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.

Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation.

OBJECTIVE: The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). BACKGROUND: Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. METHODS: Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. RESULTS: Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59). CONCLUSIONS: AF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.

Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction.

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

Atrial functional tricuspid regurgitation: An underappreciated cause of secondary tricuspid regurgitation.

Secondary tricuspid regurgitation (TR) caused by right ventricular enlargement in the setting of left heart disease/pulmonary hypertension has been well described. In contrast, that associated with right atrial enlargement-atrial functional TR (AF-TR)-remains largely underappreciated. AF-TR most often occurs in the setting of lone atrial fibrillation, although it is also seen in its absence (idiopathic AF-TR). Several recent studies have found that the prevalence, hemodynamic significance, and prognosis of AF-TR are not inconsequential, suggesting increased physician awareness of this novel clinical entity is warranted. This article discusses the pathogenesis, echocardiographic findings, and treatment of this underappreciated cause of secondary TR.

Valve Disease in Heart Failure: Secondary but Not Irrelevant.

Secondary regurgitation caused by the remodeling and dysfunction of the left or right heart chamber may complicate heart failure, worsening both symptoms and prognosis. Outcome studies have shown that patients' prognosis worsened as the severity of secondary regurgitation increases. Imaging and more specifically echocardiography plays a central role for diagnosis and serial assessment of secondary regurgitation as well as for timing the intervention and guiding the procedure.

Right Atrial Remodeling and Outcome in Patients with Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with secondary tricuspid regurgitation (STR), right atrial remodeling (RAR) is a proven marker of disease progression. However, the prognostic value of RAR, assessed by indexed right atrial volume (RAVi) and reservoir strain (RAS), remains to be clarified. Accordingly, the aim of our study is to investigate the association with outcome of RAR in patients with STR. METHODS: We enrolled 397 patients (44% men, 72.7 ± 13 years old) with mild to severe STR. Complete two-dimensional and speckle-tracking echocardiography analysis of right atrial and right ventricular (RV) size and function were obtained in all patients. The primary end point was the composite of death from any cause and heart failure hospitalization. RESULTS: After a median follow-up of 15 months (interquartile range, 6-23), the end point was reached by 158 patients (39%). Patients with RAS <13% and RAVi >48 mL/m2 had significantly lower survival rates compared to patients with RAS ≥13% and RAVi ≤48 mL/m2 (log-rank P < .001). On multivariable analysis, RAS <13% (hazard ratio, 2.11; 95% CI, 1.43-3.11; P < .001) and RAVi > 48 mL/m2 (hazard ratio, 1.49; 95% CI, 1.01-2.18; P = .04) remained associated with the combined end point, even after adjusting for RV free-wall longitudinal strain, significant chronic kidney disease, and New York Heart Association class. Secondary tricuspid regurgitation excess mortality increased exponentially with values of 18.2% and 51.3 mL/m2 for RAS and RAVi, respectively. In nested models, the addition of RAS and RAVi provided incremental prognostic value over clinical, conventional echocardiographic parameters of RV size and function and RV free-wall longitudinal strain. CONCLUSIONS: In patients with STR, RAR was independently associated with mortality and heart failure hospitalization. Assessment of RAR could improve risk stratification of patients with STR, potentially identifying those who may benefit from optimization of medical therapy and a closer follow-up.

Corrigendum: The atrial secondary tricuspid regurgitation is associated to more favorable outcome than the ventricular phenotype.

[This corrects the article DOI: 10.3389/fcvm.2022.1022755.].

A streamlined, machine learning-derived approach to risk-stratification in heart failure patients with secondary tricuspid regurgitation.

