Tricuspid Regurgitation Research Articles

Successful Anaesthetic Management of Triple Valve Surgery (Double Valve Replacement and Tricuspid Valve Ring Repair)- Challenges and Troubleshooting

Heart valve diseases are extensive and include double (mitral-aortic, mitral-tricuspid), or triple (mitral, aortic, and tricuspid) valvular regurgitation, stenotic or mixed lesions. The surgical correction of valvular lesions usually consists of the repair or replacement of all valves affected by a pathologic process.We present a challenging complex valvular case of a 61 year old hypothyroid female diagnosed with severe mitral stenosis with moderate mitral regurgitation, severe aortic stenosis with mild aortic regurgitation and severe tricuspid regurgitation with high pulmonary artery pressures.She successfully underwent Double valve replacement (Mitral and aortic) and Tricuspid Annuloplasty Ring repair.

A prospective study on etiology and clinical profile of chronic Cor pulmonale

Background: Cor pulmonale accounts for approximately 6% to 7% of all adult heart disease cases in the United States and is involved in 10% to 30% of hospital admissions for congestive heart failure nationwide. Materials and Methods: This prospective study was conducted at Al-Ameen Medical College and Hospital in Vijayapura, adhering to specific inclusion and exclusion criteria. The sample included 73 cases, with detailed medical histories and symptom analyses collected from each participant. A thorough clinical examination was also performed. Results: Among the 73 patients, 25 (34.3%) were aged 40 to 50 years, while another 25 (34.3%) were over 60 years. The majority were male (80.8%), and 50 patients (68.5%) had a history of smoking. All participants presented with symptoms of breathlessness, cough, and swelling of the feet. Physical examinations showed tachypnea, crepitations, and rhonchi in all individuals. Chronic bronchitis and emphysema were identified as the leading causes of chronic cor pulmonale in 44 patients (60.2%). Conclusion: This study found that chronic bronchitis and emphysema were common causes of chronic cor pulmonale, primarily affecting middle-aged and older individuals, with males affected more than females and smoking identified as a major contributing factor. Common symptoms included breathlessness, cough, and lower extremity swelling. Physical examinations frequently revealed tachypnea, crepitations, rhonchi, and notable signs such as epigastric pulsations, loud P2, pansystolic murmur of tricuspid regurgitation, and parasternal heave. Chronic cor pulmonale has a substantial impact on both pulmonary and cardiac function; 53.7% of patients are at risk of readmission within one year of discharge. The condition is generally associated with a poor prognosis. This highlights the importance of early detection of signs and symptoms to enhance management outcomes.

Percutaneous bicaval valve implantation for severe tricuspid regurgitation due to carcinoid syndrome.

Percutaneous bicaval valve implantation for severe tricuspid regurgitation due to carcinoid syndrome.

Insulin-like growth factor binding protein 2 predicts course of concomitant right-ventricular dilation and tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair

Abstract Aims Right ventricular (RV) dilation and secondary tricuspid regurgitation (TR) are highly prevalent comorbidities in patients with mitral regurgitation and are associated with a worse prognosis. TR improvement after successful transcatheter edge-to-edge mitral valve repair (M-TEER) is reported regularly, however specific factors contributing to the recovery of RV function and TR after M-TEER are poorly understood. Particularly the role of serum biomarkers in this context is unclear. We aimed to identify specific biomarkers associated with the course of concomitant RV dilation and TR after M-TEER. Methods and Results We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then analyzed differences in biomarker expression between patients with and without right ventricular reverse remodeling (RVRR) as defined by improvement of concomitant TR by at least one grade and/or downsizing of the basal RV diameter of at least 10%. 242 patients were included in this analysis, 94 had no/mild concomitant TR at baseline, 148 had moderate/severe TR. RV diameters correlated with TR severity and were significantly larger in patients with moderate/severe TR. At baseline, expression of numerous cardiometabolic biomarkers was significantly higher in patients with moderate/severe TR. These included NT-proBNP (1.9-fold, p < 0.001), matrix metalloproteinase 2 (1.4-fold, p < 0.001) as well as insulin-like growth factor binding proteins 1 (1.7-fold, p < 0.001), -2 (1.3-fold, p = 0.001) and -7 (1.4-fold, p < 0.001). Follow-up analysis was performed in patients with initial moderate/severe TR. The course of TR and RV dimensions three months after M-TEER could be assessed in 99 patients (56 with moderate TR, 43 with severe TR). RVRR had occurred in 50 patients (50.5%). Patients without RVRR had a higher prevalence of chronic pulmonary disease (24.5 vs. 2.2%, p < 0.001). No further differences in clinical characteristics were found. Specifically, RV diameter, systolic pulmonary artery pressure (sPAP) and right-ventricular systolic function did not differ substantially between both groups. Strikingly however, the expression of insulin-like growth factor binding protein 2 (IGFBP-2) was significantly higher in patients, who did not develop RVRR (fold change 1.3 compared to patients with RVRR, p = 0.022). After adjustment for covariates IGFBP-2 was independently associated with absence of RVRR (Odds Ratio 2.078, 95% Confidence interval 1.108 – 3.897, p = 0.023). Conclusions In patients undergoing M-TEER with concomitant moderate or severe TR, numerous cardiometabolic biomarkers including IGFBP-2 are upregulated. Higher levels of IGFBP-2 at baseline are independently associated with persistent TR and/or RV dilation after M-TEER.

