Controversies remain in the management strategy for isolated tricuspid regurgitation (TR) because of adverse prognosis and uncertainties regarding the benefits of tricuspid valve surgery. We compared the characteristics and outcomes of a large cohort of patients with isolated TR, based on downstream tricuspid valve surgery versus medical management. Consecutive patients with isolated TR graded at least moderate-to-severe by echocardiography identified between January 2004 and December 2018 (n = 9,031, age 70 ± 15 years, 60% women) were retrospectively studied. The primary end point was time to all-cause mortality during follow-up. Outcomes were compared by management strategy using unadjusted and adjusted survival and multivariable regression analyses. Tricuspid valve surgery was performed in 632 of 9,031 of the cohort (7%), including 514 valve repairs and 118 valve replacements, with in-hospital mortality in 19 patients (2.9%). Overall, there were 3,985 all-cause deaths (44%) over mean follow-up of 2.6 ± 3.3 years. Tricuspid valve surgery was independently associated with lower mortality rate during follow-up, with hazard ratios (HRs) of 0.53 (95% confidence interval [CI] 0.45 to 0.64), and the association persisted in both primary and secondary TR subgroups. Tricuspid valve surgery also had a significantly higher rate of infective endocarditis and heart failure hospitalizations rates during follow-up, at HRs of 5.55 (95% CI 4.00 to 7.71) and 1.29 (95% CI 1.16 to 1.43), respectively. In conclusion, tricuspid valve surgery is rarely performed in isolated TR, but it is independently associated with greater survival for the overall cohort and both primary and secondary etiology subgroups. Increasing the utilization of this surgery at specialized centers is encouraged to try to improve the clinical outcomes for this challenging clinical entity.
The “forgotten” tricuspid valve and tricuspid regurgitation (TR) is the next frontier in valvular heart disease because of increasing awareness of prevalence of TR and its adverse prognosis, and advances in transcatheter technology. Although comprising a minority of patients with TR, isolated TR, without other significant valvular disease, is an important clinical entity because of the controversies surrounding its management. , These include high operative mortality rates of isolated tricuspid surgery being close to 10%, the uncertainties around surgical indications expressed even in the latest guidelines, , unclear surgical benefit in some studies, , and promising early results of transcatheter tricuspid interventions. , This study aims to compare the characteristics and outcomes managed by tricuspid valve interventions or medical management alone in our large contemporary experience of isolated TR.
Methods
Institutional review board approval (IRB number 19-993) was obtained for this observational cohort study with an informed consent waiver. It was not appropriate or possible to involve patients or the public in the design, conduct, or reporting, or dissemination plans of our research. Data of consecutive adult patients ≥18 years of age who were diagnosed with isolated TR graded at least 3+ (moderate-to-severe) on transthoracic echocardiography from January 2004 to December 2018 using the multiparametric criteria from the American Society of Echocardiography guidelines were extracted from the echocardiography database and retrospectively studied. The main exclusion criteria included other concurrent valvular regurgitation of at least moderate severity, concurrent valvular stenosis of at least mild in severity, congenital heart disease such as Ebstein’s anomaly, previous heart transplantation, and those had undergone transcatheter tricuspid valve procedures during follow-up (n = 14).
Demographics, history, laboratory tests, and echocardiography data at the time of the initial echocardiography diagnosis of at least 3+ isolated TR were extracted from clinical records. TR were graded using multiparametric criteria from echocardiography guidelines at the time the study was performed, taking into account tricuspid valve structure, right heart size and function, color and continuous wave Doppler findings, tricuspid valve inflow, hepatic vein flow, vena contracta, effective regurgitant orifice area, and regurgitant volume when obtainable. , Etiologies of TR were individually adjudicated as primary or secondary TR, depending on if the pathology directly affected the tricuspid valve leaflets, or affected right atrial and/or ventricular remodeling and dysfunction leading to malcoaptation of the otherwise structurally normal leaflets, respectively. , History recorded included cardiovascular conditions, procedures, risk factors, and noncardiac co-morbidities. Echocardiography was performed using the Vivid7 or Vivid9 (GE Medical, Milwaukee, Wisconsin), or EPIQ 7C (Philips Medical Systems, N.A., Bothell, Washington) machines, recording data on left and right ventricular size and systolic function, and right ventricular systolic pressure based on chamber quantification guidelines. ,
Tricuspid valve surgery during follow-up after initial echocardiography was identified from clinical records. The surgery was classified as surgical valve repair or replacement (with bioprosthetic or mechanical valve). The primary outcome was time to all-cause mortality during follow-up, with death dates collected from clinical records and state mortality databases, or if alive, then the last date of clinical contact at our institution was used. In-hospital mortality data were also collected for those who underwent tricuspid valve surgery. Other follow-up outcomes collected included heart failure hospitalizations, stroke, myocardial infarction, and infective endocarditis.
