Carcinoid syndrome with right-sided valve involvement - a case report and review of the literature.

BACKGROUND: The survival of patients with neuroendocrine tumors has substantially improved with modern treatment options. Although the associated carcinoid syndrome can be diagnosed early and controlled effectively, cardiologists still encounter patients with cardiac manifestations, particularly among individuals with persistently high levels of vasoactive mediators. Treatment options have been limited to surgical valve replacement in fully manifested disease. Since surgery is not always feasible, transcatheter valve implantation is becoming an interesting alternative. CASE: A case of a 50-year-old woman with carcinoid syndrome and right-sided valvular heart disease is presented. Moderate pulmonary valve stenosis and severe tricuspid valve regurgitation were diagnosed during the evaluation and treatment of neuroendocrine tumor. The possibility of rare valve involvement and the need for interdisciplinary cooperation in the diagnosis, monitoring and treatment of patients with neuroendocrine tumors producing vasoactive substances must be emphasized. CONCLUSION: The patient had a typically presenting carcinoid syndrome with a rare cardiac manifestation. Although monitoring and treatment were carried out in accordance with recommendations and appropriate to the clinical condition, rapid progression of the metastatic disease ultimately precluded invasive cardiac intervention.

The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.

Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.

[Conservative treatment of valvular heart disease in adults]. / Konservative Therapie von Herzklappenvitien im Erwachsenenalter.

Currently, there is no specific medication approved for the treatment of valvular heart disease per se. Except for secondary mitral valve insufficiency and tricuspid valve insufficiency in pulmonary hypertension, drug therapy for higher-grade valvular heart disease is limited to diuretic therapy for symptom control. Conservative therapy for comorbidities and potential heart failure can be beneficial regardless of the specific valve lesion. In cases of aortic valve stenosis or insufficiency, controlling arterial hypertension is important. Patients with mitral valve stenosis benefit from rhythm and rate control. Diuretics can help reduce regurgitant volume in patients with primary mitral valve insufficiency and tricuspid valve insufficiency. In addition to drug therapy, maintaining functional capacity is crucial for the outcome of patients. Therefore, it is recommended to engage in active physical activity whenever possible, despite the presence of valvular heart disease.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

BACKGROUND: There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. METHODS AND RESULTS: A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects of warfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. CONCLUSIONS: In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Reduction of moderate to severe tricuspid regurgitation after catheter ablation for atrial fibrillation.

OBJECTIVE: Tricuspid regurgitation (TR) is a progressive disease with high mortality and limited medical treatment options, and its association with atrial fibrillation (AF) has been documented. This study aimed to investigate whether successful rhythm control through catheter ablation for AF could reduce TR severity. METHODS: A total of 106 patients with drug-refractory AF with moderate to severe secondary TR who underwent AF ablation were screened from a single-centre ablation registry. Echocardiographic parameter changes (pre-procedure vs 1 day/1 year post-procedure) were analysed. Holter monitoring was performed at 3/6/12 months to assess AF recurrence. The primary outcome was at least one grade TR reduction with its main determinants evaluated. RESULTS: After excluding 36 patients (prior tricuspid valve surgery, intracardiac devices or insufficient data), 70 patients (aged 63.8±9.7 years, 50% female) were analysed. Of these, 17 (24.3%) had severe TR, 55 (78.6%) persistent AF and all restored sinus rhythm with catheter ablation. The primary outcome was achieved in 53 (75.7%) at 1-year assessment (73.6% of moderate and 82.4% of severe TR). There were significant decreases of vena contracta (6.1→3.2 mm) and tricuspid annular diameter (37.3→32.6 mm) at 1 year. Although 25 patients experienced AF recurrence within 1 year, 56 (80%) patients finally maintained sinus rhythm with medical treatment (87% in patients with TR reduction and 59% without). From the multivariate analysis, sinus rhythm maintenance was the most significant determinant of TR reduction (OR 8.3, 95% CI 1.8 to 37.4). CONCLUSION: In patients with AF with moderate to severe TR, more than two-thirds of patients experienced reduced TR severity, with notable improvements in echocardiographic parameters. Sinus rhythm maintenance was associated with significant TR reduction.

Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation.

OBJECTIVE: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis. METHODS: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion. RESULTS: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size). CONCLUSIONS: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.

Echocardiographic estimation of pulmonary pressure in patients with severe tricuspid regurgitation.

