TRIVALVE Score: A Risk Score for Mortality/Hospitalization Prediction in Patients Undergoing Transcatheter Tricuspid Valve Intervention.

BACKGROUND: Transcatheter tricuspid valve intervention (TTVI) has been increasingly adopted in recent years for the treatment of patients with tricuspid regurgitation (TR). However, no dedicated risk stratification has been established for patients undergoing TTVI. OBJECTIVES: The aim of the present study was to propose a dedicated risk score for patients affected by severe TR undergoing TTVI. METHODS: The score was derived from the TRIVALVE (International Multisite Transcatheter Tricuspid Valve Therapies Registry; NCT03416166) registry, according to data availability. A stepwise model approach was used on predictor variables to develop a scoring system for predicting 12-month mortality or rehospitalization using multivariable logistic regression. Internal discrimination, calibration, and validation were assessed using receiver-operating characteristic curve analysis and bootstrapping with 1,000 resamples. RESULTS: A total of 483 patients were included in the study, with an overall 12-month mortality or rehospitalization rate of 19% (n = 94). The final risk score, ranging from 0 to 4.5, included the following 5 parameters (adjusted for age and gender): 1) atrial fibrillation at baseline; 2) glomerular filtration rate <30 mL/min; 3) elevated gamma-glutamyl transferase/bilirubin levels; 4) signs of right heart failure; and 5) left ventricular ejection fraction <50%. The bias-corrected area under the receiver-operating characteristic curve was 68% (95% CI: 62%-75%). A cutoff value of 2.5 demonstrated sensitivity of 65.4% and specificity of 60.5% for the outcome. CONCLUSIONS: The present study proposes a dedicated risk score for patients undergoing TTVI, providing an additional and simple tool for heart teams to select the best therapy for patients affected by severe TR.

Outcomes Following Transcatheter Mitral Valve Replacement Using Dedicated Devices in Patients With Mitral Annular Calcification.

BACKGROUND: Patients with mitral regurgitation (MR) and morphologic presence of relevant mitral annular calcification (MAC) represent a challenging phenotypic subset with limited treatment options. OBJECTIVES: The aim of this study was to assess the feasibility of transcatheter mitral valve replacement (TMVR) using dedicated devices for the treatment of MAC patients. METHODS: Consecutive patients with symptomatic MR receiving TMVR and with available computed tomography data from the CHOICE-MI (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) multicenter registry were stratified by the presence of none or mild mitral annular calcification (MACnone/mild) vs moderate or severe mitral annular calcification (MACmod/sev). RESULTS: Among 279 eligible patients (median age = 76.0 years [Q1-Q3: 71.0-81.0 years], EuroSCORE II = 6.2% [Q1-Q3: 3.9%-12.1%]), 222 (79.6%) presented with MACnone/mild and 57 (20.4%) with MACmod/sev. Patients with MACmod/sev had a higher prevalence of extracardiac arteriopathy (P = 0.011) and primary MR (P < 0.001). Although the technical success rate and the extent of MR elimination did not differ, TMVR treatment in MACmod/sev patients was associated with higher rates of postprocedural bleeding complications (P = 0.02) and renal failure (P < 0.001). Functional improvement at the 1- and 2-year follow-up did not differ between groups. At the 2-year follow-up, there were no differences between patients with MACmod/sev and MACnone/mild regarding all-cause mortality (38.5% vs 37.7%; P = 0.76), cardiovascular mortality (21.3% vs 24.9%; P = 0.97), and all-cause mortality or heart failure hospitalization (52.4% vs 46.7%; P = 0.28) CONCLUSIONS: TMVR in patients with MACmod/sev is associated with higher rates of postprocedural complications but similar rates of survival, MR resolution, and functional improvement compared to MACnone/mild. Further studies are necessary to define the role of dedicated TMVR devices in this population. (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency Registry [CHOICE-MI]; NCT04688190).

Evaluating Mitral TEER in the Management of Moderate Secondary Mitral Regurgitation Among Heart Failure Patients.

