ACS, myocardial bridging, Tako-tsubo syndrome and mitral

CASE REPORT

ACS, myocardial bridging, Tako-tsubo

syndrome and mitral regurgitation

R Michels, G. Brueren, J.-M. van Dantzig, N. Pijls, C.H. Peels, H. Post

Isolated systolic compression ofthe mid portion ofthe left anterior descending artery (LAD) by abridge ofoverlying cardiac muscle is an infrequentbut well-recognised angiographic anomaly that isoften considered harmless. The long-term prog-nosis appears to be excellent, but occasional reportsof patients with angina pectoris, myocardialinfarction and sudden death indicate that this isnot always true. The prevalence ofthe anomaly inthe normal population is unknown, but theincidence is low and ischaemic events are rare.Tako-tsubo-like left ventricular dysfunction syn-drome (ITS) is characterised by iscbaemia, anteriorST-segment elevation, no significant coronaryartery disease and reversible ampulla-like leftventricular ballooning in postmenopausal femalesafter emotional or physical stress. Dynamic leftventricular outflow tract (LVOT) obstruction is arare but potentially fatal complication of acuteanterior wall infarction.We present a patient with an acute coronarysyndrome (ACS) with ST-segment elevation in theanterior leads, transient TTS and transientLVOTobstruction with systolic anterior motion (SAM)ofthe mitral valve and severe mitral regurgitation.This is the first report of myocardial bridgingassociated with TTS, and the first report ofTTS

R. MichelsG. BruorenJ.-M. van DantzlgN. PUsC.H. PelsH. PostDepartment of Cardiology, Catharina Hospital Eindhoven

Correspondence to: R. MichelsDepartment of Cardiology, Catharina Hospital,PO Box 1350, 5602 ZA EindhovenE-mail: [email protected]

associated with dynamic LVOT obstruction withSAM and mitral regurgitation. (Neth Heart J2005;13:57-61.)

Key words: myocardial bridging, acute coronarysyndrome, tako-tsubo, mitral regurgitation

A 65-year-old female patient presented with severeP chest pain and dyspnoea provoked by a bout ofstrenuous physical exertion. The symptoms lasted forhours. She had previously been healthy. She had nocardiovascular risk factors. Cardiac examination re-vealed a holosystolic apical murmur with radiation tothe axilla, compatible with mitral regurgitation.

Upon admission the ECG showed discrete antero-lateral ST-segment elevation and Q waves (figure 1).Emergency transthoracic Doppler echocardiogramrevealed akinesia in the perfusion territory ofthe mid-LAD, with compensatory hyperkinesia of the non-dilated basal segments ofthe left ventricle. In addition,there was SAM of the mitral valve, causing moderateLVOT obstruction in resting conditions with agradient estimated at 30 mmHg. As expected in SAM,there was mitral regurgitation with a posteriorlydirected jet.

Jet size by colour Doppler and signal intensity bycontinuous wave Doppler were consistent with severeregurgitation. Using the Valsalva manoeuvre, severeoutflow tract obstruction could be provoked with agradient of80 mmHg. No left ventricular hypertrophy(LVH) was seen (figure 2).

Emergency coronary angiography showed patentcoronary arteries. The LAD had typical myocardialbridging with systolic narrowing, the so-called milkingeffect (figure 3). Left ventriculography revealed antero-apical dyskinesia, septal akinesia, hyperkinesia of thebasal area, and severe mitral regurgitation. The leftventriculogram demonstrated a peculiar end-systolicshape with a round bottom and narrow neck,

Netherlands Heart Journal, Volume 13, Number 2, February 2005 57

ACS, myocardial bridging, Tako-tsubo syndrome and mitral regurgitation

resembling a Japanese octopus trap or tako-tsubo(figure 3).

She was admitted to the coronary care unit. Shewas treated with aspirin, metoprolol and diltiazemorally and nitroglycerin intravenously. Shortly afteradmission she became asymptomatic.

The peak troponin T level 12 hours after admissionwas 17 ng/ml (cut-off <0.1 ng/ml). Creatine kinase-MB rose to a maximum of 39 U/l (normal value <9UA).

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The ECG one day after admission showed T-waveinversion in the anterior and inferior leads andprolongation ofthe QT interval (figure 1).

