JACC: CARDIOVASCULAR IMAGING

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ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

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ISSN 1936-878X/$36.00 http://dx.doi.org/10.1016/j.jcmg.2015.08.022

Mitral Annular Dimensions and Geometry in Patients With Functional Mitral Regurgitation and Mitral Valve Prolapse Implications for Transcatheter Mitral Valve Implantation Christopher Naoum, MBBS,a Jonathon Leipsic, MD,a Anson Cheung, MD,a Jian Ye, MD,a Nicolas Bilbey, MD,a George Mak, MBBS,a Adam Berger, MBBS,a Danny Dvir, MD,a Chesnal Arepalli, MD,a Jasmine Grewal, MD,a David Muller, MBBS,b Darra Murphy, MBBS,a Cameron Hague, MD,a Nicolo Piazza, MD,c John Webb, MD,a Philipp Blanke, MDa

ABSTRACT OBJECTIVES The aims of this study were to determine D-shaped mitral annulus (MA) dimensions in control subjects without significant cardiac disease and in patients with moderate to severe mitral regurgitation (MR) being considered for transcatheter mitral therapy and to determine predictors of annular size, using cardiac computed tomography. BACKGROUND The recently introduced D-shaped method of MA segmentation represents a biomechanically appropriate approach for annular sizing prior to transcatheter mitral valve implantation. METHODS Patients who had retrospectively gated cardiac computed tomography performed at our institution (2012 to 2014) and were free of significant cardiac disease were included as controls (n ¼ 88; 56  11 years of age; 47% female) and were compared with patients with moderate or severe MR due to functional mitral regurgitation (FMR) (n ¼ 27) or mitral valve prolapse (MVP) (n ¼ 32). MA dimensions (projected area, perimeter, intercommissural, and septal-to-lateral distance), maximal left atrial (LA) volumes, and phasic left ventricular volumes were measured. RESULTS MA dimensions were larger in patients with FMR or MVP compared with controls (area index 4.7  0.6 cm2/m2, 6.0  1.3 cm2/m2, and 7.3  1.7 cm2/m2; perimeter index 59  5 mm/m2, 67  9 mm/m2, and 75  10 mm/m2; intercommissural distance index 20.2  1.9 mm/m2, 21.2  3.1 mm/m2, and 24.7  3.2 mm/m2; septal-to-lateral distance index 14.8  1.6, 18.1  3.3, and 19.5  3.4 mm/m2 in controls and patients with FMR and MVP, respectively; p < 0.05 between controls and MR subgroups). Absolute MA area was 18% larger in patients with MVP than patients with FMR (13.0  2.9 cm2 vs. 11.0  2.3 cm2; p ¼ 0.006). Although LA and left ventricular volumes were both independently associated with MA area index in controls and patients with MVP, only LA volume was associated with annular size in patients with FMR. CONCLUSIONS Moderate to severe MR was associated with increased MA dimensions, especially among patients with MVP compared with control subjects without cardiac disease. Moreover, unlike in controls and patients with MVP, annular enlargement in FMR was more closely associated with LA dilation. (J Am Coll Cardiol Img 2016;-:-–-) © 2016 by the American College of Cardiology Foundation.

From aSt. Paul’s Hospital and University of British Columbia, Center for Heart Valve Innovation, Vancouver, British Columbia, Canada; bSt. Vincent’s Hospital, Sydney, Australia; and the cDepartment of Medicine, Division of Cardiology, McGill University Health Centre, Montreal, Quebec, Canada. Dr. Leipsic has served as a consultant to Edwards Lifesciences and Neovasc Inc.; and has provided CT core laboratory services to Edwards Lifesciences, Neovasc Inc., and Tendyne Holdings Inc. Dr. Cheung has served as a consultant to Edwards Lifesciences and Neovasc Inc. Drs. Ye and Webb have served as consultants to Edwards Lifesciences. Dr. Piazza has served on scientific advisory boards for Medtronic; has served as a consultant for HighLife SAS; and owns equity shares in HighLife SAS. Dr. Blanke has served as a consultant to Edwards Lifesciences, Neovasc Inc., Tendyne Holdings Inc., and Circle Imaging; and has provided CT core laboratory services to Edwards Lifesciences, Neovasc Inc., and Tendyne Holdings Inc. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received July 2, 2015; revised manuscript received August 18, 2015, accepted August 20, 2015.

