Original article
Preoperative left ventricular function in degenerative mitral valve disease Eduard Maleva, Gleb Kimb, Lubov Mitrofanovaa and Eduard Zemtsovskya Aim The aim of the study is to determine the impact of the underlying etiology (Barlow’s disease or fibroelastic deficiency) on left ventricular function in patients with degenerative mitral valve disease and severe mitral regurgitation.
patients with Barlow’s disease in comparison with fibroelastic deficiency a significant decrease of the left ventricular longitudinal systolic strain (S13.5 W 2.2 vs. S15.6 W 2.3%, P U 0.00001) and early diastolic strain rate (1.04 W 0.20 vs. 1.14 W 0.18 sS1, P U 0.0004) were detected.
Methods We studied 233 patients (mean age: 53.8 W 12.9) undergoing surgery for severe mitral regurgitation due to degenerative mitral valve disease at Almazov Federal Heart Centre between 2009 and 2011. Pathologic diagnoses for valvular tissue specimens were provided by an experienced pathologist. Preoperative strain and strain rate were determined using speckle tracking (Vivid 7 Dimension, EchoPAC’08).
Conclusion Patients with severe mitral regurgitation due to Barlow’s disease have a lower preoperative left ventricular systolic function than those with fibroelastic deficiency, which may affect their postoperative prognosis.
Results Barlow’s disease was identified by the pathologist in 60 patients (25.8%), and fibroelastic deficiency in 173 patients (74.2%). There were no significant differences between groups in preoperative mitral regurgitation volume (70.5 W 9.6 vs. 71.6 W 8.5 ml, P U 0.40), and in global systolic (ejection fraction: 52.7 W 6.6 vs. 52.0 W 7.4%, P U 0.53) and diastolic (E/e’: 12.2 W 3.9 vs. 12.8 W 4.2, P U 0.35) left ventricular function. Despite the lack of difference in ejection fraction and diastolic tissue Doppler parameters, in
Introduction Degenerative mitral valve disease (DMVD) is a common disorder affecting around 2% of the population.1,2 Barlow’s disease and fibroelastic deficiency (FED) are the two dominant forms of DMVD in which morphologic changes in the connective tissue of the mitral valve cause structural lesions that are responsible for the syndromes of billowing mitral leaflet, mitral valve prolapse (MVP), floppy mitral valve and flail leaflet.3 Barlow’s disease is characterized by diffuse excess tissue. Valve size is large, and multiple segments are affected with myxomatous pathological changes, resulting in thickened and distended ‘floppy’ leaflets. Diffuse chordal thickening, elongation and varying degrees of annular calcification may be observed.2 The pathological hallmarks are myxoid infiltration and collagen alteration, which destroys the normal three-layer leaflet architecture. Severe mitral regurgitation in Barlow’s disease results from the marginal prolapse due to chordal elongation and typically occurs in the mid-to-late phase of systole.3 In FED, the main pathological mechanism is connective tissue deficiency.4 Impaired production of connective tissue, with deficiency of collagen, elastins and 1558-2027 ß 2014 Italian Federation of Cardiology
J Cardiovasc Med 2014, 15:222–229 Keywords: Barlow’s disease, fibroelastic deficiency, preoperative left ventricular function, severe mitral regurgitation, speckle-tracking echocardiography a
Almazov Federal Heart, Blood and Endocrinology Centre and bSaint-Petersburg State University, Saint-Petersburg, Russia Correspondence to Dr Eduard Malev, Almazov Federal Heart, Blood and Endocrinology Centre, 2 Akkuratova str., Saint-Petersburg 197341, Russia Tel: +7 921 910 1394; fax: +7 812 702 3744; e-mail:
[email protected] Received 5 October 2012 Revised 13 March 2013 Accepted 20 April 2013
proteoglycans results in thinning of leaflet tissue. The three-layer architecture of the leaflet tissue is preserved.3 Alterations in FED are characterized by disrupted, fragmented and granular elastic fibers that form an amorphous clump.4 Myxoid degeneration of single prolapsing segment may occur. Rupture of thin, connective tissuedeficient chords is the mechanism of severe holosystolic mitral regurgitation in FED.3 DMVD is the most common cause of mitral regurgitation in developed countries and one of the most frequent cardiovascular disorders requiring surgery.5 Surgery is warranted in symptomatic patients with severe mitral regurgitation and has been recommended in asymptomatic patients who develop signs of left ventricular dysfunction.6 For detecting left ventricular myocardial dysfunction, parameters such as left ventricular cavity dimensions and ejection fraction have been widely used, but these standard parameters are often overestimated in the presence of severe mitral regurgitation.7 Preoperative left ventricular systolic function is also an important prognostic factor of early postoperative left ventricular decompensation and poor prognosis in patients undergoing mitral valve repair or replacement.8,9 DOI:10.2459/JCM.0b013e328362784f
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Left ventricular function in mitral valve disease Malev et al. 223
Two-dimensional speckle-tracking echocardiography (STE) is a widely available technique used for the evaluation of myocardial function. Strain and strain rate analysis increase sensitivity in detecting subclinical cardiac involvement in some conditions including severe mitral regurgitation.10 The purpose of this study was to determine the impact of the underlying etiology (Barlow’s disease or FED) on left ventricular function in patients with DMVD undergoing surgery for severe mitral regurgitation.