Is etiology of severe tricuspid regurgitation related to prognosis?

Abstract Objective Our aim was to assess the prognostic role of the etiology tricuspid valve disease in patients with severe tricuspid regurgitation (TR). Methods Multicenter, observational, and prospective registry in which all patients with severe TR have been consecutively collected within a 6-month period and followed up for one year. Results A total of 1247 patients with severe TR [mean age: 76.7±10.5 years, 876 women (70.2%)] were included: 810 (64.9%) met criteria for severe TR, 301 (24.1%) massive TR, and 136 (11%) torrential TR. The most frequent etiology was functional TR secondary to left-heart disease in 621 patients (49.9%) followed by "atriogenic" TR in 247 (19.8%). TR etiology distribution is described in Figure 1. Death due to refractory HF occurred in 9,2% of patients, hospitalization for HF in 20,8%, and 12,3% underwent TR interventions. In the univariate and multivariate analysis, age, impaired renal function, previous HF admission, and massive and torrential TR were associated with an increased risk of HF hospitalization and cardiovascular mortality. Global (p=0,476) and cardiovascular mortality (p=0,138) rates were similar when comparing different TR etiologies (Figure 2). Conclusion Severe TR is associated with high rates of CV mortality and new HF admission. These findings are and independent from TR etiology.

Tricuspid regurgitation in the context of severe concomitant left-sided valvular heart disease: patients characteristics and long-term clinical and interventional outcomes

Abstract Background The clinical features, therapeutical management and outcome of patients with significant tricuspid regurgitation (TR) in the context of multiple valvular disease (VD) are poorly defined. Purpose To assess the characteristics, management and long-term prognosis of a large cohort of patients with multiple VD, focusing on the context of significant TR and concomitant severe mitral or aortic disease. Methods Clinical and echocardiographic data were collected in 1183 patients with ≥moderate TR diagnosed at our centers from January 2012 to June 2020: after propensity score matching for age to create matched cohort with < 10% of absolute difference, 975 patients were included in this study and divided in 4 groups as shown in Figure 1. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization+any valvular intervention. Results Patients with isolated TR (356, 37%) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). TR+ severe MR patients (466, 48%) showed higher rates of concomitant coronary artery disease, NYHA class III/IV symptoms and larger left atrial volumes. The group of TR+ severe AS (131 patients, 13%) was characterized by older age, more comorbidities and lower LVEF. Patients with TR and severe AR (22, 2%) were younger, with larger LV dimensions and higher pulmonary pressures. Overall, in 37(4%) patients tricuspid intervention was performed: no differences were found between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment (p=0.444 and p= 0.624, respectively), while left-valve only surgical treatment was more common among patients with TR and severe MR and left-valve transcatheter treatment among patients with TR and severe AS (both p<0.001). After a median follow-up of 2.8 years, the primary endpoint occured in 374 (38%) of patients, and was significantly more frequent in the group of patients with TR and severe AS (p<0.001, Figure 2). In this group, after multivariate analysis, indexed stroke volume remained independenty associated with ACD (OR 0.96, CI 0.93-0.98, p =0.040). Eventually, the secondary endpoint too was more common in patients with TR and severe AS (p<0.001, Figure 2). Conclusions In the context of significant TR, concomitant severe left-sided VD is common, and each subtype presents with different clinical features and echocardiographic phenotypes; in this scenario, TR was profoundly underteated. Long-term, patients with significant TR+ severe AS have considerable worse prognosis.Figure 1Figure 2

The prevalence and impact of changes in the severity of secondary TR during hospitalization in acute heart failure

Abstract Background Secondary tricuspid regurgitation (TR) is a prevalent entity in patients hospitalized for acute heart failure (AHF), and concomitant moderate or severe TR at admission has been demonstrated to be associated with a poor prognosis. However, no study has described the trajectories of the severity of secondary TR during admission, and the prognostic implications of changes in the severity of secondary TR. Purpose This study aimed to investigate the dynamism of secondary TR observed during hospitalization due to worsening heart failure, and its prognostic impact in patients with AHF. Methods A post-hoc analysis of 1,061 consecutive patients hospitalized with AHF was performed, enrolled in the prospective, multicenter Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF). Patients included in the study underwent a comprehensive echocardiographic examination within 24 hours of admission and again prior to discharge. Patients were divided into four groups based on the TR severity at admission and discharge: none to mild TR at both admission and discharge (no/no group), moderate to severe TR at admission but improved to none to mild TR at discharge (resolution group), none to mild TR at admission but moderate to severe TR at discharge (worsening group), and moderate to severe TR at both admission and discharge (persistent group). The primary endpoint was the composite of 1-year all-cause mortality and HF re-hospitalization after discharge. Results The no/no, resolution, worsening, and persistent groups included 479 (45%), 275 (26%), 85 (8%), and 222 patients (21%), respectively. The no/no group and the resolution group had significantly lower tricuspid regurgitant pressure gradients prior to discharge compared to the worsening and persistent groups (P<0.001). Also, right ventricular dysfunction evaluated at discharge, defined by tricuspid annular plane systolic excursion <17 mm, was more prevalent in the worsening (65.7%) and persistent groups (66.4%) compared to the no/no (43.7%) and resolution (53.2%) groups (P<0.001). Compared to the no/no group, the worsening and persistent groups, but not the resolution group, were associated with a higher incidence of the primary endpoint (Log-rank: P<0.001). This association remained significant in an adjusted Cox regression analysis, with the worsening group (hazard ratio: 1.48, 95% confidence interval [CI]: 1.01–2.20) and persistent group (hazard ratio: 1.35, 95% CI: 1.01–1.83) independently associated with the primary endpoint, but not the resolution group (hazard ratio: 1.10, 95% CI: 0.81–1.49). Conclusions In patients hospitalized for AHF, the severity of secondary TR is dynamic, and changes in the severity of TR are significantly associated with prognosis. Our study results underscore the importance of repetitive evaluation of TR in hospitalized patients with AHF.