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ABBREVIATIONS AND ACRONYMS BMI = body mass index BSA = body surface area CT = computed tomography FMR = functional mitral regurgitation

IC = intercommissural LA = left atrial/atrium

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Mitral Annular Dimensions in Mitral Regurgitation

ith the rapid innovation and

than mild MA calcification seen on cardiac CT; 2)

growing

of

clinical history of congestive heart failure and/or

transcatheter mitral therapies,

reduced measured left ventricular (LV) ejection

including transcatheter mitral valve implan-

fraction 50%

mitral annular (MA) dimensions and geome-

in the left main) or prior coronary revascularization;

try

important.

4) history of atrial fibrillation; 5) prior cardiac surgery;

Given the saddle-shaped, nonplanar configu-

6) complex congenital heart disease; 7) obesity (body

ration of the MA, 3-dimensional (3D) imaging

mass index [BMI] >35 kg/m2 ); 8) increased maximal

is

becoming

clinical

adoption

increasingly

is required for comprehensive assessment.

left atrial (LA) volume index (>78 ml/m 2, a cutoff

LV = left ventricle/ventricular

Although

using

representing 2 SDs from the mean value previously

MA = mitral annular/annulus

computed tomography (CT), with its excel-

reported in healthy subjects [6]); and/or increased LV

MR = mitral regurgitation

lent spatial resolution (1–4), limited data

mass index (>103 g/m 2 for men and >89 g/m 2 for

MVP = mitral valve prolapse

exist describing CT values for MA dimensions

women [7]). Consecutive patients with moderate to

SL = septal-to-lateral

in patients with significant mitral regurgita-

severe MR referred for cardiac CT between November

TMVI = transcatheter mitral

tion (MR) in whom TMVI may be a potential

2013 and June 2015 for workup prior to potential

valve implantation

therapeutic option.

TMVI were included. Patients with MR were divided

this

can

be

achieved

We recently proposed a D-shaped concept

into 2 groups based on MR mechanism (mitral valve

of MA geometry, in which the annulus is truncated

prolapse [MVP] or functional mitral regurgitation

along a virtual line connecting both fibrous trigones,

[FMR]). Patients with a prior aortic and/or mitral

TT = trigone-to-trigone

as a standardized, reproducible, and more biome-

valve prosthesis were excluded from the MR group.

chanically appropriate method for MA sizing prior to

CARDIAC CT DATA ACQUISITION. Cardiac CT was

TMVI (5). An important characteristic of the D-shaped

performed using a 64-slice helical CT scanner (Dis-

segmentation method is that it yields a more planar

covery high-definition 750 or VCT, GE Healthcare,

annulus that closely resembles the cross-sectional

Milwaukee, Wisconsin). For controls, CT acquisition

area of current TMVI devices, which is not achieved

was undertaken according to the institutional proto-

by conventional (saddle-shaped) analyses. Annular

col for performing retrospectively gated clinical car-

size and geometry and the determinants of MA size in

diac CT. For patients with MR, a pre-specified clinical

patients with moderate to severe MR have not been

cardiac CT protocol was used. Imaging was performed

studied using the D-shaped method. Moreover, the

during a single breath-hold following injection of 80

range of D-shaped MA dimensions in patients without

to 110 ml of intravenous contrast media (Visipaque

significant cardiac disease is unknown.

