Functional Tricuspid Regurgitation Research Articles

Prevalence and clinical outcomes of isolated or combined moderate to severe mitral and tricuspid regurgitation in patients with cardiac amyloidosis.

Evidence on the epidemiology and prognostic significance of mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with cardiac amyloidosis (CA) is scarce. Overall, 538 patients with either transthyretin (ATTR, n = 359) or immunoglobulin light-chain (AL, n = 179) CA were included at three Italian referral centres. Patients were stratified according to isolated or combined moderate/severe MR and TR. Overall, 240 patients (44.6%) had no significant MR/TR, 112 (20.8%) isolated MR, 66 (12.3%) isolated TR, and 120 (22.3%) combined MR/TR. The most common aetiologies were atrial functional MR, followed by primary infiltrative MR, and secondary TR due to right ventricular (RV) overload followed by atrial functional TR. Patients with isolated or combined MR/TR had a more frequent history of heart failure (HF) hospitalization and atrial fibrillation, worse symptoms, and higher levels of NT-proBNP as compared to those without MR/TR. They also presented more severe atrial enlargement, atrial peak longitudinal strain impairment, left ventricular (LV) and RV systolic dysfunction, and higher pulmonary artery systolic pressures. TR carried the most advanced features. After adjustment for age, sex, CA subtypes, laboratory, and echocardiographic markers of CA severity, isolated TR and combined MR/TR were independently associated with an increased risk of all-cause death or worsening HF events, compared to no significant MR/TR [adjusted HR 2.75 (1.78-4.24) and 2.31 (1.44-3.70), respectively]. In a large cohort of patients with CA, MR, and TR were common. Isolated TR and combined MR/TR were associated with worse prognosis regardless of CA aetiology, LV, and RV function, with TR carrying the highest risk.

Functional tricuspid regurgitation and efficacy of electrical cardioversion in patients with atrial fibrillation and atrial functional mitral regurgitation.

Atrial functional mitral regurgitation (afMR) is common in patients with atrial fibrillation (AF). The presence of functional tricuspid regurgitation (fTR), which arises as a secondary effect of afMR, has the potential to impact the effectiveness of procedures aimed at restoring normal heart rhythm. In this study, we sought to evaluate the efficacy of electrical cardioversion (CVE) in AF regarding the presence and degree of fTR in patients with afMR. Retrospective analysis included 521 patients with persistent AF on optimal medical therapy undergoing CVE. 157 (30.1%) patients had afMR (characterized by left ventricle ejection fraction ≥ 50% and LA dilatation) and were divided into 2 groups: the group with fTR (107, 68.2%) and the group without fTR (50, 31.9%). Patients with afMR and fTR had a higher prevalence of metabolic syndrome (p = 0.02) and greater right atrial area (p < 0.01) compared to patients without fTR. The efficacy of CVE was lower in the group with fTR in comparison to patients with isolated afMR (82.2% vs. 94%; p = 0.048) and it was unrelated to the degree of fTR (p = 0.15) and RVSP (p = 0.56). The energy required for successful CVE was comparable regardless of the presence (p = 0.26) or severity of fTR (p = 0.94). The fTR frequently coexists with afMR and it significantly diminishes the effectiveness of CVE for treating AF. The degree of fTR does not appear to influence the efficacy of CVE.

A tissue-silicone integrated simulator for right ventricular pulsatile circulation with severe functional tricuspid regurgitation

There is a great demand for development of a functional tricuspid regurgitation (FTR) model for accelerating development and preclinical study of tricuspid interventional repair devices. This study aimed to develop a severe FTR model by creating a tissue-silicone integrated right ventricular pulsatile circulatory simulator. The simulator incorporates the porcine tricuspid annulus, valve leaflets, chordae tendineae, papillary muscles, and right ventricular wall as one continuous piece of tissue, thereby preserving essential anatomical relationships of the tricuspid valve (TV) complex. We dilated the TV annulus with collagenolytic enzymes under applying stepwise dilation, and successfully achieved a severe FTR model with a regurgitant volume of 45 ± 9 mL/beat and a flow jet area of 15.8 ± 2.3 cm2 (n = 6). Compared to a normal model, the severe FTR model exhibited a larger annular circumference (133.1 ± 8.2 mm vs. 115.7 ± 5.5 mm; p = 0.009) and lower coaptation height (6.6 ± 1.0 mm vs. 17.7 ± 1.3 mm; p = 0.003). Following the De-Vega annular augmentation procedure to the severe FTR model, a significant reduction in regurgitant volume and flow jet area were observed. This severe FTR model may open new avenues for the development and evaluation of transcatheter TV devices.

Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis

BackgroundFunctional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR). ObjectivesThis meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+). MethodsMEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. ResultsOut of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, −6.3% [95% CI: −11.1% to −1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, −4.4% [95% CI: −5.9% to −2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, −4.1% [95% CI: −7.6% to −0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, −1.9% [95% CI: −2.5% to −1.3%]; P < 0.001) and mortality. ConclusionsRV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)

Transcatheter tricuspid valve replacement for functional tricuspid regurgitation after left-sided valve surgery: A single-center experience.

Functional tricuspid regurgitation (FTR) following left-sided valve surgery (LSVS) is of clinical significance due to its high recurrence and mortality rates. Transcatheter therapy presents a potential solution to address this issue. The study aimed to assess the safety and efficacy of transcatheter tricuspid valve replacement using the Lux-Valve system in a single center for patients with FTR after LSVS. From June 2020 to April 2023, 20 patients with symptomatic severe FTR after LSVS were referred to our center. A multidisciplinary cardiac team evaluated these patients for suitability for transcatheter tricuspid valve replacement with Lux-Valve systems. Primary efficacy and safety endpoints were immediate postoperative tricuspid regurgitation severity ≤ moderate and major adverse events during follow-up. Twenty patients (average age 65.7 ± 7.4 years; 65.0% women) successfully underwent Lux-Valve system implantation after LSVS. All patients achieved ≤ moderate tricuspid regurgitation immediately after the procedure. Only one patient (5.0%) experienced a procedure-related major adverse event, leading to in-hospital mortality due to pulmonary infection. At the 6-month follow-up, 17 patients (89.5%) improved to New York Heart Association functional class I to II (p < 0.001). The overall Kansas City Cardiomyopathy Questionnaire score significantly improved (35.9 ± 6.7 points to 58.9 ± 5.8 points, p < 0.001). The Lux-Valve system was found to be safe and effective for treating FTR after LSVS. It resulted in positive early outcomes, including a significant reduction in FTR, improved functional status, and enhanced quality of life, especially in high-risk patients.

Myocardial work across different etiologies of right ventricular dysfunction and healthy controls.

Evaluating right ventricular (RV) function remains a challenge. Recently, novel echocardiographic assessment of RV myocardial work (RVMW) by non-invasive pressure-strain loops was proposed. This enables evaluation of right ventriculoarterial coupling and quantifies RV dyssynchrony and post-systolic shortening. We aimed to assess RVMW in patients with different etiologies of RV dysfunction and healthy controls. We investigated healthy controls (n=17), patients with severe functional tricuspid regurgitation (FTR; n=22), and patients with precapillary pulmonary hypertension (PCPH; n=20). Echocardiography and right heart catheterization were performed to assess 1) RV global constructive work (RVGCW; work needed for systolic myocardial shortening and isovolumic relaxation), 2) RV global wasted work (RVGWW; myocardial shortening following pulmonic valve closure), and 3) RV global work efficiency (RVGWE; describes the relation between RV constructive and wasted work). RVGCW correlated with invasive RV stroke work index (r=0.66, P<0.001) and increased in tandem with higher afterload, i.e., was low in healthy controls (454±73 mmHg%), moderate in patients with FTR (687±203 mmHg%), and highest among patients with PCPH (881±255 mmHg%). RVGWE was lower and RVGWW was higher in patients with FTR (86±8% and 91 mmHg% [53-140]) or PCPH (86±10% and 110 mmHg% [66-159]) as compared with healthy controls (96±3% and 10 mmHg%). RVMW by echocardiography provides a promising index of RV function to discriminate between patients with RV volume or pressure overload. The prognostic value of this measure needs to be settled in future studies.

Does concomitant tricuspid valve intervention at the time of left ventricular assist device placement for patients with significant tricuspid regurgitation lead to improved outcomes compared to isolated left ventricular assist device placement?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In patients with advanced heart failure (HF) and moderate to severe functional tricuspid regurgitation (TR) undergoing left ventricular assist device (LVAD) placement is concomitant tricuspid valve intervention (TVI) superior for the clinical outcomes of survival, right ventricular failure, rehospitalizations for HF, functional status, and quality of life?' Altogether, 56 papers were found using the reported search, of which 12 papers represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Our search found no significant clinical benefit for concomitant TVI at the time of LVAD placement. We conclude that patient with moderate-to-severe TR should not routinely undergo concomitant TVI with LVAD placement.

