Valvular Heart Disease: New Concepts in Pathophysiology and Therapeutic Approaches.

This review discusses recent advancements in the field of valvular heart disease. Topics covered include recognition of the impact of atrial fibrillation on development and assessment of valvular disease, strategies for global prevention of rheumatic heart disease, understanding and management of secondary mitral regurgitation, the updated classification of bicuspid aortic valve disease, recognition of heightened cardiovascular risk associated with moderate aortic stenosis, and a growing armamentarium of transcatheter therapies.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Secondary tricuspid regurgitation: incidence, types, and outcomes in atrial fibrillation vs. sinus rhythm.

BACKGROUND AND AIMS: Incidence and types of secondary tricuspid regurgitation (TR) are not well defined in atrial fibrillation (AFib) and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AFib; however, close to 50% of patients with A-STR do not have AFib. The aim of this study was to assess incidence, types, and outcomes of ≥ moderate TR in AFib vs. SR. METHODS: Adults with and without new-onset AFib without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular, and A-STR. RESULTS: Among 1359 patients with AFib and 20 438 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AFib related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P < .001), larger right atrial size (median 78 vs. 53 mL, P < .001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P < .001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR. CONCLUSIONS: New-onset AFib vs. SR conferred a higher risk of the individual TR types related to sequelae of AFib and higher pacemaker implantation rates, although the distribution of TR types was similar. Secondary TR was universally associated with increased mortality.

Transcatheter treatment of the tricuspid valve: current status and perspectives.

Transcatheter tricuspid valve interventions (TTVI) are emerging as alternatives to surgery in high-risk patients with isolated or concomitant tricuspid regurgitation. The development of new minimally invasive solutions potentially more adapted to this largely undertreated population of patients, has fuelled the interest for the tricuspid valve. Growing evidence and new concepts have contributed to revise obsolete and misleading perceptions around the right side of the heart. New definitions, classifications, and a better understanding of the disease pathophysiology and phenotypes, as well as their associated patient journeys have profoundly and durably changed the landscape of tricuspid disease. A number of registries and a recent randomized controlled pivotal trial provide preliminary guidance for decision-making. TTVI seem to be very safe and effective in selected patients, although clinical benefits beyond improved quality of life remain to be demonstrated. Even if more efforts are needed, increased disease awareness is gaining momentum in the community and supports the establishment of dedicated expert valve centres. This review is summarizing the achievements in the field and provides perspectives for a less invasive management of a no-more-forgotten disease.

Outcomes of tricuspid regurgitation after lead extraction.

INTRODUCTION: Transvenous leads have been implicated in tricuspid valve (TV) dysfunction, but limited data are available regarding the effect of extracting leads across the TV on valve regurgitation. The aim of this study is to quantify tricuspid regurgitation (TR) before and after lead extraction and identify predictors of worsening TR. METHODS: We studied 321 patients who had echocardiographic data before and after lead extraction. TR was graded on a scale (0 = none/trivial, 1 = mild, 2 = moderate, 3 = severe). A change of >1 grade following extraction was considered significant. RESULTS: A total of 321 patients underwent extraction of a total of 338 leads across the TV (1.05 ± 0.31 leads across the TV per patient). There was no significant difference on average TR grade pre- and postextraction (1.18 ± 0.91 vs. 1.15 ± 0.87; p = 0.79). TR severity increased after extraction in 84 patients, but was classified as significantly worse (i.e., >1 grade change in severity) in only 8 patients (2.5%). Use of laser lead extraction was associated with a higher rate of worsening TR postextraction (44.0% vs. 31.6%, p = 0.04). CONCLUSION: In our single-center analysis, extraction of leads across the TV did not significantly affect the extent of TR in most patients. Laser lead extraction was associated with a higher rate of worsening TR after extraction.

Cardiac implantable electronic device-induced tricuspid regurgitation: Implications and management.