320, GE

Healthcare)

with

a

triphasic

injection

Accordingly, we sought to determine annular di-

(contrast, contrast/saline mix, and saline) for controls

mensions, geometry, and drivers of annular size in

and a biphasic injection (contrast and saline) for pa-

patients with moderate to severe MR and compare

tients with MR. Tube voltage and current were

these findings with those of control subjects without significant

cardiac

disease

using

retrospectively

manually determined (on the basis of BMI) with subsequent ECG modulation of tube current for con-

electrocardiographically (ECG) gated cardiac CT.

trols to minimize radiation dose (median [inter-

METHODS

quartile range] effective dose 9.6 mSv [5.7 to 11.8 mSv] in controls and 14.1 mSv [11.3 to 20.2 mSv] in Review

patients with MR). Scan range extended from the

Board approved this retrospective study with a

carina to just below the inferior cardiac surface. Axial

waiver for informed consent. Two study cohorts were

images were reconstructed at 10% intervals of the

identified. Consecutive patients who underwent

cardiac cycle with a slice thickness of 0.625 mm.

STUDY

POPULATION. The

Institutional

clinically indicated, retrospectively gated cardiac CT

CT DATA ANALYSIS. CT measurements were per-

at our institution between August 2012 and February

formed offline by batch analysis using dedicated

2014 and were identified as being free of significant

software for MA segmentation (3mensio Structural

cardiac disease on the basis of CT findings and review

Heart V7.0; Pie Medical Imaging, Maastricht, the

of available clinical information were included as

Netherlands) and volumetric analyses (Aquarius

controls. Only scans performed with retrospective

iNtuition v4.4, TeraRecon, Foster City, California).

ECG gating were included so that multiphasic data

Different observers separately assessed MA parame-

could be analyzed. Exclusion criteria included: 1)

ters and cardiac volumes (P.B. and C.N. performed

known significant mitral valve disease and/or greater

all MA measurements by co-review and consensus

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agreement;

Mitral Annular Dimensions in Mitral Regurgitation

N.B.

performed

all

cardiac

volume

saddle-shaped annulus from the posterior, D-shaped

measurements).

compartment. MA area and perimeter were computed

ASSESSMENT OF MR SEVERITY AND MECHANISM IN

for the D-shaped component by projection onto the

THE MR GROUP. MR severity was graded by review

least-squares plane fitted to the 3D annular contour.

of echocardiographic data according to guidelines

Total annular perimeter was calculated by adding the

for the assessment of MR severity (8). The mecha-

TT distance to the posterior 2D perimeter. The septal-

nism of MR was determined by separate review of

to-lateral (SL) distance was defined as the projected

both echocardiographic data and multiphasic (cine)

distance from the TT line to the posterior peak and

CT datasets using multiplanar reconstructions to

the intercommissural (IC) distance as the diameter

generate 2- and 3-chamber views of the LV. MVP was

perpendicular to the SL distance and parallel to the

defined by the presence of systolic excursion of a

TT distance transecting the centroid of the MA. The

mitral leaflet more than 2 mm beyond the annular

IC/SL ratio was also calculated as a measure of overall

plane in either a 2- or 3-chamber view (9). FMR was

MA geometry (Figure 1). Intraobserver and interob-

defined as LV remodeling (dilation and/or global or

server reproducibility of D-shaped MA measurements

regional LV dysfunction) that prevents leaflet coap-

has been recently documented (5).

tation in the absence of a primary mitral valve ab-

VOLUMETRIC

normality (10).

were measured using a threshold-based, region-

ANALYSES. LV

MA ASSESSMENT. The method for segmentation and

growing, 3D segmentation algorithm (Aquarius iNtu-

assessment of the D-shaped MA has been recently

ition). Endocardial and epicardial contours of the LV

described (5,11). Briefly, mid to late diastolic image

were automatically detected with subsequent manual

reconstructions with the least artifact identified by

adjustment of the contours and level of the mitral

visual assessment were used for MA segmentation.

