European Heart Journal - Cardiovascular Imaging Advance Access published June 9, 2015 European Heart Journal – Cardiovascular Imaging doi:10.1093/ehjci/jev140

Tricuspid valve remodelling in functional tricuspid regurgitation: multidetector row computed tomography insights Philippe J. van Rosendael, Emer Joyce, Spyridon Katsanos, Philippe Debonnaire, Vasileios Kamperidis, Frank van der Kley, Martin J. Schalij, Jeroen J. Bax, Nina Ajmone Marsan, and Victoria Delgado* Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands Received 23 February 2015; accepted after revision 7 May 2015

Aims

Multidetector row computed tomography (MDCT) may help to understand the underlying mechanisms of functional tricuspid regurgitation (TR), a highly prevalent valve disease with novel transcatheter therapies under development. The purpose of the present study was to assess the geometrical changes of the tricuspid valve in patients with functional TR using MDCT and to correlate these changes with the TR grade assessed with echocardiography. ..................................................................................................................................................................................... Methods In 114 patients undergoing transcatheter aortic valve implantation (47 men, age 81 + 8 years), including 33 (28.9%) and results patients with TR ≥ 3+, the tricuspid valve and right ventricle (RV) were geometrically analysed with 320-slice MDCT. The antero-posterior and septal – lateral diameters, perimeter and area of the annulus, degree of tethering of the anterior, septal and posterior tricuspid valve leaflets, and RV volumes and ejection fraction were assessed and subsequently correlated with TR grade in multivariate models. Patients with pacemaker or implantable cardioverter defibrillator leads were excluded. Patients with TR ≥ 3+ had larger tricuspid annulus area (1539.7 + 260.2 vs.1228.4 + 243.5 mm2, P , 0.001), larger septal and anterior leaflet angles, and larger RV end-systolic volumes (93.2 + 29.8 vs. 64.2 + 23.6 mL, P , 0.001) compared with patients with TR , 3+.The antero-posterior tricuspid annulus diameter was independently correlated with TR ≥ 3+ (odds ratio 1.35; 95% confidence interval 1.07 – 1.69, P ¼ 0.010), after adjusting for estimated pulmonary pressure and RV end-systolic volume. ..................................................................................................................................................................................... Conclusion In patients with TR ≥ 3+, MDCT demonstrated larger tricuspid annulus and RV dimensions and pronounced tethering of the anterior and septal tricuspid leaflet. The antero-posterior annulus diameter was independently correlated with the grade of functional TR.

----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords

functional tricuspid regurgitation † multidetector row computed tomography † geometry

Introduction Functional tricuspid regurgitation (TR) is characterized by insufficient coaptation of the valve leaflets during systole in the presence of anatomically normal leaflets and chordae.1 – 4 Functional TR results from deformation of the right valvulo-ventricular complex and is frequently caused by left-sided heart disease or pulmonary hypertension.1 – 4 The clinical implications of moderate and severe TR are not benign and ultimately may result in right heart failure and reduced

survival.4 – 6 Therefore, surgical repair or replacement of the tricuspid valve should preferably be performed before the onset of irreversible right ventricular (RV) dysfunction.1 – 4,7 For patients undergoing left-sided valve surgery, current guidelines recommend concomitant surgical tricuspid valve repair/replacement in symptomatic patients with severe functional TR or in patients with mild or moderate TR who show severe dilation of the tricuspid annulus.1 – 3 Two-dimensional (2D) echocardiography is the imaging technique of first choice to evaluate TR grade and dimensions of the

* Corresponding author. Tel: +31 71 526 2020; Fax: +31 71 526 6809, E-mail: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].

Page 2 of 10 tricuspid annulus. 8 However, the 3-dimensional (3D) ellipticalshaped configuration of the tricuspid annulus may challenge accurate assessment of the tricuspid valve geometry using 2D echocardiography.1,9 – 13 Multidetector row computed tomography (MDCT) enables acquisition of high spatial resolution 3D data of the tricuspid valve and may provide important insights into the geometrical changes of the tricuspid valve in patients with functional TR. These insights may help to guide surgical decision-making and support the development of physiological annular ring prostheses and novel transcatheter therapies.1,3,4 The purpose of the present study was to assess the geometrical changes of the tricuspid valve in patients with functional TR using MDCT and to correlate these changes with the TR grade assessed with echocardiography.