BACKGROUND: Moderate secondary mitral regurgitation (SMR) represents a subgroup of heart failure (HF) patients with treatment restricted to medical therapy. Outcomes in patients with moderate SMR treated with mitral transcatheter edge-to-edge repair (M-TEER) are less well known. OBJECTIVES: The aim of this study was to assess the safety and effectiveness of M-TEER in subjects with moderate SMR using the EXPANDed studies. METHODS: One-year outcomes in subjects from the EXPANDed studies (EXPAND [A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices] and EXPAND G4 [A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System] MitraClip studies) with baseline moderate SMR (2+), per echocardiographic core laboratory (ECL) assessment, were compared with subjects with baseline severe SMR (≥3+). RESULTS: There were 335 subjects with moderate SMR and 525 with severe SMR at baseline per ECL review. Baseline characteristics were similar between the 2 subgroups. After treatment with M-TEER, significant MR reduction was achieved in both groups. Significant left ventricular (LV) reverse remodeling was observed through 1 year, with a >20 mL decrease in LV end-diastolic and end-systolic volumes on average in the moderate SMR group. Significant 1-year improvements in NYHA functional class (>78% NYHA functional class I or II) and quality of life (>20 points on the Kansas City Cardiomyopathy Questionnaire-Overall Summary) were observed in subjects with moderate SMR. Similarly, low rates of major adverse events, all-cause mortality, and HF hospitalizations were observed between the 2 subgroups through 1 year. CONCLUSIONS: In the EXPANDed studies, subjects with moderate SMR treated with M-TEER had improvements similar to subjects with severe SMR in quality of life and positive LV remodeling at 1 year. Future studies are needed to evaluate if M-TEER would be beneficial for HF patients with moderate SMR.

Clinical outcomes and predictors of transapical transcatheter mitral valve replacement: the Tendyne Expanded Clinical Study.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a therapeutic option for patients with severe mitral regurgitation (MR) who are ineligible for conventional surgery. There are limited data on the outcomes of large patient cohorts treated with TMVR. AIMS: This study aimed to investigate the outcomes and predictors of mortality for patients treated with transapical TMVR. METHODS: This analysis represents the clinical experience of all patients enrolled in the Tendyne Expanded Clinical Study. Patients with symptomatic MR underwent transapical TMVR with the Tendyne system between November 2014 and June 2020. Outcomes and adverse events up to 2 years, as well as predictors of short-term mortality, were assessed. RESULTS: A total of 191 patients were treated (74.1±8.0 years, 62.8% male, Society of Thoracic Surgeons Predicted Risk of Mortality 7.7±6.6%). Technical success was achieved in 96.9% (185/191), and there were no intraprocedural deaths. At 30-day, 1- and 2-year follow-up, the rates of all-cause mortality were 7.9%, 30.8% and 40.5%, respectively. Complete MR elimination (MR <1+) was observed in 99.3%, 99.1% and 96.3% of patients, respectively. TMVR treatment resulted in consistent improvement of New York Heart Association Functional Class and quality of life up to 2 years (both p<0.001). Independent predictors of early mortality were age (odds ratio [OR] 1.11; p=0.003), pulmonary hypertension (OR 3.83; p=0.007), and institutional experience (OR 0.40; p=0.047). CONCLUSIONS: This study investigated clinical outcomes in the full cohort of patients included in the Tendyne Expanded Clinical Study. The Tendyne TMVR system successfully eliminated MR with no intraprocedural deaths, resulting in an improvement in symptoms and quality of life. Continued refinement of clinical and echocardiographic risks will be important to optimise longitudinal outcomes.

Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass.

Cefazolin is an antibiotic used to prevent surgical site infections. During cardiac surgery with cardiopulmonary bypass (CPB), its efficacy target could be underachieved. We aimed to develop a population pharmacokinetic model for cefazolin in children and optimize the prophylactic dosing regimen. Children under 25 kg undergoing cardiac surgery with CPB and receiving cefazolin at standard doses (50 mg/kg IV every 4-6 h) were included in this analysis. A population pharmacokinetic model and Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) for efficacy and toxicity with the standard regimen and an alternative regimen of continuous infusion, where loading and maintenance doses were calculated from model-derived individual parameters. Twenty-two patients were included, with median (range) age, body weight, and eGFR of 19.5 (1-94) months, 8.7 (2-21) kg, and 116 (48-159) mL/min, respectively. Six patients received an additional dose in the CPB circuit. A two-compartment disposition model with an additional compartment for the CPB was developed, including weight-based allometric scaling and eGFR. For a 10 kg patient with eGFR of 120 mL/min/1.73 m2, clearance was estimated as 0.856 L/h. Simulations indicated that the standard dosing regimen fell short of achieving the efficacy target >40% of the time within a dosing duration and in patients with good renal function, PTA ranged from <20% to 70% for the smallest to the largest patients, respectively, at high MICs. In contrast, the alternative regimen consistently maintained target concentrations throughout the procedure for all patients while using a lower overall dose.