Impact of atrial fibrillation on progression of tricuspid regurgitation in patients undergoing transcatheter aortic valve replacement

Abstract Background Recent advancements in interventional cardiology have spurred growing interest in atrial tricuspid regurgitation (TR) as a potential therapeutic target. Atrial TR, a form of secondary TR, arises from the dilatation and dysfunction of the right atrium, frequently seen in the context of atrial fibrillation (AF). While the concept is increasingly recognized, the natural history of TR in relation to AF remains incompletely understood. Purpose This study aims to elucidate the impact of AF on the progression of TR in patients undergoing transcatheter aortic valve replacement (TAVR). Methods Utilizing data from a comprehensive single-center TAVR registry, this study included patients who underwent TAVR between 2016 and 2023, excluding those with severe TR post-TAVR. Subjects were categorized based on the presence or absence of paroxysmal or persistent/permanent AF/atrial flutter (AFL). The study employed the cumulative incidence function to depict the progression to severe TR, considering all-cause mortality as a competing risk. Results Among 981 eligible patients, 169 (17.2%) presented with AF/AFL, with 57 (5.8%) having persistent/permanent and 112 (11.4%) paroxysmal forms. Patients with AF/AFL had a higher surgical risk, a higher prevalence of significant mitral regurgitation and TR, and a lower left ventricular ejection fraction. The median follow-up period was 366 days, with an interquartile range from 36 to 1079 days. Over a 5-year period, 11.7% of patients with AF/AFL experienced progression to severe TR, with 14.2% in those with persistent/permanent AF/AFL and 10.6% in those with paroxysmal AF/AFL, compared to merely 0.8% in patients without AF/AFL (sub-distribution HR: 7.60, 95%CI: 2.86-20.0; P<0.001) (Figure 1). Multivariable Fine-Gray regression analysis showed that AF/AFL was associated with the progression of TR by at least one grade, independently of the TR grade post-TAVR and other echocardiographic parameters (sub-distribution HR: 1.38, 95% CI: 1.06-1.78; p=0.015). Other factors associated with progression included the TR grade post-TAVR (sub-distribution HR: 1.20, 95% CI: 1.05-1.38; p=0.009) and the presence of a permanent pacemaker (sub-distribution HR: 1.53, 95% CI: 1.18-1.71; p=0.001) (Figure 2). Conclusions The presence of AF/AFL significantly increases the risk of developing severe TR in the long-term following TAVR, underscoring the need for vigilant monitoring and potentially preemptive management strategies in this patient cohort.

Characterization of tricuspid regurgitation in patients following left bundle branch pacing

Abstract Background Pacemakers placed in the right ventricle apex can lead to mechanical and electrical dyssynchrony. There is a growing interest in more physiologically stimulating techniques, and in this context, left bundle branch pacing (LBBP) emerges as an option. In this pacemaker, the lead is positioned perpendicular to the septum approximately 15-20 mm below the tricuspid valve annulus, and the helix is advanced towards the left side (Image 1). There is limited data on the incidence of new-onset tricuspid regurgitation (TR) or deterioration of pre-existing TR following the implantation of this type of pacemaker. Purpose To characterize the incidence of TR or deterioration of pre-existing TR after LBBP and to determine if there are predictors of a higher degree of TR. Methods All patients who received a pacemaker with LBBP between January and October 2023 were consecutively recruited. A transthoracic echocardiogram following the implantation of the pacemaker was performed to assess the size and function of right heart chambers, degree of TR and position of pacemaker lead. Continuous variables are expressed as mean ± SD or median [IQR] and categorical variables as absolute (%). Results There were 31 implants with a mean age of 73.4±8.7 years and 42% women. Nine patients (22.5%) had atrial fibrillation, and 7 patients (23%) had known coronary artery disease. The main indication for implant was a complete AV block (63.3%). Two patients had TR greater than moderate before the implantation of the pacemaker. Mean time elapsed between implantation and follow-up echocardiogram was 5.8 months. The distance between the lead-implanted site to the tricuspid annulus (Lead-TA distance) was 26.7±10.5 mm, mean lead depth in the interventricular septum (IVS) was 7.7±1.8mm and the IVS thickness at the lead-implanted site was 10.6±2.1 mm. Overall, TR worsed less than 1 degree after the lead implant (table 2) and was significantly related with the Lead-TA distance (TR worsed 0.3 degrees in Lead-TA distances shorter than 26.7mm and TR reduced 0.2 degrees in Lead-TA distances longer than 26.7mm, p=0.037). Conclusions In the short term following the implantation of an LBBP pacemaker the distance from the lead to the tricuspid annulus has an acute impact on tricuspid regurgitation, with TR worsening at short Lead-TA distances and TR improving at longer distances.

