Thaden, Jeremy J.

ABSTRACT Background Incident atrial functional mitral regurgitation (AFMR) is associated with mortality. Transcatheter edge‐to‐edge repair (TEER) has shown effectiveness in improving MR and symptoms in AFMR, but previous studies lacked comparison to conservative management. We aimed to study the association of AFMR severity and mitral TEER with symptoms, heart failure hospitalizations (HFH) and all‐cause mortality in moderate/severe AFMR. Methods Consecutive adults with moderate/severe AFMR managed conservatively or with TEER 2010−2023 were identified retrospectively. To ensure similar technique in evaluation in the two groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group. In addition to multivariable analysis, the association of TEER (vs. conservative management) with HFH and mortality was assessed using propensity‐score matched analyses; the propensity score was based on age, sex, EuroSCORE II, effective regurgitant orifice area, integrative MR severity, and NYHA class III/IV (vs. I/II). Results Among 230 patients with moderate/severe AFMR [mean age 77; 56% females], 46 were managed with TEER. Severe (vs. moderate) AFMR was independently associated with baseline NYHA class III/IV (multivariable OR 2.18 [95% CI 1.13−4.26]) and HFH [multivariable HR 2.75 (95% CI 1.25−6.03)] but not mortality ( p = 0.26). TEER improved MR to ≤ moderate in 93% but was not associated with lower HFH or death rates versus conservative management on multivariable or matched analysis. However, 1‐year NYHA improved more with TEER versus conservative management in patients with baseline NYHA class III/IV (62% vs. 27%, p = 0.03). Rhythm control was associated with improved survival (HR 0.38 [0.15−0.98]). Conclusions AFMR severity was associated with symptoms and HFH but not mortality. MR severity and NYHA class improved with TEER, but the association of TEER with HF hospitalizations or death remains unproven. Randomized studies are needed to evaluate the potential role of TEER and rhythm control on outcomes in AFMR.

Abstract Aims To develop a deep learning model that: (i) utilizes transthoracic echocardiography (TTE) clips to detect left ventricular (LV) enlargement without being provided information regarding a patient’s sex and body size; and (ii) can be accurately applied to clips acquired using either standard comprehensive TTE or handheld cardiac ultrasound (HCU). Methods and results Using retrospective TTE data (training: 8722 patients; internal validation: 468 patients), we developed a deep learning model that estimates a patient’s end-diastolic LV volume (indexed to body surface area and normalized across the sexes), and then thresholds this estimate to perform the following classifications: (1) normally sized LV vs. ≥ mild LV enlargement; (2) normal/mildly enlarged LV vs. ≥ moderate LV enlargement. For retrospective datasets, the model showed strong performance in TTE across three geographically distinct locations (Minnesota and Wisconsin: 1082 patients, AUC = 0.925 and 0.953 for classifications 1 and 2, respectively; Arizona: 1475 patients, AUC = 0.935 and 0.969; and Florida: 1481 patients, AUC = 0.934 and 0.970). Additionally, performance was strong for both TTE and HCU clips collected from a prospective cohort of 410 patients who underwent HCU immediately following TTE (TTE: AUC = 0.925 and 0.971; HCU: AUC = 0.874 and 0.902, for classifications 1 and 2, respectively). Conclusion An automated deep learning model applied to TTE or HCU images accurately categorizes LV volumes. These results lay a foundation for future work aimed at optimizing clinical outcomes for heart failure patients by enabling early detection of LV enlargement across various point-of-care settings.

