Objectives: Takotsubo cardiomyopathy, also known as “broken heart syndrome,” “apical ballooning syndrome,” and “stress-induced cardiomyopathy,” was first des­cribed in Japanese patients in 1990 by Sato and colleagues. Takotsubo cardiomyopathy is an increasingly recognized syndrome characterized by transient and reversible systolic dysfunction of the apical and middle segments of the left ventricle. This syndrome resembles acute myocardial infarction in the absence of evident coronary artery occlusion. Although the precise pathophysiology of takotsubo cardiomyopathy is still unknown, it seems that it is associated with excessive sympathetic stimulation, microvascular dysfunction, coronary artery vasospasm, and abnormal myocardial tissue metabolism.

Materials and Methods: Herein, we sought to recognize and summarize the available literature data on Takotsubo cardiomyopathy regarding solid-organ transplant, in an attempt to provide the demographic and morphologic functional characteristics of patients with Takotsubo cardiomyopathy and related clinical implications.

Results and Conclusions: Transplant surgeons should maintain a high index of clinical suspicion and never underestimate takotsubo cardiomyopathy as a potential cause of heart failure following solid-organ transplant.

Key words : Apical ballooning syndrome, Broken heart syndrome, Stress-induced cardiomyopathy

Introduction

Takotsubo cardiomyopathy (TCM) is an acquired syndrome characterized by acute reversible systolic dysfunction of the apical and middle segments of the left ventricle, in the lack of significant coronary artery occlusion.^1-3 It was first described in 1990 by Sato and associates.^4,5 The term “takotsubo” stands for octopus (Tako) pot (Tsubo) and resembles a wide-based clay jar with a narrow neck and round bottom. Left ventriculography during systole in patients with TCM demonstrates such a shape.^6,7 Takotsubo cardiomyopathy should always be considered when patients with symptoms of acute coronary syndrome (ACS) are admitted to the emergency department, since there is significant overlap in clinical pre­sentation between TCM and myocardial infarction.^4,7 The prevalence of TCM among patients presenting with symptoms of ACS is approximately 1% to 2.5%, with 90% of cases diagnosed in postmenopausal women.^4,5,7 The exact mechanism of TCM remains unknown. Various factors have been reported as the main triggers for developing this condition. Generally, a stressor of some type is identifiable.^3,5,8

Until recently, the Mayo Clinic criteria, originally proposed in 2004 and subsequently modified in 2008, were the most widely used in clinical practice for the diagnosis of TCM.^3,4 Recently, new diagnostic criteria have been proposed by the Heart Failure Association of the European Society of Cardiology.⁹ In this study, we sought to recognize and summarize the available literature data on this subject regarding solid-organ transplant, in an attempt to provide the demographic and morphologic functional characteristics of patients with TCM and their related clinical implications.

Materials and Methods

Literature search and data assessment
The survey was a bibliographic review of Medline/PubMed databases, using the words “takotsubo cardiomyopathy,” “stress-induced cardio­myopathy,” “transient left ventricular apical ballooning syndrome,” and “broken-heart syndrome” and the key words “transplantation/transplant” and “solid-organ transplantation/transplant.” References of the identified studies were also searched to identify further studies. We restricted our search until December 2016. To emphasize the possible relation between the stresses that transplant poses to graft recipients and the development of TCM, we only included cases that were presented within the early posttransplant period (1 mo posttransplant).

Study characteristics
By searching for the outlined terms, we selected 10 articles^10-19 that were deemed appropriate for our research. In summary, 12 cases of TCM following solid-organ transplant were identified. Of the studies with patients presenting with TCM, there were 10 cases of TCM after orthotopic liver transplant (OLT) and 2 cases after renal transplant.

The following data were taken into consideration through the articles: sex and age of the patients, previous medical and surgical history, type of transplant, possible triggers and associated stressful factors, clinical presentation/time of onset of TCM posttransplant, preoperative ejection fraction, troponin peak level, left ventricular (LV) ejection fraction in the acute phase, wall motion abnormalities that were detected, LV recovery based on follow-up transthoracic ultrasonography, and graft and patient outcomes.

