT and Ex-PHT were defined as a systolic pulmonary arterial pressure >50 and >60 mm Hg, respectively. Ex-PHT was more frequent than resting PHT (55% versus 6%; P<0.0001). On multivariable logistic regression, the independent predictors of Ex-PHT were male sex (odds ratio, 4.3; P=0.002), resting systolic pulmonary arterial pressure (odds ratio, 1.16; P=0.002), exercise indexed left ventricular end-diastolic volume (odds ratio, 1.04; P=0.026), exercise e'-wave velocity (odds ratio, 1.35; P=0.047), and exercise-induced changes in indexed left atrial area (odds ratio, 1.36; P=0.006). Ex-PHT was associated with reduced cardiac event-free survival (at 3 years, 22±7% versus 55±9%; P=0.014). In a multivariable Cox proportional hazards model, Ex-PHT was identified as an independent predictor of cardiac events (hazard ratio, 1.8; 95% confidence interval, 1.0-3.3; P=0.047). When exercise-induced changes in mean aortic pressure gradient were added to the multivariable model, Ex-PHT remained independently associated with reduced cardiac event-free survival (hazard ratio, 2.0; 95% confidence interval, 1.1-3.6; P=0.025). CONCLUSIONS: In asymptomatic patients with severe aortic stenosis, the main determinants of Ex-PHT are male sex, resting systolic pulmonary arterial pressure, and exercise parameters of diastolic burden. Moreover, Ex-PHT is associated with a 2-fold increased risk of cardiac events. These results strongly support the use of exercise stress echocardiography in asymptomatic aortic stenosis.

Distorted views of biodiversity: spatial and temporal bias in species occurrence data.

Boakes et al. compile and analyze a historical dataset of 170,000 bird sightings over two centuries and show how changing trends in data gathering may confound a true picture of biodiversity change.

Effect of communication skills training for residents and nurse practitioners on quality of communication with patients with serious illness: a randomized trial.

IMPORTANCE: Communication about end-of-life care is a core clinical skill. Simulation-based training improves skill acquisition, but effects on patient-reported outcomes are unknown. OBJECTIVE: To assess the effects of a communication skills intervention for internal medicine and nurse practitioner trainees on patient- and family-reported outcomes. DESIGN, SETTING, AND PARTICIPANTS: Randomized trial conducted with 391 internal medicine and 81 nurse practitioner trainees between 2007 and 2013 at the University of Washington and Medical University of South Carolina. INTERVENTION: Participants were randomized to an 8-session, simulation-based, communication skills intervention (N = 232) or usual education (N = 240). MAIN OUTCOMES AND MEASURES: Primary outcome was patient-reported quality of communication (QOC; mean rating of 17 items rated from 0-10, with 0 = poor and 10 = perfect). Secondary outcomes were patient-reported quality of end-of-life care (QEOLC; mean rating of 26 items rated from 0-10) and depressive symptoms (assessed using the 8-item Personal Health Questionnaire [PHQ-8]; range, 0-24, higher scores worse) and family-reported QOC and QEOLC. Analyses were clustered by trainee. RESULTS: There were 1866 patient ratings (44% response) and 936 family ratings (68% response). The intervention was not associated with significant changes in QOC or QEOLC. Mean values for postintervention patient QOC and QEOLC were 6.5 (95% CI, 6.2 to 6.8) and 8.3 (95% CI, 8.1 to 8.5) respectively, compared with 6.3 (95% CI, 6.2 to 6.5) and 8.3 (95% CI, 8.1 to 8.4) for control conditions. After adjustment, comparing intervention with control, there was no significant difference in the QOC score for patients (difference, 0.4 points [95% CI, -0.1 to 0.9]; P = .15) or families (difference, 0.1 [95% CI, -0.8 to 1.0]; P = .81). There was no significant difference in QEOLC score for patients (difference, 0.3 points [95% CI, -0.3 to 0.8]; P = .34) or families (difference, 0.1 [95% CI, -0.7 to 0.8]; P = .88). The intervention was associated with significantly increased depression scores among patients of postintervention trainees (mean score, 10.0 [95% CI, 9.1 to 10.8], compared with 8.8 [95% CI, 8.4 to 9.2]) for control conditions; adjusted model showed an intervention effect of 2.2 (95% CI, 0.6 to 3.8; P = .006). CONCLUSIONS AND RELEVANCE: Among internal medicine and nurse practitioner trainees, simulation-based communication training compared with usual education did not improve quality of communication about end-of-life care or quality of end-of-life care but was associated with a small increase in patients' depressive symptoms. These findings raise questions about skills transfer from simulation training to actual patient care and the adequacy of communication skills assessment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00687349.

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation.

BACKGROUND: The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) - the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume - is a volumetric measure of LV myocardial shortening independent of size or geometry. AIM: To assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice. METHODS: Clinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied. RESULTS: During an estimated median follow-up of 49 (22-77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21±5% for patients with MCF <30% and 40±6% for those with ≥30% (P<0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51-3.58; P<0.001). Moreover, MCF<30% improved the predictive performance of models, with better global fit, reclassification and discrimination. CONCLUSIONS: MCF<30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.

