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Objective Tricuspid regurgitation (TR) is a prevalent valve disease associated with significant morbidity and mortality. We aimed to apply machine learning (ML) to assess risk stratification in patients with ≥moderate TR. Methods Patients with ≥moderate TR on echocardiogram between January 2005 and December 2016 were retrospectively included. We used 70% of data to train ML-based survival models including 27 clinical and echocardiographic features to predict mortality over a 3-year period on an independent test set (30%). To account for differences in baseline comorbidities, prediction was performed in groups stratified by increasing Charlson Comorbidity Index (CCI). Permutation feature importance was calculated using the best-performing model separately in these groups. Results Of 13 312 patients, mean age 72 ± 13 years and 7406 (55%) women, 7409 (56%) had moderate, 2646 (20%) had moderate–severe and 3257 (24%) had severe TR. The overall performance for 1-year mortality by 3 ML models was good, c-statistic 0.74–0.75. Interestingly, performance varied between CCI groups, (c-statistic = 0.774 in lowest CCI group and 0.661 in highest CCI group). The performance decreased over 3-year follow-up (average c-index 0.78). Furthermore, the top 10 features contributing to these predictions varied slightly with the CCI group, the top features included heart rate, right ventricular systolic pressure, blood pressure, diuretic use and age. Conclusions Machine learning of common clinical and echocardiographic features can evaluate mortality risk in patients with TR. Further refinement of models and validation in prospective studies are needed before incorporation into the clinical practice.

Abstract Background Isolated tricuspid regurgitation (TR) repair or replacement carries significant operative mortality risk mainly due to delayed referral. We have recently developed the Tricuspid Regurgitation Impact on Outcomes (TRIO) score to assess risk in TR based on 8 simple variables (age, sex, severe TR, creatinine>2 mg/dl, history of heart failure, history of chronic lung disease, AST >40 units/L, heart rate >90). Whether this score can be used in assessment of TR surgical risk and long term outcome is unknown. Purpose To examine the impact of TRIO scores on the postoperative outcomes of isolated tricuspid valve surgery. Methods Adult patients with severe functional TR who underwent isolated tricuspid valve replacement or repair between 2000-2022 were identified. Postoperative outcomes were compared across low (0-3), intermediate (4-6), and high (7-12) TRIO risk score groups. Results 177 patients were included. Mean age was 70.7 ± 12.2 years, 69 (39%) were male, 34 (19%) were low TRIO score, 111 (63%) intermediate score and 32 (18%) high score. Tricuspid repair was performed in 43 (24.3%) and valve replacement in 134 (75.7%), reflecting the advanced disease stages of this patient cohort. At short term, higher TRIO scores were associated with more frequent need for urgent surgery, prolonged ventilation (>72h) and postoperative dialysis (p<0.05 for all). Perioperative 30-day mortality increased with the TRIO risk score (low: 0%; intermediate: 4.5%; high: 9.4%) but differences did not reach statistical significance (p=0.187). Low risk patients had a shorter hospital and ICU stay (Figure 1A-B). During a mean follow-up of 5.2 ± 3.2 years, 98 (55.4%) patients died. At long term follow-up, lower TRIO scores were associated with improved survival after tricuspid surgery (Figure 1C). Conclusions Patients with higher TRIO scores have more postoperative complications, require longer hospital stay and have higher all-cause mortality at long-term follow-up. Our findings suggest that TRIO score may also be used for risk stratification in patients considered for surgical management of isolated functional TR.

