LABORATORIO DE URGENCIAS

Tricuspid Valve Regurgitation

                                                                                 Rebecca T. Hahn, M.D.
                                                 Professor of Medicine at Columbia University Irving Medical Center,
                                                         Chief Scientific Officer of the Echo Core Lab at the Cardiovascular Research Foundation
                                                         Director of Interventional Echocardiography at the Columbia Structural Heart and Valve Center. 
                                                         She  is affiliated with multiple hospitals in the area:  New York-Presbyterian-Columbia Hospital; Cornell;                                                                                     North Shore University Hospital
         
                                                                              N Engl J Med 2023;388:1876-91.
                                                                                   DOI: 10.1056/NEJMra2216709

The tricuspid valve, often referred to as the forgotten valve, has generated intense interest because of converging factors that make di-agnosis and management of tricuspid regurgitation uniquely challenging. Historically, the tricuspid valve was considered to be a passive structure, on the systemic venous side of the heart, without clinically significant function.
Surgeons believed that mitral-valve disease was the true culprit and that tricuspid regurgitation was a secondary finding that would resolve after surgical treatment of the primary mitral disease process.
Because tricuspid regurgitation is most frequently diagnosed in patients with coexisting conditions, many clinicians have viewed it as an innocent bystander to the more consequential diseases of the left heart and pulmonary vasculature.
In the absence of left heart disease, the clinical signs and symptoms of severe tricuspid regurgitation, such as edema, fatigue, and exercise intolerance, are often mistaken for normal signs and symptoms of aging, leading to delays in diagnosis and treatment.
Natural history studies highlight the need for early diagnosis; survival is progressively shorter with the increasing severity of tricuspid regurgitation, even after adjustment for coexisting conditions.1-4
Gaps in our understanding of the tricuspid-valve disease process, diagnostic challenges, and uncertainty about the appropriate timing of interventions have contributed to the high mortality among medically treated patients,4,5 as well as nonmedically treated patients,6,7 with severe tricuspid regurgitation.

Anatomy
Insight into the anatomical relationship between the tricuspid-valve apparatus and the right atrium, right ventricle, and pulmonary vasculature provides the basis for our current understanding of the pathophysiology of tricuspid regurgitation.
The tricuspid valve is the largest valve in the heart and typically has three leaflets of unequal size. However, the number of leaflets may vary in healthy persons, with the most common variant consisting of two posterior leaflets.8,9 Thinner than mitral-valve leaflets, the tricuspid-valve leaflets are supported by chordae attached to a major anterior papillary muscle along the lateral wall of the midright ventricle, as well as one or more smaller posterior papillary muscles.10 The anterior papillary muscle supplies chordae to the anterior and posterior leaflets along their line of coaptation, whereas the posterior papillary muscles supply chordae to the posterior leaflet (or leaflets) and the posterior segment of the septal leaflet.
The chordal attachments arising either from small septal papillary muscles or directly from the septum are unique to the tricuspid valve and support the anterior segment of the septal leaflet and the adjacent segments of the anterior or posterior leaflet. Given the complex chordal arcades and their attachment sites, the tricuspid valve is sen-sitive to changes in the position and function of the free wall of the right ventricle, as well as the interventricular septum.
The tricuspid annulus has very little fibrous tissue or collagen. Adipose tissue fills the inter-ventricular space between the right atrium and ventricle on the anterosuperior and inferior sides but not on the septal side.11 There are sex-related differences in the histologic features of the an-nulus. Males have more myocardial cells and elastic fibers than do females,12 and females have a larger annulus, even after correction for heart or body weight.12,13 The normal annulus is saddle-shaped and dynamic, larger in early dias-tole and during atrial systole,13 which allows for large flow volumes under low pressure. Given the large size of the tricuspid valve, benchtop modeling suggests that only 40% annular dilata-tion may result in clinically significant tricuspid regurgitation, whereas this was seen at 75% an-nular dilatation in mitral-valve studies.14 The right coronary artery and the atrioven-tricular node are adjacent to the annulus and are important anatomical considerations for surgical or transcatheter interventions. The right coronary artery lies within the atrioventricular groove along nearly the entire anterior and posterior annulus, with the separation narrow-ing to less than 3 mm inferiorly, placing the vessel at risk for injury with devices that anchor in the annulus.15 The atrioventricular node and the bundle of His cross the septal leaflet at-tachment 3 to 5 mm from the anteroseptal commissure, and injury to the node may result in heart block.