Atrial Functional Tricuspid Regurgitation in Patients Undergoing Transcatheter Aortic Valve Replacement

BackgroundKnowledge about atrial functional tricuspid regurgitation (afTR) in transcatheter aortic valve replacement (TAVR) patients is scarce. ObjectivesThe aim of the study was to analyze the association between the entity and the development of tricuspid regurgitation (TR) in patients undergoing TAVR for aortic stenosis and concomitant TR. MethodsWe analyzed patients undergoing TAVR for severe aortic stenosis from January 2013 to December 2020 and concomitant at least moderate TR at baseline. afTR was defined as enlargement of the right atrium in relation to the right ventricle. TR development after TAVR and 3-year all-cause mortality were evaluated. ResultsOut of 3,474 TAVR patients, we identified 420 patients with concomitant at least moderate TR. A total of 363 patients were included in the study, with 178 patients stratified in the afTR and 185 in the non-afTR group based on a receiver-operating characteristic curve cutoff of 1.132 of the right atrial/right ventricular area ratio. TR improvement after TAVR was observed in significantly less patients with afTR compared with non-afTR (31.1% vs 60.6%; P < 0.001). Multivariate regression analysis confirmed afTR as independent predictor for TR persistence (adjusted OR: 2.80; 95% CI: 1.66-4.76; P < 0.001). Moreover, afTR was associated with aggravation of TR after TAVR (17.0% vs 6.8%; P = 0.013). Three-year all-cause mortality was significantly higher in patients with persistence compared with patients with improvement of TR (P < 0.001). ConclusionsIn TAVR patients, afTR is an independent predictor for TR persistence. Moreover, TR persistence is associated with increased 3-year all-cause mortality.

Predictors of functional tricuspid regurgitation after successful left-sided valve surgery

Predictors of functional tricuspid regurgitation after successful left-sided valve surgery

Right heart remodeling and outcomes of patients with tricuspid regurgitation

Abstract Background Albeit long neglected, significant (at least moderate, ≥ 2+) tricuspid regurgitation (TR) is currently known to be associated with increased mortality, and has thus become a relevant therapeutic target [1-3]. Recent and somewhat preliminary evidence has shown, however, that different subtypes of TR might respond differently to current therapeutic options [4-5]. In fact, secondary TR, rather than being a single entity, can develop because of either right ventricular (RV) remodelling (i.e functional TR) or tricuspid annulus (TA) dilation secondary to right atrial (RA) dilation (i.e isolated TR). Purpose The aim of this meta-analysis was to study the association between right heart remodeling and long-term all-cause mortality in a population of patients with significant TR, independent of the treatment option. Methods MEDLINE, ISI Web of Science, and SCOPUS databases were searched for studies published up to July 2022. Studies reporting data on at least one echocardiographic RV anatomic and/or functional parameter and outcome in patients with significant TR were included. This study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The primary endpoint was long-term all-cause mortality. Results Out of 3152 studies, a total of 14 were included in the final analytic synthesis, enrolling 4394 subjects. The median follow-up was 33 [24–51] months. Overall, long-term all-cause mortality was 31% (95% confidence interval [CI]: 20-41%, p = &amp;lt;0.001; Figure 1); however, a significant difference was noted in the medical subgroup vs. the surgery subgroup (43% [32-53%] vs 11% [20-41%]). By means of a meta-regression analysis, a significant and inverse relation was found between tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC) and mortality (11 studies enrolling 3551 subjects, coefficient -0.063 [-0.111 to -0.014], p = 0.011; 9 studies, 2975 subjects, coefficient -0.044 [-0.059 to -0.029], p &amp;lt; 0.001, respectively; Figure 2A and 2B), whereas a significant and concordant relation was found between TA dimension, RA area and mortality (7 studies, 2986 subjects, coefficient 0.003 [0.002 to 0.005], p &amp;lt; 0.001; 6 studies, 1920 subjects, coefficient -0.019 [-0.025 to -0.013], p &amp;lt; 0.001, respectively; Figure 2C and 2D). Conclusions The higher mortality associated with right ventricular dysfunction and reduced mortality with increasing right atrial dilatation suggest a better prognostic outcome for isolated TR than functional TR. Careful assessment of right heart anatomy and function is warranted, as it might foster the identification of different subtypes of TR with unique prognoses.Forest plot all-cause mortalityResult of the meta-regression analysis

