Download Mechanisms of Acute Mitral Regurgitation in Patients

Mechanisms of Acute Mitral Regurgitation in Patients With
Takotsubo Cardiomyopathy
An Echocardiographic Study
Masaki Izumo, MD, PhD; Smruti Nalawadi, MD; Maiko Shiota, MD; Jayanta Das, MD;
Suhail Dohad, MD; Eiji Kuwahara, MD, PhD; Yoko Fukuoka, MD;
Robert J. Siegel, MD; Takahiro Shiota, MD, PhD
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Background—Recent studies have suggested acute mitral regurgitation (MR) as a potentially serious complication of
takotsubo cardiomyopathy (TTC); however, the mechanism of acute MR in TTC remains unclear. The aim of this study
was to elucidate the mechanisms of acute MR in patients with TTC.
Methods and Results—Echocardiography was used to assess the mitral valve and left ventricular outflow tract (LVOT)
pressure gradient in 47 patients with TTC confirmed by coronary angiography and left ventriculography. Mitral valve
assessment included coaptation distance, tenting area at mid systole in the long-axis view, and systolic anterior motion
of the mitral valve (SAM). Of the study patients, 12 (25.5%) had significant (moderate or severe) acute MR. In patients
with acute MR versus those without acute MR, we found lower ejection fraction (31.3⫾6.2% versus 41.5⫾10.6%,
P⫽0.001) and higher systolic pulmonary artery pressure (49.3⫾7.4 versus 35.5⫾8.9 mm Hg, P⬍0.001). Moreover, 6
of the 12 patients with acute MR had SAM, with peak LVOT pressure gradient ⬎20 mm Hg (average peak LVOT
pressure gradient, 81.3⫾35.8 mm Hg). The remaining 6 patients with acute MR revealed significantly greater mitral
valve coaptation distance (10.9⫾1.6 versus 7.8⫾1.4 mm, P⬍0.001) and tenting area (2.1⫾0.4 versus 0.95⫾0.25 cm2,
P⬍0.001) than those without acute MR. A multivariate analysis revealed that SAM and tenting area were independent
predictors of acute MR in patients with TTC (all P⬍0.001).
Conclusions—SAM and tethering of the mitral valve are independent mechanisms with differing pathophysiology that can
lead to acute MR in patients with TTC. (Circ Cardiovasc Imaging. 2011;4:392-398.)
Key Words: cardiomyopathy 䡲 mitral valve insufficiency 䡲 echocardiography
T
akotsubo cardiomyopathy (TTC), which also is called
apical ballooning syndrome or stress cardiomyopathy, is
recognized as transient left ventricular (LV) apical ballooning
and electrocardiographic changes that mimic acute myocardial infarction in the absence of obstructive coronary artery
disease.1–3 This syndrome generally has a favorable outcome;
however, some complications may occur in the acute
phase.4 – 6 Management of such patients remains difficult.4 – 6
Two recent studies suggested acute mitral regurgitation (MR)
as a potentially serious complication of TTC, which accounts
for 19% to 21% of patients with TTC.7,8 Both studies
concluded that the systolic anterior motion of the mitral valve
(SAM) plays a crucial role in the mechanism of acute MR
in patients with TTC, although only one third to one half
of the patients with acute MR had SAM. The mechanism of
acute MR without SAM is unclear. The aim of this study
was to elucidate the mechanisms of acute MR in patients
with TTC.
Clinical Perspective on p 398
Methods
Study Population
This study reviewed 48 consecutive patients with chest pain or
dyspnea and changes on ECGs who underwent coronary angiography and left ventriculography to confirm TTC in the Cedars-Sinai
Medical Center between October 2006 and May 2009. The inclusion
criteria were (1) balloon-like LV with apical akinesis or dyskinesis
on initial left ventriculography or echocardiogram, (2) ST-segment
or T-wave abnormalities on ECG and increases in blood concentrations of cardiac troponin level, (3) no significant coronary artery
stenosis confirmed by coronary angiography, and (4) absence of
pheochromocytoma and myocarditis.9 One patient with TTC who
had significant MR due to organic mitral valve disease was excluded;
thus, a total of 47 patients were included. All patients were given a
diagnosis of TTC by consensus of 2 experienced cardiologists. This
study was approved by the institutional review board of Cedars-Sinai
Medical Center.
Received November 3, 2010; accepted April 11, 2011.
From Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center and UCLA, Los Angeles, CA.
