Nkomo, Vuyisile T.

Introduction: Isolated functional tricuspid regurgitation (FTR) in the absence of structural heart disease may develop secondary to elevation in left heart pressures caused by left ventricular diastolic dysfunction (DD), as in heart failure with preserved ejection fraction (HFpEF). FTR may also herald the presence of occult DD or indicate greater risk for new-onset DD. However, prevalence and incidence of diastolic dysfunction (DD) in isolated FTR have not been studied. Aims: Investigate the prevalence and incidence of DD across the different severities of FTR of unclear cause. Methods: Adults with normal EF and without structural heart disease undergoing echocardiography at a tertiary medical center with a repeat study ≥6 months from baseline were identified. Severe DD was defined by ≥3/4 abnormal DD parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, left atrial volume index) and moderate DD by ≥2. Results: Among 30,428 patients (median age 60; 50% women), FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. Severe DD was present in 2%, 5%, 11%, and 13% patients, respectively, (p<.001) and moderate DD in 9%, 19%, 31%, and 48%, respectively (p<.001). The association of DD with increasing FTR was independent of all clinical characteristics. Over median 3.0 (IQR 1.5-5.4) years, incident severe and moderate DD developed more frequently with increasing FTR severity ( Figure) . Findings were confirmed in a propensity-matched subset where patients were matched for age, sex, BMI, atrial fibrillation, and comorbidities and in patients without lung disease or ≥moderate right ventricular enlargement. Conclusions: Patients with FTR of undefined etiology commonly have DD suggesting the presence of underlying left heart disease. Patients without apparent DD or HF at baseline who have FTR remain at significantly increased risk of developing DD over follow-up and may be a target population for therapies to prevent progression to clinical HFpEF.

Introduction: Tricuspid regurgitation is a common echocardiographic finding leading to excess morbidity and mortality in adult population. Hypothesis: Racial and ethnic disparities have been observed in various cardiovascular disorders’ prevalence and natural course, including valvular lesions. However, little is known about the epidemiology and clinical correlations of TR among non-Hispanic Black adults. Methods: To examine risk factors and clinical outcomes in non-Hispanic Black adults with moderate or more severe TR, 685 patients (7%) self-identified as non-Hispanic Black and 9127 (93%) self-identified as non-Hispanic White with a first echocardiographic report of moderate or more severe TR between 2005-2016 were studied. Results: Non-Hispanic Black patients had more severe TR when compared to white patients (25% vs. 20%, p<0.001). After adjusting for age and sex, non-Hispanic Black patients had significantly higher 10-year all-cause mortality (HR=1.34 (1.18, 1.52), p<0.001). Black race remained a risk factor for all-cause mortality even after adjustment for comorbidities like CHF, COPD, DM, CKD, hypertension, and ischemic heart disease (HR=1.23 (1.08, 1.40), p=0.002). Conclusions: Significant racial disparities exist in demographic, clinical and echocardiographic characteristics between non-Hispanic Black and White patients with moderate or more severe TR. Black race is a potential disease modifier leading to excess mortality.

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 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 &gt;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 &gt;mild functional MR in the absence of &gt;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 &lt;.001] and the SR group [hazard ratio 1.19 (95% CI 1.12-1.25) per 10%, p &lt;.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 Aims Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on incident AFMR are scarce. We aimed to study the incidence, risk factors, and clinical significance of AFMR in AF or sinus rhythm (SR). Methods and results Adults with new diagnosis of AF and adults in SR were identified. Patients with &gt;mild MR at baseline, primary mitral disease, cardiomyopathy, left-sided valve disease, previous cardiac surgery, or with no follow-up echocardiogram were excluded. Diastolic dysfunction (DD) was indicated by ≥2/4 abnormal diastolic function parameters [mitral medial e′, mitral medial E/e′, tricuspid regurgitation velocity, left atrial volume index (LAVI)]. Overall, 1747 patients with AF and 29 623 in SR were included. Incidence rate of &gt;mild AFMR was 2.6 per 100 person-year in new-onset AF and 0.7 per 100 person-year in SR, P &lt; 0.001. AF remained associated with AFMR in a propensity score-matched analysis based on age, sex, and comorbidities between AF and SR [hazard ratio: 3.80 (95% confidence interval 3.04–4.76)]. Independent risk factors associated with incident AFMR were age ≥65 years, female sex, LAVI, and DD in both AF and SR, in addition to rate (vs. rhythm) control in AF. Incident AFMR was independently associated with all-cause death in both groups (both P &lt; 0.001). Conclusions AF conferred a three-fold increase in the risk of incident AFMR. DD, older age, left atrial size, and female sex were independent risk factors in both SR and AF, while rhythm control was protective. AFMR was universally associated with worse mortality.