Effective RV ejection fraction by CMR: a new index of RV function in patients with severe TR

Abstract Background Right ventricle (RV) dysfunction represent an formal indication for intervention in patients with significant tricuspid regurgitation (TR). RV ejection fraction (RVEF) by Cardiac Magnetic Resonance (CMR) is considered the gold standard of RV function; however it is influenced by changes of preload conditions and may remain unaffected until late stages in severe TR. Effective RV ejection fraction (eRVEF) is corrected by the amount of TR and may reflect an earlier parameter of RV dysfunction. Purpose To compare the prognostic impact of both indices of RV function: RVEF and eRVEF in a multicentre cohort of patients with severe TR. Methods Patients with at least severe TR assessed by 2D echocardiography with a contemporary cardiac magnetic resonance (CMR) study were included in this study. In addition to conventional parameters of biventricular volume and function, eRVEF was assessed in all patients. eRVEF was calculated according to the formula: eRVEF=net pulmonary forwardflow/RV− EDV (figure). A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined. Results 271 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (age 71 ± 11 years, 67% female, 83% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 27 months (IQR: 10-53 months), 41% of the patients (n=112) experienced the combined endpoint (n=97 were admitted due to HF, n=49 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in multivariate Cox proportional models, both RVEF and eRVEF were independently associated with all-cause mortality and heart failure (adj HR for RVEF HR per 1%=0.96 [0.94-0.98], p<0.001 and for eRVEF per 1%=0.98 [0.96-0.99], p<0.001). A value of eRVEF of ≤37% were associated with impaired prognosis (figure). eRVEF identified higher rates of RV dysfunction compared to RVEF (49% vs 38%, p<0.001). eRVEF was superior to RVEF to predict outcomes (higher AUC 0.70 [0.63-0.76] vs 0.66 [0.59-0.73, p<0.001; Δ C-statistic 0.139 [0.040-0.237], p=0.05). Conclusion RV function is crucial for determining optimal timing for TR intervention. eRVEF is corrected by the amount of TR and identify higher rates of RV dysfunction in severe TR. eRVEF held stronger association with outcome compared to RVEF.eRVEF calculationKaplan Meier Curves

DELINEATE-Regurgitation: deep learning for automated assessment of aortic, mitral, and tricuspid regurgitation from echocardiography

Abstract Background Valvular heart diseases, including aortic regurgitation (AR), mitral regurgitation (MR), and tricuspid regurgitation (TR) are significant contributors to cardiovascular morbidity and mortality worldwide. Artificial intelligence (AI) may improve echocardiographic assessment, but no models to date have successfully evaluated valvular regurgitation. Purpose The goal of this study was to develop an AI system to improve the accuracy of echocardiographic AR, MR, and TR interpretation. Methods Complete transthoracic echocardiogram (TTE) studies performed at a single center were split into train (n=65,301), validation (14,018), and test sets (13,746). The Deep Learning for Echo Analysis, Tracking, and Evaluation of Valvular Regurgitation (DELINEATE-Regurgitation) system intakes entire TTE studies, identifies color Doppler clips showing each valve, and yields a study level classification of AR, MR, and TR on a 6-grade scale (none/trace, mild, mild-moderate, moderate, moderate-severe, severe) using the cardiologist interpretation as a reference standard. This system used a hybrid neural network, leveraging the spatiotemporal feature learning capabilities of convolutional neural networks with the sequential processing strengths of transformer networks. The end-to-end hybrid approach allows the model to learn nuanced representations of the data including features within and across color Doppler videos. Model accuracy was assessed using quadratically weighted Cohen’s kappa (k), area under the receiver operator characteristic curve (AUROC) for the detection of both "moderate or greater" and "severe" regurgitation, and AI-cardiologist agreement the 6-grade scale. Additionally, an analysis was conducted using a 4-grade regurgitation scale (none/trace, mild, moderate, and severe) by rolling up intermediate classes (mild-moderate and moderate-severe) into the next higher class for both cardiologist determinations and model predictions. Results The DELINEATE-Regurgitation system demonstrated a high accuracy in the classification of AR (k=0.857), MR (k=0.867), and TR (k=0.847) (Figure 1). DELINEATE predicted the same severity as cardiologists (AR 91.8%, MR 79.9%, TR 77.7%) or within ±1 grade accuracy (AR 99.5%, MR 98.6%, TR 98.6%). The models had excellent binary discrimination in the detection of moderate or greater (AR AUROC 99.4, MR 98.6, TR 98.1) and severe (AR 99.7, MR 99.3, TR 99.6) regurgitation (Figure 2). In the 4-grade scale, the model had exact agreement with cardiologists in 92.3% of AR, 82.4% of MR, and 80.6% of TR cases. Panel adjudication of AI-cardiologist disagreement and correlation with quantitative metrics at higher levels of regurgitation will be presented. Conclusions The DELINEATE-Regurgitation AI system demonstrates a high level of accuracy in the assessment of AR, MR, and TR using color Doppler TTE videos. Future work will focus on automating quantification and developing strategies for optimal clinical deployment.Figure 1 - Confusion MatricesFigure 2 - ROC Curves

