Do we really need more evidences to support early intervention for tricuspid regurgitation? The paradox of a well-tolerated disease

The manuscript from Pfannmueller et al. [1] describes the results of isolated tricuspid valve reoperative surgery in a single-centre experience over an almost 15-year period. Although there are several limitations (mainly related to the small sample size, the retrospective methodology and the absence of important data to describe the patients population), the main finding of this interesting study is once more that early timing is crucial to achieve good outcomes and possibly prognostic benefits in isolated tricuspid valve surgery. Among all the factors analysed, the only one which was associated with increased mortality was the impaired liver function measured with MELD-XI score, which is a clear signal of advanced and long-standing right-heart disease.

Once again, late treatment is associated with bad outcomes: if we wait for the systemic consequences of long-standing Tricuspid Regurgitation (TR), we lose the therapeutic window to intervene. Another important message of this study, which is in line with many other series, is that if surgery is performed early enough within the therapeutic window, outcomes are acceptable.

Although to define this ‘therapeutic window’ is matter of deep discussions since >1 decade (after many years of lack of interest in the ‘forgotten valve’), it seems that not many advancements have been done in this regards, and the referral of patients to isolated tricuspid surgery remain in the majority of the case too late. This is mainly due to a paradoxical situation: TR is well tolerated for many years with increasing doses of diuretic, which improve the symptoms without interrupting the vicious circle of TR. After many years of ongoing TR and Right Ventricle (RV) remodelling and progressive increased dosage of diuretics (with consequent worsening of the quality of life), the patients become tolerant to diuretics and the systemic consequences of RV failure become evident. The paradox is that the therapeutic window to interrupt the vicious circle of TR effectively and with low risk is delayed without modifying the progression of the disease, bringing the patient out from the therapeutic opportunity. Even in the last 2020 American Guidelines, isolated tricuspid valve surgery is recommended only in presence of right heart failure symptoms [2].

In other medical disciplines, this would be considered as a total misunderstanding of the natural history of the disease. It is clearly a provocation, but would an oncologist deny early surgery to a patient with a confined disease, that will progress over the years, just because it is asymptomatic or well tolerated? Who would wait until the disease is diffuse, highly symptomatic and possibly inoperable, before to refer for a treatment, in absence of alternative effective therapeutic methods?

As a consequence of this, there are currently 2 main attitudes inside the surgical community: reject the majority of the patients for surgery and left the disease undertreated (which is the easiest way to achieve good outcomes) or try to improve risk stratification and treat also higher risk patients, accepting a possible higher mortality. In order to do this, a better risk stratification would be required. As a matter of fact, the study from Pfannmueller et al. [1] report only 85 patients treated over a 14-year period, meaning only 6 patients per year (the study is from one of the highest-volume cardiac centre in Europe). This is probably due to the combination of the under-referral of this patients population but also to an extremely careful and restrictive patients selection, as confirmed by the young age and the normal pulmonary pressure value of the patients (it is not reported in the manuscript how many patients have been rejected for surgery in the same period, information that would be really interesting).

The inclusion of the MELD score as standard method to stratify the risk of the patients should be implemented in all the tricuspid programs, but represents only a small piece of a really complex puzzle, where many crucial issues are still open:

• How to properly define the RV function in patients with severe TR: the conventional echocardiographic methods are not careful enough to stratify the prognosis and to predict the chances of reverse remodelling after surgery;

• How to quantify the severity of TR: an expanded grading of TR severity has been recently proposed and seems to have prognostic implication [3, 4]; however, the precise role of quantification of TR in stratification of surgical risk has to be further investigated;

• The role of pulmonary hypertension and right heart catheterization;

• The role of right heart failure symptoms; and

• The role of the emerging transcatheter options to treat severe tricuspid regurgitation in high-risk candidate: there is a big potential for less invasive percutaneous methods to serve a large number of patients who are not eligible for surgery. The interventional timing is crucial also for percutaneous treatment [5].

Beside the definition of a better risk stratification, the effort to promote an early treatment for patients with isolated TR (before the onset of right ventricular failure symptoms) and the development of effective and less invasive methods to treat TR percutaneously, there is another big area where the surgical community should improve its efforts: the reduction of the incidence of late TR after left side surgery.

All the 85 patients included in this series had previous open heart surgery (mostly mitral or aortic valve interventions). Although no detailed information are reported, most likely those patient did not have severe concomitant severe TR at the time of the first operation, since no tricuspid valve repair was performed during the index procedure. A more aggressive attitude to perform concomitant ‘prophylactic’ tricuspid annuloplasty in presence of dilated tricuspid annulus, even in absence of relevant regurgitation, should be warranted in order to reduce the onset of late TR after the initial surgery. The results of a large randomized trial from the CTS Network are expected this year (NCT02675244).

The other way to reduce the incidence of late TR after left-side surgery is to improve the durability of concomitant tricuspid valve repair, when performed. Usually, if TR is severe, it is addressed with a tricuspid annuloplasty during the concomitant surgery. The use of dedicated tricuspid 3D-shaped ring prostheses over suture-based annuloplasty is fundamental to reduce the risk of late recurrent TR. If the valve geometry is too altered (i.e. in the presence of severe annular enlargement or advanced tethering), annuloplasty could not be enough to warrant durable results. Associated leaflet repair, like clover technique or expansion of the anterior leaflet, or valve replacement should be considered in order to improve durability and reduce the chance of late TR recurrence. Proper preoperative planning based on transthoracic and trans-oesophageal echocardiography is fundamental in this regard.

In conclusion, the study from Pfannmueller et al. [1] further support the importance of early treatment of isolated TR and the need for a better risk model stratification, including the standard assessment of liver function with the MELD score. Several issues remain open and are currently subjects of investigations and extensive studies, in order to improve the understanding of the interventional timing and of the risk stratification. Transcatheter tricuspid valve interventions have the great potential in the next future to expand the treatment options for this severe disease, which is at the moment still highly undertreated.

Conflict of interest: Maurizio Taramasso declares consultancies or speaker fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, 4tech, CoreMedic, Mitraltech, Simulands, Occlufit, MTEx, and Shenqi Medical. Michele De Bonis has served as consultant for Abbott Vascular and Medtronic.

REFERENCES