Pathophysiology Of Takotsubo Cardiomyopathy Research Articles

Takotsubo Cardiomyopathy Associated with Severe Hypocalcemia Secondary to Idiopathic Hypoparathyroidism

The etiology and pathophysiology of takotsubo cardiomyopathy have not yet been fully clarified. We report a case of takotsubo cardiomyopathy associated with severe hypocalcemia secondary to hypoparathyroidism. A 69-year-old woman presented with acute pulmonary edema caused by severe left ventricular dysfunction with apical ballooning compatible with takotsubo cardiomyopathy. Laboratory tests revealed severe hypocalcemia secondary to idiopathic hypoparathyroidism. Coronary angiography showed normal coronary artery function. Her symptoms and signs of heart failure improved dramatically with the correction of hypocalcemia through calcium and calcitriol replacement.

First Evidence of Increased Plasma Serotonin Levels in Tako-Tsubo Cardiomyopathy

Background. There is no data about the serotonergic activity during the acute phase of Tako-Tsubo Cardiomyopathy (TTC). The objective of our study was to investigate evidence of serotonin release from patients with TTC in comparison with patients with ST elevation myocardial infarction (STEMI) and healthy control subjects (HCS). Methods and Results. Plasma serotonin levels in 14 consecutive patients with TTC were compared with those in 14 patients with STEMI and 14 HCS. Plasma serotonin levels at admission were markedly higher in patients with TTC and STEMI as compared to HCS (3.9 ± 4.6, P = 0.02 versus control; 5.7 ± 5.6, P = 0.001 versus control; and 1 ± 0.4 ng/mL, resp.). There was no difference in serotonin levels between patients with TTC and those with STEMI (P = 0.33). Conclusion. This finding suggests that serotonin could participate to the pathophysiology of TTC.

Anxiodepressive Disorders and Chronic Psychological Stress Are Associated With Tako-Tsubo Cardiomyopathy

Recent retrospective studies suggest that psychiatric disorders could be a predisposing risk factor for Tako-tsubo cardiomyopathy (TTC). The aim of the present study was to characterize the prevalence of anxiodepressive disorders (ADD) and chronic psychological stress (CPS) in patients with TTC or acute coronary syndrome (ACS). Between January 2010 and December 2011, 45 consecutive patients with TTC were prospectively screened by systematic interview with the Mini International Neuropsychiatric Interview. CPS was systematically recorded. During the same period, 50 patients admitted for ACS with troponin elevation and matched for age and sex were prospectively included as a control group. An acute stressful event within 72 h before presentation was identified in 35 patients (78%) with TTC vs. 9 (18%) with ACS (P<0.001). Thirty-five patients (78%) and 13 (26%) had ADD in the TTC and ACS groups, respectively (P<0.001). CPS was found in 20 patients (44%) and in 9 (18%) with TTC and ACS, respectively (P=0.005). CPS and/or ADD were found in 35 patients (78%) and in 18 (36%) with TTC and ACS, respectively (P<0.001). ADD and CPS are common in patients with TTC and more frequent than in patients with ACS. This finding suggests that systemic effects of ADD and CPS could participate in the pathophysiology of TTC.

Recurrence of Takotsubo cardiomyopathy with coronary slow flow phenomenon

This report presents the case of a 54-year-old female with Takotsubo cardiomyopathy that recurred 12 years after the first episode. The coronary angiography at the first admission revealed ergonovine-induced coronary vasoconstriction in the left coronary artery, and recurrence recurred after the interruption of vasodilator therapy to prevent vasospasm. In addition, the coronary angiography both in the first and second event demonstrated coronary slow flow phenomenon, which improved after the intracoronary administration of nicorandil. These findings indicate that coronary microvascular constriction plays an important role in the pathophysiology of Takotsubo cardiomyopathy.

Abstract 17081: Risk Factors for Developing Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy (TTC) has emerged as a new clinical entity which has not been fully understood. Numerous case reports exist regarding association of TTC with high adrenergic state conditions like Pheochromocytoma. Our aim was to explore the association of common medical conditions with TTC. Methods: This was a cross sectional study using the National Inpatient Sample (NIS) 2007 database.TTC or Broken heart syndrome or Reversible left ventricular dysfunction following sudden emotional stress or Stress induced cardiomyopathy or Transient left ventricular apical ballooning syndrome was defined as patients discharged with any ICD code of 429.83 ( http://www.cdc.gov/nchs/data/icd9/agendasept05.pdf ). The common medical conditions were identified by appropriate ICD 9 codes Results: We indentified total 6229 discharges with any discharge diagnosis of TTC. The likelihood of common medical conditions with TTC is shown in Table 1. Conclusions: This is the first study to explore the association of common medical conditions associated with TTC on a nationwide basis. We conclude that the patient with hyperlipidemia, smoking, pulmonary hypertension, sub arachnoid hemorrhage, migraine, hyperthyroidism, collagen vascular diseases, anxiety state, and stress have higher odds of developing TTC. Further research needs to be done for better understanding the causes and pathophysiology of TTC which in turn will help risk stratification and define optimal therapy.

