The Tricuspid Tragedy: From Cinderella to Celebrity

Georg Nickenig; Johanna Vogelhuber

Disclosures

Eur Heart J. 2020;41(20):1930-1931. 

Mild tricuspid regurgitation (TR) can be found frequently in the general population; it is considered benign and mostly an incidental finding during routine echocardiography.[1] The population-based Framingham Heart Study showed a prevalence of TR of any grade in 82% of men and 85% of women, with the main driving factors for progression being age and female gender.[1,2] Clinically relevant TR affects ~5% of the population >70 years old totalling 1.6 million in the USA and 3 million in Europe,[3]—although reliable data are scarce. In many cases, TR is found to be secondary due to pre-existing left-sided heart diseases such as left ventricular dysfunction, and/or mitral regurgitation, and/or pulmonary hypertension.[1] Moreover, isolated TR, found in particular in older patients with a history of atrial fibrillation, has more recently come into focus—perhaps as a result of the demographic change with a growing population >70 years old.[1]

A significant functional TR (≥ moderate) is a marker for advanced congestive heart failure and has been shown to be related to increased morbidity and mortality. There have been numerous studies published suggesting a strong correlation between the severity of functional TR (FTR) and clinical progress of heart failure, morbidity, and mortality, regardless of the underlying left-sided heart disease or pulmonary hypertension (PHTN).[4–17]

In this issue of the European Heart Journal, Essayagh and colleagues tied in with these studies and analysed patients with degenerative mitral valve regurgitation (DMR) of all grades with regard to concomitant FTR, and examined its prevalence, its influence on survival, and its potential associations with clinical and echocardiographic parameters.[18] The authors are to be congratulated on this substantial contribution to the understanding of the impact of FTR in DMR patients. As existing data and studies regarding this topic are fairly limited and the potential impact of concomitant FTR in DMR patients and the indication for FTR repair/replacement currently are intensely discussed questions, this study adds important and valued information and insight. Major strenghts of this study are its large cohort size, with inclusion of DMR and FTR of all grades, and the long follow-up period of 6.8 ± 3.1 years.

Increasing FTR severity led to profound clinical consequences in DMR patients and was associated with older age, female sex, more symptoms, more extensive medical therapy, and a worse renal function; in short, the more FTR the patients suffered the sicker they were. Additionally, FTR severity was strongly linked to the degree of left atrial dilation, the impairment of left ventricular ejection fraction, left ventricular stroke volume, and right ventricular dysfunction. In particularly PHTN and atrial fibrillation appeared to be strongly and independently associated with FTR severity, with PHTN being the main predictor for severe FTR. Ultimately, the presence of FTR of any grade resulted in a significantly higher mortality with a strong association between FTR grade and mortality (the higher the worse).

Whether FTR itself causally drives morbidity and mortality or whether it is simply an integrative, very well performing biomarker cannot be answered by such a post-hoc observational study in a specialized patient cohort referred to a hospital. However, the authors added multivariate analysis trying to rule out the contribution of potential confounders such as right ventricular dysfunction, and by this generated a strong hypothesis in favour of the prognostic value of FTR in DMR patients.

The fact that TR is frequently associated with or is the result of an accompanying left heart disease such as DMR in the past led to the assumption that appropriate treatment of the left-sided pathology alone may already improve FTR severity. This turned out to be untrue since improvement of concomitant FTR during follow-up remains the exception—despite an appropriate treament of any left-sided heart diseases present; it was shown in different settings that approximately two-thirds of patients do not display relevant recovery of FTR during the course of follow-up after interventional treatment of MR. Even worse, patients suffering from concomitant FTR show poorer outcome in clinical performance and survival even though they received effective treatment of their MR.[12,14,19,20] This is also mirrored in the study under discussion, showing that even after proper surgical therapy of DMR, TR severity influenced the clinical outcome.

In addition, Essayagh et al. assessed a potentially relevant undertreatment of FTR in DMR patients: only 30% of patients with severe DMR and concomitant ≥ moderate FTR who underwent DMR surgery received additional FTR surgery. The situation is thought to be even worse for patients who do not undergo any left heart surgical or interventional approach and still suffer from severe FTR. This retentiveness may also be explained by the less impressive data or documentation of the prognostic value of TR surgery and the associated complication rate in the present study cohort.

Ongoing randomized trials investigating the role of concomitant TR surgery in MR patients may provide additional guideline-relevant data. Furthermore, it is attractive to speculate that minimal invasive surgical approaches may also help to generate favourable outcome data. Besides all the uncertainties, the medical community increasingly entertains the notion that FTR relates to poor outcome and that FTR therefore should be specifically treated. Not surprisingly, catheter-based procedures appeared on the scene a few years ago. First, leaflet treatment was reported to be potentially effective in reducing FTR. This was recently confirmed by the TRILUMINATE study revealing that clipping of the tricuspid valve significantly reduces TR and improves clinical performance.[3] Similarly, the TRILUMINATE study showed that annular reduction by Cardioband implantation reduced FTR and related clinical symptoms.[21] Several other devices including valve prosthesis are currently being tested in the clinical arena in early feasibility studies. Although all these data suggest clinical benefit for the patients, the ultimate proof that selective FTR reduction by minimal invasive procedures improves outcome is still pending. However, ongoing studies such as the TRILUMINATE Pivotal Trial which compares leaflet treatment with the TriClip device with medical treatment only in TR patients will soon inform us as to whether severe TR is indeed causally related to poor outcome and, even more importantly, whether TR reduction improves meaningful clinical endpoints such as heart failure hospitalization and death.

Essayagh et al. have now added, with their analysis of this large and widespread cohort of DMR and FTR patients, another piece of evidence supporting the medical appropriateness of an increased awareness for FTR in DMR patients in order to prevent potential adverse outcomes. Their results can be considered in favour of an earlier and more liberal treatment regimen of FTR.

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