Thaden, Jeremy J.

Background: Atrial fibrillation (AF) in severe aortic stenosis (AS) is associated with worse outcomes compared to sinus rhythm (SR). The prevalence of AF and its impact on outcomes in very severe AS (vsAS) is unknown. Objectives: To determine the prevalence and prognostic significance of AF in vsAS. Methods: A total of 563 patients with vsAS (transaortic valve peak velocity ≥5 m/sec) were identified retrospectively out of 3139 with aortic valve area ≤1.0 cm 2 or ≤0.6 cm 2 /m 2 and left ventricular ejection fraction (LVEF) ≥50%. Patients were divided by rhythm (AF vs SR) at the time of index transthoracic echocardiogram. Outcomes in AF versus SR were compared in propensity-matched analyses (2 SR:1 AF). Results: AF was present in 50/563 patients (9%) and SR in 513/563 (91%). In propensity-matched analyses (100 SR:50 AF), the mean age was 83.2±7.3 years, 54% were female. There was no difference in comorbidity index (p=0.84). There was no difference in AF compared to SR in aortic valve area (0.7±0.1 vs 0.7±0.1 cm 2 , p=0.94), peak velocity (5.3±0.3 vs 5.3±0.3 m/sec, p=0.32), LVEF (63±7 vs 65±7%, p=0.14) or E/e’ (23±13 vs 21±12, p=0.48), but patients with AF had larger left atrial volume index (60±16 vs 48±15 mL/m 2 , p<0.001), higher right ventricular systolic pressure (52±15 vs 41±16 mmHg, p<0.001), and higher prevalence of moderate or more tricuspid regurgitation (33% vs 5%, p<0.001) and right ventricular systolic dysfunction (23% vs 6%, p=0.003). Age-, sex-, comorbidity index-adjusted all-cause mortality was higher in AF vs SR (HR 2.33 [1.40, 3.87], p=0.001) ( Figure: Observed overall survival ). Aortic valve replacement (AVR) was associated with improved survival (HR 0.44 [0.25, 0.76], p=0.004) with no evidence of interaction of AVR and rhythm (p=0.15). Conclusion: AF was not uncommon among patients with vsAS and identified a subset of patients with vsAS at much higher risk of mortality. Whether AVR should be considered earlier in vsAS when associated with AF needs to be investigated.

Background Description of cerebral and retinal infarction in patients with bicuspid aortic valve (BAV) is limited to case reports. We aimed to characterize cerebral and retinal infarction and examine outcomes in patients with BAV. Methods and Results Consecutive patients from 1975 to 2015 with BAV (n=5401) were retrospectively identified from the institutional database; those with confirmed cerebral or retinal infarction were analyzed. Infarction occurring after aortic valve replacement was not included. Patients were grouped according to infarction pathogenesis: embolism from a degenerative calcific BAV (BAVi); non‐BAV, large artery atherosclerotic or lacunar infarction (LAi); and non‐BAV, non‐large artery embolic infarction (nLAi). There were 83/5401 (1.5%) patients, mean age 54±12 years and 28% female, with confirmed cerebral or retinal infarction (LAi 23/83 [28%]; nLAi 30/83 [36%]; BAVi 26/83 [31%]; other 4/83 [5%]). Infarction was embolic in 72/83 (87%), and 35/72 (49%) were cardioembolic. CHA 2 DS 2 ‐VASc score was 1.4±1.2 in BAVi ( P =0.188 versus nLAi) and 2.3±1.2 in LAi ( P =0.005). Recurrent infarction occurred in 41% overall (50% BAVi, P =0.164 and 0.803 versus LAi and nLAi). BAVi was more commonly retinal (39% BAVi versus 13% LAi, P =0.044 versus 0% nLAi, P =0.002). Patients with BAVi and LAi were more likely to have moderate‐to‐severe aortic stenosis and undergo aortic valve replacement compared with patients with nLAi. Conclusions Cardioembolism, often from degenerative calcification of the aortic valve, is a predominant cause of cerebral and retinal infarction in patients with BAV and is frequently recurrent. Cerebral and retinal infarction should be regarded as a complication of BAV.