Abstract Background/Introduction Close monitoring of aortic stenosis (AS) by follow-up echocardiography is recommended by all Cardiology and Imaging Societies’ guidelines. Whether these guidelines are strictly followed is unknown. Purpose We aimed to describe our institution’s practice patterns for echocardiographic monitoring in patients with aortic sclerosis (AScl) and AS of any severity. Methods Adult patients residing in our institution’s county with an echocardiographic diagnosis of AScl or AS between 01/2005-01/2022 were identified and classified into 4 groups: AScl, mild AS, moderate AS, or severe AS, at each echocardiogram during the study timeframe. Kaplan Meier analyses were used to evaluate the composite outcome, the occurrence of follow-up echocardiogram or death. Patients were censored at the time of aortic valve replacement/repair, heart transplant, or last clinical follow-up. Guideline follow-up was considered appropriate when the primary outcome occurred by 5 years (AScl/mild AS), 2 years (moderate AS), and 1 year (severe AS). Results A total of 23,726 echocardiograms from 9,578 unique patients were included. At index echocardiogram, median patient age was 74 years (IQR 65-82) and 4,806 (50.2%) were women. AScl was observed in 7,358 (76.8%) cases, mild AS in 1,442 (15.1%) cases, moderate AS in 479 (5%), and severe AS in 301 (3.1%) cases. Rates of composite outcome achievement by the end of the guideline-recommended interval were 81%, 90%, 80%, and 72% in AScl, mild, moderate, and severe AS, respectively. Rates for men were 83%, 92%, 82%, and 75% in these groups, while rates for women were 78%, 88%, 78%, and 68%, respectively (Figure 1). Follow-up rates were similar before and after 2012 (when transcatheter aortic valve replacement was approved for treatment of severe AS in high-risk surgical patients in the USA). Follow-up rates were higher in patients managed by cardiovascular providers compared to non-cardiovascular providers (Figure 2). Conclusion Depending on disease severity, between one fourth and one tenth of patients remained alive and unfollowed at the end of their guideline-recommended surveillance interval. There is significant variability in echocardiogram monitoring based on sex and referring provider specialty. Figure 1 Figure 2

Abstract Background Transthoracic echocardiography is the primary modality used for the assessment of the pericardial space. Guidelines recommend semi-qualitative assessment of the size of a pericardial effusion with characterization as trace, small, moderate or large. The reproducibility and association of this characterization is variable. Whether simple 2D-based quantitative measures of effusion size better associate with pericardial volumes is unclear. An accurate measure of pericardial volume would be helpful for tracking patients over time. Purpose To test whether 2D-based measures of the pericardial space could accurately predict pericardial volumes. Methods We retrospectively assessed a series of echos performed immediately prior to pericardiocentesis. 2D-based area tracings from the parasternal long and short axis at the papillary muscle level as well as 2D volumetric tracings from the apical 4 chamber view using the Simpson's method were tested with the operator blinded to the true pericardial volume (recorded at pericardiocentesis). Patients who underwent pericardiocentesis in setting of acute perforation were excluded as were patients where pericardiocentesis was unsuccessful or incomplete. Pericardial fluid area or volume was calculated by taking the difference between the measures obtained by tracing the epicardial border of the heart and pericardium (figure 1). Results The median pericardiocentesis (n=118) fluid volume was 500 mL (IQR 350 – 750 mL) with a range, 95–2300 mL. The pericardial fluid was serous (22%), sero-sanguineous (37%) and sanguineous in 41%. The effusion was malignant in 24 cases and due to inflammation in 42 cases. Pericardial area traces from either the parasternal short (r=0.56, p<.0001) or long axis (r=0.62, p<.0001) correlated modestly with measured pericardial volume. The average volume estimated echocardiographically by the Simpson’s method was 580 ± 359 mL (range, 85.8–2419 mL). There was stronger linear correlation between echocardiographic (apical 4-chamber measurement) and pericardiocentesis-derived volumes (r=0.92, p < 0.0001; figure 2A). Etiology of the pericardial effusion was not associated with estimates of pericardial volumes. There was a large overlap in pericardial volume amongst the reading physician qualitative grading of effusion size (figure 2B). Categorization of pericardial effusion size was improved when based on volumetric estimates (Kappa 0.65) rather than physician estimates (Kappa 0.32; Figure 2B). Variation between measured pericardial volume and actual pericardial volume was most related to the quality of the image and the likely extent to which the pericardial fluid was not entirely captured in the image window. Conclusion Two-dimensional transthoracic echocardiography using biplane Simpson’s method of disks can simply and reasonably accurately estimate the pericardial effusion volume. This technique may add value in the serial assessment of pericardial effusions. Figure 2

