BACKGROUND Transcatheter edge-to-edge repair (TEER) has been increasingly used for selected patients with mitral regurgitation (MR), but limited data are available regarding clinical outcomes in... Show moreBACKGROUND Transcatheter edge-to-edge repair (TEER) has been increasingly used for selected patients with mitral regurgitation (MR), but limited data are available regarding clinical outcomes in patients with varied etiology and mechanism of MR.OBJECTIVES The aim of this study was to evaluate the outcomes of TEER according to etiology and left ventricular (LV) and left atrial remodeling.METHODS Consecutive patients who underwent TEER between 2007 and 2020 were included in the analysis. Among patients with functional MR (FMR), those with predominant LV remodeling were classified as having ventricular FMR (v-FMR), whereas those without LV remodeling but predominant left atrial remodeling were classified as having atrial FMR (a-FMR). The primary outcome was a composite of all-cause mortality and heart failure hospitalization at 2 years and was compared among patients with degenerative MR (DMR), a-FMR, and v-FMR.RESULTS A total of 1,044 patients (11% with a-FMR, 48% with v-FMR, and 41% with DMR) with a mean Society of Thoracic Surgeons score of 8.6 +/- 7.8 underwent TEER. Patients with a-FMR had higher rates of atrial fibrillation and severe tricuspid regurgitation with larger left and right atria, whereas patients with v-FMR had lower LV ejection fractions with larger LV dimensions. Residual MR more than moderate at discharge was not significantly different among the 3 groups (5.2% vs 3.2% vs 2.6%; P = 0.37). Compared with patients with DMR, 2-year event rates of the primary outcome were significantly higher in patients with a-FMR and v-FMR (21.6% vs 31.5% vs 42.3%; log-rank P < 0.001).CONCLUSIONS Despite excellent procedural outcomes, patients with a-FMR and v-FMR had worse clinical outcomes compared with those with DMR. (c) 2022 by the American College of Cardiology Foundation. Show less
OBJECTIVES This study sought to evaluate the prognostic value of an increased mean mitral valve pressure gradient (MVG) in patients with primary mitral regurgitation (MR) after transcatheter edge... Show moreOBJECTIVES This study sought to evaluate the prognostic value of an increased mean mitral valve pressure gradient (MVG) in patients with primary mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER).BACKGROUND Conflicting data exist regarding impact of increased mean MVG on outcomes after TEER.METHODS This study included 419 patients with primary MR (mean age 80.6 +/- 10.4 years; 40.6% female) who underwent TEER. Patients were divided into quartiles (Qs) based on discharge echocardiographic mean MVG. Primary outcome was the composite endpoint of all-cause mortality and heart failure hospitalization. Secondary outcomes included all-cause mortality and the secondary composite endpoint of all-cause mortality, heart failure hospitalization, and mitral valve reintervention.RESULTS The median number of MitraClips used was 2 per patient. MR reduction <= moderate was achieved in 407 (97.1%) patients. Mean MVG was 1.9 +/- 0.3 mm Hg, 3.0 +/- 0.1 mm Hg, 4.0 +/- 0.1 mm Hg, and 6.0 +/- 1.2 mm Hg in Q1, Q2, Q3, and Q4, respectively. There was no significant differences across quartiles in the primary outcome (15.4%, 19.6%, 22.0%, and 21.9% in Q1-Q4, respectively; P = 0.63), all-cause mortality (15.9% vs 18.6% vs 19.4% vs 17.1%, respectively; P = 0.91), and the secondary composite endpoint at 2 years (33.3% vs 29.5% vs 22.0% vs 31.6%, respectively; P = 0.37). After multivariate adjustment for baseline clinical and procedural variables, the mean MVG in Q4 compared with Q1 to Q3 was not independently associated with the primary outcome (HR: 1.22; 95% CI: 0.82-1.83; P = 0.33), allcause mortality, and the secondary composite endpoint.CONCLUSIONS Increased mean MVG was not independently associated with adverse events after TEER in patients with primary MR. (C) 2022 by the American College of Cardiology Foundation. Show less
