Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).

In vitro characterization of the mechanisms responsible for functional tricuspid regurgitation.

BACKGROUND: Functional tricuspid regurgitation (TR) is increasingly recognized as a source of morbidity. Current repair strategies focus on annular remodeling because annular dilatation is common in patients with TR. Although papillary muscle (PM) displacement is recognized in functional mitral regurgitation, its role in TR is less well characterized. The objective of this in vitro study was to further clarify the mechanisms by which TR occurs as an effect of annular dilatation and PM displacement. METHODS AND RESULTS: Porcine tricuspid valves (n=16) were studied in an in vitro right heart simulator. The valve dynamics were quantified with isolated annular dilatation starting with a normal annular size (6 cm(2)) and incrementally dilated up to 100%, isolated PM displacement, and a combination of the 2. All valves lost competence at 40% dilatation, resulting in a TR of 7.9 ± 3.4 mL (P ≤ 0.05) compared with baseline and central residual leaflet length of 0.5 ± 0.2 cm. Multidirectional displacement of the anterior and posterior/septal PMs and all PMs significantly (P ≤ 0.05) increased TR, with normal annular area. Malcoaptation was observed where the 3 leaflets joined with all significant levels of TR. The anterior leaflet had the greatest percent change in residual leaflet length, whereas PM displacement caused a reduction in residual leaflet length for the septal leaflet for all conditions. CONCLUSIONS: This study shows that although annular dilatation alone leads to TR, isolated PM displacement can also cause TR; annular remodeling strategies should be tailored in the setting of severe PM displacement.

The right atrium and tricuspid annulus are cardinal structures in tricuspid regurgitation with or without pulmonary hypertension.

BACKGROUND: Right heart structural abnormalities occur in both tricuspid regurgitation (TR) and pulmonary hypertension (PH). They may occur independently or together, but their joint effects on cardiac structure are incompletely described. This study examined the interactions of TR severity and PH on right heart structural changes. METHODS: The study evaluated 455 patients undergoing both echocardiography and CT angiography (CTA). Cases were divided into 3 groups by TR severity: trace (n=217), mild (n=174), and significant (moderate or severe, n=64). Each TR level was subdivided into two groups by PH absent or present. Cardiac structural measurements included tricuspid annulus area (TAA), right atrial (RA) and right ventricular volume (RV) indexed to body surface area. RESULTS: Analysis by TR and PH showed that indexed RA Volume and TAA were very sensitive to TR severity. RA volume was most affected by pulmonary hypertension when TR was trace or mild, while PH had less effect on TAA. In significant TR, neither RA volume nor TAA were changed by PH. Indexed RV volume was insensitive to trace and mild TR, and PH similarly had little effect. CONCLUSIONS: RA volume and tricuspid annulus area enlarge in proportion to TR severity, trace through significant. PH impacts RA volume but only in trace and mild TR. RA volume best reflects TR impact on right heart structure, both with and without PH. Right atrial volume and tricuspid annulus area are the cardinal indices of TR-induced right heart structural disease et al.l severities. ULTRAMINI ABSTRACT: Right heart structural effects of TR and PH were examined in this study. Patients were evaluated by echo and CTA, and grouped by TR severity as trace, mild, and significant, and were subdivided by PH absence/presence. Analysis by TR severity and PH showed that Indexed RA volume is the parameter most sensitive to TR severity, and PH causes incremental RA volume increases in trace/mild TR. Indexed tricuspid annulus area (TAA) similarly increases with TR severity, but was unaffected by PH at any TR severity. RV volume is insensitive to TR severity and PH. Indexed right atrial volume and tricuspid annulus area are cardinal indices for TR-induced right heart structural disease and increase proportionally to TR severity. RA volume is more sensitive to PH than is tricuspid annular area. TR severity may be more accurately assessed by increased RA volume and annulus area. PERSPECTIVE STATEMENT: The right atrium (RA) and tricuspid annulus (TA) are the cardinal cardiac structures affected by tricuspid regurgitation (TR). They each enlarge with TR severity. The right ventricle exhibits minimal change across TR severity. Pulmonary hypertension (PH) enhances TR-mediated RA and TA dilation, but only in trace and mild TR. PH has no effect on RA, TA, or RV size in significant TR. CENTRAL MESSAGE: Right atrial volume and tricuspid annulus area are the most sensitive to TR severity, and are also sensitive to pulmonary hypertension.

Impact of pulmonary hypertension on tricuspid valve function.

