Performance of Transcatheter Direct Annuloplasty in Patients With Atrial and Nonatrial Functional Tricuspid Regurgitation.

BACKGROUND: A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. OBJECTIVES: This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. METHODS: This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). RESULTS: A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). CONCLUSIONS: Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Atrial Functional Tricuspid Regurgitation in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Knowledge about atrial functional tricuspid regurgitation (afTR) in transcatheter aortic valve replacement (TAVR) patients is scarce. OBJECTIVES: The aim of the study was to analyze the association between the entity and the development of tricuspid regurgitation (TR) in patients undergoing TAVR for aortic stenosis and concomitant TR. METHODS: We analyzed patients undergoing TAVR for severe aortic stenosis from January 2013 to December 2020 and concomitant at least moderate TR at baseline. afTR was defined as enlargement of the right atrium in relation to the right ventricle. TR development after TAVR and 3-year all-cause mortality were evaluated. RESULTS: Out of 3,474 TAVR patients, we identified 420 patients with concomitant at least moderate TR. A total of 363 patients were included in the study, with 178 patients stratified in the afTR and 185 in the non-afTR group based on a receiver-operating characteristic curve cutoff of 1.132 of the right atrial/right ventricular area ratio. TR improvement after TAVR was observed in significantly less patients with afTR compared with non-afTR (31.1% vs 60.6%; P < 0.001). Multivariate regression analysis confirmed afTR as independent predictor for TR persistence (adjusted OR: 2.80; 95% CI: 1.66-4.76; P < 0.001). Moreover, afTR was associated with aggravation of TR after TAVR (17.0% vs 6.8%; P = 0.013). Three-year all-cause mortality was significantly higher in patients with persistence compared with patients with improvement of TR (P < 0.001). CONCLUSIONS: In TAVR patients, afTR is an independent predictor for TR persistence. Moreover, TR persistence is associated with increased 3-year all-cause mortality.

Procedural success of transcatheter annuloplasty in ventricular and atrial functional tricuspid regurgitation.

Background: Transcatheter annuloplasty is meant to target annular dilatation and is therefore mainly applied in functional tricuspid regurgitation (TR). Due to recent recognition of varying disease pathophysiology and differentiation of ventricular and atrial functional TR (VFTR and AFTR), comparative data regarding procedural success for both disease entities are required. Methods: In this consecutively enrolled observational cohort study, 65 patients undergoing transcatheter annuloplasty with a Cardioband® device were divided into VFTR (n = 35, 53.8%) and AFTR (n = 30, 46.2%). Procedural success was assessed by comparing changes in annulus dilatation, vena contracta (VC) width, effective regurgitation orifice area (EROA), as well as reduction in TR severity. Results: Overall, improvement of TR by at least two grades was achieved in 59 patients (90.8%), and improvement of TR by at least three grades was realised in 32 patients (49.2%). Residual TR of ≤2 was observed in 52 patients (80.0%). No significant differences in annulus diameter reduction [VFTR: 11 mm (9-13) vs. AFTR: 12 mm (9-16), p = 0.210], VC reduction [12 mm (8-14) vs. 12 mm (7-14), p = 0.868], and EROA reduction [0.62 cm2 (0.45-1.10) vs. 0.54 cm2 (0.40-0.70), p = 0.204] were reported. Improvement by at least two grades [27 (90.0%) vs. 32 (91.4%), p = 1.0] and three grades [14 (46.7%) vs. 18 (51.4%), p = 0.805] was similar in VFTR and AFTR, respectively. No significant difference in the accomplishment of TR grade of ≤2 [21 (70.0%) vs. 31 (88.6%), p = 0.118] was noted. Conclusion: According to our results from a real-world scenario, transcatheter annuloplasty with the Cardioband® device may be applied in both VFTR and AFTR with evidence of significant procedural TR reduction.

Functional Mitral and Tricuspid Regurgitation across the Whole Spectrum of Left Ventricular Ejection Fraction: Recognizing the Elephant in the Room of Heart Failure.

Functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) occur due to cardiac remodeling in the presence of structurally normal valve apparatus. Two main mechanisms are involved, distinguishing an atrial functional form (when annulus dilatation is predominant) and a ventricular form (when ventricular remodeling and dysfunction predominate). Both affect the prognosis of patients with heart failure (HF) across the entire spectrum of left ventricle ejection fraction (LVEF), including preserved (HFpEF), mildly reduced (HFmrEF), or reduced (HFrEF). Currently, data on the management of functional valve regurgitation in the various HF phenotypes are limited. This review summarizes the epidemiology, pathophysiology, and treatment of FMR and FTR within the different patterns of HF, as defined by LVEF.

Arrythmia-Mediated Valvular Heart Disease.

