Rihal, Charanjit S.

AbstractBackgroundElevated transmitral gradient post transcatheter mitral valve edge‐to‐edge repair (TEER) has been associated with worse outcomes. Whether an elevated baseline transmitral diastolic mean gradient (MG) ≥5 mmHg is associated with hemodynamic outcomes after TEER is unknown.MethodsA total of 164 consecutive patients undergoing TEER at Mayo Clinic between June 2014 and May 2018 were analyzed in this retrospective study. Baseline demographics, as well as clinical, echocardiographic, and procedural data were obtained. Data on direct left atrial pressure (LAP) before and after TEER were recorded. Logistic regression models were constructed to evaluate the association between preprocedure transmitral diastolic mean gradient (pre‐MG) and (1) improvement in LAP following TEER, (2) postprocedure transmitral diastolic mean gradient (post‐MG). A decrease in LAP post TEER was considered an improvement in hemodynamic response. Pre‐MG was categorized as: ≥5 and <5 mmHg.ResultsMedian age of the cohort was 81.5 years (Q1: 76.3, Q3: 87) and 34% were female. At baseline, median transmitral diastolic MG was 4 mmHg (Q1: 3, Q3: 5) and median LAP was 19 mmHg (Q1:16, Q3: 23.5). In a multivariable model, adjusted for age and sex, patients with pre‐MG ≥ 5 mmHg were less likely to see an improvement in LAP post TEER (adjusted odds ratio [aOR]: 0.22, 95% confidence interval [CI]: 0.09, 0.55; p = 0.001) and more likely to have elevated post‐MG (aOR; 7.08, 95% CI: 2.93, 17.13; p < 0.001).ConclusionHigher pre‐MG (≥5 mmHg) was associated with a lower reduction in LAP and higher residual transmitral gradient following TEER suggesting other potential contributors to increased LAP besides mitral regurgitation as a cause of elevated baseline MG.

Abstract OBJECTIVES Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR. METHODS We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (&lt;60% or ≥60% predicted) and NT-Pro-BNP (&lt;1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years. RESULTS Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90–96)] and 5 [45.3% (95% CI: 35.4–58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69–83)] and 5 years [13.1% (95% CI: 7–25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6–3.2, P &lt; 0.001) with 25.7% of patients in New York Heart Association class III–IV. Patients in groups B and C had intermediate outcomes. CONCLUSIONS The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.

Background: Prior studies have reported conflicting results of persistent iatrogenic atrial septal defect (iASD) and its impact following a transcatheter edge-to-edge repair (TEER) procedure. This study aims to evaluate the incidence of iASD and its clinical and hemodynamic impact after a TEER. Methods: Consecutive patients who underwent a TEER procedure from June 2014 to September 2020 at the Mayo Clinic were identified. The presence of iASD was retrospectively identified on post-procedure transthoracic echocardiography (TTE) to group patients into an iASD+ group and an iASD− group for comparison of prognosis and cardiac function. Results: A total of 316 patients were included; the mean age was 79.1 ± 9.1 years, and 67.7% were male. Persistent iASD was diagnosed in 108 (34.2%) patients. There was no difference concerning all-cause mortality, heart failure hospitalization, and stroke/TIA between groups at follow-up (median follow-up of 9 months). Post-procedure TTE demonstrated no differences regarding right ventricle (RV) and left ventricle (LV) dimensions and function, including TAPSE (15.2 ± 4.6 vs. 15.4 ± 5.5 mm, p = 0.875), and LV ejection fraction (51.1 ± 14.0% vs. 51.3 ± 13.9%, p = 0.933). However, patients with iASD had higher RV systolic pressure (48.7 ± 14.4 vs. 45.5 ± 14.5 mmHg, p = 0.042) compared with patients without iASD. Conclusion: Notwithstanding higher RV pressures, patients with persistent iASD had no hemodynamic compromise and an equal prognosis compared with those without a residual atrial defect after a TEER procedure. These findings support the mid-term safety of procedures in which an interatrial defect needs to be created and would argue against the need for interventional closure.

