Transient Left Ventricular Apical Ballooning Syndrome

TakoTako-Tsubo / Ampulla Cardiomyopathy

Characteristics
      

First described in 1991 by Sato & Dote et al in Japanese literature Angina ST segment elevation / diffuse T wave inversion / abnormal Q waves RWMA in lower anterior wall and apex Myocardial enzyme release (mild to mod.) Hemodynamically insignificant stenosis on CAG Psychological / physical stress within minutes to hours of onset of symptoms Hemodynamic compromise, cardiac arrest Rapid resolution of RWMA & normalization of EF in 7-30 days 7-

 

Systematic Review of 7 case series

Ann Intern Med 2004

Demographics and Presenting Symptoms



82% to 100% were women Mean age was 62 to 75 years Presenting symptom chest pain (33% to 71%) Dyspnea & rarely syncope

Systematic Review
ECG findings on admission


ST-segment elevation (46% to 100%) Mostly precordial leads and more marked in V4-V6 Isolated inferior or lateral ST elevation unusual

 

New LBBB and RBBB Almost all patients developed T-wave inversions usually present in most leads. New pathologic Q waves (6% to 31%) The corrected QT interval (mean 0.45 s to 0.50 s)

 

Systematic Review
Cardiac Enzyme and Biomarker Release
   

Most patients had a modest increase in cardiac enzyme levels. 56% incidence of increase in creatine kinase 100% incidence of increase in cardiac troponin Peak levels are often those drawn at the time of initial presentation Do not follow the kinetics observed with conventional MI.

Systematic Review
Angiographic Data and LV Function
    

No angiographically detectable lesion(25% to 100%) Nonobstructive coronary disease (0% to 75%) None of the patients had epicardial stenosis greater than 50% Mean LVEF at presentation 0.39 to 0.49 LVEF improved rapidly over a period of days to weeks to mean 0.60 to 0.76 Apical and mid-ventricular RWMA completely resolved in most patients

Systematic Review
Endothelial Function and Coronary Microcirculation


Either spontaneous or provocable multivessel epicardial spasm was present in 0% to 43% Coronary flow reserve (coronary microvascular function) showed conflicting results Abnormal TIMI frame counts in all 3 major epicardial coronary arteries during the acute phase of the syndrome

Systematic Review
Clinical Complications and Outcome  n-hospital mortality rates - 0% to 8%
 

Significant LV failure during the acute phase in 3% to 46% A transient, dynamic intraventricular pressure gradient due to obstruction in the LV cavity in 13% to 18% with MR AV block, sinus bradycardia, paroxysmal atrial fibrillation, VT and Vfib Isolated cases of LV mural thrombus formation 1 case of LV freewall rupture occurred 3 days after presentation Cardiogenic shock Death

    

Systematic Review
Preceding Stressors, Incidence, and Recurrence


Most patients presented immediately after an episode of acute emotional (14% to 38%) or physiologic (17% to 77%) In 1 series, this syndrome represented 2.2% of ST elevation ACS presenting to a referral hospital during 2002 and 2003 A separate series, this syndrome was diagnosed in 1.5% of patients who had presented with an Qwave ACS Recurrence of the syndrome seems to be rare (0% to 8%)

Possible triggering factors



Systemic disorders CVA epileptic attacks exacerbation of bronchial asthma acute abdomen noncardiac surgery/procedure Pnuemothorax

Emotional/physical problems death/funeral of family member Surprise party / reunion fear of procedure public speaking court appearance tragic news sudden accidents inexperienced exercise quarreling excessive alcohol consumption vigorous excitation

Mechanism


Several mechanisms have been proposed Catecholamines mediated myocardial stunning neurogenically mediated direct metabolic injury multivessel epicardial spasm microvascular coronary spasm/dysfunction Abnormal LAD anatomy Intraventricular gradient Genetic

Neurogenic
 

Acute mental stress, a time of enhanced sympathetic outflow The distribution of apical WMA is similar to the distribution reported with catecholamine-induced cardiomyopathy (pheochromocytoma, GBS, SAH) Increased adrenergic receptor density and responsiveness in the apical segments In a rat model the RWMA could not be reproduced after pretreatment with adrenoreceptor antagonist Measurements of circulating catecholamine levels have shown inconsistent results suggesting that activation of cardiac adrenoceptors maybe the primary cause.

