Significant Functional Tricuspid Regurgitation Research Articles

Incidence and predictors of the novo significant mitral and tricuspid regurgitation in patients with permanent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is related to atrial remodeling and annular enlargement, which leads to functional mitral and tricuspid regurgitation. These two entities can derive in heart failure with preserved left ventricular ejection fraction (LVEF), the reason why it is becoming a rising concern in recent years. However, its incidence and predictors have not been well established. Purpose This study aimed to assess the incidence and predictors of significant atrial functional mitral and tricuspid regurgitation in patients with permanent AF. Methods The study population comprised 547 patients from a Spanish health area diagnosed with permanent AF between 2014 and 2019 (CardioCHUVI-AF registry; ClinicalTrials.gov identifier: NCT04364516). Individuals who presented with atrial enlargement at the diagnosis, primary moderate to severe valve disease, previous cardiac surgery (including valve replacement or repair), decreased LVEF, pulmonary hypertension, or right ventricular pacing that could interfere with tricuspid valve closure were excluded. The median age was 78.0 (IQ 70.4-85.6), and men represented 43% of the population (235 patients) compared to women, which represented 57% (312 patients). During a median follow-up of 3.5 years (IQ 2.03-4.95) we assessed the incidence of moderate to severe de novo mitral and tricuspid valve regurgitation and its predictors. Results The development of moderate to severe mitral and tricuspid valve regurgitation was higher after three years of diagnosis. The incidence of mitral regurgitation was 3.8 (3.0-4.9) per 100 persons/year. The incidence of tricuspid regurgitation was 5.5 (4.5-6.8) per 100 persons/year. In addition, multivariate analysis showed an association between the development of mitral regurgitation and older age (HR 1.05 [CI 95% 1.01-1.09]), female sex (HR 1.82 [CI 95% 1.1-3]) and prior admission for HF (HR 2.35 [CI 95% 1.18-4.7]). On the other hand, the development of tricuspid regurgitation did not show an association with age (HR 1.02 [CI 95% 0.97-1.05]), but it did with prior admission for HF (HR 2.11 [CI 95% 1.17-3.79]) and female sex (HR 2.17 [CI 95% 1.43-3.3]). Conclusion Permanent atrial fibrillation was associated with an increased risk of developing atrial functional mitral and tricuspid regurgitation, especially after three years of the diagnosis and in the female sex. Older age was associated with a higher incidence of mitral regurgitation. Prior admission for HF was associated with a higher incidence of tricuspid regurgitation. Based on the preceding, monitoring a specific profile of patients with atrial fibrillation may be especially important in preventing and early treating valve disease that can compromise their prognosis.Incidence of mitral regurgitationIncidence of tricuspid regurgitation

Failure of Tricuspid Annuloplasty for Functional Tricuspid Regurgitation: Impact of Patient's Body Size

Tricuspid repair is recommended for significant functional tricuspid regurgitation (FTR) or tricuspid annulus (TA) dilation, based on TA >40mm or >21mm/m². The concordance between both TA dimensions related to the patient's body size has not been investigated. Patients who underwent rigid ring tricuspid annuloplasty for FTR between 2009 and 2017 were included. Assuming equality between both TA diameter criteria, patients were divided per body surface area (BSA): group 1=BSA ≤1.9m² and group 2=BSA >1.9m². The primary outcome was TR recurrence at 5years. Tricuspid annuloplasty was performed in 186 patients (group 1: 130 patients [69.9%]; group 2: 56 patients [30.1%]). Group 1 comprised more female (70.8% to 23.2%, p <0.001) and older patients (77.1 ± 9.3 years; 74.2 ± 8.2 years, p=0.048). Group 1 had a smaller absolute TA diameter (group 1: 45.3 ± 5.2mm; group 2: 48.2 ± 5.6mm, p <0.001), whereas the indexed TA size was inversely higher (group 1: 26.3 ± 3.4mm/m²; group 2: 24.2 ± 2.7mm/m², p <0.001). The tenting height was comparable (group 1: 7.8 ± 3.0mm; group 2: 8.0 ± 2.7mm, p=0.714). The median ring size was 30 (interquartile range 28 to 32) and 32 (interquartile range 30 to 34) for groups 1 and 2, respectively (p <0.001). TR recurrence at 5years was noticed in 20.2% and 6.5% of group 1 and 2 (p=0.035). Indexed TA diameter (hazard ratio 1.43, 95% confidence interval 1.10 to 1.87, p=0.008) and tenting height (hazard ratio 5.52, 95% confidence interval 1.87 to 14.57, p=0.002) were independent predictors of TR recurrence. In conclusion, when the absolute TA diameter is used as the primary criterion, smaller patients are at a higher risk for TR recurrence by having a proportionally larger TA at the time of repair. An individualized approach guided by patient's body size might be more appropriate to indicate FTR correction to adjust for the annuloplasty sizing method.

