Results
The study included 103 patients with MVP and a control group of 40
people and 34 of these MVP patients (33%) had MAD. Patients were
divided into groups as MAD (+) (n=34), MAD (-) (n=69) and control
(n=40). The clinical and demographic characteristics of the study groups
are shown in Table-1. There was no statistically significant difference
between the groups in terms of gender, age, BMI, beta-blocker use and
smoking habits. When symptom types such as palpitation, dyspnea,
fatigue, chest pain and syncope were compared, no significant difference
was found between MAD (+) and MAD (-) groups. However, number of
symptoms on admission was not similar. Number of patients with 2 or more
symptoms was higher in the MAD (+) group than in the MAD (-) group
(4.3% vs 44.1%, p<0.001). T negativity in the inferior leads
on electrocardiography was more frequent in the MAD (+) group than in
the MAD (-) patients (4.3% vs 20.6%, p=0.014).
When the groups were compared in terms of echocardiographic and MRI
findings (table 2), left ventricular ejection fraction (LVEF), posterior
wall thickness (PW), interventricular septum to posterior wall ratio
(IVS/PW), left ventricular end-diastolic diameter (LVEDD) and
end-systolic diameter (LVESD), apical longitudinal strain (ALS) levels
were similar. Mitral regurgitation degree (p=0.001), frequency of
Pickelhaube sign (17.6% vs. 1.4%, p=0.005) and LGE (35.3% vs. 10.6%,
p=0.002) were higher in MAD (+) patients compared to MAD (-) patients.
When the left atrial volume index, TDI lateral Sa, global longitudinal
strain (GLS), basal longitudinal strain (BLS), mid-ventricular
longitudinal strain(MVLS) levels were compared, the difference between
the 3 groups was statistically significant. GLS of the MAD (+) group was
-23.1±2.1 and this was -23.5±2.3 for the MAD (-), -24.5±2.2 for the
control group (p<0.001). BLS of the MAD (+), MAD (-) and
control groups were -19.6±1.5, -20.5±1.9 -23.3±1.2, respectively, with a
P value <0.001. For the BLS of MAD (+), MAD (-) and control
groups, these values were -22.2±1.7, -23.2±2.2 and -24.5±1.8;
(p<0.001) and for MVLS, -22.2±1.7, -23.2±2.2 and -24.5±1.8
(P<0.001), respectively. The mean MAD distance was 7.8±3.2 mm
in MAD (+) patients.
The relationship between GLS level and MAD distance in MAD (+) patients
was evaluated by pearson correlation analysis (figure 1). It was
observed that as the GLS level decreased, the MAD distance increased
statistically significantly (r:0.694, p<0.001). Then, the
relationship between BLS level and MAD distance in MAD (+) patients was
evaluated by pearson correlation analysis (figure 2). It was observed
that as the BLS level decreased, the MAD distance increased
statistically significantly (r:0.715, p<0.001).
Discussion
The main finding of our study is the numeric decrease in longitudinal
strain in MVP patients with MAD when compared to both MAD (-) MVP and
control groups. This difference was detected for both global and
segmental longitudinal strain. We interpreted this result as a
reflection of partial loss of basal support during systole for the
ventricular myocardium in significant MAD. The normal mitral annulus has
roots located within the ventricular myocardium and these roots provide
tight anchoring of the annulus to the ventricular myocardium (7). MAD
occurs when these roots of the mitral annulus separate from the
ventricular myocardium or fail to adhere sufficiently. However, the data
about the functional implications of MAD and related ventricular
dysfunction in the literature is scarce. First study in Medline about
this subject was reported by Lee et al which investigated the 3D
structure of MAD and its functional importance. In their study 42% of
the 101 MVP patients were having MAD and mean dislodgement distance was
8.9 cm. Both results were compatible with ours. However, they found that
although MVP had a reductive effect on left ventricular global
longitudinal strain (LV-GLS) when compared to the control group with
normal mitral valve, MAD positivity didn’t have any additional effect on
LV-GLS. This result was opposing our main finding. One of the main
differences between our and their study population was age. Mean age of
our and their MAD+ MVP groups were 35.7±14.2 and 56±13 respectively. A
systematic review defining the features of MAD has revealed that average
age of these patients was 62 years in the literature. Therefore, our
study population is younger, mostly composed of Barlow’s disease,
suggesting that functional effects of MAD may show different
characteristics according to the age period in which it is detected, and
this may be due to etiological differences (8).
A case-control study by Wang et al examined the strain parameters of 21
MAD+ and 21MAD- MVP patients. MAD was causing a significant decrease in
basal longitudinal strain by TTE, basal inferolateral (BIL), basal
circumferential and basal radial strain by cardiac magnetic resonance
imaging (CMR). Moreover, they concluded that global circumferential
strain by CMR was independently associated with the diagnosis of MAD.