Clinical Presentation
Patients with severe tricuspid regurgitation pres-ent with signs and symptoms of chronic right heart failure, including systemic f luid retention, leading to elevated jugular venous pressure, periph-eral edema, and ascites; reduced intestinal ab-sorption and anasarca; decreased cardiac reserve, resulting in exercise intolerance, dyspnea, and poor functional capacity; and decreased cardiac output, with progressive end-organ damage caused by a combination of end-organ venous congestion and underperfusion.16 End-stage dis-ease is associated with cachexia resulting from poor absorption of nutrients, as well as a sys-temic proinflammatory state.
The signs and symptoms of reduced cardiac output may also be mistaken for left heart failure, further delaying a timely diagnosis of tricuspid regurgitation. Although many signs and symptoms of severe tricuspid regurgitation may initially be respon-sive to diuretics, reduced cardiac output, as well as other neurohormonal changes, may result in liver disease (the cardiohepatic syndrome) and kidney disease (the cardiorenal syndrome).16,17 The cardiohepatic syndrome not only increases the risk of bleeding in patients with tricuspid regurgitation but is also a strong independent predictor of death or hospitalization for heart failure within 1 year after transcatheter tricuspid-valve therapy.18 Atrial arrhythmias — in particular, atrial fibril-lation — are common in patients with tricuspid regurgitation and occur in both incident and progressive valvular disease.19 Atrial fibrillation has been associated with left and right atrial dilatation, annular dilatation, and atrioventricu-lar valvular regurgitation,20 and rhythm control is associated with a reduction in tricuspid regur-gitation.21,22 I n p atients w ith n ormal l eft v en-tricular function, atrial fibrillation may result in greater tricuspid annular dilatation than mitral annular dilatation.23 Patients with heart failure and a preserved ejection fraction, with or with-out atrial fibrillation, also have a high preva-lence of prognostically important tricuspid re-gurgitation resulting from dilatation of the annulus and right atrium.24,25

Epidemiology
As with other valvular heart diseases, the preva-lence of tricuspid regurgitation increases with age.26-30 Although clinically significant valvular disease is diagnosed more frequently in men than in women,28 the overall prevalence of clini-cally significant tricuspid regurgitation may be up to four times as high among women.26 Female sex is an independent predictor of the severity and progression of tricuspid regurgitation.4,19,31 Although the basis for these differences is un-known, the higher female prevalence of heart failure with a preserved ejection fraction32,33 and atrial fibrillation34 may play a part. Besides older age, female sex, and atrial fibrillation, other clinical predictors of severe and progressive tri-cuspid regurgitation include elevated pulmonary-artery systolic pressure and increased left atrial size, which suggests that both pre- and postcapilary-pulmonary hypertension contribute to this process.19 In two studies of patients with tricuspid re-gurgitation, medical management of severe dis-ease was associated with 1-year mortality rates of 42% and 36%, respectively.4,5
As compared with persons who had mild or no tricuspid re-gurgitation, those with moderate or severe regurgitation had a long-term risk of death from any cause that was increased by a factor of 2.0 to 3.2, after adjustment for age and sex.4 Even mild tricuspid regurgitation was associated with a nearly 30% increase in all-cause, long-term mor-tality.4
A recent study of outcomes for aortic-, mitral-, and tricuspid-valve disease showed that all-cause mortality was higher for tricuspid re-gurgitation (hazard ratio, 2.74; 95% confidence interval [CI], 2.24 to 3.37) than for aortic-valve disease (hazard ratio, 1.62; 95% CI, 1.44 to 1.82) or mitral-valve disease (hazard ratio, 1.25; 95% CI, 1.09 to 1.44).29 Morphologic predictors of progressive tricus-pid regurgitation depend on the primary cardio-vascular disease process. For patients with pul-monary arterial hypertension, predictors include right ventricular enlargement, increased right ven-tricular sphericity, tricuspid annular dilatation, and increased tricuspid leaflet tenting area.35 For patients with atrial fibrillation, the presence of tricuspid-valve tethering, increased left atrial volume, increased tricuspid annular diameter, and right ventricular remodeling predict severe tricuspid regurgitation.36 R apid p rogression t o severe tricuspid regurgitation has been indepen-dently associated with all-cause mortality, and predictors of rapid progression include the pres-ence of pacemaker or defibrillator leads, mild tricuspid regurgitation (vs. none), tricuspid an-nular dilatation, and any valvular heart surgery without concomitant tricuspid-valve surgery.31 In patients who have undergone mitral-valve sur-gery, the progression of tricuspid regurgitation is associated with clinical adverse events.37