Methods Patients A total of 114 patients with severe aortic stenosis who underwent clinically indicated MDCT (as per current institutional evaluation of patients who are treated with transcatheter aortic valve implantation) were included. Patients with insufficient MDCT image quality or contrast media in the right heart chambers to characterize the tricuspid valve leaflets (n ¼ 32) and patients with pacemaker or implantable cardioverter– defibrillator leads (n ¼ 29) were excluded. Patients were evaluated with transthoracic echocardiography and divided into two groups according to the TR grade (,3+ vs. ≥3+). MDCT-derived geometrical parameters of the tricuspid valve and RV were compared between the two groups. In addition, the association between MDCT-derived measures and TR grade was investigated. Clinical, echocardiographic, and MDCT data were collected in the departmental electronic clinical files (EPD vision version 8.3.3.6; Leiden, The Netherlands) and retrospectively analysed. The institutional review board approved this retrospective evaluation of clinically collected data and waived the need for a written informed consent.

MDCT data acquisition MDCT data were acquired with a 320-detector row computed tomography scanner (AquilionOne, Toshiba Medical Systems, Tochigi-ken, Japan). The collimation was set at 320 × 0.5 mm and the rotation time was 350 ms. Based on the body mass index of the patient, the tube voltages and currents varied from 100 to 135 kV and 400 to 580 mA, respectively. Beta-blockers were used in patients with heart rates .65 bpm, unless clinically contraindicated. Non-ionic contrast media (Iomeron 400, Bracco, Milan, Italy) were administered in the antecubital vein. Based on the total scan time, renal function, and body weight, 60 – 100 mL of contrast media was administered in three steps: first, 50 – 90 mL of contrast media at a flow rate of 5.0 – 6.0 mL/s, followed by a 20 mL mixture of 50% contrast/saline, which again was followed by 25 mL of saline at a flow rate of 3.0 mL/s. To synchronize the scan onset with the arrival of the contrast media, automated peak enhancement detection in the left ventricle was used to initiate craniocaudal scanning after reaching a threshold of +180 HU. The images were acquired during an inspiratory breath-hold of 8 – 10 s. With prospective electrocardiogram-triggered dose modulation, an entire cardiac cycle was scanned, while the maximal tube currents were set at 75, 65 – 85, and 30 – 80% of the RR interval in patients with, respectively, heart rates of ,60, 60 – 65, or .65 bpm. Beyond these intervals, a tube current of only 25% of the maximal tube current was used. MDCT data were reconstructed at each 10% of the RR interval in slices of 2.0 mm. For systole and diastole, additional images were reconstructed

P.J. van Rosendael et al.

with a slice thickness of 0.5 mm and a reconstruction interval of 0.25 mm at, respectively, 30 – 45 and 70 – 80% phases of the RR interval. Subsequently, the data were transferred to an external workstation for off-line post-processing and analysis (Vitrea 2, Vital Images, Plymouth, MN, USA).

MDCT data analysis To assess the tricuspid valve geometry, the end-systolic MDCT data were used (30 – 45% of cardiac cycle). Particularly, the tricuspid annular dimensions and the leaflet tethering were assessed. By aligning three orthogonal multiplanar reformation planes, the two- and four-chamber views of the RV and the short-axis view at the level of the tricuspid annulus were obtained (Figure 1 ). The maximal diameter from the anterior leaflet to the septal– posterior commissure (antero-posterior diameter) and the maximal diameter in septal to lateral direction (septal – lateral diameter) were measured and the perimeter and the cross-sectional area of the tricuspid annulus were assessed by planimetry (Figure 1). Annulus eccentricity was defined as the ratio between the septal – lateral and the antero-posterior diameter. With this ratio, a perfect circular tricuspid annulus is represented by an eccentricity index of 1, while a lower eccentricity index represents more elliptical annulus geometry. In addition, in the two- and four-chamber views, additional planes parallel to the tricuspid valve were reconstructed to allow proper visualization of the tricuspid leaflets (Figure 2). In the reconstructed two-chamber view, the degree of tethering of the anterior leaflet was assessed by measuring the angle between this leaflet and the tricuspid annular plane. Similarly, the degree of tethering of the septal and posterior tricuspid leaflets was measured in a reconstructed four-chamber view (Figure 2). For quantification of RV volumes and function, Mass software (Version 2013-EXP, LKEB, Leiden, The Netherlands) was used. The longitudinal axis of the RV was obtained in two- and four-chamber views, and the endocardial border was manually traced in short-axis slices (thickness and spacing of 4.0 mm) from apex to the pulmonary and tricuspid valve in the end-systolic and the end-diastolic phases. Using the method of discs, the areas of each generated slice were summed to calculate the RV end-diastolic and end-systolic volumes and ejection fraction (Figure 3).