Results

Demographics and clinical findings of takotsubo cardiomyopathy in solid-organ transplant recipients
The main characteristics of the 10 selected studies(12 patients) are summarized in Table 1 and Table 2. Each study was a single case description, with the exception of that by Saner and associates¹³ and Tachotti Pires and associates,¹⁶ in which 2 patients were reported in each study.

In agreement with the present knowledgeabout TCM, we found a female predominance (8/12 patients, 66.6%). The mean age of the patients was53.5 ± 11.5 years (range, 33-68 y). Of the 12 cases, 10 cases (83.3%) followed OLT, and 2 cases were reported after renal transplant. Regarding causes for end-stage liver disease in cases of OLT, 3 were due to non­alcoholic steatohepatitis and 2 were due to hepatitis-related cirrhosis. There were also cases associated with primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and hemo­chromatosis. End-stage renal disease cases were due to polycystic kidney disease and glomerulonephritis.

Based on the well-recognized fact that TCM in most cases is linked to an acute emotional or physical stressor, possible inciting agents are summarized in Table 1. Apart from the transplant itself, various factors such as graft reperfusion, cardiac arrest, catecholamine administration, tacrolimus toxicity, and several medical conditions (pulmonary embolism, Clostridium difficile colitis, renal failure, acute respiratory failure) were identified as potential triggering factors for TCM.

The most frequent clinical presentation in cases of renal transplant were chest pain, hypotension, and tachycardia, whereas in OLT cases cardiac arrest immediately after graft reperfusion was noted in 4 of 10 cases. In cases of TCM after renal transplant, the development of the symptoms occurred within postoperative day 1, whereas for 7 of 10 cases ofOLT symptoms began within the first 24 hours post­transplant.

Laboratory and imaging findings of takotsubo cardiomyopathy in solid-organ transplant recipients
Preoperative ejection fraction was only reported in 5 of 12 cases and found to be between 59% and 74% (mean of 63.2% ± 6.14%). Troponin levels after presentation of TCM ranged between 0.15 and 38 ng/mL with a mean value of 6.29 ± 10.87 ng/mL. In the case reported by Philips and associates,¹² troponin level was not available. This finding agrees with the present knowledge that TCM causes mild elevation of cardiac biomarkers in contrast with myocardial infarction.

Left ventricular ejection fraction in the acute phase of takotsubo syndrome was available in 10/12 cases of TCM, ranging from 10% to 40%. Coronary angiography and two-dimensional echocardiography were used in most cases, to confirm the typical mid-distal LV dysfunction and to exclude the possibility of myocardial infarction, except for the case described by Chrapko and associates¹⁵ in which myocardial perfusion scintigraphy was utilized to prevent contrast-induced nephropathy in the newly trans­planted kidney.

Prognosis of takotsubo cardiomyopathy in solid-organ transplant recipients
Recovery of LV dysfunction as shown by use of echocardiogram followed 15.75 ± 12.10 days posttransplant. Regarding patient outcomes, 3/12 patients (25%) died. However, in the cases reported by Tiwari and associates¹¹ and 1 of the 2 cases published by Pires and associates,¹⁶ death seemed to be unrelated to TCM itself. In the article written by Saner and associates,¹³ the patient did not recover from ventricular dysfunction that followed the development of TCM.

Discussion

General aspects of takotsubo cardiomyopathy
Takotsubo cardiomyopathy is a form of acute reversible LV dysfunction characterized by apical ballooning of a hypo- or akinetic LV apex with hyperdynamic basal walls.²⁰ Two other forms of TCM exist. “Atypical” takotsubo syndrome shows hypercontractility of the apex and akinesia of the midventricular parts, whereas “inverted” takotsubo shows hypercontractility of the apex and akinesia of the base of the heart.^4,20

Cases of TCM can be classified either as primary or secondary takotsubo syndrome. In the former case, acute cardiac symptoms are the primary reason for seeking medical care, with many patients not having identifiable stressful triggers, whereas in the latter form patients are already hospitalized for various conditions such as solid-organ transplant. In these patients, TCM seems to be a complication of their primary condition or its treatment.⁹