Computed tomographic analysis of the morphometrics and dynamics of the tricuspid annulus in secondary functional tricuspid regurgitation

ObjectivesSecondary functional tricuspid regurgitation (FTR) management remains controversial mainly due to the lack of knowledge in its pathogenesis and the difficulties to measure the actual dimensions of tricuspid annulus (TA) with current imaging methods. Using a novel method based on multiphase cardiac computed tomography (CT) scan acquisition to accurately analyze the right atrioventricular junction size, we sought to explore modifications of TA morphometry and dynamics in secondary FTR. MethodsEchocardiographic and cardiac CT studies were obtained from 21 patients with severe mitral regurgitation (MR group) and 21 patients with dilated cardiomyopathy (DCMP group). Using an in-house software, a 3-dimensiontal (3D) semiautomated delineation of the TA perimeter was assessed. Modifications of diameters, 2-dimensional/3D areas and perimeters were analyzed through time. These 2 groups of patients were compared with 30 healthy subjects, considering the presence of a significant (≥2+) versus nonsignificant (<2+) FTR in each group. ResultsMaximum TA 3D areas were 7.0 ± 1.2 cm2/m2 in healthy subjects at mid-to-late diastole and were smaller than in the MR group (9.8 ± 2.1 cm2/m2, P < .001) and the DCMP group (9.2 ± 3.0 cm2/m2, P < .001). In the MR group, patients with FTR <2+ had also larger TA areas and diameters than healthy patients (P < .01 for all 3D/2-dimensional parameters). TA shape was more circular only in the DCMP group with FTR ≥2+ compared with other patients (P < .05 for eccentricity). In multivariate analysis, both RA area (P < .001) and RV volume (P = .002) were independently related to TA dilatation. ConclusionsBased on multiphase CT image analyses, TA dilatation was directly related to RV and RA enlargement. Patients with severe mitral myxomatous disease and nondysfunctional tricuspid valve had yet dilated TA, which questioned the current cut-off recommendation for concomitant tricuspid annuloplasty in this specific population.

Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk.

Various definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes. In this French multicentre retrospective study, we included 606 patients with ≥moderate-to-severe isolated functional TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm2) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality. The relationship between the EROA and TCG was poor (R2 = 0.22), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA <60 mm2 vs. ≥60 mm2 (68 ± 3% vs. 64 ± 5%, p = 0.89). A TCG ≥10 mm was associated with lower four-year survival than a TCG <10 mm (53 ± 7% vs. 69 ± 3%, p < 0.001). After adjustment for covariates, including comorbidity, symptoms, dose of diuretics, and right ventricular dilatation and dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95% CI] = 1.47[1.13-2.21], p = 0.019) and cardiovascular mortality (adjusted HR[95% CI] = 2.12[1.33-3.25], p = 0.001), whereas an EROA ≥60 mm2 was not associated with all-cause or cardiovascular mortality (adjusted HR[95% CI]: 1.16[0.81-1.64], p = 0.416, and adjusted HR[95% CI]: 1.07[0.68-1.68], p = 0.784, respectively). The correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10 mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated significant functional TR.

Chronic Ovine Model of Right Ventricular Failure and Functional Tricuspid Regurgitation

The pathophysiology of severe functional tricuspid regurgitation (FTR) associated with right ventricular dysfunction is poorly understood, leading to suboptimal clinical results. We set out to establish a chronic ovine model of FTR and right heart failure to investigate the mechanisms of FTR. Twenty adult male sheep (6-12 months old, 62 ± 7 kg) underwent a left thoracotomy and baseline echocardiography. A pulmonary artery band (PAB) was placed and cinched around the main pulmonary artery (PA) to at least double the systolic pulmonary artery pressure (SPAP), inducing right ventricular (RV) pressure overload and signs of RV dilatation. PAB acutely increased the SPAP from 21 ± 2 mmHg to 62 ± 2 mmHg. The animals were followed for 8 weeks, symptoms of heart failure were treated with diuretics, and surveillance echocardiography was used to assess for pleural and abdominal fluid collection. Three animals died during the follow-up period due to stroke, hemorrhage, and acute heart failure. After 2 months, a median sternotomy and epicardial echocardiography were performed. Of the surviving 17 animals, 3 developed mild tricuspid regurgitation, 3 developed moderate tricuspid regurgitation, and 11 developed severe tricuspid regurgitation. Eight weeks of pulmonary artery banding resulted in a stable chronic ovine model of right ventricular dysfunction and significant FTR. This large animal platform can be used to further investigate the structural and molecular basis of RV failure and functional tricuspid regurgitation.

Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance

BackgroundLittle is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR). ObjectivesThe authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications. MethodsThe authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR. ResultsOf 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm2; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001). ConclusionsIn patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.