Abstract Aims Aortic stenosis (AS) induces characteristic changes in left ventricular (LV) mechanics that can be reversed after aortic valve replacement (AVR). We aimed to comprehensively characterize LV mechanics before and after AVR in patients with severe AS and identify predictors of short-term functional recovery and long-term survival. Methods and results We prospectively performed comprehensive strain analysis by 2D speckle-tracking echocardiography in 88 patients with severe AS and LV ejection fraction ≥50% (mean age 71 ± 12 years, 42% female) prior to and within 7 days after AVR. Patients were followed for up to 5.2 years until death from any cause or last encounter. Within days after AVR, we observed an absolute increase in global longitudinal strain (GLS) (−16.0 ± 2.0% vs. −18.5 ± 2.1%, P&lt;0.0001) and a decrease in apical rotation (10.5 ± 4.0° vs. 8.3 ± 2.8°, P = 0.0002) and peak systolic twist (18.2 ± 5.0° vs. 15.5 ± 3.8°, P = 0.0008). A baseline GLS is less negative than −16.2% was 90% sensitive and 67% specific in predicting a ≥ 20% relative increase in GLS. During a median follow-up of 3.8 years, a global circumferential systolic strain rate (GCSRs) less negative than −1.9% independently predicted lower survival. Conclusion In patients with severe AS, a reversal in GLS, apical rotation, and peak systolic twist abnormalities towards normal occurs within days of AVR. Baseline GLS is the strongest predictor of GLS recovery but neither was associated with long-term survival. In contrast, abnormal baseline GCSRs are associated with worse outcomes.

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.

Abstract Background Topological data analysis (TDA) is the state-of-the-art unsupervised machine learning framework that can provide insight into the dataset and visualize condensed information via the topological network graph. This robust approach was never used to assess the heterogeneous MitraClip population. Purpose We aim to develop a TDA model that will identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the population and their outcomes. Method Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the institutional database for baseline and follow-up data. Thirteen variables were used for TDA. The topological network graph was created using the Python Scikit-TDA Kepler-Mapper package (v. 2.0.1), and clustering was performed at the graph level with Louvain's modularity method. Kaplan-Meier survival analysis was used to assess the all-cause mortality endpoint of each cluster identified in an unsupervised manner. The dataset with cluster labels was also used to train a Light Gradient Boosted Machine model, and SHapley Additive exPlanations (SHAP) analysis was applied to determine the feature importance. Results A total of 389 consecutive patients were included in the final analysis and two major clusters consisting of 384 patients were identified. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean Society of Thoracic Surgeons Mitral Valve Replacement risk score was 9.6±6.9%. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among the two clusters (HR: 2.38; 95% CI: 1.39–4.06, p=0.001; Figure 1). Clusters 1 (n=195) was associated with &gt; mild residual mitral regurgitation and worse survival performance and was characterized with worse tricuspid regurgitation severity, a higher proportion of patients with atrial fibrillation/flutter, anterior leaflet prolapse, and mitral annular/leaflet calcification, as summarized in Table 1. Conclusion TDA can identify distinct phenotype clusters with prognostic significance in MitraClip patients based on mitral valve morphology and clinical risk factors. This simple model can facilitate clinical risk stratification for MitraClip patients regarding procedural success and survival performance. Funding Acknowledgement Type of funding sources: None.

Background Many patients with symptomatic severe aortic stenosis do not undergo aortic valve replacement (AVR) despite clinical guidelines. This study analyzed the association of managing provider type with cardiac specialist follow‐up, AVR, and mortality for patients with newly diagnosed severe aortic stenosis (sAS). Methods and Results We identified adults with newly diagnosed sAS per echocardiography performed between January 2017 and March 2019 using Optum electronic health record data. We then selected from those meeting all eligibility criteria patients managed by a primary care provider (n=1707 [25%]) or cardiac specialist (n=5039 [75%]). We evaluated the association of managing provider type with cardiac specialist follow‐up, AVR, and mortality, as well as the independent association of cardiac specialist follow‐up and AVR with mortality, within 1 year of echocardiography detecting sAS. A subgroup analysis was limited to patients with symptomatic sAS. Patient characteristics and comorbidities at baseline were used for covariate‐adjusted cause‐specific and multivariable Cox proportional hazard models assessing group differences in outcomes by managing provider type. An adjusted Cox proportional hazard model with additional time‐dependent covariates for follow‐up and AVR was used to assess these practices' association with mortality. Within 1 year of echocardiography detecting sAS, data revealed that primary care provider management was associated with lower rates of cardiac specialist follow‐up (hazard ratio [HR], 0.47 [95% CI, 0.43–0.50], P <0.0001) and AVR (HR, 0.58 [95% CI, 0.53–0.64], P <0.0001) and with higher 1‐year mortality (HR, 1.45 [95% CI, 1.26–1.66], P <0.0001). Cardiac specialist follow‐up and AVR were independently associated with lower mortality (follow‐up: HR, 0.55 [95% CI, 0.48–0.63], P <0.0001; AVR: HR, 0.70 [95% CI, 0.60–0.83], P <0.0001). Results were similar for patients with symptomatic sAS. All analyses were adjusted for baseline patient characteristics and comorbidities. Conclusions For patients newly diagnosed with sAS, we observed differences in rates of cardiac specialist follow‐up and AVR and risk of mortality between primary care provider‐ versus cardiologist‐managed patients with sAS. In addition, a lower likelihood of receiving follow‐up and AVR was independently associated with higher mortality.