Takotsubo cardiomyopathy is also known as transient LV apical ballooning syndrome, broken-heart syndrome, and stress-related cardiomyopathy. Patients with TCM account for 1% to 2% of all patients with suspected ACS.^4,5,7,21 In most cases, an acute emotional or physical stressor can be identified as a triggering factor. However, it has recently been reported that, in 28.5% of patients, there is no apparent triggering factor.^22,23 Interestingly enough, it has been reported that over 50% of TCM patients had a history of neurologic and/or psychiatric incidents or disorders, with most patients taking medications such as serotonin-reuptake inhibitors or benzodiazepines.²² Patients with TCM experience symptoms identical to those of ACS, such as dyspnea, angina-like pain, tachycardia, and signs of heart failure.^2,3 Postmenopausal women with an average age of 68 years are at increased risk of TCM.^2,7

Diagnostic criteria of takotsubo cardiomyopathy
Based on Mayo Clinic Criteria, TCM is commonly defined through the following points: (1) transient hypokinesis, akinesis, or dyskinesis in the LV midsegments with or without apical involvement and frequently, but not always, a stressful trigger; (2) the absence of obstructive coronary disease or angiographic evidence of acute plaque rupture; (3) new electrocardiogram (ECG) abnormalities (ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin; and (4) the absence of pheochromocytoma and myocarditis.^3,4

Heart Failure Association diagnostic criteria for takotsubo syndrome proposed in 2015 include the following points: (1) transient regional wall motion abnormalities of LV or right ventricular myocardium that are frequently, but not always, preceded by a stressful trigger (emotional or physical); (2) the regional wall motion abnormalities usually extending beyond a single epicardial vascular distribution and often resulting in circumferential dysfunction of the ventricular segments involved; (3) the absence of culprit atherosclerotic coronary artery disease, including acute plaque rupture, thrombus formation, and coronary dissection or other pathologic conditions to explain the pattern of temporary LV dysfunction observed (eg, hyper­trophic cardiomyopathy, viral myocarditis); (4) new and reversible ECG abnormalities (ST-segment elevation, ST depression, LBBB, T-wave inversion, and/or QTc prolongation) during the acute phase(3 mo); (5) significantly elevated serum natriuretic peptide levels (B-type natriuretic peptide [BNP] or N-terminal-prohormone BNP) during the acute phase; (6) positive but relatively small elevations in cardiac troponin measured with a conventional assay (ie, disparity between the troponin level and the amount of dysfunctional myocardium present); and (7) recovery of ventricular systolic function on cardiac imaging at follow-up (3-6 mo).⁹

Laboratory and imaging findings
Electrocardiograms in patients with TCM frequently show ST-segment elevations as seen in myocardial infarction. Other ECG abnormalities include T-wave inversions, abnormal Q waves, and QT prolongations.^2,4 These changes generally resolve within a few days. Troponin I and creatine kinase-MB show mild elevations, whereas BNP or N-terminal-prohormone BNP is significantly elevated during the acute phase, as mentioned before in the most recent diagnostic criteria from 2015.^4,9 Because of the similarities in clinical presentation of patients with TCM and ACS, coronary angiography is often justified, revealing no signs of coronary artery disease.^2-4 Transthoracic echocardiography detects wall motion abnormalities characteristic of TCM. Apical hypokinesis is the most commonly reported finding. Left ventriculography is often performed before transthoracic echocardiography, given the fact that coronary angiography is utilized to exclude myocardial infarction.² Cardiac magnetic resonance imaging is increasingly used as a diagnostic tool in patients with suspected TCM.^2,4

Prognosis and treatment
Most patients (96%) show complete resolution of cardiac function within days or weeks.⁷ The overall in-hospital mortality rate is about 4.2%.³ There is no universal treatment modality for TCM. Patients presenting with hemodynamic instability should not be administered inotropic agents because of the association of those with the development of the disease. Intra-aortic balloon pump implantation can be used in cases of cardiogenic shock. Beta blockers and calcium-sensitizing agents have also been used. The use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers at discharge was associated with improved survival, whereas survival was comparable between patients with and those without beta blockers at discharge.²² Therapeutic anticoagulation should always be considered due to the possibility of thrombus formation.^3,4,7