valve plane. LV systolic and diastolic volumes were

The MA contour was generated by cubic-spline-

measured with subsequent calculation of LV stroke

interpolation of 16 seeding points manually placed

volume and ejection fraction. LA size was assessed at

along the insertion of the posterior mitral valve

end-systole corresponding to maximal LA volume by

leaflet and along the anterior peak comprising

using a semiautomated attenuation-based algorithm

the fibrous aortomitral continuity. The lateral and

for

medial fibrous trigones were then manually identified

correction (Aquarius iNtuition). LA volume excluded

and the distance between these 2 points defined

the LA appendage and pulmonary veins (12).

endocardial

border

volumes and mass

detection

with

manual

as the trigone-to-trigone (TT) distance, which sepa-

STATISTICAL ANALYSIS. Continuous variables are

rates the anterior compartment of the traditional

expressed as mean  SD and categorical variables as

F I G U R E 1 D-Shaped Mitral Annular Segmentation

Short-axis (A) and long-axis (B) images demonstrating the D-shaped mitral annulus comprising the posterior horn (red contour) and trigoneto-trigone (TT) distance (white line), the latter virtually connecting both fibrous trigones (purple and green dots). The intercommissural (IC) distance (dotted yellow line) runs parallel to the TT distance and transects the centroid, and the septal-to-lateral (SL) distance runs perpendicular to the TT distance and transects the centroid. LA ¼ left atrium; LV ¼ left ventricle.

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Mitral Annular Dimensions in Mitral Regurgitation

number (percentage). Cardiac volumes and MA di-

association between annular size (MA area index)

mensions are indexed to body surface area (BSA)

and LA/LV volumes in patients with FMR or MVP,

calculated using the Mosteller formula (13). Indexed

nonparametric

values were compared between controls and MR

formed, given the smaller sample size in these groups.

(Spearman)

correlation

was

per-

subgroups using an unpaired Student t test or Mann-

Statistical analyses were performed using Graph-

Whitney U test as appropriate (normality determined

Pad Prism V6.0d (GraphPad Software, La Jolla,

using the Kolmogorov-Smirnov method) without

California) and SPSS Statistics 22 (IBM Corp., Armonk,

adjustment for multiple comparisons.

New York). A 2-tailed p value MAC on CT (n = 5) Prior MI or revascularization (n = 9) CHF and/or LVEF 35 (n = 13) Increased LV mass index or LA volume index (n = 2)

CONTROLS N = 88

N = 26 excluded Poor image quality annular and/or volumetric segmentation (n = 9) Aortic and/or mitral prosthesis (n = 13) Rheumatic mitral disease (n = 1) Unclear mechanism of MR (n = 3)

MVP N = 32

FMR N = 27

Patients included in the control, functional mitral regurgitation (FMR), and mitral valve prolapse (MVP) cohorts and reasons for exclusion. AF ¼ atrial fibrillation; BMI ¼ body mass index; CAD ¼ coronary artery disease; CHD ¼ congenital heart disease; CHF ¼ congestive heart failure; CT ¼ computed tomography; CTA ¼ computed tomography angiography; LVEF ¼ left ventricular ejection fraction; MAC ¼ mitral annular calcification; MI ¼ myocardial infarction; MR ¼ mitral regurgitation; other abbreviations as in Figure 1.

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Mitral Annular Dimensions in Mitral Regurgitation

whom were excluded, resulting in a total of 59 patients in the MR cohort (32 patients with MVP and 27 with FMR) (Figure 2). Baseline characteristics for the control group are presented in Table 1. Age was 56  11 years, and 47% of patients were female. LV and LA volumes and LV ejection fraction were consistent with reported values for healthy individuals (6).

