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<p class="ltrs-br-ltr-br-title"><span class="bold">Stress-Induced Cardiomyopathy and Possible Link to Cerebral Executive Function: A Case Report</span></p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold">To the Editor:</span> A complex and poorly understood relationship exists between cerebral and cardiac function.<span class="htm-cite"><a href="#ref1">1</a></span> Stress produces a range of physiological responses that are relevant to cardiovascular and cerebrovascular disease. Upon stress perception, the hypothalamic-pituitary-adrenocortical (HPA) and sympatho-adrenomedullary axes are activated, increasing bioavailability of cortisol, epinephrine, and norepinephrine.<span class="htm-cite"><a href="#ref2">2</a></span> Given the reliance of both cardiac and cerebral function on the integrity of this system, any impairment in the form of overstimulation or understimulation may manifest as cardiac and cerebrovascular pathology as illustrated in the case report below.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text"><span class="semibold-ital">Case report.</span> Ms A, a 56-year-old woman with known hypertension and hypercholesterolemia, was admitted with chest pain following an argument with a family member. She had no history of ischemic heart or neurologic disease. On presentation, she was noted to be confused.</p>
<p class="ltrs-br-ltr-br-body-text">Physical examination was unremarkable with no focal neurologic or cardiac abnormality identified. Further investigations revealed troponin T and creatine kinase peak concentrations of 1.15 μg/L (reference range, <<span class="thinspace"> </span>0.03 μg/L) and 614 U/L (reference range, <<span class="thinspace"> </span>180 U/L), respectively. Admission electrocardiogram (ECG) demonstrated sinus rhythm without ischemic changes (<span class="callout"><a target="_blank" onclick="createFigure('f1'); return false;" href="#">Figure 1</a></span>). Computed tomography scan of the brain was unremarkable. She continued to experience amnesia over the first 12 hours after her admission; amnesia had resolved by the following day. An urgent neurology consultation was sought, and the diagnosis of transient global amnesia was made on the basis of the patient’s clinical features.</p>
<div id="figure-2"> <a target="_blank" onclick="createFigure('f1'); return false;" href="#"><img border="0" id="f1" alt="Figure 1" src="13l01557f1.gif"/></a>
<p class="click-to-enlarge">Click figure to enlarge</p>
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<p class="ltrs-br-ltr-br-body-text">Ms A was admitted to the coronary care unit; serial ECG monitoring showed biphasic and deep T-wave inversion over the anterolateral leads (see <span class="callout"><a target="_blank" onclick="createFigure('f1'); return false;" href="#">Figure 1</a></span>). She underwent coronary angiography, which showed “smooth” coronary arteries and apical “ballooning” on left ventriculography consistent with takotsubo cardiomyopathy. Magnetic resonance imaging of the brain identified an incidental 6-mm left middle cerebral artery aneurysm with no associated hemorrhage or ischemia. Her final diagnoses were stress-induced (takotsubo) cardiomyopathy and transient global amnesia.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text">Adrenergic receptors are abundant throughout the brain,<span class="htm-cite"><a href="#ref3">3</a></span> myocardium,<span class="htm-cite"><a href="#ref4">4</a></span> and coronary arteries.<span class="htm-cite"><a href="#ref5">5</a></span> It is well established that catecholamine signaling through β-adrenergic receptors mediates endogenous regulation of complex central nervous system processes such as attention, arousal, learning, and memory<span class="htm-cite"><a href="#ref3">3</a>,<a href="#ref6">6–8</a></span> as well as important cardiac functions such as chronotropy, inotropy, and lusitropy. There is general consensus that this “cerebro-cardiac” process occurs via the β-adrenoceptor–mediated cyclic-AMP (cAMP)–dependent protein kinase pathway.<span class="htm-cite"><a href="#ref9">9–11</a></span></p>
