Secondary tricuspid regurgitation

Article written and reviewed by Dr Luca Moretti

Secondary tricuspid regurgitation is a disease of the entire right-sided cardiocirculatory system in which leaflets without an important primary lesion can no longer coapt. The process may begin in the right atrium and annulus, in the right ventricle and subvalvular apparatus, or with the load imposed by the pulmonary circulation, but in advanced stages these mechanisms tend to converge. The traditional term “functional” regurgitation should therefore not suggest a harmless or purely reversible condition, because remodeling can become structural, self-perpetuating, and capable of producing right-sided heart failure and multiorgan damage.

The broader framework of tricuspid regurgitation also includes leaflet lesions, congenital forms, and interference from transvenous material. This monograph instead focuses on regurgitation generated by chamber and pressure remodeling: primary tricuspid valve disease or a mechanism directly caused by a lead requires a separate diagnostic category, even when a secondary component later develops.

Modern interpretation goes beyond jet grade. The phenotype must be defined, right ventricular reserve and coupling to the pulmonary artery measured, organ congestion recognized, and whether correction occurs within a still-reversible window established. This framework explains why patients with the same echocardiographic severity may have profoundly different prognosis, procedural anatomy, and response to treatment.

Atrial and ventricular phenotypes and the remodeling continuum

The atrial phenotype, often termed A-STR, is seen mainly at older ages, with female predominance, persistent or permanent atrial fibrillation, and heart failure with preserved ejection fraction. Right atrial dilation stretches a thin, nonplanar, dynamic tricuspid annulus that loses its systolic configuration and expands predominantly along the anteroposterior axis. Leaflet surface area may increase as an adaptive response, but growth becomes insufficient relative to the annular area that must be covered; regurgitation therefore arises from a mismatch between available tissue and the orifice, initially with modest tethering.

Ventricular geometry in the atrial form is not that of a completely normal right ventricle. In early stages, dilation predominantly involves the basal region contiguous with the annulus, while the mid-ventricle remains relatively preserved and the cavity assumes a more conical than spherical shape. Consequently, a single basal diameter may overestimate global remodeling, and three-dimensional or magnetic resonance volumes, the ratio between atrial and ventricular dimensions, and the regional distribution of dilation are more informative.

The ventricular phenotype, or V-STR, instead results from right ventricular deformation and traction on the subvalvular apparatus. Left-sided valvular or myocardial disease, HFrEF or HFmrEF, postcapillary pulmonary hypertension, precapillary pulmonary vascular disease, ischemia, or right ventricular cardiomyopathy increase chamber load and volume. The free wall dilates, the cavity becomes more spherical, the papillary muscles shift laterally and apically, and the leaflets are held below the annular plane. In this configuration, annular reduction alone may fail to restore an adequate coaptation surface.

The mechanical distinction has therapeutic consequences. A form dominated by annular dilation, with mobile leaflets and a limited coaptation gap, is better suited to annuloplasty or repair strategies; a form with severe tethering, a large gap, and papillary displacement may require additional techniques or replacement. The classification should not, however, be applied as a rigid dichotomy: atrial fibrillation, HFpEF, and pulmonary hypertension can coexist, and left-sided disease may simultaneously produce pressure overload, atrial dilation, and ventricular failure.

To make the atrial phenotype reproducible, proposed criteria include at least moderate secondary regurgitation, predominant annular dilation, atrial enlargement disproportionate to ventricular size, absence of significant tethering, conical ventricular remodeling with a nondilated mid-ventricle, and preserved biventricular systolic function. Suggested measurements include an end-systolic ratio of right atrial to right ventricular volume or area of at least 1.5, tenting height no greater than 9 mm, tenting area below 2.1 cm², tenting volume below 2.5 mL, and leaflet angle below 15°. All criteria define a “definite” form and at least four a “probable” form. This is a consensus phenotyping proposal useful for research and specialist practice, not a set of thresholds mandated by guidelines.

