mechanisms of acute mitral regurgitation in patients...

Mechanisms of Acute Mitral Regurgitation in Patients WithTakotsubo 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

Background—Recent studies have suggested acute mitral regurgitation (MR) as a potentially serious complication oftakotsubo cardiomyopathy (TTC); however, the mechanism of acute MR in TTC remains unclear. The aim of this studywas 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 valveassessment included coaptation distance, tenting area at mid systole in the long-axis view, and systolic anterior motionof the mitral valve (SAM). Of the study patients, 12 (25.5%) had significant (moderate or severe) acute MR. In patientswith 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, 6of the 12 patients with acute MR had SAM, with peak LVOT pressure gradient �20 mm Hg (average peak LVOTpressure gradient, 81.3�35.8 mm Hg). The remaining 6 patients with acute MR revealed significantly greater mitralvalve 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 independentpredictors 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 canlead to acute MR in patients with TTC. (Circ Cardiovasc Imaging. 2011;4:392-398.)

Key Words: cardiomyopathy � mitral valve insufficiency � echocardiography

Takotsubo cardiomyopathy (TTC), which also is calledapical ballooning syndrome or stress cardiomyopathy, is

recognized as transient left ventricular (LV) apical ballooningand electrocardiographic changes that mimic acute myocar-dial infarction in the absence of obstructive coronary arterydisease.1–3 This syndrome generally has a favorable outcome;however, some complications may occur in the acutephase.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 accountsfor 19% to 21% of patients with TTC.7,8 Both studiesconcluded that the systolic anterior motion of the mitral valve(SAM) plays a crucial role in the mechanism of acute MRin patients with TTC, although only one third to one halfof the patients with acute MR had SAM. The mechanism ofacute MR without SAM is unclear. The aim of this studywas to elucidate the mechanisms of acute MR in patientswith TTC.

Clinical Perspective on p 398

Methods

Study PopulationThis study reviewed 48 consecutive patients with chest pain ordyspnea and changes on ECGs who underwent coronary angiogra-phy and left ventriculography to confirm TTC in the Cedars-SinaiMedical Center between October 2006 and May 2009. The inclusioncriteria were (1) balloon-like LV with apical akinesis or dyskinesison initial left ventriculography or echocardiogram, (2) ST-segmentor T-wave abnormalities on ECG and increases in blood concentra-tions of cardiac troponin level, (3) no significant coronary arterystenosis confirmed by coronary angiography, and (4) absence ofpheochromocytoma and myocarditis.9 One patient with TTC whohad significant MR due to organic mitral valve disease was excluded;thus, a total of 47 patients were included. All patients were given adiagnosis of TTC by consensus of 2 experienced cardiologists. Thisstudy was approved by the institutional review board of Cedars-SinaiMedical 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 DOI: 10.1161/CIRCIMAGING.110.962845

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Cardiac Catheterization and Blood TestAll patients underwent coronary angiography and left ventriculog-raphy within 24 hours after symptom onset. Left ventriculographywas used to calculate LV ejection fraction (EF) and LV volume usingthe Simpson method. Venous blood was collected every 3 hours tomeasure the troponin I concentration in the acute phase and contin-ued until a peak value was observed.

Echocardiographic ExaminationAll patients with TTC underwent 2D and Doppler echocardiographicexaminations with an iE-33 system (Philips Medical Systems;Andover, MA) within 24 hours of admission. Follow-up echocardi-ography was performed within 4 weeks (range, 1 to 4 weeks) afterinitial presentation. The LV wall motion score index (WMSI) wascalculated on the basis of a 16-segment model recommended by theAmerican Society of Echocardiography.10 Mitral valve configurationat mid systole was assessed in a parasternal long-axis view. Mitralvalve coaptation distance was defined as the distance from the mitralannular plane to mitral leaflet coaptation point. The mitral valvetenting area was measured by the area enclosed between the annularplane and mitral leaflets (Figure 1).11

MR was quantitated by measuring the vena contracta (narrowestjet origin) in a long-axis view perpendicular to the coaptation lineaveraged in 3 cardiac cycles. Additionally, MR jet area and left atrial(LA) area at mid systole was measured by area trace method on the4-chamber view, and their ratio (MR jet area/LA area) was calcu-lated as previously reported.12 Vena contracta width (VCW) �0.3cm and MR jet area/LA area �20% were considered as moderate indegree.13 All parameters of mitral deformation were obtained at midsystole.

