Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation.

OBJECTIVE: Severe secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis. METHODS: Consecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion. RESULTS: A total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size). CONCLUSIONS: Patients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.

Right Ventricular Reverse Remodeling After Tricuspid Valve Surgery for Significant Tricuspid Regurgitation.

Background: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study evaluated RV reverse remodeling, based on changes in RV dimensions and function, after TV surgery for significant (moderate or severe) tricuspid regurgitation (TR) and their association with outcome. Methods: A total of 121 patients (mean age 63 ± 12 years, 47% males) with significant TR treated with TV surgery were included in this analysis. The population was stratified by tertiles of percentage reduction of RV end-systolic area (RVESA) and absolute change of RV fractional area change (RVFAC). Five-year mortality rates were compared across the tertiles of RV remodeling and independent associates of mortality were investigated. Results: Tertile 3 consisted of patients presenting with a reduction in RVESA ≥17.2% and an improvement in RVFAC ≥2.3% after TV surgery. Cumulative survival rates were significantly better in patients within tertile 3 of RVESA reduction: 90% vs. 49% for tertile 1 and 69% for tertile 2 (log-rank p = 0.002) and within tertile 3 of RVFAC improvement: 87% vs. 57% for tertile 1 and 65% for tertile 2 (log-rank p = 0.02). Tertiles 3 of RVESA reduction and RVFAC improvement were both independently associated with better survival after TV surgery compared to tertiles 1 (hazard ratio: 0.221 [95% CI: 0.074-0.658] and 0.327 [95% CI: 0.118-0.907], respectively). Conclusions: The extent of RV reverse remodeling, based on reduction in RVESA and improvement in RVFAC, was associated with better survival at 5-year follow-up of TV surgery for significant 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.

Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics.

AIMS: To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF). METHODS AND RESULTS: ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation. CONCLUSION: ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.

Staging right heart failure in patients with tricuspid regurgitation undergoing tricuspid surgery.

OBJECTIVES: This study evaluated the prognostic value of staging right heart failure in patients with significant tricuspid regurgitation (TR) undergoing tricuspid valve (TV) surgery. METHODS: Patients with significant TR who underwent TV surgery were divided into 4 right heart failure stages according to the presence of right ventricular (RV) dysfunction and clinical signs of right heart failure: stage 1 was defined as no RV dysfunction and no signs of right heart failure; stage 2 indicated RV dysfunction without signs of right heart failure; stage 3 included RV dysfunction and signs of right heart failure; and stage 4 was defined as RV dysfunction and refractory signs of right heart failure at rest. RESULTS: A total of 278 patients [mean age 64 (12), 49% males] were included, of whom 34 (12%) patients were classified as stages 1 and 2, 141 (51%) as stage 3 and 103 (37%) as stage 4 right heart failure. The majority of patients (91%) had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting and 95% underwent TV annuloplasty. Cumulative survival rates were 89%, 78% and 61% at 1 month, 1 year and 5 years, respectively. Stages 1 and 2 and stage 3 were independently associated with better survival compared to stage 4 (hazard ratio: 0.391 [95% confidence interval: 0.186-0.823] and 0.548 [95% confidence interval: 0.369-0.813], respectively). CONCLUSIONS: Patients with significant TR undergoing TV surgery and diagnosed without advanced right heart failure have better survival as compared to patients with right heart failure.

Prognostic Implications of Right Ventricular Free Wall Strain in Recipients of Cardiac Resynchronization Therapy.