Causes and Classification
The atrioventricular valves promote the transit of blood into the ventricles during diastole and prevent regurgitation during systole. Function-ing under lower pressures, the right heart ejects the same stroke volume as the high-pressure left heart but in the presence of a closed mitral valve thus relying on the compliance of the pulmonary vasculature and left atrium.
The large tricuspid-valve apparatus is particularly suited to optimiz-ing diastolic filling of the right ventricle with the dynamic motion of the lateral annulus during ventricular relaxation (from the apex to-ward the base) allowing passive transfer of right atrial blood volume into the right ventricle.
Changes in leaflet structure and annular size and dynamics, as well as changes in right ven-tricular support structures or function, can dis-rupt tricuspid-valve function.
The traditional subdivision of tricuspid regurgitation into:
* Primary leaflet disorders and sec-ondary (nonleaflet) disorders has been refined with the current classification scheme, reflecting a more comprehensive understanding of differ-ent mechanisms of tricuspid regurgitation38,39 and their associated outcomes.40,41
* Secondary tricuspid regurgitation has been subdivided into atrial secondary tricuspid regurgitation and ven-tricular secondary tricuspid regurgitate on, and tricuspid regurgitation associated with a lead from a cardiac implantable electronic device is now a distinct category, separate from primary causes

Primary Tricuspid Regurgitation
Primary tricuspid regurgitation occurs as a re-sult of intrinsic valve disease and is attributable to congenital anomalies, infective endocarditis, rheumatic disease, carcinoid heart disease, toxic effects of chemicals, tumors, blunt trauma, or myxomatous degeneration. Congenital tricuspid regurgitation includes Ebstein’s anomaly, tricus-pid atresia, and the presence of a cleft valve typically associated with an atrioventricular ca-nal defect, all of which are rare. An initial pre-sentation of Ebstein’s anomaly in adulthood is common and is frequently accompanied by atrial arrhythmias; however, biventricular failure and ventricular arrhythmias are associated with re-duced survival.42 The incidence of tricuspid-valve endocarditis in the United States is increasing in parallel with increases in intravenous drug use, antibiotic re-sistance, and use of cardiac implantable elec-tronic devices.43 T he u se o f A ngioVac-assisted vegetation debulking is also increasing,44 and a recent meta-analysis of 44 studies that included 301 patients undergoing this procedure showed that the vegetation size was reduced by more than 50% in 89.2% of the patients.45 Although valvectomy may be associated with higher opera-tive mortality,46 a meta-analysis of surgical man-agement of infective tricuspid-valve endocarditis showed no significant difference in short-term outcomes between valvectomy and surgical valve replacement.47 Nonetheless, valvectomy remains a controversial management strategy but may be an acceptable bridge to definitive surgery.48 There is probably no difference in outcomes between repair and replacement, although repair is associated with a lower risk of a need for a permanent pacemaker.49 Thickening and restriction of tricuspid leaflet motion are commonly seen with rheumatic or carcinoid tricuspid-valve disease. Concomitant surgical management of rheumatic tricuspid re-gurgitation at the time of mitral-valve surgery reduces the progression of tricuspid regurgita-tion if the baseline disease is mild,50 w ith a n improvement in long-term survival when the baseline disease is moderate or severe (hazard ratio for death, 0.44; 95% CI, 0.23 to 0.87).51 Carcinoid heart disease, which occurs in 20 to 50% of patients with the carcinoid syndrome, is due to fibrosis and endocardial thickening of the heart valves, probably as the result of chron-ic exposure of valve tissue to high levels of sero-tonin.
Valve replacement for tricuspid regurgita-tion due to carcinoid heart disease may be challenging because of the systemic effects of the carcinoid syndrome, especially in patients with impaired hepatic function. The short-term mortality associated with valve replacement may be lower with earlier intervention and with care-ful preoperative planning.52 Other causes of primary tricuspid regurgita-tion include traumatic rupture of the tricuspid-valve apparatus from blunt chest trauma, a rare condition that may go undiagnosed until the chronic effects of volume overload result in symptoms of right heart failure.53,54 The overall prevalence of tricuspid regurgitation after heart transplantation is approximately 20% but is highest in the first month after transplantation and decreases over time.
There are multiple causes of tricuspid regurgitation in the trans-planted heart. However, late tricuspid regurgi-tation in the recipient of a heart transplant is predominantly related to cardiac allograft vas-culopathy and endomyocardial biopsy procedures