Incidence and predictors of the novo significant mitral and tricuspid regurgitation in patients with permanent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is related to atrial remodeling and annular enlargement, which leads to functional mitral and tricuspid regurgitation. These two entities can derive in heart failure with preserved left ventricular ejection fraction (LVEF), the reason why it is becoming a rising concern in recent years. However, its incidence and predictors have not been well established. Purpose This study aimed to assess the incidence and predictors of significant atrial functional mitral and tricuspid regurgitation in patients with permanent AF. Methods The study population comprised 547 patients from a Spanish health area diagnosed with permanent AF between 2014 and 2019 (CardioCHUVI-AF registry; ClinicalTrials.gov identifier: NCT04364516). Individuals who presented with atrial enlargement at the diagnosis, primary moderate to severe valve disease, previous cardiac surgery (including valve replacement or repair), decreased LVEF, pulmonary hypertension, or right ventricular pacing that could interfere with tricuspid valve closure were excluded. The median age was 78.0 (IQ 70.4-85.6), and men represented 43% of the population (235 patients) compared to women, which represented 57% (312 patients). During a median follow-up of 3.5 years (IQ 2.03-4.95) we assessed the incidence of moderate to severe de novo mitral and tricuspid valve regurgitation and its predictors. Results The development of moderate to severe mitral and tricuspid valve regurgitation was higher after three years of diagnosis. The incidence of mitral regurgitation was 3.8 (3.0-4.9) per 100 persons/year. The incidence of tricuspid regurgitation was 5.5 (4.5-6.8) per 100 persons/year. In addition, multivariate analysis showed an association between the development of mitral regurgitation and older age (HR 1.05 [CI 95% 1.01-1.09]), female sex (HR 1.82 [CI 95% 1.1-3]) and prior admission for HF (HR 2.35 [CI 95% 1.18-4.7]). On the other hand, the development of tricuspid regurgitation did not show an association with age (HR 1.02 [CI 95% 0.97-1.05]), but it did with prior admission for HF (HR 2.11 [CI 95% 1.17-3.79]) and female sex (HR 2.17 [CI 95% 1.43-3.3]). Conclusion Permanent atrial fibrillation was associated with an increased risk of developing atrial functional mitral and tricuspid regurgitation, especially after three years of the diagnosis and in the female sex. Older age was associated with a higher incidence of mitral regurgitation. Prior admission for HF was associated with a higher incidence of tricuspid regurgitation. Based on the preceding, monitoring a specific profile of patients with atrial fibrillation may be especially important in preventing and early treating valve disease that can compromise their prognosis.Incidence of mitral regurgitationIncidence of tricuspid regurgitation

Preoperative predictors of recurrent tricuspid regurgitation after annuloplasty: insights into the role of 3D echocardiography

Abstract Introduction There is a growing concern regarding the recurrence of tricuspid regurgitation (TR) after tricuspid annuloplasty (TA) in patients with functional tricuspid regurgitation (FTR). While TA is an effective treatment option, understanding the echocardiographic factors contributing to recurrent TR can help in developing more effective preventive measures to reduce the rate of recurrent TR after TA. Aim The aim is to investigate the relationship between tricuspid valve (TV) and right ventricular geometry and function parameters with recurrent TR after TA. Methods This study was designed as a prospective observational cohort study to investigate factors contributing to recurrent TR following surgical TV repair in patients with moderate or severe functional TR caused by left heart valvular disease, with severe mitral regurgitation as the dominant pathology. Patients with ischemic heart disease were excluded from the analysis. The study included 65 patients who underwent preoperative 2D and 3D echocardiographic assessments, which included the quantification of right ventricular (RV) and right atrial (RA) geometry, functional and TV parameters. The severity of TR was measured according to the recent ESC guidelines, and patients were divided into two groups based on the outcomes of TA: effective TA (43 patients) and recurrent TR group (22 patients). Effective TA was defined as mild TR one year after surgery, while recurrent TR group was defined as moderate or severe TR. Statistical analysis was conducted using SPSS statistical software. Results Of the patients, 54% were male, and the mean age was 68±9 years. The distribution of echocardiography parameters among the study groups are shown in Table 1. Analysis revealed that gender, left ventricular and atrial geometrical and functional parameters, or preoperative effective regurgitant TV orifice area did not differ between the groups (recurrent TR vs. effective TA: 33 [28] mm2 vs. 29 [18] mm2, p=0.113 respectively). However, recurrent TR was associated with dilated RV and RA parameters and an increased septal-lateral diameter of tricuspid annulus. RV functional parameters did not show significant associations. Of all preoperative parameters, RV middle (sensitivity 82%, specificity 63%; AUC 0.731) and basal (sensitivity 73%, specificity 65%; AUC 0.725) diameters, tricuspid annulus sphericity index (sensitivity 59%, specificity 70%; AUC 0.718), septal-lateral systolic (sensitivity 59%, specificity 76%; AUC 0.686) diameter, have the highest predictive value for recurrent TR. Conclusion Recurrent moderate or severe functional TR after TA is associated with preoperative tricuspid annulus size, RA and RV geometry, but not with changes of RV function. This information can guide surgical decision-making. To conclude with, improving our understanding of the factors contributing to recurrent TR after TA can improve patient outcomes and reduce the need for reoperations.

