Abstract
Background:
Characteristics of tricuspid valve prolapse (TVP) on transthoracic echocardiography (TTE) are not well defined. As tricuspid valve interventions are increasingly considered, information on the definition and clinical significance of TVP is needed.
Methods:
At our institution, 410 patients (0.3%), 1/26/2000–9/20/2018, were determined to have suspected TVP (sTVP). These TTEs and those of 97 age- and sex-matched normal controls were reviewed. Inter-rater agreement on TVP by visual inspection was assessed in a blinded subset. Leaflet atrial displacement (AD) > 2 standard deviations above the mean in normal controls was used to identify an empiric definition of TVP (eTVP). Features of patients with eTVP were evaluated.
Results:
312 TTEs with available and interpretable images (76.1%) were included. Inter-rater agreement on TVP diagnosis by visual inspection was moderate. Normal values of AD were up to 4 mm in the right ventricular inflow view, and 2 mm in all other views. An AD > 2 mm in the parasternal short axis view had the best accuracy against sTVP to identify TVP. Those with TVP by this definition more frequently had 3–4+ tricuspid regurgitation (TR) (22.2% vs. 3.1%; p < 0.001), MVP (75.0% vs. 3.1%; p < 0.001), and more clinically significant MVP (greater Prevalence of 3–4+ mitral regurgitation). No difference in mortality was observed in those with isolated TVP vs. TVP and MVP (log rank p = 0.93)
Conclusions:
In the largest study of TVP to date, inter-rater agreement on TVP diagnosis by visual inspection was moderate. A cutoff of > 2 mm of AD in the parasternal short axis view was optimal to define TVP. Those with TVP by this definition had more significant TR, larger right ventricles, and more clinically significant MVP. Overall, these results suggest an increased role for surveillance for TVP and the need for clear diagnostic criteria in updated guidelines.
Keywords: Tricuspid valve, prolapse, mitral valve prolapse
INTRODUCTION
Tricuspid valve prolapse (TVP) leading to systolic prolapse of leaflets across the tricuspid annular plane, is a rare finding on transthoracic echocardiography (TTE) and of uncertain clinical significance. In totality, less than fifty cases have been reported in the literature (1–8), leading to uncertainty about the true prevalence of TVP, associated clinical disorders, and its impact on outcomes. Moreover, as diagnostic criteria for TVP have not yet been established, TVP diagnosis is based on visual inspection of the tricuspid valve, yet agreement between physicians on the diagnosis of TVP using this method remains unclear.
Given the emergence of transcatheter interventions for tricuspid regurgitation (TR) and recent data suggesting the adverse impact of isolated TR on clinical outcomes (9), there is a growing need to understand the prevalence TVP and associated clinical conditions. As such, we 1) sought to define clinical TVP from a clinical database of 218,943 TTE reports at the Beth Israel Deaconess Medical Center (BIDMC), and 2) identify associations between TVP and associated clinical conditions and echocardiographic findings, most notably mitral valve prolapse (MVP).
METHODS
Study Population
Structured echocardiographic report data from 218,943 consecutive TTEs performed from 1/1/2000–9/20/2018 at the BIDMC and stored in the ENCOR dataset were queried. As part of routine care at BIDMC, echocardiographic data were entered, at the time of clinical interpretation, by National Board of Echocardiography (NBE) Level III certified faculty echocardiographers into a reporting software that stores echocardiographic measurements and findings in a large electronic database (the “ENCOR” database). The ENCOR database is maintained by Clinical Informatics and is evaluated routinely for accuracy and completeness. All echocardiographic images were acquired using General Electric E-95, Vivid 7 and 9, Vivid Q, Vivid i, Vivid S70 and Hewlett Packard Medical Products 5000 and 5500 echocardiographs.
