Pislaru, S V

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is known to cause dilation in both the mitral (MA) and the tricuspid (TA) annuli. Few studies have investigated MA dynamics and function in AF compared to sinus rhythm (SR). However, no study addressed this issue in TA. Hence, we set forth to describe TA dynamics in AF and SR and its relationship with severity of tricuspid regurgitation (TR). Methods 3D echocardiographic imaging data were acquired from adult patients in AF or SR with varying degrees of TR between 2018 and 2020. TA was automatically tracked throughout the cardiac cycle using a commercially available software (TomTec 4MV software; Figure 1) over 4-6 cardiac cycles per patient. Time to minimal area as percentage of the R-R interval was recorded in each of the cycles. Absolute change in TA area was calculated as the difference between maximal and minimal TA area in each cardiac cycle and was averaged over 4-6 cycles per patient. This measurement was used to reflect the dynamic range of TA deformation during the cardiac cycle. Right atrial (RA) and right ventricular (RV) volumes and longitudinal strain were also measured (speckle tracking, 4-ch view). Results A total of 70 patients were studied (35 AF; 35 SR; 54% males in each group). Patients with AF were older [median (IQR) of 81 (72-86) years vs. 69 (59-78) years in SR, p < 0.001], had larger maximal TA area and circumference (p < 0.001 for both), larger RA size (p < 0.001), lower RA reservoir strain (p < 0.001) and RV free-wall strain (p < 0.001). Absolute change in TA area was significantly decreased in AF [2.3 (1.7-2.7) cm2] vs. 3.1 (2.3-3.5) cm2 in SR, p = 0.002. Patients with ≥ moderate TR (n = 41, 59%) had lower absolute change in TA area [2.4 (1.7-3.1) cm2 vs. 2.8 (2.2-3.5) cm2 in < moderate TR, p = 0.05]. Female sex was associated with lower absolute change in TA area [2.3 (1.7-3.2) cm2 vs. 2.7 (2.2-3.6) cm2 in males, p = 0.02] on univariate analysis. AF patients had more frequently ≥ moderate TR [28 AF vs. 13 SR, p < 0.001]. On multivariate analysis including sex, rhythm, TR severity, RA and RV strains, and averaged maximal TA area, independent factors associated with lower absolute change in TA area were AF, ≥ moderate TR, and larger maximal TA area (p < 0.05 for all). Time to minimal TA size was achieved in (0-40%) of the R-R interval in 70% of patients in SR compared to only 41% of patients in AF (Figure 2) and in 73% in patients with < moderate TR compared to 43% in patients with ≥ moderate TR. Conclusion AF is associated with blunted TA dynamics resulting in lower decrease in TA size and with a heterogenous timing of minimal TA size throughout the cardiac cycle. The blunted and discoordinated annular contraction may reduce systolic tricuspid valve competence and be involved in the pathophysiology of functional TR. Future studies are needed to confirm this hypothesis and evaluate the effect of restoration of SR on TA dynamics and time to minimal TA size. Abstract Figure 1Abstract Figure 2

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: Transesophageal echocardiography (TEE) has long provided excellent diagnostic imaging of left-sided valvular pathology with an excellent safety profile; however, recent data has suggested an increased risk of injury related to TEE guidance. Purpose This study aims to evaluate the incidence and nature of TEE-related oropharyngeal or esophageal complications in patients undergoing TEE-guided structural heart procedures and identify associated risk factors. Methods We reviewed consecutive patients undergoing TEE-guided structural heart procedures from 2005-2020. All procedures were performed under general anesthesia. TEE-related oropharyngeal or esophageal complications were defined as those occurring within 30 days of the procedure resulting in i) persistent dysphagia, odynophagia, or upper gastrointestinal bleeding requiring prolonged endotracheal intubation, therapeutic endoscopic or surgical intervention, or diagnostic imaging that demonstrated oropharyngeal or esophageal injury. ii) upper gastrointestinal bleed requiring transfusion, hemodynamic compromise warranting mechanical or pharmacologic support; or iii) oropharyngeal or esophageal complications leading to death. For multivariate analysis, all variables with a p < 0.15 at univariate analysis were included in the model. Results Among 1229 adult patients undergoing TEE-guided structural heart procedures between 2005-2020, 274 underwent a transcatheter aortic valve replacement (TAVR) with the remaining 955 undergoing either mitral valve transcatheter edge-to-edge repair (mTEER, n = 278), mitral paravalvular leak closure (PVLC, n = 354), mitral valve-in-valve replacement (VIV, n = 41), or left atrial appendage closure (LAAO, n = 282). Of these, 6 (0.5 %) had TEE-related complications; 0% TAVR, 0% VIV, 0.36% LAAO, 0.28% PVLC, 1.41% mTEER (p = 0.14). Of the six patients with complications 3 required at least one day of prolonged tracheal intubation and one a blood transfusion. None required surgical repair. Factors associated with increased complication risk (Table) included a prior history of gastrointestinal bleed (Odds ratio 5.44 [0.98-30.04; p = 0.05]) and longer procedural time (OR per 30 min 1.15 [1.01-1.31, p = 0.03]). Patients undergoing mTEER had an increased risk of complication (OR 6.76 [1.23-37.1 p = 0.03]) and longer procedural time (OR per 30 mins 1.15[1.01-1.31, p = 0.04]) compared to other all other procedures. Conclusion(s): In a large series of patients undergoing cardiac structural interventions under general anesthesia with TEE-guidance, rates of TEE-induced injury were low. Risk of oropharyngeal or esophageal complications was increased with longer procedure times, prior gastrointestinal bleeding history, increased age, increased pre-procedural creatinine, procedural type being mTEER and in male patients, lower height. Abstract Table