Incidence of atrial functional tricuspid regurgitation and its correlation with tricuspid valvular deformation in patients with persistent atrial fibrillation.

With the growing prevalence of atrial fibrillation (AF), concomitant atrial functional tricuspid regurgitation (FTR) is increasing. In this study, we aimed to elucidate the incidence of significant atrial FTR and its association with tricuspid valvular (TV) deformation in patients with persistent AF. We retrospectively enrolled 344 patients (73.0 ± 9.3 years, 95 female) with persistent AF who underwent 2-dimensional echocardiography. We excluded patients with left-sided heart disease, pulmonary hypertension treated with pulmonary vasodilators, and congenital heart disease. We defined significant TR as having TR ≥ moderate; and tricuspid annulus (TA) diameter, tethering height, and area were measured in all patients. Among the study population, 80 (23.3%) patients had significant TR. TA diameter, tethering height, and area were significantly greater in the significant TR group (all p < 0.001). In multivariable analysis, TA diameter was independently associated with significant TR (odds ratio 1.1 per mm, p = 0.03), whereas TV tethering height was not. Receiver operating characteristic curve for significant TR exhibited the best predictive value of TA diameter indexed for body surface area [23 mm/m2; area under the curve (AUC) = 0.87] compared with absolute TA diameter (39 mm; AUC = 0.74) and TA diameter indexed for height (0.22 mm/cm; AUC = 0.80). Approximately 25% of patients with persistent AF had significant TR. The BSA-corrected TA diameter was strongly associated with significant TR, which might be helpful for predicting the development of significant TR and considering its therapeutic strategy in patients with persistent AF.

Isolated functional tricuspid regurgitation, how define patient at-risk for event?

Abstract Introduction Functional tricuspid regurgitation (TR) is a turning point in cardiac diseases. Symptoms typically appear late, and the optimal timing for proposing a valve repair remains a challenge. We sought to analyse the characteristics of right heart remodelling in patients with significant functional TR to identify the parameters that could be used in an easily achievable and fair prognostic model predicting clinical events. Methods We designed a prospective observational French multicentre study including 160 patients with significant functional TR (effective regurgitant orifice area &amp;gt;30mm2) and LVEF &amp;gt;40%. Clinical, echocardiographic, and ECG data were collected at baseline, and at the 1- and 2-year follow-up. The primary outcome was all-cause death or hospitalization for heart failure. Results At 2 years, 56 patients (35%) achieved the primary outcome. The subset with events showed more advanced right heart remodelling at baseline, but similar TR severity. Right atrial volume index (RAVI) and the TAPSE/sPAP ratio, reflecting right-ventricle-pulmonary artery coupling, were 73 mL/m2 and 0.40 versus 64.7 mL/m2 and 0.50 in the event vs event-free group, respectively (both p&amp;lt;0.05). None among all the clinical and imaging parameters tested had a significant group × time interaction. In multivariable analysis, the model including TAPSE/sPAP ratio &amp;gt;0.4 (OR=0.41, 95%CL 0.2 to 0.82) and RAVI &amp;gt;60 mL/m2 (OR=2.13, 95%CL 0.96 to 4.75) permitted the fairest and most parsimonious prognostic evaluation. Conclusion RAVI and TAPSE/sPAP are relevant for predicting the risk for event at 2-year follow-up in patient with an isolated functional TR. Funding Acknowledgement Type of funding sources: None.

Transcatheter versus surgical closure of atrial septal defect in adult patients with tricuspid regurgitation

ObjectivesTranscatheter closure using a device has been established as an effective atrial septal defect (ASD) treatment, but its value in treating patients with concomitant functional tricuspid regurgitation (TR) is relatively...

Restructuring the Heart From Failure to Success: Role of Structural Interventions in the Realm of Heart Failure.

Heart failure through the spectrum of reduced (HFrEF), mid-range (or mildly reduced or HFmEF), and preserved ejection fraction (HFpEF), continues to plague patients' quality of life through recurrent admissions and high mortality rates. Despite tremendous innovation in medical therapy, patients continue to experience refractory congestive symptoms due to adverse left ventricular remodeling, significant functional mitral regurgitation (FMR), and right-sided failure symptoms due to significant functional tricuspid regurgitation (FTR). As most of these patients are surgically challenging for open cardiac surgery, the past decade has seen the development and evolution of different percutaneous structural interventions targeted at improving FMR and FTR. There is renewed interest in the sphere of left ventricular restorative devices to effect reverse remodeling and thereby improve effective stroke volume and patient outcomes. For patients suffering from HFpEF, there is still a paucity of disease-modifying effective medical therapies, and these patients continue to have recurrent heart failure exacerbations due to impaired left ventricular relaxation and high filling pressures. Structural therapies involving the implantation of inter-atrial shunt devices to decrease left atrial pressure and the development of implantable devices in the pulmonary artery for real-time hemodynamic monitoring would help redefine treatment and outcomes for patients with HFpEF. Lastly, there is pre-clinical data supportive of soft robotic cardiac sleeves that serve to improve cardiac function, can assist contraction as well as relaxation of the heart, and have the potential to be customized for each patient. In this review, we focus on the role of structural interventions in heart failure as it stands in current clinical practice, evaluate the evidence amassed so far, and review promising structural therapies that may transform the future of heart failure management.