Abstract Background and Aims Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are unknown. This study aimed to assess lifetime morbidity and long-term survival in BAV patients in the community. Methods The authors retrospectively identified all Olmsted County (Minnesota) residents with an echocardiographic diagnosis of BAV from 1 January 1980 to 31 December 2009, including patients with typical valvulo-aortopathy (BAV without accelerated valvulo-aortopathy or associated disorders), and those with complex valvulo-aortopathy (BAV with accelerated valvulo-aortopathy or associated disorders). Results 652 consecutive diagnosed BAV patients [median (IQR) age 37 (22–53) years; 525 (81%) adult and 127 (19%) paediatric] were followed for a median (IQR) of 19.1 (12.9–25.8) years. The total cumulative lifetime morbidity burden (from birth to age 90) was 86% (95% CI 82.5–89.7); cumulative lifetime progression to ≥ moderate aortic stenosis or regurgitation, aortic valve surgery, aortic aneurysm ≥45 mm or z-score ≥3, aorta surgery, infective endocarditis and aortic dissection was 80.3%, 68.5%, 75.4%, 27%, 6% and 1.6%, respectively. Survival of patients with typical valvulo-aortopathy [562 (86%), age 40 (28–55) years, 86% adults] was similar to age-sex-matched Minnesota population (P = .12). Conversely, survival of patients with complex valvulo-aortopathy [90 (14%), age 14 (3–26) years, 57% paediatric] was lower than expected, with a relative excess mortality risk of 2.25 (95% CI 1.21–4.19) (P = .01). Conclusion The BAV condition exhibits a high lifetime morbidity burden where valvulo-aortopathy is close to unavoidable by age 90. The lifetime incidence of infective endocarditis is higher than that of aortic dissection. The most common BAV clinical presentation is the typical valvulo-aortopathy with preserved expected long-term survival, while the complex valvulo-aortopathy presentation incurs higher mortality.

Introduction: Bioprosthetic valve thrombosis is a recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated bioprosthetic degeneration and higher rates of valve re-replacement. Hypothesis: Warfarin for 3 months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet (DAPT) and single antiplatelet therapies (SAPT). Methods: Adult patients who underwent TAVR (2012-2019) were identified retrospectively (n=1,501). Patients with atrial fibrillation were excluded (n=657). Patients were classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen. Structural valve degeneration (SVD) was considered when patients developed new ≥ moderate trans-prosthetic regurgitation, increase in mean gradients ≥10 mmHg from baseline, or when gradients exceeded 20 mmHg. Discharge date was considered time zero. Results: Overall, 844 patients [mean age 80 (±9), 43% females, mean Society of Thoracic Surgeons risk score 6.7 (±5.0)] were included. Warfarin was used in 633 (75%) patients, DAPT in 164 (19%), and SAPT in 47 (6%). Median follow-up time was 2.5 (IQR 1.2-3.9) years. There was no difference in outcomes of ischemic stroke, death, valve re-intervention, SVD, their composite endpoint, or hemorrhagic stroke and hemorrhagic stroke/RBC transfusion events (Figures 1 & 2), even after adjustment for confounders. Conclusion: Warfarin after TAVR was not associated with better clinical or hemodynamic outcomes or with worse adverse events compared to DAPT and SAPT.

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.

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.