Worsening tricuspid regurgitation following a successful mitral valve how to manage

Authors: Francesco Maisano, Marco Metra

Combination of mitral and tricuspid regurgitation (TR) is common, either as the result of the increased post-capillary pulmonary pressure due to mitral disease impacting on right ventricular dilatation and secondary tricuspid regurgitation, or because of a common aetiology such as rheumatic, myxomatous disease or in case of secondary atrial regurgitation.

While there is a tendency to treat both valves at the time of the index procedure, a subset of patients undergoing mitral valve interventions may initially present with mild or non-critical TR and eventually develops worsening tricuspid regurgitation (WTR) during follow-up. According to a recent metanalysis, the rate of WTR (new-onset or recurrent) following mitral valve surgery is between 9% and 14% at 5–15 years, and up to 25% at 2–3 years in some studies.^1^

WTR is a complex condition requiring a specific work-up to identify the root cause and to select the appropriate management. Patients who develop significant WTR after mitral interventions may experience recurrence of symptoms similar to those present before the mitral intervention, although several patients remain only mildly symptomatic or report vague, non-specific complaints. Early clinical suspicion and prompt activation of a structured diagnostic–decisional pathway are essential, given the substantial impact of WTR on quality of life and long-term prognosis.

Burden of tricuspid regurgitation

Tricuspid regurgitation is recognized as an independent risk factor for increased cardiovascular mortality, In a metanalysis on 70 studies and more than 30 000 patients with a mean follow-up of 3 ± 2 years, moderate/severe TR was associated with a two-fold increased mortality risk compared with no/mild TR, irrespective of right ventricular function and of pulmonary hypertension.^2^ In addition, more than mild TR was associated with a 1.78 relative risk hazard for heart failure hospitalization.

Approximatively one third of patients with diagnosis of severe TR die within 1 year of diagnosis.^3^ The poorest survival is observed in patients with functional TR associated with left valvular disease, or associated with left ventricular systolic dysfunction, followed by functional TR associated with pulmonary hypertension and organic TR.^4^

Concomitant tricuspid regurgitation in patients undergoing mitral valve interventions (whether surgical or transcatheter) negatively influences long-term outcomes, contributing to higher rates of heart failure hospitalization, reduced functional capacity, and increased mortality. In the surgical setting, the presence of moderate-to-severe tricuspid regurgitation at the time of mitral valve repair is a strong predictor of progression to severe TR, late right-sided heart failure, and reduced survival when the tricuspid valve is left untreated. Patients with untreated moderate-or-more TR had reduced survival and worse symptoms as compared with patients with untreated less-than-moderate regurgitation at 5-year follow-up.^5^ In transcatheter mitral interventions and more specifically following mitral transcatheter edge-to-edge (M-TEER), the presence of moderate or greater tricuspid regurgitation at baseline or persisting after the procedure has been found to be an independent risk factor for cardiovascular death and heart failure hospitalization^6^

Phenotyping WTR: physiopathology and mechanisms of regurgitation

Phenotyping WTR is crucial, since the underlying risk factors for progression, mechanism of failure, and management (Figure 1) can differ according to the original disease. The mechanism of WTR is influenced by a variety of factors, often acting in an additive fashion (Figure 2) and include primary and secondary disorders.

WTR in primary mitral disease

As an example, WTR in a patient treated for primary mitral disease can be either secondary (or functional) or share the same substrate. Common examples for the latter are tricuspid valve with leaflet billowing and or prolapse in myxomatous disease or restricted leaflet motion in patients with rheumatic disease. Some of these patients could present with minimal lesions and in absence of significant regurgitation at the time of the index mitral procedure and are not therefore treated. In case the lesions develop further and become significant they will require treatment in the follow-up.

In addition to the underlying primary disease, secondary TR can develop as the consequence of persisting or worsening pulmonary arterial hypertension and right heart remodelling. Although a successful mitral intervention is usually inducing a decrease of pulmonary resistances, ongoing remodelling of the right heart, as well as persistent post capillary or pre-capillary pulmonary hypertension can induce TR in the follow-up. Right chamber remodelling can also occur because of chronic TR, inducing a vicious cycle of ‘TR begets TR’. Cardiac Implantable Electronic Device (CIED) related TR is also a potential form of WTR in patients who require permanent pacing after mitral interventions. De-novo TR can occur in case of new-onset atrial fibrillation. Ablation at the time of the index mitral procedure have been found to be protective against the risk of developing TR in the follow-up.^7^ There are some reports linking mitral patient prosthesis mismatch to the development of late WTR as the result of residual pulmonary hypertension. Recurrent or residual mitral regurgitation has been associated to WTR and has an impact on prognosis.