Secondary Tricuspid Regurgitation
In patients with secondary tricuspid regurgita-tion, the intrinsic structure of the leaflets ap-pears normal, but there can be abnormalities of the right atrium, tricuspid annulus, or right ventricle that result in leaflet malcoaptation.
Atrial abnormalities are seen in 10 to 25% of patients with secondary tricuspid regurgitation
Atrial secondary tricuspid regurgitation pressures, and the absence of left-side valve is characterized by normal-appearing leafease.
Patients with ventricular secondary tricuspid regurgitation is associated with the presence of atrial regurgitation have dilatation of the right ventricular fibrillation, a normal left ventricular ejection fraction, minimal elevation of pulmonary pressures and de absence of left valve desease
Patients with ventricular secondary tricuspid regurgitation have dilatation of the right ventri-cle (mainly the midventricular free wall), leading to apical displacement of the papillary muscles and tethering of the leaflets.56,59,63
Right ventricu-lar dilatation and dysfunction are most frequently due to remodeling in the context of elevated pulmonary artery pressures resulting from precapillary or postcapillary pulmonary hypertension. However, ventricular secondary tricuspid regur-gitation may also be attributable to other causes of right ventricular remodeling, including pri-mary cardiomyopathies with right ventricular involvement, right ventricular ischemia, and in-farction and arrhythmias.64 In addition, left ven-tricular dilatation or dysfunction or concomitant left-side valvular disease may be present, con-tributing to septal abnormalities that may affect septal leaflet tethering and coaptation. Discriminating atrial tricuspid regurgitation from the ventricular forms has prognostic and treatment implications.56,65-67
Patients with ventricular secondary tricuspid regurgitation (and either pulmonary arterial hypertension or left heart disease) have higher mortality than patients with atrial secondary tricuspid regurgitation or primary disease.68 In a study involving 211 pa-tients with secondary tricuspid regurgitation, the ventricular form was associated with a risk of death or hospitalization for heart failure that was 2.7 times (95% CI, 1.3 to 5.7) the risk with the atrial form.
Outcomes were predicted on the basis of the severity of tricuspid regurgitation in the group of patients with atrial secondary tri-cuspid regurgitation and on the basis of both the severity of tricuspid regurgitation and right ventricular function in those with ventricular secondary tricuspid regurgitation.56 A large retro-spective registry study supports these findings.69 Risk scores for medically treated and surgically treated patients (see the Supplementary Appen-dix, available with the full text of this article at NEJM.org) require further validation.

Tricuspid Regurgitation Associated with an Implantable Electronic Device
Although tricuspid regurgitation associated with cardiac implantable electronic devices was once categorized as a primary form of tricuspid re-gurgitation, it has features of both primary and secondary tricuspid regurgitation.70-72 However, implantable electronic device–induced tricuspid regurgitation has distinct epidemiologic features and management and therapeutic options. The diagnosis can be made noninvasively with the use of advanced imaging techniques such as three-dimensional echocardiography71 and com-puted tomography (CT),73 although in most stud-ies, electronic device interference with valve function has been assumed in patients with worsening tricuspid regurgitation.74,75 Device leads can interfere with any component of the tricus-pid-valve apparatus.71 The proportion of patients with tricuspid re-gurgitation related to or mediated by a cardiac implantable electronic device is expected to in-crease because of the aging of the population, an increasing number of device implantations, and device complications requiring lead extrac-tion.31,76,77 Approximately 25 to 29% of patients with permanent pacemakers have tricuspid re-gurgitation,78 and the cardiac implantable elec-tronic device is thought to be the cause of tricus-pid regurgitation in 7 to 45% of patients.71 In one study, moderate-to-severe tricuspid regurgi-tation occurred in 27% of patients after implan-tation of a cardiac implantable electronic device and was associated with an increased number of hospitalizations for heart failure.74 However, not all cardiac implantable electronic devices cause tricuspid regurgitation; it may instead be an in-cidental finding. In one study, up to 60% of cases of worsened tricuspid regurgitation after implantation of a cardiac implantable electronic device were of another origin, such as atrial fi-brillation or previous open-heart surgery.79 If tricuspid regurgitation is caused by the cardiac implantable electronic device, lead removal per-formed in a timely fashion may prevent the de-velopment of severe right ventricular dilatation and dysfunction,80 but removal results in wors-ening of tricuspid regurgitation in approximate-ly 10% of patients, with injury to the valve in approximately 3%.81