Novel miRNAs are key predictors of heart failure and mortality in functional tricuspid regurgitation

Abstract Background Functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, in particular heart failure (HF), but optimal timing for intervention remains controversial. Surgery is often performed late mainly because symptoms might go unnoticed until advance stage of the disease. While microRNA have been recently identified as prognostic biomarkers in different cardiovascular conditions, no study has been focus on patients with TR. Purpose To evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients with severe FTR. Methods Consecutive patients with severe FTR evaluated in the Heart Valve Clinic were prospectively included and underwent a comprehensive clinical protocol. Patients with non-valvular permanent atrial fibrillation (and no TR) undergoing anticoagulant therapy unit were prospectively recruited as a control group. The experimental design included a first screening phase in 16 subjects (8 atrial FTR and 8 AF controls) to identify candidate miRNAs differentially expressed in a miRNA qPCR panel containing 192 specific miRNAs, and a second validation phase in which selected miRNAs were screened for further validation by qRT-PCR in 118 additional patients (77 FTR and 41 controls). A combined endpoint of hospital admission due to HF and all-cause mortality at follow-up was defined. Results The initial screening revealed 16 differentially expressed miRNAs in atrial FTR vs. AF subjects matched by age, gender and atrial dimensions. The candidate miRNAs were subsequently validated in 118 subjects. After a median follow up of 20.4 months (ICR 8-35 months), 25 (32%) reached the combined endpoint. Patients with events showed different levels of miR-15a-5p, miR-152-3p, miR101-3p, miR-92a-3p, miR-363-3p, miR-324-3p and miR-22-3p (Table 1, p&amp;lt;0.05 for all). Based on the high or low relative expression of selected miRNAs (below or above the median value) patients were stratified; those patients with low relative expression of miR-15a-5p, miR-92a-3p, miR101-3p, and miR-363-3p, miR-324-3p and miR-22-3p, showed significantly higher rates of events (log rank test for all p &amp;lt; 0.01, figure). In a multivariate cox regression the analysis, the level of miR-15a-5p (HR: 3.97 [1.58-9.96], miR-92a-3p (HR: 2.64 [1.13-6.13] , and miR-363-3p (HR: 2.41 [1.04-5.60] were predictive of events independently of NYHA functional class and RV dimensions (p &amp;lt; 0.05 for all). Conclusions We identify for the first time circulating miRNAs in patients with severe FTR. We further show that several miRNA predict heart failure and all-cause mortality independently of RV dimension and symptomatic status. These novel biomarkers may help to identify those patients that benefit from earlier valve interventions.Differences in patients with eventsKaplan Meier Curves

Incidence and types of significant tricuspid regurgitation in atrial fibrillation and sinus rhythm

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) &amp;lt;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 &amp;gt;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, &amp;gt;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 &amp;lt;.001]. All types of incident ≥moderate TR occurred more frequently in AF (p &amp;lt;.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 &amp; TR after

Tricuspid regurgitation impact on outcomes (TRIO) score: an evaluation tool for patients undergoing tricuspid valve surgery?

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&amp;gt;2 mg/dl, history of heart failure, history of chronic lung disease, AST &amp;gt;40 units/L, heart rate &amp;gt;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 (&amp;gt;72h) and postoperative dialysis (p&amp;lt;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.