Mortality based right ventricle functional echocardiographic cutoffs in patients with compared to without tricuspid regurgitation

Abstract Introduction Tricuspid-annular-plane-systolic-excursion (TAPSE) and peak-lateral-tricuspid-annular-systolic-velocity (S’) are frequently used echocardiographic indices of right-ventricle (RV) function. Tricuspid regurgitation (TR) is present in 70-90% of the general population, and while trivial or mild TR may not have prognostic implications, several studies have demonstrated that ≥moderate TR is an independent predictor of adverse outcomes, and that increasing TR severity incurs an increased risk of mortality. The abnormality thresholds for TAPSE and S' are based on published mean and standard deviation data obtained from healthy adults, but not on outcome data. The effect of significant TR on the abnormality threshold of TAPSE and S’ prime is currently unknown. Purpose We aimed to re-examine the abnormality thresholds for TAPSE and S' based on their association with mortality in consecutive patients, stratified to with, or without, significant tricuspid regurgitation (TR). Methods We performed a retrospective analysis of consecutive patients undergoing echocardiography between 2011-2021 in a large tertiary center. TR was assessed using a semi-quantitative method. Cut-off values associated with excess mortality were assessed using spline curves in univariate, and multivariate Cox logistic regression analyses. Results A total of 24717 subjects were included in the current analysis with a median (interquartile range) follow up of 1321 (581-1902) days. 1143 (4.6%) subjects had clinically significant (≥moderate) TR. In the entire cohort, TAPSE<20.9 mm and S’ <10.9 cm/s were associated with excess mortality. In sub-group analysis, among subjects with significant TR, TAPSE<18.0 mm and S'<10.0 cm/s was the cutoff associated with excess mortality, while subjects without TR had a higher cutoff of TAPSE<21.5 mm and S'<10.9 cm/s. In a multivariate model adjusted for the presence of TR and baseline characteristics, TAPSE<20.9 mm (HR 1.20, 95% CI 1.14-1.27; p<0.001) and S’<10.9 cm/s (HR 1.07, 95% CI 1.01-1.13; p=0.015) were independent predictors for mortality. A sensitivity analysis, which included 14,664 patients with additional echocardiographic indices, demonstrated that low TAPSE remained an independent predictor of mortality (aOR=1.15; 95% CI: 1.07-1.24; p<0.001) Conclusion TAPSE and S’ thresholds associated with excess mortality are higher than those previously reported in healthy adults. The TAPSE and S' cutoffs associated with excess mortality were lower in patients with significant TR compared to patients without, suggesting that a personalized approach for their interpretation is needed.Central illustration

Predictive factors for recurrent tricuspid regurgitation after tricuspid annuloplasty: 3D echocardiography study

Abstract Introduction There is growing concern about the recurrence of tricuspid regurgitation (TR) after tricuspid annuloplasty (TA) in individuals with functional tricuspid regurgitation (FTR). While TA is effective in treating FTR, a comprehensive understanding of the echocardiographic factors influencing TR recurrence is crucial. Aim This study aims to employ multivariate regression analysis to investigate the prognostic significance of tricuspid valve (TV) geometry and echocardiographic parameters associated with both RV geometry and function. The focus is on comprehending these relationships in the context of recurrent TR subsequent to TA. Methods This prospective observational cohort study aimed to explore factors contributing to recurrent tricuspid regurgitation (TR) after tricuspid annuloplasty (TA). The focus was on patients with moderate or severe functional TR due to left heart valvular disease, particularly severe mitral regurgitation, excluding those with ischemic heart disease. The cohort included 66 individuals undergoing preoperative assessments with 2D and 3D echocardiography, quantifying RV and right atrial (RA) geometry, functional, and tricuspid valve (TV) parameters. TR severity followed ESC guidelines. Patients were categorized into effective TA (50 patients) and recurrent TR (16 patients) groups, defined by mild-moderate TR and significant moderate-severe TR one year post-surgery, respectively. SPSS software facilitated statistical analysis, with adjusted logistic regression considering parameters such as age and gender. Results Among the patients (54% male, mean age 68±9 years), no significant differences were found in gender, left ventricular and atrial parameters, or preoperative TV orifice area between groups (recurrent TR vs. effective TA: 38 [33] mm2 vs. 29 [15] mm2, p=0.117). Univariate logistic regression analysis identified Septal-Lateral Systolic TA Diameter (OR 1.62), Septal-Lateral Diastolic TA Diameter (OR 1.99), and Major Axis Diastolic TA Diameter (OR 1.59) as key predictors. For diagnostic efficacy, ROC analysis revealed Major Axis Diastolic TA Diameter (AUC 0.848; cut-off 52.5 mm), TV Leaflet Tenting Volume (AUC 0.778; cut-off 5.1 ml), and RV Basal Diameter (AUC 0.763; cut-off 47.5 mm) as the most predictive parameters. The combined use of predefined RV basal diameter and Major Axis Diastolic TA Diameter showed the highest odds ratio for recurrent TR. Conclusion Key predictors, including Septal-Lateral Systolic and Diastolic TA Diameters, and Major Axis Diastolic TA Diameter, were identified, emphasizing their significance in understanding TR recurrence after tricuspid annuloplasty. The combination of predefined RV basal diameter and Major Axis Diastolic TA Diameter showed the highest odds ratio for recurrent TR, offering valuable insights for clinical assessment and preventive strategies.