Prediction of Mortality and Heart Failure Hospitalization After Transcatheter Tricuspid Valve Interventions: Validation of TRISCORE.

BACKGROUND: Data on the prognostic role of the TRI-SCORE in patients undergoing transcatheter tricuspid valve intervention (TTVI) are limited. OBJECTIVES: The aim of this study was to evaluate the performance of the TRI-SCORE in predicting outcomes of patients undergoing TTVI. METHODS: TriValve (Transcatheter Tricuspid Valve Therapies) is a large multicenter multinational registry including patients undergoing TTVI. The TRI-SCORE is a risk model recently proposed to predict in-hospital mortality after tricuspid valve surgery. The TriValve population was stratified based on the TRI-SCORE tertiles. The outcomes of interest were all-cause death and all-cause death or heart failure hospitalization. Procedural complications and changes in NYHA functional class were also reported. RESULTS: Among the 634 patients included, 223 patients (35.2%) had a TRI-SCORE between 0 and 5, 221 (34.8%) had 6 or 7, and 190 (30%) had ≥8 points. Postprocedural blood transfusion, acute kidney injury, new atrial fibrillation, and in-hospital mortality were more frequent in the highest TRI-SCORE tertile. Postprocedure length of stay increased with a TRI-SCORE increase. A TRI-SCORE ≥8 was associated with an increased risk of 30-day all-cause mortality and all-cause mortality and the composite endpoint assessed at a median follow-up of 186 days (OR: 3.00; 95% CI: 1.38-6.55; HR: 2.17; 95% CI: 1.78-4.13; HR: 2.08, 95% CI: 1.57-2.74, respectively) even after adjustment for procedural success and EuroSCORE II or Society of Thoracic Surgeons Predicted Risk of Mortality. The NYHA functional class improved across all TRI-SCORE values. CONCLUSIONS: In the TriValve registry, the TRI-SCORE has a suboptimal performance in predicting clinical outcomes. However, a TRISCORE ≥8 is associated with an increased risk of clinical events and a lack of prognostic benefit after successful TTVI.

Transseptal BATMAN for High-Risk Valve-in-Ring Procedures: A Case Series.

Valve-in-ring procedures represent a feasible solution for high-risk patients with surgical repair failure. The risk of left ventricular outflow tract obstruction increases the challenge, and transcatheter approaches to prevent it are technically demanding and often do not resolve it. We demonstrate the feasibility and safety of a transseptal balloon-assisted translocation of the anterior mitral leaflet for valve-in-ring implantation.

Transcatheter edge-to-edge repair in papillary muscle injury complicating acute myocardial infarction.

AIMS: Acute mitral regurgitation (MR) in the setting of myocardial infarction (MI) may be the result of papillary muscle rupture (PMR). This condition is associated with high morbidity and mortality. We aim to evaluate the feasibility of transcatheter edge-to-edge mitral valve repair (TEER) in this acute setting. METHODS AND RESULTS: We analysed data from the International Registry of MitraClip in Acute Mitral Regurgitation following acute Myocardial Infarction (IREMMI) of 30 centres in Europe, North America, and the middle east. We included patients with post-MI PMR treated with TEER as a salvage procedure, and we evaluated immediate and 30-day outcomes. Twenty-three patients were included in this analysis (9 patients suffered complete papillary muscle rupture, 9 partial and 5 chordal rupture). The patients' mean age was 68 ± 14 years. Patients were at high surgical risk with median EuroSCORE II 27% (IQR 16, 28) and 20 out of 23 (87% were in cardiogenic shock). All patients were treated with vasopressors, and 17 out of 23 patients required mechanical support. TEER procedure was performed on the median 6 days after the index MI date IQR (3, 11). Procedural success was achieved in 87% of patients. The grade of MR was significantly decreased after the procedure. MR reduction to 0 or 1 + was achieved in 13 patients (57%), to 2 + in 7 patients (30%), P < 0.01. V-Wave was reduced from 49 ± 8 mmHg to 26 ± 10 mmHg post-procedure, P < 0.01. Sixteen out of 23 patients (70%) were discharged from hospital and 5 of them required reintervention with surgical mitral valve replacement. No additional death at 1 year was documented. CONCLUSIONS: TEER is a feasible therapy in critically ill patients with PMR due to a recent MI. TEER may have a role as salvage treatment or bridge to surgery in this population.