Adderall induced inverted‐Takotsubo cardiomyopathy

Takotsubo Cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, was initially described in Japan in 1990. Both illicit and prescription drugs have added to the growing list of insulting stressors. We describe an interesting case of atypical TTC triggered by adderall overdose. A 19-year-old female was brought to the Emergency Department after ingesting 30 Adderall tablets. She was complaining of pressure like chest pain and shortness of breath. Her cardiac enzymes were elevated but the electrocardiogram was unremarkable. Echocardiography identified an ejection fraction (EF) of 25-30% with severe hypokinesis of the base and a preserved apex. Cardiac angiography demonstrated normal coronary arteries with an EF of 35%, hyperkinetic apex and akinetic base consistent with the diagnosis of inverted-TTC. Her symptoms resolved in 24 hrs. Repeat echocardiogram performed 3 days later showed an EF of 60% with no regional wall motion abnormalities. TTC can be identified as a rapid development of severe and reversible left ventricular dysfunction extending beyond the territory of a single epicardial coronary artery in the absence of coronary artery disease or pheochromocytoma. Clinical presentation can be challenging and very hard to distinguish from acute myocardial infarction. Medication induced-TTC has been reported. In our case, the patient overdosed on Adderall which is a sympathomimetic medication. Cardiac imaging identified wall motion abnormalities consistent with inverted type TTC. Restoration of left ventricular function within days confirms the diagnosis of TTC. In conclusion, this case offers an interesting insight into the pathophysiology of TTC.

Historische und gegenwärtige pathophysiologische Konzepte der Tako-Tsubo-Kardiomyopathie

Tako-Tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy (SCM), was first described in the 1990s and is characterized by transient left ventricular dysfunction. Its incidence represents 1-2% of all acute coronary syndromes (ACS). In most cases extreme emotional or physical stress precedes this syndrome. The majority of patients affected are postmenopausal women. Since its first description, various hypotheses regarding the pathophysiology of TTC have been discussed. From a historical perspective, coronary vasospasm has often been proposed as a possible cause of this disorder. However, reviews from numerous registries were able to demonstrate that coronary vasospasm plays only a minor role in the pathogenesis of TTC. Several groups showed disturbances in myocardial microcirculation and energy metabolism in the acute phase of TTC. Nevertheless, with regard to the data currently available, it cannot be differentiated whether these changes are the cause or rather the result of TTC. However, recent concepts include an excessive catecholamine overload and morphological changes which are unequivocally documented in TTC. The relation between elevated catecholamine levels and myocardial dysfunction analogous to TTC could be confirmed in animal experiments.In summary, it can be assumed that TTC is caused by an excessive cardiotoxic release of catecholamines. Ventricular dysfunction can be explained by increased numbers of β-adrenergic receptors in the apex, leading to greater vulnerability to catecholamine overload. Individual anatomical differences in the sympathoadrenergic system and distribution from β-adrenergic receptors are presumably responsible for the interindividual occurrence of wall motion abnormalities in TTC.