Transthoracic echocardiography Two-dimensional, continuous, pulsed, and colour Doppler echocardiographic data were acquired with commercially available ultrasound systems equipped with 3.5 MHz or M5S transducers (Vivid-7 or E9 systems, General Electric Vingmed, Horten, Norway). With the patients in the left lateral decubitus position, parasternal (long- and short-axis), apical (two-, three-, and four-chamber), and subcostal views were acquired. Data were stored in cine-loop format in the departmental echocardiographic database to allow for off-line analysis (EchoPac 112.0.1, GE Medical Systems, Horten, Norway). The most recent transthoracic echocardiography, coinciding with the date of the MDCT, was selected. Left ventricular (LV) ejection fraction was quantified from the apical two- and four-chamber views using the Simpson’s biplane method.14 Severity of functional TR was graded semi-quantitatively from colour and continuous wave Doppler data using a multiparametric approach: none or trivial (0 – 1+), mild (2+), moderate (3+), or severe (4+).1,2 The tricuspid annulus diameter was measured in end-diastole in the apical four-chamber view.2 The RV systolic pressure gradient was calculated from the maximum velocity of the TR jet according to the modified Bernoulli equation and was subsequently added to right atrial pressure to determine pulmonary artery systolic pressure. Right atrial

Tricuspid valve remodelling in functional tricuspid regurgitation

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Figure 1 Assessment of the tricuspid valve annulus geometry. From the long-axis two- and four-chamber views (A and B), a short-axis view at the level of the tricuspid valve annulus was reconstructed (C and D). In these planes, the maximal diameter from the anterior leaflet to the septalposterior commissure and the maximal diameter in septal to lateral direction were measured and the perimeter (C) and cross-sectional area (D) of the annulus were assessed by planimetry.

pressure was estimated by measuring the diameter and inspiratory collapsibility of the inferior vena cava.1,15 The presence of concomitant significant (moderate to severe) left-sided valvular heart disease was also evaluated. The peak and mean transaortic pressure gradients were measured on continuous wave Doppler recordings obtained at the apical five- or three-chamber views, as previously described.2,16 The aortic valve area was calculated using the continuity equation.2,16 The presence of significant aortic regurgitation was assessed using the colour and continuous wave Doppler recordings of the regurgitant jet.2,16 In addition, significant mitral valve disease (stenosis or regurgitation) was assessed according to current guidelines.1,2

Statistical analysis Categorical variables are expressed as frequencies and percentages; continuous variables are presented as mean + standard deviation.

Linear regression analysis was performed to explore the association between the echocardiographically assessed tricuspid annulus diameter and the MDCT-derived antero-posterior and the septal – lateral tricuspid annulus diameter. Differences between patients with TR , 3+ vs. those with TR ≥ 3+ were compared using the x 2 test for categorical variables and with the unpaired Student t-test for continuous variables. To explore echocardiographic and MDCT-derived correlates of the presence of TR ≥ 3+, univariate logistic regression analysis was performed. Subsequently, those variables achieving a univariate P-value of ,0.05 were selected for multivariate analysis to identify independent echocardiographic and MDCT-derived correlates of the presence of TR ≥ 3+. To avoid multi-collinearity, multivariate analysis was performed with four non-nested logistic regression models to assess the independent correlation between the MDCT-derived tricuspid annulus dimensions (antero-posterior and septal – lateral diameter, perimeter and area) and the presence of TR ≥ 3+ separately. In addition, RV

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P.J. van Rosendael et al.

Figure 2 Assessment of the tricuspid valve geometry. Two- and four-chamber views that clearly visualized the tricuspid commissures were reconstructed to assess the degree of tethering of the anterior (A), septal (B), and posterior (C ) leaflets.

Figure 3 Quantification of right ventricular volumes and function. After obtaining the long axis of the right ventricle in the two- and fourchamber views (A and B), the endocardial borders were manually traced in short-axis slices (thickness and spacing of 4.0 mm) from apex to the pulmonary and tricuspid valve in the end-systolic and the end-diastolic phases (C).

