Transient Left Ventricular Dysfunction Syndrome Research Articles

AMPHETAMINE-INDUCED TAKOTSUBO CARDIOMYOPATHY COMPLICATED BY RECURRENT TORSADES DE POINTES AND CARDIAC ARREST: A CASE REPORT

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricular dysfunction in the absence of coronary artery disease. 36% of TCM cases had a physical stressor such as illness, while 27.7% reported an emotional trigger which lead to an inappropriate catecholamine release and response. TCM then presents with substernal chest pain, EKG changes, transient systolic dysfunction and rarely arrythmias such as Torsades de Pointes (TdP). Patients will usually recover systolic left ventricular function within 4 weeks. CASE PRESENTATION: A 63 year old female was brought to the ED after being found altered. History and urine toxicology showed she was taking Adderall. She initially presented with no focal neurologic deficits and an EKG at the time showed a QTc interval of 600ms (QTc baseline 485 from records). Patient underwent further workup before being noted ot have seizure like activity and agonal breathing. Repeat EKG at this time showed a lengthening of the QTc to 641 before the patient went into ventricular fibrillation cardiac arrest. Magnesium was administered, ROSC was achieved and patient was transferred to the ICU.In the ICU the patient had another episode of TdP and cardiac arrest. Immediately prior an EKG showed a QTc >700ms. ROSC was achieved but QTc remained >600ms and isoproterenol was begun. Patient tolerated this treatment well and her QTc normalized to 459ms. Her first TTE showed an EF of 35% and wall motion abnormalities. Repeat TTE in 6 days showed resolution of wall motion abnormalities and improved EF to 75%. DISCUSSION: TCM affects approximately 1% of all troponin positive acute coronary syndrome patients.2,3,4,5 QTc prolongation was seen in 86% of patients and VF in 3.4%.6,7,8 Only 15 cases have been reported of TCM leading to TdP and none secondary to amphetamine overdose. An overdose of amphetamines (Adderall) precipitated this patient’s TCM. Supportive care was provided for the amphetamine overdose and β-agonist support was initiated in order to shorten the QTc, a temporary measure that can be used in refractory TdP.9 The data on pharmacologic treatment of TCM is largely empiric, with pressors and beta agonists recommended only when absolutely necessary, due to the similar catecholamine mechanism of TCM.9,10,11 Treatment is largely centered around supportive care until resolution of myocardial dysfunction. CONCLUSIONS: Takotsubo cardiomyopathy is associated with prolonged QTc intervals, rarely progressing to torsades de pointes. Management is supportive therapy. Beta agonists can be given to accelerate rhythm to shorten QTc but care must be taken due to sympathetic overload driving TCM. Amphetamines and other sympathomimetic drugs should be considered as a source of stressor when diagnosing TCM. Reference #1: Tsuchihashi K, et. al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol. 2001;38(1):11. Reference #2: Sharkey SW, Lesser JR, Maron MS, et al. Why not just call it tako-tsubo cardiomyopathy: a discussion of nomenclature. J Am Coll Cardiol 2011;57:1496–7. 10.1016/j.jacc.2010.11.029 Reference #3: Kurowski V, Kaiser A, von Hof K, Killermann DP, Mayer B, Hartmann F, Schunkert H, Radke PW. Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest. 2007;132(3):809. DISCLOSURES: No relevant relationships by Young Lee, source=Web Response No relevant relationships by Steven Lim, source=Web Response

The ATAK complex (Adrenaline, Takotsubo, Anaphylaxis, and Kounis hypersensitivity -associated coronary syndrome) in neurological conditions.