Tricuspid regurgitation (TR) secondary to cardiac implantable electronic devices (CIEDs) has been well documented and is associated with worse cardiovascular outcomes. A variety of mechanisms have been proposed including lead-induced mechanical disruption of the tricuspid valvular or subvalvular apparatus and pacing-induced electrical dyssynchrony. Patient characteristics such as age, sex, baseline atrial fibrillation, and pre-existing TR have not been consistent predictors of CIED-induced TR. While two-dimensional echocardiography is helpful in assessing the severity of TR, three-dimensional echocardiography has significantly improved accuracy in identifying the etiology of TR and whether lead position contributes to TR. Three-dimensional echocardiography may therefore play a future role in optimizing lead positioning during implant to reduce the risk of CIED-induced TR. Optimal lead management strategies in addition to percutaneous interventions and surgery in alleviating TR are very important.

Incidence and economics of transvenous ICD lead complications: Implications for tricuspid valve function and interventions.

BACKGROUND: Implantable cardioverter-defibrillators are used globally and are reliable, but complications related to transvenous leads remain a concern. Evidence related to the incidence and costs of those complications is heterogeneous with respect to scope and healthcare system. This analysis aims to create estimates of the incidence and costs of tricuspid valve (TV) complications, lead failures, and lead extractions from a single large real-world data set. METHODS AND RESULTS: This retrospective longitudinal cohort study used the deidentified Medicare Fee for Service administrative claims database. A total of 116 036 patients with de novo transvenous ICD implant were analyzed. Mean hospital costs were $26 903 for tricuspid valve complications, $20 851 for lead failures, and $22 278 for lead extractions. CONCLUSIONS: Transvenous ICD lead complications incur significant costs to patients, hospitals, and payers when they occur. Advancements in lead technology that reduce these complications could bring significant clinical and economic value.

Implantable cardioverter-defibrillator lead failure and revision following transcutaneous bicaval valve (TricValve®) implantation.

INTRODUCTION: Tricuspid regurgitation is associated with significant morbidity and mortality, and occurs at a higher rate in patients with cardiovascular implantable electronic devices. Percutaneous strategies for managing tricuspid regurgitation are evolving, including the development of bicaval valve implantation which has been successfully used in patients with pacing leads. METHODS AND RESULTS: We present the first documented case of lead failure following TricValve® implantation, a dedicated self-expanding system for bicaval valve implantation, and the first successful lead revision procedure in this setting. CONCLUSION: The case illustrates important considerations in undertaking percutaneous intervention in patients with cardiovascular implantable electronic devices, and their ongoing management.

Present and Future Surgical Options for Tricuspid Regurgitation.

Tricuspid regurgitation, once considered a relatively benign condition, has now gathered significant attention due to new evidence showing its impact on both short- and long-term follow-up. While surgical intervention remains the established standard approach for treating severe tricuspid regurgitation, current guidelines provide Class I indication for intervention in only a limited set of scenarios. This review delves into the present and future perspectives of surgical tricuspid regurgitation management, examining aspects such as disease prognosis, surgical indications, outcomes, and a comprehensive overview of past and upcoming clinical trials.

Surgical Treatment Strategy of Functional Tricuspid Regurgitation.

Functional tricuspid regurgitation (FTR) is a common type of tricuspid regurgitation (TR), particularly in cases of left heart valve disease. Historically, cardiac surgeons have not placed much emphasis on FTR and instead focused primarily on managing left heart valve disease. However, as research has progressed, it has become evident that severe TR significantly impacts the prognosis of heart valve surgery. Furthermore, significant improvements in postoperative cardiac function and quality of life have been observed when addressing the tricuspid valve alongside left heart disease management. This article aims to review current approaches for and timing of the surgical management of FTR while also analyzing the limitations of existing tricuspid surgical strategies.

Change in Tricuspid Valve Function after Transvenous Lead Extraction, Predisposing Factors and Prognostic Roles.