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Tricuspid valve remodelling in functional tricuspid regurgitation

end-diastolic volume and ejection fraction were excluded from the multivariate models to avoid co-linearity with RV end-systolic volume. Reproducibility of the tricuspid valve geometry measurements was analysed with repeated measurements by one observer at two different time points and by a second observer blinded to the measurements of the first observer. Intra- and inter-observer agreements for these measurements were evaluated using Bland – Altman analysis and intraclass correlation coefficients. The statistical tests were two-sided, and P-values were considered to be statistical significant if ,0.05. All the statistical analyses were performed with the SPSS software (version 20.0, SPSS Inc., Chicago, IL, USA).

Results Among 114 patients (mean age 81 + 8 years, 47 (41%) male), 16 (14%) did not have evidence of TR, 28 patients (25%) had trivial TR (1+), 37 (33%) had mild TR (2+), 24 (21%) had moderate TR

Table 1

(3+), and 9 (8%) had severe TR (4+). The clinical characteristics of the patients are presented in Table 1, divided according to the presence of TR ≥ 3+ (n ¼ 33) vs. TR , 3+ (n ¼ 81). Patient groups were comparable in age, sex, and body surface area. Patients with TR ≥ 3+ had a significantly higher prevalence of ischaemic heart disease (33 vs. 15%, P ¼ 0.03), were more often in atrial fibrillation (36 vs. 11%, P ¼ 0.002), and had significantly lower LV ejection fraction (50 + 16 vs. 57 + 13%, P ¼ 0.02), compared with patients with TR , 3+. In patients with TR ≥ 3+, the mean RV systolic pressure was 38 + 14 mmHg, and the mean pulmonary artery systolic pressure was 46 + 15 mmHg, and as expected, these values were significantly higher compared with patients with TR , 3+ (Table 1). In addition, patients with TR ≥ 3+ more frequently had moderate – severe mitral regurgitation than patients with TR , 3+ (53 vs. 25%, P ¼ 0.006). Peak and mean transaortic pressure gradients and the grade of aortic regurgitation were comparable between patients with TR ≥ 3+ and TR , 3+ (Table 1).

Baseline clinical and echocardiographic characteristics Overall population (n 5 114)

Patients with TR < 31 (n 5 81)

Patients with TR ≥ 31 (n 5 33)

P-value

............................................................................................................................................................................... Age (years)

81 + 8

81 + 8

81 + 8

0.64

Male (%) Body surface area (m2)

47 (41) 1.8 + 0.2

34 (42) 1.8 + 0.2

13 (39) 1.8 + 0.1

0.80 0.91

93 (81) 21 (18)

72 (89) 9 (11)

21 (64) 12 (36)

Hypertension (%)

83 (73)

62 (77)

21 (64)

0.16

Diabetes (%)

29 (25)

24 (30)

5 (15)

0.11

Hypercholesterolaemia (%) Smoking (%)

66 (58) 43 (38)

49 (61) 34 (42)

17 (52) 9 (27)

0.38 0.14

Previous myocardial infarction (%)

23 (20)

12 (15)

11 (33)

0.03

Previous PCI (%) Previous CABG (%)

26 (23) 36 (32)

19 (24) 23 (28)

7 (21) 13 (39)

0.51 0.51

Heart rhythm (%) Sinus rhythm Atrial fibrillation

0.002

Chronic obstructive pulmonary disease (%)

31 (27)

25 (31)

6 (18)

0.17

Left ventricular ejection fraction (%) Tricuspid annulus diameter (mm)

55 + 14 32 + 6

57 + 13 31 + 6

50 + 16 35 + 6

0.02 0.001

Systolic pulmonary artery pressure (mmHg)

38 + 14

34 + 12

46 + 15

,0.001

Peak transaortic pressure gradient (mmHg) Mean transaortic pressure gradient (mmHg)

62 + 31 37 + 21

61 + 31 37 + 21

64 + 30 39 + 21

0.63 0.70

Aortic valve area (cm2)

0.8 + 0.5

0.9 + 0.5

0.8 + 0.4

0.10

Aortic regurgitation (%) None

22 (22)

17 (25)

5 (15)

0.64

Mild

46 (46)

31 (46)

15 (45)

Moderate Severe

28 (28) 5 (5.0)

17 (25) 3 (4)

11 (33) 2 (6)

None Mild

17 (18) 46 (48)

14 (22) 35 (54)

3 (10) 11 (37)

Moderate

23 (24)

13 (20)

10 (33)

9 (10)

3 (5)

6 (20)

Mitral regurgitation (%)

Severe

0.02

CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; TR, tricuspid regurgitation.