Right ventricular (RV) function is an important prognostic marker in cardiac resynchronization therapy (CRT) recipients. Measuring RV systolic function with echocardiography, however, remains challenging due to the complexity of right heart morphology. Evaluation of RV function with RV free wall strain (FWS) may improve risk stratification in recipients of CRT compared with conventional RV function parameters. In 871 recipients of CRT (mean age 65 ± 11 years, 75% were men), RV function was assessed by RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and RV FWS measured by speckle tracking echocardiography. RV dysfunction was defined as RV FWS <23%, RV FAC <35%, and TAPSE <17 mm according to present guidelines. Patients were followed up for the primary end point of all-cause mortality. RV FWS identified a higher percentage of patients with RV systolic dysfunction (80.6%) in comparison with RV FAC (44.1%) and TAPSE (60.6%). During a median follow-up of 97 (53 to 145) months, 521 patients (59.8%) died. Recipients of CRT with RV FWS <23% had higher event rates than those with RV FWS ≥23% (p <0.001). On multivariable analysis, RV FWS <23% was independently associated with all-cause mortality (hazard ratio 1.618; 95% confidence interval 1.252 to 2.092; p <0.001) and demonstrated incremental prognostic value over baseline clinical parameters as well as conventional RV function parameters. In conclusion, RV FWS is more sensitive than conventional echocardiographic markers of RV function in detecting impaired RV function. RV FWS is independently associated with all-cause mortality and demonstrates incremental prognostic value over conventional RV function parameters in recipients of CRT.

Late Clinical Valve Thrombosis After Transcatheter Aortic Valve Replacement Despite Non-Vitamin K Anticoagulant.

This study presents the case of a late clinical leaflet thrombosis 1.5 years after percutaneous aortic valve replacement, despite adequate non-vitamin K anticoagulant therapy. Optimal antithrombotic therapy after transcatheter aortic valve replacement remains undetermined. After switching to vitamin K antagonist therapy, complete resolution occurred at 3 months follow-up. (Level of Difficulty: Intermediate.).

Prognostic Value of Multilayer Left Ventricular Global Longitudinal Strain in Patients with ST-segment Elevation Myocardial Infarction with Mildly Reduced Left Ventricular Ejection Fractions.

Multilayer (epi-, mid- and endocardium) left ventricular (LV) global longitudinal strain (GLS) reflects the extent of myocardial damage after ST-segment myocardial infarction (STEMI). However, the prognostic implications of multilayer LV GLS remain unclear. We studied the association between multilayer LV GLS and prognosis in patients with mildly reduced or preserved LV ejection fraction (EF) after STEMI. Patients with first STEMI and LVEF>45% were evaluated retrospectively. Baseline multilayer (endocardial, mid-myocardial and epicardial) LV GLS were measured on 2-dimensional speckle tracking echocardiography. Patients were followed up for of all-cause mortality. A total of 569 patients (77% male, 60 ± 11 years) were included. After a median follow-up of 117 (interquartile range 106-132) months, 95 (17%) patients died. We observed no differences in baseline LVEF and peak troponin levels between survivors and non-survivors. However, non-survivors showed more impaired GLS at all layers (epicardium: -11.9 ± 2.8% vs. -13.4 ± 2.8%; mid-myocardium: -14.2 ± 3.2% vs. -15.6 ± 3.2%; endocardium: -16.5 ± 3.7% vs. -17.7 ± 3.6%, p <0.05, for all). On multivariable analysis, increasing age (hazard ratio 1.095; p<0.001) and impaired LV GLS of the epicardial layer (hazard ratio 1.085; p = 0.047) were independently associated with higher risk of all-cause mortality. In addition, LV GLS at the epicardium had incremental prognostic value for all-cause mortality (χ2 = 114, p = 0.044). In conclusion, in contemporary STEMI patients with mildly reduced or preserved LVEF, ageing and reduced LV GLS of the epicardium (reflecting transmural scar formation) were independently associated with all-cause mortality after adjusting for clinical and echocardiographic variables.

Ratio between Vena Contracta Width and Tricuspid Annular Diameter: Prognostic Value in Secondary Tricuspid Regurgitation.