AIMS: Secondary tricuspid regurgitation (sTR) is the most frequent valvular heart disease and has a significant impact on mortality. A high burden of comorbidities often worsens the already dismal prognosis of sTR, while tricuspid interventions remain underused and initiated too late. The aim was to examine the most powerful predictors of all-cause mortality in moderate and severe sTR using machine learning techniques and to provide a streamlined approach to risk-stratification using readily available clinical, echocardiographic and laboratory parameters. METHODS AND RESULTS: This large-scale, long-term observational study included 3359 moderate and 1509 severe sTR patients encompassing the entire heart failure spectrum (preserved, mid-range and reduced ejection fraction). A random survival forest was applied to investigate the most important predictors and group patients according to their number of adverse features.The identified predictors and thresholds, that were associated with significantly worse mortality were lower glomerular filtration rate (<60 mL/min/1.73m2), higher NT-proBNP, increased high sensitivity C-reactive protein, serum albumin < 40 g/L and hemoglobin < 13 g/dL. Additionally, grouping patients according to the number of adverse features yielded important prognostic information, as patients with 4 or 5 adverse features had a fourfold risk increase in moderate sTR [4.81(3.56-6.50) HR 95%CI, P < 0.001] and fivefold risk increase in severe sTR [5.33 (3.28-8.66) HR 95%CI, P < 0.001]. CONCLUSION: This study presents a streamlined, machine learning-derived and internally validated approach to risk-stratification in patients with moderate and severe sTR, that adds important prognostic information to aid clinical-decision-making.

Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge-to-edge repair - Results from the TriValve registry.

AIM: Functional or secondary tricuspid regurgitation (STR) is the most common phenotype of tricuspid regurgitation (TR) with atrial STR (ASTR) and ventricular STR (VSTR) being recently identified as two distinct entities. Data on tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with STR according to phenotype (i.e. ASTR vs. VSTR) are lacking. The aim of this study was to assess characteristics and outcomes of patients with ASTR versus VSTR undergoing T-TEER. METHODS AND RESULTS: Patients with STR undergoing T-TEER were selected from the Transcatheter Tricuspid Valve Therapies (TriValve) registry. ASTR was defined by (i) left ventricular ejection fraction ≥50%, (ii) atrial fibrillation, and (iii) systolic pulmonary artery pressure <50 mmHg. Patients not matching these criteria were classified as VSTR. Patients with primary TR and cardiac implantable electronic device were excluded. Key endpoints included procedural success and survival at follow-up. A total of 298 patients were enrolled in the study: 65 (22%) with ASTR and 233 (78%) with VSTR. Procedural success was similar in the two groups (80% vs. 83% for ASTR vs. VSTR, p = 0.56) and TEER was effective in reducing TR in both groups (from 97% of patients with baseline TR ≥3+ to 23% in ASTR and to 15% in VSTR, all p = 0.001). At 12-month follow-up, survival was significantly higher in the ASTR versus VSTR cohort (91% vs. 72%, log-rank p = 0.02), with VSTR being an independent predictor of mortality at multivariable analysis (hazard ratio 4.75). CONCLUSIONS: In a real-world, multicentre registry, T-TEER was effective in reducing TR grade in both ASTR and VSTR. At 12-month follow-up, ASTR showed better survival than VSTR.

Contemporary insights into the epidemiology, impact and treatment of secondary tricuspid regurgitation across the heart failure spectrum.

AIM: Tricuspid regurgitation secondary to heart failure (HF) is common with considerable impact on survival and hospitalization rates. Currently, insights into epidemiology, impact, and treatment of secondary tricuspid regurgitation (sTR) across the entire HF spectrum are lacking, yet are necessary for healthcare decision-making. METHODS AND RESULTS: This population-based study included data from 13 469 patients with HF and sTR from the Viennese community over a 10-year period. The primary outcome was long-term mortality. Overall, HF with preserved ejection fraction was the most frequent (57%, n = 7733) HF subtype and the burden of comorbidities was high. Severe sTR was present in 1514 patients (11%), most common among patients with HF with reduced ejection fraction (20%, n = 496). Mortality of patients with sTR was higher than expected survival of sex- and age-matched community and independent of HF subtype (moderate sTR: hazard ratio [HR] 6.32, 95% confidence interval [CI] 5.88-6.80, p < 0.001; severe sTR: HR 9.04; 95% CI 8.27-9.87, p < 0.001). In comparison to HF and no/mild sTR patients, mortality increased for moderate sTR (HR 1.58, 95% CI 1.48-1.69, p < 0.001) and for severe sTR (HR 2.19, 95% CI 2.01-2.38, p < 0.001). This effect prevailed after multivariate adjustment and was similar across all HF subtypes. In subgroup analysis, severe sTR mortality risk was more pronounced in younger patients (<70 years). Moderate and severe sTR were rarely treated (3%, n = 147), despite availability of state-of-the-art facilities and universal health care. CONCLUSION: Secondary tricuspid regurgitation is frequent, increasing with age and associated with excess mortality independent of HF subtype. Nevertheless, sTR is rarely treated surgically or percutaneously. With the projected increase in HF prevalence and population ageing, the data suggest a major burden for healthcare systems that needs to be adequately addressed. Low-risk transcatheter treatment options may provide a suitable alternative.