Direct metabolic injury



Elevated catecholamine level decrease the viability of myocytes through cAMP mediated calcium overload and formation of free radicals causing necrosis Transient exposure to excessive catecholamines, may result in stunning with cellular metabolic abnormalities rather than necrosis Pulmonary sympathetic stimulation increases the pore size in the pulmonary capillaries, leading to alveolar transudation Studies have demonstrated a reduction of the fatty acid metabolism and mitochondrial function in the apical myocardium by using isotopes, suggesting direct myocardial toxicity

Coronary spasm


In an angiographic studies, spontaneous spasm seen very occasionally 70 % had coronary spasm (single/multivessel) in response to provocative maneuvers (ergonovine or acetylcholine) ST elevation was common at presentation

Multivessel coronary vasospasm (which could probably produce diffuse wall-motion abnormalities), was found in 18% patients tested across series Transient multivessel epicardial spasm may be responsible for some cases of the syndrome

Microcirculatory spasm/dysfunction


Coronary microvascular function has been shown to be diffusely abnormal when assessed using CFR and TIMI frame counts IC nicorandil during the acute phase acutely reduced the extent of ST elevation Regional defects on cardiac imaging suggests sympathetically mediated microcirculatory dysfunction. ? primary mechanism or secondary phenomenon

Abnormal LAD anatomy



In a series of 5 tako-tsubo patients, the LAD had a long course around the LV apex, supplying an extensive portion of the diaphragmatic LV aspect Transient coronary artery occlusion/reperfusion episodes may lead to stunning and akinesia also the minimal release of biomarkers with total recovery of cardiac function Pathogenesis of this disorder could be similar to that of AMI: coronary atherosclerotic plaque complicated by thrombotic occlusion Evidence supporting the hypothesis is weak and hardly explains characteristics of this syndrome

Intraventricular gradient ntraventricular



Clinical and hemodynamic situation improved when the gradient disappeared and in some cardiogenic shock persisted until the dynamic obstruction was present Dynamic obstruction raise intraventricular pressures in the distal chamber and reduce myocardial perfusion, leading to ischemia and dyskinesia Exposure to an exogenous catecholamine (dobutamine), can provoke dynamic LVOT obstruction even in normal hearts Some women might have a geometric predisposition (sigmoid septum, narrow LVOT, reduced LV volume) to the development of dynamic subaortic obstruction that would only manifest with intense adrenergic stimulation

Proposed pathophysiological mechanism of TLVABS

Female Preponderance


Sex hormones exert important influences on the sympathetic neurohormonal axis as well as on coronary vasoreactivity. Women are more vulnerable to sympathetically mediated myocardial stunning (transient LV dysfunction after SAH) Explanation - alterations of endothelial function and microcirculatory vasomotor reactivity due to reduced estrogen levels Estradiol supplementation attenuates emotional stress induced changes in LV function in ovariectomized female rats.

PATHOLOGICAL FINDINGS


Interstitial fibrosis was a common finding and no significant inflammation necrosis during the acute phase Later myocytolysis, with cell infiltrates including mononuclear cells and increase of loose connective tissue. The histologic findings in this heart syndrome, were similar to those observed in catecholamine-induced cardiomyopathy catecholamineThere was no evidence of acute myocarditis in any series.

Proposed Mayo Criteria for the Clinical Diagnosis

1. Transient akinesis or dyskinesis of the left ventricular apical and midventricular segments with regional wall-motion abnormalities extending beyond a single epicardial vascular distribution 2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture 3. New electrocardiographic abnormalities (either ST-segment elevation or T wave inversion) 4. Absence of Recent significant head trauma Intracranial bleeding Pheochromocytoma Obstructive epicardial coronary artery disease Myocarditis Hypertrophic cardiomyopathy
* All 4 criteria must be met

Diagnosis of TLVABS


Prior conditions (both obligatory): Evidence of transient apical dysfunction of LV with a typical shape in the systole, diagnosed by angio, echo, isotopes, or cardiac MRI. Normal ventricular mobility returns in 2-3 weeks Absence of other conditions associated with transient regional systolic dysfunction of the LV: SAH, pheochromocytoma, cardiac ischemia, toxic substances (cocaine), myocarditis, etc. Diagnostic Criteria Major criteria Early coronary angiography (first 24 h) without anatomical lesions Minor criteria 1. Early coronary angiography with non-significant lesions 2. Late coronary angiography(2 to 7 days) without significant lesions 3. Disorder triggered by physical or emotional stress 4. Typical ECG changes ST segment elevation in acute phase, Q waves that disappear after acute phase, T inversion prominent in V1-V6 and prolongation of QTc 5. Woman aged >50 years

Management


Beta-blockers ACEI (in patients without an intracavitary gradient) Aspirin IV diuretics Pts with hypotension must be evaluated for a dynamic intraventricular pressure gradient in the LV cavity and LVOT which is managed by beta-blockers, phenylephrine fluid resuscitation Beta-blockers and phenylephrine are not recommended in documented epicardial coronary vasospasm (diltiazem or verapamil) Short-term anticoagulation if significant LV dysfunction and continued until LV function has improved Monitoring for atrial and ventricular arrhythmias, heart failure, and mechanical complications.