Background: Left ventricular (LV) global longitudinal strain (GLS) is a sensitive marker of LV function and may help identify patients with heart failure (HF) and secondary mitral regurgitation who... Show moreBackground: Left ventricular (LV) global longitudinal strain (GLS) is a sensitive marker of LV function and may help identify patients with heart failure (HF) and secondary mitral regurgitation who would have a better prognosis and are more likely to benefit from edge-to-edge transcatheter mitral valve repair with the MitraClip. The aim of this study was to assess the prognostic utility of baseline LV GLS during 2-year follow-up of patients with HF with secondary mitral regurgitation enrolled in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation trial. Methods: Patients with symptomatic HF with moderate to severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT) were randomized to transcatheter mitral valve repair plus GDMT or GDMT alone. Speckle-tracking-derived LV GLS from baseline echocardiograms was obtained in 565 patients and categorized in tertiles. Death and HF hospitalization at 2-year follow-up were the principal outcomes of interest. Results: Patients with better baseline LV GLS had higher blood pressure, greater LV ejection fraction and stroke volume, lower levels of B-type natriuretic peptide, and smaller LV size. No significant difference in outcomes at 2-year follow-up were noted according to LV GLS. However, the rate of death or HF hospitalization between 10 and 24 months was lower in patients with better LV GLS (P = .03), with no differences before 10 months. There was no interaction between GLS tertile and treatment group with respect to 2-year clinical outcomes. Conclusions: Baseline LV GLS did not predict death or HF hospitalization throughout 2-year follow-up, but it did predict outcomes after 10 months. The benefit of transcatheter mitral valve repair over GDMT alone was consistent in all subgroups irrespective of baseline LV GLS. (J Am Soc Echocardiogr 2021;34:955-65.) Show less
Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.Genome-wide association studies have... Show moreFine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes. Show less
Aims We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring... Show moreAims We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)].Methods and results From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 +/- 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation >= moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27 - 3.12; P 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29 - 8.51; P < 0.001].Conclusion The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV. Show less
OBJECTIVES The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR).BACKGROUND LVOT obstruction... Show moreOBJECTIVES The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR).BACKGROUND LVOT obstruction is a major concern with TMVR, but limited data exist regarding its predictors and impact on outcomes.METHODS Patients with pre-procedural multidetector row computed tomography (MDCT) undergoing TMVR for failed mitral bioprosthetic valves (valve-in-valve), annuloplasty rings (valve-in-ring), and mitral annular calcification (valve-in-MAC) were included in this study. Echocardiographic and procedural characteristics were recorded, and comprehensive assessment with MDCT was performed to identify the predictors of LVOT obstruction (defined as an increment of mean LVOT gradient >= 10 mm Hg from baseline). The new LVOT (neo-LVOT) area left after TMVR was estimated by embedding a virtual valve into the mitral annulus on MDCT, simulating the procedure.RESULTS Among 194 patients with pre-procedural MDCT undergoing TMVR (valve-in-valve, 107 patients; valve-in-ring, 50 patients; valve-in-MAC, 37 patients), LVOT obstruction was observed in 26 patients (13.4%), with a higher rate after valve-in-MAC than valve-in-ring and valve-in-valve (54.1% vs. 8.0% vs. 1.9%; p < 0.001). Patients with LVOT obstruction had significantly higher procedural mortality compared with those without LVOT obstruction (34.6% vs. 2.4%; p < 0.001). Receiver-operating characteristic curve analysis showed that an estimated neo-LVOT area <= 1.7 cm(2) predicted LVOT obstruction with sensitivity of 96.2% and specificity of 92.3%.CONCLUSIONS LVOT obstruction after TMVR was associated with higher procedural mortality. A small estimated neo-LVOT area was significantly associated with LVOT obstruction after TMVR and may help identify patients at high risk for LVOT obstruction. (c) 2019 by the American College of Cardiology Foundation. Show less
Ghoussaini, M.; Edwards, S.L.; Michailidou, K.; Nord, S.; Lari, R.C.S.; Desai, K.; ... ; Australian Ovarian Canc Management 2018
