Oh, J K

Abstract Background Elevated left ventricular filling pressure (LVFP) is associated with an increased risk of heart failure and mortality. Pulmonary artery wedge pressure (PAWP) is considered the gold standard for assessing LVFP. Recently, we validated an artificial intelligence-enabled electrocardiogram (AI-ECG) to assess LV diastolic function (LVDF) and LVFP. Herein, we compare AI-ECG with PAWP in predicting long-term mortality. Methods We included adults who had comprehensive echocardiography with available ECG within 14-days and right-heart-catheterization (RHC) within 30-days of echocardiography. Elevated-LVFP was defined as PAWP>15 mmHg by RHC, grades 2-3 LVDF by echocardiography, or as adjudicated by the AI-ECG algorithm. Prognosis by AI-ECG was compared to that by echocardiography and PAWP. Results Among 4,168 patients (median age 64 years, 47.7% female), 1,841 had normal-LVFP, and 2,327 had elevated-LVFP by RHC. Echocardiography classified 1,502 patients as normal-LVFP, 1,643 as elevated-LVFP, and 1,023 as indeterminate-LVFP. AI-ECG demonstrated an area-under-the-curve of 0.879 (95%-confidence-interval 0.867-0.891) for predicting elevated-LVFP as determined by echocardiography and 0.742 (95%-confidence-interval 0.724-0.759) for predicting elevated-LVFP as determined by RHC. Over a median follow-up of 7.7 years, 2,735 (34.4%) patients died. In multivariable models, elevated-LVFP by any modality was associated with an increased risk of death (AI-ECG: adjusted-hazard-ratio 1.80, 95% confidence-interval 1.55-2.09; echocardiography: adjusted-hazard-ratio 1.74, 95% confidence-interval 1.51-2.02; PAWP: adjusted-hazard-ratio 1.26, 95% confidence-interval 1.11-1.43). AI-ECG-derived LVFP provided incremental prognostic discrimination compared to echocardiography- or RHC-derived LVFP. Conclusions AI-ECG-derived LVFP offers an accessible, affordable, and noninvasive alternative for detecting elevated LVFP, with potential independent prognostic value beyond traditional echocardiographic and invasive assessments.Survival across LVFP concordance

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 > 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.

Abstract Background The MITRAL Trial (Mitral Implantation of TRAnscatheter vaLves) evaluates the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with severe mitral valve disease with mitral annular calcification (MAC), failed surgical rings or failed bioprostheses. Purpose We sought to evaluate 4-year outcomes of patients enrolled in the MITRAL trial. Methods This is a prospective study that enrolled 91 high surgical risk patients at 13 sites in the U.S. 30 patients underwent Mitral Valve-in-Valve (MViV), 30 Valve-in-Ring (MViR) and 31 Valve-in-MAC (ViMAC). 4-year outcomes of these patients were evaluated in this analysis. Primary endpoints and key serious adverse events including deaths were adjudicated by an independent Clinical Events Committee. Cardiac computed tomography (CT) and echocardiographic images were evaluated by independent CT and Echocardiographic Core Laboratories. Results Mean age was 74.3±8.9 years. Most patients undergoing MViV and ViMAC were female (MVIV=63.3%, MViR=36.7% and ViMAC=71%). Mean STS score was 9.2±6.6% (MViV 10.2±6.5%, MViR 8.7±4.7%, ViMAC=8.6±8.2%). All-cause mortality at 4 years was higher for ViMAC and MViR: MViV=6.9% (cardiovascular 3.4%), MViR=48.1% (cardiovascular 18.5%), ViMAC=51.9% (cardiovascular 29.6%), p=0.002 (Figure 1). At 4 years, all survivors had ≤1+ mitral regurgitation and most had none or trace mitral regurgitation (MViV=87.5, MViR=33.3% and ViMAC=100%). Mean mitral valve gradients remained stable (MViV=5.9±2.2 mmHg, MViR= 6.6±5.1 mmHg, ViMAC=5.1±1.0 mmHg), Figure 2. Most survivors experienced significant improvement of symptoms and were in NYHA class I-II at 4-year follow-up (MViV=78.9%, MViR=66.7% and ViMAC=66.7%). Conclusions MViV is associated with excellent outcomes at 4 years. MViR and ViMAC were associated with higher mortality at 4 years. However, most survivors in all groups experienced sustained improvement of symptoms and stable THV performance at 4 years. Whether survival bias had an impact on THV performance and improved symptoms at follow-up is not known and deserves further evaluation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted Research Grant from Edwards Lifesciences.