LV outflow tract (LVOT) pressure gradients were measured bycontinuous-wave Doppler echocardiography through the LVOT. Adynamic gradient was considered significant if peak LVOT pressuregradient was �20 mm Hg by continuous-wave Doppler echocardi-ography based on the modified Bernoulli equation.4 Withcontinuous-wave Doppler echocardiography, the maximum peaktricuspid regurgitant velocity recorded from any view was used todetermine the pulmonary artery systolic pressure (PASP) with thesimplified Bernoulli equation [PASP�4(peak velocity)2�mean rightatrial pressure]14; mean right atrial pressure was estimated based onthe most recent American Society of Echocardiographyrecommendation.15

Statistical AnalysisAll values are expressed as mean�SD. An unpaired t test was usedto compare the continuous variables between the patients with MR

and those without MR, and the �2 and Fisher exact test were used forthe categorical variables. A paired t test was used to compare initialand follow-up measurements. Univariate logistic regressions wereused to relate clinical and echocardiographic variables to prevalenceof MR. Multivariate logistic regression was performed to identifyfactors associated with prevalence of MR. Significant variables onunivariate analysis entered into models were peak LVOT pressuregradient, PASP, and WMSI on clinical and echocardiographicparameters in patients with TTC MR with SAM and LVEF, LVend-systolic volume, tenting area, coaptation distance, mitral annulardimension, and PASP on clinical and echocardiographic parametersin patients with TTC MR without SAM. Differences were consideredsignificant if P�0.05. Both intraobserver and interobserver variabil-ities for measurements of mitral valve tenting area, coaptationdistance, VCW, and MR jet area/LA area were obtained by analysisof 10 random images by 2 independent, blinded observers and by thesame observers at 2 different times. The results were analyzed byboth the intraclass correlation coefficient and the Bland-Altmanmethod.16 Statistical analyses were performed using SPSS version17.0 (SPSS, Inc; Chicago, IL) software.

ResultsOf 47 patients with TTC (mean age, 68.5�15.4 years; range,28 to 89 years), 44 (93.6%) were women. Physical stressorssuch as pneumonia, asthma attack, traffic accident, hemate-mesis, 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-waveinversion in 18 (38.3%). Twelve (25.5%) patients had signif-icant (moderate or severe) acute MR on presentation (meanVCW, 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 andEchocardiographic CharacteristicsComparison of clinical and echocardiographic characteristicsbetween patients with TTC with MR and those without MRare listed in Table 1. Age, sex, and troponin I levels did notsignificantly differ between the 2 groups. We found lowerLVEF (P�0.006) and higher mitral tenting area, peak LVOTpressure gradient, and PASP (all P�0.001) in patients withTTC with MR. The ratio of patients with TTC who presentedwith shortness of breath on admission also was greater inthose with MR than in those without MR (75.0% versus28.5%, P�0.003). Moreover, we stratified 12 patients withMR into 2 groups based on the presence or absence of a peakLVOT pressure gradient �20 mm Hg. All 6 patients withincreased LVOT pressure gradients had SAM, and the re-maining 6 patients had significantly higher mitral valvecoaptation 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 versus49.1�4.9 mL, P�0.035), and lower EF (28.0�6.9 versus34.8�2.9, P�0.001) than patients with TTC with MR due toSAM. All patients with MR are listed in Table 2.

Figure 1. Mitral leaflet configurations in the parasternal long-axis echocardiogram.