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.

A significant proportion of patients diagnosed with symptomatic severe aortic stenosis (ssAS) do not receive treatment with aortic valve replacement (AVR) despite current ACC/AHA guidelines. Delayed care leads to increased hospitalizations, worsening heart failure and death. Timely referral to a cardiac specialist is a critical step in the treatment pathway. We sought to identify the impact of managing provider type on follow-up care for newly diagnosed patients with severe aortic stenosis (sAS). We analyzed Optum® electronic medical records to identify adults with a new outpatient sAS echo diagnosis in the pre-COVID era (1/2017 - 3/2019). We identified integrated delivery network patients alive 1d post echo excluding those with missing data or AVR within 3d of echo, then selected those managed by a primary care provider (PCP) or a cardiologist (n=5,683). Baseline characteristics were used for covariate-adjusted Cumulative Incidence Function and Fine-Gray subdistribution hazard models. We estimated the impact of managing provider type on the specialist follow-up visit rate (cardiologist, interventional cardiologist and/or cardiothoracic surgeon) for all sAS patients and of surgical or transcatheter AVR for ssAS patients within 1 year of diagnosis. Within 90d of sAS diagnosis, 47% of PCP- vs. 73% of cardiologist-managed patients had a follow-up visit (1-year rates: PCP, 69% vs. cardiologist, 90%; Hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.49-0.59, p<0.0001). Within 1 year of diagnosis, 36% of PCP- vs. 51% of cardiologist-managed ssAS patients underwent AVR (HR=0.72, CI: 0.63-0.82, p<0.0001) (Figure). Analysis suggests lower referral rates for PCP- than cardiologist-managed patients. In ssAS, 1-year AVR rates were low, particularly for PCPs. These data underscore the importance of timely follow up of all severe AS patients for symptom assessment and appropriate treatment, presenting an opportunity for initiatives to drive behavior change.

AbstractBackgroundTranscatheter mitral valve replacement (TMVR) has emerged as a feasible alternative to redo surgical mitral valve replacement (SMVR) in patients with degenerated mitral prostheses, with limited comparative data.MethodsWe compared mid‐term outcomes in patients with degenerated mitral valve prostheses treated with TMVR or redo SMVR. The primary endpoint was survival at 5 years of follow‐up.ResultsFrom 2014 to 2020, 215 patients presented with degenerated mitral valve prostheses. Of whom 86 (40%) were treated with TMVR (75[87%] valve‐in‐valve and 11[13%] valve‐in‐ring), while 129 patients (60%) underwent SMVR. The TMVR cohort was older (p < 0.0001), more symptomatic (p = 0.0003) and had more chronic lung disease (p = 0.02), worse renal function (p = 0.02) and higher right ventricular systolic pressures (p < 0.0001). Thirty‐day mortality was lower with TMVR versus SMVR (2.4% vs. 10.2%, OR4.69 [95% CI 1.25–30.5], p = 0.04) with probability of mortality at 1, 2, and 5 years being 14.7% versus 17.5%, 24.5% versus 20.7%, and 49.9% versus 34.0%, respectively. Mode of prosthesis degeneration, baseline hemodynamics, and valve selection did not appreciably impact outcomes.ConclusionsTMVR for degenerated mitral prostheses is associated with better early survival compared to SMVR despite a greater burden of comorbidities. In contrast, 5 year survival rates appear more favorable with SMVR, which may reflect the lower baseline risk of this population. Clinical, hemodynamic, and echocardiographic follow‐up support the mid‐term durability of TMVR for degenerated mitral prostheses. Further dedicated studies, however, are required to optimize outcomes in this challenging patient cohort and to navigate the choice of approach for each individual patient.

Abstract Aims Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR. Methods and results In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all-cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00–4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13–9.47; P = 0.028). In the overall cohort, mitral annulus diameter &lt; 3 cm (OR 1.74, 95% CI 1.02–2.97; P = 0.041) and QRS duration &lt; 115 ms (OR 1.73, 95% CI 1.00–2.98; P = 0.049) were independently associated with improvement in MR. During median follow-up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90–3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40–8.05; P &lt; 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44–3.47; P = 0.68). Conclusions In nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter &lt; 3 cm and QRS duration &lt; 115 ms in the overall population were associated with MR improvement. Post-operative improvement in organic MR was associated with better survival.