Concomitant Transcatheter Edge-to-Edge Treatment of Secondary Tricuspid and Mitral Regurgitation: An Expert Opinion.

Secondary (functional) tricuspid regurgitation (sTR) is common in patients with mitral regurgitation (MR). Because combined valvular heart disease affects long-term survival, in comparison with isolated MR or tricuspid regurgitation, it is essential to offer patients adequate treatment. Despite considerable experience, no conclusive data are yet available on the prognostic impact of concomitant tricuspid valve surgery at the time of mitral valve surgery. Emerging transcatheter treatments offer the opportunity to treat both conditions (MR and sTR) simultaneously or in a stepwise fashion. This review provides a clinical overview on available data regarding the rationale for treatment of sTR in patients with relevant MR undergoing mitral transcatheter edge-to-edge repair, focusing on clinical and anatomical selection criteria.

The atrial secondary tricuspid regurgitation is associated to more favorable outcome than the ventricular phenotype.

Aim: We sought to evaluate the differences in prognosis between the atrial (A-STR) and the ventricular (V-STR) phenotypes of secondary tricuspid regurgitation. Materials and methods: Consecutive patients with moderate or severe STR referred for echocardiography were enrolled. A-STR and V-STR were defined according to the last ACC/AHA guidelines criteria. The primary endpoint was the composite of all-cause death and heart failure (HF) hospitalizations. Results: A total of 211 patients were enrolled. The prevalence of A-STR in our cohort was 26%. Patients with A- STR were significantly older and with lower NYHA functional class than V-STR patients. The prevalence of severe STR was similar (28% in A-STR vs. 37% in V-STR, p = 0.291). A-STR patients had smaller tenting height (TH) (10 ± 4 mm vs. 12 ± 7 mm, p = 0.023), larger end-diastolic tricuspid annulus area (9 ± 2 cm2 vs. 7 ± 6 cm2/m2, p = 0.007), smaller right ventricular (RV) end-diastolic volumes (72 ± 27 ml/m2 vs. 92 ± 38 ml/m2; p = 0.001), and better RV longitudinal function (18 ± 7 mm vs. 16 ± 6 mm; p = 0.126 for TAPSE, and -21 ± 5% vs. -18 ± 5%; p = 0.006, for RV free-wall longitudinal strain, RVFWLS) than V-STR patients. Conversely, RV ejection fraction (RVEF, 48 ± 10% vs. 46 ± 11%, p = 0.257) and maximal right atrial volumes (64 ± 38 ml/m2 vs. 55 ± 23 ml/m2, p = 0.327) were similar between the two groups. After a median follow-up of 10 months, patients with V-STR had a 2.7-fold higher risk (HR: 2.7, 95% CI 95% = 1.3-5.7) of experiencing the combined endpoint than A-STR patients. The factors related to outcomes resulted different between the two STR phenotypes: TR-severity (HR: 5.8, CI 95% = 1, 4-25, P = 0.019) in A-STR patients; TR severity (HR 2.9, 95% CI 1.4-6.3, p = 0.005), RVEF (HR: 0.97, 95% CI 0.94-0.99, p = 0.044), and RVFWLS (HR: 0.93, 95% CI 0.85-0.98, p = 0.009) in V-STR. Conclusion: Almost one-third of patients referred to the echocardiography laboratory for significant STR have A-STR. A-STR patients had a lower incidence of the combined endpoint than V-STR patients. Moreover, while TR severity was the only independent factor associated to outcome in A-STR patients, TR severity and RV function were independently associated with outcome in V-STR patients.

