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Isolated severe tricuspid regurgitation: an unrecognised and undertreated problem of the forgotten valve
  1. Yogesh N V Reddy,
  2. Mohamad Alkhouli,
  3. Rick A Nishimura
  1. Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
  1. Correspondence to Dr Rick A Nishimura, Cardiovascular Disease, Mayo Clinic, Rochester, MN 55905, USA; rnishimura{at}mayo.edu

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Until recently, there has been little attention paid to the treatment of tricuspid regurgitation (TR) aside from small series of patients with congenital disease or infective endocarditis. This reflects both the relative rarity of ‘primary TR’, as well as the perception that most TR was felt to be ‘secondary’ to pulmonary hypertension or a cardiomyopathic process, in which case the treatment was directed towards the underlying cause. However, there is now recognition of an increasing number of patients who present with ‘isolated’ TR. ‘Isolated TR’ is defined as the absence of primary tricuspid leaflet pathology, the absence of pulmonary hypertension and normal or near-normal left ventricular (LV) systolic function: in such cases, it is the TR itself that results in the signs and symptoms of right heart failure (HF). Such isolated TR is commonly associated with (1) chronic atrial fibrillation, (2) prior left heart surgery or (3) pacemaker device leads.

Even with increased recognition of isolated TR, there is a reluctance to operate, in part due to a high reported operative mortality. Notably, despite increasing numbers of operations across the country, a high mortality rate of 10%–15% persisted in several studies.1 2 Therefore, patients are often conservatively managed or referred only at a late stage for surgery with advanced right HF and end-organ damage; and this approach has not unsurprisingly been associated with poor outcomes. In a recent cohort study from the national readmission database (2016–2017), >40% of patients who underwent isolated tricuspid valve (TV) surgery were referred late for surgery, with a fourfold higher operative mortality compared with those who had a timely referral.3

Summary of the current study

In this setting, Park et al 4 have contributed to an important observational study of 238 patients undergoing isolated TV surgery over nearly two decades at a large medical centre in South Korea. Similar to other series, the population represented a mixed cohort of aetiologies of TR, which was predominantly functional in origin (78%) with a minority representing primary TR (22%). Consistent with a predominant functional mechanism, there was a high prevalence of predisposing risk factors for isolated TR of atrial fibrillation (62%) and prior left-sided heart surgery (40%). Echo imaging suggested normal LV ejection fraction and lack of pulmonary hypertension consistent with isolated TR. There was evidence of right heart dysfunction from the severe TR, with abnormal elevation in right atrial (RA) pressure in nearly 80% of patients due to exhaustion of RA compliance reserve. Ultimately, 132 patients underwent TV repair with 106 requiring valve replacement, with an overall early mortality of 4.6%. Notably, this lower operative mortality of <5% is consistent with more contemporary reports5 6 and contrasts with poor surgical outcomes from older series7 (table 1).

Table 1

Published characteristics and predictors of outcome with surgery for severe TR in current study compared with other series

Over a median of 4.1 years of follow-up, 22% of patients died and 13% of patients had subsequent hospitalisation for HF despite correction of the TR, which is better than previously published outcomes of patients with isolated TR who were managed medically.8 Multivariable analysis showed that evidence of delayed intervention with hepatic dysfunction from chronic congestion (increased bilirubin), as well as haemodynamic evidence of greater TR severity (TR jet area) and right HF (increased RA pressure) were independently predictive of mortality. Adjusted analyses suggested no differences in outcomes based on the type of valve intervention; except for a subset of patients with substantial tricuspid annular dilation (>44 mm), where outcomes appeared more favourable with replacement versus repair.

Clinical implications

This important study adds to a growing body of literature, which highlights this under-recognised group of patients with isolated TR. As opposed to patients with TR secondary to pulmonary arterial hypertension or dilated cardiomyopathy, patients with isolated TR as the primary problem represent a group that potentially stands to benefit from targeted TV interventions. Earlier surgical series combined multiple mixed aetiologies of secondary TR including patients with pulmonary hypertension and left HF, which may have in part accounted for the high surgical mortality and these patients would not be expected to benefit from surgical TR reduction. Additionally, patients operated in earlier series had a higher mortality perhaps related to late referral, but other studies have demonstrated more acceptable risk with a mortality <5% likely due to earlier intervention.6 Indeed, timely referred patients in a recent US nationwide survey had an in-hospital mortality of <3% despite the infrequency of isolated TV surgery.3 Further supporting the impact of disease stage on survival, the published literature suggests that surgical outcomes are negatively impacted by markers of late-stage right HF by haemodynamics (RA pressure elevation or right ventricular (RV) dysfunction), or evidence of end-organ dysfunction from chronic systemic venous congestion (renal/hepatic dysfunction) (table 1) (figure 1).