They claimed the difference between TTE and CMR as the TTE strain
analysis couldn’t catch the significant difference in strain parameters
of MAD+ and MAD- MVP patients however CMR could. These results may be
attributable to some confounding factors as the relatively small sample
size and study design. In our study, all the strain differences were
found by TTE evaluation (5). More recently, Sanoglioni et al analyzed 93
MVP patients, 34.4% of which were MAD+ and showed significantly
impaired LV-GLS (-17.2 ± 1.4 vs -19.4 ± 3.0%, p < 0.001) and
LV-GCS (-16.3 ± 4.1 vs -20.4 ± 4.9, p < 0.001) in MAD+ MVP
patients compared to MAD- MVP cases, despite similar LV ejection
fraction (9).
In our study 103 MVP patients and 40 control subjects were included and
MAD was detected in 34(33%) of the MVP patients, compatible with most
other studies in the literature. MAD is detected in 20 to 58 percent of
the patients diagnosed with MVP and the prevalence is even higher in
myxomatous MVP (1). Nonetheless, 21% of MAD patients don’t have MVP
(4). In our study, all MAD patients were having MVP.
Our results provided that longitudinal strain is significantly affected
in MAD+ patients when compared to MAD- MVP patients. Longitudinal strain
and especially the GLS provides information about the functioning of
longitudinal fibres and LV remodelling. It is known to be a predictor of
cardiovascular outcome (10). Therefore our results are important in
terms of detecting early myocardial dysfunction related to MAD
especially in the younger patients. Moreover, in our study MVP patients
with MAD had more severe mitral insufficiency when compared to the
MAD-group. This result may be explained by the changes observed in
annulus dynamics in patients with MAD. The mitral annulus enlarge more
at the end of the systole (paradoxical systolic dilatation) and
flattening of the annulus rather than physiologic saddling (paradoxical
annular unsaddling) is a feature of MAD. It has been shown that MAD is
associated with deformity of mitral leaflets and chordae tendienae.
Furthermore, extend of disjunction and degree of mitral regurgitation
are shown to be correlated (8). Likewise, Dumont et al have proved that
annular dilatation due to MAD+ Barlow’s mitral valve disease causes more
severe mitral regurgitation (11).
All the above mentioned features of MAD positivity in patients with MAD
also may explain the increased number of symptoms in this group, another
finding of our study, when compared to MAD- group, owing to more severe
functional deformation.
Malignant MVP is characterized with increased sudden cardiac death risk,
bileaflet prolapse, ECG repolarization abnormalities, papillary muscle
and inferobasal wall fibrosis and its main echo finding is MAD. This
entity also includes another term arrhythmic MVP (AMVP) which usually
presents with frequent premature ventricular contractions and T-wave
inversion in the inferolateral leads (12). Although we didn’t define a
subgroup as malignant MVP of AMVP, our results were compatible with the
literature such that T wave inversion in the inferolateral leads was
detected in 20.6% of MAD+ group which was significantly more common
than the MAD (-) group (4.3%) (P=0.014). LV fibrosis especially at the
papillary muscles and inferobasal wall of the left ventricle can be
detected as late gadolinium enhancement(LGE) in patients with MAD and
previous reports showed that LGE can be seen as high as 40-47% of these
patients (5,13). Likewise, in our study 35.3% of MAD+ MVP patients had
LGE in CMR whereas this percentage was only 10% for MAD- MVP patients.
Actually these areas of LGE in MAD+ MVP patients were found to be
related with unipolar low voltage areas which are accepted as a
potential substrate for ventricular arrhythmias(VA) and sudden cardiac
death(SCD) (14). This relationship between LGE and VA and SCD in
patients with MVP was also supported by other studies (3,15).
Another important finding of our study was the higher frequency of
Pickelhaube sign in MAD+ MVP patients. This sign is a high velocity
mid-systolic spike gathered from the lateral mitral annulus by tissue
Doppler imaging, due to the stretching effect of prolapsing leaflet on
posteromedial papillary muscle. As LGE, this sign was found to be a
noninvasive imaging marker associated with SCD in MVP in previous
studies (16).
We detected this sign in 17.6% of MAD+ MVP patients whereas only %1.4
of the MAD- MVP group had this sign on TTE.
In our study, mean disjunction distance was 7.8±3.2 mm There is no limit
to define the movement of annulus as disjunction. In fact, detachment of
the mitral annulus from myocardium may range between a few millimeters
to more than 1 centimeter in the literature (17). Increased distance
also increases the risk of SCD and it is reported that disjunction
> 8.5 mm was predictive of VA (18).