Severe tricuspid regurgitation (TR) may remain clinically silent for a prolonged period, as symptoms and signs of right ventricular dysfunction may be masked by diuretic therapy. Right heart (RH) dysfunction is an independent risk factor for operative mortality, postoperative complications, and TR recurrence after tricuspid valve repair.1,2 Delayed surgery is associated with poor results and decreased survival.1 Some authors have suggested that avoiding surgical delay in severe TR might decrease operative mortality and the development of RH failure.1,3 However, the optimal timing of surgery is not clear. In patients undergoing left-sided surgery, the European (European Society of Cardiology][ESC]/ European Association for Cardio-Thoracic Surgery [EACTS]) and American (American Heart Association [AHA]/American College of Cardiology [ACC]) guidelines recommend tricuspid valve surgery in symptomatic patients with severe primary TR (recommendation class I level C ESC/EACTS), in patients with severe secondary TR (recommendation class I level B ESC/EACTS) and in patients with mild or moderate secondary TR associated with tricuspid annular dilatation (≥ 40 mm or>21 mm/m2) and RH failure (recommendation class IIa level B ESC/EACTS).4,5

In patients with concomitant left-sided surgery, severe TR is not the main surgical indication. We hypothesized that delayed intervention in severe TR might increase operative mortality, allowing the development of RH dysfunction. We aimed to analyze the influence of latency between diagnosis and surgery in operative and mid-term mortality and the factors associated with mortality during follow-up in patients with severe TR concomitant to left-valve surgery. As secondary objective, we aimed to identify the factors associated with postoperative RH failure.

We conducted a retrospective and longitudinal study with a cohort design in patients older than 18 years with a diagnosis of severe TR concomitant to left-valve disease undergoing surgery. Clinical and demographic variables were prospectively collected. Time (in months) from first diagnosis of severe TR was retrospectively collected from echocardiographic patient information. The study was performed according to the strengthening the reporting of observational studies in epidemiology (STROBE) guidelines.6 The study protocol (identification number PI19-1435) received full approval by both the local Institutional research review committee and the clinical research ethics committee. The study period was from January 2012 to June 2020. We prospectively gathered data through follow-up of surviving patients. The patients were followed up either in person, by telephone, by contact with the cardiologist, and through medical records. No patients were lost to follow-up. All patients gave their written informed consent for analysis of their data.

A cohort of 253 consecutive patients with a diagnosis of severe TR concomitant to left-valve disease undergoing surgery were analyzed. The analyzed populations corresponded to 14.9% of patients who underwent valve surgery during the study period. The clinical and demographic variables are detailed in table 1. The etiology of severe TR was mostly functional (82.6%), although it could also be due to rheumatic heart disease (12.3%), infective endocarditis (2%), cardiac implantable devices (0.4%) and tricuspid valve repair failure (2.8%). The mean age of the patients was 69±9.5 years, with a predominance of the female sex (68.8%). Preoperative TR grade was severe in 81% of the patients and massive in the remaining patients. All patients underwent concomitant left-sided valve surgery: mitral in 64%, mitral and aortic in 24.1%, and aortic in 11.9%. The tricuspid valve interventions performed included 22 tricuspid valve replacements and 231 repairs. A total of 19.8% of patients had undergone at least 1 previous open-heart surgical intervention. TR after repair was moderate in 2 patients and none or mild the rest. Median latency between diagnosis of severe TR and surgery was 24 months, with an interquartile range (IQR) of 51 months.

Operative mortality was 12.2%. The mortality of concomitant tricuspid and left-sided valve surgery was 9.9% among patients undergoing mitral valve surgery, 10% among patients undergoing aortic valve surgery, and 19.7% among those undergoing concomitant mitral and aortic valve surgery (P = .128). No significant differences were found in crude and standardized mortality ratios. The standardized mortality ratio was 1.28, 95% confidence interval (95%CI, 0.59-2.15) for concomitant tricuspid and mitral valve surgery; 0.80, 95%CI, 0.00001-1.88 for concomitant tricuspid and aortic valve surgery, and 1.92, 95%CI, 0.82-13.10 for concomitant tricuspid, mitral and aortic valve surgery. Although the mean latency between severe TR diagnosis and surgery was similar, a higher IQR was observed in nonsurvivors (figure 1) (P=.007)

Figure 1.

Mean latency between severe TR diagnosis and surgery in survivors (A) and nonsurvivors (B).

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Age, triple valve surgery, worse functional status as assessed by NYHA functional class, and preoperative anemia and hyponatremia increased operative mortality (table 2). During the postoperative period, RH failure was diagnosed in 25.3% of all patients, which was the immediate cause of death in 32.8% of them. In the remaining patients, the immediate cause of death was hemorrhagic complications (4 patients), neurological damage (1 patient), respiratory disease (1 patient), left heart failure (2 patients) and infection (2 patients). The risk factors for postoperative RH failure are detailed in table 3.