DIAGNOSIS

Echocardiography remains the primary imaging technique for identifying the cause, morphologic features, and severity of tricuspid regurgitation, with the recognition that cardiac magnetic reso-nance imaging (MRI) and cardiac CT have ex-panding roles, particularly for patients who are being considered for transcatheter therapies.39 Echocardiography guidelines recommend a multiparametric approach to assess tricuspid regurgitation, with the use of a three-grade scheme (mild [1+], moderate [2+], and severe[3+]) to describe the degree of regurgitation.39,82 However, patients presenting for catheter-based interventions frequently present late in the disease process, and an extended grading scheme (severe [3+], massive [4+], and torrential [5+]) was developed to more precisely describe the severity of tricuspid regurgitation in such pa-tients 83
Data from early trials of transcatheter therapy for tricuspid regurgitation that used this grading scheme showed that even improvement limited to a single grade reduction was associ-ated with short-term improvement in function-ing and quality of life.84,85 An additional s tudy has shown that the extended severity of tricuspid regurgitation grades are associated with worse outcomes.86 In light of these results, the Euro-pean Society of Cardiology77 and European As-sociation of Cardiovascular Imaging39 guidelines suggest use of the five-grade scheme to subcat-egorize patients referred for transcatheter inter-vention. Color Doppler imaging is not recom-mended as the primary method for assessing the severity of tricuspid regurgitation, given the lower pressures of the right heart and the poten-tial to underestimate severity.
When mild tricuspid regurgitation is seen on color Doppler imag-ing, patients should undergo a comprehensive, multiparametric, and multimodal echocardiographic assessment.39,77 Cardiac MRI is considered the reference stan-dard for assessing right ventricular chamber size and volumes and can be used to quantify the severity of tricuspid regurgitation.39,82,87 A regur-gitant volume of at least 45 ml or a regurgitant fraction of at least 50% may identify patients at highest risk for death.87 In general, cardiac MRI is indicated when the echocardiographic assess-ment is suboptimal or there is discordance be-tween the echocardiographic grading of tricuspid regurgitation and the patient’s clinical presenta-tion.
A comprehensive cardiac MRI study also quantitates cardiac remodeling (both atrial and ventricular) and provides insights into the mech-anism of tricuspid regurgitation. Alternatively, three-dimensional echocardiography may be use-ful for assessing right ventricular and tricuspid annular dimensions.59,88 Cardiac CT may also con-firm chamber remodeling, with planimetric as-sessment of the anatomical orifice area in deter-mining the severity of tricuspid regurgitation still investigational. In addition, CT has become a standard imaging technique for assessment of the tricuspid valve and right heart in patients who are candidates for transcatheter device therapies

THERAPY

A.Medical and Rhythm Management
In the absence of robust evidence, guideline-directed medical therapy for tricuspid regurgita-tion is currently limited to diuretics and the treatment of underlying causes of secondary tricuspid regurgitation, both of which are class IIa recommendations.39,62,77,89 Although conges-tive symptoms associated with tricuspid regur-gitation can respond initially to diuretics, un-responsiveness may develop as a result of neurohormonal activation (i.e., up-regulation of the renin–angiotensin–aldosterone system axis), an increased volume of diuretic distribution, vis-ceral edema causing impaired drug absorption and tubular drug delivery, and rebound sodium absorption in the hypertrophied distal renal nephrons.16 In patients with tricuspid regurgita-tion who are being treated for heart failure, di-uretic resistance is associated with a worse prog-nosis,90 and stage D right heart failure, defined as refractory right heart failure at rest,17 is associ-ated with an increased risk of death.91 A step-wise approach to diuretic management is sug-gested, with loop diuretics initially used to reduce volume load and thereby reduce pulmo-nary pressures (i.e., right ventricular afterload) and mineralocorticoid antagonists in natriuretic doses added to reduce decongestion in patients with more advanced disease.
Medical treatment of secondary tricuspid re-gurgitation requires a comprehensive evaluation of the type and severity of pulmonary hyperten-sion, assessment of left ventricular function, and consideration of rhythm control for atrial fibril-lation.62,77 Current management of pulmonary arterial hypertension requires an understanding of the underlying arterial disease and directed therapy to promote pulmonary vasodilatation or reduce pulmonary vasoconstriction.92 Because of the poor prognosis for patients with tricuspid regurgitation and precapillary pulmonary hyper-tension, recent European Society of Cardiology and European Association for Cardio-Thoracic Surgery guidelines for managing pulmonary hypertension give a class I recommendation for right heart catheterization in patients who have severe tricuspid regurgitation with or without left heart disease, before surgical or catheter-based valve interventions are performed.92 Medi-cal treatment of pulmonary arterial hyperten-sion is associated with right ventricular reverse remodeling and reversal of tricuspid annular dilatation, tricuspid-valve tenting, and regres-sion of tricuspid regurgitation, with improved clinical outcomes.35