Right ventricular longitudinal strain remains unimpaired in severe primary mitral regurgitation and functional tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION The right ventricular global longitudinal strain (RV GLS) increasingly has been used for the prognosis of mortality in the heart failure patients. However, the relationship of RV strains to other RV functional parameters and its dependency of functional tricuspid regurgitation (TR) as a result of left heart valvular disease is not well studied. PURPOSE To investigate the relationship of RV geometry, functional and strain parameters to the predominant left heart aetiology in patients with functional TR as a result of left heart valvular disease. METHODS Prospective observational cohort study enrolled patients with functional TR caused by left heart valvular disease for whom surgical valvular repairment is scheduled. Patients with ischemic heart disease (assessed by coronary angiography) were excluded from the analysis. The current study included 52 patients with full sets of preoperative echocardiographic parameters. Echocardiographic quantification included the following parameters: the RV geometry (RV diameters, RV area), functional (velocity of the tricuspid annular systolic motion (S’) and RV fractional area change (FAC)) and strain parameters (RV GLS, longitudinal RV free wall strain (RVFWS) and longitudinal strains of each segment of RV free wall). The severity of TR was measured quantitively according the recent ESC guidelines. Patients were divided into groups according to the predominant left heart valvular disease causing moderate or severe functional TR: 1. TR caused by primary severe mitral regurgitation (MR) due to mitral valve (MV) prolapse and MV chordae rupture; 2. TR caused by other left heart valvular pathologies (severe aortic stenosis [16 pts.], severe rheumatic aortic and MV disease [11 pts], severe aortic regurgitation [3 pts]). The statistical analyses were performed using SPSS statistical software. RESULTS In 52 patients of current analysis 64% were female, mean age was 67 ± 9. The distribution of echocardiography parameters in study groups are shown in Table 1. The RV geometry parameters and parameter of TR severity (effective regurgitant orifice area (EROA) did not differ significantly between these two groups. The RV longitudinal function (S’) and RV strain parameters (RV GLS and longitudinal RVFWS) were better in severe MR group. CONCLUSIONS Although the right ventricular geometry and severity of functional tricuspid regurgitation does not depend on different predominant left heart valvular disease causing significant functional tricuspid regurgitation, the right ventricular longitudinal function and longitudinal right ventricular free wall strain are less affected and remains unimpaired in patients with functional tricuspid regurgitation caused by severe primary mitral regurgitation. Abstract Figure.

Relationship between right ventricular geometry and function parameters and tricuspid annuloplasty efficacy

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION The prevalence of untreated moderate and severe functional tricuspid regurgitation (TR) eventually leads to heart failure and is associated with poor prognosis. Therefore, tricuspid annuloplasty (TA) is offered as a first-line treatment for significant functional TR. However, studies to investigate factors leading to recurrent TR after TA are still scarce. AIM The aim is to investigate the relationship between right ventricular (RV) geometry and function parameters and recurrent TR after TA. METHODS Prospective observational cohort study enrolled patients with moderate or severe functional TR caused by left heart valvular disease who underwent surgical tricuspid valve (TV) repair. The dominant pathology was severe mitral regurgitation. Patients with ischemic heart disease (assessed by coronary angiography) were excluded from the analysis. The current study included 60 patients with full sets of preoperative 2D and 3D echocardiographic parameters. Echocardiographic quantification included the following parameters: the RV and RA geometry, functional (velocity of the tricuspid annular systolic motion [S’] and RV fractional area change [FAC], tricuspid annular plane systolic excursion [TAPSE] and RV ejection fraction (EF)). The severity of TR was measured quantitatively according to the recent ESC guidelines. Patients were divided into two groups according to the outcomes of TA: effective (38 pts.) and ineffective (22 pts.) TV repair. Effective TA was considered if TR 1 year after surgery was mild, while ineffective – TR was moderate or severe (recurrent TR). The statistical analysis was performed using SPSS statistical software, univariate logistic regression was used. RESULTS In 60 patients of current analysis 67% were female, mean age was 67 ± 9 years. The odds ratio for risk of ineffective TA are shown in Table 1. Age, gender, body mass index, left ventricular (LV) functional, as well as left atrial parameters did not differ between effective and ineffective TA groups. When analysing echocardiographic parameters in univariate logistic regression, RV and RA geometry, TV annulus diameter had predictive value for ineffective TA. Preoperative effective regurgitant orifice area (EROA) did not differ significantly between two groups (ineffective TA vs. effective TA; 31 [60] mm2 vs. 24 [17] mm2, p = 0.308 respectively). Meanwhile, none of the RV functional parameters were significant. CONCLUSION Recurrent moderate or severe functional tricuspid regurgitation after tricuspid annuloplasty is associated with preoperative tricuspid annulus size, RA and RV geometry, but not with changes of RV function. Abstract Figure.