T A B L E 2 Absolute and Indexed Mitral Annular Dimensions in Control Subjects

All (n ¼ 88)

Female (n ¼ 41)

Male (n ¼ 47)

Mean  SD

8.9  1.5

8.4  1.2

9.3  1.6

Range

5.5–13.8

5.5–11.2

6.5–13.8

110.0  9.0

107.0  7.0

113.0  10.0

87.0–138.0

87.0–123.0

93.0–138.0

Mitral Annular Dimensions

p Value*

Absolute value Area, cm2 0.004

Perimeter, mm

In control subjects, mean MA area, MA area index, 2

2

and IC/SL ratio were 8.9  1.5 cm , 4.7  0.6 cm/m , and 1.38  0.14, respectively (Table 2). There was wide intersubject variability noted in MA area (Figure 3). Although annular dimensions were gener-

Mean  SD Range TT distance, mm Mean  SD

28.5  3.4

27.3  2.5

29.5  3.8

Range

20.0–38.0

20.0–33.0

21.0–38.0

27.5  2.7

27.1  2.3

27.8  3.0

21.5–35.1

22.1–31.4

21.5–35.1

0.001

SL distance, mm

ally larger in men compared with women, the differ-

Mean  SD

ences largely disappeared after values were indexed

Range

to BSA (Table 2).

0.001

0.21

IC distance, mm

MA dimensions correlated positively with BSA, as expected (Figure 4). Univariate and multivariate predictors of MA area index in controls are presented in Table 3. Age and sex were not associated with MA area index. Both LV and LA volumes were independently associated with MA area index, with LV systolic vol-

Mean  SD

37.6  3.7

36.1  2.9

38.8  3.9

Range

28.6–48.6

28.6–42.8

28.8–48.6

Mean  SD

4.7  0.6

4.7  0.7

4.8  0.5

Range

3.3–7.4

3.3–7.4

3.7–6.0

59.0  5.0

60.0  6.0

58.0  5.0

47.0–81.0

47.0–69.0

47.0–69.0

Mean  SD

15.3  1.9

15.4  1.8

15.2  1.9

Range

10.8–20.3

11.3–20.3

10.8–20.0

Mean  SD

14.8  1.6

15.2  1.7

14.4  1.5

Range

11.2–20.6

12.2–20.6

11.2–18.5

20.2  1.9

20.3  2.1

20.0  1.8

16.4–27.3

16.4–27.3

17.0–25.1

Mean  SD

1.38  0.14

1.34  0.12

1.41  0.16

Range

1.04–1.75

Value indexed to BSA Area, cm2/m2

ume index (beta ¼ 0.40; p < 0.001) slightly more

Mean  SD Range

T A B L E 1 Baseline Characteristics for Control Subjects (n ¼ 105)

Demographics 56  11 55 (47–65)

Female

41 (47)

Body mass index, kg/m2

26.7  3.7

Body surface area, m2

1.88  0.21

Cardiac CT parameters LV diastolic volume index, ml/m2 All

58  13

Female

58  15

Male

59  12

All

21  7

Female

19  7

Male

22  7

Mean  SD Range

1.12–1.57

1.04–1.75

*p Value compares differences between women and men. BSA ¼ body surface area; IC ¼ intercommissural; SL ¼ septal-to-lateral; TT ¼ trigone-to-trigone.

MA dimensions and cardiac volumes among MR Controls were younger compared with both patients

51–81

with MVP and FMR and had higher mean BMI and

LV diastolic mass index, g/m2 All

67  12

Female

62  11 72  12

Male 2

Maximal LA volume index, ml/m

BSA values compared with patients with MVP. MA dimensions were generally larger in MR subgroups compared with controls, even after BSA was indexed to account for the differences in BSA. The range of

All

46  8

absolute annular areas observed in patients with FMR

Female

48  9

and MVP is shown in Figure 5.

Male

45  8

Values are mean  SD, unless otherwise indicated. CT ¼ computed tomography; LA ¼ left atrial; LV ¼ left ventricular.

0.50

IC/SL ratio

65  7

Range

0.01

IC distance, mm/m2

subgroups and controls are compared in Table 4.

LV ejection fraction, %

0.69

SL distance, mm/m2

LV systolic volume index, ml/m2

Mean  SD

0.15

TT distance, mm/m2

index (beta ¼ 0.31; p ¼ 0.001).

Median (interquartile range)

0.66

Perimeter, mm/m2

predictive of MA area index than maximal LA volume

Age, yrs