Sir, Takotsubo syndrome, transient left ventricular apical ballooning, takotsubo cardiomyopathy, apical ballooning syndrome, atypical apical ballooning, ampulla cardiomyopathy, broken heart syndrome, transient left ventricular dysfunction syndrome, and stress cardiomyopathy were named after a round-bottomed and narrow-necked fishing pot - takotsubo in Japanese - for trapping octopus because of its resemblance to left ventriculogram. In the interesting report published in Indian Journal of Critical Care Medicine,[1] a 48-year-old man with progressive loss of vision, hypotension, tachycardia, and acidosis was found to have takotsubo syndrome while the coronary arteries were normal. Computerized tomography revealed dense sellar-suprasellar mass lesion extending into the hypothalamus resembling pituitary adenoma with hypocortisolism suggesting hypopituitarism. With dobutamine, atenolol, and noradrenaline, his condition improved. This case raises some issues concerning neurological conditions, mental stress adrenaline, anaphylaxis, and Kounis syndrome. Mental stress commences with impulses from high brain cortical centers that are relayed through the limbic system to hypothalamus resulting in the release of corticotropin-releasing hormone (main coordinator of the mental stress response) and norepinephrine, serotonin, acetylcholine, proopiomelanocortin, adrenocorticotropic hormone, glucagon, growth hormone, and homocysteine that stimulate sympathetic nervous system. These substances can induce heightened cardiovascular activity, endothelial injury, induction of adhesion molecules on the endothelial cells, to which recruited inflammatory cells adhere and translocate to the arterial wall and finally myocardial damage. An acute phase response is engendered, resulting in production of cytokines interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha, acute phase proteins, macrophage, mast cell, and platelet activation that eventually culminate in the development of Kounis syndrome.[2] Stress-induced cytokine production has been incriminated for multivessel coronary artery spasm at epicardial or microvascular levels that induce takotsubo cardiomyopathy. Inflammatory mediators released during anaphylaxis can induce coronary spasm and takotsubo syndrome and adrenaline given for anaphylaxis might contribute to coronary spasm and transient takotsubo syndrome. Adrenaline and noradrenaline released by the renin-angiotensin-aldosterone system together with histamine stimulate the release of more catecholamines by direct action on the adrenal medullary cells. Administration of catecholamines for hemodynamic support of anaphylactic shock would also increase the plasma catecholamines. Catecholamine increase in patients with angina, renders blood platelets more sensitive and more prone to aggregation and thrombosis. Therefore, measurement of anaphylactic inflammatory mediators including histamine, chymase, leukotrienes, thromboxane, and platelet activating factor or the use of corticosteroids or mast cell stabilizers for prevention and treatment may shed light on etiology and pathophysiology of takotsubo cardiomyopathy. The concurrence of acute coronary syndromes with conditions associated with mast cell activation, involving interrelated and interacting inflammatory cells constitute the Kounis syndrome.[3] Inflammatory cells, such as mast cells, T-cells, and macrophages, activate each other via multidirectional stimuli and release mediators capable to induce coronary events. Experimental findings suggest that cardiac mast cell activation by acute stress may contribute to myocardial ischemia through the release of histamine or proinflammatory mediators.[4] Therefore, takotsubo cardiomyopathy should be always considered in neurological conditions with prolonged addisonian crisis. Furthermore, Adrenaline, takotsubo, Anaphylaxis, and Kounis syndrome (ATAK) seem to constitute a challenging contemporary complex that needs inexorable “attack” to elucidate its etiology, pathophysiology, and treatment.[5] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest

Attack the ATAK : “οὓς ὁ θεὸς συνέζευξε, ἄνθρωπος μὴ χωριζέτω” (ous o theos synezeuxe anthropos me horizeto) “what therefore God hath joined together, let not man put asunder”

“Voodoo Death”was the title of a paper published, more than half a century ago [1], by the renowned American physiologist Walter B. Cannon and was based on anecdotal experiences, largely from the anthropology literature, dealing with death from fright. “Voodoo” is of African origin and concerns superstitious beliefs and practices found among Negroes of West Indies and Southern United States. Canon was the first to postulate that death from fright is caused by a lasting and intense action of sympathico-adrenal system. Phrases such as “scared to death” and “a broken heart”, are still used today and are deeply rooted in folk wisdom and reflect potentially lethal consequences of emotional, depressogenic or mental stress. Indeed, terms such as broken heart syndrome, transient left ventricular apical ballooning, stress-induced cardiomyopathy, apical ballooning syndrome, atypical apical ballooning, ampulla cardiomyopathy or transient left ventricular dysfunction syndrome characterize the takotsubo syndrome that usually follows emotional distress. This clinical entity has been excessively discussed nowadays but there are many questions regarding its etiology, pathophysiology and treatment which still remain unanswered. It has been emphasized recently [2] that adrenaline, takotsubo, anaphylaxis, and Kounis syndrome (ATAK) constitute a challenging contemporary complex that needs “attacking” in order to elucidate its etiology and pathophysiology and apply the proper preventive and therapeutic measures.