TVP is a structured field in the ENCOR dataset. All TTE reports with suspected TVP (sTVP) were identified and images manually reviewed by two resident physicians (M.K.L., M.J.B), trained in image interpretation by a board certified echocardiographer (J.B.S.). The maximal systolic atrial displacement (AD) of each of the tricuspid valve leaflets from the tricuspid annular plane to the belly of the leaflets was measured in three views (apical 4-chamber view [4CH], parasternal short-axis view at the level of the aortic valve [PSAX], and right ventricular inflow view [RVI]) (Figure 1). Leaflets in each view were named according to published convention (10). Additionally, annular dimensions were measured in mid-systole and presence of tricuspid annular disjunction or mid to late systolic TR was recorded. If the tricuspid leaflets did not extend beyond the tricuspid annular plane into the right atrium during systole, AD was recorded using negative values as the maximal distance from the tricuspid annular plane to the belly of the leaflets (Figure 2). Tricuspid leaflet excursion above the tricuspid annular plane was recorded using positive values (Figure 2). Those TTEs not available for review in EchoPACS v2.0 (General Electric, Boston, MA) or with insufficient image quality in all three views for accurate measurements were excluded. Additionally, stress echocardiograms, intracardiac echocardiograms, transesophageal echocardiograms, and TTEs with a tricuspid valve replacement or demonstrating mitral or tricuspid valve endocarditis were excluded. All measurements were made with a leading edge to leading edge convention as per American Society of Echocardiography (ASE) guidelines (11). Only an individual’s first TTE was used. This study was approved by the Institutional Review Board at BIDMC with a waiver of informed consent.
Figure 1: Sample Transthoracic Echocardiogram Images Demonstrating Location of Tricuspid Annular Plane in Multiple Views.
Transthoracic Echocardiogram views of individuals with tricuspid valve prolapse demonstrating the location of the tricuspid annular plane (blue double-headed arrow) in the right ventricular inflow view (Panel A), the parasternal short-axis view at the level of the aortic valve (Panel B), and the apical four-chamber view (Panel C). Yellow letters indicate the respective tricuspid valve leaflets identified (A = anterior; S = septal; P = posterior; A/S = anterior or septal). RA = right atrium; RV = right ventricle.
Figure 2: Schematic of the Right Ventricular Inflow View Demonstrating Measurement of Tricuspid Leaflet Atrial Displacement.
Schematic demonstrating sample measurements of tricuspid leaflet atrial displacement (AD) in the right ventricular inflow view. Displacement of the leaflets beyond the tricuspid annular plane into the right atrium is denoted with positive numbers (left panel) and displacement below the tricuspid annular plane with negative numbers (right panel). Absence of displacement in either direction is denoted by zero values. Measurements are done from the annular plane to the midpoint of the belly of the leaflets using a leading edge to leading edge technique. RA = right atrium; RV = right ventricle.
Definition of Tricuspid Valve Prolapse
To identify AD cutoffs that best distinguished TVP from normal controls, a random subset of 100 age- and sex-matched individuals with normal tricuspid valves and no history of MVP were manually reviewed by two physicians (M.K.L., M.J.B) and both AD and annular dimensions were measured in all three views. In a random subset of 40 TTEs (20 with sTVP and 20 controls), images were reviewed in a blinded fashion by two reviewers (M.K.L., J.B.S.) to determine agreement on visual assessment of TVP status.
Covariates and Outcomes
Basic demographics (age, sex, blood pressure, heart rate, height, weight, inpatient/outpatient status) and echocardiographic variables were extracted from the TTE demonstrating TVP. All linear measurements were indexed for body surface area according to the Mosteller formula (12). Echocardiographic variables included left atrial anteroposterior and superoinferior linear dimensions, right atrial superoinferior length, left ventricular end-diastolic and end-systolic diameter, interventricular and inferolateral wall thickness, left ventricular ejection fraction (as recorded in the TTE report), right ventricular basal diastolic diameter, peak aortic valve velocity by continuous wave Doppler, transmitral valve peak E-wave and A-wave velocities by pulsed wave Doppler at the mitral valve tips (and their ratio), E/e’ using an average of lateral and septal e’ velocity measurements and the estimated peak TR pressure gradient by the modified Bernoulli equation. Mitral (MR), tricuspid (TR), and aortic regurgitation severity were semiquantatively graded (0+, 1+, 2+, 3+, 4+) as per the American Society of Echocardiography (ASE) guidelines (13). The presence of mitral valve prolapse, flail or partial flail mitral valve leaflet, aortic valve prolapse, at the time of the TTE demonstrating TVP was determined by query of structured data fields. The primary outcome included all-cause mortality determined from linkage to the Social Security Death Master File.