She remained asymptomatic during hospital stay.Before discharge she underwent maximal exercise stresstesting on the bicycle ergometer. She reached 150% ofthe age-predicted maximum of 140 Watt, withoutanginal complaints or ischaemic ECG changes.Transthoracic Doppler echocardiogram one monthafter discharge demonstrated a normal left ventricle

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Figure 1. Upperpanel: electrocardiogram at admission, showing discrete ST-segment ekvation in the anterior kads, and Q-waves. Lowerpanel: ekctroeardiogram after one day showing T-wave inversion and QT-intervalprolongation.

Netherlands Heart Journal, Volume 13, Number 2, February 2005

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Figure 2. Acute echocardiogram. Leftpanel (A) shows apical 3-chamber view with apical dilatation and systolic anterior motion of themitral valve. Colourflow in middlepanel (B) revealssystolicturbulnce inleftventricularoutflowtrac; indicatingobstrction. Furthermore,posteriorly directedjetofsevere mitral regurgitation is evident. Rightpanel (C) showscontinuouswave Doppler recording ofleftventricularoutflow velocities during Valsalva manoeuvre, corresponding to a dynamicgradient ofapproximately 80 mmHg.

and only slight mitral regurgitation without SAM.Cardiac magnetic resonance imaging two months afterthe acute episode showed a normal and completelyviable left ventricular myocardium.

Currently she is asymptomatic on aspirin, meto-prolol, diltiazem and quinapril. She has been advisedto avoid excessive emotional or physical stress.

DiscussionThe patient presented with an acute coronary syndromewith transient anteroseptal and apical left ventricular

dysfunction, severe mitral regurgitation and SAM.Acute leftventriculography revealed a peculiar asynergy,with an end-systolic round bottom and narrow neck,compatible with TTS,' but this diagnosis was made inthe absence of visible coronary abnormalities. Thispatient had a visible coronary anomaly, myocardialbridging of the LAD, together with a long recurrentsegment ofthe LAD. This is the first report ofTTS inthe setting ofmyocardial bridging ofthe LAD.

Echocardiography showed SAMwith severe mitralregurgitation, but without (asymmetrical septal) hyper-

Figure 3. Left and middle panel: coronaty angiogram in the left lateral position, with bridging of the left anterior descending artey,showing the t,pical systolic milkingeffect (middlepanel). Rightpanelshows the end-systolic leftventiculogram, which looks likea tako-tsubo,with a round bottom and narrow neck.



trophy. Dynamic LVOT obstruction in the setting ofacute anterior myocardial infarction has been reportedpreviously,2 but this is the first report of dynamicLVOT obstruction with SAM and severe mitral re-gurgitation in the setting of TTS. We attribute thetransient mitral regurgitation and SAM to the acuteanatomical distortion and to the Venturi effect createdby turbulent flow through the LV outflow tract, sub-sequent to ischaemia-induced increased adrenergictone, leading to hyperkinesia of the basal LV withreduction ofthe basal LVvolume. The ECG after oneday demonstrated T-wave inversion and prolongationofthe QT interval compatible with previous findingsin TTS (figure 1).'

Hypertrophic obstructive cardiomyopathy wasexduded by the echocardiogram. The absence ofLVHis of diagnostic importance. Myocardial bridging is afrequent phenomenon and of diagnostic importancein hypertrophic cardiomyopathy,3'4 whereas isolatedmyocardial bridging in the absence ofany other cardiacabnormality is considered a benign anomaly.5 Childrenwith hypertrophic cardiomyopathy have an incidenceofmyocardial bridging of28%, and those with bridginghave a much higher incidence ofsudden cardiac deathor resuscitation within five years than those withoutbridging.3 The prevalence of myocardial bridging inadults with hypertrophic cardiomyopathy is 30 to50%.36 Adults withLVH and myocardial bridging havea higher incidence ofsudden cardiac death, wall motionabnormalities and positive thallium-201 scintigraphythan those without bridging.34

The overall incidence ofisolated myocardial bridgeswas 0.82% (from 0.41 to 1.16% per year) in a long-termfollow-up study among 7467 consecutive coronaryangiograms over eight years. The patients with isolatedso called milking at baseline had an excellent long-term prognosis (11±3 years), independent of theseverity of systolic narrowing, although over 50% ofpatients were on antianginal drugs and patients withsevere (>50%) narrowing had more clinical symptoms(70% vs. 50%) than those with less narrowing.5