Pathophysiology of takotsubo cardiomyopathy
Coronary microvascular dysfunction, coronary artery spasm, catecholamine-induced myocardial stunning, reperfusion injury after ACS, myocardial microinfarction, and abnormalities in cardiac fatty acid metabolism have all been suggested as possible pathophysiologic mechanisms.^3,7 Autopsy findings from TCM patients have shown myofibrillar degen­eration and contraction band necrosis. Lyon and associates²⁴ advocated a theory called “stimulus trafficking,” explaining the decline of myocyte contraction strength in patients with TCM.^4,7 G-protein-coupled receptors (GPCR) constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses. These coupled G protein receptors are called seven-transmembrane receptors because they pass through the cell membrane 7 times. The GPCR second messengers include stimulating Gs proteins, which activate adenyl cyclase, and inhibitory Gi proteins, which inhibit adenyl cyclase. Supra­physiologic release of catecholamines after a stressful incident induces β2-coupling from stimulating Gs to inhibitory Gi proteins. The rationale behind stimulus trafficking is that a switch to Gi occurs to protect myocytes from the stimulation caused by Gs, which eventually causes apoptosis.^4,7

A dramatic increase in catecholamines has been associated with the development of TCM. Much of the evidence is from case control studies.²¹ Direct evidence for the role of stress hormones in disease pathogenesis was obtained from animal studies after iatrogenic administration of catecholamines.^21,25,26 Catecholamine-induced takotsubo cardiac dysfunc­tion appears to be afterload dependent rather than dependent on stimulation of a specific adrenergic receptor subtype in rat models.²⁵

The sympathetic nervous system is a central regulator of the activities of organs in response to stressful events. There is evidence of the role of the sympathetic nervous system in the pathophysiology of TCM via the increased levels of endogenous catecholamines after emotional or physical stress. Consequently, therapy with drugs with direct or indirect action on the sympathetic nervous system may trigger TCM.²⁷ It is necessary for physicians to suspect and easily recognize the possibility of the development of drug-associated TCM, given the fact that these drugs are extensively used in the setting of solid-organ transplant.

Although coronary vasospasm has been con­sidered as a main element in the pathophysiology of TCM, previous studies have shown that it is only induced in about 28% of provocation tests during coronary angiography in patients with TCM. Involvement of coronary vasospasm in some TCM patients is at least undeniable. A hypothesis explained that this disease could be caused by plaque rupture not resulting in obstructive coronary disease. However, it has been pointed out that wall motion abnormality does not always correlate with the coronary artery vascular distribution, and histo­pathologic findings are different from those observed in ischemic stunning. Thus, coronary vasospasm involvement is not considered by many scientists to be a causative factor for the development of TCM.^3,28,29

Special considerations in takotsubo cardiomyopathy cases after solid-organ transplant
As far as the pathophysiology of TCM in transplant recipients is concerned, it is noteworthy that solid-organ transplant is a situation associated with a state of large exposure to catecholamines, posing a great risk to potential organ recipients in developing cardiac complications postoperatively. In addition, coronary vasospasm, as opposed to the current knowledge, has been linked to the development of TCM in a case of a 64-year-old man who underwent OLT due to end-stage liver disease secondary to nonalcoholic steatohepatitis. The patient developed severe right coronary artery vasospasm and apical ballooning syndrome 15 minutes after portal reperfusion, supporting either a common mechanism or distinct but simultaneous mechanisms.¹⁴

It is undoubtable that liver transplant candidates comprise a population of people at high risk of having cardiovascular comorbidities. Apart from their increased age as a factor, the characteristic cardiovascular complications of cirrhosis increase the possibility for development of postoperative cardiac complications.¹⁷ Increased cardiac output after liver transplant and preexisting cirrhotic cardiomyopathy predispose to the development of cardiovascular complications when liver transplant recipients are exposed to the hemodynamic stress in the immediate postoperative period.

Compared with that shown in the International Takotsubo Registry, the proportion of women (66.6%) in solid-organ transplant cases was smaller and the mean age was younger (53.5 y). This disproportion probably is explained not only from the limited number of cases reported after solid-organ transplant but also from the great variability of primary diseases that cause end-stage organ failure and their different epidemiologic profiles. Interestingly enough, we found an extremely high mortality rate (25%) in transplant recipients with TCM that needs to be elucidated in the future through further studies.