 B.Surgical Management
The late presentation of patients with severe symptomatic tricuspid regurgitation is largely responsible for the 10 to 12% in-hospital mortal-ity associated with isolated surgical tricuspid-valve replacement.6,7 Guidelines give a class I level of recommendation for surgical treatment of severe tricuspid regurgitation at the time of left heart surgery.62 Management of severe, symptom-atic secondary tricuspid regurgitation remains controversial, in part because of the heteroge-neous patient population, the delay in diagnosis resulting from a late clinical presentation, and the absence of appropriate risk scores.
The guidelines give a class IIa recom-mendation for isolated tricuspid-valve surgery for symptomatic, severe primary tricuspid regur-gitation or symptomatic, severe secondary tri-cuspid regurgitation in patients in whom medi-cal therapy has failed and who have no pulmonary hypertension or left heart disease. Given the high mortality rate associated with reoperation, guidelines give a class IIb recommendation for tricuspid-valve surgery in patients with symptom-atic, severe tricuspid regurgitation and prior left-sided valve surgery in the absence of severe pulmonary hypertension or right ventricular sys-tolic dysfunction. A class IIb recommendation is also given for surgical intervention in patients with severe, asymptomatic primary tricuspid re-gurgitation and progressive right ventricular dilatation or dysfunction. The new classification of atrial and ventricu-lar secondary tricuspid regurgitation based on valvular and ventricular morphologic features is supported by the differences in surgical annulo-plasty outcomes.38 Although surgical repair with an annuloplasty ring is the preferred procedure, recurrent tricuspid regurgitation is seen more frequently in patients with marked tethering of the leaflets and right ventricular dysfunction — features of ventricular secondary tricuspid re-gurgitation — prompting surgeons to replace valves in these patients.62,77 Given the association of tricuspid-valve tethering and right ventricular remodeling with disease that is chronic and se-vere, adjusted outcomes for repair and replace-ment therapies do not appear to differ substan-tially, although the outcomes are more favorable with valve replacement in patients with a tricus-pid annular diameter larger than 44 mm.