The aging population is rising at record pace worldwide. Along with it, a steep increase in the prevalence of atrial fibrillation and heart failure with preserved ejection fraction is to be expected. Similarly, both atrial functional mitral and tricuspid regurgitation (AFMR and AFTR) are increasingly observed in daily clinical practice. This article summarizes all current evidence regarding the epidemiology, prognosis, pathophysiology, and therapeutic options. Specific attention is addressed to discern AFMR and AFTR from their ventricular counterparts, given their different pathophysiology and therapeutic needs.

Tricuspid Valve Geometrical Changes in Patients with Functional Tricuspid Regurgitation: Insights from a CT Scan Analysis Focusing on Commissures.

BACKGROUND: Cardiac computed tomography (CT) provides important insights into the geometrical configuration of the tricuspid valve (TV). The purpose of the present study was to assess the geometrical changes of TV in patients with functional tricuspid regurgitation (TR) using novel CT scan parameters and to correlate these findings with echocardiography. METHODS: This single-center study enrolled 86 patients undergoing cardiac CT and divided them into two groups according to the presence or not of severe TR (43 patients with TR ≥ 3+ and 43 controls). The measurements collected were as follows: TV annulus area and perimeter, septal-lateral and antero-posterior annulus diameters, eccentricity, distance between commissures, segment between the geometrical centroid and commissures, and the angles of commissures. RESULTS: We found a significant correlation between all annulus measurements and the grade of TR, except in regard to angles. TR ≥ 3+ patients had significantly larger TV annulus area and perimeter, larger septal-lateral, and antero-posterior annulus dimensions, as well as larger commissural distance and centroid-commissural distance. In patients with TR ≥ 3+ and controls, the eccentricity index predicted a circular shape and an oval shape of the annulus, respectively. CONCLUSIONS: These novel CT variables focusing on commissures increase the anatomical understanding of the TV apparatus and the TV geometrical changes in patients with severe functional TR.

Prognostic implications of atrial vs. ventricular functional tricuspid regurgitation.

AIMS: Atrial functional tricuspid regurgitation (AFTR) has shown distinctive pathophysiological and anatomical differences compared with ventricular functional tricuspid regurgitation (VFTR) with potential implications for interventions. However, little is known about the difference in long-term prognosis between these two FTR-aetiologies, which was investigated in the current study. METHODS AND RESULTS: Patients with severe FTR were divided into two aetiologies, based on echocardiography: AFTR and VFTR. VFTR was further subdivided into (i) left-sided cardiac disease; (ii) pulmonary hypertension; and (iii) right ventricular dysfunction. Long-term mortality rates were compared and independent associates of all-cause mortality were investigated.A total of 1037 patients with severe FTR were included, of which 129 patients (23%) were classified as AFTR and compared with 425 patients (78%) classified as VFTR and in sinus rhythm. Of the 425 VFTR patients, 340 patients (61%) had left-sided cardiac disease, 37 patients (7%) had pulmonary hypertension, and 48 patients (9%) had right ventricular dysfunction. Cumulative 10-year survival rates were significantly better for patients with AFTR (78%) compared with VFTR (46%, log-rank P < 0.001). On multivariable Cox regression analysis, VFTR as well as all VFTR subtypes were independently associated with worse overall survival compared with AFTR (HR: 2.292, P < 0.001 for VFTR). CONCLUSION: Patients with AFTR had significantly better survival as compared with patients with VFTR, as well as all VFTR subtypes, independently of other clinical and echocardiographic characteristics.

Percutaneous Repair of Atrial Functional Tricuspid Regurgitation in Cardiac Amyloidosis: Combining Linear With Lateral Thinking.

Restrictive physiology, such as cardiac amyloidosis, compromises atrial and ventricular performance, often leading to "atrial" functional valvular regurgitation. While focusing on atrial functional tricuspid regurgitation we aimed at summarizing the pathophysiological characteristics of, and therapeutic options in, cardiac amyloidosis. (Level of Difficulty: Intermediate.).

Pathophysiology, Echocardiographic Diagnosis, and Treatment of Atrial Functional Mitral Regurgitation: JACC State-of-the-Art Review.

The conventional view holds that functional mitral regurgitation (MR) is caused by restriction of leaflet motion resulting from displacement of the papillary muscle-bearing segments of the left ventricle. In the past decade, evidence has accrued suggesting functional MR can also be caused by left atrial enlargement. This underrecognized cause of secondary MR-atrial functional MR (AF-MR)-is mechanistically linked to annular enlargement, perturbations of annular contraction, and atriogenic leaflet tethering. AF-MR has been described in patients with atrial fibrillation and heart failure with preserved ejection fraction. Preliminary data suggest rhythm control may decrease MR severity in patients with atrial fibrillation. Additionally, several studies have reported reductions in MR and symptomatic improvement with restrictive annuloplasty and transcatheter edge-to-edge repair. This review discusses the pathophysiology, echocardiographic diagnosis, and treatment of AF-MR. AF-tricuspid regurgitation is also discussed.

