Presenter :- DR.Rajesh M. DandaleUniversità degli Studi di Verona
A 64 year-old post-menopausal female presented with sudden onset of chest discomfort which started after she experienced severe emotional stress. She was transported to Department of Cardiology by Emergency Service. The pain resolved with administration of sublingual nitroglycerin during transportation . She was dyslipidemic, non diabetic, non HTN, no P/H of MI. No history of similar episodes in other family members.
Initial electrocardiogram revealed sinus bradycardia with diffuse ST – segement elevation, QRS and and QT interval prolongation. CK-MB -13,5 ug/L. Troponin I- 1.02 ug/L (ULN: <0.5). Chest X-ray: WNL
Akinetic apical and anteroseptal wall with reduction in EF. Minimal MR
In hospital day 4,ECG and cardiac biomarker normalized, TTE after 7 days show no RWM abnormality and EF-60% Patient was discharged from hospital with healthy condition, advised for regular follow up.
Tako-Tsubo cardiomyopathy Apical ballooning syndrome Stress cardiomyopathy Ampulla cardiomyopathy Neurological cardiomyopathy (stunning) Broken heart syndrome Int J Cardiol 2007;116:405 Synonyms for same clinical syndrome
Cardiac Syndrome – defined as presence of transient left ventricular apical ballooning after ACS in patients with angiographically normal coronary arteries. Iga reported first case. Described in 1990 by Sito et al, as Tako-Tsubo cardiomyopathy. Named after the octopus trapping pot with a round bottom and narrow neck, which resembles the end systolic left ventriculogram in these patients. Sporadic cases found around world. In 2006 , the American Heart association included ABS into its classification of cardiomyopathy as a primary acquired cardiomyopathy. Circ.2006;113:1807-16.
1-2% of ACS / MI AHA-732.000 hospital discharges with diagnosis of AMI /year so annual rate of ABS may be 7.000-14.000 cases. Worldwide, the incidence of ABS appeared to be on the rise- recent advances in the work-up of patients with chest pain. Am Heart J 2008;155:408-17. Circulation 2008;118:2754-2762.
Postmenopausal women 88.8% (Gianni et al.14 major studies involving 286 patients), mean age 58-75 yrs- suggest hormonal predisposition -further investigation to find out potential mechanisms Underlying hormonal predisposition-research Genetic contribution- ( Pison et al. 2 middle- aged sisters involvement) Cardiovasc Drug Ther 2008;22:71-77 Eur Heart J 2006;27:1523-9
Chest pain at rest- 50-60% Dyspnea Pulmonary edema Ischemic changes on ECG- diffuse T-wave inversion and QT prolongation( myocardial stunning) Elevated cardiac biomarkers Hypotension 2/3 presented after emotional/physical stressful condition (“broken heart” syndrom) Am Heart J 2008;155:408-17.
MC- ST-segment elevation-mimicking STEMI Typically in precordial leads, but it maybe seen in the inferior and lateral leads. Non-specific T-wave abnormality, new bundle branch block and in some cases ECG may be normal at presentation. Resolution of ST-segment elevation, development of diffuse and often deep T-wave inversion that involves most leads. Resolution occur within 4-6 weeks Am Heart J 2008;155:408-17
Coronary angiography- normal coronary arteries /mild atherosclerosis, Left ventriculography- hypokinesia, akinesia or even dyskinesia of the mid and or apical segment of LV. TTE-RW abnormality is beyond the distribution of single coronary artery (30% right ventricle shows similar RWA) Magnetic resonance- extent of the RWM abnormality and differentiating myocardial infarction and myocarditis. Circulation . 2008;118:2754-2762.
Classical situation:- a postmenopausal woman In intensive care unit:- Mayo clinic criteria-1. Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always present.2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.3. New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin.4. Absence of: Pheochromocytoma Myocarditis American Heart Journal Volume 155, Isssue3, March 2008,408-417
Rare cases precipitated by1. Hypoglycemia2. Hyperthyroidism3. Cocaine4. Alcohol withdrawal5. Pneumothorax6. Subdural hematomaAll these associated with increased sympathetic drive.
Heterogeneous condition, which lacks a disease specific etiology. Catecholamine –mediated toxicity- increases in sympathetic tone following a stressful event and could result in direct cardio toxicity. Multi-vessel epicardial coronary artery spasm Microvascular dysfunction Spontaneous aborted myocardial infarction Cardiovasc Drugs Ther 2008; 22:71-77
Myocarditis A lack of supporting histological and microbiological evidence Mild interstitial fibrosis and limited mononuclear cellular infiltration- ABS Gadolinium-enhanced MRI studies failed to detect regional T2 enhancement, indicating inflammation and necrosis seen in myocarditis JACC, 2003;41:737-42.
Elevated circulating catecholamine-( Wittstein et al. 13 ABS and 7 MI), 1) levels remained dramatically raised even after cardiac function was restored. 2) not every patient with ABS shows elevated catecholamine. 3) all patients had suffered emotional stress prior to the cardiac event. Kurisu et al.`s (30pt) six had normal serum nonadrenaline One review mention 74.3% had elevated nonadrenaline Disease affecting catecholamine levels (pheocromocytona, subarachnoid hemorrage) can cause reversible LV dysfunction. Sepsis and respiratory faillure- increase sympathetic Anaphalaxis –histamine- adrenal medulla-catecholamine Wealth of evidence point towards a pathogenic role for catecholamine in ABS though exact nature remain unclear. Cardiovasc Drugs Ther 2008;22:71-77Elevated catecholamine levels in ABS is a result of the disease process or is it the cause???????????