Correspondence to Takahiro Shiota, MD, PhD, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center and UCLA, 8700 Beverly Blvd, Los Angeles,
CA 90048. E-mail [email protected]
© 2011 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
392
DOI: 10.1161/CIRCIMAGING.110.962845
Izumo et al
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Figure 1. Mitral leaflet configurations in the parasternal longaxis echocardiogram.
Cardiac Catheterization and Blood Test
All patients underwent coronary angiography and left ventriculography within 24 hours after symptom onset. Left ventriculography
was used to calculate LV ejection fraction (EF) and LV volume using
the Simpson method. Venous blood was collected every 3 hours to
measure the troponin I concentration in the acute phase and continued until a peak value was observed.
Echocardiographic Examination
All patients with TTC underwent 2D and Doppler echocardiographic
examinations with an iE-33 system (Philips Medical Systems;
Andover, MA) within 24 hours of admission. Follow-up echocardiography was performed within 4 weeks (range, 1 to 4 weeks) after
initial presentation. The LV wall motion score index (WMSI) was
calculated on the basis of a 16-segment model recommended by the
American Society of Echocardiography.10 Mitral valve configuration
at mid systole was assessed in a parasternal long-axis view. Mitral
valve coaptation distance was defined as the distance from the mitral
annular plane to mitral leaflet coaptation point. The mitral valve
tenting area was measured by the area enclosed between the annular
plane and mitral leaflets (Figure 1).11
MR was quantitated by measuring the vena contracta (narrowest
jet origin) in a long-axis view perpendicular to the coaptation line
averaged in 3 cardiac cycles. Additionally, MR jet area and left atrial
(LA) area at mid systole was measured by area trace method on the
4-chamber view, and their ratio (MR jet area/LA area) was calculated as previously reported.12 Vena contracta width (VCW) ⱖ0.3
cm and MR jet area/LA area ⱖ20% were considered as moderate in
degree.13 All parameters of mitral deformation were obtained at mid
systole.
LV outflow tract (LVOT) pressure gradients were measured by
continuous-wave Doppler echocardiography through the LVOT. A
dynamic gradient was considered significant if peak LVOT pressure
gradient was ⬎20 mm Hg by continuous-wave Doppler echocardiography based on the modified Bernoulli equation. 4 With
continuous-wave Doppler echocardiography, the maximum peak
tricuspid regurgitant velocity recorded from any view was used to
determine the pulmonary artery systolic pressure (PASP) with the
simplified Bernoulli equation [PASP⫽4(peak velocity)2⫹mean right
atrial pressure]14; mean right atrial pressure was estimated based on
the most recent American Society of Echocardiography
recommendation.15
Statistical Analysis
All values are expressed as mean⫾SD. An unpaired t test was used
to compare the continuous variables between the patients with MR
Acute MR in Takotsubo Cardiomyopathy
393
and those without MR, and the ␹2 and Fisher exact test were used for
the categorical variables. A paired t test was used to compare initial
and follow-up measurements. Univariate logistic regressions were
used to relate clinical and echocardiographic variables to prevalence
of MR. Multivariate logistic regression was performed to identify
factors associated with prevalence of MR. Significant variables on
univariate analysis entered into models were peak LVOT pressure
gradient, PASP, and WMSI on clinical and echocardiographic
parameters in patients with TTC MR with SAM and LVEF, LV
end-systolic volume, tenting area, coaptation distance, mitral annular
dimension, and PASP on clinical and echocardiographic parameters
in patients with TTC MR without SAM. Differences were considered
significant if P⬍0.05. Both intraobserver and interobserver variabilities for measurements of mitral valve tenting area, coaptation
distance, VCW, and MR jet area/LA area were obtained by analysis
of 10 random images by 2 independent, blinded observers and by the
same observers at 2 different times. The results were analyzed by
both the intraclass correlation coefficient and the Bland-Altman
method.16 Statistical analyses were performed using SPSS version
17.0 (SPSS, Inc; Chicago, IL) software.
Results
Of 47 patients with TTC (mean age, 68.5⫾15.4 years; range,
28 to 89 years), 44 (93.6%) were women. Physical stressors
such as pneumonia, asthma attack, traffic accident, hematemesis, and overwork were identified in 22 (46.8%) patients,
and emotional stressors were also identified in 9 (19.1%)
patients. On ECG, ST-segment elevation was present in 24
(51.0%) patients, ST depression in 5 (10.6%), and T-wave
inversion in 18 (38.3%). Twelve (25.5%) patients had significant (moderate or severe) acute MR on presentation (mean
VCW, 0.60⫾0.19 cm; MR jet area/LA area, 53.2⫾10.9%).