ВЛИЯНИЕ ЛЕГОЧНОЙ ГИПЕРТЕНЗИИ НА ИСХОДЫ КОРРЕКЦИИ ОТНОСИТЕЛЬНОЙ ТРИКУСПИДАЛЬНОЙ НЕДОСТАТОЧНОСТИ У БОЛЬНЫХ, ОПЕРИРОВАННЫХ ПО ПОВОДУ КЛАПАННЫХ ПОРОКОВ СЕРДЦА

Aim. The aim of the study is to compare the effect of pulmonary hypertension on the outcome of tricuspid valve plasty in the groups with moderate and significant pulmonary hypertension. Material and methods. The results of surgical treatment of 620 patients with cardiac valve diseases were analyzed. Pulmonary artery systolic pressure (PASP) measured by echocardiography. Two groups were distinguished: Group 1 – pulmonary artery systolic pressure ˂ 50 mmHg. – 250 patients, Group 2-systolic pulmonary artery pressure ≥50 mm Hg. – 370 patients. Depending on the method of tricuspid insufficiency correction, subgroups were identified in each group: subgroup A – suture plasty was used, subgroup B – annuloplasty ring. Mann-Whitney U test was used to compare two independent samples. Chi-square test was used to compare the percentages in the groups. Results and discussion. In group I (PASP up to 50 mmHg) pressure in the PA decreased in the postoperative period, however in the long-term period in the suture plasty subgroup (subgroup A) PASP increased (p=0.01), in the annuloplasty ring subgroup (subgroup B) PASP after surgery and in the long-term period has not changed significantly. The mean value of tricuspid regurgitation (TR) was 1.27±0.4 in subgroup B and 2.1±0.6 in subgroup A (p=0.0227). In group II (significant pulmonary hypertension), postoperative PASP decreased to 50.5±13.2 (subgroup A) and 53.4±8.0 (subgroup B) mm Hg, however in the long-term follow-up there was an increase of pressure in PA to 58.3±10.7 and 56.4±11.8 mm Hg, respectively. In subgroup B, the long-term results were better in terms of TR degree, 1.6±0.5, in contrast to subgroup A, where the average degree was 2.6±0.7 (p=0.001). Tricuspid valve (TV) plasty with a annuloplasty ring preserved coaptation of the TV cusps and prevented residual tricuspid insufficiency despite the intensity of pulmonary hypertension. Conclusion. Surgical treatment of mitral and aortic heart diseases leads to decrease or normalization of pulmonary artery pressure. Pulmonary hypertension in the postoperative period is a factor that influences the intensity of TR. All patients with significant functional TR as an outcome of left heart valve pathology should undergo TV annuloplasty. Correction with annuloplasty ring only is recommended for patients with significant pulmonary hypertension and significant TR.

Analysis of right ventricle echocardiographic function parameters for the prediction of outcomes in significant functional tricuspid regurgitation

Abstract Introduction Functional tricuspid regurgitation is a common disease that significantly impairs survival and quality of life. The role of echocardiographic right ventricular (RV) function parameters to detect patients with worse prognosis that may benefit from invasive treatment is still under debate. Methods 121 consecutive patients with grade III and IV functional tricuspid regurgitation were evaluated. RV function parameters and clinical variables were assessed at baseline, and then patients were prospectively followed-up. The primary endpoint was the combination of death or heart failure (HF) admissions. Comparison of imaging parameters was done using receiver-operating characteristics (ROC) curves. Multivariate logistic regression analysis was preformed to establish independent predictors of outcomes. Results Median follow up was 27.3 months. 73.6% of the patients were female, and mean age was 80.4 years. 63.6% were grade IV tricuspid regurgitation. In the univariate analysis using the area under the ROC curve (AUC), RV-free wall strain (RVS, AUC=0.633) and pulmonary artery systolic pressure (PASP, AUC=0.605) were the best predictors of death and HF admissions, although the individual diagnostic performance was weak. In the multivariate analysis including either clinical and echocardiographic variables, independent predictors of death and HF admissions were Age (OR 1.07, p=0.029), RVS &amp;gt;−16 (OR 5.0, p=0.001), Diabetes mellitus (OR 3.0, p=0.011), eGFR (ml/min, OR 0.96, p=0.001) and Hemoglobin (g/dL, OR=0.74, p=0.048). The model including these variables was superior than RVS and PASP alone (AUC 0.884, p&amp;lt;0.001) (graph 1), showing high sensitivity (78.8%) and specificity (67.3%). Conclusions In patients with significant functional tricuspid regurgitation, RVS and PASP show the best performance for the detection of death and HF admissions. A multivariate model including age, diabetes, eGFR, hemoglobin and RVS was superior than the individual imaging parameters. Funding Acknowledgement Type of funding sources: None. Table 1Graph 1

