Camilli M

Crea F.

Del Buono MG

Fracassi F

Gurgoglione FL

Ingrasciotta G

Meucci MC

Montone RA

Niccoli G

English

Archivio istituzionale della Ricerca -  Università degli Studi di Parma

Contents lists available at ScienceDirectAutonomic Neuroscience: Basic and Clinicaljournal homepage: www.elsevier.com/locate/autneuTakotsubo syndrome and left ventricular non-compaction cardiomyopathy:Casualty or causality?Marco Giuseppe Del Buonoa, Rocco Antonio Montoneb, Massimiliano Camillia,Filippo Luca Gurgoglionea, Gessica Ingrasciottaa, Maria Chiara Meuccia, Francesco Fracassia,Giampaolo Niccolia,b,⁎, Filippo Creaa,ba Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Rome, Italyb Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, ItalyA R T I C L E I N F OKeywords:Takotsubo syndromeLeft ventricular non-compactionCardiomyopathyStressPsychiatric illnessA B S T R A C TTakotsubo syndrome (TS) is a condition of transient regional ventricular systolic dysfunction, usually presentingwith acute chest pain and/or dyspnea, that is increasingly recognized especially in post-menopausal womenfollowing a psychological or physical stress. Initially considered as a benign condition with an isolated and self-limiting episode, it is now recognized that it is associated with a significant risk of in-hospital mortality and ofrecurrence. We herein describe a case of a 61-year-old female with left ventricular non-compaction cardio-myopathy (LVNC) who experienced a recurrence of TS, highlighting the potential pathophysiological role forLVNC in predisposing this syndrome and its recurrence. Moreover, we underscored possible therapeutic im-plications deriving from this case.1. Case reportA 61-year-old post-menopausal Caucasian female with history ofanxiety, tobacco consumption, hypercholesterolemia and an episode ofapical Takotsubo Syndrome (TS) in the previous six months, wasbrought to the emergency department because of the onset of squeezingchest pain a few hours earlier. Blood pressure was 100/60mmHg,temperature 35.7 °C, heart rate 76 beats per minute, respiratory rate 16breaths per minute. She was not taking any medication. She relatedintense emotional stress in the days preceding admission.Cardiopulmonary examination revealed an S3 galop without signs ofsystemic and/or pulmonary congestion. A 12‑lead electrocardiogram(ECG) showed sinus rhythm, heart rate of 61 beats per minute, QTcinterval of 471ms and deep inverted T waves involving the inferior andanterolateral leads. There were no significant ST segment deviationand/or pathological Q waves (Fig. 1). Ultra-sensitive Troponin I and N-terminal pro b-type natriuretic peptide at admission were 0.059 ng/ml(normal values< 0.04 ng/ml) and 4750 pg/ml (normal values< 150pg/ml) respectively. The InterTAK score calculated, which takes intoaccount clinical and diagnostic test results, was 78 with a probability ofTS of 96.3% (female sex: 25 points; emotional stress: 24 points; no ST-segment depression: 12 points; acute, former or chronic psychiatricdisorder: 11 points; prolonged QTc Time, female> 460ms: 6 points).Transthoracic echocardiogram showed normal ventricular size, mod-erate–severe left ventricular (LV) systolic dysfunction most prominentin the mid-apical segments (ejection fraction [EF] 35%), no mitral re-gurgitation and/or LV outflow tract obstruction, and evidence of hyper-trabeculation of the apical segments. She was admitted to the coronarycare unit and urgent coronary angiography documented non-obstructedcoronary arteries. The ventriculogram showed apical ballooning withregional akinesia localized to the apical segments and relative sparingof the mid-basal segments (Fig. 2A). Beta (β)-adrenergic receptorblockers, diuretics, and angiotensin converting enzyme (ACE) inhibitorswere initiated with a progressive recovery of the LV systolic functionduring the following days, without need of inotropic support and/orevidence of arrhythmias. Seven days after the initial presentation,cardiovascular magnetic resonance (CMR) documented a global re-covery of LV systolic function (EF 53%), hypokinesia of the apicalsegments, absence of delayed gadolinium enhancement and/or edema,and prominent trabeculation at apical segments (ratio between thethickness of the non-compacted and compacted myocardial layers inend-diastole> 2.3) (Fig. 2B) consistent with the diagnosis of LV non-compaction cardiomyopathy (LVNC) (Petersen et al., 