Background: Changes in tricuspid valve (TV) function following transvenous lead extraction (TLE) and their impact on long-term survival have not yet been investigated. Methods: From 3633 patients undergoing lead extraction between 2006 and 2021, TV function before and after TLE was evaluated in 2693 patients. Results: After TLE, the TV function remained unchanged in 82.36% of patients, worsened in 9.54%, and improved in 8.10%. Abandoned leads (odds ratio, OR = 1.712; p = 0.044), fibrotic adhesions between leads and TV apparatus (OR = 3.596; p < 0.001), or right ventricular wall (OR = 2.478; p < 0.001) were predisposed to TV worsening. Non-infectious indications for TLE (OR = 1.925; p < 0.001), the severity of tricuspid valve regurgitation (TVR) before TLE (OR = 3.125; p < 0.001), and lead encapsulation (OR = 2.159; p < 0.001) were predictors of improvement in TV function. Although either worsening or improving TV function had no impact on long-term survival in all patients, decreased TVR severity in the subgroup of patients with initial regurgitation grades 3-4 was associated with a better prognosis (hazard ratio, HR = 0.622; p = 0.005). Conclusions: 1. Changes in TV function after TLE were observed in 17.64% of patients. 2. Various factors can predispose to lead-related TV changes, although the common denominator in these events is an extensive buildup of scar tissue. 3. Worsening TV function had no impact on survival after TLE. In patients with severe TV dysfunction, reduction in TVR following TLE was associated with a 40% reduction in mortality during a mean follow-up of 1673 days.

Severe Aortic Stenosis Associated with Other Valve Diseases: Open Surgery or Percutaneous Treatment?

Treatment decisions in the context of severe aortic stenosis (AS) associated with other valvular heart diseases (VHDs) have become a major challenge in recent years. Transcatheter aortic valve replacement (TAVR) in AS has increased significantly in younger patients with lower surgical risk, which has complicated the choice of the best treatment in cases of other associated valvulopathies. The most frequently associated lesions in this clinical scenario are mitral regurgitation (MR), mitral stenosis, and tricuspid regurgitation (TR). Furthermore, it should be noted that different percutaneous techniques are now available to accommodate any associated valvulopathies, which has considerably broadened the range of therapeutic options. The management of AS treated in isolation, especially by TAVR, has also shown that many cases of significant MR or TR are substantially reduced without any intervention. However, although some parameters have been described as potential risk factors in predicting the poor outcome of untreated VHDs, which cases will progress in a clinically more aggressive way remains uncertain. This review aimed to evaluate the most recent publications to provide the pathophysiology and prognosis of severe AS associated with other significant VHDs and to evaluate the best invasive therapeutic approach depending on the associated valvular disease.

Right ventricular remodeling and clinical outcomes following transcatheter tricuspid valve intervention.

AIMS: Characterize the impact of residual tricuspid regurgitation (TR) on right ventricle (RV) remodeling and clinical outcomes after transcatheter tricuspid valve intervention. METHODS: We performed a single-center retrospective analysis of transcatheter tricuspid valve repair (TTVr) or replacement (TTVR) patients. The primary outcomes were longitudinal tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulmonary artery systolic pressure (PASP), and RV dimensions (RVd). We used multivariable linear mixed models to evaluate association with replacement versus repair and degree of TR reduction with changes in these echo measures over time. Multivariable Cox regression was used to identify associations between changes in these echo measures and a composite clinical outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention. RESULTS: We included a total of 61 patients; mean age was 77.5 ± 11.7 and 62% were female. TTVR was performed in 25 (41%) and TTVr in 36 (59%). Initially, 72% (n = 44) had ≤ severe TR and 28% (n = 17) had massive or torrential TR. The median number of follow up echos was 2: time to 1st follow-up was 50 days (interquartile range [IQR]: 20, 91) and last follow-up was 147 (IQR: 90, 327). Median TR reduction was 1 (IQR: 0, 2) versus 4 (IQR: 3, 6) grades in TTVr versus TTVR (p < 0.0001). In linear mixed modeling, TTVR was associated with decline in TAPSE and PASP, and TR reduction was associated with decreased RVd. In multivariable Cox regression, greater RVd was associated with the clinical outcome (hazard ratio: 9.27, 95% confidence interval: 1.23-69.88, p = 0.03). CONCLUSION: Greater TR reduction is achieved by TTVR versus TTVr, which is in turn associated with RV reverse remodeling. RV dimension in follow-up is associated with increased risk of a composite outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention.

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

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Association of elevated tricuspid regurgitation velocity with cerebrovascular and kidney disease in children with sickle cell disease.