Methods Study population
A total of 233 patients undergoing surgery for severe mitral regurgitation due to DMVD at Almazov Heart Centre between 2009 and 2011 were enrolled in our retrospective, single-center study. Only patients with surgically excised mitral valves (segment of the posterior leaflet or the entire valve) suitable for pathomorphological examination were included in this study. Mean age of the patients was 53.8 12.9 years. Patients with severe mitral regurgitation due to ischemic heart disease or cardiomyopathy (based on the preoperative coronary angiogram), with Marfan syndrome, with associated mitral stenosis, or any other form of valve disease were excluded. All patients gave informed consent and the protocol was approved by the local ethics committee. Patients were qualified for surgery according to the American Heart Association/American College of Cardiology (AHA/ACC) guideline.6 Seventy-three patients (31%) were symptomatic (I class of indication), 132 patients (57%) were asymptomatic with ejection fraction less than 60% and/or end systolic diameter more than 40 mm (I class), and 28 (12%) asymptomatic patients had pulmonary hypertension more than 50 mmHg (IIa class of indication). Repair was feasible in 196 (84%) patients. Quadrangular or triangular resection of prolapsed scallop, ring annuloplasty, and additionally, when required, artificial cords were used. In 37 patients (16%), including five patients (2%) with unsuccessful primary repair, mitral valve replacement with chordal sparing procedure was performed.
noted as a protruding, highly mobile segment with torn chordae. The localization of the pathology was performed according to the Carpentier nomenclature. Mitral regurgitation was assessed according to the European Association of Echocardiography (EAE) recommendations,11 vena contracta imaging of the mitral regurgitation jet was obtained, and proximal isovelocity surface area (PISA) imaging was performed (Fig. 1). An effective regurgitant orifice area (EROA) at least 0.3 cm2 or a regurgitant volume at least 60 ml indicated severe mitral regurgitation. The end-diastolic and end-systolic left ventricular diameters were measured using B-mode echocardiography. The left ventricular end-diastolic and endsystolic volumes, and left ventricular ejection fraction were calculated using a modified Simpson’s rule. The transmitral flow velocity was recorded from the apical four-chamber view. The mitral annular motion velocity was recorded at the septum and lateral wall using pulsed tissue Doppler imaging. Two-dimensional speckle-tracking echocardiography
Longitudinal strain and strain rate were determined from three standard apical views, as well as radial and circumferential strain rate from three parasternal short-axis views at basal, mid-papillar and apical levels, using two-dimensional STE with a gray-scale frame rate of 50–85 fps by two experienced physician echocardiographers, blinded to each other’s recordings. At each plane, one cardiac cycle was acquired (while the participant held his or her breath) and stored. Image analysis was performed offline on an EchoPAC’08 workstation (GE Healthcare) with automatically tracked speckles frame by frame throughout the cardiac cycle. The left ventricle was divided into 16 segments, with Fig. 1
Echocardiography
Standard echocardiography extended with STE (strain rate and strain imaging) was performed in all patients before surgery. All echocardiographic measurements were performed by an experienced, certified echocardiographer using a Vivid 7 ultrasound system (GE Healthcare, Milwaukee, Wisconsin, USA), equipped with a harmonic 3.5 MHz phased-array transducer. The presence of prolapsed or flail segments was reported. MVP was diagnosed by billowing of one or both mitral leaflets more than 2 mm above the mitral annulus in the long-axis parasternal view, whereas a flail segment was
Measure of the proximal isovelocity surface area radius for quantitative assessment of mitral regurgitation severity (apical four-chamber view, color-flow display).
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224 Journal of Cardiovascular Medicine 2014, Vol 15 No 3
only four segments at the apical level. Segments with tracking difficulties, reverberations or poor image quality were excluded manually [from 7456 recorded left ventricular segments, only 5854 (78.5%) were accepted for deformation analysis].
Fig. 2
Systolic strain rate was determined as the maximal negative (for longitudinal and circumferential) or positive (for radial) value during the ejection phase, and peak systolic strain as the magnitude of strain at the aortic valve closure. Peak longitudinal early diastolic filling strain rate was also measured. Pathology
Surgically excised valve tissue, consisting of the resected abnormal segment of the leaflet with chordae tendineae, was examined by an experienced pathologist, blinded to echocardiographic findings. Gross examination of excised mitral valve segment from patients with Barlow’s disease revealed the thickened leaflet. The chordae tendinae were irregularly thickened. In patients with FED, prolapsed segments were irregularly thickened with areas appearing more transparent than the remaining leaflet. The chordae tendinae showed irregular thinning or thickening. Almost one-quarter of patients with fibroelastic deficiency (39 patients, 22.5%) showed thickened prolapsed segment by gross examination. In these cases, the distinction was based on the condition of adjacent leaflet segments (thinned) according to direct visual assessment by the surgeon. For histologic examination, 5-mm thick sections were cut and stained with hematoxylin-eosin and with orcein, with a Van Gieson counterstain. The slides were examined under light microscopy. Myxomatous infiltration was characterized by significant thickening of the spongiosa with pooling of glycosaminoglycans. The spongiosa proliferates (Fig. 2) and invades the fibrosa. FED was characterized by fragmentation of the collagenous bundles within fibrosa (Fig. 3) and fragmentation, splitting and coiling of elastic fibers.