Abstract Funding Acknowledgements Type of funding sources: None. Background Tricuspid regurgitation (TR) is a prevalent valvular lesion with three broad morphologic subtypes: primary due to intrinsic pathology of the valve or subvalvular apparatus; secondary due to pulmonary hypertension; and isolated TR associated with chronic atrial fibrillation. The complex pathophysiological, clinical and echocardiographic features between these subtypes require further investigation. Purpose We aimed to identify the different phenotypes of TR using cluster analysis, and determine differences (if present) in clinical outcomes associated with these phenotypes. Methods We included 13611 patients with ≥ moderate TR, either primary or secondary, in the final analyses. The demographic, clinical and echocardiographic data of these patients were evaluated using Ward’s minimum variance cluster analysis including a total of 38 variables. Survival analysis for all-cause mortality was performed using the Kaplan-Meier method, and groups were compared using the log-rank test. Results The mean age of patients was 72.5 ± 13.4 years, 7590 (56%) were females. The clustering identified 5 distinct phenotypes. Cluster 1 represented "low-risk TR" with lesser severity likely related to chronic atrial fibrillation. This cluster had less severe TR, normal sized right ventricle and fewer comorbidities. Clusters 2-5 represented "higher severity TR", "TR associated with lung disease", "TR associated with coronary artery disease and ischemic cardiomyopathy" and "TR associated with chronic kidney disease" respectively (Figure 1). Cluster 1 had the best overall survival, followed by clusters 2, 3 and 4, and lastly cluster 5, with the worst outcome (Figure 2). Conclusions Cluster analysis identifies 5 phenotypically distinct novel subgroups of TR with differences in all-cause mortality. This phenotype-based classification improves our understanding of interaction of different co-morbidities with this complex valve lesion and can inform clinical decision making. Abstract Figure. Cluster Dendrogram Abstract Figure. Kaplan-Meier survival curves

Abstract Funding Acknowledgements Type of funding sources: None. Background Aortic regurgitation (AR) is a common valvular lesion associated with left ventricular (LV) enlargement and dysfunction and increased risk of death with onset of symptoms, significant LV enlargement, or systolic dysfunction. The current guidelines are based on symptoms, LV size and LV function to evaluate the candidacy for surgery in patients with severe AR. Purpose We propose a machine-learning (ML) based algorithm to identify patients at risk for death from AR independent of aortic valve replacement (AVR) surgery (patients were censored at AVR event unless the operation occurred within 100 days of the first visit, in which case baseline AVR is included as a predictor). Methods The model was trained with 5-fold cross-validation on a dataset of 1035 patients. Model performance is reported on an independent dataset of 207 patients. Optimal predictive performance was observed with a Conditional Random Survival Forest model. A subset of 19 / 41 variables were selected for inclusion in the final model. Variable selection was performed with 10-fold cross validation using Random Survival Forest model; variables that were on an average selected by less than 6/10 splits were excluded. Results The mean age of patients was 60 ± 17 years and 198 (18%) were females. The variables included in the models were age, end-diastolic volume, end systolic dimension, body surface area, ejection fraction, NYHA class, body mass index, diastolic blood pressure, bicuspid valve, regurgitant volume, filling pressure, mid ascending aorta diameter, mitral tissue early relaxation velocity, pulmonary artery systolic pressure, and comorbidities, and the relative variable importances averaged across five splits of cross validation in each repeat were evaluated (Figure). The predictive AUC for predicting survival of the best-performing model was 0.84 at 1 year, 0.86 at 2 years, and 0.87 overall, respectively. Conclusion Using commonly observed echo parameters and patient characteristics we successfully trained a ML model to predict survival in patients with severe AR. This technique could identify high-risk patients who would benefit from early intervention, thereby improving patient outcomes. Abstract Figure.