Mortality and heart failure in patients with severe tricuspid regurgitation. Impact of RV volumes and function by CMR.

Abstract Background Beyond symptoms, right ventricle (RV) dilatation and dysfunction are established criteria for intervention in patients with significant tricuspid regurgitation (TR); however defined thresholds to support intervention are lacking. As a result, the optimal timing for intervention remains controversial and it is commonly undertaken at a late stage. Purpose To describe prognostic cut-off values of RV size and function by Cardiac Magnetic Resonance in a multicentre cohort of patients with at least severe TR. Methods The study enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. Conventional parameters of biventricular volume and function were assessed in all patients. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 28 months (IQR: 10-54 months), 42% of the patients (n=134) experienced the combined endpoint (n=113 were admitted due to HF, n=61 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in a multivariate Cox proportional model (LR Chi-Square: 88.01, p<0.001), RV-EDV and RVEF were independently associated with all-cause mortality and heart failure (adjusted HR for RV-EDV per ml/m2 =1.008 [1.005-1.012], p<0.001 and RVEF HR per 1%=0.961 [0.942-0.981], p<0.001). Thresholds of RV-EDV ≥ 93 ml/m2, RV-ESV ≥ 39 ml/m2 and RVEF ≤ 58% held the best accuracy to predict outcomes (figure). In multivariable analysis, prognostic cut-off values of RV-EDV, RV-ESV and RVEF was associated with 1.91, 2.03, and 1.76-fold increased risk of HF or all-cause mortality respectively (RV-EDV HR: 1.91 [1.34-2.71], p<0.001, RV-ESV HR 2.03 [1.42-2.89], p<0.001 and RVEF HR1.76 [1.25-2.49], p=0.001). Conclusion RV size and function are crucial for determining optimal timing for TR intervention. CMR remains the gold standard to assess RV remodeling. Cut-off values of RV volume and function by CMR are defined in a multicentre cohort of patients based on outcome data; proposed thresholds differ from those previously established by echocardiography.Kaplan Meier curves

Gender-specific differences in severe tricuspid regurgitation. Finding from a TR multicentre CMR registry

Abstract Background Observational studies have suggested that severe tricuspid regurgitation (TR) is more prevalent in women than in men, although the pathophysiological causes that justify this difference are unknown. Purpose 1) to assess clinical and imaging differences by Cardiac Magnetic Resonance (CMR) between men and women and 2) to examine the relationship between gender and all-cause mortality in a multicentre cohort of patients with at least severe TR. Methods The study-enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. The primary outcome was all-cause mortality. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. Women showed a non-significant tend to lower prevalence of comorbidities, lower BNP and significantly lower creatinine values (table). Regarding CMR variables, women showed smaller indexed right ventricle (RV) volumes higher RVEF and lower TR regurgitant volume (table, p<0.05 for all). Left ventricle (LV) volumes were smaller and LVEF higher in women compared to men (p<0.001). During a median follow-up of 28 months (IQR: 10-54 months), there were 61 deaths (19%) with an estimated 5-year survival of 74%. Cumulative all-cause mortality was significantly worse in men compared to women (27% vs. 15%, p<0.001, figure). Male gender was significantly associated with all-cause mortality independently of age, RV volumes, RVEF and LVEF (HR 2,2 [1.34-3,68], p =0.002). Different cut-off values of index RV volumes and EF were predictive of mortality in men and women. In men a RV-EDV >110 ml/m2 and RVEF<57%; in women a RV-EDV >90 ml/m2 and RVEF< 60% were predictive of all-cause mortality (p<0.01). Conclusion Severe TR is more prevalent in women; however, it shows lower RV remodeling, better RV function and lower rate of events compared to men. Different prognostic RV cut-off values are provided based on CMR data.Gender differencesKaplan Meier Curves

Prognostic preoperative factors for recurrence of tricuspid regurgitation following annuloplasty: examining the influence of 3d echocardiography