BACKGROUND: Conventional approaches for the assessment of secondary tricuspid regurgitation (STR) severity do not correct for right heart dimensions. The authors hypothesized that STR severity can be proportional or disproportional to the dilation of the tricuspid annulus (TA) and investigated the prognostic impact of this novel definition. METHODS: A total of 334 patients with moderate to severe STR and preserved left ventricular systolic function were included. The ratio between vena contracta (VC) width and tricuspid annular diameter was calculated. The cutoff value for VC/TA ratio associated with increased risk for all-cause death was identified using spline-curve analysis. RESULTS: The cutoff value of VC/TA ratio associated with a mortality excess was 0.24, and 165 patients (49%) had VC/TA ratios ≥ 0.24. Compared with those with VC/TA ratios < 0.24, patients with VC/TA ratios ≥ 0.24 had a higher prevalence of moderate to severe mitral regurgitation, had higher pulmonary pressures, and were more frequently treated with diuretics. During a median follow-up period of 62 months (interquartile range, 28-101 months), 128 patients (38%) died. The cumulative 5-year survival rate was significantly worse in patients with VC/TA ratios ≥ 0.24 (55% vs 71%, P = .001). VC/TA ratio ≥ 0.24 was independently associated with poor outcomes on multivariate analysis (hazard ratio, 1.567; 95% CI, 1.044-2.352; P = .030) together with coronary artery disease, renal impairment, right ventricular systolic function (evaluated using either tricuspid annular plane systolic excursion or right ventricular free wall strain), and pulmonary pressures. CONCLUSIONS: VC/TA ratio ≥ 0.24 is independently associated with poor prognosis in patients with STR. This parameter may be considered as a marker of disproportionate STR and could improve risk stratification and clinical decision-making.

Right Ventricular-Pulmonary Arterial Coupling in Secondary Tricuspid Regurgitation.

Chronic pressure-overload induces right ventricular (RV) adaptation to maintain RV-pulmonary arterial (PA) coupling. RV remodeling is frequently associated with secondary tricuspid regurgitation (TR) which may accelerate uncoupling. Our aim is to determine whether the non-invasive analysis of RV-PA coupling could improve risk stratification in patients with secondary TR. A total of 1,149 patients (median age 72[IQR, 63 to 79] years, 51% men) with moderate or severe secondary TR were included. RV-PA coupling was estimated using the ratio between two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). The risk of all-cause mortality across different values of TAPSE/PASP was analyzed with a spline analysis. The cut-off value of TAPSE/PASP to identify RV-PA uncoupling was based on the spline curve analysis. At the time of significant secondary TR diagnosis the median TAPSE/PASP was 0.35 (IQR, 0.25 to 0.49) mm/mm Hg. A total of 470 patients (41%) demonstrated RV-PA uncoupling (<0.31 mm/mm Hg). Patients with RV-PA uncoupling presented more frequently with heart failure symptoms had larger RV and left ventricular dimensions, and more severe TR compared to those with RV-PA coupling. During a median follow-up of 51 (IQR, 17 to 86) months, 586 patients (51%) died. The cumulative 5-year survival rate was lower in patients with RV-PA uncoupling compared to their counterparts (37% vs 64%, p < 0.001). After correcting for potential confounders, RV-PA uncoupling was the only echocardiographic parameter independently associated with all-cause mortality (HR 1.462; 95% CI 1.192 to 1.793; p < 0.001). In conclusion, RV-PA uncoupling in patients with secondary TR is independently associated with poor prognosis and may improve risk stratification.

Sex-Specific Differences in Etiology and Prognosis in Patients With Significant Tricuspid Regurgitation.

The aim of this study was to assess differences in etiology, comorbidities, echocardiographic parameters, and prognosis between men and women with significant tricuspid regurgitation (TR). Clinical and echocardiographic characteristics of 1569 patients (age 71 [62 to 78] years) at first diagnosis of significant TR were compared between men and women. Patients with congenital heart disease or previous tricuspid valve surgery were excluded. TR etiologies were defined as primary, left valvular disease related, left ventricular (LV) dysfunction related, pulmonary hypertension related, or isolated. The primary endpoint was all-cause mortality. Sex-specific differences in outcomes were compared in the total population and after propensity score matching. There were 798 (51%) women and 771 (49%) men in the study population. Women were diagnosed with significant TR at an older age compared with men (72 [62 to 79] years vs. 70 [61 to 77] years; p = 0.003). The TR etiology in women was more often left valvular disease related and isolated whereas men more often had LV dysfunction related TR. In the total population women had better 10-year survival compared with men (49% vs. 39%; p=0.001). After propensity score matching, the influence of sex on survival was neutralized (p = 0.228) but the TR etiologies remained significantly associated with all-cause mortality. Patients with left valvular disease or LV dysfunction related TR had lower survival compared with patients with primary TR (p = 0.004 and p = 0.019, respectively). In conclusion, long-term survival of patients with significant TR was similar between men and women after propensity score matching, while the etiology of TR remained significantly associated with all-cause mortality.