The pathologic concept of TCM has been almost established, but a number of questions remain, such as the establishment of acute phase treatment, risk assessment, prophylactic measures against recurrence, and long-term prognosis. Many questions also remain regarding the pathogenic mechanisms underlying TCM, especially in solid-organ transplant where, despite the limited number of reported cases, there seems to be significant differences in patho­physiology and prognosis. Further research is expected with the accumulation of cases in databases.

Conclusions

Transplant candidates are increasingly older with cardiovascular comorbidities and heart conditions that predispose to postoperative complications when exposed to the hemodynamic stress that follows the immediate posttransplant period. Transplant candidates must be thoroughly evaluated before placement on wait lists to minimize the risk of adverse cardiovascular events after transplant. Transplant surgeons should maintain a high index of clinical suspicion and never underestimate TCM as a potential cause of heart failure after solid-organ transplant.

Although many facets of the exact cause and treatment of TCM remain incompletely understood or characterized, there is evidence of a relation between TCM and coronary vasospasm in the setting of organ reperfusion following solid-organ transplant.¹⁴ Prognosis in healthy populations is generally favorable with appropriate management in the acute setting. However, our research in transplant patients revealed a high mortality rate of 25%; this rate could be explained by the fact that individuals with end-stage liver disease and end-stage renal disease have several comorbidities and undergo a quite stressful procedure.

Discovered less than 25 years ago and officially recognized as a cardiomyopathy for less than 10 years, the field of TCM is rapidly evolving. Further elucidation of underlying mechanisms and potential recognition of genetic predisposition will aid in prompt recognition of TCM. The potential for early identification of high-risk patient groups may lead to a decrease in both morbidity and mortality.

References:

1. Redfors B, Shao Y, Ali A, Omerovic E. Current hypotheses regarding the pathophysiology behind the takotsubo syndrome. Int J Cardiol. 2014;177(3):771-779.
   CrossRef - PubMed
   
2. Peters MN, George P, Irimpen AM. The broken heart syndrome: Takotsubo cardiomyopathy. Trends Cardiovasc Med. 2015;25(4):351-357.
   CrossRef - PubMed
   
3. Yoshikawa T. Takotsubo cardiomyopathy, a new concept of cardiomyopathy: clinical features and pathophysiology. Int J Cardiol. 2015;182:297-303.
   CrossRef - PubMed
   
4. Sinning C, Keller T, Abegunewardene N, Kreitner KF, Munzel T, Blankenberg S. Tako-Tsubo syndrome: dying of a broken heart? Clin Res Cardiol. 2010;99(12):771-780.
   CrossRef - PubMed
   
5. Roshanzamir S, Showkathali R. Takotsubo cardiomyopathy a short review. Curr Cardiol Rev. 2013;9(3):191-196.
   CrossRef - PubMed
   
6. Scantlebury DC, Prasad A. Takotsubo cardiomyopathy. Circ J. 2014;78(11):2803.
   CrossRef - PubMed
   
7. Komamura K, Fukui M, Iwasaku T, Hirotani S, Masuyama T. Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment. World J Cardiol. 2014;6(7):602-609.
   CrossRef - PubMed
   
8. Ripa C, Olivieri F, Antonicelli R. Tako-tsubo-like syndrome with atypical clinical presentation: case report and literature review. Angiology. 2009;60(4):513-517.
   CrossRef - PubMed
   
9. Lyon AR, Bossone E, Schneider B, et al. Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2016;18(1):8-27.
   CrossRef - PubMed
   
10. Lee HR, Hurst RT, Vargas HE. Transient left ventricular apical ballooning syndrome (Takotsubo cardiomyopathy) following orthotopic liver transplantation. Liver Transpl. 2007;13(9):1343-1345.
    CrossRef - PubMed
    
11. Tiwari AK, D'Attellis N. Intraoperative left ventricular apical ballooning: transient Takotsubo cardiomyopathy during orthotopic liver transplantation. J Cardiothorac Vasc Anesth. 2008;22(3):442-445.
    CrossRef - PubMed
    