Pulmonary arterial hypertension (PAH) results in increased right ventricle (RV) afterload leading to RV remodeling, tricuspid regurgitation (TR), and RV failure. Though characterizing the mechanisms of TR in PAH may suggest new treatment strategies, the mechanisms leading to TR in PAH have not been characterized. In the present study, eleven porcine tricuspid valves were studied in an in vitro right heart simulator. Annular dilatations of 1.2 and 1.4 times normal area, papillary muscle (PM) displacement simulating concentric RV dilatation and eccentric RV dilatation due to concomitant left ventricle dysfunction, and two levels of PAH hemodynamics were simulated independently and in combination. Relative TR, tenting area (TA) along each coaptation line, and coaptation area (CA) of each leaflet were quantified. Results showed a significant increase (p ≤ 0.05) in TR with both increased mean pulmonary artery pressure (mPAP) and annular dilatation of 1.4 times normal. Increased mPAP significantly decreased TA but tended to increase CA, while PM displacement significantly increased TA but did not affect CA, suggesting competing effects of transvalvular pressure and leaflet tethering. Annular dilatation significantly decreased anterior and posterior CA but did not affect TA. These results may inform future TV repairs in PAH to reduce TR and improve RV hemodynamics.

Measurement of strut chordal forces of the tricuspid valve using miniature C ring transducers.

Tricuspid valve (TV) leaflets, papillary muscles (PM), and tendinous chords must work together to ensure proper coaptation. Alterations in valvular mechanics, including chordal forces, may lead to improper coaptation resulting in tricuspid regurgitation. Little is known about TV mechanics as right-sided heart diseases have been overlooked. We sought to fill this gap by understanding the role of TV strut chords with the objective to understand how strut chordal force varies depending on papillary muscle (PM) origin and leaflet attachment in the normal state. Additionally we investigated how these forces are altered with abnormal geometry. Porcine TVs (n=18) were studied in a right-heart simulator capable of reproducing physiological and pathological conditions. Miniature force transducers were placed on strut chords to measure forces throughout the cardiac cycle. In the normal state, chordal force depended upon PM attachment in which chords branching from the septal PM (SPM) carried significantly less force compared to those branching from the anterior PM (APM) (p≤0.05). Annular dilatation resulted in significant increase in chordal force (p≤0.05) on all strut chords. Severe PM displacement led to increased chordal force in chords attaching the APM to the posterior leaflet as well as chords attaching the PPM to the septal leaflet. Elevated chordal force due to isolated annular dilatation was further increased only with addition of apical displacement of the APM. These results provide initial knowledge of TV chordal force mechanics and may be applied to future studies on TV repair techniques.

The effects of a three-dimensional, saddle-shaped annulus on anterior and posterior leaflet stretch and regurgitation of the tricuspid valve.

Tricuspid regurgitation (TR) is present in trace amounts or more in 82-86% of the population and is greater than mild in 14% of the population. In severe cases, it can contribute to right heart failure and adversely affect mitral valve repair durability. One major cause of TR is the dilation of the tricuspid annulus, which alters the geometry of the annulus from a saddle-shape to a more planar profile. Another cause of TR is the displacement of the papillary muscles (PMs), which results from right ventricular dilation. The objective of this study was to identify the effect of a saddle-shaped annulus on native tricuspid leaflet stretch mechanics and TR. In addition, the effects of geometric alterations, including annular dilatation and PM displacement, on leaflet stretch was investigated. Fresh porcine tricuspid valves (TVs) (n = 8) were excised and sutured to an adjustable three-dimensional annulus plate (allowing for dilatation and saddle-shape) and three PM attachment rods. The valve was then placed in the in vitro Georgia Tech right heart simulator. Dual-camera photogrammetry, was used to quantify the stretch ratio experienced by the valve leaflets at peak systole for the following conditions: physiologically normal, 100% annular dilatation, displaced PMs, and a combination of annular dilatation and PM displacement. In addition, a saddle and flat annulus were implemented for each of the four conditions. PM displacement was simulated by displacing all PMs by 10 mm in all directions (laterally, apically, posteriorly/anteriorly). The physiologically normal condition-normal annulus area, saddle-shaped annulus with PMs in a normal position, was used as a control. The results showed that the posterior leaflet exhibited significantly (p ≤ 0.05) higher major and areal stretch ratios as compared to the anterior leaflet at peak systole for all conditions tested. No significant difference was seen in stretch when a flat annulus was compared to saddle for the anterior or posterior leaflet for normal or disease conditions. Investigation of the impact of disease found a significant increase (p ≤ 0.10) in stretch in the posterior leaflet with a combination of annular dilatation and PM displacement (2.01 ± 0.68) as compared to the normal condition with a saddle annulus (1.43 ± 0.20). In addition displacement of the PMs resulted in a significant (p ≤ 0.01) reduction in TR, although the actual volume reduced was minimal (1.2 mL). Stretch values were measured for the anterior and posterior leaflet under both physiologic and pathologic conditions for the first time. Further, these results provide an understanding of the effects of geometric parameters on valve mechanics and function, which may lead to improved TV repairs.

Correlates of tricuspid regurgitation as determined by 3D echocardiography: pulmonary arterial pressure, ventricle geometry, annular dilatation, and papillary muscle displacement.