69-year-old woman acute chest pain CPK MB was elevated urgent CAG - normal coronaries LV angio-apical ballooning in systole LVEF of 33% & severe MR Midcavity gradient of 25 mmHg Supportive therapy Clinical recovery within 1 week LV function normal at 40 days

80-year80-year-old woman with hypertension 3-hour history of dyspnoea and precordial discomfort trop T, CPK and CPK-MB were CPKnormal patient developed haemodynamic instability, cardiac cath was done The patient s condition improved after an IABP was placed Echo 3 weeks later showed normal LV size and function.

78-year-old woman with hypertension acute epigastric pain since 12 hours melena and Hb of 8g/L. After transfusion of 2 units of packed RBCs, the symptoms disappeared and the ECG evidenced extensive anterior subepicardial ischemia. The trop I was 8.5 ng/mL. Echo showed anteroapical akinesia and dynamic subaortic obstruction with a peak gradient of 42 mm Hg Cath performed 5 days later showed normal coronaries and apical ballooning She has remained asymptomatic after 15 months of follow-up, with normalized ECG and LV wall motion

 

 

64 year old woman No coronary risk factors continuous atypical chest pain-2d Maximal CPK and trop I values were 159 U/l (normal 0 170) and 7.4 ng/ml (0 0.1) CAG-normal coronaries LV angio - apical ballooning, apical thrombus. LVEF 40%. Confirmed with TTE (IV gradient 75mmHg) Pathologic Q waves developed from V1-V3 discharged under anticoagulants 3 months later T in V3 V6 TTE - normal LVwall motion, LVEF 62%, complete resolution of the apical thrombus and IV pressure gradient

Apical thrombus in TLVABS

Indian Heart Journal

 

5 cases (all females) aged 22 40 years Presenting with severe transient LV dysfunction, and cardiogenic shock following surgery (cesarean section 2, laparoscopic cholecystectomy 3) All the patients had ECG changes in multiple leads, suggestive of STEMI in 2 cases, and NSTE MI in 3 cases, raised cardiac enzymes, severe LV dysfunction, and normal coronaries IABP support was required in 3 cases. All the patients made a complete recovery, and are asymptomatic at 1-month to 6-year follow-up. 6follow-

 

Unanswered Questions


Why do middle-aged/elderly women appear middlesusceptible to this disorder? Exactly how does psychological stress trigger its sudden onset? Why is the LV apex selectively vulnerable to regional ballooning? Is this really a new disease with increasing incidence, or has it previously been unrecognized? Should pharmacological therapy be continued indefinitely?

Clinical Relevance


Although rare, TLVABS must be considered as a d/d of ACS or STEMI Especially when extent of ECG abnormaliries exceed biomarker evidence for myocardial necrosis and CAG confirms noncritical CAD.


Prompt recognition and aggressive t/t (pharmacological / mechanical)

THANK YOU

ST-Segment Elevation in Various Conditions

Condition Normal (male pattern) Early repolarization Feature 90 percent of healthy young men Concave, 1 3mm, most marked in V2 Most marked in V4, notching at J point Tall, upright T waves Reciprocal ST depression in aVR V3- V5, inverted T waves Short QT, high QRS voltage Concave, Other features of LVH Concave ST deviation discordant from the QRS Diffuse ST elevation, Reciprocal ST depression in aVR, Elevation seldom>5mm, PR-segment depression

ST elevation normal variant LVH LBBB Acute Pericarditis

Condition Hyperkalemia Brugada Syndrome Pulmonary embolism Cardioversion

Feature Other features of hyperkalemia present rSR' in V1-2, ST- elevation in V1-2, typically downsloping Changes simulating MI in both inferior and anteroseptal leads ST elevation, often >10 mm, lasting only a minute or two immediately after DC shock Same as ST-segment elevation in infarction, but transient

Prinzmetal Angina