The expression of selected microRNAs enables identification of patients with functional atrial tricuspid regurgitation. New insights into TR pathophysiology

Abstract Background Functional tricuspid regurgitation (FTR) is a powerful and independent predictor of patients’ morbidity and mortality. Atrial FTR (A-FTR) is a recently defined phenotype associated with permanent atrial fibrillation. In A-FTR, the underlying pathophysiological factors behind tricuspid annulus (TA) enlargement and the subsequent development of atrial TRF are still unclear, given that despite RA enlargement, a significant fraction of patients presenting long-term persistent atrial fibrillation (AF) will fail to develop significant TR during follow-up. Different microRNAs (miRNAs) have been studied as regulators and diagnostic biomarkers in mitral and aortic valve disease, but no study has been focus on FTR so far. Purpose Our current study aims to identify and validate a selection of circulating miRNAs as potential regulators of A-FTR Methods Consecutive patients with severe A-FTR and patients with non-valvular permanent atrial fibrillation (AF without TR) undergoing anticoagulant therapy were prospectively recruited. The experimental design included a first screening phase in 16 subjects ((8 A-FTR and 8 AF controls) to identify candidate miRNAs differentially expressed in a miRNA qPCR panel containing 192 specific miRNAs, and a second validation phase in which selected miRNAs were screened for further validation by qRT-PCR in 80 additional patients (40 TR and 40 AF). Results The initial screening revealed 16 differentially expressed miRNAs in atrial FTR vs. AF subjects matched by age, gender and atrial dimensions (figure 1). In the validation phase, the expression of miR-29b-3p, miR-152-3p, miR-30e-5p, miR-186-5p, miR-126-5p and miR-148a-3p (p&amp;lt;0.05) were significantly different in A-FTR compared to AF. Among all, miR-186-5p, miR-152-3p and miR-30e-5p yielded the highest predictive values for the detection of A-FTR with areas under the curve of 0.96 (0.92-0.99), 0.90 (0.83-0.97) and 0.87 (0.79-0.95) respectively (p&amp;lt;0,001 for all, figure 2). Conclusions Patients with atrial FTR exhibited different miRNA fingerprint compared to patients with permanent AF without TR but similar degree of atrial enlargement. Additionally, our study identified 3 novel miRNAs as potential diagnostic biomarkers of A-FTR: miR-186-5p, miR-152-3p and miR-30e-5p which excellent accuracy. Whether the differential expression of such miRNAs precedes or follows the development of FTR or the subsequent leaflet adaptation or growth, will be further explored in future studies.Table and volcano plot of miRNAmiRNA ROC curves in A-FTR

Differential microRNA expression in atrial vs. ventricular functional tricuspid regurgitation. New insights into TR pathophysiology

Abstract Background Functional tricuspid regurgitation (FTR) is associated with poor cardiovascular outcomes. Different pathophysiologic process can lead to the onset and progression of tricuspid valve disease. While atrial FTR (A-FTR) is a recently defined phenotype associated with permanent atrial fibrillation, ventricular FTR (V-FTR) has classically been related to leaflet tethering in the context of RV remodelling due to pulmonary hypertension. Although the correct identification of both phenotypes carry important therapeutic and prognostic implications, A-FTR and V-FTR overlap in a significant number of patients. Purpose The present work study aims to study the differential expression of serum miRNAs in A-FTR vs V-FTR Methods Consecutive patients with severe A-FTR and V-FTR evaluated in the Heart Valve Clinic were prospectively recruited. Patients with non-valvular permanent atrial fibrillation without TR undergoing anticoagulant therapy unit were prospectively recruited as a control group. The experimental design included a first screening phase in 16 subjects ((8 A-FTR and 8 AF controls) to identify candidate miRNAs differentially expressed in a miRNA qPCR panel containing 192 specific miRNAs, and a second validation phase in which selected miRNAs were screened for further validation by qRT-PCR in 118 additional patients (40 A-FTR, 37 V-FTR and 41 controls). Results The initial screening revealed 16 differentially expressed miRNAs in atrial FTR vs. AF subjets matched by age, gender and atrial dimensions (figure 1). Table 1 demonstrates differential miRNA expression in atrial and ventricular TR compared to controls in the validation phase (n=118). Among all the miRNAs, miR-152-3p, miR 22-3p, miR-324-3p and miR-29c-3p were differentially expressed in the A-FTR compared to V-FTR (p&amp;lt;0.05 for both). A-FTR exhibited significantly different levels of expression of miR-29b-3p, miR-152-3p, miR-30e-5p, miR-186-5p and miR-126-5p (p&amp;lt;0.05), whereas V-FTR expressed differentially miR-15a-5p, miR-152-3p, miR-30e-5p and miR-186-5p, miR-22-3p respectively (p&amp;lt;0.05). Conclusions The current study shows for the first time differential miRNA expression in patients with FTR. It further shows a different expression of several miRNA in atrial compared to ventricular FTR. These findings provide needed insights on the pathophysiological pathway of the atrial vs. the ventricular phenotype of FTR, and important implications towards specific therapeutic options.miRNA in A-FTR and V-FTR