Atrial fibrillation is not merely an epidemiologic association: loss of atrial contraction, cycle irregularity, chronically increased filling pressures, and fibrosis promote enlargement of the atrium and annulus, which in turn facilitates persistence of the arrhythmia. In patients with HFpEF, left ventricular stiffness, increased postcapillary pulmonary pressure during exercise, and atrial dysfunction may accelerate the process even when estimated resting pressure is not markedly elevated; simply calling this form “idiopathic” therefore conceals recognizable pathophysiologic determinants.

Progression transforms the phenotype. Regurgitant volume returns to the ventricle with each diastole, dilates the base and then the entire cavity, displaces the papillary muscles, and adds tethering to a disease that began in the atrium. In parallel, the ventricular phenotype may develop marked atrial dilation and atrial fibrillation. In the mixed stage, reconstructing the trajectory from previous studies, arrhythmia duration, history of left-sided heart disease, and hemodynamics is more informative than forcing the current anatomy into a pure category.

Prognostic data confirm that etiology remains meaningful beyond grade. In the CARE-TR registry, which included 648 patients with severe secondary regurgitation, 22.1% had the atrial phenotype and 77.9% the ventricular phenotype. At two years, survival free from death or heart-failure hospitalization was 73.5% in the atrial form and 54.4% in the ventricular form; after adjustment, the ventricular phenotype carried a twofold risk, with a hazard ratio of 2.00 and 95% confidence interval of 1.33-3.02. A precapillary component of pulmonary hypertension identified the worst prognosis in the ventricular group, while the combination of atrial fibrillation and HFpEF was less favorable than either condition alone in the atrial group.

Right ventricular pathophysiology and right ventricular-pulmonary arterial coupling

The normal right ventricle is a thin-walled chamber adapted to eject volume against low impedance. It tolerates an acute increase in preload relatively well but is sensitive to persistently increased afterload. In the atrial form, volume overload initially predominates; in the ventricular form, combinations of volume and pressure overload are common. In both, dilation displaces the annulus and subvalvular apparatus, regurgitation increases, and a vicious cycle develops among geometry, valvular incompetence, and further remodeling.

Total right ventricular stroke output includes both forward pulmonary flow and the volume ejected backward into the atrium. When the regurgitant orifice is large, the atrium provides a low-impedance pathway, so an apparently preserved ejection fraction may coexist with reduced effective stroke volume and impaired contractility. TAPSE, S′ velocity, and fractional area change are also load-dependent and describe only selected aspects of a chamber with complex three-dimensional contraction, creating a risk of overestimating reserve in extreme regurgitation.

Right ventricular function should therefore be reconstructed by integrating annular excursion, S′, fractional area change, free-wall strain, three-dimensional volumes and ejection fraction, cardiac magnetic resonance data, and forward output. Strain may identify longitudinal dysfunction early but depends on image quality, software, and loading conditions; 3D or CMR ejection fraction better describes global remodeling without becoming a pure measure of contractility, and no single value universally defines severe dysfunction or futility of intervention.

RV-PA coupling expresses how adequately right ventricular contractility matches pulmonary arterial load. The physiologic reference is the invasive ratio of ventricular end-systolic elastance to arterial elastance, Ees/Ea, derived from pressure-volume loops; a falling ratio indicates that contractile adaptation no longer compensates for afterload. This measurement is difficult to obtain routinely. The TAPSE/PASP ratio is a pragmatic surrogate because it combines a longitudinal measure of function with an estimate of pulmonary pressure, but it does not fully reproduce Ees/Ea and loses accuracy when either term is unreliable.

In a cohort of secondary regurgitation, a TAPSE/PASP ratio below 0.31 mm/mmHg identified uncoupling and was associated with five-year survival of 37%, compared with 64% in coupled patients, with an adjusted hazard ratio of 1.462. Other populations have produced thresholds around 0.36 or different values after intervention. This variability reflects selection, severity, and load dependence: 0.31 mm/mmHg is a prognostic finding from a specific cohort, not a universal threshold for accepting or rejecting surgery or transcatheter therapy.