Background: Left ventricular outflow tract obstruction may occur following transcatheter mitral valve replacement in the setting of mitral annular calcification. Methods: We present a case series whereby preemptive septal radiofrequency ablation (RADIO-TMVR) was used to augment the left ventricular outflow tract for transcatheter mitral valve replacement in 4 patients at risk for left ventricular outflow tract obstruction despite alcohol septal ablation. Results: All patients were female, average age of 74.9 (68.8–80.4) years. Baseline ejection fraction was 71% (63%–75%). Mean mitral valve area was 1.28 (range, 1.0–1.59) cm 2 . Mean mitral valve gradient at rest was 9.5 (range, 7–11) mm Hg. New York Heart Association symptoms were III to IV at baseline. Patients underwent preemptive septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement a range between 69 and 154 days after alcohol septal ablation. Procedural time was 384 (337–424) minutes with a fluoroscopic time of 31 (14–71) minutes. Radiofrequency ablation time was 132 (100–175) minutes. As anticipated, 3 patients developed complete heart block and underwent pacemaker implantation, whereas 1 had a preexisting pacemaker. One patient developed groin hematoma and heart failure exacerbation. There were no peri-procedural deaths. Preemptive septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement resulted in septal end-diastolic wall thickness reduction compared with baseline (28.6%, 30.4%, 30.3%, and 11.1%) and following alcohol septal ablation (23.1%, 12%, 8.5%). Valve replacement in the setting of mitral annular calcification was performed in all patients 89 (range, 38–45) days after preemptive septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement. Two patients had concomitant laceration of the anterior mitral leaflet to further augment the neo-left ventricular outflow tract. Postprocedure, New York Heart Association symptoms improved to class I (3 patients) and class II (1 patient). Conclusions: In at-risk individuals, preemptive septal radiofrequency ablation may be an effective strategy at preventing left ventricular outflow tract obstruction with transcatheter mitral valve replacement.

Background The management of severe mitral regurgitation (MR) after transcatheter edge‐to‐edge repair (TEER) remains a clinical conundrum. Considering the growing volume of TEER, more outcomes data for mitral surgery in this cohort are needed. Methods and Results Symptomatic patients with persistent or recurrent severe MR after TEER evaluated between May 2014 and June 2021 were included. The primary outcome was all‐cause mortality in patients who were treated with surgery versus medical therapy. The Kaplan–Meier and Cox regression methods were used to report risk‐adjusted survival analyses. Among the 142 included patients, 44 (31.0%) underwent mitral surgery. Patients who underwent surgery were younger than those treated medically (74.1±8.9 versus 78.6±10.5 years, P =0.01). Major comorbidities were similar except obesity, sleep apnea, left ventricular dimensions, and ejection fraction. Society of Thoracic Surgeons Predicted Risk of Operative Mortality was 9.0±4.7 versus 7.9±4.9 in the surgical versus medical therapy groups, respectively, P =0.22. Time from TEER to detection of severe MR was similar in both groups (median [interquartile range] 97.5 [39.5–384] versus 93.5 [40–389] days in the surgical versus medical groups, respectively [ P >0.05]). In the surgical group, valve replacement was performed in all patients. Operative mortality was 4.5% (observed/expected ratio 0.55), and major complications were uncommon. After risk‐adjustment, surgery was associated with significantly lower all‐cause mortality (adjusted hazard ratio, 0.33 [95% CI, 0.12–0.92], P =0.001) compared with medial therapy. Conclusions Compared with medical therapy, mitral surgery in patients with severe persistent or recurrent MR after TEER is associated with lower mortality despite the high‐risk profile of these patients. Patients with severe MR after TEER should be considered for surgery at a referral mitral surgical center.

Abstract Background Transcatheter mitral edge-to-edge repair (TEER) with MitraClip offers a less invasive alternative for patients with severe, symptomatic mitral regurgitation (MR) who are considered high risk for surgery. However, patient selection for TEER remains challenging given the variability in underlying MR pathology and current discordance among studies regarding predictors of procedural efficacy and clinical outcomes. Purpose This study aimed to assess acute procedural changes and long-term outcomes in patients who underwent TEER according to the proportionality of MR, defined as the ratio of the effective regurgitant orifice area (EROA) and left ventricular end-diastolic volume (LVEDV). Methods We analyzed patients who underwent TEER at our institution between 2014 and 2020 with available biplane left ventricular volume measurement. Relevant clinical comorbidities, demographics, and anthropometrics, along with pertinent pre- and post-procedural echocardiogram measurements, were obtained by review of the electronic medical record. The EROA to LVEDV index was calculated for all patients who were then stratified by quartiles. Patients with an EROA/LVEDV index in the lowest quartile were defined as having the most proportionate MR and those with an index in the highest quartile were defined as the most disproportionate MR. Baseline and post-TEER parameters were used to assess acute procedural and longitudinal outcomes. Results Baseline clinical and echocardiographic parameters of the 230 subjects according to quartile are shown in the table. Following TEER, there was a larger reduction in the left ventricular end-diastolic diameter and increased MR reduction with increasingly disproportionate MR (p=0.03 and p=0.05, respectively). The change in ejection fraction pre- versus post-TEER did not significantly differ across groups (p=0.64). Median follow up time was 1.7 (0.7–3.5) years; mortality occurred in 77 patients (33.5%) and heart failure hospitalizations occurred in 20 patients (8.7%) during follow up. No significant difference in all-cause mortality or post-procedural heart failure hospitalizations was identified across groups. Conclusions In our series, patients with proportionate MR were similarly symptomatic to those with disproportionate MR but had less severe MR with increased comorbidities. Post-TEER MR grade was similar between groups. Longer-term follow up in larger groups of patients is needed to determine the clinical implications. Funding Acknowledgement Type of funding sources: None.