Statistical Analysis
Among the 40 TTEs with blinded review, kappa statistics were used to quantify inter-reader agreement on TVP status by visual inspection. Subsequently, TVP was empirically defined (eTVP) as an AD > 2 standard deviations above the mean value in the control population. For a given view, if the AD differed between the two leaflets, the AD with the highest standard deviation was used to determine the eTVP definition. Using this definition, TTEs with sTVP were reclassified and the extent of reclassification determined. Agreement between the eTVP and the sTVP definitions was determined using sTVP as the criterion standard. The sensitivity, specificity, positive (PPV), and negative predictive values (NPV) for eTVP against sTVP were determined in each view.
Subsequently, demographic and echocardiographic features of those TTEs with eTVP were compared to TTEs without TVP in the overall ENCOR dataset. Continuous variables were described via means and standard deviations (SD) or medians and interquartile range, and categorical variables via counts and percentages. Characteristics of TTEs with and without TVP were compared using Student’s t-tests, Wilcoxon Rank Sum tests, or Fisher’s exact tests for continuous and categorical variables respectively. Kaplan Meier estimates were used to evaluate time to all-cause mortality for those with isolated TVP versus TVP with concomitant MVP and compared using the log-rank test, censoring at the end of death follow-up (December 31, 2017). All statistical analyses were performed using JMP v14.0 (SAS Institute, Cary, NC) using a two-sided p-value < 0.05 to define statistical significance.
RESULTS
Overall Results and Agreement Between Physicians
Of 218,943 TTEs on 118,442 individuals in the ENCOR dataset after exclusions, suspected TVP was identified in 410 individuals (0.3%) (Figure 3). Of these, 91 (22.2%) were excluded from manual review as images were unavailable for review in EchoPACS (all but two TTEs were performed prior to the start of digital image acquisition and storage in July 2005), and 7 (1.7%) were determined to have insufficient image quality. Thus, a total of 312 individuals with subjectively-determined TVP were included. Among 100 age- and sex-matched controls, images were unavailable for review in 3 (3.0%) and thus 97 control patients were included.
Figure 3: Flow Diagram Illustrating Study Inclusions and Exclusions.
N = number of individuals; sTVP = suspected tricuspid valve prolapse; TTEs = transthoracic echocardiograms
Agreement on Tricuspid Valve Prolapse Status by Visual Inspection
Inter-individual agreement (i.e. between reviewers 1 and 2) on TVP status by visual inspection was poor (kappa [95% CI], 0.15 [−0.15 – 0.45]). However, compared to the reference standard (i.e. the sTVP definition), both reviewer 1 (kappa [95% CI] 0.46 [0.18–0.74]) and reviewer 2 (kappa [95% CI], 0.47, 0.19–0.74]) had moderate agreement on TVP status by visual inspection.
Definition of Tricuspid Valve Prolapse
Using 2 standard deviations above the mean in the control group as the definition for eTVP, eTVP was defined an AD > 2 mm in the 4CH or PSAX view or > 4 mm in the RVI view (Table 1). Comparing against sTVP as the criterion standard, eTVP ascertained via the PSAX and RVI had the highest specificity and PPV (100.0% for all) but lowest sensitivity (15.5% and 4.3% respectively) (Table 2).Similarly, eTVP ascertained based on meeting criteria in any view had the highest sensitivity (44.6%) but lowest specificity (98.4%). The highest overall accuracy was achieved by use of an eTVP definition of > 2 mm AD in the PSAX view (99.8%). Using this definition, 276 (88.5%) of those with sTVP would be reclassified as not having TVP.