Abstract Introduction The increasing worry revolves around the reappearance of tricuspid regurgitation (TR) following tricuspid annuloplasty (TA) among individuals dealing with functional tricuspid regurgitation (FTR). Despite TA's efficacy as a treatment, a complete understanding of the echocardiographic elements influencing the recurrence of TR is pivotal. This knowledge holds the potential to guide the development of more robust preventive strategies, aiming to ease the incidence of recurrent TR after TA. Aim The aim of this study was to examine the prognostic value of tricuspid valve (TV) and echocardiographic parameters related to both right ventricular (RV) geometry and function. Specifically, our focus is on understanding these relationships in the context of recurrent TR following TA. Methods This prospective observational cohort study aimed to investigate determinants of recurrent TR post-surgical TV repair. The focus was on patients with moderate or severe functional TR related to left heart valvular disease, primarily severe mitral regurgitation, excluding those with ischemic heart disease. The study involved 66 participants, assessed preoperatively with 2D and 3D echocardiography, examining RV and right atrial (RA) geometry, functional, and TV parameters. TR severity followed ESC guidelines. Two groups were formed: effective TA group (50 patients) and recurrent TR group (16 patients), defined by mild to moderate TR and significant moderate-severe TR one year post-surgery, respectively. Statistical analysis employed SPSS software, with adjusted univariate logistic regression considering age and gender. Results Of the patients, 54% were male, with a mean age of 68±9 years. Echocardiography parameters in Table 1 showed no significant differences in gender, left ventricular, atrial geometrical, functional parameters, or preoperative effective regurgitant TV orifice area between groups (recurrent TR vs. effective TA: 38 [33] mm2 vs. 29 [15] mm2, p=0.117). Univariate logistic regression analysis highlighted RV and RA geometry, along with TV diameter, as predictors for recurrent TR. Notably, 3D TV geometrical parameters had prognostic significance, as confirmed by univariate adjusted logistic regression analysis. Functional RV parameters did not exhibit statistical significance in this analysis. Conclusion In conclusion, the recurrence of moderate-severe functional tricuspid regurgitation following tricuspid annuloplasty is linked to the tricuspid annulus size, as well as the geometry of the right atrium and right ventricle before surgery. Notably, no correlation was identified between the recurrence of TR and alterations in RV function.

Edge-to-edge repair for tricuspid valve regurgitation: 1-year follow up and clinical implications from the TR- Interventional Study (TRIS)

Abstract Background Tricuspid regurgitation (TR) affects 7% of the population, contributing significantly to heart failure-related hospitalizations. Traditional treatments have several limitations, prompting the exploration of innovative interventions. Purpose The present study aims to investigate the efficacy of tricuspid valve transcatheter edge-to-edge repair (T-TEER) in real-world patients with severe and symptomatic TR deemed at high surgical risk. Primary objectives focus on assessing T-TEER-induced TR reduction and reverse structural remodeling of the RV. Secondary objectives include assessment of functional status, quality of life, and residual regurgitation during the 12-month follow-up period. Methods The TR-Interventional study (TRIS) is a prospective, single-arm study. From January 2021 to December 2023, we enrolled 44 symptomatic patients with at least severe TR referred for TEER. Outcomes included safety and effectiveness along with assessment of clinical status. Results The study cohort had a mean age of 78.3±7 years, with 77.3% women and a mean TRISCORE of 5.1±1.9. Seventeen patients (38.6%) had massive, 7 (15.9%) had torrential, and 20 (45.5%) patients had severe TR. Etiologies included functional (40.9%), degenerative (13.64%), lead-induced (15.9%), and mixed (29.54%) origin. The primary efficacy endpoint, which assesses the successful implantation and performance of the device at the 30-day mark, was attained in 82.9% of patients. The secondary efficacy endpoint, assessing the stability of TR reduction at the 12-month, was achieved in 82,3% of patients. Post-procedural TR reduction of at least 2 degrees was achieved in 84% of patients. Echocardiographic assessments indicate ongoing beneficial remodeling over the one-year follow-up (Figure 1). Effects on RV remodeling also became apparent at the one-year follow-up, including reductions in the RV end-diastolic basal (p<0.01) and medium (p= 0.04) diameters of the TA septal-lateral diameter (p< 0.01). Significant reduction in vena contracta width (9 mm to 3 mm; p=<0.01), regurgitant volume (58 ml to 30 ml; p<0.01), and effective regurgitant orifice area (EROA) (0.6 cm2 to 0.3 cm2; p<0.01), occurred between baseline and one-year follow-up (Figure 2). The NYHA Functional Class and KCCQ scores were improved from 30 days to 1 year (Figure 2). Conclusion TRIS suggests that T-TEER is a durable, effective, and safe therapeutic option for high-risk patients with severe TR. The enduring nature of TR reduction at one year correlates with sustained clinical benefits and reverse structural remodeling of the right ventricle.TR reductionNYHA and functional status

A decade of follow-up: atrial fibrillation, pulmonary pressure, and the progression of tricuspid regurgitation