Right heart dysfunction and readmission risk across left ventricular ejection fraction status in patients with acute heart failure

Abstract Background Right heart dysfunction (RHD) parameters, such as right ventricular to pulmonary artery uncoupling or significant tricuspid regurgitation (TR) are increasingly important in heart failure (HF), especially in patients with preserved ejection fraction. In this study, we aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF). Methods We included 3,383 consecutive patients discharged for acute HF (AHF). Of them, in 1,435 (42.4%) pulmonary artery systolic pressure (PASP) could not be accurately measured, leaving a final sample size of 1,948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion (TAPSE)/PASP&amp;lt;0.36 and a significant functional TR (n=196, 10.2%). Negative binomial regression analyses were used to evaluate the risk of recurrent admissions. Results At a median follow up of 2.2 years (IQR=0.63–4.71), 3,782 readmissions were registered in 1,296 patients (66.5%). Patients with advanced RHD showed higher rates of readmissions, but only if LVEF≥40% (p&amp;lt;0.001). In multivariable analyses, this differential association persisted for CV and HF recurrent admissions (p-value for interaction=0.016 and p=0.020; respectively). Advanced RHD was independently associated with the risk of recurrent CV and HF admissions if HF with LVEF≥40% (IRR: 1.99, 95% CI: 1.47–2.69, p&amp;lt;0.001; and IRR: 2.02, 95% CI: 1.45–2.81, p&amp;lt;0.001; respectively). In contrast, it was not associated with readmission risks if LVEF&amp;lt;40%. Conclusion Following an admission for AHF, advanced RHD was strongly associated with a higher risk of recurrent CV and HF admissions, but only in patients with LVEF≥40%. Funding Acknowledgement Type of funding sources: None.

Multivariate analysis of right ventricle echocardiographic function parameters for the prediction of outcomes in significant functional tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Functional tricuspid regurgitation is a common disease that significantly impairs survival and quality of life. The role of echocardiographic right ventricular (RV) function parameters to detect patients with worse prognosis that may benefit from invasive treatment is still under debate. Methods 121 consecutive patients with grade III and IV functional tricuspid regurgitation were evaluated. RV function parameters and clinical variables were assessed at baseline, and then patients were prospectively followed-up. The primary endpoint was the combination of death or heart failure (HF) admissions. Comparison of imaging parameters was done using receiver-operating characteristics (ROC) curves. Multivariate logistic regression analysis was preformed to establish independent predictors of outcomes. Results Median follow up was 27.3 months. 73.6% of the patients were female, and mean age was 80.4 years. 63.6% were grade IV tricuspid regurgitation. In the univariate analysis using the area under the ROC curve (AUC), RV-free wall strain (RVS, AUC = 0.633) and pulmonary artery systolic pressure (PASP, AUC = 0.605) were the best predictors of death and HF admissions, showing better diagnostic performance than tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and tricuspid S’ (p &amp;lt; 0.001 for each comparison) (graph 1A). In the multivariate analysis including either clinical and echocardiographic variables, independent predictors of death and HF admissions were Age (OR 1.07, p = 0.029), RVS&amp;gt;-16 (OR 5.0, p = 0.001), Diabetes mellitus (OR 3.0, p = 0.011), eGFR (ml/min, OR 0.96, p = 0.001) and Hemoglobin (g/dL, OR = 0.74, p = 0.048) (table 1). The model including these variables was superior than RVS and PASP alone (AUC 0.884, p &amp;lt; 0.001) (graph 1B), showing high sensitivity (78.8%) and moderate specificity (67.3%). Conclusions In patients with significant functional tricuspid regurgitation, RVS and PASP show the best performance for the detection of death and HF admissions. A multivariate model including age, diabetes, eGFR, hemoglobin and RVS was superior than the individual imaging parameters. Table 1 Variable OR 95% CI P value Age (years) 1.07 1.01-1.13 0.029 Diabetes Mellitus 3.00 1.29-7.00 0.011 RV free wall strain &amp;gt;-16 5.01 1.87-13.4 0.001 Hemoglobin (d/dL) 0.74 0.55-1.00 0.048 eGFR (ml/min) 0.96 0.94-0.98 0.001 OR odds ratio. CI: confidence interval. eGFR: estimated glomerular filtration rate (CKD-EPI formula). Abstract Figure. Graph 1

Prevalence and prognosis of severe tricuspid regurgitation in patients with atrial fibrillation with normal left ventricular systolic function