Impact of transcatheter heart valve type on outcomes of surgical explantation after failed transcatheter aortic valve replacement: the EXPLANT-TAVR international registry.

BACKGROUND: There are limited data on the impact of transcatheter heart valve (THV) type on the outcomes of surgical explantation after THV failure. AIMS: We sought to determine the outcomes of transcatheter aortic valve replacement (TAVR) explantation for failed balloon-expandable valves (BEV) versus self-expanding valves (SEV). METHODS: From November 2009 to February 2022, 401 patients across 42 centres in the EXPLANT-TAVR registry underwent TAVR explantation during a separate admission from the initial TAVR. Mechanically expandable valves (N=10, 2.5%) were excluded. The outcomes of TAVR explantation were compared for 202 (51.7%) failed BEV and 189 (48.3%) failed SEV. RESULTS: Among 391 patients analysed (mean age: 73.0±9.8 years; 33.8% female), the median time from index TAVR to TAVR explantation was 13.3 months (interquartile range 5.1-34.8), with no differences between groups. Indications for TAVR explantation included endocarditis (36.0% failed SEV vs 55.4% failed BEV; p<0.001), paravalvular leak (21.2% vs 11.9%; p=0.014), structural valve deterioration (30.2% vs 21.8%; p=0.065) and prosthesis-patient mismatch (8.5% vs 10.4%; p=0.61). The SEV group trended fewer urgent/emergency surgeries (52.0% vs 62.3%; p=0.057) and more root replacement (15.3% vs 7.4%; p=0.016). Concomitant cardiac procedures were performed in 57.8% of patients, including coronary artery bypass graft (24.8%), and mitral (38.9%) and tricuspid (14.6%) valve surgery, with no differences between groups. In-hospital, 30-day, and 1-year mortality and stroke rates were similar between groups (allp>0.05), with no differences in cumulative mortality at 3 years (log-rank p=0.95). On multivariable analysis, concomitant mitral surgery was an independent predictor of 1-year mortality after BEV explant (hazard ratio [HR] 2.00, 95% confidence interval [CI]: 1.07-3.72) and SEV explant (HR 2.00, 95% CI: 1.08-3.69). CONCLUSIONS: In the EXPLANT-TAVR global registry, BEV and SEV groups had different indications for surgical explantation, with more root replacements in SEV failure, but no differences in midterm mortality and morbidities. Further refinement of TAVR explantation techniques are important to improving outcomes.

Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.

BACKGROUND: The current World Health Organization (WHO) pediatric tuberculosis dosing guidelines lead to suboptimal drug exposures. Identifying factors altering the exposure of these drugs in children is essential for dose optimization. Pediatric pharmacokinetic studies are usually small, leading to high variability and uncertainty in pharmacokinetic results between studies. We pooled data from large pharmacokinetic studies to identify key covariates influencing drug exposure to optimize tuberculosis dosing in children. METHODS AND FINDINGS: We used nonlinear mixed-effects modeling to characterize the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide, and investigated the association of human immunodeficiency virus (HIV), antiretroviral therapy (ART), drug formulation, age, and body size with their pharmacokinetics. Data from 387 children from South Africa, Zambia, Malawi, and India were available for analysis; 47% were female and 39% living with HIV (95% on ART). Median (range) age was 2.2 (0.2 to 15.0) years and weight 10.9 (3.2 to 59.3) kg. Body size (allometry) was used to scale clearance and volume of distribution of all 3 drugs. Age affected the bioavailability of rifampicin and isoniazid; at birth, children had 48.9% (95% confidence interval (CI) [36.0%, 61.8%]; p < 0.001) and 64.5% (95% CI [52.1%, 78.9%]; p < 0.001) of adult rifampicin and isoniazid bioavailability, respectively, and reached full adult bioavailability after 2 years of age for both drugs. Age also affected the clearance of all drugs (maturation), children reached 50% adult drug clearing capacity at around 3 months after birth and neared full maturation around 3 years of age. While HIV per se did not affect the pharmacokinetics of first-line tuberculosis drugs, rifampicin clearance was 22% lower (95% CI [13%, 28%]; p < 0.001) and pyrazinamide clearance was 49% higher (95% CI [39%, 57%]; p < 0.001) in children on lopinavir/ritonavir; isoniazid bioavailability was reduced by 39% (95% CI [32%, 45%]; p < 0.001) when simultaneously coadministered with lopinavir/ritonavir and was 37% lower (95% CI [22%, 52%]; p < 0.001) in children on efavirenz. Simulations of 2010 WHO-recommended pediatric tuberculosis doses revealed that, compared to adult values, rifampicin exposures are lower in most children, except those younger than 3 months, who experience relatively higher exposure for all drugs, due to immature clearance. Increasing the rifampicin doses in children older than 3 months by 75 mg for children weighing <25 kg and 150 mg for children weighing >25 kg could improve rifampicin exposures. Our analysis was limited by the differences in availability of covariates among the pooled studies. CONCLUSIONS: Children older than 3 months have lower rifampicin exposures than adults and increasing their dose by 75 or 150 mg could improve therapy. Altered exposures in children with HIV is most likely caused by concomitant ART and not HIV per se. The importance of the drug-drug interactions with lopinavir/ritonavir and efavirenz should be evaluated further and considered in future dosing guidance. TRIAL REGISTRATION: ClinicalTrials.gov registration numbers; NCT02348177, NCT01637558, ISRCTN63579542.