Abstract Background/Introduction Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) in patients with TR and to investigate their association with outcomes. Various echo parameters have emerged that assess RV-PA coupling, including the ratio of TAPSE to RV systolic pressure (RVSP) and the PA pulsatility index (PAPi). The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the measure of the pulmonary vascular load that the RV must overcome to eject blood into the PA. PA Ea is simple to estimate by echo and found to be an independent haemodynamic risk measure in various left heart and pulmonary hypertension (PH) diseases. Whether PA Ea discriminates risk in unselected patients with significant TR and how it compares to other measures of RV-PA coupling is untested. Purpose To ascertain the prognostic value of PA Ea in patients with TR. Methods In consecutive patients with a first diagnosis of ≥ moderate TR (regardless of aetiology), we compared all-cause mortality at five years based on the PA Ea (defined as the RVSP/stroke volume as measured by transthoracic echocardiography). As stroke volume was measured by Doppler at the left ventricular (LV) outflow tract, patients with > moderate aortic valve regurgitation were excluded. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score was calculated as previously described. PA Ea was separated into 4 groups for comparison based on the separation of quartiles of PA Ea rounded to one decimal place. Results In the 13,608 patients studied, PA Ea could be calculated in 12,682 patients (94.4%). The median PA Ea was 0.68 mmHg/mL (IQR 0.50, 0.92). Increasing levels of PA Ea were associated with clinical comorbidities including heart failure, liver and kidney disease and clinical markers of risk such as the TRIO score. Increasing levels of PA Ea were also associated with larger RVs, worse RV systolic function, higher NT-pro BNP levels, and greater degrees of right heart failure (Table). Each quartile of PA Ea was associated with a significant increase in all-cause mortality (Figure). After adjusting for age and sex, PA Ea was associated with higher risk of death (HR 2.41 (2.28-2.56); p<.0001). While worsening degrees of PA Ea correlated with both declining levels of TAPSE/PASP and PAPi (Table), PA Ea was independently predictive of outcome in a combined model: PA Ea HR 1.65 (1.51-1.80, Chi-squ 120, p<.0001); PAPi HR 0.84 (0.80-0.89, Chi-squ 48, p<.0001) and TAPSE/PASP HR 0.32 (017-0.60, Chi-squ 12, p=.0004). Conclusion(s) In patients with significant TR, PA Ea is highly feasible and higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify disease severity in patients with significant TR. Table Assoc. of PA Ea with mortality in TR

ABSTRACTBackgroundMitral transcatheter edge‐to‐edge repair (TEER) is a minimally invasive therapy for severe mitral regurgitation (MR) in patients with high surgical risk. TEER results in a tissue bridge that decreases mitral valve area, potentially leading to elevated mean gradient. The clinical impact of elevated gradient on outcomes is unclear.MethodsThis systematic review and meta‐analysis was based on a comprehensive search of five databases. We included studies that evaluated post mitral TEER gradient on one of the following outcomes: all‐cause mortality, combined endpoints, symptoms, hospitalizations, and mitral valve re‐intervention. Meta‐analysis was conducted using the random‐effects model.ResultsOut of 6458 citations, 17 studies were included (2017−2024) reporting on 7748 patients. There was significant heterogeneity between studies related to the cutoff used to define elevated gradient, etiology of MR, and outcomes. Elevated mitral gradient post TEER (4, 4.5, 5 mmHg) was associated with worse combined endpoint (HR = 1.35, 95% CI 1.07−1.71; I2 64%), but not all‐cause mortality (HR = 1.25, 95% CI 0.97−1.59; I2 45%) or risk of hospitalization. For the combined endpoint, this association was mainly significant in patients who had mitral gradient assessed using discharge echocardiogram (HR = 1.39, 95% CI 1.07−1.81; I2 62%) for all patients and for those with degenerative MR.ConclusionDespite the heterogeneity between studies, the current analysis suggests that patients with elevated mitral gradient post TEER are at risk of worse clinical outcomes, particularly in patients who had mitral gradient assessed using discharge transthoracic echocardiogram.