Of these, 10 (83.3%) patients with MR were women, and 6
(50%) had a peak LVOT pressure gradient ⬎20 mm Hg
(average peak LVOT pressure gradient, 81.3⫾35.8 mm Hg)
and SAM.
Comparison of Clinical and
Echocardiographic Characteristics
Comparison of clinical and echocardiographic characteristics
between patients with TTC with MR and those without MR
are listed in Table 1. Age, sex, and troponin I levels did not
significantly differ between the 2 groups. We found lower
LVEF (P⫽0.006) and higher mitral tenting area, peak LVOT
pressure gradient, and PASP (all P⬍0.001) in patients with
TTC with MR. The ratio of patients with TTC who presented
with shortness of breath on admission also was greater in
those with MR than in those without MR (75.0% versus
28.5%, P⫽0.003). Moreover, we stratified 12 patients with
MR into 2 groups based on the presence or absence of a peak
LVOT pressure gradient ⬎20 mm Hg. All 6 patients with
increased LVOT pressure gradients had SAM, and the remaining 6 patients had significantly higher mitral valve
coaptation distance (10.9⫾1.6 versus 6.8⫾0.6 mm,
P⬍0.001) and tenting area (2.1⫾0.4 versus 1.0⫾0.1 cm2,
P⬍0.001), larger LV end-systolic volume (61.8⫾17.2 versus
49.1⫾4.9 mL, P⫽0.035), and lower EF (28.0⫾6.9 versus
34.8⫾2.9, P⫽0.001) than patients with TTC with MR due to
SAM. All patients with MR are listed in Table 2.
394
Circ Cardiovasc Imaging
Table 1.
July 2011
Patient Characteristics
Patients With Significant MR
Patients Without
Significant MR (n⫽35)
Age, y
All (n⫽12)
68.5⫾15.4
Female, %
71.6⫾8.8
97.1
Troponin I, ␮g/L
With SAM (n⫽6)
71.6⫾7.3
83.3
Without SAM (n⫽6)
71.5⫾10.7
83.3
83.3
4.2⫾5.7
5.1⫾3.1
6.6⫾3.7
4.1⫾1.5
LVEF, %
41.5⫾10.6
31.3⫾6.2*
34.8⫾2.9*
28.0⫾6.9*†
LVEDV, mL
89.5⫾15.4
84.9⫾14.9
81.3⫾9.3
86.0⫾18.9
LVESV, mL
50.4⫾12.4
56.0⫾14.2
49.1⫾4.9
61.8⫾17.2*†
MR VCW, cm
0.02⫾0.08
0.60⫾0.19*
0.70⫾0.14*
0.52⫾0.20*
MR jet area/LA area, %
1.2⫾4.0
53.2⫾10.9*
56.0⫾10.1*
50.5⫾11.8*
Peak LVOT pressure gradient,
mm Hg
9.7⫾13.3
43.0⫾46.8*
81.3⫾35.8*†
4.7⫾1.9
0.95⫾0.25
1.5⫾0.6*
1.0⫾0.1
2.1⫾0.4*†
7.8⫾1.4
9.0⫾2.4
6.8⫾0.6
10.9⫾1.6*†
Mitral annular dimension, mm
26.6⫾3.6
30.2⫾3.5*
29.3⫾3.2
31.2⫾3.7*
PASP, mm Hg
35.5⫾8.9
49.3⫾7.4*
50.3⫾9.6*
48.2⫾5.9*
1.9⫾0.1
2.2⫾0.2*
2.1⫾0.2*
Tenting area, cm2
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Coaptation distance, mm
WMSI
2.3⫾0.2*†
Data are presented as mean⫾SD, unless otherwise indicated. LA indicates left atrium; LVEDV, left ventricular
end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVOT, left
ventricular outflow tract; MR, mitral regurgitation; PASP, pulmonary artery systolic pressure; VCW, vena contracta
width; WMSI, wall motion score index.
*Significant difference (P⬍0.05) patients without MR vs each group.
†Significant difference (P⬍0.05) patients with SAM vs without SAM.
Relationship Between Clinical and
Echocardiographic Findings and Acute MR
in TTC
significant variables obtained by the univariate analysis,
resulting in peak LVOT pressure gradient and mitral valve
tenting area (all P⬍0.001) as independent predictors of acute
MR in patients with TTC (Tables 3 and 4).
