Abstract Context Catecholamine-related factors are the most popular explanation for the occurrence of Takotsubo syndrome. An aldosterone-related mechanism, however, has not been proposed. Case Description A 45-year-old male patient presenting with ST-segment elevation myocardial infarction was diagnosed with primary aldosteronism, severe hypokalemia, and Takotsubo syndrome. After excluding the known conditions of apical ballooning and the factors of vasospasm, primary aldosteronism is considered as the major contributor to the development of Takotsubo syndrome. The potential mechanisms are discussed. Conclusions The case suggests a possible hyperaldosteronism-induced and vasoconstriction-mediated mechanism in the development of Takotsubo syndrome. Patients with Takotsubo syndrome usually present with acute coronary syndrome (1). Catecholamine-related hypotheses, which involve coronary spasm, are currently the most widely accepted pathophysiological mechanism of the disease (1). A few previous studies have proposed other mechanisms. In the present case, we reveal a potential aldosterone-related mechanism in the occurrence of Takotsubo syndrome. Case Presentation A 45-year-old male patient presenting with severe chest pain for more than 3 hours was admitted to our center. The patient had a history of chest tightness for more than 1 year and uncontrolled hypertension for 2 years. Blood pressure on admission was 166/107 mm Hg. Electrocardiogram (ECG) suggested anterior ST-segment elevation myocardial infarction (STEMI) [Fig. 1(a)]. Biochemistry tests revealed elevated cardiac biomarkers, with myoglobin reaching 753.5 ng/mL, troponin-T of 269.2 ng/L, creatine kinase-MB of 16.52 ng/mL, and serum potassium of 2.64 mmol/L. Figure 1. View largeDownload slide (a) ECG identified a normal sinus rhythm with ST-segment elevation in leads V1, V2, and V3, whereas Q valves are found in leads II, III, and aVF. (b) The ECG identified a normal sinus rhythm with ST-segment elevation in leads I, II, and V6. (c) The ECG, taken at 1-year follow-up, illustrated no significant residual ST-T wave changes. Figure 1. View largeDownload slide (a) ECG identified a normal sinus rhythm with ST-segment elevation in leads V1, V2, and V3, whereas Q valves are found in leads II, III, and aVF. (b) The ECG identified a normal sinus rhythm with ST-segment elevation in leads I, II, and V6. (c) The ECG, taken at 1-year follow-up, illustrated no significant residual ST-T wave changes. The patient was given nitroglycerin and potassium replenishment and underwent emergency coronary angiography, which revealed patent coronary arteries with no substantial stenosis. However, cardiac ventriculography revealed hypokinesis of the left ventricular (LV) apical wall (Fig. 2). Echocardiography demonstrated consistent findings (LV ejection fraction, 60%). The echocardiography also showed thickening in both the interventricular septum (13 mm) and the LV posterior wall (10 mm), which suggested ventricular remodeling. Four hours later, the patient had another episode of severe chest pain with a drop of blood pressure from 162/115 to 80/52 mm Hg. ECG was performed immediately and revealed inferior and lateral STEMI [Fig. 1(b)]. Medications were used, including nitroglycerin, morphine, dopamine, and isoprenaline. Ten minutes later, the patient’s symptom was partially relieved, with blood pressure returning to 118/75 mm Hg and ECG reverting to the previous state, with ST-segment elevation in leads V1, V2, and V3 suggesting coronary spasm. Multiple catecholamine tests showed no increase in plasma or 24-hour urine. Repeated renin-aldosterone tests suggested increased levels of aldosterone and angiotensin II, with plasma aldosterone reaching 32.04 ng/dL, plasma renin activity reaching 0.24 ng/mL/h, and the aldosterone-to-renin ratio reaching 133.5 ng/dl:ng/mL/h. Captopril trial showed no inhibition of aldosterone. Enhanced abdominal computed tomography scan revealed bilateral adrenal gland enlargement. The adrenal venous sample showed a higher aldosterone level in the right suprarenal vein than in the left (264.29 vs 47.54 ng/dL). Thus, the diagnosis of primary hyperaldosteronism was confirmed. Figure 2. View largeDownload slide (a) Ventriculography showed hypokinesis of the apical wall. (b–f) Coronary angiogram showed the absence of substantial coronary stenosis. Figure 2. View largeDownload slide (a) Ventriculography showed hypokinesis of the apical wall. (b–f) Coronary angiogram showed the absence of substantial coronary stenosis. The patient was scheduled to undergo laparoscopic right adrenalectomy. Intraoperative pathological examination revealed nodular hyperplasia of adrenal cortex, with four 0.4 cm adenomatous nodules dispersed