<p class="ltrs-br-ltr-br-body-text">A growing body of evidence suggests that cortisone and epinephrine may also impair memory retrieval and therefore contribute to the mechanism of peritraumatic amnesia. de Quervain and colleagues reported that stress and infusion of cortisone impair memory retrieval in rats<span class="htm-cite"><a href="#ref12">12</a></span> and humans.<span class="htm-cite"><a href="#ref13">13</a></span> Sadowski et al<span class="htm-cite"><a href="#ref10">10</a></span> demonstrated that infusion of epinephrine resulted in impairment of place and response learning. Furthermore, detrimental effects of cortisone on hippocampal function during memory retrieval have been shown to require concurrent norepinephrine-dependent activation of the basolateral part of the amygdala,<span class="htm-cite"><a href="#ref14">14</a>,<a href="#ref15">15</a></span> which may be via an inhibitory G protein–coupled suppression of cAMP signaling.<span class="htm-cite"><a href="#ref16">16</a>,<a href="#ref17">17</a></span> Altogether, memory formation, consolidation, and retrieval seem to be a function of β<span class="subscript">1</span>-adrenergic receptor function, and stress impairs memory retrieval by exerting its action on the β<span class="subscript">2</span>-adrenergic receptor.</p>
<p class="ltrs-br-ltr-br-body-text">Catecholamine overstimulation has been suggested as the key pathogenetic factor in takotsubo cardiomyopathy. This cardiac syndrome is now increasingly recognized by the mental health practitioner as either a disease association<span class="htm-cite"><a href="#ref18">18</a>,<a href="#ref19">19</a></span> or a complication of a psychiatric treatment, such as electroconvulsive therapy.<span class="htm-cite"><a href="#ref20">20</a>,<a href="#ref21">21</a></span> Although the exact pathogenesis has not been fully elucidated, data from animal,<span class="htm-cite"><a href="#ref22">22</a></span> imaging,<span class="htm-cite"><a href="#ref23">23</a></span> and myocardial histologic<span class="htm-cite"><a href="#ref24">24</a></span> studies indicate that overactive β-adrenergic signaling, in the presence of supraphysiological catecholamine concentrations, plays a significant role in mediating this phenomenon. Given the density of β-adrenergic receptors are greatest<span class="htm-cite"><a href="#ref25">25</a></span> in the apical segments of the myocardium, Lyon and colleagues<span class="htm-cite"><a href="#ref4">4</a></span> suggest these receptors are important in this disease phenomenon, which explains the apical propensity of transient myocardial stunning seen in takotsubo cardiomyopathy.</p>
<p class="ltrs-br-ltr-br-body-text">Our case report provides a collection of cardiac and cerebral clinical findings that would support the common mechanistic link described in our review. Further understanding of this complex, dynamic relationship is required to formulate a more targeted preventive and therapeutic management strategy.</p>
<p class="ltrs-br-ltr-br-references-head"><span class="smallcaps">References</span></p>
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<p class="ltrs-br-ltr-br-author"><span class="bold">Samuel L. Sidharta, MBBS, BMedSc</span></p>
<p class="ltrs-br-ltr-br-author"><a href="
mailto:samuel.sidharta@adelaide.edu.au">
samuel.sidharta@adelaide.edu.au</a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Jithin K. Sajeev, MBBS</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Adam J. Nelson, MBBS, BMedSc</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Jennifer C. Cooke, MBBS</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Matthew I. Worthley, MBBS, PhD</span></p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Author affiliations:</span> Cardiovascular Research Centre, Department of Medicine, University of Adelaide, Adelaide (Drs Sidharta, Nelson, and Worthley); and Eastern Health, Department of Cardiology, Box Hill Hospital, Victoria (Drs Sajeev and Cooke), Australia.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Potential conflicts of interest</span>: None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Funding/support:</span> None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="semibold-ital">Published online:</span><span class="semibold"> </span>December 5, 2013.</p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">Prim Care Companion CNS Disord 2013;15(6):</span><span class="doi">doi:10.4088/PCC.13l01557</span></p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">© Copyright 2013 Physicians Postgraduate Press, Inc.</span></p>
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