Outcomes After Transcatheter Mitral Valve Replacement According to Regurgitation Etiology.

BACKGROUND: Whether transcatheter mitral valve replacement (TMVR) devices perform similarly with respect to the underlying mitral regurgitation (MR) etiology remains unknown. The aim of the present analysis was to assess outcomes of TMVR according to the MR underlying etiology among the CHoice of OptImal transCatheter trEatment for Mitral Insufficiency (CHOICE-MI) registry. METHODS: Of 746 patients, 229 patients (30.7%) underwent TMVR. The study population was subdivided according to primary, secondary, or mixed MR. Patients with mitral annular calcification were excluded. The primary study endpoint was a composite endpoint of all-cause mortality or hospitalization for heart failure at 1 year. Secondary study endpoints were all-cause and cardiovascular mortality at 1 year, New York Heart Association functional class, and residual MR, both at discharge and 1 year. RESULTS: The predominant MR etiology was secondary MR (58.4%), followed by primary MR (28.7%) and mixed MR (12.9%). Technical success and procedural mortality were similar according to MR etiology. Discharge echocardiography revealed residual MR 2+ in 11.3%, 3.7%, and 5.3% of patients with primary, secondary, and mixed MR, respectively (P = .1). MR elimination was similar in all groups up to the 1-year follow-up. There was no difference in terms of primary combined outcome occurrence according to MR etiology. One-year all-cause mortality was reported in 28.8%, 24.2%, and 32.1% of patients with primary, secondary, and mixed MR, respectively (P = .07). CONCLUSIONS: In our study we did not find differences in short-term and 1-year outcomes after TMVR according to MR etiology.

Acute Reduction in Left Ventricular Function Following Transcatheter Mitral Edge-to-Edge Repair.

Background Little is known about the impact of transcatheter mitral valve edge-to-edge repair on changes in left ventricular ejection fraction (LVEF) and the effect of an acute reduction in LVEF on prognosis. We aimed to assess changes in LVEF after transcatheter mitral valve edge-to-edge repair for both primary and secondary mitral regurgitation (PMR and SMR, respectively), identify rates and predictors of LVEF reduction, and estimate its impact on prognosis. Methods and Results In this international multicenter registry, patients with both PMR and SMR undergoing transcatheter mitral valve edge-to-edge repair were included. We assessed rates of acute LVEF reduction (LVEFR), defined as an acute relative decrease of >15% in LVEF, its impact on all-cause mortality, major adverse cardiac event (composite end point of all-cause death, mitral valve surgery, and residual mitral regurgitation grade ≥2), and LVEF at 12 months, as well as predictors for LVEFR. Of 2534 patients included (727 with PMR, and 1807 with SMR), 469 (18.5%) developed LVEFR. Patients with PMR were older (79.0±9.2 versus 71.8±8.9 years; P<0.001) and had higher mean LVEF (54.8±14.0% versus 32.7±10.4%; P<0.001) at baseline. After 6 to 12 months (median, 9.9 months; interquartile range, 7.8-11.9 months), LVEF was significantly lower in patients with PMR (53.0% versus 56.0%; P<0.001) but not in patients with SMR. The 1-year mortality was higher in patients with PMR with LVEFR (16.9% versus 9.7%; P<0.001) but not in those with SMR (P=0.236). LVEF at baseline (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=0.002) was predictive of LVEFR for patients with PMR, but not those with SMR (P=0.092). Conclusions Reduction in LVEF is not uncommon after transcatheter mitral valve edge-to-edge repair and is correlated with worsened prognosis in patients with PMR but not patients with SMR. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05311163.