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Prior studies have demonstrated abnormalities of diastolic function are independent predictors of heart failure and all-cause mortality. The optimal way to classify diastolic function has continued to evolve over time, particularly in those with preserved left ventricular ejection fraction. A notable change in the 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guidelines is that individuals with impaired myocardial relaxation and normal filling pressure can be classified as normal diastolic function. Purpose To determine whether the association of diastolic dysfunction with increased risk of all-cause mortality is driven by cardiovascular or non-cardiovascular death. Second, to evaluate if the presence of an impaired myocardial relaxation inflow pattern without other diastolic abnormalities conveys a marker of increased risk. Methods This study utilized the Olmsted County Heart Function Study (OCHFS), a well characterized prospective adult community cohort with comprehensive echocardiography between 2001 and 2004 and long-term follow-up. Only individuals with measurable diastolic function were included (n = 1,104). Those with reduced left ventricular ejection fraction, more than moderate valve disease, or a clinical diagnosis of heart failure (n = 52); or indeterminate diastolic function (n = 47) were excluded. Diastolic function was assessed by the current Mayo Clinic diagnostic algorithm (Figure). Results A total of 695 individuals were classified as normal, 265 with impaired myocardial relaxation or grade 1 diastolic dysfunction, and 45 with grade 2-3 diastolic dysfunction. Those with diastolic dysfunction were older and had more comorbidities including diabetes, hypertension and coronary disease (Table). There were 264 deaths in the median follow up period of 15.2 years (IQR 14.4 – 18.0), including 173 non-cardiovascular and 81 cardiovascular deaths. Both cardiovascular and non-cardiovascular mortality were associated with the presence and grade of diastolic dysfunction (Table 1). Individuals classified as normal by 2016 ASE/EACVI criteria, but grade 1 by the Mayo algorithm had an increased risk of all-cause mortality after univariate analysis (HR 4.35, 95% CI (3.35, 5.65), p < 0.0001) compared to normal subjects and remained associated after adjustment for age (HR 1.55, 95% CI (1.15, 2.09), p < 0.0001. Subjects with a grade 1 pattern had a higher rate of cardiovascular mortality (ꭕ2 70.1, p < 0.0001). Conclusions Individuals with diastolic dysfunction, including those with an impaired relaxation mitral inflow, were at increased risk of mortality, particularly cardiovascular mortality. This study highlights the importance of separating grade 1 diastolic dysfunction from normal in the assessment of diastolic function as it represents a clinically significant risk marker of myocardial disease. Abstract Figure. Abstract Figure.