Echocardiographic PASP deserves particular caution. In massive or torrential regurgitation, a large orifice may cause early equalization of right ventricular and atrial pressures and a low-velocity jet; the gradient derived from the Bernoulli equation then underestimates ventricular systolic pressure. An imprecise estimate of right atrial pressure amplifies the error. When the presence of precapillary pulmonary hypertension changes indication and prognosis, right-heart catheterization should define mean pulmonary artery pressure, wedge pressure, cardiac output, and pulmonary vascular resistance.

Correction of regurgitation abruptly changes loading conditions. Once the retrograde pathway is eliminated, the entire systolic volume must be ejected into the pulmonary circulation: effective afterload increases and afterload mismatch may occur, especially after complete valve replacement. A postprocedural decrease in functional indices does not always signify new injury because it may reveal true contractility previously masked by regurgitation; however, a ventricle that is already uncoupled or exposed to high pulmonary vascular resistance can develop low output and acute failure. Selection must therefore assess reserve, not anatomical feasibility alone.

Chronic elevation of atrial pressure is transmitted to the venae cavae, liver, kidneys, and intestine. Hepatic congestion, cholestasis, and fibrosis combine with reduced perfusion; in the kidneys, elevated venous pressure reduces the filtration gradient and promotes diuretic resistance. Edema of the intestinal wall impairs absorption and nutrition. This multiorgan congestion may become only partially reversible even after a technically perfect procedure and explains why recurrent ascites, hypoalbuminemia, elevated bilirubin, and worsening renal function are signs of late referral.

Phenotypic diagnosis, multimodality quantification, and prognosis

Echocardiography should be performed, when clinically feasible, after reasonable decongestion and under documented hemodynamic conditions. Preload, afterload, respiration, blood pressure, rhythm, and therapy modify regurgitation. In atrial fibrillation, it is incorrect to rely on a random beat: cycles with comparable preceding RR intervals should be averaged, avoiding post-pause beats. An examination under general anesthesia or positive-pressure ventilation may underestimate outpatient severity.

Dedicated transthoracic views define the dimensions of the atrium, annulus, and ventricle, leaflet number and mobility, jet origin, tenting, and coaptation gap. Color jet area alone does not quantify severity: it depends on gain, Nyquist scale, pressure difference, and the Coanda effect, while extremely large regurgitation may appear less turbulent because of low velocity. Vena contracta should be sought perpendicular to the jet; with multiple jets, measuring only the largest does not represent the sum of the orifices.

Multiparametric assessment includes vena contracta, PISA radius, EROA and regurgitant volume, density and contour of the continuous-wave Doppler signal, hepatic vein flow, and chamber consequences. Conventional thresholds compatible with severe regurgitation are a vena contracta of at least 7 mm, EROA of at least 40 mm², and regurgitant volume of at least 45 mL. A dense, triangular continuous-wave profile with an early peak and systolic hepatic flow reversal support the diagnosis, but no parameter is absolute: atrial fibrillation, pacemakers, atrial compliance, and pressure modify contour and flows.

The PISA method assumes hemispheric convergence and a substantially circular orifice. In secondary regurgitation, the orifice is often elliptical, elongated along the coaptation line, dynamic, and sometimes multiple, leading to frequent underestimation of EROA. Three-dimensional measurement of vena contracta area avoids the geometric assumption but requires adequate spatial and temporal resolution. Discordant values should lead to physiologic synthesis and, when necessary, a complementary modality, not opportunistic selection of the most favorable number.

The grading system used in transcatheter trials extends severe regurgitation with massive and torrential categories. In this scheme, vena contracta 7-13 mm and EROA 40-59 mm² correspond to severe; vena contracta 14-20 mm, EROA 60-79 mm², or regurgitant volume 60-74 mL to massive; and values of at least 21 mm, at least 80 mm², or at least 75 mL, respectively, to torrential. The five-grade scale better captures substantial reductions among extreme regurgitant lesions. The 2025 European guidelines, however, did not turn it into a normative classification, to avoid normalizing late referral or considering a residual lesion that remains severe as satisfactory.