Background TAILOR‐PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype‐guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss‐of‐function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex‐specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional‐hazards models. Among 5276 randomized patients, loss‐of‐function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P =0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P =0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value ( P int =0.59) or BARC bleeding ( P int =0.47) nor for sex and genotype (MACE P int =0.15, and BARC bleeding P int =0.60). Conclusions CYP2C19 loss‐of‐function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype‐guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01742117.

Background The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification. Methods and Results A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification–related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4–76.7 years), and 53.3% were women. The median MVA was 1.7 cm 2 (1.3–2.3 cm 2 ) and MVG was 7.3 mm Hg (5.3–10.3 mm Hg); left ventricular end‐diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7–4.5 years), there were 63 deaths; 1‐ and 5‐year survival were 76% and 40%, respectively. There was no association between left ventricular end‐diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm 2 ; 95% CI, 0.34–0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05–1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm 2 ; 95% CI, 0.33–0.79) while MVG was not. Conclusions In patients with mitral annular calcification–related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.

AbstractBackgroundMitral transcatheter edge‐to‐edge repair (MTEER) is an established therapeutic approach for mitral regurgitation (MR). Functional mitral regurgitation originating from atrial myopathy (A‐FMR) has been described.ObjectivesWe sought to assess the clinical, echocardiographic and hemodynamic considerations in A‐FMR patients undergoing MTEER.MethodsFrom 2014 to 2020, patients undergoing MTEER for degenerative MR (DMR), functional MR (FMR), and mixed MR were assessed. A‐FMR was defined by the presence of MR > moderate in severity; left ventricular (LV) ejection fraction (LVEF) ≥ 50%; and severe left atrial (LA) enlargement in the absence of LV dysfunction, leaflet pathology, or LV tethering. The diagnosis of A‐FMR (vs. ventricular‐FMR [V‐FMR]) was confirmed by three independent echocardiographers. Baseline characteristics, procedural outcomes as well as clinical and echocardiographic follow‐up are reported. Device success was defined as final MR grade ≤ moderate; MR reduction ≥1 grade; and final transmitral gradient <5 mmHg.Results306 patients underwent MTEER, including DMR (62%), FMR (19%), and mixed MR (19%). FMR cases included 37 (63.8%) V‐FMR and 21 (36.2%) A‐FMR. Tricuspid regurgitation (≥ moderate) was higher in A‐FMR (80.1%) compared to V‐FMR (54%) and DMR (42%). Device success did not significantly differ between A‐FMR and V‐FMR (57% vs. 73%, p = 0.34) or DMR (57% vs. 64%, p = 1.0). The A‐FMR cohort was less likely to achieve ≥3 grades of MR reduction compared to V‐FMR (19% vs. 54%, p = 0.01) and DMR (19% vs. 49.7%, p = 0.01). Patients with V‐FMR and DMR demonstrated significant reductions in mean left atrial pressure (LAP) and peak LA V‐wave, though A‐FMR did not (LAP −0.24 ± 4.9, p = 0.83; peak V‐wave −1.76 ± 9.1, p = 0.39). In follow‐up, echocardiographic and clinical outcomes were similar.ConclusionsIn patients undergoing MTEER, A‐FMR represents one‐third of FMR cases. A‐FMR demonstrates similar procedural success but blunted acute hemodynamic responses compared with DMR and V‐FMR following MTEER. Dedicated studies specifically considering A‐FMR are needed to discern the optimal therapeutic approaches.

Introduction: Unsupervised machine learning (ML) can provide insight into a dataset without significant expert time for annotation and labeling, but was never used to assess the heterogeneous MitraClip population. Hypothesis: We hypothesized that unsupervised k-means ML could identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the dataset. Methods: Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the Mayo institutional NCDR database for baseline and follow-up data. Variables with ≥ 50% missing data were excluded. A k-means algorithm was used for clustering analysis. Input variables were grouped according to 4 distinct k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 389 consecutive patients were included in the final analysis, and 95 unique variables were used. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean STS MV Replace score was 9.1±5.7. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among clusters (Figure 1). The cluster (cluster 2, n=120) with best survival performance (all-cause mortality 3.3%) had features of non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation. Cluster 3 (n=66) had the worst survival performance (all-cause mortality 27.3%) and opposite features than cluster 2. Conclusions: Unsupervised ML can identify distinct phenotype clusters with prognostic significance in MitraClip patients. Patients with non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation are intrinsically different from other MitraClip patients and should be considered the potential optimal candidates.