International Journal of Cardiology 184 (2015) 545–546

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Letter to the Editor

Can thyroid break your heart? Role of thyroid in Takotsubo cardiomyopathy: A single center retrospective study Sourabh Aggarwal a,⁎, Ravikanth Papani a, Vishal Gupta b a b

Western Michigan University School of Medicine, 1000 Oakland Drive, Kalamazoo, MI 49008, United States Cardiovascular Research Institute, Echo Lab, Borgess Cardiology Institute, Kalamazoo, Michigan

a r t i c l e

i n f o

Article history: Received 6 January 2015 Accepted 21 February 2015 Available online 25 February 2015 Keywords: Takotsubo cardiomyopathy Thyroid Stress Length of stay

Takotsubo cardiomyopathy (TC), also known as stress induced cardiomyopathy, is a transient systolic dysfunction of the apical and/or mid segments of the left ventricle that mimics myocardial infarction (MI) but in the absence of obstructive coronary artery disease [1]. Although this condition was initially considered rare, it is thought to be responsible for 1% to 2% of all admissions for acute coronary syndrome [2]. TC is being increasingly diagnosed now however its etio-pathogenesis is still unclear. Various authors have reported possible association of TC and hyperadrenergic state [3]. There have been few case reports published for possible link between varied thyroid functional status and TC, ranging from severe hypothyroidism, apathetic or subclinical hyperthyroidism, endogenous or exogenous thyrotoxicosis, transient hyperthyroidism, thyroid storm, euthyroid status, following radioiodine therapy and surgical treatment for thyroid disorders [4–6]. However, clinical study to define association of thyroid status with TC is still lacking. The study was done to find the association of thyroid profile with TC. This was a single center retrospective study. Institutional Review Board at our center approved the study. All the patients diagnosed with TC between January 2006 and December 2012 at our hospital were identified retrospectively. Mayo's revised criteria for TC was used to confirm the diagnosis which included, a) Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid segments with or

⁎ Corresponding author. E-mail address: [email protected] (S. Aggarwal).

http://dx.doi.org/10.1016/j.ijcard.2015.02.058 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.

without apical involvement; b) Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture; c) New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin and d) Absence of pheochromocytoma and/or myocarditis [1]. All patients with incomplete data and angiographic evidence of obstructive lesion were excluded from the study. Baseline parameters including demographic profile, cardiac markers, thyroid studies, neutrophilic count, angiographic and echocardiographic findings were extracted. Length of stay during hospitalization and any recurrent events were noted. Student's t-test was used for all the continuous variables and chisquare test used for all the categorical variables. Pearson's correlation was used to identify correlation between length of stay and cardiac markers, white cell count, neutrophilic count and ejection fraction on left ventriculogram. P value b0.05 was considered statistically significant for the purpose of study. Seventy eight patient were identified as diagnosed with TC with 72 females (92.3%) and 6 males (7.6%) with mean age of 66.33 ± 13.37 years (range 23–91). Ten patients (12.82%) had history of coronary artery disease, 45 patients (57.69%) had history of hypertension, 16 patients (20.51%) had history of diabetes mellitus, and 29 (37.18%) patients had history of hyperlipidemia. Twenty patients (25.64%) were smoker. Mean ejection fraction on left ventriculogram on left heart catheterization was 33.77 ± 11.07 % (Median 35%, Range 10% to 60%). Emotional stressful event precipitating TC was identified only in 19 patients (24.36%) at the time of admission. Twenty seven patients (34.61%) had history of hypothyroidism and 25 patients (31.05%) were on levothyroxine replacement. Thyroid profile was available for 44 patients at time of admission and 5 patients (11.36%) were found to be in hyperthyroid state based on low TSH and/or high free T4. During a mean follow up of 2.8 ± 1.5 years, 4 patients (5.13%) had a recurrent episode of TC. Only 1 patient (1.28%) died in-hospital secondary to cardiogenic shock. Mean length of stay was 4.4 ± 3.9 days (Median 3 days, Range 1–23 days). There was a significant positive correlation between neutrophil count and length of stay and significant negative correlation between TSH value and ejection fraction on Left Ventriculogram with length of stay (P b 0.05). There was no significant correlation between length of stay and cardiac markers and total white cell count (P N 0.05) (Table 1). In this first retrospective study describing the association of Takotsubo cardiomyopathy with thyroid status, precipitating stress

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S. Aggarwal et al. / International Journal of Cardiology 184 (2015) 545–546

Table 1 Correlation of length of stay with different biomarkers.