Abstract 19613: Ventricular Repolarization in Transient Apical And Midventricular Ballooning

The aim of the present study was to assess potential differences in cardiac repolarization dynamics in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB). Even though repolarization abnormalities and QT interval prolongation in the surface electrocardiogram (ECG) have been consistently reported, repolarization dynamics have not yet been investigated in the AB and MB variants. We hypothesized that differences in regional sympathetic denervation may induce differential effects on cardiac repolarization. METHODS: In a prospective single-center study, 49 consecutive patients with transient left ventricular dysfunction syndrome underwent 3-channel-Holter-ECG-recording on the third day after admission. A total of 27 recordings of patients with AB and 10 recordings of patients with MB were valid for beat-to-beat-QT-interval-analyses. RESULTS: There were no significant differences in baseline clinical characteristics between AB and MB patients. Patients with MB showed significantly lower values for mean RR interval (835 ± 104 vs. 908 ± 118 ms; P<.05). Both, Bazett- and Fridericia-corrected QT-intervals were significantly longer in MB patients (QTcB 441.9 ± 38 vs. 483.4 ± 40ms; P<.05; QTcF 435.0 ± 36 vs.469.4 ± 36.5 ms; P<.05). Parameters of QT-interval variability (QTSD) and QT-interval dynamicity (QT/RR-slope) also exhibited significant differences between groups (diagram). CONCLUSION: There are significant differences in cardiac repolarization between AB and MB syndromes. Patients with MB show more prolonged QT-intervals and a higher degree of heterogeneity of ventricular repolarization. Thus, regional midventricular sympathetic denervation may be associated with even higher arrhythmic risk in transient left ventricular dysfunction syndrome.

Mast cell activation disorders presenting with cerebral vasospasm-related symptoms: A “Kounis-like” syndrome?

Kounis syndrome is characterized by acute coronary events occurring throughout anaphylactic or anaphylactoid reactions, even in patients with normal coronary arteries. Clinical manifestations of this syndrome have been attributed to coronary artery spasm or plaque erosion or rupture induced by acute inflammatory mediators release during these reactions [ 1 Kounis N.G. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm?. Int J Cardiol. 2006; 110: 7-14 Abstract Full Text Full Text PDF PubMed Scopus (385) Google Scholar , 2 Cevik C. Nugent K. Shome G.P. Kounis N.G. Treatment of Kounis syndrome. Int J Cardiol. 2010; 143: 223-226 Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar , 3 Morel O. Jesel L. Morel N. Nguyen A. Trinh A. Ohlmann P. Imperiale A. Transient left ventricular dysfunction syndrome during anaphylactic shock: vasospasm, Kounis syndrome or epinephrine-induced stunned myocardium?. Int J Cardiol. 2010; 145: 501-503 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar , 4 Biteker M. A new classification of Kounis syndrome. Int J Cardiol. 2010; 145: 553 Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar ]. Similarly, vasospasm-related symptoms involving organs other than the heart might also occur in patients with conditions characterized by acute mast cells (MC)-mediator release, as in systemic mastocytosis (SM) and MC activation disorders (MCAD). We report two patients with MC-related disorders who developed transient ischemic attacks while they had previous history of chest pain and Kounis syndrome.