Patients were divided into those who underwent tricuspid valve surgery during follow-up or not (medical management) subgroups for comparative analysis. Mean ± standard deviation and frequency (%) were used to present continuous and categorical variables, respectively. Univariable analysis between the 2 groups was performed using t test and Fisher’s exact test for continuous and categorical variables, respectively. In addition, the survival was also compared with the survival of an age- and sex-matched US population. Kaplan-Meier survival curves were used to present longitudinal mortality and morbidity outcomes in unadjusted analysis by management subgroup, and compared using log-rank tests. Univariable Cox proportional hazards regression was used to find parameters associated with the primary end point with p <0.10. All of these parameters that qualified were entered using a stepwise forward approach into the multivariable Cox proportional hazards regression to produce the final model. Because of the short mean time frame of 0.3 years between initial echocardiography and tricuspid valve surgery, tricuspid valve surgery was analyzed as a categorical variable in the final models, although sensitivity analysis was performed using tricuspid valve surgery as a time-dependent variable also.
Furthermore, we used overlap propensity score (PS) weighting analysis to adjust for measured confounders between the 2 groups (tricuspid valve surgery and medical management). First, a nonparsimonious multivariable logistic regression model was performed, adjusting for age, gender, race, co-morbidities, laboratory, and echocardiography variables. Then, patients’ weights were derived from the overlap PS weighting methods, in which each patient’s weight is the probability of that patient being assigned to the opposite group. The balance between groups after overlap PS weighting adjustment was demonstrated by reporting the weighted covariate means (or proportions) for the 2 groups being compared. Adjusted survival curves were created and compared with log-rank tests as previously described for the primary end point for tricuspid valve surgery versus medical management in the total cohort, and separately in primary and secondary TR. , All tests were 2-tailed, and statistical significance set at p value <0.05. Statistical analyses and survival figures were performed using SAS version 9.4 (SAS Institute, Cary, North Carolina) and R 3.4.3 (R Foundation for Statistical Computing, Vienna, Austria). Data are available on reasonable request.
Results
A total of 9,031 patients with isolated TR were studied, with 632 patients (7.0%) undergoing tricuspid valve surgery during follow-up and 8,399 patients (93%) with medical management only. There were 514 patients (81%) with tricuspid valve repair (of which 98% had an annuloplasty ring placed) and 118 patients (19%) with tricuspid valve replacement, including 113 with bioprosthetic valves and 5 with mechanical valves. Table 1 lists the cohort characteristics by management strategy. The intervention group was younger, with higher prevalence of primary TR, heart failure, endocarditis, previous valve surgery, smoking currently, and a lower prevalence of Black race, myocardial infarction, cardiac implantable electronic device, hypertension, diabetes, stroke, peripheral vascular disease, chronic lung disease, and chronic kidney disease. Supplementary Table 1 lists baseline characteristics of the 2 management groups (medical and surgery) after overlap PS weighting adjustment, which were well balanced.