Prognostic Implications of a Novel Algorithm to Grade Secondary Tricuspid Regurgitation.

OBJECTIVES: A novel tricuspid regurgitation (TR) grading system, using vena contracta (VC) width and effective regurgitant orifice area (EROA), was proposed and validated based on its prognostic usefulness. BACKGROUND: The clinical need of a new grading system for TR has recently been emphasized to depict the whole spectrum of TR severity, particularly beyond severe TR (massive or torrential). METHODS: TR severity was characterized in 1,129 patients with moderate or severe secondary TR (STR). Recently proposed cutoff values of VC width were more effective in differentiating the prognosis of patients with moderate STR, whereas EROA cutoff values performed better in characterizing the risk of patients with more severe STR. Therefore, these 2 parameters were combined into a novel grading system to define moderate (VC <7 mm), severe (VC ≥7 mm and EROA <80 mm2), and torrential (VC ≥7 mm and EROA ≥80 mm2) STR. RESULTS: A total of 143 patients (13%) showed moderate STR, whereas 536 patients (47%) had severe STR, and 450 (40%) had torrential STR. Patients with torrential STR had larger right ventricular (RV) dimensions, lower RV systolic function, and were more likely to receive diuretics. The cumulative 10-year survival rate was 53% for moderate, 45% for severe, and 35% for torrential STR (p = 0.007). After adjusting for potential confounders, torrential STR retained an association with worse prognosis compared with other STR grades (hazard ratio: 1.245; 95% confidence interval: 1.023 to 1.516; p = 0.029). CONCLUSIONS: A novel STR grading system was able to capture the whole range of STR severity and identified patients with torrential STR who were characterized by a worse prognosis.

The Obesity Paradox in Patients with Significant Tricuspid Regurgitation: Effects of Obesity on Right Ventricular Remodeling and Long-Term Prognosis.

BACKGROUND: Obesity may cause right ventricular (RV) remodeling due to volume overload. However, obesity is also associated with better prognosis compared with normal weight in patients with various cardiac diseases. The aim of this study was to assess the impact of obesity on RV remodeling and long-term prognosis in patients with significant (moderate and severe) tricuspid regurgitation (TR). METHODS: A total of 951 patients with significant TR (median age, 70 years; interquartile range, 61-77 years; 50% men) were divided into three groups according to body mass index (BMI): normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). Patients with congenital heart disease, peripheral edema, active endocarditis, and BMI < 18.5 kg/m2 were excluded. RV size and function for each group were measured using transthoracic echocardiography and compared with reference values of healthy study populations. The primary end point was all-cause mortality. Event rates were compared across the three BMI categories. RESULTS: Four hundred seventy-six patients (50%) with significant TR had normal weight, 356 (37%) were overweight, and 119 (13%) were obese. RV end-diastolic and end-systolic areas were larger in overweight and obese patients compared with normal-weight patients. However, no differences in RV systolic function were observed. During a median follow-up period of 5 years, 358 patients (38%) died. Five-year survival rates were significantly better in overweight and obese patients compared with patients with normal weight (65% and 67% vs 58%, respectively, P < .001 and P = .005). In multivariate analysis, overweight and obesity were independently associated with lower rates of all-cause mortality compared with normal weight (hazard ratios, 0.628 [95% CI, 0.493-0.800] and 0.573 [95% CI, 0.387-0.848], respectively). CONCLUSIONS: In patients with significant TR, overweight and obese patients demonstrated more RV remodeling compared with patients with normal weight. Nevertheless, a higher BMI was independently associated with better long-term survival, confirming the obesity paradox in this context.

A special case of hypertrophic cardiomyopathy with a differential diagnosis of isolated cardiac amyloidosis or junctophilin type 2 associated cardiomyopathy.