Abstract Background While Atrial fibrillation is considered a risk factor for tricuspid regurgitation (TR), prospective long term data in the field is lacking. This analysis aimed to identify risk factors of TR progression during a decade of follow up among patients with and without AF. Methods Patients with full echocardiographic and clinical follow of at least 5 years were included. Individuals presenting with significant TR at baseline were excluded. Patients were divided into two groups based on baseline diagnosis of AF, followed by stratification according to systolic pulmonary artery pressure (sPAP). The primary outcome was the occurrence of new significant TR (≥ Moderate). Results Study population included 15,957 patients with a median age of 63 (IQR: 54-72) of whom 6,068 (38%) were women and 1,837 (11.5%) had baseline AF. During a median follow-up period of 11 years (8.5 – 13.5), 1,191 (7.5%) patients developed significant TR. Compared with sinus rhythm, patients with AF were 4 and 2 times more likely to develop significant TR during follow up in a univariate and multivariate models, respectively (95% CI 3.66 - 4.68 and 1.98 – 2.56, p < 0.001 for both). Older age, female sex, chronic kidney disease (CKD), left heart disease (LHD) and impaired right ventricular (RV) function, rate control and permanent AF were all risk factors for TR progression. The association of baseline AF with TR during follow up was sPAP – dependent, such that among patients with normal sPAP AF associated risk was high while among patients with high baseline sPAP AF-associated risk was significantly lower (HR 2.87 vs. 1.77; p for interaction < 0.001). Competing risk analysis with death as competing event yielded consisted results. Conclusions Baseline AF is a strong and independent risk factor for TR development. This association is more pronounced among patients with normal pulmonary arterial pressures, emphasizing the need for focused research on preventing TR development in this population.

Residual tricuspid regurgitation after transcatheter tricuspid valve edge-to-edge repair: the EuroTR Registry

Abstract Background Data on the prognostic impact of residual tricuspid regurgitation (TR) after transcatheter tricuspid valve edge-to-edge repair (T-TEER) are scarce. Purpose The aim of this analysis was to evaluate two-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. Methods Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR Registry) we investigated the impact of residual TR on two-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. Results The study included a total of 1286 T-TEER patients (53.6% females, mean age 78.0 ± 8.9 years). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of two-year all-cause mortality (hazard ratio 2.06, confidence interval 1.30-3.26, p=0.002, Figure 1). The prevalence of residual TR ≥3+ was 4-times higher in patients with higher baseline TR (vena contracta > 11.1 mm) and more severe TV tenting (tenting area >1.92 cm2) (Figure 2). Of note, no survival difference was observed in patients with residual TR ≤1+ vs. 2+ (76.2% vs. 73.1%, p=0.461). The rate of NYHA functional class ≥ III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p<0.001). Of note, the degree of TR reduction significantly correlated with the extend of symptomatic improvement (p=0.012). Conclusions T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ vs. 2+. Symptomatic improvement correlated with the degree of TR reduction.Figure 1- Residual TR after T-TEERFigure 2 - Predicting residual TR

Lead-related tricuspid regurgitation: an important phenotype seen through the lens of computed tomography

Abstract Background The imaging diagnostic approach of patients with cardiac implantable electronic devices (CIED)-related tricuspid regurgitation (TR) is undefined. Functional cardiac computed tomography angiography (4D-CTA) provides a complementary role to echocardiography in the evaluation of tricuspid valve (TV) apparatus and right ventricle (RV) remodeling, but the capability to assess lead-leaflet interaction is unknown. Purpose To evaluate the role of 4D-CTA anatomical and morphological diagnostic assessment in a cohort of patients with severe TR and CIED vs those without. Methods Clinical, echocardiographic and CTA data were collected from two quaternary centers for patients with severe TR and a CIED evaluated between January 2017 to October 2023. Functional and morphological CTA information assessed lead-leaflet relationship to divide patients in those with lead-related TR, those with no lead-TR causal relationship, and those with severe isolated TR but without CIED. Primary end-point was the occurrence of all-cause death. Results A total of 143 patients were identified, roughly dividng the cohort into thirds. Baseline characteristics and imaging characteristics of these 3 groups revealed important differences suggesting a more advanced patophysiology phenotype for those with lead-related TR, particularly presenting both the largest 4D-CTA-derived TV maximum coaptation gap and anatomical regurgitant orifice area (see Figure 1). At regression analysis, time from CIED implantation (OR 1.01, CI 1.00-1.09, p=0.031) and >3 leaflets valve morphology (OR 2.90, CI 1.01-8.32, p=0.040) were independently associated with lead-related TR. After a median follow-up of 18 months, the primary end-point occurred in 36 patients (25%) and was more common among patients with lead-related TR (p-value overall= 0.007, see Figure 2). While no differences in the rate of TV intervention were found, excessive mortality persisted for lead-related TR group even after adjustement for age and gender (HR 6.49, CI 1.72-14.47, p=0.006). Conclusion Systematic 4D-CTA in patients with severe TR and presence of a CIED, identified a large number of patients with lead-related TR with important functional and anatomical implications including greater TR severity and > 3 leaflets. These findings appear to have prognostic relevance that might have decision-making implications for patient management.Figure 1Figure 2