TAKOTSUBO CARDIOMYOPATHY WITH HYPERVASOPRESSINEMIA

To the Editor: An 88-year-old woman presented with shortness of breath and appetite loss. Chest X-ray revealed significant right pleural effusion, and blood examination showed hyponatremia (119 mmol/L). She had no contributory medical history, and electrocardiography (ECG) was normal at admission. Findings on routine laboratory tests were not remarkable except for hyponatremia. The cytological examination of pleural effusion and chest computed tomography demonstrated that pleural metastasis of lung adenocarcinoma caused the effusion. Further blood examinations showed a high serum arginine vasopressin (AVP) concentration (25.0 pg/mL; normal range 0.3–3.5 pg/mL), low serum osmolality (246 mOsm/L), and high urine osmolality (625 mOsm/L). Her thyroid function and adrenal function were normal. Because of these results, she was diagnosed with syndrome of inappropriate secretion of antidiuretic hormone1 caused by high intrathoracic pressure due to marked pleural effusion. On her 14th hospital day, she suddenly complained of chest pain and chest oppression. ECG showed ST-segment elevation in the V3, V4, and V5 leads. She was diagnosed with acute ST-elevation myocardial infarction (STEMI) and transferred to the cardiovascular center. However, before coronary angiography (CAG) could be performed, chest pain and oppression disappeared, and we no longer found ST-segment elevation on ECG. There was no coronary artery atherosclerosis or spasm identified by CAG, and left ventriculography did not detect any abnormality. Blood examination after CAG showed no enzymatic evidence of myocardial necrosis. A diagnosis of Takotsubo cardiomyopathy2 was considered at this point. Follow-up ECG showed T-wave inversion in the V3, V4, and V5 leads on the 19th hospital day. On the 21st hospital day, the pleural effusion was drained and the intrathoracic pressure lowered. Blood examinations on the 30th hospital day showed a decrease in serum AVP concentration (1.5 pg/mL), increased serum osmolality (268 mOsm/L), decreased urine osmolality (339 mOsm/L), and normalization of serum sodium concentration (137 mmol/L). Many previous articles have reported that recurrence of Takotsubo cardiomyopathy is rare,2, 3 and this patient has not complained of chest pain and chest oppression since the initial episode. Takotsubo cardiomyopathy has cardiac symptoms that are difficult to distinguish from acute STEMI and is observed especially in women aged 60 and older.2 The patients diagnosed with Takotsubo cardiomyopathy complain of chest pain and chest oppression. ECG shows ST-segment elevation, and left ventriculography shows wall motion abnormalities, but CAG shows no evidence of obstructive atherosclerosis of the coronary arteries. Takotsubo cardiomyopathy is associated with several clinical events, such as subarachnoid hemorrhage,4 pheochromocytoma,5 Guillain-Barré syndrome,6 and mental stress.7 Although the pathophysiology and the reason for the strong elderly female predominance remain unknown, and accepted criteria for diagnosis have not been established, some hypotheses are suggested: catecholamine-mediated myocardial stunning, catecholamine-induced microcardiac artery spasm, and epicardial coronary artery spasm.2 AVP is a hormone produced in the cells located predominantly in the supraoptic and paraventricular hypothalamic nuclei, the axons of which terminate in the posterior lobe of the pituitary gland, and is well known as a antidiuretic hormone.8 There are three subtypes of receptors for AVP: V1a, V1b, and V2. AVP also functions as a vasoconstrictor and myocardial contractor through V1a receptors, which are located on vascular smooth muscle cells and cardiomyocytes.9 Because AVP causes peripheral vasoconstriction in the skin, skeletal muscles, gastrointestinal organs, fat tissue, renal arterioles, and coronary arteries, it is used as a vasoconstrictor to support blood pressure in refractory septic shock.10 This case showed hypervasopressinemia (20 times as high as normal level) before she was diagnosed with Takotsubo cardiomyopathy. Her blood pressure was always normal (108/66 mmHg), but it went up to 142/82 mmHg when she complained of chest pain. AVP may have been one of the causes of high blood pressure, working as a strong vasoconstrictor. Because of these results, this case can suggest a new hypothesis in the pathophysiology of Takotsubo cardiomyopathy; AVP may have induced microcardiovascular spasm, causing left ventricular wall motion abnormalities “Takotsubo cardiomyopathy.” Although Takotsubo cardiomyopathy is becoming recognized as a common heart disease, especially in elderly women, acceptable criteria for diagnosis are not established, and the pathophysiology remains unknown. More cases and studies are needed to ascertain the pathophysiology and management of this syndrome. We first demonstrated a relation between Takotsubo cardiomyopathy and hypervasopressinemia. Hypervasopressinemia may be an important trigger of reversible left ventricular dysfunction “Takotsubo cardiomyopathy.” Financial Disclosure: Norinaga Urahama's research has no financial and material support. None of the authors have any potential conflicts of interest associated with this study, and no authors have anything to disclose. Author Contribution: Norinaga Urahama participated in the study concept and design and contributed significantly to the treatment of the patient, acquisition of data, and preparation of manuscript. Hideki Nakashima, Hirokazu Kurose, and Tadatsugu Ohno treated the patient and prepared the manuscript. Sponsor's Role: No sponsor.

Transthoracic Doppler ultrasound coronary flow reserve evaluation: preliminary insights into pathophysiology of Takotsubo cardiomyopathy

The aim of this study was to elucidate the role of coronary microvascular function in the pathophysiological scenario of Takotsubo cardiomyopathy. Noninvasive evaluations of coronary flow reserve through transthoracic Doppler ultrasound imaging of the left anterior descending coronary artery, a reliable marker of coronary microcirculation performance in the absence of epicardial coronary artery stenosis, were performed both in the acute and recovery phases of Takotsubo cardiomyopathy in consecutive patients strictly selected on the basis of absence of risk factors, concomitant diseases, or both impairing coronary microvascular function. Resting and hyperemic diastolic flow velocity tracings and corresponding velocity time integrals were obtained in seven consecutive patients, six of them women, aged 65-86 years (76 +/- 6.5) at admission and 23 +/- 4 days after, when left ventricular wall motion alterations recovered. In addiction, thrombolysis in myocardial infarction frame count of the two branches of the left coronary artery was evaluated on the cineangiogram obtained at admission. It was normal in both branches of the left coronary artery (left anterior descending, 30.6 +/- 8.79; circumflex, 23.4 +/- 2.96). In each patient, coronary flow reserve, calculated both on velocity time integrals (2.6 +/- 0.2) and average peak diastolic blood flow velocity (2.48 +/- 0.1) values, was in the normal range (>2.0) and did not significantly change when reevaluated in the recovery phase (2.55 +/- 0.1, 2.44 +/- 0.1). These data suggest that coronary microvascular function may not be impaired in Takotsubo patients when negative influences on coronary flow reserve by concomitant diseases and coronary risk factors are excluded. Its noninvasive evaluation with transthoracic Doppler ultrasound of the distal left anterior descending appears simple and useful in this type of patients.