Three-dimensional echocardiography reconstructs the annulus, coaptation line, and variable leaflet arrangement, often more complex than the three-cusp anatomical model. Transesophageal imaging identifies the grasping zone, tissue length and quality, gap, and device trajectory and is essential for TEER guidance. The anterior position of the tricuspid valve, acoustic shadowing, and distance from the probe may limit images: procedural feasibility requires reproducible projections, not merely theoretically favorable anatomy.

Right ventricular function should be reported using multiple indices. TAPSE, S′, and fractional area change are accessible, while free-wall strain and 3D RVEF increase sensitivity and completeness. Cardiac magnetic resonance is the reference for volumes and ejection fraction and can quantify regurgitant volume and fraction from the difference between ventricular stroke volume and pulmonary flow or with flow techniques; shunts, other regurgitant lesions, and arrhythmias must be considered. Cardiac CT measures annular area and perimeter, the relationship with the right coronary artery, venae cavae, access routes, and landing zones for annuloplasty and replacement.

Right-heart catheterization is part of the pathway for intervention candidates and becomes particularly informative when echocardiography does not define pulmonary pressure or when distinguishing postcapillary from precapillary disease determines treatment. In severe regurgitation, thermodilution may be less reliable; the Fick method depends on accurate oxygen consumption. Measurements must be interpreted with volume status and therapy. Mean atrial pressure and v waves describe congestion, but a single study after intensive diuresis does not replace the clinical trajectory.

Prognostic stratification integrates severity, symptoms, KCCQ, exercise capacity, hospitalizations, RV function and coupling, pulmonary pressure and resistance, renal and hepatic function, albumin, bilirubin, and natriuretic peptides. The TRI-SCORE combines eight clinical and biological variables to estimate risk after isolated surgery. In the TRIGISTRY registry, two-year survival was 83%, 74%, and 59% in the low-, intermediate-, and high-risk groups. The association between successful intervention and improved survival was evident in the first two groups but not in the high-risk group; because this was an observational analysis, it does not demonstrate individual futility and should not become a means of delaying evaluation.

The appropriate time for intervention precedes severe ventricular dysfunction, advanced precapillary pulmonary hypertension, and irreversible hepatorenal damage. A person who progressively reduces activity may report few symptoms despite major limitation, and edema controlled by increasing doses of diuretics is not equivalent to stability. Progressive ventricular enlargement, worsening strain or coupling, hospitalizations, ascites, and increasing diuretic requirements should trigger evaluation at a Heart Valve Centre before the late window.

Etiologic therapy, decongestion, and surgical timing

Medical therapy targets the underlying substrate and congestion. HFrEF and HFmrEF require guideline-directed disease-modifying therapy; in HFpEF, comorbidities, blood pressure, ischemia, and volume overload should be treated, while left-sided valve disease or pulmonary disease should receive appropriate specific treatment. Loop diuretics, potentially combined with sequential nephron blockade and a mineralocorticoid receptor antagonist, reduce venous pressures and symptoms. No drug, however, has been shown to directly restore coaptation in advanced disease or confer a survival benefit specific to tricuspid regurgitation.

In the atrial phenotype, rhythm control may interrupt part of the cycle linking atrial fibrillation, atrial dilation, and loss of coaptation. Observational studies describe reverse remodeling and reduced regurgitation after restoration and maintenance of sinus rhythm, especially before marked dilation and tethering develop. There is, however, no TR-specific randomized evidence of improved events, and the probability of maintaining rhythm depends on arrhythmia duration and substrate. Anticoagulation follows thromboembolic risk from atrial fibrillation, not regurgitation grade.

Decongestion should not become a strategy of indefinite waiting. An apparent reduction in the jet after diuresis demonstrates a dynamic component but does not exclude anatomy destined to recur when preload rises. Escalating doses, hyponatremia, worsening renal function, ascites, or hospitalizations indicate progression. Waiting for overt diuretic refractoriness exposes the patient to malnutrition, hepatic fibrosis, and loss of RV-PA reserve, reducing the benefit obtainable from surgery or transcatheter intervention.