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Table 2

P.J. van Rosendael et al.

Tricuspid valve and right ventricular geometry assessed with MDCT in patients with and without TR ≥ 31 Overall population (n 5 114)

Patients with TR < 31 (n 5 81)

Patients with TR ≥ 31 (n 5 33)

P-value

............................................................................................................................................................................... Tricuspid valve annulus Antero-posterior diameter (mm) Septal–lateral diameter (mm) Perimeter (mm) Annulus area (mm2) Eccentricity Degree of tethering

44.7 + 4.7

43.0 + 3.5

49.0 + 4.5

,0.001

37.3 + 5.1 133.9 + 15.1

36.1 + 4.6 129.2 + 12.8

40.2 + 5.1 145.3 + 14.4

,0.001 ,0.001

1318.5 + 285.0

1228.4 + 243.5

1539.7 + 260.2

,0.001

0.84 + 0.09

0.84 + 0.09

0.82 + 0.10

0.358

Anterior leaflet (8)

16.1 + 4.5

15.4 + 4.1

18.1 + 4.9

0.003

Septal leaflet (8) Posterior leaflet (8)

15.6 + 4.3 12.9 + 3.5

14.9 + 4.0 12.6 + 3.0

17.5 + 4.5 13.5 + 4.4

0.002 0.272

135.1 + 34.9 72.4 + 28.6

124.8 + 29.1 64.2 + 23.6

161.0 + 35.5 93.2 + 29.8

,0.001 ,0.001

47.3 + 10.2

49.2 + 9.7

42.5 + 10.2

0.002

Right ventricle EDV (mL) ESV (mL) Ejection fraction (%) EDV, end-diastolic volume; ESV, end-systolic volume.

Tricuspid valve and RV remodelling: MDCT analysis In all patients, adequate systolic MDCT images for the evaluation of tricuspid valve geometry were available. The results of the MDCT data analysis are summarized in Table 2. Tricuspid valve annulus The mean antero-posterior diameter of the tricuspid valve annulus (from the anterior leaflet to the septal-posterior commissure) was 44.7 + 4.7 mm, whereas the mean septal – lateral diameter was 37.3 + 5.1 mm. Consequently, the eccentricity index was 0.84 + 0.09, indicating an oval shape of the tricuspid valve annulus. The mean perimeter of the tricuspid valve annulus was 133.9 + 15.1 mm; the mean cross-sectional area was 1318.5 + 285.0 mm2. In patients with TR ≥ 3+, the antero-posterior and septal – lateral tricuspid annulus diameters (49.0 + 4.5 vs. 43.0 + 3.5 mm, P , 0.001, and 40.2 + 5.1 vs. 36.1 + 4.6 mm, P , 0.001, respectively), and the perimeter and area were significantly larger (145.3 + 14.4 vs. 129.2 + 12.8 mm, P , 0.001, and 1539.7 + 260.2 vs.1228.4 + 243.5 mm2, P , 0.001, respectively) compared with patients with TR , 3+ (Table 2). In contrast, the eccentricity index was comparable between groups. MDCT data of patients with TR , 3 and with TR ≥ 3 are presented in Figures 4 and 5, respectively. Linear regression analysis demonstrated a weak correlation between the echocardiographically assessed tricuspid annulus diameter and the antero-posterior (r 2 ¼ 0.147) and the septal – lateral (r 2 ¼ 0.247) tricuspid annulus diameter from MDCT. Tricuspid leaflet tethering The angles of the respective anterior, septal, and posterior leaflet of the tricuspid valve were 16.1 + 4.58, 15.6 + 4.38, and 12.9 + 3.58, respectively.