Table 1:
Characteristics of the Tricuspid Valve, Right Atrium, and Right Ventricle in Individuals with and without Tricuspid Valve Prolapse on Transthoracic Echocardiogram
| Morphologic Parameter | N obs | Measurement in Individuals with sTVP (N = 312) | Measurement in Individuals with eTVP (N = 36) | Measurement in Age-, Sex- matched Controls (N = 97) | p-value* | p-value† |
|---|---|---|---|---|---|---|
| 4CH Atrial Displacement (mm) | ||||||
| PSAX Atrial Displacement (mm) | ||||||
| RV Inflow Atrial Displacement (mm) | ||||||
| Mid-to-end systolic TR – no. (%) | 407 | 25 (8.0) | 4 (11.1) | 1 (10) | 0.01 | 0.26 |
| Indexed right atrial size (cm/m2) | 374 | 2.9 ± 0.6 (1.7 to 5.5) | 2.9 ± 0.5 (2.0 to 4.4) | 2.7 ± 0.6 (1.6 to 8.7) | 0.003 | 0.03 |
| Indexed right ventricular size (cm/m2) | 112 | 2.2 ± 0.5 (1.0 to 3.9) | 2.5 ± 0.5 (1.8 to 3.1) | 1.8 ± 0.3 (0.8 to 6.1) | 0.0002 | 0.0008 |
Represents the p-value for the comparison of sTVP to controls.
Represents the p-value for the comparison of eTVP to controls. All values are listed as means ± standard deviations (range) unless specified. No patients had tricuspid annular disjunction. eTVP was determined as > 2 mm AD in the PSAX view. 4CH = apical 4-chamber view; PSAX = parasternal short axis view at the aortic valve level; RV inflow = right ventricular inflow view; no. = number; N obs = number of observations; septal = septal leaflet of tricuspid valve; anterior = anterior leaflet of tricuspid valve; posterior = posterior leaflet of tricuspid valve; anterior/septal = either anterior or septal leaflet of the tricuspid valve; annulus = annular measurement in mid-systole.
Table 2:
Performance Characteristics of View-specific eTVP Definitions Compared to sTVP as the Criterion Standard
| View | No. (%) of cases with TVP by eTVP Definition (N = 312) | No. (%) of controls with TVP by eTVP Definition (N = 97) | Sensitivity (%) (95% CI) | Specificity (%) (95% CI) | PPV (%) (95% CI) | NPV (%) (95% CI) | Accuracy (%) (95% CI) |
|---|---|---|---|---|---|---|---|
| Apical 4-chamber | 77 (24.7) | 1 (10) | 24.7 (20.0–29.9) | 99.0 (94.4–99.9) | 6.7 (1.00–33.8) | 99.8 (99.8–99.8) | 98.8 (97.1–99.6) |
| Parasternal short axis | 36 (11.5) | 0 (0.0) | 15.5 (11.1–20.7) | 100.0 (95.1–100.0) | 100.0 | 99.8 (99.7–99.8) | 99.8 (98.3–100.0) |
| RV Inflow | 10 (3.2) | 0 (0.0) | 4.3 (2.1–7.8) | 100.0 (95.1–100.0) | 100.0 | 99.7 (99.7–99.7 | 99.7 (98.3–100.0) |
| Any | 100 (32.1) | 1 (1.0) | 44.6 (38.0–51.4) | 98.4 (91.2–100.0) | 7.6 (12–36.5) | 99.8 (99.8–99.9) | 98.2 (95.9–99.4) |
The number of cases (those with sTVP) and controls determined to have TVP by the empiric definition (eTVP) is listed along with the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each definition against the sTVP definition. Disease prevalence is assumed for calculations to be 0.3% (prevalence of TVP in the current study population).
Echocardiographic and Clinical Characteristics of Individuals with TVP
Demographic and echocardiographic characteristics of TTEs with and without TVP (according to the eTVP definition in the PSAX view) are presented in Table 3. Those with TVP were more frequently female (p = 0.04) and more frequently had 3–4+ TR (TVP vs. no TVP, 22.2% vs. 3.1%, p < 0.001). MVP was present in 75.0% of TTEs with TVP vs. 3.1% of those without (p < 0.001). TVP was associated with higher rates of 3–4+ MR overall (TVP vs. no TVP, 13.9% vs. 2.7%; p < 0.001). TVP was present in 0.4% of TTEs with MVP vs. 0.004% without (p < 0.0001). Aortic valve prolapse was unrelated to TVP status (p > 0.99).