2005; Finstereret al., 2017). Neurological examination showed no evidence of anymotor, sensory and/or coordination deficits. She denied family historyof neurological or neuromuscular disorders. Patient was dischargedhttps://doi.org/10.1016/j.autneu.2019.02.008Received 26 November 2018; Received in revised form 27 February 2019; Accepted 27 February 2019⁎ Corresponding author at: Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, L.go F. Vito, 1, 00168 Rome, Italy.E-mail address: gniccoli73@hotmail.it (G. Niccoli).Autonomic Neuroscience: Basic and Clinical 218 (2019) 64–671566-0702/ © 2019 Elsevier B.V. All rights reserved.Twith cardiovascular (ACE inhibitor and β-blocker) and psychiatricmedications.2. DiscussionTS, also known as stress cardiomyopathy, is a neurocardiogenicform of acute and transient regional LV myocardial dysfunction with anon-coronary artery distribution, usually affecting elderly women fol-lowing the experience of an emotional or physical stress (Medina deChazal et al., 2018). Despite the increasing awareness, it is still un-derdiagnosed and is estimated to represent 1–2% of patients with in-itially suspected acute coronary syndrome (ACS) (Medina de Chazalet al., 2018). Previously considered a benign condition due the rever-sibility of disease process, in-hospital mortality risk is similar to thosepatients presenting with ACS, with a risk of recurrence of 2–4% perpatient year (Medina de Chazal et al., 2018; Templin et al., 2015).Despite the elusive pathophysiology, the brain-heart axis and neuro-hormonal activation are assuming a pivotal role in the pathogenesis ofthis syndrome (Medina de Chazal et al., 2018; Pelliccia et al., 2017).The complex neocortical and limbic integration following the inter-pretation of a threatening stimulus activates the neural stress responsemediated by the brain stem and arcuate nucleus in the hypothalamus(Medina de Chazal et al., 2018; Pelliccia et al., 2017). This results in theabrupt release of stress-related neuropeptides stored in the pre-synapticterminations (i.e. norepinephrine and neuropeptide Y) and circulatingcatecholamines at myocardial level and, through a direct catecholaminetoxicity and/or an acute microvascular dysfunction, may explain themyocardial stunning (Medina de Chazal et al., 2018; Pelliccia et al.,2017; Sonnino et al., 2017). An increased sympathetic drive and con-ditions associated with endothelial dysfunction (i.e. diabetes, post-menopausal state, asthma) may therefore predispose to acute micro-vascular and myocardial dysfunction (Medina de Chazal et al., 2018).TS has been associated with LVNC in few case reports (Table 1) (DeRosa et al., 2011; Karamitsos et al., 2008; Finsterer et al., 2013). LVNCis an uncommon form of cardiomyopathy, sporadic or familial, moreprevalent in male and often described in association with neuromus-cular disorders, characterized by a meshwork of interwoven myocardialstrings lined with endocardium, resulting in thickened myocardiumwith two layers consisting of a non-compacted and a thin compactedlayer of myocardium (Petersen et al., 2005; Finsterer et al., 2017). In-trauterine failure of the fetal myocardial compaction is considered onlyone of the potential pathophysiological mechanisms (Finsterer et al.,2017). Echocardiography is the basic tool for diagnosis, however it failsto detect LVNC in a consistent proportion of patients then confirmedwith LVNC at CMR, due to suboptimal image quality, lack of uniformityaccepted criteria, technical limitations and clinical setting where thetest is performed (Diwadkar et al., 2017).Whether LVNC and TS might be pathophysiologically linked re-mains elusive. The apical a/hypo-kinesis during TS, may more easilyunmask the appearance of hyper-trabeculated myocardium and in-crease the diagnostic power. However, in patients with LVNC the sub-verted myocardial architecture has been associated with coronary mi-crovascular dysfunction and impaired coronary flow reserve (Jenniet al., 2002), therefore potentially facilitating the occurrence (and re-currence) of TS in predisposed individuals in response to emotional orphysical stress (Medina de Chazal et al., 2018; Finsterer et al., 2013;Galiuto et al., 2010). Additionally, heart rate variability has been re-ported to be impaired in adults with LVNC, suggesting a vagal with-drawal or sympathetic enhancement (Kawasaki et al., 2005).In the absence of randomized studies, long-term