Surgical Explantation of Failed Transcatheter Aortic Valve Replacement.

BACKGROUND: Recent reports have demonstrated worse than expected outcomes of surgical explantation after transcatheter aortic valve replacement (TAVR). However in-depth analysis of the short- and mid-term risk of concomitant cardiac surgery at the time of TAVR explant is lacking. METHODS: Data from the multicenter EXPLANT-TAVR registry of patients undergoing TAVR-explant between November 2009 and September 2020 were retrospectively analyzed. Patients undergoing concomitant procedures were included, but explants performed during the same admission as the initial TAVR or concomitant procedures performed on the aortic root, ascending aorta, or arch were excluded. Outcomes were evaluated between the isolated surgical aortic valve replacement (SAVR) and concomitant SAVR groups. Median follow-up was 6.6 months. RESULTS: Among 199 patients, concomitant SAVR was performed in 94 patients (47.2%), primarily with mitral valve surgery (n = 45) followed by coronary artery bypass grafting (n = 23). Despite similar mean ages between groups (72.8 vs 73.4 years), concomitant SAVR had a higher median Society of Thoracic Surgeons Predicted Risk of Mortality score at the index TAVR (5.9% vs 3.7%, P = .001). There were no differences in median time-to-explant between groups (12.9 vs 8.7 months, P = .78). However concomitant SAVR had longer mean cardiopulmonary bypass (166 vs 114 minutes, P = .001) and cross-clamp times (123 vs 81 minutes, P = .001). Both 30-day (16.7% vs 9.9%) and 1-year mortality (36.1% vs 22.1%) were higher with concomitant SAVR but did not reach statistical significance (both P > .05). On Kaplan-Meier analysis, actuarial estimates of cumulative survival were significantly lower with concomitant SAVR at 3 years (56.8% vs 81.1%, P = .020). CONCLUSIONS: For surgical explantation after TAVR failure, concomitant SAVR is associated with increased mortality. Further studies with longer follow-up are warranted to examine the benefit from earlier intervention before concomitant disease develops.

TRI-SCORE: a single-centre validation study.

OBJECTIVES: The TRI-SCORE is a recently published risk score for predicting in-hospital mortality in patients undergoing isolated tricuspid valve surgery (ITVS). The aim of this study is to externally validate the ability of the TRI-SCORE in predicting in-hospital and long-term mortality following ITVS. METHODS: A retrospective review of our institutional database was carried out to identify all patients undergoing isolated tricuspid valve repair or replacement from March 1997 to March 2021. The TRI-SCORE was calculated for all patients. Discrimination of the TRI-SCORE was assessed using receiver operating characteristic curves. Accuracy of the models was tested calculating the Brier score. Finally, a COX regression was employed to evaluate the relationship between the TRI-SCORE value and long-term mortality. RESULTS: A total of 176 patients were identified and the median TRI-SCORE was 3 (1-5). The cut-off value identified for increased risk of isolated ITVS was 5. Regarding in-hospital outcomes, the TRI-SCORE showed high discrimination (area under the curve 0.82), and high accuracy (Brier score 0.054). This score showed also very good performance in predicting long-term mortality (at 10 years, hazard ratio: 1.47, 95% confidence interval [1.31-1.66], P < 0.001), with high discrimination (area under the curve >0.80 at 1-5 and 10 years) and high accuracy values (Brier score 0.179). CONCLUSIONS: This external validation confirms the good performance of the TRI-SCORE in predicting in-hospital mortality. Moreover, the score showed also very good performance in predicting the long-term mortality.

Impact of Mitral Regurgitation Etiology on Mitral Surgery After Transcatheter Edge-to-Edge Repair: From the CUTTING-EDGE Registry.