Troponin Total CK CK-MB TSH WBC Neutrophil count EF on heart cath

Correlation coefficient

P value

0.15577 0.213081 0.178024 −0.228437 0.183737 0.344814 −0.244159

0.17 0.06 0.12 0.04 0.11 0.002 0.03

was identifiable in only 24% patients whereas 35% of the patients had a history of hypothyroidism with majority on levothyroxine replacement. Our study revealed that 92.3% of patients were females and mean age of patients with TC was 66.33 years. Previous studies have shown similar results of female preponderance ranging from 88.8% to 95% and mean age of 66 years [1,7,8]. Baseline parameters of patients in our study (including chest pain, history of hypertension, diabetes mellitus, dyslipidemia, and current smokers) were comparable to previous studies on TC [1,7,8]. So our study population was fairly comparable to previous studies on Takotsubo cardiomyopathy. Mean ejection fraction on left ventriculogram on left heart catheterization was 33.77% compared to range of 20–49% previously reported [1,7]. Recurrence rate over a mean follow up of 2.8 years was 5.13% compared to previous reported rates of 3.65% and 11.45% over mean follow up of 4.4 years [1,7]. We report in-hospital mortality of only 1.28% which is similar to 1.1% reported previously [7]. Mean length of stay in our patients was 4.4 days compared to previously reported range from 3.6 to 5 days [1,9] Thus severity of TC in our patient group was similar to those reported previously. Only 24.26% of the patients in our study had identifiable emotionally stressful event before the onset of TC, compared to previous reports of around 26% [1,7]. We now also report that significantly higher number (34.61%) had history of hypothyroidism and 25 patients (31.05%) were on levothyroxine replacement, which is significantly higher than national US average of hypothyroidism (4.6%) as per US Department of Health and Human Services [10]. Thyroid profile was available for 44 patients at time of admission and 11.36% were found to be in hyperthyroid state based on low TSH and/or high free T4. Moreover, our study also showed a significant negative correlation between TSH value and length of hospital stay in these patients. Various theories have been postulated for pathogenesis of TC including hyper-catecholaminergic state which is believed to decrease myocyte viability through calcium overload resulting in contraction

band necrosis, a histologic pattern of myocyte injury seen in TC [11]. Clinically, hyperthyroidism also mimics a state of adrenergic excess. Thyroid hormone is believed to have both direct and indirect action on myocytes partially mediated by up-regulation of β-adrenergic receptors [11]. There are few limitations in our study. It was a retrospective chart review for a single center, so the applicability of the results to general population at large is not certain. Thyroid profile was not available for all patients diagnosed with TC, which could have biased the results. Nonetheless, this is the first study to date which has analyzed the role of thyroid hormone status in TC and its predictive role in length of stay. Further, multi-centric larger studies will be needed to supplement the result and better define the association. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] A.A. Elesber, A. Prasad, R.J. Lennon, R.S. Wright, A. Lerman, C.S. Rihal, Four-year recurrence rate and prognosis of the apical ballooning syndrome, J. Am. Coll. Cardiol. 50 (5) (Jul 31 2007) 448–452. [2] P. Eshtehardi, S.C. Koestner, P. Adorjan, et al., Transient apical ballooning syndrome—clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population, Int. J. Cardiol. 135 (2009) 370–375. [3] B. Bradbury, F. Cohen, Early postoperative Takotsubo cardiomyopathy: a case report, AANA J. 79 (3) (Jun 2011) 181–188. [4] T. Micallef, M. Gruppetta, A. Cassar, S. Fava, Takotsubo cardiomyopathy and severe hypothyroidism, J. Cardiovasc. Med. (Hagerstown) 12 (11) (2011) 824–827. [5] Z. Dahdouh, V. Roule, M. Bignon, G. Grollier, Recurrent tako tsubo related to subclinical hyperthyroidism, Rev. Esp. Cardiol. 64 (11) (2011) 1069–1071. [6] R. Hatzakorzian, H. Bui, T. Schricker, S.B. Backman, Broken heart syndrome triggered by an obstructive goiter not associated with thyrotoxicosis, Can. J. Anaesth. 60 (8) (2013) 808–812. [7] M. Gianni, F. Dentali, A.M. Grandi, G. Sumner, R. Hiralal, E. Lonn, Apical ballooning syndrome or Takotsubo cardiomyopathy: a systematic review, Eur. Heart J. 27 (13) (Jul 2006) 1523–1529. [8] A. Deshmukh, G. Kumar, S. Pant, C. Rihal, K. Murugiah, J.L. Mehta, Prevalence of Takotsubo cardiomyopathy in the United States, Am. Heart J. 164 (1) (Jul 2012) 66–71.e1. [9] R.H. Hajali, A.B. Schuett, G. Suero, B. Susco, Importance of coronary angiography in the diagnosis of Takotsubo cardiomyopathy, Paper Presented at: ACC 2013. 63rd Annual Scientific Session & Expo, March 9–11 2013 (San Francisco, USA). [10] Available from http://www.endocrine.niddk.nih.gov/pubs/hypothyroidism (Accessed on May 13, 2014). [11] M. Eliades, D. El-Maouche, C. Choudhary, B. Zinsmeister, K.D. Burman, Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature, Thyroid 24 (2) (Feb 2014) 383–389.

Can thyroid break your heart? Role of thyroid in Takotsubo cardiomyopathy: A single center retrospective study.

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