Geometrical differences in tricuspid valve anatomy between patients with and without TR ≥ 3+ are presented in Table 2. Compared with patients with TR , 3+, the degree of tethering of the anterior and septal tricuspid leaflets was significantly increased in patients with ≥TR3+ (18.1 + 4.98 vs. 15.4 + 4.18, P ¼ 0.003, and 17.5 + 4.58 vs. 14.9 + 4.08, P ¼ 0.002, respectively), whereas no significant differences were observed in the tethering of the posterior tricuspid leaflet (Table 2). Right ventricular remodelling Among the patients with TR ≥ 3+, RV end-diastolic (161.0 + 35.5 vs. 124.8 + 29.1 mL, P , 0.001) and end-systolic volumes (93.2 + 29.8 vs. 64.2 + 23.6 mL, P , 0.001) were significantly larger, while RV ejection fraction was significantly lower (42.5 + 10.2 vs. 49.2 + 9.7 mL, P ¼ 0.002) compared with their counterparts (Table 2).

MDCT and echocardiographic correlates of TR ≥ 31 Results of the non-nested multivariate logistic regression models are presented in Table 3. LV ejection fraction, the presence of moderate –severe mitral regurgitation, pulmonary artery systolic pressure, tethering of the anterior and septal tricuspid leaflet, RV dimensions, RV function, and all tricuspid annular dimensions were significantly correlated with TR ≥ 3+ at univariate analysis. Subsequently, pulmonary artery systolic pressure, RV end-systolic volume, tethering of the anterior and septal tricuspid leaflets, LV ejection fraction, and moderate – severe mitral regurgitation formed the basis of four separate multivariate logistic regression models to which the antero-posterior diameter, septal – lateral diameter, perimeter, or area of the tricuspid annulus was included. The independent correlates of TR ≥ 3+ included pulmonary artery systolic pressure [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01–1.12, P ¼ 0.030],

Tricuspid valve remodelling in functional tricuspid regurgitation

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Figure 4 Tricuspid annulus geometry of a patient with TR , 3. MDCT-derived tricuspid valve annulus reconstruction of a patient with TR , 3.

Figure 5 Tricuspid annulus geometry of a patient with TR ≥ 3. MDCT-derived tricuspid valve annulus reconstruction of a patient with TR ≥ 3.

RV end-systolic volume (OR 1.03; 95% CI 1.01–1.06, P ¼ 0.015), and the antero-posterior tricuspid annulus diameter (OR 1.35; 95% CI 1.07–1.69, P ¼ 0.01) (Table 3).

Reproducibility data In 20 patients, the inter-observer and intra-observer variability was assessed. For intra-observer variability, the respective mean bias (95% confidence intervals) and intra-class correlation coefficients

were 0.4 + 1.3 mm (20.2 to 1.0) and 0.979 for the anteroposterior diameter, 0.1 + 2.2 mm (20.9 to 1.1) and 0.933 for the septal –lateral diameter, 1.7 + 5.3 mm (20.8 to 4.2) and 0.959 for the perimeter, 2.9 + 64.3 mm2 (227.3 to 33.0) and 0.985 for the area, 0.3 + 1.78 (20.4 to 1.1) and 0.908 for the anterior leaflet tethering, 0.7 + 1.68 (20.1 to 1.4) and 0.901 for the septal leaflet tethering, and 0.03 + 1.38 (20.6 to 0.7) and 0.703 for the posterior leaflet tethering.

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Table 3 MDCT-derived and echocardiographic determinants of TR ≥ 31: univariate and multivariate logistic regression analysis Multivariate

.................................................................. Odds ratio (95% CI)

P-value

............................................................................................................................................................................... Baseline model Systolic pulmonary artery pressure (mmHg)

1.06 (1.01–1.12)

0.030

Right ventricular end-systolic volume (mL) Tethering anterior tricuspid leaflet (8)

1.03 (1.01–1.06) 0.94 (0.79–1.13)

0.015 0.522

Tethering septal tricuspid leaflet (8)

1.18 (0.98–1.41)

0.079

Left ventricular ejection fraction (%) Moderate–severe mitral regurgitation (%)

0.95 (0.91–1.00) 3.40 (0.88–13.10)

0.052 0.075

Baseline model + tricuspid annular antero-posterior diameter (mm)

1.35 (1.07–1.69)

0.010

Baseline model + tricuspid annular septal–lateral diameter (mm)

1.09 (0.94–1.26)

0.254

Baseline model + tricuspid annular perimeter (mm) Baseline model + tricuspid annular area (mm2)

1.06 (1.00–1.13) 1.00 (1.00–1.01)

0.074 0.058

For inter-observer variability, the mean differences and intra-class correlation coefficients were 1.8 + 3.5 mm (0.2 to 3.5) and 0.836 for the antero-posterior diameter, 2.6 + 2.8 mm (1.3 to 3.9) and 0.807 for the septal– lateral diameter, 1.6 + 7.7 mm (22.0 to 5.2) and 0.917 for the perimeter, 95.5 + 134.1 mm2 (32.7 to 158.3) and 0.906 for the area, 0.4 + 2.08 (20.5 to 1.3) and 0.844 for the anterior leaflet tethering, 0.5 + 1.98 (20.4 to 1.4) and 0.902 for the septal leaflet tethering, and 0.2 + 1.78 (20.6 to 1.1) and 0.752 for the posterior leaflet tethering.