Histologic section of mitral valve showing extensive myxomatous changes in the leaflet in Barlow’s disease. Hematoxylin-eosin, 400.
reproducibility was expressed by the coefficient of repeatability (COR), interclass correlation coefficient (ICC), and the mean error (%). Statistical significance was set at P < 0.05. All statistical analyses were performed using Statistica 8 software (StatSoft Inc., Tulsa, Oklahoma, USA).
Results According to results of gross and histologic examination of the resected abnormal mitral valve segments, patients were divided into two groups. Barlow’s disease was identified by pathologist in 60 patients (25.8%), and FED in 173 patients (74.2%). The main pathologic findings by microscopy of valvular tissue specimens in Fig. 3
Statistical analysis
The variables are presented as mean SD. The categorical variables are presented as percentages. Differences between groups were analyzed using the two-sided Student’s t-test for continuous variables and the x2 test for categorical variables. Effect sizes for deformation indices were measured by Cohen’s d using means and standard deviations. Accuracy and predictive value of echocardiography for the detection of Barlow’s disease and FED were calculated according to standard formulae. The relationship between pairs of continuous variables was expressed by the Pearson correlation. Myocardial deformation indices were tested as dependent variables using univariate linear regression analyses to explore the significance of possible influencing factors. The
Alterations of collagenous bundles in mitral valve leaflet. Collagenous bundles are fragmented and coiled. Hematoxylin-eosin, 200.
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Left ventricular function in mitral valve disease Malev et al. 225
Table 1
Clinical characteristics of groups of patients with Barlow’s disease or fibroelastic deficiency before surgery Barlow’s disease (n ¼ 60)
FED (n ¼ 173)
P
48.2 12.7 66%
55.8 13.3 65%
0.0002 0.89
11 (18%) 25 (42%) 20 (33%) 4 (7%) 7.9 2.7 6.5 2.1 7 (12%) 73.9 15.2 135.2 14.3 79.8 8.7 24 (40%) 3 (5%)
36 (21%) 88 (51%) 40 (23%) 9 (5%) 8.2 2.9 6.8 2.4 26 (15%) 75.4 16.8 137.9 16.2 77.4 9.4 82 (47%) 10 (6%)
0.68 0.22 0.12 0.67 0.48 0.39 0.57 0.54 0.25 0.08 0.35 0.82
25 (42%) 37 (62%) 16 (27%) 1.98 0.18
83 (48%) 102 (59%) 58 (34%) 1.97 0.16
0.42 0.68 0.32 0.69
Age (years) Sex (men, %) NYHA class I II III IV Preoperative duration of the symptoms (mo.) Mitral regurgitation recognition to operation time (mo.) Atrial fibrillation (%) Heart rate (b.p.m.) SBP (mmHg) DBP (mmHg) Arterial hypertension, % Diabetes (%) Medical therapy b-Blockers (%) ACEI/ARB (%) Diuretics (%) BSA (m2)
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BSA, body surface area; FED, fibroelastic deficiency; NYHA, New York Heart Association.
Barlow’s disease patients were myxomatous degeneration in 100% and fibrosis in 33.2% of cases. Patients with Barlow’s disease, not surprisingly,3 were significantly younger than those with FED (Table 1). Both groups contained more men than women. Preoperatively, most patients in each group had mild symptoms (New York Heart Association, NYHA class I or II) and reported the same duration of symptoms (shortness of breath or fatigue). Also, according to the case reports, patients in both groups had a similar period between the first recognition of severe mitral regurgitation and surgery (Table 1). Atrial fibrillation was present only in 12% patients of Barlow’s disease group and 15% of FED group. There were no significant differences between groups in medical treatment, heart rate and blood pressure.
Table 2
Standard echocardiographic parameters of the studied patients before surgery are presented in Table 2. There were no significant differences in left ventricular dimensions and volumes nor in global systolic function between the groups (preoperative left ventricular end diastolic volume was increased and ejection fraction slightly decreased in both). Also there were no significant differences between the groups in number of patients with left ventricular enlargement and systolic dysfunction. Other chamber dimensions and volumes did not vary significantly from group to group. Preoperative global diastolic left ventricular function, evaluated by transmitral and tissue Doppler, was depressed equally in FED and Barlow’s disease groups. There was no difference between groups in systolic pulmonary pressure.
Preoperative echocardiographic parameters of the two groups of patients
EDD (mm) ESD (mm) ESD >40 mm (n/%) EDV (ml) ESV (ml) SV (ml) LVEF (%) LVEF