We conducted the follow-up of patients, with a mean time of 33.7±26.2 months, and median [IQR] of 35 [46.5] months. During this period, 11.3% of the patients died. Survival at 1 and 5 years was 85.2% and 73.7%, respectively (figure 2A). Male sex, latency from diagnosis of severe TR to surgery and preoperative diagnosis of massive TR were associated with higher mortality during follow-up, with c-index 0.687, 95%CI (0.611-0.765) (table 4 and figure 2B,C).

Figure 2.

Kaplan-Meier curve showing the estimated survival function (A) survival time related to sex (B), and preoperative echocardiographic grade of TR (C).

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In this research, we first aimed to analyze the influence on operative and mid-term mortality of delay between diagnosis of severe TR and surgery in patients with concomitant left-valve surgery. We observed that mid-term mortality increased in patients with left-valve surgery associated with long-standing severe TR. The etiology of severe TR was mostly functional and, not infrequently, there was a latency of years between the first echocardiographic diagnosis and surgery. Surgical treatment in functional severe TR used to be influenced by the indications for left-heart valve surgery, facilitating temporal progression of TR until surgical decision. The progression of tricuspid valve disease reduced the mid-term survival of patients, even after adequate surgical correction.

Until now, the benefit of surgical correction of isolated functional TR compared with medical treatment has not been well established. Surgery should be considered early in selected symptomatic patients, but periprocedural morbidity and mortality is higher when patients present late and thresholds for severe RV dysfunction making intervention futile have not yet been defined.4,5 In this context, after diagnosis of nonsevere left-valve disease, aortic and/or mitral valve clinical and imaging studies prevail over evaluation of severe functional TR and usually determine the optimal surgical timing. Consecutively, the impact of the severity of tricuspid valve disease and right ventricular function remain underestimated. Since survival is affected, even after surgical correction of severe TR, a more exhaustive sequential echocardiographic study of the right ventricle and tricuspid valve would be advisable. In this setting, magnetic resonance imaging (MRI) can provide additional information that allows identification, over time, patients with higher surgical risk and lower mid-term survival.11

We also aimed to identify risk factors for mortality. Lower functional status was associated with increased operative mortality. We also found some preoperative biochemical markers related to an increase in operative mortality such as anemia and hyponatremia, which predicted a poor prognosis. The etiology of anemia in the study population was multifactorial: occult gastrointestinal bleeding secondary to chronic anticoagulant therapy, iron and vitamin B deficiencies, chronic disease (associated with an age-related inflammatory process)12 and dilutional anemia, associated with hyponatremia. All patients received chronic diuretic therapy before surgery and a quarter was under polytherapy with 2 or more diuretics; however, preoperative hyponatremia was related to increased operative mortality, regardless of the type and doses of diuretic treatment.

Compared with data described by other authors, crude mortality after concomitant tricuspid and left-sided valve surgery was higher in our population, but these differences were not significant when the risk-adjusted mortality rate was calculated.13–15 Nevertheless, triple valve surgery is associated with higher postoperative mortality due to right ventricular dysfunction, not related to repair or tricuspid valve replacement procedures16,17 (figure 3).

Figure 3.

Central illustration. Risk factors associated with operative and mid-term mortality in patients with severe tricuspid regurgitation concomitant to left-valve surgery. NYHA, New York Heart Association; TR, tricuspid regurgitation.

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We also aimed to identify risk factors for postoperative RH dysfunction. Postoperative RH failure was observed in a quarter of patients undergoing tricuspid surgery and was the immediate cause of death in a third of them. The etiology of the postoperative RH failure was multifactorial. On the one hand, right ventricular function is reduced during cardiac surgery, independent of procedural characteristics18; on the other hand, preoperative anemia is an independent risk factor for low postoperative cardiac output.19 We observed an increased probability of postoperative RH failure after triple valve surgery; however, no correlation between preoperative right ventricular dysfunction and postoperative RH failure was identified. An explanation is that, in these patients, left-sided valve disease is the main indication for cardiac surgery and right ventricular dysfunction was underdiagnosed. Therefore, we consider that exhaustive preoperative echocardiographic and MRI evaluation of tricuspid valve and right ventricular function might identify patients at higher risk of developing postoperative RH failure.

In conclusion, our study shows that, in patients with severe TR and concomitant left-valve disease, triple valve surgery and worse preoperative functional class increases operative mortality. Longer latency between diagnosis of severe TR and surgery decreased mid-term survival, even after adequate surgical correction. We consider that, after the first diagnosis of severe TR, sequential echocardiographic and MRI studies, focused on right ventricular and tricuspid valve function, may help to determine the most appropriate timing of surgery.

None.

All authors contributed to the acquisition, analysis, or interpretation of the data for the work and final approval of the version to be published. B. Segura and Y. Carrascal also contributed to the conception, design, drafting and critically revision of the work for important intellectual content.

None declared.

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