Afferent baroreflex failure and tako-tsubo cardiomyopathy

Tako-tsubo is a Japanese fisherman’s octopus trapping pot. The word has become popular to describe a type of cardiomyopathy in which the left ventricle of the heart transiently balloons at the apex and mid portions and, with a little imagination, looks like a tako-tsubo [1]. Variant forms of transient left ventricular dysfunction in which the apex is not affected have also been described [2]. Additional names for this clinical syndrome are transient left ventricular dysfunction syndrome, stress cardiomyopathy or apical ballooning cardiomyopathy. Patients present similarly to those with myocardial infarction, typically with chest pain and dyspnea and with findings on electrocardiography which are characteristic of myocardial infarction such as ST segment elevation and T wave inversion [3–5]. However, elevation of cardiac biomarkers such as troponin is modest and, in addition, the coronary arteries show no flow-limiting stenosis on conventional angiography [3]. Tako-tsubo cardiomyopathy resolves spontaneously and nearly all patients completely recover within a few weeks [6]. Thus, tako-tsubo cardiomyopathy may be considered to represent myocardial ‘‘stunning’’ rather than a permanent injury. What is so special about this peculiar ballooning of the heart? First, it affects women much more often than men, and perhaps most intriguingly, it occurs frequently after a catastrophic emotional stress, such as an earthquake [7] or the unexpected death of a close friend or relative [3, 4]. Of course, events that occur after emotionally charged situations are always suspected to be caused by high levels of catecholamines, both norepinephrine, the neurotransmitter of the sympathetic nervous system, and epinephrine, the hormone that classically increases with stress. Indeed, patients with tako-tsubo cardiomyopathy have a 30-fold increase in their plasma levels of norepinephrine and epinephrine, which is substantially higher than the increase seen in patients with acute myocardial infarction [4]. Moreover, cases of tako-tsubo cardiomyopathy have been reported following intravenous infusion of epinephrine [8] or norephinephrine [9] as well as in patients with pheochromocytoma who have endogenous catecholamine surges [10–12]. Furthermore, microscopic analysis of myocardium in patients with tako-tsubo syndrome may show contraction band necrosis and focal inflammatory infiltrates, as seen in syndromes of catecholamine excess [13]. Recently, analysis of endomyocardial biopsies taken from patients who have tako-tsubo cardiomyopathy has shown alteration in expression of the sarcoplasmic reticulum calcium ATPase and dephosphorylation of phospholamban, changes which suggest overstimulation of myocardial beta adrenoceptors in this syndrome [14]. In this issue of clinical autonomic research Berganzo et al. suggest a possible link between afferent baroreflex dysfunction and tako-tsubo cardiomyopathy. This is not surprising. Normally, increases in sympathetic activity are restrained by the baroreflexes, which are classic negative feedback loops. Afferent baroreflex dysfunction (also called baroreflex failure to distinguish it from autonomic efferent failure) is a neuro-visceral disorder that selectively affects the relay of afferent baroreceptor information from the carotid sinus and aortic arch to the nucleus tractus solitarius (NTS) in the brainstem [15–17]. In patients with L. J. Norcliffe-Kaufmann (&) Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA e-mail: lucynorcliffe@gmail.com

Síndrome de tako-tsubo. Discinesia transitoria del ventrículo izquierdo. Presentación de nuestra casuística

This syndrome was described in 1990. It is characterized by chest pain that simulates an acute coronary syndrome (ACS), with alterations in the ECG, but with normal coronary arteries. We present 16 patients admitted in our ICU, who met the criteria of transient left ventricular dysfunction syndrome (TLVDS). All but 1 patient were women, with age in general higher than 55 years. Chest pain was detected in the 75% of them. A total of 43% had emotional stress as 56% had an elevation of the ST segment, essentially anterolateral. The increase of the biomarkers was slight-to-moderate, with the exception of one patient in whom it was especially high. All of them had undergone a coronary arteriogram and ventriculography, and either septal or anterolateral dyskinesia had been detected, with normal ejection fraction. In 75% of the cases the dyskinesia had disappeared between 4 days to 6 weeks.