BACKGROUND: Although >150,000 mitral TEER procedures have been performed worldwide, the impact of MR etiology on MV surgery after TEER remains unknown. OBJECTIVES: The authors sought to compare outcomes of mitral valve (MV) surgery after failed transcatheter edge-to-edge repair (TEER) stratified by mitral regurgitation (MR) etiology. METHODS: Data from the CUTTING-EDGE registry were retrospectively analyzed. Surgeries were stratified by MR etiology: primary (PMR) and secondary (SMR). MVARC (Mitral Valve Academic Research Consortium) outcomes at 30 days and 1 year were evaluated. Median follow-up was 9.1 months (IQR: 1.1-25.8 months) after surgery. RESULTS: From July 2009 to July 2020, 330 patients underwent MV surgery after TEER, of which 47% had PMR and 53.0% had SMR. Mean age was 73.8 ± 10.1 years, median STS risk at initial TEER was 4.0% (IQR: 2.2%-7.3%). Compared with PMR, SMR had a higher EuroSCORE, more comorbidities, lower LVEF pre-TEER and presurgery (all P < 0.05). SMR patients had more aborted TEER (25.7% vs 16.3%; P = 0.043), more surgery for mitral stenosis after TEER (19.4% vs 9.0%; P = 0.008), and fewer MV repairs (4.0% vs 11.0%; P = 0.019). Thirty-day mortality was numerically higher in SMR (20.4% vs 12.7%; P = 0.072), with an observed-to-expected ratio of 3.6 (95% CI: 1.9-5.3) overall, 2.6 (95% CI: 1.2-4.0) in PMR, and 4.6 (95% CI: 2.6-6.6) in SMR. SMR had significantly higher 1-year mortality (38.3% vs 23.2%; P = 0.019). On Kaplan-Meier analysis, the actuarial estimates of cumulative survival were significantly lower in SMR at 1 and 3 years. CONCLUSIONS: The risk of MV surgery after TEER is nontrivial, with higher mortality after surgery, especially in SMR patients. These findings provide valuable data for further research to improve these outcomes.

Feasibility and reliability of comprehensive three-dimensional transoesophageal echocardiography screening process for transcatheter mitral valve replacement.

AIMS: The procedural planning of transcatheter mitral valve replacement (TMVR) requires a specific imaging assessment to establish patient eligibility. Computed tomography (CT) is considered the reference method. In this setting, data regarding the role of transoesophageal echocardiography (TOE) are lacking. We evaluated the feasibility and reliability of a comprehensive 3D-TOE screening in TMVR candidates. METHODS AND RESULTS: We performed a retrospective observational study including 72 consecutive patients who underwent a pre-procedural CT and 3D-TOE for TMVR evaluation. The measurements of mitral annulus (MA), length of anterior mitral leaflet (AML), native left ventricular outflow tract (LVOT), and predicted neo-LVOT acquired with CT and 3D-TOE were compared using a novel semi-automated software for post processing analysis (3 mensio Structural Heart 10.1-3mSH, Pie Medical Imaging, Bilthoven, Netherlands). The final suitability decision was given by the valve manufacturer based on CT measurements and clinical conditions. Among 72 patients screened, all patients had adequate image quality for 3D-TOE analysis. 3D-TOE and CT measurements for AML length (r = 0.97), MA area (r = 0.90), perimeter (r = 0.68), anteroposterior (r = 0.88), and posteromedial-anterolateral (r = 0.74) diameters were found highly correlated, as well as for native LVOT (r = 0.86) and predicted neo-LVOT areas (r = 0.96) (all P-values <0.0001). An almost perfect agreement between CT and 3DTOE was found in assessing the eligibility for TMVR implantation (Cohen kappa 0.83, P < 0.001). CONCLUSION: 3D-TOE appraisements showed good correlations with CT measurements and high accuracy to predict TMVR screening success.

Aortic valve versus root surgery after failed transcatheter aortic valve replacement.

OBJECTIVE: We sought to determine outcomes of aortic valve replacement (AVR) versus root replacement after transcatheter AVR (TAVR) explantation because they remain unknown. METHODS: From November 2009 to September 2020, data from the EXPLANT-TAVR International Registry of patients who underwent TAVR explant were retrospectively reviewed, divided by AVR versus root replacement. After excluding explants performed during the same admission as the initial TAVR and concomitant procedures involving the other valves, 168 AVR cases were compared with 28 root replacements, and outcomes were reported at 30 days and 1 year. RESULTS: Among 196 patients (mean age, 73.5 ± 9.9 years) who had primary aortic valve intervention at TAVR explant, the median time from TAVR to surgical explant was 11.2 months (interquartile range, 4.4-32.9 months). Indications for explant were similar between the 2 groups. Compared with AVR, patients requiring root replacement had fewer comorbidities but more unfavorable anatomy for redo TAVR (52.6% vs 26.4%; P = .032), fewer urgent/emergency cases (32.1% vs 58.3%; P = .013), longer median interval from index TAVR to TAVR explant (17.6 vs 9.9 months; P = .047), and more concomitant ascending aortic replacement (58.8% vs 14.0%; P < .001). Median follow-up was 6.9 months (interquartile range, 1.4-21.6 months) after TAVR explant and 97.4% complete. Overall survival at follow-up was 81.2% with no differences between groups (log rank P = .54). In-hospital, 30-day, and 1-year mortality rates and stroke rates were not different between the 2 groups. CONCLUSIONS: In the EXPLANT-TAVR Registry, AVR and root replacement groups had different clinical characteristics, but no differences in short-term mortality and morbidities. Further investigations are necessary to identify patients at risk of root replacement in TAVR explant.