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Relationship Between Clinical andEchocardiographic Findings and Acute MRin TTCUnivariate analysis was performed in patients with TTC MRwith SAM (versus patients without MR) and those withoutSAM (versus patients without MR) (Tables 3 and 4). Theresults of the univariate analysis demonstrated that the occur-rence of acute MR in patients with TTC was significantlyassociated with LV ejection fraction, peak LVOT pressuregradient, mitral valve tenting area, PASP, and WMSI, respec-tively. The multivariate analysis also was performed to assess

significant variables obtained by the univariate analysis,resulting in peak LVOT pressure gradient and mitral valvetenting area (all P�0.001) as independent predictors of acuteMR in patients with TTC (Tables 3 and 4).

Follow-Up Echocardiographic FindingsFollow-up echocardiography was performed in 39 patientswith TTC (83.0%) within 4 weeks after initial presentation.Figures 2 and 3 show 2D echocardiograms obtained at initialpresentation and at follow-up in 2 typical patients with TTCwith MR due to SAM and tethering. LVEF, WMSI, VCW,

Table 1. Patient Characteristics

Patients With Significant MR

Patients WithoutSignificant MR (n�35) All (n�12) With SAM (n�6) Without SAM (n�6)

Age, y 68.5�15.4 71.6�8.8 71.6�7.3 71.5�10.7

Female, % 97.1 83.3 83.3 83.3

Troponin I, �g/L 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

Tenting area, cm2 0.95�0.25 1.5�0.6* 1.0�0.1 2.1�0.4*†

Coaptation distance, mm 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*

WMSI 1.9�0.1 2.2�0.2* 2.1�0.2* 2.3�0.2*†

Data are presented as mean�SD, unless otherwise indicated. LA indicates left atrium; LVEDV, left ventricularend-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVOT, leftventricular outflow tract; MR, mitral regurgitation; PASP, pulmonary artery systolic pressure; VCW, vena contractawidth; 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.

Table 2. Characteristics of 12 Patients With TTC MR

PatientNo.

Age/Sex,y

TriggeredEvent

ECG onAdmission

LVEF,%

Peak LVOT PressureGradient, mm Hg SAM

TentingArea, cm2

CoaptationDistance, 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

12 79/M Physical stress (colitis) T inversion 34 38 � 1 6.3 40

ECG indicates electrocardiography; SAM, systolic anterior motion of the mitral valve; TTC, takotsubo cardiomyopathy. Other abbreviations as in Table 1.

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and MR jet area/LA area values were significantly improvedat follow-up compared with initial presentation (LVEF,41.2�11.7% versus 58.3�11.3%; WMSI, 2.0�0.2 versus1.1�0.2; VCW, 0.60�0.19 versus 0.1�0.05 cm; MR jetarea/LA area, 53.2�10.9% versus 8.2�2.5%; all P�0.001).Recovery in LV systolic function was similar in patients withand without MR (58.4�6.7% versus 59.4�11.9%, P�0.845).No abnormal LVOT pressure gradients were observed atfollow-up. In patients with MR without SAM, coaptationdistance and tenting area significantly decreased at follow-upcompared to initial presentation (coaptation distance,10.9�1.6 versus 7.9�0.5 mm; tenting area, 2.1�0.4 versus1.1�0.2 cm2; all P�0.001). No other significant echocardio-graphic changes were detected by 2D and Doppler echocar-diography. During the mean follow-up period of 25.5�6.7months, no patients had recurrence of TTC.

Reproducibility ofEchocardiographic MeasurementsThe intraobserver variability as assessed by intraclass coeffi-cient 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 coaptationdistance, 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. Theinterobserver 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 intrao-bserver and interobserver variabilities, respectively, were0.17 and 0.17 cm2 for mitral valve tenting area, 0.5 and0.6 mm for mitral valve coaptation distance, 0.05 and 0.06 cmfor VCW, and 3.2% and 4.1% for MR jet area/LA area.