Prognostic Impact of Severe Atrial Functional Tricuspid Regurgitation in Atrial Fibrillation Patients.

Background and Aim: Atrial fibrillation (AF) is an epidemic disease with a significant global health impact. Atrial functional tricuspid regurgitation (AF-TR) is a more recently acknowledged complication of AF. The main purpose of this study was to determine the prognostic value of severe AF-TR in patients with AF, and its determinants. Methods: In this retrospective, observational study, we included AF patients admitted consecutively to a tertiary clinical hospital between January 2018 and February 2020, irrespective of cause of hospitalization. Patients with organic TR, significant pulmonary hypertension, left ventricular ejection fraction < 50%, those with implanted cardiac devices and those with in-hospital mortality were excluded. Severe TR was defined according to current guidelines. Median follow-up time was 34 (28−39) months. Primary endpoint was all-cause mortality. Results: We included 246 AF patients, with a mean age of 71.5 ± 9.4 years. 86.2% had AF-TR, while 8.1% had severe AF-TR. Mortality rate was 8.5%. Right atrial diameter (p = 0.005), systolic pulmonary artery pressure (sPAP) (p = 0.015) and NT-proBNP (p = 0.026) were independent predictors for the presence of severe valvular dysfunction. In multivariable survival analysis, severe AF-TR, was an independent predictor of all-cause mortality (HR 5.4, 95% CI 1.1−26.2, p = 0.035). Conclusion: Severe AF-TR was an independent predictor of mortality in AF patients, while mild/moderate AF-TR apparently had no impact on prognosis.

Atrial Functional Tricuspid Regurgitation as a Distinct Pathophysiological and Clinical Entity: No Idiopathic Tricuspid Regurgitation Anymore.

Functional tricuspid regurgitation (FTR) is a strong and independent predictor of patient morbidity and mortality if left untreated. The development of transcatheter procedures to either repair or replace the tricuspid valve (TV) has fueled the interest in the pathophysiology, severity assessment, and clinical consequences of FTR. FTR has been considered to be secondary to tricuspid annulus (TA) dilation and leaflet tethering, associated to right ventricular (RV) dilation and/or dysfunction (the "classical", ventricular form of FTR, V-FTR) for a long time. Atrial FTR (A-FTR) has recently emerged as a distinct pathophysiological entity. A-FTR typically occurs in patients with persistent/permanent atrial fibrillation, in whom an imbalance between the TA and leaflet areas results in leaflets malcoaptation, associated with the dilation and loss of the sphincter-like function of the TA, due to right atrium enlargement and dysfunction. According to its distinct pathophysiology, A-FTR poses different needs of clinical management, and the various interventional treatment options will likely have different outcomes than in V-FTR patients. This review aims to provide an insight into the anatomy of the TV, and the distinct pathophysiology of A-FTR, which are key concepts to understanding the objectives of therapy, the choice of transcatheter TV interventions, and to properly use pre-, intra-, and post-procedural imaging.

Right heart chambers geometry and function in patients with the atrial and the ventricular phenotypes of functional tricuspid regurgitation.

AIMS: Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of functional tricuspid regurgitation (FTR) associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the right ventricle, right atrium, and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Accordingly, we sought to: (i) study the geometry and function of the right ventricle, right atrium, and TA in A-FTR by two- and three-dimensional transthoracic echocardiography; and (ii) compare them with those found in V-FTR. METHODS AND RESULTS: We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Severity of FTR was similar in A-FTR and V-FTR patients. Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (P < 0.001 for all). The right atrium was significantly enlarged in both A-FTR and V-FTR compared to controls (P < 0.001, Z-scores > 2), with similar right atrial (RA) maximum volume (RAVmax) between A-FTR and V-FTR (P = 0.2). Whereas, the RA minimum volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (P = 0.001). CONCLUSION: Despite similar degrees of FTR and RAVmax size, A-FTR patients show larger RAVmin and smaller TA areas than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic and dysfunctional right ventricle than A-FTR patients.

Atrial functional tricuspid regurgitation: An underappreciated cause of secondary tricuspid regurgitation.

Secondary tricuspid regurgitation (TR) caused by right ventricular enlargement in the setting of left heart disease/pulmonary hypertension has been well described. In contrast, that associated with right atrial enlargement-atrial functional TR (AF-TR)-remains largely underappreciated. AF-TR most often occurs in the setting of lone atrial fibrillation, although it is also seen in its absence (idiopathic AF-TR). Several recent studies have found that the prevalence, hemodynamic significance, and prognosis of AF-TR are not inconsequential, suggesting increased physician awareness of this novel clinical entity is warranted. This article discusses the pathogenesis, echocardiographic findings, and treatment of this underappreciated cause of secondary TR.