Table 3:
Demographic and Echocardiographic Characteristics of Transthoracic Echocardiograms Performed on Individuals with and without Tricuspid Valve Prolapse
| Variable | N obs | Tricuspid Valve Prolapse (N = 36) | No Tricuspid Valve Prolapse (N = 218907) | p-value |
|---|---|---|---|---|
| Age (year) | 218929 | 63.3 ± 18.1 | 62.4 ± 18.0 | 0.77 |
| Female gender – no. (%) | 218868 | 24 (66.7) | 109774 (50.2) | 0.04 |
| Inpatient status – no. (%) | 218943 | 12 (33.3) | 102344 (46.8) | 0.13 |
| Suboptimal image quality – no. (%) | 218943 | 5 (13.9) | 37561 (17.2) | 0.82 |
| Height (cm) | 209595 | 169.2 ± 12.6 | 168.4 ± 10.7 | 0.73 |
| Weight (kg) | 211090 | 64.8 ± 11.8 | 80.2 ± 22.2 | < 0.001 |
| Body Surface Area (m2) | 208940 | 1.74 ± 0.20 | 1.92 ± 0.29 | < 0.001 |
| Systolic blood pressure (mmHg) | 209272 | 120.7 ± 19.4 | 127.2 ± 31.0 | 0.054 |
| Diastolic blood pressure (mmHg) | 20883 | 70.9 ± 11.1 | 72.5 ± 32.6 | 0.40 |
| Heart rate (bpm) | 183093 | 73.7 ± 18.4 | 75.2 ± 20.5 | 0.64 |
| Indexed left atrial anteroposterior dimension (cm/m2) | 196294 | 2.1 ± 0.5 | 2.1 ± 0.5 | 0.80 |
| Indexed left atrial superoinferior dimension (cm/m2) | 183691 | 2.8 ± 0.6 | 2.8 ± 0.5 | 0.60 |
| Indexed right atrial length (cm/m2) | 182438 | 2.9 ± 0.5 | 2.7 ± 0.5 | 0.03 |
| Interventricular septal wall thickness (cm) | 193480 | 1.0 ± 0.1 | 1.1 ± 0.2 | < 0.001 |
| Inferolateral wall thickness (cm) | 193239 | 1.0 ± 0.2 | 1.1 ± 0.2 | 0.0009 |
| Indexed left ventricular diastolic diameter (cm/m2) | 194776 | 2.6 ± 0.4 | 2.5 ± 0.4 | 0.03 |
| Indexed left ventricular systolic diameter (cm/m2) | 146461 | 1.6 ± 0.3 | 1.6 ± 0.4 | 0.32 |
| Left ventricular ejection fraction (%) | 193305 | 64.1 ± 10.8 | 60.3 ± 17.4 | 0.045 |
| Indexed right ventricular basal diastolic diameter (cm/m2) | 33839 | 2.5 ± 0.5 | 1.9 ± 0.5 | 0.0008 |
| Peak aortic valve transvalvular velocity (m/s) | 165402 | 1.3 ± 0.3 | 1.7 ± 0.7 | < 0.001 |
| Transmitral Doppler Peak E-wave velocity (m/s) | 183195 | 0.9 ± 0.4 | 0.9 ± 0.3 | 0.71 |
| Transmitral Doppler Peak A-wave velocity (m/s) | 166275 | 0.7 ± 0.2 | 0.8 ± 0.4 | 0.004 |
| Transmitral Doppler E/A ratio | 166091 | 1.4 ± 0.7 | 1.2 ± 0.6 | 0.08 |
| Average E/e’ ratio | 112194 | 9.7 ± 5.9 | 10.5 ± 5.3 | 0.50 |
| Estimated tricuspid regurgitant pressure gradient (mmHg) – mean (SD) | 150477 | 30.4 ± 14.2 | 29.0 ± 11.5 | 0.57 |
| Tricuspid regurgitation grade | 176947 | < 0.001 | ||
| Mitral regurgitation grade | 175410 | < 0.001 | ||
| Aortic regurgitation grade | 119813 | < 0.001 | ||
| Mitral Valve Prolapse – no. (%) | 218943 | 27 (75.0) | 6767 (3.1) | < 0.001 |
| Flail or partial flail mitral valve leaflet – no. (%) | 6794 | 1 (2.8) | 568 (0.3) | 0.72 |
All values are means ± standard deviations unless otherwise specified. cm = centimeters; m/s = meters per second; no. = number;
The mean LVEF was higher in those with TVP than without (p = 0.045). Right ventricular dimensions (p = 0.0008) were larger in those with TVP. Amongst those TTEs with ≤ 2+ MR, the indexed right ventricular basal diameter continued to be larger in those with TVP (2.5 ± 0.5 vs. 1.9 ± 0.5 cm/m2, p = 0.002). Using the ASE reference standards for normal RV and RA size (> 4.1 cm and > 5.3 cm respectively), 50.0% of eTVP patients vs. 21.6% of non-TVP patients had a dilated RV (p = 0.03) and 25.7% of eTVP patients vs. 31.4% of non-TVP patients had a dilated RA (p = 0.59) (14). The estimated TR pressure gradient was not different by TVP status (p = 0.57).
