Tricuspid Regurgitation

Authors, Journal, Affiliations, Type, DOI

• Author: Rebecca T. Hahn, MD
• Affiliation: Department of Medicine, Columbia University Irving Medical Center, New York–Presbyterian Hospital, New York
• Journal: New England Journal of Medicine
• Type: Review article (CME)
• DOI: https://doi.org/10.1056/NEJMra2216709
• Published: May 18, 2023 (Vol. 388, No. 20, pp. 1876–1891)

Overview

This comprehensive NEJM review by Hahn reconceptualises tricuspid regurgitation (TR) as a clinically significant and frequently fatal condition, overturning the historical view of the tricuspid valve as a "forgotten valve." The article covers tricuspid valve anatomy, the epidemiology and natural history of TR (all-severity TR independently increases mortality, even mild TR raising all-cause mortality ~30%), the refined classification of TR into primary, atrial secondary, ventricular secondary, and CIED-related subtypes, and multimodality diagnostic approaches. Therapeutic options are systematically reviewed — medical, surgical, and the rapidly expanding transcatheter landscape including TEER devices and orthotopic transcatheter tricuspid valve replacement — with commentary on gaps in evidence and knowledge.

Keywords

Tricuspid regurgitation, tricuspid valve, secondary TR, atrial TR, ventricular TR, CIED-related TR, transcatheter edge-to-edge repair (TEER), tricuspid annuloplasty, transcatheter tricuspid valve replacement, right heart failure, pulmonary hypertension, atrial fibrillation, TRILUMINATE Pivotal, TriValve Registry, echocardiography, cardiac MRI

Key Takeaways

Anatomy

• The tricuspid valve is the largest cardiac valve with typically 3 leaflets (anterior, posterior, septal) of unequal size; the most common variant has 2 posterior leaflets
• Leaflets are thinner than mitral valve leaflets; anterior papillary muscle serves anterior and posterior leaflets; chordal attachments from septal papillary muscles or directly from the septum are unique to the tricuspid valve
• The tricuspid annulus has very little fibrous tissue or collagen — it is saddle-shaped and dynamic (larger in early diastole and atrial systole)
• Key threshold: Only 40% annular dilatation may cause clinically significant TR in the tricuspid valve (vs 75% annular dilatation in mitral valve studies), reflecting the valve's greater sensitivity to annular changes
• Sex differences: Females have a larger tricuspid annulus (even after body weight correction); males have more myocardial cells and elastic fibres histologically
• Adjacent at-risk structures: RCA lies within the AV groove along nearly the entire anterior and posterior annulus, narrowing to <3 mm inferiorly (risk of injury with annular devices); AV node and bundle of His cross the septal leaflet 3–5 mm from the anteroseptal commissure (risk of heart block)

Clinical Presentation

• Severe TR presents with signs of chronic right heart failure: elevated JVP, peripheral oedema, ascites, exercise intolerance, dyspnea, reduced cardiac output with progressive end-organ damage (cardiohepatic and cardiorenal syndromes)
• Symptoms often confused with left heart failure or normal ageing → delayed diagnosis
• Cardiohepatic syndrome is a strong independent predictor of death or HF hospitalisation within 1 year after transcatheter tricuspid-valve therapy
• Atrial fibrillation is common in TR and is associated with left and right atrial dilatation, annular dilatation, and AV valvular regurgitation; rhythm control is associated with TR reduction
• In patients with normal LV function, AF causes greater tricuspid annular dilatation than mitral annular dilatation
• HFpEF (with or without AF) has a high prevalence of prognostically important TR from RA/annular dilatation

Epidemiology

• Prevalence of clinically significant TR may be up to 4× higher in women than men; female sex is an independent predictor of severity and progression
• 1-year mortality with medical management of severe TR: 36–42% across two major studies
• All-cause mortality hazard ratios vs no/mild TR: HR 2.0–3.2 for moderate–severe TR; even mild TR = ~30% increased long-term all-cause mortality
• All-cause mortality is higher for TR (HR 2.74) than for aortic valve disease (HR 1.62) or mitral valve disease (HR 1.25) in the UK Biobank
• Predictors of progression include: AF, elevated PA systolic pressure, increased LA size, pacemaker/defibrillator leads, mild TR at baseline, annular dilatation, and prior valve surgery without concomitant TV surgery
• Morphologic predictors vary by cause: for PAH — RV enlargement, sphericity, annular dilatation, tenting area; for AF — leaflet tethering, LA volume, annular diameter, RV remodelling