Abstract Background Atrial functional mitral regurgitation (AFMR) is an increasingly recognized cause of functional MR thought to result from left atrial enlargement and myopathy in the setting of preserved left ventricular geometry and function. AFMR mostly occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction. Purpose We investigated whether the use of an artificial intelligence-based electrocardiogram (AI-ECG) can identify patients with new-onset AF and sinus rhythm (SR) who are at highest risk of developing AFMR. Methods Adults with a new diagnosis of AF between 2010 and 2021 who had a transthoracic echocardiogram (TTE) within 1 month after AF diagnosis were identified. Similarly, adults in SR who never had AF diagnosis and had a TTE during the same period were identified. Exclusion criteria from both groups included >mild MR at baseline, primary mitral valve disease, cardiomyopathy, ≥moderate aortic valve disease, current or previous low ejection fraction, enlarged left ventricle, cardiac devices, previous cardiac surgeries, and the absence of follow-up TTE ≥6 months from baseline. Only patients who had ECG within 10 days of the TTE were included. When multiple ECGs were available, the closest was considered. A previously trained AI-ECG algorithm to detect the probability of AF was utilized. Incident AFMR was defined as >mild functional MR in the absence of >mild left ventricle enlargement or dysfunction. Diastolic dysfunction was defined according to ASE/EACVI guidelines. Results Overall, 1,570 patients with new-onset AF (median age 67 years; 34% females) and 16,802 patients in SR (median age 59 years; 46% females) were included. The median AI ECG probability for AF was 43% (IQR 26%-59%) in the new-onset AF group and 2% (0.5%-7%) in the SR group, Figure 1. Incident AFMR occurred in 152 patients in the AF group over median 3.06 (IQR 1.5-5.2) years of follow-up and in 482 patients in the SR group over median 3.0 (1.5-5.6) years of follow-up. The probability of silent AF by the AI-ECG was associated with incident AFMR in the new-onset AF group [hazard ratio 1.19 (95% CI 1.11-1.28) per 10%, p <.001] and the SR group [hazard ratio 1.19 (95% CI 1.12-1.25) per 10%, p <.001]. The AI ECG-derived AF probability remained as an independent risk factor for AFMR in multivariable analysis in both AF and SR, Table 1. Conclusion The AI ECG for AF might be able to reflect the degree of left atrial myopathy and thus the risk of incident AFMR in patients with AF and SR.Distribution of AI ECG probability of AFMultivariable risk factors for AFMR

Abstract Background Atrial fibrillation (AF) is associated with increased risk of incident tricuspid regurgitation (TR), but types of incident TR in AF versus sinus rhythm (SR) are not well-defined. Purpose We aimed to compare the risk of the different types of incident ≥moderate TR in AF and SR. Methods Adults first diagnosed with AF (2010-2021) who had a transthoracic echocardiogram (TTE) within 30 days after AF and adults with no diagnosis of AF who had a TTE in the same period were identified. Patients with previous cardiac surgeries, congenital heart disease, cardiomyopathy, cardiac devices, primary valve disease, previous or current ejection fraction (EF) <50%, severe diastolic dysfunction (SDD), ≥moderate left-sided valve disease (LVD), right ventricular systolic pressure (RVSP) ≥50 mmHg, ≥moderate TR, any tricuspid stenosis, or with no follow-up TTE ≥6 months from baseline were excluded. Patients were followed for the development of ≥moderate TR, the type of which was identified in a hierarchal order: 1) pacemaker-associated TR, 2) LVD-associated TR in the setting of ≥moderate LVD, 3) low EF or SDD-related TR, 4) pulmonary hypertension (PH)-associated TR if RVSP was ≥50 mmHg, 5) other ventricular functional TR (VFTR) if there was >mild RV enlargement or dysfunction, and 6) atrial functional TR (AFTR) when none of the previous was present. Patients were also followed for the occurrence of risk factors for TR (pacemaker insertion, ≥moderate LVD, low EF or SDD, PH, >mild RV enlargement or dysfunction) in a hierarchal order, and both the prevalence and future risk of the corresponding type of ≥moderate TR was determined at the onset of these conditions in AF and SR. Results Overall, 1,360 patients with new-onset AF (median age 67 years, 34% females) and 20,438 patients in SR (median age 60 years; 54% females) were included. Over median 3.8 (IQR 1.8-6.6) years, incident ≥moderate TR occurred in 110 patients with new-onset AF [2.13 per 100-person years] compared to 378 patients in SR [0.41 per 100-person years, p <.001]. All types of incident ≥moderate TR occurred more frequently in AF (p <.001 for all). The distribution and incidence of each type of TR in AF and SR are shown in Figure 1. The incidence of risk factors associated with the development of TR was higher in the AF group, except for pre-capillary PH, Figure 2A. At time of diagnosis or occurrence of these conditions, the prevalence of the corresponding TR types was higher in AF, except for pacemaker-TR, Figure 2B. The incidence of the corresponding TR type after occurrence of TR risk factors was higher in the AF group for LVD-TR and low EF/SDD-associated TR (p ≤0.03); although numerically higher in AF, the association was only borderline for PH-TR (p =0.05), Figure 2C. Conclusion Incident ≥moderate TR of all types occurred more frequently in patients with AF vs. SR and the distribution of TR types differed by rhythm. Patients with AF may benefit from a closer follow-up.Distribution and incidence rates of TRIncidence of TR risk factors & TR after