within the cortex. Postsurgery recovery was uneventful, with plasma aldosterone dropping to 16.01 ng/dL, plasma renin activity of 3.06 ng/mL/h, and aldosterone-to-renin ratio of 5.23 ng/dL:ng/mL/h. During the first year of follow up, repeated biochemistry tests demonstrated normal serum potassium without potassium supplement, and continual blood pressure monitoring showed an average blood pressure around 120/70 mm Hg (only metoprolol was taken). No recurrence of the aforementioned cardiac symptoms was observed, and echocardiography, which was performed at 6 months and 1 year, showed a well-functioning heart (LV ejection fraction, 70% and 66%) with no hypokinesis of the apical wall and with interventricular septum and LV posterior wall thickness reversed to 8 mm. ECG and plasma aldosterone were normal at 1 year [Fig. 2(c)]. Discussion The patient was diagnosed with primary hyperaldosteronism, severe hypokalemia, STEMI, and Takotsubo syndrome. Other known factors that might lead to vasospasm or apical ballooning, including emotional stress, myocardial bridging, hypertrophic cardiomyopathy, cigarette smoking, and vasoactive drug abuse, were absent. There was no recurrence of a cardiac ischemic symptom during the 1-year follow-up period, and the patient’s hyperaldosteronism was cured. Therefore, primary aldosteronism is considered to be the major contributor to the development of Takotsubo syndrome, even if no previous studies have revealed an aldosterone-related mechanism (1). Multiple mechanisms might be involved in this case because an abnormal renin-angiotensin-aldosterone system could induce not only coronary vasoconstriction but also cardiac remodeling. Uncontrolled chronic hyperaldosteronemia could lead to coronary constriction by impairing vascular smooth muscle cell function via the suppression of SERCA 2a expression and reduction of NO synthesis through affecting the submembranous actin network of endotheliocytes (2, 3). These could affect medium-sized arteries and arterioles. Thus, multivessel coronary vasospasm and coronary microvascular vasoconstriction could be induced. Also, LV remodeling was observed in this case, which might lead to functional and structural alterations of the coronary microcirculation (4). Under the combined effects of these possible factors, diffuse impairment of cardiac microcirculation and further reduction of LV wall movement were expected. The patient’s cardiac impairment was relieved after the removal of etiology, indicating that the adverse effects of aldosterone were reversible in this case. Also, previous studies demonstrated that angiotensin-converting enzyme inhibitors/angiotensin receptor blocker is the only effective treatment to reduce the recurrence rate of Takotsubo syndrome, suggesting the renin-angiotensin-aldosterone system plays, at least, a potential role in the recurrence of this disease (5). Our results link hyperaldosteronism with Takotsubo syndrome. Although future studies are warranted to verify the precise mechanism, the potential role of aldosterone in the development and recurrence of Takotsubo syndrome should not be ignored. Abbreviations: ECG electrocardiogram LV left ventricular STEMI ST-segment elevation myocardial infarction. Acknowledgments Financial Support: This work was supported by the Sichuan Provincial Innovation Team of Science and Technology Grant 2017TD0004. Disclosure Summary: The authors have nothing to disclose. References 1. Akashi YJ, Nef HM, Lyon AR. Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol . 2015; 12( 7): 387– 397. Google Scholar CrossRef Search ADS PubMed 2. Chou CH, Chen YH, Hung CS, Chang YY, Tzeng YL, Wu XM, Wu VC, Tsai CT, Wu CK, Ho YL, Wu KD, Lin YH, Group TS; TAIPAI Study Group. Aldosterone impairs vascular smooth muscle function: from clinical to bench research. J Clin Endocrinol Metab . 2015; 100( 11): 4339– 4347. Google Scholar CrossRef Search ADS PubMed 3. Oberleithner H, Kusche-Vihrog K, Schillers H. Endothelial cells as vascular salt sensors. Kidney Int . 2010; 77( 6): 490– 494. Google Scholar CrossRef Search ADS PubMed 4. Rodriguez-Porcel M, Zhu XY, Chade AR, Amores-Arriaga B, Caplice NM, Ritman EL, Lerman A, Lerman LO. Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension. Am J Physiol Heart Circ Physiol . 2006; 290( 3): H978– H984. Google Scholar CrossRef Search ADS PubMed 5. Singh K, Carson K, Usmani Z, Sawhney G, Shah R, Horowitz J. Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy. Int J Cardiol . 2014; 174( 3): 696– 701. Google Scholar CrossRef Search ADS PubMed Copyright © 2018 Endocrine Society
Journal of Clinical Endocrinology and Metabolism – Oxford University Press
Published: Jan 1, 2018
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