Causes and Classification

• Primary TR (~10–20% of cases): Intrinsic valve disease — congenital anomalies (Ebstein's, tricuspid atresia, cleft valve), infective endocarditis, rheumatic disease, carcinoid (20–50% of carcinoid syndrome patients), toxic chemicals, tumours, blunt trauma, myxomatous degeneration, post-transplant
• Secondary TR (~80% of cases):
  • Atrial secondary TR: Marked RA and annular dilatation with normally appearing leaflets, minimal tethering, preserved RV function; associated with AF, normal LVEF, minimal PA pressure elevation, absence of left-sided valve disease
  • Ventricular secondary TR: RV dilatation (mainly midventricular free wall), apical papillary muscle displacement, and leaflet tethering; most commonly due to precapillary or postcapillary PH with RV remodelling; also from cardiomyopathies, RV ischaemia/infarction, arrhythmias
• CIED-related TR (~10–15% of cases): Distinct from primary and secondary — device leads can interfere with any component of the TV apparatus; ~25–29% of patients with permanent pacemakers have TR; CIED is causative in 7–45% of TR cases; up to 60% of worsened TR after CIED implantation is of another origin (e.g., AF, prior cardiac surgery)
• Prognostic distinction: Ventricular secondary TR has 2.7× higher risk of death/HF hospitalisation than atrial secondary TR; outcomes in atrial TR predicted by TR severity alone; outcomes in ventricular TR predicted by TR severity and RV function

Diagnosis

• Echocardiography: Primary modality; multiparametric approach recommended; standard 3-grade scheme (mild/moderate/severe); extended 5-grade scheme (severe/massive/torrential) developed for transcatheter intervention candidates — even 1-grade reduction associates with short-term improvement in function and QoL
• Color Doppler not recommended as primary assessment method (underestimates TR due to low right heart pressures); multiparametric assessment required even for mild TR on colour Doppler
• Cardiac MRI: Reference standard for RV chamber size/volume and TR quantification; regurgitant volume ≥45 ml or regurgitant fraction ≥50% identifies patients at highest risk for death; indicated when echo is suboptimal or discordant with clinical presentation
• 3D echocardiography: Useful for RV and tricuspid annular dimensions
• Cardiac CT: Standard for pre-transcatheter device planning; CT planimetric assessment of anatomical orifice area for TR severity still investigational

Therapy

Medical and Rhythm Management

• No robust evidence base; guideline-directed medical therapy limited to diuretics (Class IIa) and treating underlying causes of secondary TR (Class IIa)
• Stepwise diuretic approach: loop diuretics first → mineralocorticoid antagonists for advanced disease
• Diuretic resistance is associated with worse prognosis; stage D right heart failure (refractory at rest) = increased death risk
• Right heart catheterisation is Class I recommendation before surgical or catheter-based valve interventions in severe TR with precapillary PH
• Medical treatment of PAH is associated with RV reverse remodelling and regression of TR
• CRT for left heart failure: ~41% of patients had TR severity reduction; severe TR at follow-up after CRT independently associated with all-cause mortality
• TEER for secondary mitral regurgitation: >1/3 of patients had TR reduction; TR ≤2+ independently associated with 42% relative risk reduction in long-term all-cause mortality
• Rhythm control (cardioversion or ablation) for AF: reduces right and left atrial volumes → improves TR

Surgical Management

• Isolated surgical TV replacement: 10–12% in-hospital mortality due to late presentation
• Class I: TV surgery for severe TR at time of left heart surgery
• Class IIa: Isolated TV surgery for symptomatic severe primary TR or symptomatic severe secondary TR failing medical therapy without PH or left heart disease
• Class IIb: TV surgery in symptomatic severe TR with prior left-sided valve surgery (without severe PH or RV systolic dysfunction); asymptomatic severe primary TR with progressive RV dilatation or dysfunction
• Annuloplasty ring is the preferred procedure; recurrent TR more frequent with marked leaflet tethering and RV dysfunction (ventricular secondary TR) → may favour valve replacement
• Replacement superior to repair when tricuspid annular diameter >44 mm; adjusted outcomes for repair vs replacement otherwise do not differ substantially