Abstract Background Prevalence of calcific mitral stenosis (MS) increases with age. Mitral valve interventions for calcific MS are often delayed until symptoms are severely limiting because the natural history of calcific MS and its relation to cardiac symptoms or comorbidities have not been well assessed. Objectives We assessed the prevalence of symptoms, comorbidities and determinants of all-cause mortality in patients with severe calcific MS. Methods We retrospectively investigated adults with echocardiographic isolated severe MS, defined as mitral valve area (MVA by the continuity equation) ≤1.5 cm2, from July 2003 to December 2017. Among them, calcific MS was identified as obstruction of left ventricular inflow due to degenerative calcification of the mitral annulus using echocardiography and, whenever available, operative findings including histopathological examination. Inactivity was defined as requirement for assistance with activities of daily living. Follow up was obtained by review of medical records. Results Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78±11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index (CCI) was 5.1±1.7 and 14 (7%) were inactive. MVA and transmitral gradient (TMG) were 1.26±0.19 cm2 and 8.1±3.8 mmHg, respectively. Symptoms were present at baseline in 120 (60%) including dyspnea in 97, chest discomfort in 12, syncope in 3, lower extremity edema in 3, thrombosis in 3 and fatigue in 2. Of them, mitral valve interventions including surgical or transcatheter mitral valve replacement and mitral valve bypass were performed in 27 (23%): within 1 year after index TTE in 23 (19%) and at 2, 4, 5 and 6 years in 1 each. Of 80 patients without symptoms at index TTE, 20 (25%) developed symptoms at mean 2.9±3.2 years and interventions were performed in 5 (6%). Of 168 who did not receive interventions, 60 (36%) did not develop symptoms during follow up, 58 (35%) were considered to have moderate MS, 46 (27%) were not offered surgery because of high risk due to advanced age, multiple comorbidities or heavy calcification, and 2 (1%) declined interventions. During follow-up of 2.8±3.0 years, Kaplan-Meier survival at 1 and 3 years without intervention were 72% and 52%, respectively (Fig. A). Inactivity, CCI >5, left ventricular ejection fraction (LVEF) <50%, TMG ≥8 mmHg (the mean TMG) and right ventricular systolic pressure (RVSP) ≥50 mmHg were independently associated with mortality (Fig. B). Symptoms were associated with referral for interventions (OR 3.43, 95% CI 1.22–9.65; p=0.019), but not with mortality. Conclusion Patients with isolated severe calcific MS had a high burden of comorbidities and had high mortality without intervention. Symptoms were common (60%), but were not associated with mortality. TMG ≥8 mmHg, RVSP ≥50 mmHg, LVEF<50%, CCI >5 and inactivity were independently associated with mortality. Funding Acknowledgement Type of funding source: None