OBJECTIVES: The estimation of systolic pulmonary artery pressure (sPAP) by transthoracic echocardiography (TTE) is challenging in patients with severe tricuspid regurgitation (TR). The study aimed to determine the reliability of the assessment of sPAP by TTE in this population. METHODS: This study was a single-centre analysis of consecutive patients at the University Hospital of Rennes with right heart catheterisation and TTE, performed with a maximum delay of 48 hours. Lin's concordance coefficient (LCC) and Bland-Altman analysis were used to compare the values. RESULTS: After applying the exclusion criteria, 236 patients were included in the analysis (age 71±11.5 years old; male 56%). The two principal indications were TR (34.3%) and mitral regurgitation (32.2%). The correlation between the two procedures was good in the total population (LCC=0.80; 95% limits of agreement (LOA): 0.74, 0.84), but weaker in the 78 patients (33%) with severe TR (LCC=0.67; 95% LOA: 0.49, 0.80), with a propensity to an underestimation by TTE. An elevated right atrial pressure (RAP) was associated with an underestimation by TTE of about 8 mmHg. The presence of a 'V-wave cut-off' sign on continuous-wave Doppler (OR=3.74; 95% CI 1.48, 9.30; p<0.01), found exclusively in patients with severe TR, was an independent predictor of sPAP misestimation by TTE. CONCLUSION: The reliability of the estimation of sPAP in patients with severe TR could be altered by high RAP which cannot be estimated with current thresholds.

Relationship between duration of atrial fibrillation and right heart structure remodeling as assessed by 3-dimensional transesophageal echocardiography.

BACKGROUND: Tricuspid valve (TV) remodeling occurs in patients with atrial fibrillation (AF); however, the affecting factor related to TV remodeling in AF remains to be elucidated. We sought to explore whether the AF persistence itself affects right heart remodeling. METHODS: A total of 372 lone AF patients (234 paroxysmal AF [paroxAF] and 138 persistent AF [persAF]) who underwent 3-dimensional transesophageal echocardiography (3D-TEE) was retrospectively reviewed. The duration from first-detected episode of AF to the TEE exam date was defined as AF duration. RESULTS: PersAF patients had a larger TV area index (625.4 vs 719.0 mm2/m2; P < 0.001) and a higher right atrium area-to-right ventricle end-systolic area ratio (RA/RVESA ratio, 1.7 vs 1.9; P = 0.005) than paroxAF patients. The prevalence of AF-tricuspid regurgitation was higher in persAF than in paroxAF patients (1.3% vs 12.3%; P < 0.001). In persAF patients, AF duration was moderately correlated with TV diameter and 3D-TEE-derived TV annular area but not in paroxAF. On multivariable analysis, AF duration was independently associated with TV annular dilatation even after adjustment for RA/RVESA ratio and tricuspid regurgitation severity (ß 0.37 [95% CI: 0.77-1.81]; P < 0.001). Additionally, AF duration with cutoff values of 20 months for predicting TV annular dilatation and 37 months for predicting RA/RVESA ratio > 2.1 had both high diagnostic accuracies among persAF patients (both P < 0.01). CONCLUSIONS: AF duration itself is independently associated with right heart remodeling in persAF but not in paroxAF, such as TV annular dilatation and predominant RA remodeling which may lead to subsequent TR progression and adverse outcomes.

Reversible Tricuspid Regurgitation Due to Beriberi.

We report a case of cardiac beriberi in a 76-year-old man who was hospitalized with a congestive condition of subacute onset, diagnosed as high-output heart failure associated with severe tricuspid regurgitation and indication for caval valve implantation, which, after thiamine replacement, resulted in improvement of all conditions. (Level of Difficulty: Beginner.).

Tricuspid Edge-to-Edge Repair Versus Tricuspid Valve Replacement for Severe Tricuspid Regurgitation.