WTR in secondary (ventricular) mitral regurgitation

Heart failure patients with secondary ventricular mitral regurgitation may develop concomitant TR due to pulmonary hypertension, biventricular systolic dysfunction, and remodelling and the implant of defibrillator leads. WTR, can develop later after a mitral intervention due to a variety of factors, including residual or recurrent MR, persistent pulmonary hypertension, ongoing right ventricular remodelling, the presence of a CIED or in case of recurrent or new-onset atrial fibrillation (Figure 2).

WTR in secondary (atrial) mitral regurgitation

Finally, atrial secondary tricuspid regurgitation represents a distinct form of functional TR, characterized by predominant right atrial dilation with preserved right and left ventricular function. This phenotype is most frequently observed in elderly women, particularly in the setting of atrial fibrillation, and in patients with heart failure with preserved ejection fraction. In patients with the atrial form of secondary mitral regurgitation, concomitant TR is frequently present at the time of the index mitral procedure. The mechanism of regurgitation is primarily driven by marked tricuspid annular dilation secondary to right atrial enlargement. In parallel, the tricuspid leaflets fail to undergo sufficient adaptive growth, becoming unable to cover the expanded annular area. Unlike the ventricular phenotype, leaflet tethering in atriogenic TR is usually minimal or absent. Recurrent or de novo atriogenic TR in patients who have undergone mitral valve interventions without concomitant tricuspid repair may arise from the same mechanisms described for the ventricular form of secondary TR. A specific feature of the atrial phenotype, however, is its potential responsiveness to early rhythm-control strategies in selected patients with new-onset or recurrent atrial fibrillation.^8^

Surgery has been advocated as the preferred treatment of the atrial forms of functional mitral regurgitation in the recent guidelines, with the potential of concomitant TR treatment and preventive ablation. The largest surgical series of atriogenic secondary MR patients consisting of 123 patients who underwent annuloplasty, adjunctive tricuspid annuloplasty and maze procedure with LA appendage elimination was performed in 50% and 60% of them, respectively.^9^

WTR in patients with failed tricuspid repair at the time of the index procedure

In addition to the above phenotypes, also patients who undergo concomitant tricuspid repair at the time of the index procedure may later present with recurrent TR. This can result from disease progression, persistent or recurrent right-sided remodelling, or technical and anatomical factors influencing the durability of the repair. Among these, the preoperative degree of leaflet tethering has consistently emerged as one of the strongest predictors of recurrent TR following annuloplasty.^10^

Epidemiology and burden of WTR

WTR is not uncommon after mitral valve surgery, and the latest ESC/EACTS valvular heart disease guidelines recommend (class IB) concomitant tricuspid valve surgery in patients with severe primary or secondary TR undergoing left heart surgery to avoid this complication. In the recent years, there has been a trend to offer preventive tricuspid repair in order to avoid WTR. Long-term data suggest that new or recurrent moderate-to-severe TR develops in 13.6% of patients at 15 years after mitral valve repair for degenerative disease.^11^ In a recent randomized trial enrolling patients undergoing mitral repair for degenerative disease and moderate concomitant tricuspid regurgitation (or less than moderate with annular dilation), the addition of tricuspid annuloplasty resulted in a lower incidence of a primary-end-point event at 2 years, mainly driven by less progression to severe tricuspid regurgitation. On the other hand, concomitant tricuspid repair resulted in more frequent permanent pacemaker implantation. In addition, no benefit in quality of life or other clinical meaningful outcomes was recorded at two years.^12^ As a result of this trial, the current ESC/EACTS guidelines have downgraded the recommendation for prophylactic tricuspid repair in patients with mild TR and annular dilation undergoing mitral repair to class IIb, level of evidence B. Conversely, patients presenting with moderate TR at the time of mitral surgery should still be considered for concomitant tricuspid repair to reduce the risk of TR progression.

Transcatheter interventions offer the opportunity of staging procedures, therefore combined mitral and tricuspid transcatheter interventions are rarely performed.

The rate of WTR following mitral transcatheter edge-to-edge repair according to the Japanese OCEAN (Optimized CathEter vAlvular iNtervention) registry is approximately 8–10% for new-onset significant TR (≥ moderate) at short-term follow-up, and 19–25% for worsening or recurrent TR over 1–3 years, depending on baseline TR severity and patient characteristics.^13^ According to Adamo et al., a successful mitral TEER procedure is associated with improvement of TR in about 30% of patients with secondary MR. A TR less than moderate at short-term follow-up was associated with a 42% decreased risk of mortality at 3 years.^14^

When to suspect residual TR in patients with an history of left heart valve repair replacement

Suspicion of WTR in patients under regular follow-up should arise from new signs or symptoms and be screened by routine Doppler echocardiography. The development of significant TR is typically accompanied by a decline in quality of life. Patients who have undergone mitral interventions and are at risk for TR should be informed about the possibility of staged treatment, particularly after percutaneous procedures. Any recurrence or new onset of symptoms should prompt a comprehensive evaluation, including physical examination, laboratory testing, ECG, and echocardiography. WTR may present with overt signs of right-sided heart failure or with subtle, non-specific complaints (particularly in elderly individuals or in those receiving high-dose diuretics) such as fatigue, weakness, dyspnoea, cachexia, abdominal bloating, or gastrointestinal discomfort.^15^ New-onset atrial fibrillation should likewise trigger further diagnostic assessment.