Too sympathetic? Role of sympathoexcitation in Takotsubo cardiomyopathy

Takotsubo cardiomyopathy is classically described as sudden and transient left ventricular apical ballooning in the absence of significant coronary artery disease. First described by Dote et al, 1 Dote K. Sato H. Tateishi H. Uchida T. Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol. 1991; 21: 203-214 PubMed Google Scholar the cardiomyopathy was named “Takotsubo” because the narrow neck and round-bottomed left ventricle resemble a traditional Japanese octopus trap. Since the initial description of the condition, patients with transient left ventricular dysfunction have been identified with both the typical apical ballooning (AB) pattern and an alternative mid-left ventricular ballooning (MB) pattern, the “inverted Takotsubo.” 2 Kurowski V. Kaiser A. von H.K. et al. Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis. Chest. 2007; 132: 809-816 Crossref PubMed Scopus (432) Google Scholar Patients present with symptoms resembling those of acute myocardial infarction, including chest pain, ST-segment elevation, and elevated cardiac enzymes. A high proportion of patients are women who develop symptoms after episodes of high emotion (after receiving bad news or being in a severe argument), and the disorder has captured the public's imagination with names such as “broken heart syndrome.” The interest of the medical profession also has been piqued, with almost 400 hits in PubMed for a search of “Takotsubo AND 2009.” Differential heart rate dynamics in transient left ventricular apical and midventricular ballooningHeart RhythmVol. 7Issue 12PreviewThe aim of the present study was to assess potential differences in cardiac autonomic nervous modulation in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB) of this syndrome. Full-Text PDF To the Editor—Takotsubo Cardiomyopathy: A Role for Magnesium?Heart RhythmVol. 7Issue 12PreviewI read with interest the original research article on the role of sympathoexcitation in Takotsubo cardiomyopathy by Raj.1 Both classic and inverted patterns of stress cardiomyopathy have been reported in association with disorders associated with catecholamine excess, including pheochromocytoma, high-dose epinephrine infusion, and Irukandji syndrome following jellyfish envenomation.2,3 Full-Text PDF

Differential heart rate dynamics in transient left ventricular apical and midventricular ballooning

The aim of the present study was to assess potential differences in cardiac autonomic nervous modulation in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB) of this syndrome. We hypothesized that differences in regional distribution of cardiac autonomic innervation in AB and MB may induce alterations in autonomic modulation, and we tested this assumption by using a combination of traditional and novel nonlinear parameters of heart rate variability (HRV). In a prospective single-center study, 49 consecutive patients with transient left ventricular dysfunction syndrome underwent Holter electrocardiographic recording on the third day after admission. A total of 27 recordings of patients with AB and 10 recordings of patients with MB were valid for analysis of HRV, nonlinear dynamic measures of HRV, detrended fluctuation analysis (DFA), and phase-rectified signal averaging (PRSA). There were no significant differences in baseline clinical characteristics between AB and MB patients. Patients with MB showed significantly lower values for mean RR interval (835 ± 104 ms vs. 908 ± 118 ms; P < .05), 1/f power law slope (-1.28 ± 0.2 vs. -1.13 ± 0.2; P < .01), and deceleration capacity (DC) (4.6 ± 1.4 ms vs. 6.0 ± 1.4 ms; P < .01), and significantly higher values for low-frequency (LF) spectral component (5.3 ± 0.5 ln ms(2)/Hz vs. 4.8 ± 0.5 ln ms(2)/Hz), LF/high-frequency (HF) (1.7 ± 0.9 ms vs. 1.3 ± 0.6 ms; P < .05), and DFA α1 (1.09 ± 0.1 vs. 0.99 ± 0.1; P < .01) than patients with AB. There were no significant correlations between parameters of HRV, DFA, 1/f power law slope, and PRSA. There are significant differences in heart rate dynamics between AB and MB syndromes. Patients with MB show stronger fractal correlations of heart rate dynamics. Thus, inhomogeneous efferent bilateral sympathetic coactivation and differences in reflex autonomic regulation may be underlying pathophysiological mechanisms for AB and MB syndromes.

Takotsubo (Stress) Cardiomyopathy and the Anesthesiologist: Enough Case Reports. Let's Try to Answer Some Specific Questions!

Takotsubo cardiomyopathy (also known as takotsubo syndrome, broken heart syndrome, ampulla cardiomyopathy, transient left ventricular apical ballooning, apical ballooning syndrome, transient left ventricular dysfunction syndrome, and stress [induced] cardiomyopathy) was first described in Japan in 1990. 1 ** It was initially characterized by a unique pattern of transient (hours to weeks) wall motion abnormality (“transient left ventricular apical ballooning”) occurring in the absence of significant epicardial coronary artery disease, presenting as an acute coronary syndrome, most frequently in postmenopausal elderly women, often triggered by stressful situations. It has since been observed throughout the world and under various circumstances.†† This condition was first described in the perioperative period in the North American anesthesia literature via case reports that appeared in the September 2006 issues of Anesthesia & Analgesia 4 and Anesthesiology. 5 Since that time, multiple case reports of periprocedural (e.g., endoscopy, catheterization, and electroconvulsive therapy) and at least 25 to 38 perioperative cases of takotsubo cardiomyopathy have appeared 6–23 with the latest in this issue of Anesthesia & Analgesia. 24,25 Anesthesiologists may also confront this syndrome while caring for patients with aneurysmal subarachnoid hemorrhage (A-SAH), 26–29 pheochromocytoma, 30–37 and other critical illnesses. 3,38,39 In this issue of Anesthesia & Analgesia, Daly and Dixon 24 report on 2 cases of takotsubo cardiomyopathy that occurred in an elderly (76- and 78-year-old) man and woman,