Abstract Introduction Aortic stenosis (AS) presents diagnostic challenges, especially in patients with discordant low gradient AS (LGAS), i.e., small aortic valve area (AVA) and low Doppler mean gradient (MG). LGAS is associated with worse outcomes compared to concordant AS. Aortic valve calcium score (AVCS) is a measure of AS severity independent of flow and helps diagnose severe AS. It is unknown if the degree of discordance in AVCS and MG is of any clinical significance. A high AVCS/MG ratio may indicate impaired ventricular function and response to pressure overload despite preserved LVEF, potentially contributing to worse outcomes. Purpose This study aims to elucidate the prognostic significance of the AVCS/MG ratio in patients with severe AS and preserved left ventricular ejection fraction (LVEF) undergoing TAVR. We hypothesized a higher AVCS/MG ratio correlates with increased mortality. Methods Patients who underwent transcatheter aortic valve replacement (TAVR) from 2010 to 2020 for native valve severe AS with LVEF≥50% were identified from an institutional database. AVCS were obtained within 90 days of pre-TAVR echocardiography. Patients were divided into tertiles based on their AVCS/MG ratio. Primary outcome was overall mortality. Results The analysis included 1067 patients (mean age 79±9 years, 43% female); overall AVA was 0.80±0.14 cm², LVEF 63±6%, MG 46±12 mmHg, AVCS 2630±1528 AU, and AVCS/MG ratio 58±31. Patients stratified by AVCS/MG tertiles showed no difference in overall comorbidity index across tertiles (Figure 1). However, the group in the highest tertile was the oldest (80±8 vs 79±8 vs 77±9 years), predominantly male (87% vs 61% vs 24%), with the highest prevalent atrial fibrillation (44% vs 28% vs 25%) and stroke volume index <35 mL/m² (16% vs 11% vs 5%). 9-year survival was 15% vs 25% vs 36% (p<0.001, Figure 2). In multivariate analysis adjusted for age, sex, comorbidities, LVEF and AVA, AVCS/MG ratio was independently associated with increased risk of mortality (HR 1.005; 95% CI [1.001-1.008], p=0.005). Conclusion Higher AVCS/MG discordance is associated with increased risk of mortality following TAVR. Serial AVCS measurements during progressive AS may help identify patients at higher risk who may potentially benefit from earlier aortic valve intervention.

Introduction: A significant portion of patients with aortic stenosis (AS) have low-gradient AS (LGAS) defined as aortic valve area ≤ 1.0 cm 2 and a trans-aortic mean systolic gradient and peak velocity < 40 mmHg and < 4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Etiologies for LGAS include diastolic dysfunction, heart failure, other significant valvular disease, and atrial fibrillation (AF). AF is associated with worse outcomes compared to sinus rhythm (SR) in HGAS. AF is common in LGAS, but whether AF is associated with worse outcomes versus SR in LGAS has not been elucidated. Hypothesis: We hypothesize that AF is associated with higher mortality compared to SR in patients with LGAS. Methods: We retrospectively identified and reviewed charts of patients who were diagnosed with LGAS on transthoracic echocardiogram (TTE) from 2010-2020 at Mayo Clinic. Patient were classified according to rhythm at the time of TTE and history of AF was ascertained among those in SR. Patents were divided into 3 groups; SR without history of AF (group 1), SR with history of AF (group 2), and AF during TTE (group 3). Primary endpoints of overall mortality and cardiac mortality were ascertained. Results: A total of 3400 patients were included: n=2036 in group 1, n=519 in group 2, and n=845 in group 3. After adjusting for age, sex, and the Charlson index, group 2 and group 3 patient had significantly higher overall mortality (HR 1.22 and HR 1.52, respectively, p<0.0001 for both) and cardiac mortality (HR 1.37 and HR 2.05, respectively, p<0.0001 for both), Figure . Conclusions: In LGAS, AF is a significant prognostic indicator of overall mortality and cardiac mortality. LAGS associated with AF may need different management strategies given the higher mortality associated with the presence of AF.