Myocardial bridging is not always innocent.7'2Isolated myocardial bridging has been reported as thecause ofsudden death,8 myocardial infarction,8 throm-botic ocdusion'0"1' and spasm.12 In young athleteswhodied suddenly, tunnelled coronary artery was deemedthe cause ofdeath in 2.8% in the absence ofany othercardiac abnormality.'3 The idea that the condition isinnocent is based on the relative benign outcome inprevalence studies and on the misconception that onlydiastolic blood flow which is not compromised by thebridge is ofimportance in coronary arteries. In normalleft coronary arteries, blood flow at rest is low ornegligible during systole and high during diastole. Atmaximal vasodilatation, diastolic flow further increasesand also some increase in systolic flow occurs. Athyperaemia the systolic component is generally lessthan 25% of total flow.'4 In myocardial bridging thesystolic component decreases significantly or disappears

completely, which means that maximum blood flowin some patients may decrease by up to 25% of itsnormal value, which is compatible with reversibleischaemia.'5Phasic systolic compression is followed by a persistentmid-to-late delay in diastolic relaxation.'6 This factorgains importance with shortening of diastole, withincreased heart rate.'17,8 The investigators, who firstquestioned whether myocardial bridging is a normalvariant or an obstruction,19 have recently recom-mended diagnostic and treatment strategies, includingnudear scintigraphy, quantitave coronary angiography(QCA), intravascular ultrasound (IVUS) andintracoronary Doppler.20

Intracoronary Doppler reveals increased diastolicflow velocities, with a characteristic early diastolicfinger-tip flow velocity acceleration, and loss ofantegrade systolic flow, with a retrograde systolic flowphenomenon at the entry site of the bridge, and areduced coronary flow reserve (CFR).20 During rapidatrial pacing a significant increase in mean diastolic/systolic flow velocity ratio (DSVR) was the mostprominent flow alteration within the myocardialbridge, which in fact represents the significant decreaseof the systolic component of flow in myocardialbridges.

The application offractional flow reserve measure-ment (FFR, the ratio of mean hyperaemic coronarypressure:mean aortic pressure, normal value >75%)using the pressure wire has been described in one casereport.2' However, in our view coronary pressuremeasurement is less suitable to assess the functionalsignificance of a myocardial bridge, because an initialgradient due to the presence of the bridge may dis-appear again when total systolic occlusion occurs.Therefore for invasive functional testing in myocardialbridging, Doppler velocity measurement is the methodofchoice.

In symptomatic patients not responding to medicaltherapy, we perform nudear scintigraphy with pharma-cological vasodilatation, QCA, intracoronary Dopplerwith dobutamine and dobutamine stress echocar-diography as independent tests to detect perfusiondefects, flow abnormalities, and ischaemia-related wallmotion abnormalities, respectively. Combination ofthese independent tests virtually eliminates the risk ofa false-positive test result. Therapy in symptomaticpatients is not different from that of atheroscleroticcoronary artery disease.

Medical therapy indudes platelet inhibition, nitrates,calcium antagonists and 5-blockers. Beta blockersalleviate anginal symptoms by a reduction ofvascularcompression by the myocardial bridge.22 Patientsresistant to medical therapy are candidates forintervention including periarterial musde resection,23left internal mammary artery grafting to the distalLAD24 or coronary stenting.24 ITS is more frequent inpostmenopausal females after emotional or physicaldistress.'

Netherlands Heart Journal, Volume 13, Number 2, February 200560


In males, TTS has been reported in pheochromo-cytoma25 and in Main's syndrome.26

Rat immobilization stress reproduced the character-istic ECG and LV changes, which were attenuated byan increase ofserum oestrogen and normalized by a-and P-adrenoceptor blockade.27'28 Aipha-adrenoceptorstimulation can produce spasm in spasm-pronecoronary segments. Coronary flow reserve tests indicateacute damage ofthe microcirculation.29 The character-istic finding of antero-apical ballooning is related tothe presence of a long recurrent LAD segment.30Recovery ofITS is remarkable, but the acute stagemay be complicated by thrombus formation in the leftventricle.3'-33

Our patient had no findings ofpheochromocytomaor subarachnoidal bleeding. We did not determinecatecholamines in serum or urine. We speculate thatstrenuous exertion provoked ischaemia and induced(or enhanced) abnormally high adrenergic tone leadingtoITS and dynamicLVOT obstruction with SAM andmitral regurgitation. In condusion, myocardial bridgingis a pluriform condition which in itself is not alwaysinnocent, and which may lose its innocence underspecific conditions, such as abnormally high adrenergicstimulation. In postmenopausal womenwho are at riskofITS during emotional or physical distress, myocardialbridging of the LAD may induce or aggravate acuteischaemia leading to transient dynamic LVOT ob-struction and mitral regurgitation. U

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ACS, myocardial bridging, Tako-tsubo syndrome and mitral