Tako-Tsubo Cardiomyopathy in a Patient with Advanced Colorectal Adenocarcinoma

Transient left ventricular dysfunction syndrome (TLVDS), or Tako-Tsubo cardiomyopathy (TC), is a clinical entity in which patients present with features of acute coronary syndrome, electrocardiogram abnormalities, and transient left ventricular (apical or mid-ventricular) dysfunction. Patients usually recover from this condition four to six weeks after the event. The etiology or triggering factors of TC remains unknown. Various triggering factors have been associated with this syndrome, with one of the most recent being malignancies. In this case report we present a postmenopausal female with underlying advanced malignancy who presented with TC. This is consistent with a recent hypothesis that in addition to currently known triggering factors, malignancies might well trigger TC in the context of a stressor or paraneoplastic phenomenon.

Transient left ventricular dysfunction syndrome during anaphylactic shock

Transient left ventricular dysfunction syndrome (TVLDS) has been rarely observed during anaphylactic shock and its pathophysiology remains still enigmatic. Multivessel epiicardial coronary spasm or coronary microvascular impairment were suggested as primary causative mechanism. Alternatively, the release of various inflammatory mediators including histamine could induce a coronary artery spasm or erosion/rupture of an atheromatous plaque contributing to TLVDS. Challenging this paradigm, a direct catecholamine acute toxicity was recently proposed as a causative mechanism of the stunned myocardium observed in TLVDS. We report a patient with severe TLVDS during anaphylactic shock. Whilst ECG depicted a drastic ST segment elevation in the anterior leads, cardiac catheterism confirms the co-existence of severe reduction of systemic vascular resistance and normal coronary angiogram. In the absence of any documented spasm or perfusion abnormalities, the defective uptake of 123I-metaiodobenzyl-guanidine (123I-mIBG) in the hypocontractile LV segments suggests that epinephrine-induced stunned myocardium is the main mechanism of LV systolic dysfunction. This report highlights that excess doses of epinephrine might contribute to TLVDS through direct myocardial stunning. The possible noxious contribution of other mediators such as histamine or cytokines released in the Kounis syndrome remains to be established.

Recurrent form of neurogenic stunned myocardium: Is myocardial adrenergic receptor distribution a dynamic process?

Neurogenic stunned myocardium mediated by stress-induced catecholamine acute release is considered as the central causative mechanism of transient left ventricular dysfunction syndrome (TVLDS). Interindividual differences in both LV β-adrenergic receptor density and sympathetic innervation were proposed to explain the atypical forms of TVLDS. Whether this distribution is independent of age or may vary during ageing still remains unclear. We report a recurrent form of TLVDS characterized by two different patterns. Whilst myocardial receptor distribution or sympathetic innervation appears to follow a dynamic process, the precise determinants of these variations remain largely unknown.

Transient left ventricular dysfunction syndrome: Patho-physiological bases through nuclear medicine imaging