Introduction: Acceleration time (AT) and Doppler Velocity Index (DVI) are critical parameters in assessment of bioprosthetic aortic valve dysfunction (BAVD). AT>100ms and DVI < 0.25 are highly suggestive of prosthetic obstruction and are incorporated in all triage algorithms. Little is known about their relationship with flow. Hypothesis: AT and DVI may be affected by transprosthetic flow in patients with significant bioprosthetic aortic valve dysfunction (BAVD). Methods: Single center, retrospective analysis of patients with severe BAVD (confirmed at surgical re-replacement, transcatheter valve-in-valve implantation, or successfully treated bioprosthetic valve thrombosis). Standard prosthetic parameters (AT, DVI, effective orifice area (EOA), mean gradient, presence and degree of regurgitation), flow (stroke volume index, Svi; transprosthetic flow rate, FR) were measured on the transthoracic echocardiogram at the time of diagnosis with severe BAVD. Results: A total of 266 patients with severe BAVD underwent treatment between 2008-2020. BAVD mechanism was obstruction (N=192, 72%), regurgitation (n=48, 18%) mixed stenosis and regurgitation (n=15, 6%) and patient-prosthetic mismatch (n=12, 5%). DVI was moderately correlated with FR (r=0.50, p<0.001); AT had a weak but significant inverse correlation with FR (r=0.24, p<0.001). SVi had a weaker influence on DVI (r=0.35, p<0.001) and no correlation with AT. Conclusions: AT and DVI are influenced by transprosthetic flow rate. This flow-dependency should be considered when assessing the mechanism of BAVD.

Background: The bicuspid aortic valve (BAV) exhibits abnormal geometry and transvalvular flow and is susceptible to calcification with subsequent cardioembolic stroke from calcific embolic material. However, the description of embolic ischemic strokes in patients with BAV is limited to case reports. Methods: Consecutive patients from 1975-2015 with BAV (n=5401) at our institution were retrospectively identified. Patients with ischemic stroke before aortic valve replacement (AVR) were analyzed, and the stroke was characterized. Patients were grouped according to stroke etiology: calcific embolism from a BAV (BAV stroke); large artery atherosclerotic or lacunar stroke (LA stroke); and non-BAV, non-large artery embolic stroke (nLA stroke). Results: There were 83/5401 (1.5%) patients with ischemic stroke. Mean age was 54 ± 12 years and 28% were female. Stroke etiology was BAV stroke in 26/83 (31%), LA stroke in 23/83 (28%), nLA stroke in 30/83 (36%), and other in 4/83 (5%). Stroke was embolic in 72/83 (87%), as shown in Figure 1. CHA 2 DS 2 -VASc score was not different in patients with BAV stroke (1.4 ± 1.2) versus nLA stroke (1.8 ± 1.2, p=0.188) but was higher in LA stroke (2.3 ± 1.2, p=0.005 vs. BAV stroke). Recurrent stroke occurred in 41% overall (50% BAV stroke vs. 30% LA stroke vs. 47% nLA stroke, both p=NS vs. BAV stroke). BAV stroke was more commonly located in the retinal circulation (39% BAV stroke vs. 13% LA stroke [p=0.044] vs. 0% nLA stroke [p=0.002]). Patients with BAV and LA stroke were more likely to have moderate-to-severe aortic stenosis and undergo AVR sooner after stroke compared to patients with nLA stroke. Conclusions: Stroke is an important complication in patients with BAV. The most common type of stroke in BAV is embolic. Greater than one-third of embolic stroke resulted from embolism from a calcific aortic valve. Patients with BAV stroke commonly have a history of recurrent cerebral ischemic events, severe valvular disease, and proceed to AVR soon after stroke.