Differential diagnosis between hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) is mandatory since the prognosis is very different, but not always possible as both diseases present with increased myocardial thickness and mass. Despite better knowledge of the pathophysiology of both HCM and CA, and new developments in diagnosis, many patients with cardiac involvement in systemic amyloidosis are still only diagnosed in an advanced stage. Improvements in non-invasive diagnostic methods such as ultrasound techniques and cardiac magnetic resonance imaging will eventually obviate the need for invasive studies in order to prove amyloid cardiomyopathy. Nevertheless, today, an endomyocardial biopsy still remains the golden standard. We present an 86-year-old man, diagnosed with hypertrophic cardiomyopathy, in whom echocardiography and cardiac magnetic resonance imaging strongly suggested amyloidosis to be the underlying cause. Interestingly, a new variant of the junctophilin 2 (JPH2) gene, related to hypertrophic cardiomyopathies, was found in our patient.

Prognostic Implications of Increased Right Ventricular Wall Tension in Secondary Tricuspid Regurgitation.

Secondary tricuspid regurgitation (TR) imposes a chronic volume overload on the right ventricle (RV) which can increase RV wall tension (RVWT). The aim of this study was to investigate the prognostic implications of increased RVWT in patients with significant secondary TR. A total of 1,142 patients with moderate-to-severe secondary TR were included. Based on the simplified Laplace-Young's law, RVWT was defined as the product between pulmonary artery systolic pressure (PASP) and RV base-to-apex length. The association between RVWT and risk of all-cause death was identified with spline curve analysis and patients were divided according to the cut-off of RVWT beyond which the hazard ratio (HR) and 95% confidence interval for all-cause mortality were above 1. Four hundred sixty-five (41%) patients had RVWT >3,300 mm Hg x mm and formed the group with increased RVWT. Patients with increased RVWT were more likely male, had more frequent heart failure symptoms and presented with more co-morbidities, larger RV and left ventricular (LV) dimensions, worse LV function, more severe secondary TR and higher PASP compared with patients with nonincreased RVWT. During a median follow-up of 51 (17 to 86) months, 586 (51%) patients died. The cumulative 5-year survival rate was significantly worse in patients with increased RVWT as compared with patients with nonincreased RVWT (38% vs 63% p <0.001). After correcting for potential confounders, increased RVWT retained an independent association with all-cause mortality (HR 1.555; 95% CI 1.268 to 1.907; p <0.001). In conclusion, increased RVWT is independently associated with worse prognosis and its evaluation may improve risk stratification in patients with significant secondary TR.

Prognostic Implications of Significant Isolated Tricuspid Regurgitation in Patients With Atrial Fibrillation Without Left-Sided Heart Disease or Pulmonary Hypertension.

The prognostic impact of isolated tricuspid regurgitation (TR) in patients with atrial fibrillation (AF) has not been investigated. The purpose of this study was to investigate the prognostic implications of significant isolated TR in AF patients without left-sided heart disease, pulmonary hypertension, or primary structural abnormalities of the tricuspid valve. A total of 63 AF patients with moderate and severe TR were matched for age and gender to 116 AF patients without significant TR. Patients were followed for the occurrence of all-cause mortality, hospitalization for heart failure and stroke. Patients with significant isolated TR (mean age 71 ± 8 years, 57% men) more often had paroxysmal AF as compared with patients without TR (mean age 71 ± 7 years, 60% men) (60% vs 43%, p = 0.028). In addition, right atrial size and tricuspid annular diameter were significantly larger in patients with significant isolated TR compared with their counterparts. During follow-up (median 62 [34 to 95] months), 53 events for the combined endpoint occurred. One- and 5-year event-free survival rates for patients with significant isolated TR were 76% and 56%, compared with 92% and 85% for patients without significant TR, respectively (Log rank Chi-Square p <0.001). The presence of significant isolated TR was independently associated with the combined endpoint (hazard ratio, 2.853; 95% confidence interval, 1.458 to 5.584; p = 0.002). In conclusion, in the absence of left-sided heart disease and pulmonary hypertension, significant isolated TR is independently associated with worse event-free survival in patients with AF.