Percutaneous Transcatheter Edge-to-Edge Mitral Valve Repair With MitraClip System in the Era of G4.

The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.

Integrating Echocardiography Parameters With Explainable Artificial Intelligence for Data-Driven Clustering of Primary Mitral Regurgitation Phenotypes.

BACKGROUND: Primary mitral regurgitation (MR) is a heterogeneous clinical disease requiring integration of echocardiographic parameters using guideline-driven recommendations to identify severe disease. OBJECTIVES: The purpose of this preliminary study was to explore novel data-driven approaches to delineate phenotypes of MR severity that benefit from surgery. METHODS: The authors used unsupervised and supervised machine learning and explainable artificial intelligence (AI) to integrate 24 echocardiographic parameters in 400 primary MR subjects from France (n = 243; development cohort) and Canada (n = 157; validation cohort) followed up during a median time of 3.2 years (IQR: 1.3-5.3 years) and 6.8 (IQR: 4.0-8.5 years), respectively. The authors compared the phenogroups' incremental prognostic value over conventional MR profiles and for the primary endpoint of all-cause mortality incorporating time-to-mitral valve repair/replacement surgery as a covariate for survival analysis (time-dependent exposure). RESULTS: High-severity (HS) phenogroups from the French cohort (HS: n = 117; low-severity [LS]: n = 126) and the Canadian cohort (HS: n = 87; LS: n = 70) showed improved event-free survival in surgical HS subjects over nonsurgical subjects (P = 0.047 and P = 0.020, respectively). A similar benefit of surgery was not seen in the LS phenogroup in both cohorts (P = 0.70 and P = 0.50, respectively). Phenogrouping showed incremental prognostic value in conventionally severe or moderate-severe MR subjects (Harrell C statistic improvement; P = 0.480; and categorical net reclassification improvement; P = 0.002). Explainable AI specified how each echocardiographic parameter contributed to phenogroup distribution. CONCLUSIONS: Novel data-driven phenogrouping and explainable AI aided in improved integration of echocardiographic data to identify patients with primary MR and improved event-free survival after mitral valve repair/replacement surgery.

Experience of Combined Procedure during Percutaneous LAA Closure.

INTRODUCTION: Percutaneous left atrial appendage closure (LAAC) is an alternative to oral anticoagulants (OAC) in patients with non-valvular atrial fibrillation (AF) and contraindication to long-term OAC. Combined strategy with percutaneous LAAC at the same time of other cardiac structural or electrophysiological procedures has emerged as an alternative to a staged strategy. AIM: To describe our experience with combined LAAC procedures using Watchman™ devices. METHODS: All patients with combined LAAC procedures using Watchman™ (WN) devices performed from 2016 to 2021 were included. The primary safety endpoint was a composite of periprocedural complications and adverse events during the follow-up. The primary efficacy endpoint included strokes, systemic embolisms, major bleeding and cardiovascular death. RESULTS: From 2016, among 160 patients who underwent LAAC using WN devices, 19 underwent a combined strategy: 7 transcatheter edge-to-edge mitral valve repair (TEMVR) (37%), 6 typical atrial flutter ablation (31%), 2 leadless pacemaker (LP) implantation (10%) and 4 AF ablation (22%). The WN device was successfully implanted in 98% and 100% of cases for single and combined LAAC procedures, respectively (p = 0.63). Median follow-up was 13 months (IQR 25/75 3/24). Device-related complications occurred in 6 out of 141 patients (4%) who underwent single LAAC and in no (0/19) patient in the combined LAAC procedure (p = ns). The procedural-related complications did not differ significantly between groups (5% vs. 10%, respectively, in the single and combined group, p = 0.1). CONCLUSION: Combined procedure using the Watchman™ devices and one other structural or electrophysiological procedure appears safe and effective. Larger series are needed to confirm these results.

Significance of Left Ventricular Ejection Time in Primary Mitral Regurgitation.

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed. Patients were retrospectively stratified by quartiles of LVET. The primary end point of the study was the composite of need for MV surgery or all-cause mortality. During a median follow-up time of 66 (25th to 75th percentile, 33 to 95) months, 178 patients reached the primary end point. Patients in the lowest quartile of LVET (<260 ms) were at high risk for adverse events compared with those in the other quartiles of LVET (global p = 0.005), whereas the rate of events was similar for the other quartiles (p = NS for all). After adjustment for clinical predictors of outcome, including age, gender, history of atrial fibrillation, MR severity, and current recommended triggers for MV surgery in asymptomatic primary MR, LVET <260 ms was associated with an increased risk of events (adjusted hazard ratio 1.49, 95% confidence interval 1.03 to 2.16, p = 0.033). In conclusion, we observed that shorter LVET is associated with increased risk of adverse events in patients with moderate or severe primary MR because of prolapse. Further studies are required to investigate whether shorter LVET has a direct effect on outcomes or is solely a risk marker in primary MR.