Abstract Background Significant functional tricuspid regurgitation (FTR) can be found in some patients with atrial fibrillation (AF). The results of the previous studies are still controversial whether significant FTR in patients with AF can cause worse outcomes such as heart failure or death. Purpose To study the prevalence, predictors and prognosis of significant FTR in patients with AF with normal left ventricular (LV) systolic function. Methods We conducted a retrospective cohort study in patients with AF and normal LV ejection fraction (LVEF) from May 2013 through January 2018. Significant FTR was defined as moderate to severe FTR. Pulmonary hypertension (PH) was defined as right ventricular systolic pressure &amp;gt;50 mmHg or mean pulmonary artery pressure &amp;gt;25 mmHg. We evaluated the prevalence of significant FTR and evaluated the adverse outcomes between significant and insignificant FTR groups. The adverse outcomes were defined as heart failure visit or hospitalization and all cause death within 2 years of follow up. We also evaluated the factors associated with significant FTR in AF patients. Results There were 498 patients with AF and 300 (mean age 68.8±10.8 years, 50% female) were included in the study. Paroxysmal, persistent and permanent AF were found in 34.7%, 44.7% and 20.6% respectively. Mean LVEF was 65.3±6.3%. PH and significant FTR were reported in 30.7% and 21.7%, respectively. All cause death and heart failure (visit and hospitalization) were found in 26 (8.7%) and 39 (13%) patients, respectively. There was no statistically significant difference in death between patients with significant and insignificant FTR (12.3% vs. 7.7%; 95% confidence interval (CI) 0.70–4.08, p=0.24). Patients with significant FTR had heart failure more often than those with insignificant FTR (61.5% vs. 38.5%; 95% CI 4.15 - 17.75, OR 8.58, p&amp;lt;0.001). The multivariate analysis showed that the predictors of significant FTR were female gender, permanent AF and presence of PH (OR 2.5, 3.6 and 6.1, respectively). The predictors of the adverse outcomes in patients with AF were high CHA2DS2-VASc score (95% CI 1.09 - 1.92, p=0.01) and significant FTR (95% CI 9.61 - 698.17, p&amp;lt;0.01). Conclusions Significant FTR was common in patients with AF and associated with heart failure outcomes. Female gender, permanent AF and presence of PH were independent predictors of significant FTR, while high CHA2DS2-VASc score and significant FTR were independent predictors of the adverse outcomes in patients with AF and normal LVEF. Funding Acknowledgement Type of funding source: None

A matter of proportions: a novel framework to classify functional tricuspid regurgitation

Abstract Background Current approaches for the assessment of tricuspid regurgitation (TR) severity do not correct for right ventricular (RV) size. Similarly to what recently proposed for the left heart, we hypothesized that TR severity can be proportional or disproportional to RV dilation. Purpose To characterize the clinical features and the prognosis of patients with disproportionate vs proportionate functional TR (FTR). Methods A total of 345 patients (mean age: 70±12 years; 40% male) with significant (≥ moderate) FTR, preserved left ventricular systolic function and who did not undergo tricuspid valvular repair during follow-up were included. Proportional and disproportional FTR were defined according to the ratio between TR severity (vena contracta [VC] width) and RV size (tricuspid annulus [TA] diameter). A prognostic relevant cut-off for VC/TA was identified with spline curve analysis. The primary end-point was all-cause mortality and the event rates were compared between patients with proportionate and disproportionate FTR. Results The cut-off for disproportionate FTR associated with an increase in all-cause mortality was identified at 0.24 (Figure 1: left panel). According to this cut-off, 172 (50%) patients showed disproportionate FTR, while the remaining had proportionate FTR. Patients with disproportionate FTR were more frequently symptomatic, had smaller RV basal diameter, higher TR severity, greater left atrial volume, higher prevalence of mitral regurgitation, and higher pulmonary artery pressures compared to those with proportionate FTR. During a median follow-up of 61 (interquartile range, 28–101) months, 135 (39%) patients died. The cumulative 5-year survival rate was significantly worse in patients with disproportionate FTR (57% vs 74%, P=0.001; Figure 1: right panel) and on multivariable Cox regression analysis disproportionate FTR was independently associated with poor outcome (HR 1.56; 95% CI 1.06–2.29; P=0.023) together with age, coronary artery disease, renal impairment, reduced RV systolic function, and increased pulmonary artery pressures. Importantly, this novel framework outperformed the TR grading system recommended by current guidelines, which in this population was not able to effectively stratify the prognosis (HR for severe FTR vs moderate FTR 1.09; 95% CI 0.72–1.64; P=0.694). Conclusions In patients with significant FTR, characterization of TR severity in relation to RV size significantly improves risk-stratification since disproportionate FTR if left untreated is associated with worse prognosis compared with proportionate FTR. Figure 1 Funding Acknowledgement Type of funding source: None