The 2025 ESC/EACTS guidelines recommend concomitant tricuspid surgery for severe regurgitation when the patient is undergoing left-sided valve surgery, class I B. In moderate regurgitation, repair should be considered, class IIa B; in mild secondary regurgitation with an annulus of at least 40 mm or greater than 21 mm/m², it may be considered only in selected patients, class IIb B. The aim is to prevent progression after correction of the left-sided lesion because normalization of pressures does not guarantee reverse remodeling of an already dilated annulus, and late reoperation carries high risk.

The randomized CTSN trial evaluated 401 patients undergoing surgery for degenerative mitral regurgitation who had moderate tricuspid regurgitation or lesser regurgitation with a dilated annulus. At two years, concomitant repair reduced the composite endpoint from 10.2% to 3.9%, mainly by preventing progression to severe regurgitation, 0.6% versus 6.1%; it did not demonstrate a benefit in mortality or rehospitalization and increased permanent pacemaker implantation from 2.5% to 14.1%. This evidence informs the concomitant decision but cannot automatically be extrapolated to isolated surgery for secondary tricuspid regurgitation.

In severe isolated disease, symptoms or progressive ventricular dilation and deterioration justify surgical assessment in the absence of severe biventricular dysfunction and severe pulmonary hypertension. Risk does not depend on sternotomy alone: reoperation, prior irradiation, cirrhosis, renal function, frailty, and nutritional status influence outcomes. The indication should be discussed before terminal congestion; the traditional strategy of waiting for striking symptoms is inadequate in a disease in which patients adapt their lifestyle early.

Annular repair with a prosthetic ring is preferred when durable coaptation is expected. Suture repair alone is more prone to recurrence; important tethering may require leaflet or subvalvular techniques and makes success from annular reduction alone less likely. Replacement is considered when gap, deformation, and tissue quality do not permit reliable repair. The risk of conduction disturbances, pacing strategy, and potential future transcatheter accessibility should be part of planning.

A successful procedure does not immediately erase the pathophysiology. After correction, volume, function, output, and pulmonary pressure should be reassessed, distinguishing physiologic adaptation to the new afterload from right ventricular failure. Treatment of the causal heart disease continues; rhythm, volume status, and organ function remain determinants. Clinical success includes less congestion, functional recovery, and fewer hospitalizations, not merely a postoperative image with a smaller jet.

Transcatheter interventions: TEER, annuloplasty, and replacement

The 2025 European guidelines consider transcatheter intervention in patients with severe symptomatic regurgitation despite optimal therapy, high surgical risk, and suitable anatomy, provided severe right ventricular dysfunction or advanced precapillary pulmonary hypertension is absent. The class IIa, level A recommendation reflects randomized evidence on quality of life and remodeling. Selection remains the responsibility of an experienced Heart Team because the same severity may require repair, replacement, or conservative treatment depending on geometry and hemodynamic reserve.

Transcatheter edge-to-edge repair approximates the leaflets and reduces orifice area. Favorable features include a central or anteroseptal jet, mobile tissue of sufficient length for grasping, good visualization, and a limited coaptation gap; a gap up to about 7 mm is generally favorable, whereas 10 mm or more is often technically unfavorable and has been an exclusion criterion in several studies. Extreme tethering, widely separated multiple jets, short leaflets, or inadequate imaging reduce success. Residual valve area and gradient must be monitored because multiple devices can create functional stenosis.

In TRILUMINATE Pivotal, TEER was superior to medical therapy alone for the hierarchical endpoint at one year, driven by improvement in quality of life; initially there were no clear differences in death or heart-failure hospitalization. In the two-year analysis of the complete randomized cohort of 572 patients, the recurrent hospitalization rate was 0.19 versus 0.26 per patient-year, hazard ratio 0.72, while mortality was similar, 17.9% versus 17.1%. Eighty-four percent of treated patients had regurgitation no greater than moderate. Crossover of 61.5% of controls after the first year complicates some long-term comparisons.