Discussion The present study demonstrated that significant functional TR (≥3+) is associated with remodelling of the tricuspid annulus, tethering of the anterior and septal leaflets, and RV remodelling. Particularly, the antero-posterior annulus diameter was independently correlated with the grade of functional TR, after adjusting for estimated pulmonary artery systolic pressure and RV end-systolic volume. The additional information that 320-row MDCT provides may help in the decision-making of patients with symptomatic severe aortic stenosis and concomitant significant functional TR who are evaluated for eventual aortic valve replacement and tricuspid annuloplasty.

Imaging techniques for the assessment of tricuspid valve geometry While TR is usually graded with 2D echocardiography, the elliptical shape of the tricuspid annulus challenges the assessment of valve geometry using this imaging technique.1,9 – 13 The normal 3D configuration of the tricuspid annulus is characterized by an asymmetrical saddle shape with the highest and lowest points in antero-posterior and medio-lateral orientation, respectively.13 With 3D transthoracic echocardiography, Ton-Nu and co-workers13 demonstrated the non-planar configuration of the tricuspid annulus and the changes in tricuspid annulus dimensions and configuration in 35 patients

with functional TR. Compared with healthy individuals, patients with significant functional TR had larger tricuspid annulus area (1724 + 475 vs. 983 + 218 mm2, P , 0.001) and lower distance between the highest and lowest points of the annulus (4.14 + 1.05 vs. 7.21 + 1.09 mm, P , 0.001) which suggest a flatter configuration of the tricuspid annulus.13 In addition, the increase in tricuspid annulus dimensions were more pronounced in the antero-posterior than in the medial –lateral orientation (88 vs. 31%), indicating that the remodelling of the tricuspid annulus occurs along its free-wall aspect.13 In addition, tethering of the tricuspid leaflets may be also observed in patients with functional TR. In a series of 54 patients with various grades of TR, Park et al.17 measured the leaflet angles with 3D transthoracic echocardiography. A gradual increase in leaflet angles was observed; patients with severe TR showed the largest angles (27.8 + 12.28 for the septal leaflet, 23.2 + 9.68 for the anterior leaflet, and 24.3 + 7.58 for the posterior).17 Interestingly, the increase in leaflet tethering across patient subgroups (mild, moderate, and severe TR) was more pronounced for the anterior (from 9.3 + 4.48 to 15.5 + 7.78 and further 23.2 + 9.68) and septal (from 13.3 + 6.88 to 18.2 + 7.98 and further 27.8 + 12.28) leaflets than the posterior leaflet (from 16.8 + 4.98 to 20.4 + 7.88 and to 24.3 + 7.58).17 The present evaluation supports these previous studies. By using MDCT, a non-invasive imaging technique with higher spatial resolution than 3D transthoracic echocardiography, patients with TR ≥ 3+ had larger tricuspid annulus area, increased tethering of the tricuspid leaflets, and larger RV volumes compared with patients with TR , 3+. Similar to the results reported by Park et al.,17 leaflet tethering was more pronounced in the septal and anterior leaflets than in the posterior leaflet. These findings may be related to the anatomical disposition of the subvalvular apparatus. The anterior leaflet receives chorda from the anterior papillary muscle, the septal leaflet from the medial papillary muscle, and the posterior leaflet from both papillary muscles.4 In addition, the presence of chorda arising from the septal wall, RV free-wall, and moderator band may influence the leaflet tethering if there is concomitant RV

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Tricuspid valve remodelling in functional tricuspid regurgitation

dysfunction and dilatation. Using 3D transthoracic echocardiography, Spinner et al. 18 evaluated the effect of RV remodelling on TR and demonstrated that patients (n ¼ 17) with RV dilatation had an apical displacement of all papillary muscles (anterior: 1.9 + 0.8 cm/m2, septal: 1.1 + 0.3 cm/m2, posterior: 1.3 + 0.4 cm/m2) and a lateral displacement towards the LV of the septal (1.0 + 0.5 cm/m2) and posterior (0.9 + 0.5 cm/m2) papillary muscle compared with controls (n ¼ 21).18 Consequently, increased leaflet tethering area and height were observed.