Univariate analysis was performed in patients with TTC MR
with SAM (versus patients without MR) and those without
SAM (versus patients without MR) (Tables 3 and 4). The
results of the univariate analysis demonstrated that the occurrence of acute MR in patients with TTC was significantly
associated with LV ejection fraction, peak LVOT pressure
gradient, mitral valve tenting area, PASP, and WMSI, respectively. The multivariate analysis also was performed to assess
Table 2.
Patient
No.
Follow-Up Echocardiographic Findings
Follow-up echocardiography was performed in 39 patients
with TTC (83.0%) within 4 weeks after initial presentation.
Figures 2 and 3 show 2D echocardiograms obtained at initial
presentation and at follow-up in 2 typical patients with TTC
with MR due to SAM and tethering. LVEF, WMSI, VCW,
Characteristics of 12 Patients With TTC MR
Age/Sex,
y
Triggered
Event
ECG on
Admission
LVEF,
%
Peak LVOT Pressure
Gradient, mm Hg
SAM
Tenting
Area, cm2
Coaptation
Distance, mm
PASP,
mm Hg
1
70/F
Physical stress (overwork)
ST depression
35
104
⫹
0.99
6.1
43
2
76/F
Emotional stress
ST elevation
32
5
⫺
1.75
9.1
40
3
79/F
Unknown
ST elevation
35
84
⫹
0.91
7.5
56
4
75/F
Emotional stress
ST elevation
33
114
⫹
1.01
6.6
50
5
66/F
Physical stress (pneumonia)
T inversion
40
83
⫹
1.22
7.4
43
6
66/M
Physical stress (chemotherapy)
ST elevation
20
4
⫺
2.5
12.3
52
7
61/F
Physical stress (hematemesis)
T inversion
22
3
⫺
2.52
12.4
45
8
86/F
Unknown
T inversion
30
8
⫺
1.92
9.1
45
9
80/F
Unknown
T inversion
34
3
⫺
1.8
6.8
44
10
60/F
Unknown
ST elevation
32
5
⫺
1.84
10.2
43
11
61/F
Physical stress (overwork)
ST elevation
32
45
⫹
0.93
10.2
65
79/M
Physical stress (colitis)
T inversion
34
38
⫹
1
6.3
40
12
ECG indicates electrocardiography; SAM, systolic anterior motion of the mitral valve; TTC, takotsubo cardiomyopathy. Other abbreviations as in Table 1.
Izumo et al
Acute MR in Takotsubo Cardiomyopathy
395
Table 3. Analysis of Clinical and Echocardiographic Parameters in Patients With TTC MR
With SAM
Univariate Analysis
OR (95% CI)
Multivariate Analysis
P
Age, y
1.14 (0.82–1.72)
0.078
LVEF, %
0.91 (0.80–1.04)
0.107
LVEDV, mL
0.71 (0.39–1.27)
0.238
LVESV, mL
0.988 (0.87–1.12)
0.967
3.64 (1.64–8.07)
⬍0.001
Peak LVOT pressure gradient, mm Hg
2
OR (95% CI)
P
3.16 (1.26–7.92)
⬍0.001
Tenting area, cm
1.02 (0.98–1.05)
0.496
Coaptation distance, mm
1.16 (0.79–1.76)
0.695
Mitral annular dimension, mm
1.10 (0.99–1.24)
0.087
PASP, mm Hg
1.44 (1.06–1.95)
0.004
1.56 (0.92–2.02)
0.065
WMSI
1.71 (1.17–2.52)
0.003
1.14 (0.24–3.21)
0.805
OR indicates odds ratio. Other abbreviations as in Tables 1 and 2.
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and MR jet area/LA area values were significantly improved
at follow-up compared with initial presentation (LVEF,
41.2⫾11.7% versus 58.3⫾11.3%; WMSI, 2.0⫾0.2 versus
1.1⫾0.2; VCW, 0.60⫾0.19 versus 0.1⫾0.05 cm; MR jet
area/LA area, 53.2⫾10.9% versus 8.2⫾2.5%; all P⬍0.001).
Recovery in LV systolic function was similar in patients with
and without MR (58.4⫾6.7% versus 59.4⫾11.9%, P⫽0.845).
No abnormal LVOT pressure gradients were observed at
follow-up. In patients with MR without SAM, coaptation
distance and tenting area significantly decreased at follow-up
compared to initial presentation (coaptation distance,
10.9⫾1.6 versus 7.9⫾0.5 mm; tenting area, 2.1⫾0.4 versus
1.1⫾0.2 cm2; all P⬍0.001). No other significant echocardiographic changes were detected by 2D and Doppler echocardiography. During the mean follow-up period of 25.5⫾6.7
months, no patients had recurrence of TTC.