DiscussionTo our knowledge, this study is the first to demonstrate that(1) there are 2 entirely different mechanisms responsible foracute MR in patients with TTC and (2) PASP is significantlyhigher in patients with TTC with MR than in those withoutMR. In patients with TTC, complications may occur in theacute phase.4–6 Heart failure with or without pulmonaryedema is the most common clinical complication.17 In the

Table 3. Analysis of Clinical and Echocardiographic Parameters in Patients With TTC MRWith SAM

Univariate Analysis Multivariate Analysis

OR (95% CI) P OR (95% CI) 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

Peak LVOT pressure gradient, mm Hg 3.64 (1.64–8.07) �0.001 3.16 (1.26–7.92) �0.001

Tenting area, cm2 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.

Table 4. Analysis of Clinical and Echocardiographic Parameters in Patients With TTC MRWithout SAM

Univariate Analysis Multivariate Analysis

OR (95% CI) P OR (95% CI) P

Age, y 0.98 (0.96–1.00) 0.706

LVEF, % 1.49 (1.02–2.17) 0.048 0.60 (0.13–2.78) 0.563

LVEDV, mL 0.97 (0.55–1.72) 0.846

LVESV, mL 1.04 (1.02–1.12) 0.047 0.80 (0.47–1.37) 0.476

Peak LVOT pressure gradient, mm Hg 0.80 (0.55–1.16) 0.288

Tenting area, cm2 5.46 (2.54–9.62) �0.001 3.17 (1.04–8.62) �0.001

Coaptation distance, mm 3.67 (1.11–12.1) 0.013 1.69 (0.91–3.17) 0.212

Mitral annular dimension, mm 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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present study, we found that �25% of the patients with TTChad acute MR, which supported the results of earlier stud-ies.7,8 Approximately one fifth of patients with TTC haveclinically significant acute MR. Despite the favorable out-come of TTC, the associated presence of significant acuteMR increases the risks of acute deterioration and adverseoutcome in patients with TTC.8,18 In the present study, acuteMR was identified in patients with TTC with lower EF; PASPwas higher in patients with TTC with MR than in thosewithout MR. The number of patients who presented withshortness of breath was greater in those with MR than in thosewithout MR. Therefore, special attention should be paid tothe hemodynamics in the acute phase of TTC, which oftencorrespond to New York Heart Association class III heartfailure.19

Earlier studies indicated that SAM was regarded as 1 of thecauses of significant MR.7,20 Parodi et al7 reported thatapproximately one third of patients with TTC with significantMR had SAM. It is well-known that in patients with hyper-trophic cardiomyopathy, SAM is associated with significantMR.21,22 Some case reports also demonstrated LVOT obstruc-tion with SAM and acute MR in TTC.23,24 In the presentstudy, 12% of all patients with TTC, 50% of the patients withTTC with significant MR, had SAM, which was identified as1 of the predictors of acute MR in patients with TTC bymultivariate analysis.

However, we found another independent factor of acuteMR in patients with TTC: mitral valve tenting area. Severe

mitral valve tenting is known as an important cause ofischemic MR.25–27 Ischemic MR, a relatively common com-plication of coronary artery disease, occasionally occurs inthe acute or chronic phase.27 Leaflet tethering by papillarymuscle displacement due to regional or global LV dysfunc-tion has been suggested as the main mechanism of chronicischemic MR.25–27 In the present study, patients with MRwithout SAM had lower EF and higher WMSI and end-sys-tolic volume than those with MR due to SAM. These findingssuggest the presence of LV systolic dysfunction and LVenlargement in patients with MR without SAM rather than inthose with MR due to SAM. This finding is consistent withprevious explanations for the etiology of ischemic MR.25–27

Our finding of simultaneous improvement of mitral valvetethering and MR severity in patients with TTC is particularlyimportant for the understanding of the mechanism of acuteMR. Of note, another study suggested papillary muscledysfunction or displacement as a potential cause of MR inpatients with TTC without any quantitative data.8

Clinical ImplicationThe present study observations imply that TTC should bekept in mind as a potential cause of acute MR. Early detectionis important for proper management of patients with thiscondition. Recognition of the difference in mitral geometrygives new insight into the mechanisms of acute MR in TTC.The current American College of Cardiology/American Heart

Figure 2. Two-dimensional transthoracic echocardiography inpatients with mitral regurgitation (MR) due to systolic anteriormotion of the mitral valve (SAM). A, Severe MR at initial presen-tation. B, Mitral valve SAM at initial presentation. C, Only trivialMR was found at follow-up. D, Mitral valve SAM was not foundat follow-up. Note that all 4 images are from apical long-axisviews. LA indicates left atrium; LV, left ventricle.

