Lara-Breitinger, Kyla M

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 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.