Reproducibility of
Echocardiographic Measurements
The intraobserver variability as assessed by intraclass coefficient were 0.91 (95% CI, 0.75 to 0.97) for mitral valve tenting
area, 0.87 (95% CI, 0.72 to 0.94) for mitral valve coaptation
distance, 0.88 (95% CI, 0.78 to 0.93) for VCW, and 0.90
(95% CI, 0.77 to 0.96) for MR jet area/LA area. The
interobserver variability on these measurements were 0.89
(95% CI, 0.48 to 0.99), 0.84 (95% CI, 0.36 to 0.94), 0.88
(95% CI, 0.41 to 0.98), and 0.89 (95% CI, 0.48 to 0.97),
respectively. The Bland-Altman method showed that intraobserver and interobserver variabilities, respectively, were
0.17 and 0.17 cm2 for mitral valve tenting area, 0.5 and
0.6 mm for mitral valve coaptation distance, 0.05 and 0.06 cm
for VCW, and 3.2% and 4.1% for MR jet area/LA area.
Discussion
To our knowledge, this study is the first to demonstrate that
(1) there are 2 entirely different mechanisms responsible for
acute MR in patients with TTC and (2) PASP is significantly
higher in patients with TTC with MR than in those without
MR. In patients with TTC, complications may occur in the
acute phase.4 – 6 Heart failure with or without pulmonary
edema is the most common clinical complication.17 In the
Table 4. Analysis of Clinical and Echocardiographic Parameters in Patients With TTC MR
Without SAM
Univariate Analysis
OR (95% CI)
Multivariate Analysis
P
Age, y
0.98 (0.96 –1.00)
0.706
LVEF, %
1.49 (1.02–2.17)
0.048
LVEDV, mL
0.97 (0.55–1.72)
0.846
LVESV, mL
1.04 (1.02–1.12)
0.047
Peak LVOT pressure gradient, mm Hg
0.80 (0.55–1.16)
0.288
Tenting area, cm2
5.46 (2.54–9.62)
Coaptation distance, mm
3.67 (1.11–12.1)
Mitral annular dimension, mm
OR (95% CI)
P
0.60 (0.13–2.78)
0.563
0.80 (0.47–1.37)
0.476
⬍0.001
3.17 (1.04–8.62)
⬍0.001
0.013
1.69 (0.91–3.17)
0.212
1.44 (1.05–2.06)
0.023
0.97 (0.55–1.77)
0.328
PASP, mm Hg
1.44 (1.06–1.95)
0.029
1.27 (0.91–1.76)
0.363
WMSI
1.30 (0.86–1.93)
0.288
OR indicates odds ratio. Other abbreviations as in Tables 1 and 2.
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July 2011
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Figure 2. Two-dimensional transthoracic echocardiography in
patients with mitral regurgitation (MR) due to systolic anterior
motion of the mitral valve (SAM). A, Severe MR at initial presentation. B, Mitral valve SAM at initial presentation. C, Only trivial
MR was found at follow-up. D, Mitral valve SAM was not found
at follow-up. Note that all 4 images are from apical long-axis
views. LA indicates left atrium; LV, left ventricle.
present study, we found that ⬇25% of the patients with TTC
had acute MR, which supported the results of earlier studies.7,8 Approximately one fifth of patients with TTC have
clinically significant acute MR. Despite the favorable outcome of TTC, the associated presence of significant acute
MR increases the risks of acute deterioration and adverse
outcome in patients with TTC.8,18 In the present study, acute
MR was identified in patients with TTC with lower EF; PASP
was higher in patients with TTC with MR than in those
without MR. The number of patients who presented with
shortness of breath was greater in those with MR than in those
without MR. Therefore, special attention should be paid to
the hemodynamics in the acute phase of TTC, which often
correspond to New York Heart Association class III heart
failure.19
Earlier studies indicated that SAM was regarded as 1 of the
causes of significant MR.7,20 Parodi et al7 reported that
approximately one third of patients with TTC with significant
MR had SAM. It is well-known that in patients with hypertrophic cardiomyopathy, SAM is associated with significant
MR.21,22 Some case reports also demonstrated LVOT obstruction with SAM and acute MR in TTC.23,24 In the present
study, 12% of all patients with TTC, 50% of the patients with
TTC with significant MR, had SAM, which was identified as
1 of the predictors of acute MR in patients with TTC by
multivariate analysis.