Functional tricuspid regurgitation associated with left-side valvulopathy: clinical profile and long term evolution based on pulmonary pressure

Abstract Introduction Tricuspid regurgitation (TR) is an entity with multiple etiologies, with functional TR associated with left-sided valvulopathy being the most frequent group in clinical practice, accounting for approximately 50%. This group has traditionally been considered a consequence of pulmonary hypertension (PH) secondary to left-sided valvulopathy, although this dogma has hardly been evaluated despite new clinical and pathophysiological knowledge of TR. In this study we aimed to evaluate the clinical profile and evolution of a large series of patients with significant TR based on pulmonary pressure. Methods Multicenter and retrospective study that included a series of consecutive patients with significant TR (moderate to severe or greater) diagnosed between 2002 and 2017. After excluding patients with organic TR (congenital or acquired), those with TR associated with left-sided valvular disease were included, defined by the presence of mild mitral stenosis, previous left-sided surgery, left-sided valvular prosthesis or other left-sided valvular disease of at least moderate grade. Patients were classified according to the absence or presence of PH which was estimated by echocardiography, defining a systolic pulmonary arterial pressure (PASP) ≥ 50 mmHg. Subsequently, the baseline clinical characteristics of the sample were compared and a follow-up was carried out to evaluate long-term mortality and hospitalization events due to heart failure (HF). Results A total of 422 patients were were included (160 with PASP &amp;lt;50 and 262 with PASP ≥50). The attached table shows the baseline characteristics of both groups. Patients with PASP &amp;lt;50 were younger, had a higher percentage of previous valvular surgery, AF, HTN, and DM, along with a lower percentage of pulmonary disease and right HF. After follow-up (median 42.6 months), significant differences were observed between the two groups (Figures 1 and 2) with higher overall long-term survival (p&amp;lt;0.001) and higher freedom from HF hospitalization (p 0.013) in the group without PH. Cox regression analysis showed that female sex was a predictor of higher survival (p&amp;lt;0.001) while age and previous diagnosis of RHF were predictors of mortality (p&amp;lt;0.001). Similarly, the presence of previous RHF and previous hospitalizations for HF were predictors of the HF hospitalization event (p&amp;lt;0.001). Conclusions In a large series of patients with left-sided valvular heart disease and TR, cases with estimated absence of significant PH were frequent (37.9%). Furthermore, it was observed that pulmonary disease (a possible concomitant cause of PH) was more frequent in the group with significant PH. The group without PH had a different clinical profile and a better long-term prognosis. All of this suggests that there are different factors that determine the development of significant TR associated with left-sided valvular heart disease, beyond secondary PH itself. These factors could influence the patient's prognosis.Baseline clinical characteristics.Kaplan Meier survival curves.

Atrial functional tricuspid regurgitation in patients undergoing transcatheter aortic valve replacement