BACKGROUND AND OBJECTIVES: Tricuspid valve (TV) repair techniques other than annuloplasty remain challenging and frequently end in tricuspid valve replacement (TVR) in complicated cases. However, the results of TVR are suboptimal compared with TV repair. This study aimed to evaluate the clinical effectiveness of TV edge-to-edge repair (E2E) compared to TVR for severe tricuspid regurgitation (TR). METHODS: We retrospectively reviewed 230 patients with severe TR who underwent E2E (n=139) or TVR (n=91) from 2001 to 2020. Clinical and echocardiographic results were analyzed using inverse probability of treatment weighting analysis and propensity score matching. RESULTS: The two groups showed no significant differences in early mortality and morbidities. During the mean follow-up of 106.2±68.8 months, late severe TR and TV reoperation rates were not significantly different between groups. E2E group, however, showed better outcomes in overall survival (p=0.023), freedom from significant tricuspid stenosis (TS) (trans-tricuspid pressure gradient ≥5 mmHg, p=0.021), and freedom from TV-related events (p<0.001). Matched analysis showed consistent results. CONCLUSIONS: E2E for severe TR presented more favorable clinical outcomes than TVR. Our study supports that E2E might be a valuable option in severe TR surgery, avoiding TVR.

Machine learning facilitates the prediction of long-term mortality in patients with tricuspid regurgitation.

OBJECTIVE: Tricuspid regurgitation (TR) is a prevalent valve disease associated with significant morbidity and mortality. We aimed to apply machine learning (ML) to assess risk stratification in patients with ≥moderate TR. METHODS: Patients with ≥moderate TR on echocardiogram between January 2005 and December 2016 were retrospectively included. We used 70% of data to train ML-based survival models including 27 clinical and echocardiographic features to predict mortality over a 3-year period on an independent test set (30%). To account for differences in baseline comorbidities, prediction was performed in groups stratified by increasing Charlson Comorbidity Index (CCI). Permutation feature importance was calculated using the best-performing model separately in these groups. RESULTS: Of 13 312 patients, mean age 72 ± 13 years and 7406 (55%) women, 7409 (56%) had moderate, 2646 (20%) had moderate-severe and 3257 (24%) had severe TR. The overall performance for 1-year mortality by 3 ML models was good, c-statistic 0.74-0.75. Interestingly, performance varied between CCI groups, (c-statistic = 0.774 in lowest CCI group and 0.661 in highest CCI group). The performance decreased over 3-year follow-up (average c-index 0.78). Furthermore, the top 10 features contributing to these predictions varied slightly with the CCI group, the top features included heart rate, right ventricular systolic pressure, blood pressure, diuretic use and age. CONCLUSIONS: Machine learning of common clinical and echocardiographic features can evaluate mortality risk in patients with TR. Further refinement of models and validation in prospective studies are needed before incorporation into the clinical practice.

Transfemoral Transcatheter Tricuspid Valve Replacement Using the EVOQUE System in an Octogenarian for Severe Tricuspid Valve Regurgitation.

Tricuspid regurgitation is a frequent condition that is linked to an elevated risk of cardiovascular events and significant mortality but is often overshadowed by left-sided valve diseases. Isolated surgical tricuspid valve surgery is still considered a high-risk surgery, and over recent years, various transcatheter procedures for tricuspid treatment have emerged as an alternative solution. Among the available transcatheter procedures, the EVOQUE system's transcatheter tricuspid valve replacement could potentially offer a solution, especially in patients considered non-eligible for transcatheter edge-to-edge tricuspid valve repair. We present a case report of an octogenarian patient considered at prohibitive risk for conventional surgery and not eligible for transcatheter edge-to-edge repair who was eventually treated with a transfemoral transcatheter tricuspid 52-mm EVOQUE valve implantation. Postprocedural recovery and follow-up at 18 months were uneventful, with a well-functioning tricuspid valve bioprosthesis.

[T-TEER: description of a development process]. / T-TEER: Beschreibung eines Entwicklungsprozesses.

Tricuspid valve regurgitation (TR) is becoming increasingly more clinically important. While considered as an accompanying symptom of left heart pathologies in the past, TR is now seen as an independent and clinically significant condition. TR can lead to volume overload of the right ventricle, resulting in dilatation of the tricuspid valve annulus and worsening of the regurgitation. Undetected or untreated severe TR can lead to recurrent cardiac decompensation with hospitalization, reduced quality of life and death. Previous treatment options were limited to cardiac surgery and associated with high complication and mortality rates, especially in isolated TR. Therefore, many patients are considered inoperable so that the new interventional treatment measures nowadays often represent the only treatment option. Interventional treatment options such as the edge-to-edge procedure (T-TEER) with TriClip™ or the PASCAL™ system are very safe interventions that have already shown promising results, including reduction of TR, improvement in heart failure symptoms and the quality of life. The influence on the mortality and the necessity for hospitalization due to heart failure are currently being investigated in several randomized studies. Patient selection and timing of the intervention are crucial. Cardiovascular imaging plays a decisive role in selecting the appropriate method and timing of the intervention. The prognosis depends on factors, such as the severity of TR, right ventricular dysfunction, and pulmonary arterial hypertension. Overall, interventional TR treatment is a promising advancement in treatment from which many patients can benefit in the future.