The Tri.Fr trial randomized 300 patients with severe isolated symptomatic regurgitation to TEER plus medical therapy or medical therapy alone. At one year, the hierarchical clinical composite was improved in 74.1% of treated patients versus 40.6% of controls; mean KCCQ score was 69.9 versus 55.4, and persistent massive or torrential regurgitation remained in 6.8% versus 53.5%. The study strengthens evidence for benefit in functional status and perceived health without providing, at that follow-up, definitive proof of reduced mortality.

Direct transcatheter annuloplasty reproduces the surgical rationale by applying anchors and tension to the annulus. It is particularly coherent with an early atrial form dominated by annular dilation, mobile leaflets, and modest tethering. CT should define distance from the right coronary artery, tissue quality, perimeter, and anchor trajectory; advanced ventricular deformation limits recovery of coaptation. In the prospective TRI-REPAIR study, 30 patients treated with Cardioband had regurgitation no greater than moderate in 72%, NYHA class I-II in 82%, and survival of 73% at two years. The nonrandomized design makes these findings evidence of feasibility, not superiority.

Orthotopic transcatheter replacement, or TTVR, offers an alternative when a large gap, severe tethering, or multiple jets make effective repair unlikely. CT verifies annular dimensions, landing zone, venous access, and anatomical relationships. The advantage is near-complete abolition of regurgitation; physiologic and procedural costs include an immediate increase in afterload, bleeding, conduction disturbances requiring pacemaker implantation, and thrombotic risk, requiring an individualized antithrombotic strategy. Pre-existing transvenous material must be mapped, but its potential causal role belongs to the specific diagnosis of device-related regurgitation.

In TRISCEND II, 400 patients were assigned in a 2:1 ratio to TTVR plus medical therapy or medical therapy alone. At one year, the hierarchical composite favored replacement with a win ratio of 2.02, driven mainly by symptoms and quality of life; 95.2% of treated patients had absent or mild regurgitation, compared with 2.3% of controls. Mortality, 12.6% versus 15.2%, and heart-failure hospitalization, 20.9% versus 26.1%, did not differ significantly. Severe bleeding occurred in 15.4% versus 5.3%, and new pacemaker implantation in 17.4% versus 2.3%, highlighting the trade-off between valve efficacy and risk.

A peer-reviewed 18-month analysis of TRISCEND II showed regurgitation no greater than mild in approximately 95% of patients undergoing replacement, regardless of baseline severity. In the subgroup with massive or torrential regurgitation, there was a signal of fewer hospitalizations, 23.6% versus 38.8%, an absolute difference of 15.2 percentage points. Because the analysis by baseline severity was post hoc, the finding is hypothesis-generating and does not prove that TTVR reduces events in every patient with extreme regurgitation.

TEER, annuloplasty, and TTVR have not been compared directly in randomized trials. TEER preserves the native valve and has a favorable procedural profile but more often leaves residual regurgitation; annuloplasty corrects the annular substrate without resolving advanced tethering; TTVR provides the most complete reduction at the cost of greater afterload and complications. Choice follows the dominant mechanism: gap, jet location, leaflet mobility and length, annular dimensions, pulmonary pressure, coupling, and imaging feasibility must be assessed together.

Follow-up after treatment documents residual regurgitation, gradient, device stability, volumes, function, and pulmonary pressure, as well as KCCQ, functional class, diuretic dose, and hospitalizations. A ventricle may decrease in size without normalizing function; kidneys and liver may recover only partially. The strongest evidence demonstrates improvement in regurgitation, symptoms, quality of life, and remodeling, with a signal toward fewer hospitalizations over longer follow-up. A definite mortality benefit has not yet been established and should not be promised.

Secondary tricuspid regurgitation therefore requires a temporal diagnosis, not merely an anatomical one. Recognizing the atrial phenotype before it evolves into ventricular remodeling, distinguishing postcapillary from precapillary pressure, measuring RV-PA reserve, and intervening before multiorgan damage are the steps that turn technically feasible correction into a clinically plausible benefit. Jet severity identifies the diseased valve; timing, phenotype, and reversibility identify the patient who can truly benefit from therapy.