Abstract Introduction Recently, a novel entity of tricuspid regurgitation (TR) – atrial functional TR, which is caused by enlargement of the right atrium – has gained in awareness. In comparison, ventricular functional TR occurs in the setting of left heart disease with pulmonary hypertension and subsequent enlargement of the right ventricle. While it could be demonstrated that in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), an improvement of moderate or severe tricuspid regurgitation (TR) can be observed in many patients, knowledge about the association between entity and improvement of TR is scarce. Purpose The aim of this study was to analyse if atrial functional TR, defined by the enlargement of the right atrium is associated with the persistence of TR after TAVR in patients with severe AS and at least moderate concomitant TR at baseline. Moreover, 3-year all-cause mortality in patients with atrial and ventricular TR was assessed. Methods We retrospectively examined 363 patients with at least moderate tricuspid regurgitation undergoing TAVR from January 2013 to December 2020 due to severe AS. Patients with primary TR, a history of tricuspid valve surgery or with TAVR due to severe aortic regurgitation were excluded. Endsystolic area of the right atrium (RA) and enddiastolic area of the right ventricle (RV) were assessed in transthoracic echocardiography and atrial TR was defined as RA/RV area ratio above the median value of 1.125. Results TR improvement of at least one grade after transcatheter aortic valve replacement was significantly less frequent in patients with atrial compared to patients with ventricular TR (29.2% vs. 60.3%, p &amp;lt; 0.001, Figure 1). Multivariate logistic regression analysis with adjustment for left ventricular ejection fraction, Vena contracta and CT-determined tricuspid annulus diameter confirmed that atrial functional TR was an independent predictor for absence of TR improvement after TAVR (adjusted odds ratio: 3.03, 95% CI 1.65-5.64; p&amp;lt;0.001). Moreover, improvement of TR was associated with a significantly lower 3-year all-cause mortality compared to patients with persistence of TR (log rank test p&amp;lt;0.001, Figure 2A). However, no difference could be observed regarding 3-year all-cause mortality between patients with atrial and ventricular TR (log-rank test p=0.500, Figure 2B). Conclusion In patients undergoing TAVR for severe AS and at least moderate concomitant TR, atrial functional TR is an independent predictor for TR persistence. In addition, TR persistence is associated with increased 3-year all-cause mortality.Figure 1:Development of TR after TAVRFigure 2:3-year all-cause mortality

Early deterioration of right ventricular strain in patients undergoing transcatheter tricuspid valve intervention

Abstract Background Severe tricuspid regurgitation (TR) leads to volume overload and increased wall stress causing detrimental right ventricular (RV) remodelling and dysfunction and is associated with excess mortality. Transcatheter tricuspid valve interventions (TTVI) emerged to treat patients with severe TR and high surgical risk, but predictors of outcome remain largely unknown. RV free wall longitudinal strain (RVFWLS) is a sensitive parameter for RV dysfunction and has shown prognostic value in patients with functional TR treated conservatively. Periinterventional changes in RVFWLS and right atrial (RA) strain have not been evaluated in patients undergoing TTVI. Purpose To analyse the effect of transcatheter tricuspid valve annuloplasty (TTVA) and transcatheter edge-to-edge repair (TEER) on RVFWLS and RA strain, assessed by speckle tracking echocardiography, and their association with outcome. Methods We retrospectively analysed consecutive patients with severe TR that underwent TTVI at our centre between 2020 and 2022. 126 patients were included (n=48 underwent TTVA with the Cardioband system, n=78 underwent TEER with the PASCAL system). Established parameters for RV function (TAPSE, FAC) as well as RVFWLS and RA reservoir strain (RASR) were analysed at baseline and one month after TTVI. Results All patients (median age 80 years, 69% female, 79% in NYHA III/IV functional class) were at prohibitive surgical risk. RV function at baseline was slightly reduced according to FAC (34% [29-39]) and preserved according to TAPSE (18mm [15-20]), whereas RVFWLS (-18.6±5.7%) and RASR (10.0% [7.0-14.0]) were severely reduced in markedly dilated right heart chambers (RV basal 45mm [41-49], RA area 34 cm2 [28-41]). TR reduction following TTVI to TR grade ≤ 2 was achieved in 77%. Right heart chamber size significantly decreased after one month (RV basal 41mm [38-45], RA area 29cm2 [25-38], P&amp;lt;0.001), with no improvement of FAC (37% [30-40], P=0.668) or RASR (10% [7-13], P=0.143) but deterioration of RV longitudinal function (TAPSE 17mm [13-20], P=0.002; RFWLS -16.1±5.7%, P=0.001) compared to baseline. RVFWLS reduction occurred irrespective of the procedure performed (TEER [-9.2±41.4] vs. TTVA [-7.0±31.3], P=0.783). RVFWLS deterioration occurred in 63%, whereas it improved in 37% of patients. Symptomatic and clinical outcome did not differ in patients with deteriorated vs. improved RVFWLS (improvement of at least one NYHA class 61.9% vs. 58.3%, P=0.569, one-year mortality 13.7% vs. 12.3%, P=0.940, one-year heart failure rehospitalization 10.8% vs. 17.1%, P=0.701). Conclusion Deterioration of RVFWLS after TTVI possibly reflects the decreased wall stress due to TR and consecutive preload reduction. However, symptomatic and clinical outcomes did not differ in patients with deteriorated RVFWLS vs. patients with improved RVFWLS. Reduction of RA size after TTVI did not translate into improvement of RASR, indicating an already advanced pre-existing RA dysfunction.