Long-term outcomes of pericardial strip versus prosthetic ring annuloplasty for secondary tricuspid regurgitation by a minimally invasive approach.

BACKGROUND: This study was conducted to compare the outcomes of prosthetic ring versus autologous pericardial strip for the treatment of functional tricuspid regurgitation during left-sided valve surgery by minimally invasive approach. METHODS: From January 2008 and July 2016, autologous pericardial strip (group P-TAP) was used in 109 patients, and prosthetic ring (group R-TAP) in 115 patients. The primary outcomes were long-term overall survival, development of patch degeneration, and significant tricuspid regurgitation recurrence. The second outcome was the assessment of right ventricular functional parameters. RESULTS: Operative mortality was 1 case (0.9%) in the R-TAP group. At the time of hospital discharge only one patient (0.9%) in the R-TAP group had grade III+ tricuspid regurgitation, and none had grade IV+. Mean follow-up was 94.1 ± 24.5 months. Mild and moderate tricuspid regurgitation recurrence was 3.7% and 4.5% (P-TAP vs. R-TAP groups, p = 0.99). Severe regurgitation was observed in 1.8% of cases only in the R-TAP group (p = 0.49). There were no reoperations. Late mortality was 3.7% and 5.4% (P-TAP vs. R-TAP groups, p = 0.75). Freedom from death, all causes, were comparable among groups (log-rank p = 0.45). There were no statistically significant differences between two groups in TAPSE, left ventricular end-diastolic diameter, left ventricular ejection fraction, and left atrial diameter. CONCLUSIONS: Tricuspid annuloplasty using an autologous pericardial strip in patients undergoing minimally invasive surgery is associated to similar long results (survival, late tricuspid regurgitation, and functional echocardiographic parameters) than annuloplasty with a prosthetic ring. In particular, the pericardial strip over time does not develop any degeneration or retraction.

Secondary Tricuspid Regurgitation: Pathophysiology, Incidence and Prognosis.

Tricuspid regurgitation (TR) can be divided into primary and secondary origins. Primary TR is mostly caused by infective endocarditis, leaflet perforation, entrapment after device placement and congenital abnormalities. The natural cause of secondary (functional) TR is not well-understood and underdiagnoses is likely. Because symptoms such as ascites, edema and hepatomegaly usually manifest at a late state, assessment of TR is challenging requiring a multiparametric approach. Secondary TR can be subdivided into four morphologic types according to the underlying mechanism: Left-heart related TR, precapillary pulmonary hypertension related TR, right ventricular disease related TR and isolated TR.

Natural Course of Nonsevere Secondary Tricuspid Regurgitation.