Treating TR in patients with previous surgery or transcatheter interventions

The timing of intervention and risk stratification for WTR follow the same principles applied to other forms of isolated TR. Accurate patient phenotyping and comprehensive risk assessment are essential for the management of these complex cases. The diagnostic workup should clarify the underlying mechanism of regurgitation and identify potential preliminary therapeutic targets, including pulmonary or systemic hypertension, rhythm disturbances, congestion, and concomitant pulmonary disease.^15^ Anatomy of the tricuspid valve, analysis of the mechanism of regurgitation and comprehensive assessment of right ventricular function require a combination of Doppler echocardiography, right heart catheterization, cardiac tomography, and magnetic resonance. The latter has been recently used to quantify abdominal organ damage as a new potential biomarker.^16^ A comprehensive evaluation of these patients requires the use of standardized risk-prediction models. Several validated tools are available to support risk stratification, guide therapeutic selection, and inform heart team decision-making. Since the common surgical scores are unreliable in the setting of TR, the society of thoracic surgeons has introduced a dedicate surgical risk model specific for isolated tricuspid interventions available online (https://www.sts.org/resources/isolated-tricuspid-valve-surgery-risk-calculator). The most widely used surgical risk tool is the TRI-SCORE, available both online and as a mobile application. It has shown superior discriminatory ability for in-hospital mortality compared with EuroSCORE II and STS, and it remains applicable in the setting of reinterventions. More recently, the TRI-SCORE (TRIcuspid Regurgitation Surgical SCORE) has also been validated as a general risk-profiling instrument for patients with TR managed conservatively or with transcatheter procedures. A TRISCORE lower than 4 is associated with acceptable surgical risk (below 5% hospital mortality), while a score above 5 is associated with subpotimal outcomes irrespective of the therapeutical strategy. High TRI-SCORE is encountered in late referrals with right heart dysfunction and organ damage. In these patients, heart team discussion is required to define the threshold between benefit and futility. The GLIDE (Gap, Location, Image quality, density, en-face TR morphology) score is an anatomical score that predicts the success of tricuspid TEER according to leaflet anatomy, mechanism of regurgitation and quality of the imaging.^17^ Such scores could be useful to guide the decision between surgical vs. percutaneous treatments as well as between valve repair and replacement (Figure 3).

Surgery for isolated WTR

Surgery for isolated TR after mitral valve interventions has historically been perceived as carrying high mortality; however, this view is misleading. Contemporary data clearly show that, when performed at an early stage and in patients without major comorbidities, surgical treatment is both safe and effective.^18^ Surgery remains the preferred option for younger patients without comorbidities and for older individuals with complex anatomy who maintain a low surgical risk profile, characterized by preserved right ventricular function and absence of end-organ impairment. In contemporary practice, most procedures are performed through minimally invasive approaches, often on the beating heart, to optimize recovery and preserve right ventricular function. Most patients with functional TR benefit from annuloplasty alone, whereas those with leaflet tethering and more advanced right-heart remodelling are more likely to require adjunctive leaflet techniques including the clover technique and leaflet augmentation. Patients with organic lesions (e.g. endocarditis, CIED related TR, rheumatic retraction of the leaflets), with extreme right ventricular remodelling or those with recurrent TR after a prior repair attempt are generally better suited for valve replacement.

Transcatheter interventions for WTR

In patients at high surgical risk, transcatheter tricuspid valve interventions (TTVI) have emerged as a valuable option to improve clinical status. Transcatheter edge-to-edge repair (T-TEER) is currently the most widely adopted approach. Its versatility, broad availability, and, above all, its favourable safety profile has been instrumental in establishing TTVI and continue to represent a major advantage among the alternative techniques. The safety of T-TEER has been consistently demonstrated across trials and real-world registries. In the early TriValve (International Multisite Transcatheter Tricuspid Valve Therapies) registry, which included a substantial proportion of patients with prior left-sided valve surgery, the 30-day rate of major adverse events was low, and T-TEER was associated with reduced mortality and rehospitalization compared with medical therapy alone.^19^ Safety has been consistently confirmed in subsequent studies, including the B-right registry and the TRILUMINATE (Clinical Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System) randomized trial. In these cohorts, T-TEER achieved 98.3% freedom from major adverse events at 30 days and a 7.1% all-cause mortality at 1 year in a high-risk population, with no excess procedural risk linked to prior mitral interventions. T-TEER is also a viable option for treating recurrent TR after failed annuloplasty.