Figure 3. Two-dimensional transthoracic echocardiography inpatients with mitral regurgitation (MR) due to apical displace-ment of the mitral valve. A, Severe MR at initial presentation. B,Apical displacement of the mitral leaflets was found at initialpresentation. C, Only trivial MR was found at follow-up. D, Nor-mal mitral leaflets close at the annular level at follow-up. Notethat all 4 images are from the apical 4-chamber view. Abbrevia-tions as in Figure 2.




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Association guidelines recommend mitral valve surgery insymptomatic patients with severe acute MR28; however, ourresults support the idea that aggressive medical treatment ofTTC would be the first priority because acute MR in TTC isreversible.

Study LimitationsBecause this study was retrospective, the timing of follow-upechocardiography varied. However, LV function and wallmotion and MR were improved at follow-up as expected. Thelogistic regressions are not necessarily representative of thepopulation given the relatively low number of subjects versusthe number of predictors. We could not conduct a large-scalestudy because of the low prevalence of the condition. Furtherprospective investigation with a larger population iswarranted.

ConclusionsSAM and tethering of the mitral valve are independentmechanisms with differing pathophysiology that can lead toacute MR in patients with TTC. These findings imply thatechocardiography should be performed systematically inpatients with TTC to identify whether MR is present as wellas to assess its mechanism.

AcknowledgmentsWe would like to thank Dr. and Mrs. Paul I. Terasaki for their kindsupport and encouragement.

DisclosuresNone.

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CLINICAL PERSPECTIVEDespite the favorable outcome of takotsubo cardiomyopathy (TTC) in general, the presence of significant acute mitralregurgitation (MR) increases the risks of acute deterioration and adverse outcome in TTC. However, the mechanism ofacute MR in TTC remains unclear. In this study, we elucidated the mechanisms of acute MR in TTC; apical tethering andsystolic anterior motion of the mitral valve are 2 independent mechanisms that can lead to acute MR in TTC. Our findingof simultaneous improvement of apical tethering and MR severity in the patients with TTC is particularly important for theunderstanding of the mechanism of acute MR. Based on the study results, TTC should be regarded as a potential cause ofacute MR. In addition, pulmonary artery systolic pressure is significantly higher in patients with TTC with MR than inthose without MR. Therefore, early detection of MR is important for proper management of patients with TTC. The currentAmerican College of Cardiology/American Heart Association guidelines recommend mitral valve surgery in symptomaticpatients with severe acute MR; however, the present results support the idea that aggressive medical treatment of TTCwould be the first priority because acute MR in TTC is reversible. These findings imply that echocardiography should besystematically performed in patients with TTC to identify MR and assess its mechanism.




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Yoko Fukuoka, Robert J. Siegel and Takahiro ShiotaMasaki Izumo, Smruti Nalawadi, Maiko Shiota, Jayanta Das, Suhail Dohad, Eiji Kuwahara,

An Echocardiographic StudyMechanisms of Acute Mitral Regurgitation in Patients With Takotsubo Cardiomyopathy:

Print ISSN: 1941-9651. Online ISSN: 1942-0080 Copyright © 2011 American Heart Association, Inc. All rights reserved.

Dallas, TX 75231is published by the American Heart Association, 7272 Greenville Avenue,Circulation: Cardiovascular Imaging

doi: 10.1161/CIRCIMAGING.110.9628452011;4:392-398; originally published online April 15, 2011;Circ Cardiovasc Imaging.

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