A Phase 2A Trial of the Safety and Tolerability of Increased Dose Rifampicin and Adjunctive Linezolid, With or Without Aspirin, for Human Immunodeficiency Virus-Associated Tuberculous Meningitis: The LASER-TBM Trial.

BACKGROUND: Drug regimens that include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in tuberculous meningitis (TBM). Safety data on their use in combination and in the context of human immunodeficiency virus (HIV) are needed to inform clinical trial design. METHODS: We conducted a phase 2, open-label, parallel-design, randomized, controlled trial to assess the safety of high-dose rifampicin, linezolid, and high-dose aspirin in HIV-associated TBM. Participants were randomized (1.4:1:1) to 3 treatment arms (1, standard of care [SOC]; 2, SOC + additional rifampicin [up to 35 mg/kg/d] + linezolid 1200 mg/d reducing after 28 days to 600 mg/d; 3, as per arm 2 + aspirin 1000 mg/d) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed. RESULTS: A total of 52 participants with HIV-associated TBM were randomized; 59% had mild disease (British Medical Research Council (MRC) grade 1) vs 39% (grade 2) vs 2% (grade 3). AESI or death occurred in 10 of 16 (63%; arm 3) vs 4 of 14 (29%; arm 2) vs 6 of 20 (30%; arm 1; P = .083). The cumulative proportion of AESI or death (Kaplan-Meier) demonstrated worse outcomes in arm 3 vs arm 1 (P = .04); however, only 1 event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (modified Rankin scale) between arms. CONCLUSIONS: High-dose rifampicin and adjunctive linezolid can safely be added to the standard of care in HIV-associated TBM. Larger studies are required to determine whether potential toxicity associated with these interventions, particularly high-dose aspirin, is outweighed by mortality or morbidity benefit. CLINICAL TRIALS REGISTRATION: NCT03927313.

Decreased Dolutegravir and Efavirenz Concentrations With Preserved Virological Suppression in Patients With Tuberculosis and Human Immunodeficiency Virus Receiving High-Dose Rifampicin.

BACKGROUND: Higher doses of rifampicin may improve treatment outcomes and reduce the duration of tuberculosis (TB) therapy. However, drug-drug interactions with antiretroviral therapy (ART) and safety in people with human immunodeficiency virus (HIV) have not been evaluated. METHODS: This was a randomized, open-label trial where newly diagnosed TB patients were randomized to higher (35 mg/kg) or standard (10 mg/kg) daily-dose rifampicin. ART treatment-naive patients were randomized to dolutegravir- or efavirenz-based ART. At week 6, trough dolutegravir or mid-dose efavirenz plasma concentrations were assayed. HIV viral load was measured at week 24. RESULTS: Among 128 patients randomized, the median CD4 count was 191 cells/mm3. The geometric mean ratio (GMR) for trough dolutegravir concentrations on higher- vs standard-dose rifampicin was 0.57 (95% confidence interval [CI], .34-.97; P = .039) and the GMR for mid-dose efavirenz was 0.63 (95% CI, .38-1.07; P = .083). There was no significant difference in attainment of targets for dolutegravir trough or efavirenz mid-dose concentrations between rifampicin doses. The incidence of HIV treatment failure at week 24 was similar between rifampicin doses (14.9% vs 14.0%, P = .901), as was the incidence of drug-related grade 3-4 adverse events (9.8% vs 6%). At week 8, fewer patients remained sputum culture positive on higher-dose rifampicin (18.6% vs 37.0%, P = .063). CONCLUSIONS: Compared with standard-dose rifampicin, high-dose rifampicin reduced dolutegravir and efavirenz exposures, but HIV suppression was similar across treatment arms. Higher-dose rifampicin was well tolerated among people with HIV and associated with a trend toward faster sputum culture conversion. CLINICAL TRIALS REGISTRATION: NCT03982277.