treatment of TSremains empirical and retrospective data showed that ACE inhibitorsand angiotensin-receptor blockers were associated with a lower in-cidence of recurrence (Singh et al., 2014). Unexpectedly, no benefit wasobserved with β-blockers use (Singh et al., 2014) despite their potentialtherapeutic effects in conditions of increased sympathetic tone, in an-xiety and in the context of coronary microvascular dysfunction. Cur-rently, no pharmacological treatments are recommended in asympto-matic patients with LVNC and without LV dysfunction or dilatation. Assimilarly reported by Finsterer et al. (2013), TS may recur in patientswith LVNC because of the predisposing substrate of chronic coronaryFig. 1. ECG at presentation showed sinus rhythm, prolonged QTc interval (471ms), deep inverted T waves in infero- and anterolateral leads.M.G. Del Buono, et al. Autonomic Neuroscience: Basic and Clinical 218 (2019) 64–6765Fig. 2. Left ventriculography showed the typical apical ballooning in end-systole (Panel A). CMR performed during the recovery phase confirmed the apical hy-pertrabeculation with a maximum end-diastolic non-compacted to compacted myocardial thickness ratio of 2.7 (> 2.3) (Panel B).Table 1Clinical characteristics of patients presenting with TS and underlying LVNC.Case 1Finsterer et al. (2013)Case 2Karamitsos et al. (2008)Case 3De Rosa et al. (2011)Case 4Del Buono MG, et al.Age (years) 47 76 12 61Race Caucasian – – CaucasianSex Female Female Female FemaleTakotsuboDiagnostic modality Trans-esophageal echocardiography Ventriculography Trans-thoracic echocardiography VentriculographyPattern Apical Apical Apical ApicalTrigger Physical (post-surgery) – Physical (intracranial astrocytoma withhypertensive hydrocephalus)EmotionalClinical presentation Cardiac arrest due to ventricularfibrillationChest pain Respiratory arrest and pulmonaryedemaChest painComplications Ventricular arrhythmias – Ventricular arrhythmias andcardiogenic shockNoRecurrent episodes Yes, 10months later (presenting withchest pain and dyspnea)– – Yes, 8months later (presentingwith chest pain)LVNCAreas of hypertrabeculation Apical Mid-ventricular andapicalMid-ventricular and apical Apical segmentsDiagnostic modality Trans-esophageal echocardiography CMR CMR CMRNeuromuscular disorder Yes (myotonic dystrophy type 1) – – NoAbbreviations: CMR: cardiac magnetic resonance; LVNC: left ventricular non-compaction cardiomyopathy.M.G. Del Buono, et al. Autonomic Neuroscience: Basic and Clinical 218 (2019) 64–6766microvascular dysfunction and sympathetic overdrive. Therefore, inpatients with LVNC, long term treatment with ACE inhibitors and β-blockers, after the first episode of TS, might be useful to prevent itsrecurrence. It is worth noting that in the case reviewed ACE inhibitorsand β-blockers were stopped six-months after the first episode of TS.Whether β-blockers and/or ACE inhibitors could have prevented re-currence of TS is unknown.Finally, this patient experienced a recurrent episode of TS likelyrelated to the persistence of the untreated underlying psychiatric ill-ness. This may contribute to the risk of recurrence and long-term out-comes of this syndrome (Medina de Chazal et al., 2018; Templin et al.,2015), therefore requiring special attention and an integrated assess-ment and care involving different providers.In conclusion, our report supports the potential of role of LVNCrelated myocardial structural and functional changes predisposing toTS, and the need of an individualized pharmacological approach forthese patients. Further efforts are warranted to elucidate the mechan-isms underlying TS and LVNC, their potential causative relation andpossible therapeutic implications.Conflict of interest and sources of fundingNone declared.AcknowledgementWe would like to thank Antonio Abbate, MD, PhD (VCU PauleyHeart Center, Virginia Commonwealth University, Richmond, VA) forthe critical revision of the manuscript.ReferencesDe Rosa, G., Pardeo, M., Di Rocco, C., et al., 2011. 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Takotsubo syndrome and left ventricular non-compaction cardiomyopathy: Casualty or causality?

https://air.unipr.it/bitstream/11381/2883967/1/Takotsubo%20syndrome%20and%20left%20ventricular%20non-compaction%20cardiomyopathy.pdf

Takotsubo syndrome and left ventricular non-compaction cardiomyopathy: Casualty or causality?

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