Abstract Background Noninvasive parameters of LV filling pressure (E/e’) and pulmonary pressures (RVSP) by Doppler echocardiography correlate with functional capacity and outcome in sinus rhythm (SR). Their role in AF is less clear. Elevated left ventricular filling pressures (E/e’) and pulmonary artery systolic pressures (PASP) by Doppler stress echocardiography correlate with impaired functional capacity in patients in sinus rhythm (SR). However, there is limited data in atrial fibrillation (AF). Purpose The aim of this study was to delineate the characteristics of patients with AF referred for exercise stress echocardiography and determine the prevalence and significance of E/e’ and PASP elevations in AF. Methods Subjects were patients referred for exercise treadmill stress echocardiography (n= 14,937) and underwent regional wall motion assessment, Doppler assessment of mitral inflow (E) and early tissue relaxation (e’) velocities and PASP at rest and immediately following maximum symptom limited exercise. Exclusion criteria included significant valvular heart disease (moderate or greater stenosis and/or regurgitation of any cardiac valve or previous valve repair or replacement) (1%), congenital heart disease (<1%) or refusal to participate in research (<1%). Results Patients with AF (n = 310, 2%) were older (71 ± 10 vs 59 ± 13 years, p < 0.001). While resting blood pressure was similar, resting heart rates were higher in AF (80 ± 17 bpm vs 73 ± 13 bpm, p < 0.0001). AF patients achieved lower workloads (6.4 ± 2.4 METS vs 9 ± 2.4 METS, p < 0.001) with lower peak double products (22336 ± 6677 vs 25148 ± 5438, p < 0.001). Rates of resting (27% vs 10%, p < 0.0001) and exercise-induced (37% vs 20%, p < 0.0001) regional wall motion abnormalities were higher in AF. Mean E/e’ was higher in AF at rest (12 ± 5 vs 9 ± 3, p < 0.001) and with exercise (12 ± 5 vs 10 ± 4, p < 0.001), with a higher percentage of patients in AF having E/e’ ≥15 at rest (20% vs 6% in SR, p= <0.001) and with exercise in (23% vs 8%, p < 0.001). PASP was higher in AF at rest (33 ± 8 mm Hg vs 28 ± 6 mm Hg, p < 0.001) and with exercise (48 ± 12 vs 42 ± 11, p < 0.001) compared to SR. E/e’ correlated with exercise capacity in AF and in SR, with an E/e’ cutoff of 11.7 that was best predictive of impaired functional capacity (< 5 METS in women and < 7 METS in men). Conclusions Abnormalities of E/e’ and PASP are more prevalent in patients with AF and correlate with impaired functional capacity. In patients with AF, a medial E/e’ ratio of ≥ 12 immediately following exercise is best associated with impaired functional capacity.

Abstract Background Currently data on the risk stratification of patients with moderate aortic stenosis (AS) are very limited. Method Patients diagnosed with moderate AS in 2012 (aortic valve area [AVA]: >1 and ≤1.5cm2) were identified. Patients were stratifying by LV diastolic function (normal vs high filling pressure), left ventricular ejection fraction (LVEF ≥50 vs <50%) and stroke volume index (SVI ≥35 vs <35 ml/m2). High filling pressure was defined as average E/e' ≥14 or septal E/e' ≥11 when atrial fibrillation was present. The prognosis was compared to age- and sex-matched general population. Results 898 patients were included (age 74 years, 58% male, AVA 1.25 cm2). During a median follow-up of 2.9 years, there were 346 deaths. In patients with moderate AS, mortality was higher than expected (P<0.001, Fig 1A). LV high filling pressure, LVEF<50% and SVI<35ml/m2 were present in 416 (55%), 140 (17%) and 81 (9%) patients, respectively. Those with normal filling pressure had similar prognosis when compared to controls (Fig 1C, P=0.35); whereas mortality rates remained higher than reference even when LVEF≥50% or SVI≥35ml/m2 (Fig 1E, 1G, P<0.001). Amongst all groups, mortality rates were the highest in patients with LVEF <50% or SVI <35 ml/m2 (Fig 1D, 1F, P<0.001); mortality ratios were 3.78 (95% CI 3.01–4.67) and 6.91 (95% CI 5.13–9.11), respectively. Noteworthy, high filling pressure allowed further risk stratification when LVEF or SVI was preserved (Fig 2, P<0.001). Figures 1 & 2 Conclusions Patients with moderate AS showed poor survival. A clinical trial examining role of aortic valve replacement would be beneficial not only in patients with reduced LVEF or SVI but also in those with high LV filling pressures.