Determinants of functional TR Functional TR grade is strongly influenced by both RV preload and afterload and RV function. 4 However, significant functional TR causes remodelling of the RV and tricuspid valve apparatus that eventually can increase TR. The association between tricuspid valve geometry and TR grade has been evaluated with 3D transthoracic echocardiography.13,17,18 Ton-Nu and co-workers13 demonstrated that tricuspid valve annulus area and circularity (measured as the ratio between antero-posterior and lateromedial diameters) were significantly associated with TR grade after correcting for RV dimensions and LV ejection fraction. In addition, Spinner et al. 18 demonstrated that tricuspid annulus area and apical displacement of the anterior papillary muscle remained independently associated with TR grade after correcting for RV dimensions and pulmonary arterial pressure. In contrast, Park et al. showed that only tricuspid tenting volume was significantly associated with TR grade, whereas tricuspid annulus diameters and leaflet angles were not independently associated.17 Therefore, the present evaluation is in agreement with the series reported by Ton-Nu et al. 13 and Spinner et al. 18 by demonstrating the independent association between anteroposterior tricuspid diameter and TR grade after correcting for pulmonary artery systolic pressures, RV end-systolic volume, and significant mitral regurgitation.

Clinical implications Functional TR is relatively common in patients with left-sided heart disease and associated with heart failure symptoms and poor prognosis.4 – 6 As preload, afterload and RV function interfere with the occurrence and severity of functional TR, the extent of tricuspid annulus dilatation may be considered a more robust indicator for tricuspid valve surgery. Several studies have demonstrated that tricuspid valve annuloplasty performed during surgery for left-sided heart disease is associated with improved surgical outcomes.7,19,20 Accordingly, in addition to TR severity, current guidelines recommend surgical tricuspid valve repair during left-sided valve surgery in patients with tricuspid annulus diameter .40 mm. 1,2 Twodimensional echocardiography remains the first available imaging technique to assess the dimensions of the tricuspid annulus in routine clinical practice. However, how to measure the tricuspid annulus with this technique remains controversial. By providing 3D images with high spatial resolution, MDCT enables more accurate measurements of the tricuspid annular geometry than 2D echocardiography. In addition, MDCT may further facilitate the decision regarding the type of surgery by enabling accurate characterization of leaflet tethering. Leaflet tethering is an important determinant of significant residual TR after tricuspid annuloplasty.21,22 Therefore, the presence of significant leaflet tethering may help to decide the

surgical repair/replacement strategy. As for the other valves, MDCT also has the potential to facilitate emerging transcatheter procedures of the tricuspid valve through providing invaluable anatomical and geometrical information.4,23

Limitations Some limitations should be acknowledged. The present evaluation comprised patients who were referred for transcatheter aortic valve implantation, and prospective studies are needed to confirm the incremental value of MDCT in the surgical decision-making of patients with functional TR. In addition, only patients with adequate MDCT images for the evaluation of the tricuspid valve geometry were included. To ensure a good characterization of the tricuspid valve with MDCT, the contrast injection protocol should be optimized for visualization of the right heart by using lower flow rates of contrast medium injection and earlier initiation of the scan.24,25

Conclusions MDCT allows accurate assessment of the tricuspid valve geometry. Patients with functional TR ≥ 3+ showed larger tricuspid annular dimensions, more pronounced tethering of the anterior and septal tricuspid leaflet, and RV remodelling. The antero-posterior tricuspid annulus diameter was independently correlated with TR ≥ 3+. Accurate assessment of the tricuspid valve geometry with MDCT may be of value for surgical decision-making and the improvement of surgical and transcatheter tricuspid valve prosthesis and techniques. Conflict of interest: V.D. received speaking fees from Abbott Vascular.

Funding The Department of Cardiology received research grants from Biotronik, Medtronic and Boston Scientific. V.K. received a European Society of Cardiology training grant, a European Association of Cardiovascular Imaging research grant, a Hellenic Cardiological Society training grant and a Hellenic Foundation of Cardiology research grant.

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