While TEER is a safe and versatile procedure, its outcomes are highly anatomy and operator dependent; failure rates as high as 30% have been reported in the literature. Suboptimal results may significantly limit the clinical benefit of the intervention. It is now clear that the ideal target of TR repair is to obtain a residual TR less than moderate at discharge.^20^

Current guidelines endorse TTVI for high-risk surgical candidates with isolated TR to improve quality of life and promote reverse remodelling, both of which are closely tied to the degree of TR reduction achieved with T-TEER. In the TRILUMINATE trial, improvements in quality of life were substantial and directly proportional to the extent of TR reduction.^21^ Similarly, right ventricular reverse remodelling was linearly correlated to the reduction of the regurgitant volume as determined by magnetic resonance.^22^ Therefore, in patients with risk factors for residual TR following TEER, transcatheter replacement is becoming an alternative.

In the TRISCEND (TRanscatheter tricuspId valve Safety and Clinical Efficacy using a Novel Device) trial, transcatheter tricuspid valve replacement (TTVR) achieved a sustained reduction of TR to mild or less in 97.6% of patients at one year, accompanied by marked improvements in functional status and quality of life, and low rates of mortality (9.1%) and heart failure hospitalization (10.2%). Notably, the mean Kansas City Cardiomyopathy Questionnaire improvement was impressive and substantially greater than that reported in the TRILUMINATE trial.

Despite offering predictable and reproducible TR elimination, TTVR has several limitations that restrict its widespread use in patients who remain suitable for repair. In the TRISCEND trial, TTVR was associated with a significant incidence of conduction disturbances, resulting in a high rate of permanent pacemaker implantation. As observed in surgical experience, valve replacement with tissue prostheses in the right heart introduces specific challenges. First, current TTVR systems are limited by device design and anatomical feasibility, including annular dimensions, right ventricular geometry, and caval orientation. Second, the procedural risk appears higher than with T-TEER, in part due to the potential for acute right ventricular failure following abrupt correction of chronic TR. Third, the occurrence of valve thrombosis and leaflet hypoattenuation indicates the need for long-term anticoagulation, unlike TEER, although many patients already have concurrent indications for anticoagulation. Finally, the large device profile complicates the management of complications such as embolization or endocarditis, particularly in a population already burdened by significant comorbidities.

Specifically for patients with recurrent TR following failed procedures, there are several TTVI options. Tricuspid valve in ring implantation with balloon expandable valves has been performed but often with suboptimal outcomes, particularly in the case of rigid rings, due to the oval design of the disease specific rings used for surgical tricuspid annuloplasty and the risk of residual perivalvular leaks or embolization.

Dedicated tricuspid valve implantation (Lux valve, China) has been successfully used to treat a patient with a failing ring annuloplasty, with the support of 3D printing simulation and planning. TTVR implants with Evoque (Edwards Lifesciences, Irvine CA) have been successfully conducted in patients after failed T-TEER and transcatheter annuloplasty.

When to perform concomitant MR and TR treatment

Guidelines are explicit regarding in patients undergoing mitral valve intervention, concomitant tricuspid repair is mandatory when TR is significant. Although the recommendation class for prophylactic repair has been downgraded, mainly due to the risk of pacemaker implantation. Tricuspid intervention may still be considered in patients with less-than-moderate TR when substantial annular dilation is present.

In the transcatheter setting, decision-making is more nuanced and influenced by multiple clinical and non-clinical factors. One key advantage of transcatheter therapies is the ability to stage interventions. In patients with concomitant tricuspid disease but non-significant TR at the time of the mitral procedure, treating the mitral valve first and monitoring the evolution of TR is an appealing and widely adopted strategy. This approach recognizes that TR may improve or stabilize following mitral correction, thereby avoiding an unnecessary combined procedure. Moreover, if TR progresses, a second-step transcatheter treatment can usually be performed without additional risk, provided that the diagnosis is timely.

A similar staged strategy is commonly applied to patients with significant TR undergoing mitral TEER or transcatheter mitral valve replacement. Most experience a meaningful reduction in TR after the mitral intervention, and only a minority develop WTR requiring subsequent tricuspid treatment. While partly driven by financial and logistical considerations, this approach also aims to avoid unwarranted procedures.

Combined transcatheter interventions may be appropriate in selected patients and in highly experienced centres, particularly in those with atriogenic MR and TR, where persistent biatrial remodelling makes improvement of TR unlikely and increases the risk of WTR if left untreated.^23^