A novel quantitative grading system to further characterize the prognosis of patients with functional tricuspid regurgitation

Abstract Background Recent studies have suggested that current grading of tricuspid regurgitation (TR) has significant limitations and specifically cannot identify the various grades of severe TR (such as torrential). New cut-off values for the recommended measures of vena contracta (VC) width and effective regurgitant orifice area (EROA) have been proposed but not yet validated. Purpose To test the prognostic utility of new cut-offs for VC width and EROA in a large registry of patients with functional TR (FTR) and to integrate them into a novel comprehensive grading system. Methods FTR severity was evaluated in 1148 patients (mean age: 69±13 years, 50% male) with significant FTR (≥ moderate). Patients with congenital heart disease or who underwent tricuspid valve repair during follow-up were excluded. The primary endpoint was all-cause mortality. Based on Kaplan-Meier survival analyses, VC width significantly differentiated the prognosis of patients with moderate FTR vs severe FTR (with a cut-off value of 7 mm), whereas EROA was able to further stratify patients with more than severe (torrential) FTR. Therefore these two parameters were combined into a novel grading system (Figure: Upper Panel) to define: moderate FTR (VC &amp;lt;7 mm), severe FTR (VC ≥7 mm, EROA &amp;lt;80 mm2) and torrential FTR (VC ≥7 mm, EROA ≥80 mm2). Results According to our novel grading system a total of 146 patients (13%) showed moderate FTR, 547 patients (48%) had severe FTR and 454 patients (39%) presented with torrential FTR. Patients with torrential FTR had greater right ventricular (RV) dimensions, lower RV systolic function and were more likely to receive diuretics. The cumulative 10-year survival rates were significantly different among the groups: 54% for moderate FTR, 43% for severe FTR and 32% for torrential FTR (P=0.004 Figure – Lower Panel). After adjusting for potential confounders, torrential FTR retained its association with worse prognosis compared with other FTR grades (HR 1.28; 95% CI 1.07–1.54; P=0.007) together with age, coronary artery disease, diabetes, severe renal impairment, lower RV or left ventricular systolic function, higher pulmonary artery pressures, and dilated tricuspid annulus. Differently, severe FTR graded according to current guidelines did not show any association with the primary outcome (HR for severe FTR vs moderate FTR 1.17; 95% CI 0.96–1.42; P=0.128). Conclusion The proposed novel grading system combining measures of VC width and EROA is able to further risk stratify patients with FTR and specifically to identify patients with torrential FTR, a new clinical condition associated with even worse mortality than severe FTR. Figure 1 Funding Acknowledgement Type of funding source: None

Significant functional tricuspid regurgitation portends poor outcomes in patients with atrial fibrillation and preserved left ventricular ejection fraction

BackgroundSignificant tricuspid regurgitation (TR) can be found in patients with atrial fibrillation (AF). The results of previous studies are controversial about whether significant functional TR (FTR) in patients with AF leads to worse clinical outcomes. The aims of the study were to investigate the prevalence, predictors and prognosis of significant FTR in patients with AF with preserved left ventricular ejection fraction (LVEF).MethodsThe present study was a retrospective cohort study in patients with AF and preserved LVEF from May 2013 through January 2018. Significant FTR was defined as moderate to severe TR without structural abnormality of the tricuspid valve. Pulmonary hypertension (PH) was defined as pulmonary artery systolic pressure ≥ 50 mmHg or mean pulmonary artery pressure ≥ 25 mmHg determined by echocardiography. The adverse outcomes were defined as heart failure and death from any cause within 2 years of follow up.ResultsA total of 300 patients with AF (mean age 68.8 ± 10.8 years, 50% male) were included in the study. Paroxysmal and non-paroxysmal AF were reported in 34.7 and 65.3% of patients, respectively. Mean LVEF was 65.3 ± 6.3%. PH and significant FTR were observed in 31.3 and 21.7% of patients, respectively. Patients with significant FTR were significantly older, more female gender and non-paroxysmal AF, and had higher left atrial volume index and pulmonary artery pressure than those without. A total of 26 (8.7%) patients died and heart failure occurred in 39 (13.0%) patients. There was a statistically significant difference in the adverse outcomes between patients with significant and insignificant FTR (44.6% vs. 11.9%, p < 0.010). Multivariable analysis showed that factors associated with significant FTR were female gender, presence of PH and left atrial volume index (OR = 2.61, 1.87, and 1.04, respectively). The predictors of the adverse outcomes in patients with AF were significant FTR, presence of PH and high CHA2DS2-VASc score (OR = 5.23, 2.23 and 1.60, respectively).ConclusionsSignificant FTR was common in patients with AF, and independently associated with adverse outcomes. Thus, comprehensive echocardiographic assessment of FTR in patients with AF and preserved LVEF is fundamental in determining the optimal management.