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are closely associated diseases that frequently coexist. However, due to the overlapping symptoms, the diagnosis of HFpEF can be overlooked with symptoms being attributed to AF. Purpose We aimed to investigate the prevalence of diastolic dysfunction (DD) in patients with new-onset AF compared to sinus rhythm (SR), study changes in diastolic function parameters over time in the two groups and compare the incidence of DD at follow-up. Methods Adults with new diagnosis of AF and adults in SR were identified. Patients with previous cardiac surgeries, congenital heart disease, hypertrophic or infiltrative cardiomyopathy, primary mitral disease, left-sided valve disease, low ejection fraction, enlarged left ventricle, or with no 6-month follow-up echocardiogram were excluded. Diastolic function was assessed through 4 components: mitral medial e’ <0.07 m/sec, mitral medial E/e’ >15 in SR and >11 in AF, TR velocity >2.80 m/sec, and left atrial volume index >34 ml/m2, with severe DD (SDD) defined by ≥3/4 findings and moderate DD (MDD) by ≥2/4 abnormal diastolic function parameters. Annualized changes were calculated as the difference between follow-up and baseline values divided by years in between. In a secondary analysis, patients with new-onset AF were propensity score-matched to patients with SR in a 3:1 ratio based on age, sex, body mass index, and comorbidities. Results Overall, 1,747 patients with incident AF (median age 67 years; 34% females) and 29,623 in SR (median age 59 years; 51% females) were included. New-onset AF was independently associated with the presence of SDD vs SR (8% vs 2%) and MDD (25% vs 11%, p<.001 for both in adjusted analysis). Over median follow-up of 3.2 (IQR 1.6-5.8) years, annualized severity progression in each of the 4 diastolic function parameters was greater in the AF group (p<.001 for all), Table. The incidence rates of SDD and MDD were 3.7 and 8.8 per 100-person year, respectively, in AF versus 1.1 and 3.6 per 100-person years, respectively, in SR (p<.001 for both at univariate and multivariable analysis), Figure. Results were similar in the propensity-score matched analysis. Conclusions Patients with new-onset AF more commonly have moderate or severe diastolic dysfunction that indicates the presence of potentially overlooked clinical HFpEF (when symptoms exist) or preclinical HFpEF (when symptoms are absent) compared to patients in SR. In long-term follow-up, patients with AF display accelerated progression in DD; suggesting that therapies to prevent progression to symptomatic HFpEF may be highest value in this patient population.