BACKGROUND: Secondary tricuspid regurgitation (sTR) is frequent in patients with heart failure with reduced ejection fraction and is associated with adverse outcomes despite guideline-directed therapy. However, little is known about the natural course of nonsevere sTR and its relation to cardiac remodeling and outcomes. The aims of this study were therefore to investigate the natural course of sTR progression using quantitative measurements, to assess the prognostic impact on long-term mortality, and to identify risk factors associated with progressive sTR. METHODS: A total of 216 patients with heart failure with reduced ejection fraction receiving guideline-directed therapy were included in this long-term observational study. Progression of sTR was quantitatively defined as an increase of 0.2 cm2 in effective regurgitant orifice area or 15 mL in regurgitant volume, with transition to at least moderate sTR. Kaplan-Meier and Cox regression analyses were applied to assess survival during a 5-year follow-up period. RESULTS: Among patients with nonsevere sTR at baseline, 62 (29%) experienced sTR progression. Progressive sTR was accompanied by larger left and right atrial volumes (P = .02 and P < .02, respectively) and a higher prevalence of atrial fibrillation (P < .04). During a median follow-up period of 60 months (interquartile range, 37-60 months), 82 patients died. Progression of sTR conveyed a higher risk for long-term mortality (hazard ratio, 1.77; 95% CI, 1.1-2.83; P < .02), even after multivariate adjustment for bootstrap-selected (adjusted hazard ratio, 1.70; 95% CI, 1.06-2.74; P < .03) and clinical confounder (adjusted hazard ratio, 1.80; 95% CI, 1.07-3.05; P < .03) models. CONCLUSIONS: The incidence of progressive sTR despite guideline-directed therapy is associated with adverse cardiac and valvular remodeling as well as a significantly higher long-term mortality. Biatrial enlargement as well as atrial fibrillation are associated with the development of subsequent progressive sTR and may help identify patients at risk for sTR progression, potentially creating a window of opportunity for closer follow-up and newly arising minimally invasive transcatheter repair therapies.

Prognostic Implications of Staging Right Heart Failure in Patients With Significant Secondary Tricuspid Regurgitation.

OBJECTIVES: The purpose of this study was to evaluate the prognostic value of staging right heart failure (RHF) in patients with significant secondary tricuspid regurgitation (TR). BACKGROUND: Right ventricular dysfunction (RVD), defined as tricuspid annular plane systolic excursion <17 mm and clinical signs of RHF, defined as New York Heart Association functional class ≥II, peripheral edema, or use of diuretics, do not always coincide in patients with significant secondary TR and may have different prognostic implications. METHODS: A total of 1,311 patients with significant secondary TR (median age: 71 [interquartile range: 62 to 78] years; 50% male) were divided into 4 RHF Stages according to the presence or absence of RVD and clinical signs of RHF: Stage 1 was defined as no RVD and no signs of RHF; Stage 2 indicated RVD but no signs of RHF; Stage 3 included RVD and signs of RHF; Stage 4 was defined as RVD and refractory signs of RHF at rest. Five-year mortality rates were compared across the 4 Stages of RHF, and the independent associates of mortality were identified by using multivariate Cox proportional hazards models. RESULTS: A total of 101 patients (8%) were classified as Stage 1, 124 (10%) as Stage 2, 683 (52%) as Stage 3, and 403 (31%) as Stage 4. Patients in higher Stages of RHF had more comorbidities and worse renal and left ventricular systolic function. Cumulative 5-year survival was 54%. RHF Stages 3 and 4 were independently associated with increased mortality compared to Stage 1 (hazard ratio: 2.110 [95% confidence interval (CI): 1.163 to 3.828] and 3.318 [95% CI: 1.795 to 6.133], respectively). CONCLUSIONS: In patients with significant secondary TR, higher Stages of RHF are independently associated with all-cause mortality at long-term follow-up.

An Integrated Imaging and Circulating Biomarker Approach for Secondary Tricuspid Regurgitation.

Secondary tricuspid regurgitation (sTR) is frequent among patients with heart failure with reduced ejection fraction (HFrEF), however it confers considerable diagnostic challenges. The assessment of neurohumoral activation may constitute a valuable supplement to the current imaging-based diagnostic process. This study sought to investigate the expression of complementary biomarkers in sTR and to evaluate the effectiveness of integrating their assessment into the diagnostic process. We enrolled 576 HFrEF patients recording echocardiographic and biochemical measurements, i.e., N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin, C-terminal pro-endothelin-1 (CT-pro-ET1), and copeptin. Plasma levels of the aforementioned neurohormones were significantly elevated with increasing sTR severity (p < 0.001 for all). CT-pro-ET1 and MR-proANP were the closest related to severe sTR (adj. OR 1.46; 95%CI 1.11-1.91, p = 0.006 and adj. OR 1.45, 95%CI 1.13-1.87, p = 0.004, respectively). In patients with moderate-to-severe sTR, adding selected biomarkers (i.e., CT-pro-ET1 and MR-proANP) resulted in a substantial improvement in the discriminatory power regarding long-term mortality (C-statistic: 0.54 vs. 0.65, p < 0.001; continuous NRI 57%, p < 0.001). Circulating biomarkers closely relate to sTR severity and correlate with hemodynamic and morphologic mechanisms of sTR. Specifically, MR-proANP and CT-pro-ET1 are closely linked to the presence of severe sTR, and a combined assessment with the guideline recommended echocardiographic grading significantly improves individual risk stratification.