Time to All-Cause Mortality
Over a median follow-up of 8.0 years (IQR 3.7–12.3), there were 70 deaths at a median of 344.5 days (IQR 96.8–1177.8) after the TTE. The median time to death was not different amongst those with MVP and TVP (1026 days [IQR 51.5–2014]), isolated TVP (648.5 days [IQR 645–652]), or neither (324 days [IQR 104.5–1137.5]) (log rank p = 0.93).
DISCUSSION
At a single large academic medical center over 18 years, suspected TVP was identified in only 0.3% of individuals. Visual assessment of TVP demonstrated, at best, moderate agreement between reviewers. An empirically derived threshold value of > 2 mm of AD in the PSAX view to define TVP had the overall highest accuracy for TVP diagnosis compared to visual assessment. Using this definition, TVP was present in 0.4% of TTEs with MVP and 75.0% of TTEs with TVP had associated MVP. TVP was associated with worsened TR severity, right ventricular dilation, and greater degrees of 3–4+ MR. Though limited by small numbers, mortality was not different between those with isolated TVP or TVP and MVP. These results in totality suggest that TVP, while uncommon outside of concomitant MVP, is associated with adverse echocardiographic features and the diagnosis should be sought in individuals with MVP.
Prior Literature on Tricuspid Valve Prolapse
Previous literature on TVP has been limited to small case series, describing a total of 34 cases of isolated TVP (1,2,4–8,15). While associations between TVP and comorbid conditions such as coronary artery disease, dilated cardiomyopathy, endocarditis, and others, have been previously noted, these findings have not been consistent across studies (16).
Additionally, multiple case reports have separately described the prevalence of TVP amongst individuals with MVP (2,3,6,15,17–20). With a reported TVP prevalence of 5–52%, this wide range may in part be related to differences in the views used to assess for TVP (i.e. RVI view alone vs. all views of the tricuspid valve).
To our knowledge, the current study represents the largest study of TVP to date. We found 25% of TVP cases occurred in isolation, with 75% occurring in the context of concomitant MVP. TVP was far less common than in prior studies, occurring in only 0.3% of individuals, though was more prevalent among individuals with MVP.
Diagnosis of Tricuspid Valve Prolapse
In the absence of diagnostic guidelines or consensus criteria for TVP, the diagnosis of TVP has largely been made by visual inspection of the tricuspid valvular leaflets and subvalvular apparatus. In the current study, we demonstrate that visual inspection of TVP status has, at best, only moderate inter-rater agreement. One potential reason for this finding is the observation that up to 2 mm of AD in the 4CH and PSAX view and up to 4 mm of AD in the RVI view can occur in normal individuals. Like the mitral valve, the tricuspid valve has a three-dimensional saddle-shaped structure (21). The high points of the tricuspid valve annulus are visualized in the RVI view, making AD in this view theoretically most specific for TVP (21). Congruent with this, a definition of TVP based on ADs in the RVI and PSAX views had the highest specificity (100.0% for both) for identifying TVP by visual inspection. The cutoff with the best overall accuracy was > 2 mm of AD in the PSAX view. We suggest that this cutoff be used in the guidelines and future studies to define the presence of TVP. Using this definition, 11.1% of patients with TVP had mid-late systolic TR. Overall, annular measurements in those with TVP were larger than controls, suggesting that, like MVP, annular dilation may contribute to the pathophysiology of regurgitation (22). No patients in the current study had tricuspid annular disjunction. The degree of AD observed was similar across tricuspid leaflets in a given view.