12. Phillips MS, Pruett TL, Berg CL, Hagspiel KD, Sawyer RG, Bonatti HJ. Takotsubo cardiomyopathy in a liver transplant recipient: a diagnosis of exclusion? J Cardiothorac Vasc Anesth. 2009;23(2):268-269.
    CrossRef - PubMed
    
13. Saner FH, Plicht B, Treckmann J, et al. Tako-Tsubo syndrome as a rare cause of cardiac failure in liver transplantation. Liver Int. 2010;30(1):159-160.
    CrossRef - PubMed
    
14. Eagle SS, Thompson A, Fong PP, et al. Takotsubo cardiomyopathy and coronary vasospasm during orthotopic liver transplantation: separate entities or common mechanism? J Cardiothorac Vasc Anesth. 2010;24(4):629-632.
    CrossRef - PubMed
    
15. Chrapko BE, Tomaszewski A, Jaroszynski AJ, Furmaga J, Wysokinski A, Rudzki S. Takotsubo syndrome in a patient after renal transplantation. Med Sci Monit. 2012;18(3):CS26-30.
    CrossRef - PubMed
    
16. Tachotti Pires LJ, Cardoso Curiati MN, Vissoci Reiche F, et al. Stress-induced cardiomyopathy (takotsubo cardiomyopathy) after liver transplantation-report of two cases. Transplant Proc. 2012;44(8):2497-2500.
    CrossRef - PubMed
    
17. Bedanova H, Orban M, Nemec P. Postoperative left ventricular apical ballooning: Transient Takotsubo cardiomyopathy following orthotopic liver transplantation. Am J Case Rep. 2013;14:494-497.
    CrossRef - PubMed
    
18. Golebiewska J, Stopczynska I, Debska-Slizien A, Bohdan M, Gruchala M, Rutkowski B. Tako-tsubo cardiomyopathy on the first day after renal transplantation---case report and literature review. Transplant Proc. 2014;46(8):2920-2922.
    CrossRef - PubMed
    
19. Harika R, Bermas K, Hughes C, Al-Khafaji A, Iyer M, Wallace DJ. Cardiac arrest after liver transplantation in a patient with takotsubo cardiomyopathy. Br J Anaesth. 2014;112(3):594-595.
    CrossRef - PubMed
    
20. Subramaniam A, Cooke JC, Ernest D. “Inverted” tako-tsubo cardiomyopathy due to exogenous catecholamines. Crit Care Resusc. 2010;12(2):104-108.
    PubMed
    
21. Izumi Y. Drug-induced takotsubo cardiomyopathy. Heart Fail Clin. 2013;9(2):225-231, ix-x.
    CrossRef - PubMed
    
22. Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015;373(10):929-938.
    CrossRef - PubMed
    
23. Deshmukh A, Kumar G, Pant S, Rihal C, Murugiah K, Mehta JL. Prevalence of Takotsubo cardiomyopathy in the United States. Am Heart J. 2012;164(1):66-71.e1.
    CrossRef - PubMed
    
24. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med. 2008;5(1):22-29.
    CrossRef - PubMed
    
25. Redfors B, Ali A, Shao Y, Lundgren J, Gan LM, Omerovic E. Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner. Int J Cardiol. 2014;174(2):330-336.
    CrossRef - PubMed
    
26. Izumi Y, Okatani H, Shiota M, et al. Effects of metoprolol on epinephrine-induced takotsubo-like left ventricular dysfunction in non-human primates. Hypertens Res. 2009;32(5):339-346.
    CrossRef - PubMed
    
27. Amariles P. A comprehensive literature search: drugs as possible triggers of Takotsubo cardiomyopathy. Curr Clin Pharmacol. 2011;6(1):1-11.
    CrossRef - PubMed
    
28. Patel SM, Lerman A, Lennon RJ, Prasad A. Impaired coronary microvascular reactivity in women with apical ballooning syndrome (Takotsubo/stress cardiomyopathy). Eur Heart J Acute Cardiovasc Care. 2013;2(2):147-152.
    CrossRef - PubMed
    
29. Vailas MG, Vernadakis S, Kakavia K, et al. A Heartbreaking Renal Transplantation: Is Norepinephrine the Culprit to Blame? Transplant Proc. 2016;48(9):3088-3091.
    CrossRef - PubMed