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’>14; and left ventricular ejection fraction <50%); stage 2 (left atrial volume index >34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension> 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p<0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p <0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p<0.001, CT HR 4.49 CI (2.27 – 8.89) p<0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage >3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p<0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Abstract Background Atrial fibrillation (AF) occurs more frequently in men, but women suffer more AF recurrence; mechanisms are not completely understood. Purpose To explore whether sex related differences in LA stiffness (LAstiffn) in patients with AF ablation could potentially explain differences in AF recurrence. Methods We screened patients with catheter ablation for AF, in sinus rhythm at 3 months post-ablation, with no significant mitral valve disease (< moderate), and with prospectively measured LA volumes [maximum (LAVI) and minimum volume index] by echocardiography. LAStiffn index was estimated as (E/e’)/LA emptying fraction. Outcome endpoint was AF recurrence up to 14 years post ablation. Results A total of 591 patients with AF ablation were studied (mean age 60±10 years; 25% women; Table1). At 3 months post-ablation, LAVI was 36±10 mL/m2 and LAstiffn was 0.31±0.21 1/%. Compared to males, female patients were slightly older, had more frequently hypertension, congestive heart failure, prior stroke/TIA, higher CHA2DS2-VASc score; they less often had persistent AF, coronary artery disease, or dilated cardiomyopathy. Women also had higher LAstiffn (0.37±0.24 vs. 0.29±0.19, P <.0001, Figure 1), despite similar indexed LA volumes (Table1). Rates of AF recurrence at follow-up (median 7.5 years; 347 patients with events) were higher in women vs. men (Figure 2, left; log-rank P<.001) and persisted after adjustment for age, type and duration of AF, body mass index, cardiovascular risk factors and comorbidities, CHA2DS2-VASc score ≥2, LV ejection fraction, and LAVI (adjusted HR 1.58 [1.20-2.08], P=.001). Overall, LA volumes and LAstiffn were higher in patients with older age and more comorbidities (hypertension, congestive heart failure, coronary artery disease, persistent AF, CHA2DS2-VASc score ≥2, etc; P<.01 for all). At multivariable regression analysis, LAVI and LAstiffn correlated with E/e’, LV size and mass, degree of mitral/tricuspid regurgitation, and LV stroke volume index (only LAVI). In addition, LAstiffn was higher in patients with elevated right ventricular systolic pressure (RVSP) >35 mmHg and increase in RVSP more than 10 mmHg from pre-ablation (P<.0001) (correlation R=0.44, P<.0001). At follow-up, after adjusting for age and LAVI, higher LAstiffn remained associated with AF recurrence in women (P=.02, HR 2.82 per unit change, 95% CI, 1.08-6.72; Figure 2, right), but not in men (P=.30). Conclusions LAStiffn is higher in women vs. men and correlates with burden of comorbidities, aging, diastolic dysfunction and pulmonary hypertension, possibly reflecting more extensive LA myopathy, and potentially contributing to sex differences in AF recurrence.Figure 1Table 1

Case: A 65-year-old patient presented 4 months after mitral valve repair (annuloplasty band, commissuroplasty, neo-chordae to the anterior mitral leaflet (AL)). At follow up, he developed significant hemolytic anemia (Hemoglobin 10.1g/dL, LDH 650U/L, Bilirubin 1.4mg/dL and haptoglobin<14 mg/dL). TEE revealed the substrate for hemolysis: moderate-severe mitral regurgitation (MR) starting at the coaptation of A2 and P2 scallops due to AL overriding the posterior (PL). The jet was then directed posteriorly to a small (3 x 6 mm confirmed by cardiac CT) area of annuloplasty band dehiscence at the base of the P2 scallop, with the band in direct path of the flow. The unique feature was that AL retained coaptation with the annuloplasty band, thus forming a small tunnel from the A2-P2 coaptation defect to the dehisced area. Given that redo surgery early after initial intervention would be challenging, the Heart Team decided to pursue percutaneous closure at the level of the dehisced annuloplasty to reduce regurgitation and mitigate hemolysis. Under 3D TEE guidance closure with a 12mm AVP plug was attempted but resulted in interference with PL motion with a new jet of regurgitation laterally. Using two 8mm AVP plugs was successful in closing the dehiscence with minimal impact on PL. Overall regurgitation was reduced to mild. Within a week hemolysis labs improved: LDH337 U/L, Bilirubin0.7 mg/dL. Discussion: Annuloplasty band dehiscence is a known cause of recurrent MR after repair. As regurgitation occurs at the leaflet coaptation zone, percutaneous closure of these defects is usually futile. In this patient we took advantage of the maintained coaptation between the AL and annuloplasty band.

Abstract Background and Aims Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR). Methods Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (&gt;MDD) by ≥2/4. Annualized changes in DD indices were determined. Results New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6–5.8) years, DD progressed two–four-fold more rapidly in those with new-onset AF (P &lt; .001 for all). The risk for incident DD was increased in new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19–3.32) for SDD and 1.73 (1.49–2.02) for ≥MDD]. Conclusions Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.