Case report: Transcatheter valve repair with Cardioband: a new treatment option for secondary tricuspid regurgitation in cardiac transplant patients.

BACKGROUND: Tricuspid regurgitation (TR) is the most frequent valvular complication after cardiac transplantation. As in native hearts, the role of surgical therapy particularly in secondary TR is unclear due to high procedural risk and unsatisfying results. Currently, percutaneous techniques are under development for TR repair with less procedural risk and promising preliminary results. CASE SUMMARY: We present a 67-year-old man who underwent heart transplantation (biatrial anastomosis) because of ischaemic heart disease 15 years ago and aortic valve replacement in 2010. Because of progressive severe dyspnoea (New York Heart Association Class III) in 2018 and signs of right heart failure with ascites he underwent transthoracic echocardiography which showed normal graft function, but massive TR of functional aetiology. The heart team decision was an interventional approach using the Cardioband System (Edwards Lifesciences) to treat TR based on the high risk associated with a third cardiac surgery and impaired right ventricular function. The procedure was performed in general anaesthesia with transoesophageal echocardiography and fluoroscopic guidance. Tricuspid regurgitation improved from massive to mild with a mean pressure gradient of 2.9 mmHg. DISCUSSION: This is the first case report of Cardioband implantation in tricuspid position in a heart transplant patient with the good technical and clinical result, suggesting that this technique might offer a treatment option to highly selected post-transplant patients with secondary severe TR and high surgical risk.

Natural history of bivalvular functional regurgitation.

AIMS: Bivalvular functional regurgitation (BVFR) defined as concomitant mitral and tricuspid insufficiency has not been described or systematically assessed before. Therefore, this study sought to define incidence, impact and natural history of BVFR in heart failure with reduced ejection fraction (HFrEF) to provide the foundation for risk assessment and directions for potential treatment strategies. METHODS AND RESULTS: We enrolled 1021 consecutive patients with HFrEF under guideline-directed medical therapy and performed comprehensive echocardiographic and neurohumoral profiling. All-cause mortality during a 5 years of follow-up served as the primary endpoint. Thirty percent of patients suffered from moderate or severe BVFR. Long-term mortality increased with the presence and severity of functional regurgitation (FR) with severe BVFR representing the highest risk-subset (P < 0.001). Severe BVFR patients were more symptomatic and displayed an adverse remodelling and neurohumoral activation pattern (all P < 0.05). Severe BVFR was associated with excess mortality independently of clinical [adjusted hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.39-1.84; P < 0.001] and echocardiographic (adjusted HR 1.31, 95% CI 1.11-1.54; P = 0.001) confounders, guideline-directed medical therapy (adjusted HR 1.55, 95% CI 1.35-1.79; P < 0.001) and neurohumoral activation (adjusted HR 1.31, 95% CI 1.07-1.59; P = 0.009). Moderate BVFR (n = 99) comprised equal baseline characteristics and similar risk as isolated severe FR (HR 0.95, 95% CI 0.69-1.30; P = 0.73). CONCLUSION: This long-term outcome study shows the multi-faceted nature of FR and defines BVFR as an important clinical entity associated with impaired functional class, adverse cardiac remodelling, and excess risk of mortality. Moderate BVFR conveys similar risk as isolated severe FR reflecting the deleterious impact of the global regurgitant load on the failing heart and the need of an integrated understanding for risk-assessment.