Owa et al. serial SPECT scan Functional sympathetic innervations- 123 I-MIBG Fatty acid metabolism(C function)- 123 I- BMIPP Myocardial perfusion- 201 Thallium scan Based on the 201Tl images, myocardial perfusion did not seem to be severely impaired even in the acute phase, whereas fatty acid metabolism was profoundly depressed in the apical myocardium in parallel with myocardial contraction abnormalities. The defective uptake seen on both BMIPP and 201Tl improved within 3 weeks. However, the MIBG images showed that sympathetic denervation persisted for 1 year after onset, which suggests that the primary cause of AB cardiomyopathy is a disturbance of the cardiac sympathetic innervations. Sympathetic dysfunction and transiently disturbed cardiac function in the presence of normal perfusion.
Contraction-band necrosis is the classic histological finding in catecholamine excess induced cardiovascular injury; seen in pheochromocytoma and subarachnoid hemorrhage, Only one patient of TTS studied by Wittstein et al. Recently published Inverted TT syndrome case report -shows same findings Akashi et al. 7/ 5 biopsies -fatty infiltration-1;mild interstitial fibrosis-1; small num of mononuclear cells (chronic myocarditis)-2; last patient shows only adipose tissue Int. Journal of cardiology 2010 Vol.8:no. 1
TCM: Pathological Insight from a fatal case Positive C4d staining Triphenyl tetrazolium chloride stainingVery strong C4d staining along the microvasculature and in the rare myocyteswith contraction band suggest that there was recent activation of thecomplement cascade which is likely secondary to subendocardial ischemia dueto catecholamine surge.C4d staining of a right ventricular endomyocardial biopsy may be used asdiagnostic tool to better predict the presence of injury?? The Int. Journal of Cardiology vol.8.
Central hypothesis is challenged by the gender discrepancy. If this is the predominant mechanism, one would expect a similar incidence in men and women. In fact, males have a greater adrenergic response to mental stress.In women, estrogen plays a protective role on the vascular bed from theadverse effects of catecholamine surge.So relative deficiency of estrogen after menopause may predispose them toABS
A possible animal model of a ‘Tako-Tsubo’ cardiomyopathyUeyama et al.• Characteristic LV apical ballooning in 8/10 rat subjected to the stress of remaining immobilized on their back for 30 mins.• Pre-administration of alfa/beta blockers (but no CCB/NTG), averted anticipated ventricular dysfunction.• Anatomical variation in (high) apical adrenergic receptor density may explain the largely apical involvement.• Basal myocardium has a somewhat higher norepinephrine content and greater density of sympathetic nerves than apical. Circ J 2002; 66: 712–713. Adrenergic receptor activation is central to the etiology of ABS
The available pathophysiological information indicates that the apical ballooning syndrome is result of toxic high local concentration of catecholamine, not coronary artery or microvascular disease. Individual differences in the anatomy of cardiac sympathetic innervation or the distributions of adrenoceptors might result in the involvement of a variety of left ventricular myocardial segments. In typical ballooning , high conc. of norepinephrine might evoke basal hyperkinesia.Elevated catecholamine level and adrenergic receptorhypersensitivity is most accepted theory
In absence of significant comorbidities, prognosis is good. The systolic dysfunction and RWM abnormalities are transient and resolve completely within days to few weeks (4-8 week). This is such a uniform finding. In hospital mortality is very low (1-2%) Long term survival is similar to that of the general age- matched population. Rate of recurrence is not > 10% Complications are heart failure, ventricular arrhythmias, LV free wall rupture, mural thrombus formation JACC 2007; 50:448-52
Presumed to be suffering from an acute coronary syndrome and immediate appropriate management should follow. Aspirin, B-blockers and diuretics Short term anticoagulation to prevent mural thrombus is indicated B-blocker continued indefinitely due to the chance of a late recurrence Due to prolonged QT interval leads to arrhythmia- VT- magnesium sulfate (if cQT>600mSec) Estrogen treatment – animal modelNo specific treatment for left ventricular failure- cardiac function normalized within few weeks.B-blockers (Sotalol) prolongs QT interval, potentiate adverse effect of high conc. of catecholamine at alfa receptorsABS has high risk of cardiac rupture, it is still controversial whether to treat with aspirin /heparin Ann Intern Med 2004;141:858-5 Circulation 2005; 111:388-90
A very small proportion of the population appears to be at risk for ABS, suggesting a role for genetic predisposition Whether estrogen replacement therapy will help to reduce incidence and recurrence of ABS Investigate the distribution of the adrenergic receptor that may explain the segmental involvement Only 30% of cases involve right ventricle The recurrence rate is low despite the repeated exposure to stressful events over lifetime Need to establish a registry for ABS to investigate natural history and to conduct randomized trials
Take home message• ABS is not a rare entity. Represents 1-2 % of ACS.• Prognosis is good, complete recovery within days to weeks, < 10% recurrence.• Initial management should be directed towards the treatment of MI with continuous ECG monitoring, administration of aspirin, heparin and B-blockers. Consider diuretics and ACE-inhibitors in patients presenting with heart failure .• Confirmation of diagnosis- particularly important if fibrinolytic therapy is being consider for presumed diagnosis of STEMI.• Free wall rupture, severe MR, ventricular arrhythmia are rare but fatal complications.• In the absence of contraindication, chronic B-blocker therapy will aim to reducing likelihood of a recurrent episodes.• On the basis of rat immobilization model, supplementation of estrogen in postmenopausal women might be protective.• Annual clinical follow-up is advisable as natural history of ABS remains unknown.