C.Transcatheter Management
Transcatheter solutions are being pursued ag-gressively as lower-risk interventions in higher-risk patients with tricuspid regurgitation . Leveraging the success of the TEER devices for mitral regurgitation, proceduralists began using the commercially available mitral-valve devices to treat tricuspid regurgitation. Given the wide availability of this device, tricus-pid TEER currently remains the most common transcatheter therapy around the world.38
The multinational TriValve Registry was de-veloped to better understand the characteristics of patients undergoing transcatheter interven-tions and the treatment outcomes.97 In a study of registry data, the average age (±SD) of the pa-tients was 76±9 years and 60.4% were women. More than one third of the patients had previ-ously undergone left heart surgery (in most cases, valve surgery), and 79.0% were in perma-nent atrial fibrillation. Peripheral edema was observed in 81.0% of the patients, and 27.3% had ascites, despite the maximal tolerated di-uretic therapy. A total of 56.6% of the patients had been hospitalized in the preceding 6 months for right ventricular heart failure.
The baseline median N-terminal pro–B-type natriuretic peptide level was 2253 pg per milliliter (interquar-tile range, 1416 to 5252), and nearly all the pa-tients were being treated with a diuretic. These clinical characteristics have been consistent among patients treated with a transcatheter tri-cuspid valve.98 When patients in the registry were propensity-matched with a medically treated cohort, trans-catheter tricuspid-valve intervention was asso-ciated with a lower incidence (±SD) of the composite end point of death and rehospitaliza-tion (32±4% vs. 49±3%), as well as a lower inci-dence of the individual outcomes of death (23±3% vs. 36±3%) and rehospitalization (26±3% vs. 47±3%).5 A meta-analysis t hat i ncluded 2 1 transcatheter device studies showed an overall mortality of 5% (95% CI, 4 to 8) at 30 days, and an analysis of 6 studies showed an overall mor-tality of 25% (95% CI, 12 to 45) at 1 year.98 Outcomes were improved for patients in whom the procedure was successful, with success de-fined as a reduction in the tricuspid regurgita-tion grade to 2+ or less, as compared with those in whom the procedure failed (odds ratio, 0.42; 95% CI, 0.27 to 0.66).98 Predictors of short- and long-term outcomes after transcatheter interventions remain ill de-fined, in part because of the wide range of coex-isting conditions in patients who undergo these procedures, as well as the range of pathophysi-ological and morphologic features that define the anatomical restrictions for specific device therapies. As with surgical repair, isolated trans-catheter annuloplasty devices may be most use-ful primarily in patients who have annular dila-tation without marked leaflet tethering.
The success of the TEER devices has been studied most extensively, with the location of the regur-gitant jet, leaflet coaptation gap, extent of pace-maker lead impingement, complexity of leaflet structure, and chordal density identified as the major determinants of success.38 These limita-tions may result in reduced efficacy of the de-vice. TEER devices can reduce tricuspid regurgi-tation to moderate or less in 80 to 85% of patients and to mild or less in only 30 to 50% of patients.
Early feasibility studies suggested that the class of device with the greatest efficacy in re-ducing tricuspid regurgitation is the orthotopic tricuspid-valve replacement, which reduces tri-cuspid regurgitation to mild or less in more than 90% of patients; mortality at 1 year may be lower with this intervention than 1-year mortal-ity in natural history studies of severe tricuspid regurgitation and in recent meta-analyses of mainly repair devices.99 Elimination of tricuspid regurgitation, however, is associated with an increase in effective afterload to the right ven-tricle and unmasking of mechanical dysfunc-tion, which may limit the hemodynamic benefits of this device.
Despite reductions in right ven-tricular function, however, improvements in forward stroke volume can be seen.100 Device therapy continues to evolve, and both early feasibility studies and randomized, con-trolled trials of transcatheter devices as com-pared with medical therapy will help define the appropriate treatment, patient population, and management approach. These trials should help fill the current gaps in our understanding of optimal medical therapy and anatomical limita-tions of specific devices, as well as the efficacy of the devices and their impact on outcomes.
Understanding the role of left ventricular dysfunction, pulmonary arterial hypertension, right ventricular dysfunction, and concomitant valvu-lar heart disease, as well as renal and hepatic dysfunction, will also help inform physicians about treatment options.

CONCLUSIONS

The grim natural history of tricuspid regurgitation has stimulated the search for a better understanding of the pathophysiology of the disease, early detection, optimal medical man-agement, and ideal interventional timing and technique. Our understanding of clinical out-comes for patients with tricuspid regurgitation continues to expand, with the most recent large observational study suggesting that even mild tricuspid-valve disease is associated with reduced long-term survival.4
Recognition of the complex-ity of tricuspid-valve disease has led to a better classification scheme, which is supported by studies showing differences in patient outcomes that are associated with the refined disease cat-egories.56 Finally, there has been rapid growth in the development of less invasive transcatheter options for disease management as a means of overcoming the reported poor outcomes of iso-lated tricuspid-valve surgery.38
The pitfalls of current algorithms for detect-ing tricuspid-valve disease have necessitated the adoption of new methods for quantitation and grading of tricuspid regurgitation and have fos-tered an appreciation of the role of the right heart and pulmonary vasculature. Because of our nascent understanding of the pathophysiology, detection, and medical management of tricuspid regurgitation, patients are sent for surgical intervention late in the disease process, thereby in-creasing the risk of adverse outcomes. In this new era of transcatheter therapeutics, the number of devices to treat tricuspid regurgitation is rapidly increasing. Several knowledge gaps, how-ever, impede our management of severe, symptomatic tricuspid regurgitation. Improve-ment in outcomes will rely heavily on early recognition of tricuspid regurgitation by clinicians and referral to a level 1 comprehensive valve center, which has the medical, surgical, and interventional expertise to evaluate and manage this complex disease.

NOTE: This is a broad summary of a published article. Full text, references (101), tables, graphs, figures, and further details can be found
           in the journal mentioned at the beginning.