| Characteristics | Operation | Medical | p Value |
|---|---|---|---|
| (n = 632) | (n = 8,399) | ||
| Age (years) | 61 ± 16 | 71 ± 15 | <0.001 ⁎ |
| Female | 394 (62%) | 5,047 (60%) | 0.273 |
| Race, n = 8,824 | <0.001 ⁎ | ||
| White | 553 (90%) | 6,250 (76%) | |
| Black | 47 (8%) | 1,781 (22%) | |
| Asian | 5 (1%) | 48 (1%) | |
| Other | 13 (2%) | 113 (1%) | |
| Body mass index (kg/m 2 ) | 27.3 ± 6.3 | 27.9 ± 8.1 | 0.088 |
| Body surface area (m 2 ) | 1.87 ± 0.26 | 1.85 ± 0.28 | 0.046 ⁎ |
| Primary tricuspid regurgitation | 159 (25%) | 311 (4%) | <0.001 ⁎ |
| Secondary tricuspid regurgitation | 487 (75%) | 8,088 (96%) | |
| Heart failure | 396 (63%) | 4,733 (56%) | 0.002 |
| Atrial fibrillation | 361 (57%) | 562 (54%) | 0.185 |
| Myocardial infarction | 43 (7%) | 812 (10%) | 0.016 ⁎ |
| Infective endocarditis | 116 (18%) | 361 (4%) | <0.001 ⁎ |
| Rheumatic heart disease | 90 (1%) | 23 (4%) | <0.001 ⁎ |
| Cardiac surgery | 196 (31%) | 2,423 (20%) | 0.256 |
| Valve surgery | 113 (18%) | 1,085 (13%) | 0.001 ⁎ |
| Tricuspid valve surgery | 43 (7%) | 105 (1%) | <0.001 ⁎ |
| Coronary artery bypass grafting | 100 (16%) | 1,490 (18%) | 0.234 |
| Percutaneous valve intervention | 0 (0%) | 105 (1%) | 0.001 ⁎ |
| Percutaneous coronary intervention | 24 (4%) | 417 (5%) | 0.213 |
| Cardiac implantable electronic device | 153 (24%) | 1,760 (21%) | 0.055 |
| Hypertension | 323 (51%) | 5,118 (61%) | <0.001 ⁎ |
| Diabetes mellitus | 133 (21%) | 2,283 (27%) | 0.001 ⁎ |
| Smoker | 326 (52%) | 4,256 (51%) | 0.680 |
| Current | 66 (10%) | 584 (7.0%) | 0.002 ⁎ |
| Stroke | 46 (7%) | 816 (9%) | 0.049 ⁎ |
| Peripheral vascular disease | 25 (4%) | 872 (10%) | <0.001 ⁎ |
| Chronic lung disease | 137 (22%) | 2,778 (33%) | <0.001 ⁎ |
| Cirrhosis | 29 (5%) | 431 (5%) | 0.639 |
| Chronic kidney disease | 135 (21%) | 232 (28%) | 0.001 ⁎ |
| Dialysis | 28 (4%) | 424 (5%) | 0.570 |
| Creatinine (mg/dL), n = 8,905 | 1.4 ± 1.2 | 1.6 ± 1.4 | 0.001 ⁎ |
| Creatinine clearance (ml/min) | 73 ± 42 | 59 ± 39 | <0.001 ⁎ |
| Hemoglobin (g/dL), n = 8,871 | 10.5 ± 2.3 | 11.1 ± 2.3 | <0.001 ⁎ |
| Platelets (k/µL), n = 8,874 | 178 ± 90 | 192 ± 92 | <0.001 ⁎ |
| Albumin (g/dL), n = 8,785 | 3.3 ± 0.8 | 3.5 ± 1.0 | 0.001 ⁎ |
| International normalized ratio, n = 8,520 | 1.4 ± 0.7 | 1.6 ± 0.9 | <0.001 ⁎ |
| Echocardiography | |||
| Right ventricular cavity dilation, n = 8,741 | <0.001 ⁎ | ||
| None | 142 (23%) | 2,826 (35%) | |
| Mild | 79 (13%) | 1,030 (13%) | |
| Moderate | 292 (47%) | 3,352 (41%) | |
| Severe | 110 (19%) | 910 (11%) | |
| Right ventricular systolic function, n = 8,806 | <0.001 ⁎ | ||
| Normal | 310 (49%) | 3,524 (43%) | |
| Mild dysfunction | 128 (20%) | 1,741 (21%) | |
| Moderate dysfunction | 144 (23%) | 1,530 (19%) | |
| Severe dysfunction | 48 (8%) | 1,381 (17%) | |
| Right ventricular systolic pressure (mm Hg), n = 7,856 | 45 ± 19 | 53 ± 21 | <0.001 ⁎ |
| Left ventricular cavity dilation, n = 8,752 | 0.974 | ||
| None | 540 (87%) | 7,056 (87%) | |
| Mild | 30 (5%) | 353 (4%) | |
| Moderate | 39 (6%) | 492 (6%) | |
| Severe | 15 (2%) | 227 (3%) | |
| Left ventricular ejection fraction (%), n = 8,907 | 52 ± 13 | 50 ± 15 | <0.001 ⁎ |
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