Figure 1

Timing of intervention in isolated severe tricuspid regurgitation. JVP;Jugular Venous Pressure. Currently, patients are typically operated on at an advanced stage of disease with cirrhosis and renal failure with high operative mortality. Earlier intervention with onset of symptoms might improve outcomes. In isolated severe TR, intervention should be considered in the symptomatic patient once jugular venous pressure elevation is noted as a reflection of RA pressure elevation.

Therefore, in patients who are surgical candidates with definite isolated TR, it appears prudent to consider intervention before the development of right heart myocardial abnormalities or end-organ damage. Among patients who have atrial fibrillation-associated TR with progressive symptoms, restoration of sinus rhythm may decrease the size of the right atrium and tricuspid annulus with reduction in TR severity. If this is not feasible, we would consider surgery earlier than we have traditionally performed. The ideal method to assess right heart size and function by echocardiography in severe TR, as well as thresholds beyond which surgery should be performed have not been well defined. However, an abnormal elevation in the jugular venous pressure (ie, RA pressure) with a large v wave coupled with progressive changes in RV size or function over serial imaging studies should trigger consideration for surgery before irreversible RV dysfunction or end-organ damage occurs.

In addition to earlier referral, careful patient selection is critical to maximise the risk–benefit ratio of surgical intervention. In the subset of isolated TR due to atrial fibrillation, there are frequently comorbidities that may be associated with LV diastolic dysfunction or pulmonary hypertension. These coexisting pulmonary vascular or diastolic dysfunction processes are even more common in patients who have previously undergone left-sided valve surgery or pacemaker implantation. The non-invasive estimation of pulmonary artery pressures is frequently underestimated in the setting of severe RA hypertension with severe TR.9 Furthermore, left heart filling pressures are often elevated in these patients due to coexisting diastolic dysfunction or from ventricular interaction and pericardial restraint from the TR itself,9 10 and this is challenging to assess non-invasively. Therefore, before considering surgical intervention for isolated TR, there should be a low threshold for invasive haemodynamic evaluation to confirm that the TR is indeed truly isolated and the predominant pathophysiological driver.

The unprecedented advances in transcatheter valve interventions might further accelerate the paradigm shift in treating isolated TR.11 The documented safety of tricuspid edge-to-edge repair and of novel transcatheter valve replacement systems may lower the threshold to treat patients with isolated TR. However, long-term data remains necessary before widespread adoption of these techniques. In addition, due to the natural evolution of transcatheter therapeutics, it is likely that they will first be approved in high-risk patients with advanced disease.12 Therefore, it is prudent that the process of evaluating new transcatheter therapies includes parallel studies of early stages of severe isolated TR considering the substantial impact of late treatment of isolated TR on short-term and long-term outcomes.

Conclusion

Although traditionally understudied and undertreated, in recent years there has been an accumulating body of evidence to help guide therapy of severe TR. As suggested by the recent 2020 ACC/AHA guidelines,13 it is reasonable to consider surgery for symptomatic severe TR that is either (1) primary to intrinsic valve pathology or (2) isolated in the absence of pulmonary hypertension or cardiomyopathy. From observational series such as this, it appears inadvisable to wait until end-organ dysfunction develops from chronic venous congestion before considering surgery. We should however acknowledge with patients that the mortality impact of surgery has not been established, although it likely improves symptoms and mitigates the risk of HF. The current thresholds for intervention for severe TR are driven in part by the risks of surgical intervention, and until safer and effective catheter-based approaches are available, careful patient selection and earlier surgical referral are critical to improve patient outcomes.

References

Footnotes

  • Contributors All authors contributed to the drafting and revision of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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