Takotsubo cardiomyopathy (TTC) is a novel heart disease, mimicking acute myocardial infarction. The term "transient left ventricular dysfunction syndrome" (TLVDS) seems to be more appropriate since variant forms of TTC sparing apical segments (mid-ventricular ballooning syndrome (MVBS) and inverted TTC) have been described. Patho-physiological bases of TLVDS remain poorly understood and its optimal management is until now empirical. Our aim was to characterize patho-physiological mechanisms of TLVDS by means of nuclear medicine procedures and to discuss the clinical usefulness of isotopic imaging for a non-invasive diagnosis of TLVDS. During the sub acute phase, eighteen patients with TLVDS (13 TTC and 5 MVBS) underwent myocardial (99m)Tc-tetrofosmin or (201)Thallium Gated Single Photon Emission Computed Tomography (G-SPECT) (n=11), (123)I-mIBG SPECT (n=8) and (18)F-FDG Gated Positron Emission Tomography (G-PET) (n=15), assessing respectively LV perfusion, sympathetic innervation and glucose metabolism. Hypocontractile LV segments were characterized by normal perfusion but reduced uptake of (18)F-FDG and (123)I-mIBG. Topography and extent of metabolic defects and innervation abnormalities were largely overlapping. Follow-up (123)I-mIBG SPECT and (18)F-FDG G-PET were performed in selected patients showing rapid normalization of LV motion and progressive improvement of both glucose metabolism and sympathetic innervation. With the hypothesis of neurogenic stunned myocardium as the central causative mechanism of TLVDS, (123)I-mIBG SPECT seems to be the most specific diagnostic technique. Sympathetic function and glucose metabolism seem to be strictly correlated in the hypocontractile LV segments. Finally, our results underline the role of nuclear imaging in the setting of patho-physiological mechanisms of TLVDS.

Long‐term prognosis of the transient left ventricular dysfunction syndrome (Tako‐Tsubo cardiomyopathy): Focus on malignancies

The pathophysiology and long-term prognosis of the transient left ventricular dysfunction syndrome (LVDS, Tako-Tsubo cardiomyopathy) is largely unknown. To investigate the prevalence of malignancies and long-term mortality in patients with LVDS. Fifty patients with LVDS (47 females and 3 men, age 70+/-10 years) and 50 age- and gender-matched control patients with acute anterior myocardial infarction (MI) were evaluated. Nine patients (18%) with LVDS and 3 patients (6%) with MI had a previous history of malignancy at the time of the index event. On follow-up (2.9+/-1.6 years), 7 malignancies were newly diagnosed in the LVDS cohort whereas no new case of malignancy was found in the control group (p=0.01, odds ratio 16.95, 95% confidence interval [CI] 1.93-304.60). Overall mortality during follow-up did not differ significantly between both groups (hazard ratio 1.44 for death in LVDS patients, 95% CI 0.52-3.95, p=0.49); however, of those patients who died, cardiac deaths were more frequent in patients with MI (100% versus 11% in patients with LVDS, p<0.001). Our data suggest an association of LVDS with malignancies, potentially as a result of paraneoplastic phenomena. Long-term prognosis of patients with LVDS is no better than in patients with acute MI.

Apical Ballooning Syndrome or Takotsubo Syndrome: A Novel Cardiac Syndrome

Apical Ballooning Syndrome or Takotsubo Syndrome: A Novel Cardiac Syndrome

Apical and Midventricular Transient Left Ventricular Dysfunction Syndrome (Tako-Tsubo Cardiomyopathy) Frequency, Mechanisms, and Prognosis

The frequency and potential differences between patients with apical ("typical") and midventricular ("atypical") ballooning have not been described. Consecutive patients with the diagnosis of a troponin-positive acute coronary syndrome (ACS) were prospectively included into a registry (n = 3,265). Of those, 2,944 patients underwent left-heart catheterization and form the study population. Demographic, clinical, and angiographic data including assessment of microvascular dysfunction (Thrombolysis in Myocardial Infarction [TIMI] blush grade, corrected TIMI frame count), as well as clinical outcome were assessed in all patients. In patients with troponin-positive ACS, the frequency of transient cardiomyopathy was 1.2% (35 of 2,944 patients). Typical apical wall motion abnormality was observed in 21 of 35 patients (60%), as compared to an atypical (midventricular) pattern in 14 of 35 patients (40%). Both groups did not differ regarding demographic, clinical, laboratory, or angiographic parameters. Scintigraphy and PET studies were performed in 17 of 35 patients (49%) with transient cardiomyopathy, and showed a strong correlation between location of wall motion abnormality and myocardial metabolism defects, with a significantly higher apical decrease in glucose uptake in patients with a typical pattern. Transient cardiomyopathy affects approximately 1% of patients with a troponin-positive ACS. A typical apical wall motion abnormality is seen in only 60% of patients. Transient cardiomyopathy, also termed Tako-Tsubo cardiomyopathy, therefore should no longer be regarded as an exclusively apical ballooning syndrome, but rather a transient left ventricular dysfunction syndrome with an apical or midventricular pattern of wall motion abnormality.