The Relationship of Tricuspid Valve Prolapse to Mitral Valve Prolapse
A finding consistent across studies of TVP, including the current analysis, is the strong association between MVP and TVP. MVP was present in the vast majority of TTEs with TVP and TVP was present in 0.4% of TTEs with MVP. Additionally, TVP was associated with more clinically significant MVP, as evidenced by worsened mitral regurgitation and a numerically higher proportion with flail or partial flail mitral valve leaflets. Thus, TVP may serve as a risk marker for severe myxomatous disease and suggest a more malignant presentation of MVP, and suggests need for increased awareness of possible TVP in patients with MVP. Consistent with known data regarding MVP (23), TVP was also significantly more common in females than males.
Tricuspid Valve Prolapse and Right Ventricular Remodeling
Individuals with TVP also had increased severity of TR and larger indexed right ventricular diameters, despite equivalent TR gradients, which may reflect the greater degree of TR among these patients. As TVP was associated with larger indexed right ventricular diameters even in the setting of ≤ 2+ MR, this suggests the larger right ventricular sizes observed are possibly due to volume loading of the right ventricle from primary tricuspid valvular insufficiency rather than TVP’s association with worsened MVP and mitral regurgitation causing World Health Association Group II pulmonary hypertension (24) and subsequent right ventricular remodeling. Although limited by small numbers of individuals with adverse outcomes, there was no significant difference in all-cause mortality observed between those with isolated TVP and TVP with concomitant MVP.
Limitations
Our study has several limitations. Our results are from retrospective review of a single center echocardiographic database. Though large, it may not generalize to other settings. Furthermore, due to ascertainment bias, estimates of TVP rates may not reflect prevalence in the community or general population. Second, as it was not feasible for the physician performing manual image review to evaluate the entire ENCOR dataset, it is possible that the prevalence of TVP is underestimated. Third, as there is no clear consensus definition for TVP, estimates of TVP were made via comparison with normal controls without pathologic confirmation and thus misclassification is possible. Though we use sTVP as the reference standard, we do not mean to imply that it represents a true gold standard, but rather represents an alternate definition for comparison. Fourth, longitudinal changes in echocardiographic variables were not evaluated and should be the topic of future investigation. Fifth, as the prevalence of TVP may differ across laboratories, the performance of the eTVP definition used should be evaluated in an external sample. Sixth, as control patients were not matched on echocardiograph, image quality and thus measurement variability may differ across the study. Lastly, as transesophageal echocardiograms, intracardiac echocardiograms, and stress echocardiograms were not included, results of this analysis may not generalize to these other settings.
CONCLUSIONS
In this large, single center, multidecade study, TVP was overall uncommon. Visual assessment of TVP had, at best, moderate inter-rater agreement. An empirically derived threshold AD value of > 2 mm in the PSAX view to define TVP had the overall highest accuracy compared to visual assessment. TVP was associated with worsened TR, larger right ventricular size, and more clinically significant MVP. In total, these results suggest an increased role for surveillance for TVP and the need for diagnostic criteria in updated guidelines.
HIGHLIGHTS.
Tricuspid valve prolapse (TVP) is rare on TTE and of uncertain significance.
Over 18 years, suspected TVP was present in 0.3% of individuals.
75% of those with TVP had associated mitral valve prolapse (MVP)
Leaflet atrial displacement > 2 mm in the parasternal short axis view best defined TVP.
TVP was associated with more tricuspid regurgitation and clinically significant MVP.
Funding:
Dr. Strom is funded by a grant from the NIH/NHLBI (1K23HL144907) outside of the current work. All other authors report no funding.
ABBREVIATIONS:
- ASE
American Society of Echocardiography
- 4CH
apical four-chamber view
- EF
ejection fraction
- eTVP
empiric definition of tricuspid valve prolapse
- sTVP
suspected tricuspid valve prolapse
- MR
mitral regurgitation
- MVP
mitral valve prolapse
- NBE
National Board of Echocardiography
- PSAX
parasternal short-axis view
- RVI
right ventricular inflow view
- TR
tricuspid regurgitation
- TTE
transthoracic echocardiogram
- TVP
tricuspid valve prolapse
- TR
tricuspid regurgitation
Footnotes
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Disclosures: Dr. Strom reports grant funding from Edwards Lifesciences, speaker fees for Northwest Imaging Forums, and consulting for Philips Healthcare, outside of the submitted work.
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