However, we found another independent factor of acute
MR in patients with TTC: mitral valve tenting area. Severe
Figure 3. Two-dimensional transthoracic echocardiography in
patients with mitral regurgitation (MR) due to apical displacement of the mitral valve. A, Severe MR at initial presentation. B,
Apical displacement of the mitral leaflets was found at initial
presentation. C, Only trivial MR was found at follow-up. D, Normal mitral leaflets close at the annular level at follow-up. Note
that all 4 images are from the apical 4-chamber view. Abbreviations as in Figure 2.
mitral valve tenting is known as an important cause of
ischemic MR.25–27 Ischemic MR, a relatively common complication of coronary artery disease, occasionally occurs in
the acute or chronic phase.27 Leaflet tethering by papillary
muscle displacement due to regional or global LV dysfunction has been suggested as the main mechanism of chronic
ischemic MR.25–27 In the present study, patients with MR
without SAM had lower EF and higher WMSI and end-systolic volume than those with MR due to SAM. These findings
suggest the presence of LV systolic dysfunction and LV
enlargement in patients with MR without SAM rather than in
those with MR due to SAM. This finding is consistent with
previous explanations for the etiology of ischemic MR.25–27
Our finding of simultaneous improvement of mitral valve
tethering and MR severity in patients with TTC is particularly
important for the understanding of the mechanism of acute
MR. Of note, another study suggested papillary muscle
dysfunction or displacement as a potential cause of MR in
patients with TTC without any quantitative data.8
Clinical Implication
The present study observations imply that TTC should be
kept in mind as a potential cause of acute MR. Early detection
is important for proper management of patients with this
condition. Recognition of the difference in mitral geometry
gives new insight into the mechanisms of acute MR in TTC.
The current American College of Cardiology/American Heart
Izumo et al
Association guidelines recommend mitral valve surgery in
symptomatic patients with severe acute MR28; however, our
results support the idea that aggressive medical treatment of
TTC would be the first priority because acute MR in TTC is
reversible.
Study Limitations
Because this study was retrospective, the timing of follow-up
echocardiography varied. However, LV function and wall
motion and MR were improved at follow-up as expected. The
logistic regressions are not necessarily representative of the
population given the relatively low number of subjects versus
the number of predictors. We could not conduct a large-scale
study because of the low prevalence of the condition. Further
prospective investigation with a larger population is
warranted.
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Conclusions
SAM and tethering of the mitral valve are independent
mechanisms with differing pathophysiology that can lead to
acute MR in patients with TTC. These findings imply that
echocardiography should be performed systematically in
patients with TTC to identify whether MR is present as well
as to assess its mechanism.
Acknowledgments
We would like to thank Dr. and Mrs. Paul I. Terasaki for their kind
support and encouragement.
Disclosures
None.
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CLINICAL PERSPECTIVE
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Despite the favorable outcome of takotsubo cardiomyopathy (TTC) in general, the presence of significant acute mitral
regurgitation (MR) increases the risks of acute deterioration and adverse outcome in TTC. However, the mechanism of
acute MR in TTC remains unclear. In this study, we elucidated the mechanisms of acute MR in TTC; apical tethering and
systolic anterior motion of the mitral valve are 2 independent mechanisms that can lead to acute MR in TTC. Our finding
of simultaneous improvement of apical tethering and MR severity in the patients with TTC is particularly important for the
understanding of the mechanism of acute MR. Based on the study results, TTC should be regarded as a potential cause of
acute MR. In addition, pulmonary artery systolic pressure is significantly higher in patients with TTC with MR than in
those without MR. Therefore, early detection of MR is important for proper management of patients with TTC. The current
American College of Cardiology/American Heart Association guidelines recommend mitral valve surgery in symptomatic
patients with severe acute MR; however, the present results support the idea that aggressive medical treatment of TTC
would be the first priority because acute MR in TTC is reversible. These findings imply that echocardiography should be
systematically performed in patients with TTC to identify MR and assess its mechanism.
Mechanisms of Acute Mitral Regurgitation in Patients With Takotsubo Cardiomyopathy:
An Echocardiographic Study
Masaki Izumo, Smruti Nalawadi, Maiko Shiota, Jayanta Das, Suhail Dohad, Eiji Kuwahara,
Yoko Fukuoka, Robert J. Siegel and Takahiro Shiota
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Circ Cardiovasc Imaging. 2011;4:392-398; originally published online April 15, 2011;
doi: 10.1161/CIRCIMAGING.110.962845
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