BACKGROUND: Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end-organ disease. METHODS: We conducted a cross-sectional study that evaluated the prevalence of elevated TRV ≥2.5 m/s and its associations with renal and cerebrovascular outcomes in children with sickle cell disease (SCD) 1-21 years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical Research and Intervention Program (SCCRIP) cohort at St. Jude Children's Research Hospital. We hypothesized that patients with SCD and elevated TRV would have higher odds of having either persistent albuminuria or cerebrovascular disease. RESULTS: We identified 166 children from the UAB cohort (mean age: 13.49 ± 4.47 years) and 325 children from the SCCRIP cohort (mean age: 13.41 ± 3.99 years) with echocardiograms. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (odds ratio [OR] 1.88, 95% confidence interval [CI]: 1.12-3.15; p = .017) and persistent albuminuria (OR 1.81, 95% CI: 1.07-3.06; p = .028) after adjusting for age, sex, treatment, and site. CONCLUSION: This cross-sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end-organ disease.

Evolution and prognosis of tricuspid and mitral regurgitation following cardiac implantable electronic devices: a systematic review and meta-analysis.

AIMS: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIEDs) are increasingly recognized. However, uncertainty remains as to whether the risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared with cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). The study aims to synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS AND RESULTS: We searched PubMed, EMBASE, and Cochrane Library databases published until 31 October 2023. Significant post-CIED TR and MR were defined as ≥ moderate. Fifty-seven TR studies (n = 13 723 patients) and 90 MR studies (n = 14 387 patients) were included. For all CIED, the risk of post-CIED TR increased [pooled odds ratio (OR) = 2.46 and 95% CI = 1.88-3.22], while the risk of post-CIED MR reduced (OR = 0.74, 95% CI = 0.58-0.94) after 12 and 6 months of median follow-up, respectively. Right ventricular pacing via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR = 4.54, 95% CI = 3.14-6.57) and post-CIED MR (OR = 2.24, 95% CI = 1.18-4.26). Binarily, CSP did not alter TR risk (OR = 0.37, 95% CI = 0.13-1.02), but significantly reduced MR (OR = 0.15, 95% CI = 0.03-0.62). Cardiac resynchronization therapy did not significantly change TR risk (OR = 1.09, 95% CI = 0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR = 0.49, 95% CI = 0.40-0.61). There was no significant association of LP with post-CIED TR (OR = 1.15, 95% CI = 0.83-1.59) or MR (OR = 1.31, 95% CI = 0.72-2.39). Cardiac implantable electronic device-associated TR was independently predictive of all-cause mortality [pooled hazard ratio (HR) = 1.64, 95% CI = 1.40-1.90] after median of 53 months. Mitral regurgitation persisting post-CRT independently predicted all-cause mortality (HR = 2.00, 95% CI = 1.57-2.55) after 38 months. CONCLUSION: Our findings suggest that, when possible, adoption of pacing strategies that avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Right Ventricular Dysfunction in Patients With Concomitant Tricuspid Regurgitation Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: This study investigated the impact and predictive factors of concomitant significant tricuspid regurgitation (TR) and evaluated the roles of right ventricle (RV) function and the etiology of TR in the clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).Methods and Results: We assessed grading of TR severity, TR etiology, and RV function in pre- and post-TAVI transthoracic echocardiograms for 678 patients at Keio University School of Medicine. TR etiology was divided into 3 groups: primary TR, ventricular functional TR (FTR), and atrial FTR. The primary outcomes were all-cause and cardiovascular death. At baseline, moderate or greater TR was found in 55 (8%) patients and, after adjustment for comorbidities, was associated with increased all-cause death (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.19-3.77; P=0.011) and cardiovascular death (HR 2.29; 95% CI 1.06-4.99; P=0.036). RV dysfunction (RVD) also remained an independent predictor of cardiovascular death (HR 2.06; 95% CI 1.03-4.14; P=0.042). Among the TR etiology groups, patients with ventricular FTR had the lowest survival rate (P<0.001). Patients with persistent RVD after TAVI had a higher risk of cardiovascular death than those with a normal or recovered RV function (P<0.001). CONCLUSIONS: The etiology of TR and RV function play an important role in predicting outcomes in concomitant TR patients undergoing TAVI.

Risk stratification by systemic manifestations secondary to hemodynamic disorders of patients with severe tricuspid regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown. METHODS: Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization. RESULTS: A total of 258 patients were identified with a median age of 73 (interquartile range [IQR]: 62-83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183-324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.0 to 3.7, P = 0.049). CONCLUSIONS: Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.