Clinical outcomes and progression rate of tricuspid regurgitation in patients with rheumatic mitral valve disease.

OBJECTIVE: A substantial proportion of patients with rheumatic heart disease (RHD) have tricuspid regurgitation (TR). This study aimed to identify the impact of functional TR on clinical outcomes and predictors of progression in a large population of patients with RHD. METHODS: A total of 645 patients with RHD were enrolled, mean age of 47±12 years, 85% female. Functional TR was graded as absent, mild, moderate or severe. TR progression was defined either as worsening of TR degree from baseline to the last follow-up echocardiogram or severe TR at baseline that required surgery or died. Incidence of TR progression was estimated accounting for competing risks. RESULTS: Functional TR was absent in 3.4%, mild in 83.7%, moderate in 8.5% and severe in 4.3%. Moderate and severe functional TR was associated with adverse outcome (HR 1.91 (95% CI 1.15 to 3.2) for moderate, and 2.30 (95% CI 1.28 to 4.13) for severe TR, after adjustment for other prognostic variables. Event-free survival rate at 3-year follow-up was 91%, 72% and 62% in patients with no or mild, moderate and severe TR, respectively. During mean follow-up of 4.1 years, TR progression occurred in 83 patients (13%) with an overall incidence of 3.7 events (95% CI 2.9 to 4.5) per 100 patient-years. In the Cox model, age (HR 1.71, 95% CI 1.34 to 2.17), New York Heart Association functional class III/IV (HR 2.57, 95% CI 1.54 to 4.30), right atrial area (HR 1.52, 95% CI 1.10 to 2.10) and right ventricular (RV) dysfunction (HR 2.02, 95% CI 1.07 to 3.84) were predictors of TR progression. By considering competing risk, the effect of RV dysfunction on TR progression risk was attenuated. CONCLUSIONS: In patients with RHD, functional TR was frequent and associated with adverse outcomes. TR may progress over time, mainly related to right-sided cardiac chambers remodelling.

Two-Year Outcomes for Tricuspid Repair With a Transcatheter Edge-to-Edge Valve Repair From the Transatlantic TRILUMINATE Trial.

BACKGROUND: Tricuspid regurgitation (TR) is a common and progressive valve disease with significant mortality and hospitalization burden. Tricuspid transcatheter edge-to-edge repair provides a treatment option for high-risk patients with primary and secondary TR. METHODS: The TRILUMINATE trial ([Trial to Evaluate Treatment With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater Tricuspid Regurgitation]; n=85) is an international, prospective, single-arm, multicenter study to investigate the safety and performance of tricuspid transcatheter edge-to-edge repair with the TriClip implant in patients with symptomatic moderate or greater TR. Echocardiographic assessment was performed at a core laboratory. Outcomes included safety and clinical effectiveness and echocardiographic assessment of TR. RESULTS: At 2 years, TR was reduced to moderate or less in 60% of subjects, and reduction of at least 1 grade was achieved in 85.4% of subjects. TR reduction was sustained in 75% of the patients. While most metrics suggest the majority of favorable remodeling occurred within the first 30 days post-procedure, both right ventricular end diastolic diameter and tricuspid annular plane systolic excursion show signals of continued favorable remodeling through 2 years. Substantial improvements in 6-minute walking distance, New York Heart Association functional class, and Kansas City Cardiomyopathy Questionnaire score were sustained from 30 days to 2 years. Even with low rates of cardiovascular mortality (15.3%) and all-cause mortality (18.7%) noted at 2 years, all-cause hospitalization rate decreased from 1.30 events per patient-year 1 year before device implantation to 0.66 events per patient-year 2 years after the TriClip procedure, representing a reduction of 49% (P<0.0001). CONCLUSIONS: Tricuspid transcatheter edge-to-edge repair using the TriClip implant was found to be safe and effective, with sustained benefits at 2 years in subjects with symptomatic moderate or greater TR. Repair efficacy was durable at 2 years in 75% of the patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03227757.