Transcatheter Management

• TriValve Registry (multinational): mean age 76±9 years; 60.4% women; 79% in permanent AF; 81% with peripheral oedema; 56.6% hospitalised for RHF in preceding 6 months; median NT-proBNP 2253 pg/ml
• Propensity-matched vs medical therapy: transcatheter intervention → lower composite death+rehospitalisation (32% vs 49%), lower death (23% vs 36%), lower rehospitalisation (26% vs 47%)
• Meta-analysis (21 device studies): 30-day overall mortality 5%; 1-year overall mortality 25% (6 studies)
• Procedural success (TR reduced to ≤2+) associated with improved outcomes (OR 0.42 for death)
• TEER devices (TriClip, PASCAL): Reduces TR to ≤moderate in 80–85% of patients; to ≤mild in only 30–50%
• Isolated transcatheter annuloplasty devices: Most useful for annular dilatation without significant leaflet tethering
• Orthotopic transcatheter TV replacement (e.g., EVOQUE): Reduces TR to ≤mild in >90% of patients; however, elimination of TR may unmask RV mechanical dysfunction due to increased afterload, though improvements in forward stroke volume can still be seen
• TRILUMINATE Pivotal (RCT — TEER vs medical therapy): Win ratio 1.48 (95% CI 1.06–2.13; p=0.02) favouring TEER — driven by QoL improvement (KCCQ); no significant difference in 1-year death or TV surgery rates or HF hospitalisation rates between groups
• Device therapy continues to evolve; several ongoing RCTs will define optimal patient populations and management strategies

Conclusions

• Early recognition by clinicians and referral to a level 1 comprehensive valve centre is critical
• Gaps remain: optimal medical therapy, anatomical limitations of specific devices, identification of patients who will benefit from device therapy, impact on mortality
• RV and pulmonary vascular disease, renal and hepatic dysfunction must be evaluated before any intervention

Limitations of the Document

• Review article — not a systematic review or meta-analysis; subject to author selection bias
• Transcatheter trial data cited (TriValve Registry, early feasibility studies) had small sample sizes and were not randomised at time of publication; TRILUMINATE Pivotal is first published RCT data mentioned
• TRILUMINATE Pivotal met its hierarchical primary end point on QoL alone — no mortality or HF hospitalisation benefit demonstrated; the clinical significance of QoL-driven win ratios is debated
• Long-term outcomes data for transcatheter TR devices were not available at time of publication
• Guideline recommendations cited are pre-2023 (2020 ACC/AHA, 2021 ESC/EACTS); subsequent guidelines (ESC 2025, AHA 2024 Scientific Statement) have since updated class recommendations

Key Concepts Mentioned

• concepts/Tricuspid-Regurgitation — primary subject; detailed anatomy, classification, diagnosis, and management
• concepts/Right-Ventricular-Failure — clinical consequence of severe TR; cardiohepatic and cardiorenal syndromes
• concepts/Pulmonary-Hypertension — precapillary and postcapillary PH as causes of ventricular secondary TR

Key Entities Mentioned

• entities/Atrial-Fibrillation — major driver of atrial secondary TR; rhythm control improves TR
• entities/Heart-Failure — HFpEF as common context for TR; cardiohepatic and cardiorenal syndromes
• entities/Pulmonary-Hypertension — key cause and prognostic factor in ventricular secondary TR

Wiki Pages Updated

• wiki/sources/tr-nejm-2023.md — created (this file)
• wiki/concepts/Tricuspid-Regurgitation.md — updated with anatomy details, epidemiology mortality data, historical medical therapy context, and foundational TR classification framework
• wiki/sourceindex.md — added entry
• wiki/wikiindex.md — no new concept pages needed (TR concept page already exists)
• log.md — appended