BACKGROUND: While it is understood that annular dilatation contributes to tricuspid regurgitation (TR), other factors are less clear. The geometry of the right ventricle (RV) and left ventricle (LV) may alter tricuspid annulus size and papillary muscle (PM) positions leading to TR. METHODS AND RESULTS: Three-dimensional echocardiographic images were obtained at Emory University Hospital using a GE Vivid 7 ultrasound system. End-diastolic area was used to classify ventricle geometry: control (n=21), isolated RV dilatation (n=17), isolated LV dilatation (n=13), and both RV and LV dilatation (n=13). GE EchoPAC was used to measure annulus area and position of the PM tips. Patients with RV dilatation had significant (P≤ 0.05) displacement of all PMs apically and the septal PM and posterior PM away from the center of the RV toward the LV. Patients with LV dilatation had significant (P≤0.05) apical displacement of the anterior PM. Pulmonary arterial pressure (r=0.66), annulus area (r=0.51), apical displacement of the anterior PM (r=0.26), posterior PM (r=0.49), and septal PM (r=0.40), lateral displacement of the septal PM (r=0.37) and posterior PM (r=0.40), and tenting area and height (r=0.54, 0.49), were significantly (P≤0.05) correlated to the grade of TR. Ventricle classification (r=0.46) and RV end-diastolic area (r=0.48) also were correlated with the grade of TR. A regression analysis found ventricle classification (P=0.001), pulmonary arterial pressure (P≤0.001) annulus area (P=0.027), and apical displacement of the anterior PM (P=0.061) to be associated with the grade of TR. CONCLUSIONS: Alterations in ventricular geometry can lead to TR by altering both tricuspid annulus size and PM position. Understanding these geometric interactions with the aim of correcting pathological alterations of the tricuspid valve apparatus may lead to more robust repairs.

Peak mechanical loads induced in the in vitro edge-to-edge repair of posterior leaflet flail.

BACKGROUND: Percutaneous edge-to-edge mitral valve (MV) repair is a potential therapeutic option for patients presenting with mitral regurgitation, who may not be suitable for surgery. We characterized the edge-to-edge repair forces in a posterior leaflet flail MV model to identify potential modes of mechanical failure. METHODS: Porcine MVs were evaluated in two different sizes (Physio II 32 and 40) in a left-side heart simulator under physiologic hemodynamic conditions. Edge-to-edge repair was simulated by suturing miniature force transducers near the free edge of the anterior and posterior leaflets, on the ventricular side, resulting in a double orifice MV. Posterior leaflet flail was created by selective chordal cutting. RESULTS: Chordal cutting resulted in posterior leaflet flail and mitral regurgitation; all valves coapted normally before chordal cutting. Peak systolic control forces (size 32, 0.098 ± 0.058 N; size 40, 0.236 ± 0.149 N) were not significantly different from systolic flail forces (size 32, 0.136 ± 0.107 N; size 40, 0.220 ± 0.128 N) for either MV size. No correlation was observed between force magnitude and flail height or width. Peak systolic force was greater (p = 0.08) for the larger MVs (size 40 compared with size 32). Finally, peak diastolic force was significantly smaller (p = 0.04) than peak systolic force regardless of valve size. CONCLUSIONS: For the first time, forces imparted on an edge-to-edge MV repair were quantified for a posterior leaflet flail model. Force magnitude was not significantly altered with flail compared with control; it was greatest during peak systole and increased with valve size.

Altered right ventricular papillary muscle position and orientation in patients with a dilated left ventricle.

OBJECTIVE: To investigate the impact of left ventricular dilatation on right ventricular papillary muscle displacement. METHODS: Thirteen patients underwent high-resolution cardiac magnetic resonance imaging at Emory University Hospital: Seven patients with congestive heart failure and a dilated left ventricle composed the dilated left ventricular group, and 6 normal subjects were used as a control. A total of 120 cardiac magnetic resonance imaging slices were acquired in a short-axis view at end diastole for each subject. Cardiac magnetic resonance imaging slices were used to identify the papillary muscle tip position in 3-dimensional coordinates for the septal, posterior, and anterior papillary muscles. The centroid of the papillary muscle coordinates was used as the reference point for comparison between subjects. The relative orientation between the right ventricular papillary muscles was evaluated and compared between the dilated left ventricular group and normal subjects. RESULTS: Dilatation of the left ventricle resulted in a significant (P = .05) displacement of the septal right ventricular papillary muscle toward the centroid: normal group, 0.0285 ± 0.036 mm/mm versus dilated left ventricular group, 0.1437 ± 0.026 mm/mm. More specifically, the septal papillary muscle significantly (P = .03) moved away from the septal wall (normal group: 0.61 ± 0.09 mm/mm, dilated left ventricular group: 0.379 ± 0.037 mm/mm). Specific locations of all 3 right ventricular papillary muscles were reported for normal subjects and patients with a dilated left ventricle. CONCLUSIONS: Patients with a dilated left ventricle have significantly increased displacement of the septal right ventricular papillary muscle away from the septum when compared with normal controls. This demonstrates pathophysiologic contribution of the left ventricle to specific papillary muscle alterations within the right ventricle.