Abstract Background The left ventricle (LV) in obese patients undergoes different patterns of remodeling in order to normalize wall stress. However, little is known about how LV volume indices, LV global longitudinal strain and right ventricular free wall strain (GLS) vary according to the pattern of LV remodeling. Aim To define the echocardiographic reference values of LV volumes and biventricular GLS across the different LV remodeling patterns in obese patients with a preserved ejection fraction. Methods 2393 adult obese patients (1428 females, 965 males) with a normal ejection fraction who underwent echocardiography from January 2008 to December 2018 were selected. They were categorized according to 4 cardiac remodeling groups defined by LV mass index (102g/m2 in males, 88g/m2 in females) and relative ventricular wall thickness (0.42): normal geometry (NG), eccentric hypertrophy (EH), concentric remodeling (CR) and concentric hypertrophy (CH). Obese subjects were further categorized by BMI class (30–35, 35–40, >40 kg/m2). Obese subjects were gender matched to controls with a normal BMI (18.5–25 kg/m2) and normal cardiac geometry. Mean ± SD, One-way Anova and Tukey- Kramer HSD were applied. P<0.05 is considered significant. Results The mean age of controls and obese patients' were 50±16 and 57±13.6 years respectively (P<0.0001). LV GLS for controls compared to obese subjects with NG, EH, CR and CH was −21.1±2 vs. −20.2±1.9, −19.6±2.8, −18.5±2.9, −17.5±3.4 respectively (p<0.0001 for all), and for RV GLS it was −27.9±4 vs −26.7±3.9, −25.1±5, −23.5±5.5, −24.1±5.2 respectively (p<0.01 for all, except for NG where p=0.2). The distribution of LV indices according to cardiac remodeling subtypes is shown in the figure. Indexed end diastolic and end systolic volumes were smaller in NG, CH and CR compared to controls (p<0.001 for each respectively). LV GLS and ejection fraction were higher in females, while indexed LV volumes were higher in males within each remodeling category (P<0.0001). No significant difference in LV GLS or indexed LV volume was seen across BMI categories within each remodeling pattern (P>0.05). Obese subjects with CH had the highest incidence of the cardiovascular risk factors hyperlipidemia, hypertension and history of myocardial infarction or stroke, compared to those with other remodeling patterns (p<0.0001 for each, vs. NG, EH and CR). Conclusion To our knowledge, this is the largest study to define LV volumes and left and right ventricular GLS according to LV remodeling pattern and BMI category. The Lowest GLS was noted in CH. Ejection fraction was similar across the LV remodeling patterns. There were no differences in GLS and LV indexed volumes across BMI categories within each remodeling group. These results can be applied as a reference values for the obese population with a normal LV ejection fraction. Funding Acknowledgement Type of funding source: None

Abstract Background Transcatheter edge-to-edge mitral valve repair (TMVR; MitraClip, Abbott Vascular) is clinically approved for treatment of severe, symptomatic mitral regurgitation (MR) in high or prohibitive surgical risk patients. Iatrogenic mitral stenosis is a known complication of TMVR, but determinants of increased post-procedure mean diastolic gradient are not well defined. Purpose We aimed to investigate the determinants of increased mitral mean diastolic gradient after TMVR. Methods We retrospectively reviewed 59 patients. 2D and 3D TEE data sets acquired before and immediately after procedure were analyzed. 4D Cardio-View and 4D MV-Assessment (TomTec, Germany) were used for the analysis of the 3D volume data set. Quantitative mitral valve analysis was done at the end of systole. Increased mitral mean diastolic gradient after TMVR was correlated with pre-procedure 2D and 3D echocardiographic data. Results 34 patients had primary MR, 25 patients had mixed/secondary MR. Baseline mean mitral diastolic gradient was 2.0 ± 0.9mmHg and increased to 3.9 ± 1.8mmHg post-TMVR and the mean 3D planimetric mitral valve area decreased from 5.3 ± 1.5cm2 to 2.6 ± 1.0cm2. Implantation of multiple clips was performed less frequently in patients with smaller baseline mitral valve area; 8% vs 47% in the lowest quartile vs all others (p = 0.006). 12(20%) of patients had a mean diastolic gradient >5mmHg post-TMVR and 15(25%) of patients had a post-TMVR mitral valve area <2.0 cm2. There was no significant difference in post-procedure heart rate between patients with mean diastolic gradient ≤5mmHg vs >5mmHg (p = 0.08). Patient characteristics according to post-TMVR mean diastolic gradient are shown in the Table. Post-TMVR mean diastolic gradient >5mmHg was more common in patients with increased pre-procedure mean diastolic gradient(p = 0.006), post-TMVR mitral valve area <2.0 cm2(40% vs 14%, p = 0.03), and ≥moderate residual mitral regurgitation(38% vs 11%, p = 0.02). Post-TMVR mitral valve area <2.0cm2 was present in 50% vs 19% of patients with vs without a mean gradient >5mmHg(p = 0.04). Conclusions Elevated post-TMVR mean diastolic gradient is multifactorial and related to mitral stenosis, but residual mitral regurgitation also appears to be an important contributor to increased gradients in some patients. Larger cohorts are likely needed to assess the concurrent impact of mitral annular calcification, leaflet calcification, and other variables on post-TMVR mean gradient. Abstract P1798 Figure. 2D and 3D Echocardiographic Parameters

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.