A rare case of Takotsubo cardiomyopathy.

BACKGROUND: The recent advent of the cyclin-dependent kinase (CDK) 4/6 inhibitors has considerably evolved hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer treatment. Palbociclib, an orally administered pyridopyrimidine derivative, was the first CDK4/6 inhibitor to be introduced into daily clinical practice in combination with classic endocrine backbone, based on progression-free survival (PFS) benefit assessed in the pivotal PALOMA series of randomized clinical trials. Regarding its safety profile, neutropenia and leukopenia are the most common and well-defined adverse effects, while cardiac complications are rather scarce. CASE REPORT: We present the rare case of a middle-aged female patient with HR+/HER2- metastatic breast cancer, without prior exposure to cardiotoxic antineoplastic agents, who developed Takotsubo cardiomyopathy (TTC) in the context of systemic therapy with palbociclib plus letrozole combination. CONCLUSIONS: Pharmacovigilance and experimental studies are warranted to confirm any causative relationship and to explore the underlying pathophysiology, respectively.

Possible association between lithium intoxication and Takotsubo syndrome.

More than 25 years after being diagnosed with bipolar disorder and receiving continuous treatment with lithium, a woman develops Takotsubo syndrome.

Pharmacological Triggers of Takotsubo Cardiomyopathy: An Updated Review of Evidence and Recommendations.

BACKGROUND: Previous publications in 2011, 2016, and 2022 have presented lists of drugs associated with takotsubo cardiomyopathy (TCM). This review aims to provide updated drug lists that have been reported as potential causes of TCM. METHODS: Following the same methodology employed in previous reviews, a detailed investigation was carried out in the PubMed/Medline database from June 2022 to July 2023 to identify drug-induced TCM (DITC) case reports. Various search terms related to the drug-induced transient left ventricular ballooning syndrome, ampulla cardiomyopathy, apical ballooning syndrome, drug-induced broken heart syndrome, drug triggered takotsubo cardiomyopathy, takotsubo cardiomyopathy, and iatrogenic takotsubo cardiomyopathy were utilized. Filters for fulltext availability, case reports, human studies, and English language were applied. Articles reporting drugs associated with TCM development were included in the analysis. RESULTS: Foremost 192 case reports were initially identified, with 75 drugs meeting the inclusion criteria after a thorough review. The latest revision identified seven drugs that might lead to TCM, with four drugs (57.14%) already reported in previous reviews and three drugs (42.86%) newly identified. Consequently, the updated drug list potentially triggering TCM in 2023 comprises a sum of 75 drugs. CONCLUSION: The recent 75 drugs provided additional evidence linking to TCM development. The updated list predominantly includes drugs that induce sympathetic overstimulation, although some drugs on the list have unclear associations with sympathetic nervous system activation.

Ketamine's love story with the heart: A Takotsubo twist.

INTRODUCTION: Ketamine is a dissociative anesthetic with N-methyl-d-aspartate and glutamate receptor antagonist properties. It has been the most popular agent to facilitate emergency department procedures for three decades. Considered a safe and effective option for procedural sedation, ketamine has rapid onset, short effective sedation time, and a low risk profile. Ketamine's sympathomimetic effects could theoretically induce stress-related cardiac dysfunction, including cardiomyopathy. A review of the literature demonstrates one prior report of stress (Takotsubo) cardiomyopathy after ketamine sedation. CASE REPORT: In this case report, we present a case of Takotsubo cardiomyopathy after ketamine sedation for distal radius fracture reduction. The patient presented hemodynamically normal with an unremarkable cardiac ultrasound and progressed to hypoxia from bilateral pulmonary edema, eventually requiring intubation. Inpatient evaluation revealed elevated high sensitivity troponin, non-obstructive coronary arteries on catheterization, and echocardiogram findings of Takotsubo cardiomyopathy. She received operative fixation of her radius fracture by orthopedics and was discharged home on hospital day 9. She had an unremarkable follow up with cardiology but had no echocardiogram to determine full resolution. CONCLUSION: Although ketamine has robust evidence of safety and efficacy, physicians should be aware of the potential complications of its sympathomimetic effects, from hypertension and tachycardia to overt Takotsubo cardiomyopathy.

Takotsubo Cardiomyopathy Related to Duloxetine-Atomoxetine Combination in an Adolescent with ADHD and Comorbid GAD.

Authors report on an interesting case of a teenager with attention-deficit/hyperactivity disorder and comorbid generalized anxiety disorder, who developed takotsubo cardiomyopathy subsequent to pharmacokinetic and pharmacodynamic interactions between atomoxetine, a selective norepinephrine reuptake inhibitor, and the antidepressant duloxetine. Clinicians should be mindful of the potential for cardiovascular adverse effects when prescribing agents that target noradrenergic receptors.

Polymyoclonus, ventricular fibrillation and Takotsubo after accidental spinal injection of tranexamic acid.

Several factors have been identified as contributing to medication administration errors, including look-alike, sound-alike (LASA) errors. LASA errors are important causes of serious adverse events arising from spinal injection of tranexamic acid, which can be confused with ampoules of local anaesthesia.We present a case of accidental injection of 250 mg of tranexamic acid rather than prilocaine during spinal anaesthesia. The patient developed lower extremities myoclonus, followed by generalised convulsions and ventricular fibrillation, that was reverted within 6 min. Severe cardiogenic shock requiring both inotropic and vasopressor therapy followed, along with a classic apical ballooning pattern on echocardiography and elevated myocardial injury markers, indicating Takotsubo cardiomyopathy. The patient's condition progressively improved to full recovery, and she was discharged from hospital after 1 month with no neurological deficit or cardiac dysfunction.To our knowledge, this is the 28th reported case of accidental spinal injection of tranexamic acid. We present a brief review of previously published cases.

Drugs as Possible Triggers of Takotsubo Cardiomyopathy- Update 2022: Systematic Review.

BACKGROUND: A list of drugs that can induce takotsubo cardiomyopathy (TCM) was published in 2011 and 2016. The aim of the present review was to update this list. METHODS: Similar to the 2011 and 2016 reviews, from April 2015 to May 2022 case reports of druginduced TCM were identified by a comprehensive search in Medline/PubMed database. The search terms were: takotsubo cardiomyopathy, tako-tsubo cardiomyopathy, stress cardiomyopathy, transientleft- ventricular ballooning syndrome, apical ballooning syndrome, ampulla cardiomyopathy OR broken heart syndrome; together with "iatrogenic", "induced by" OR "drug-induced". Registers published in English or Spanish, in humans, and with full texts were retrieved. Articles that recognized any drug associated with the development of TCM were selected. RESULTS: Overall, 184 manuscripts were identified by the search. A total of 39 articles were included after an exhaustive revision. Eighteen drugs as possible triggers of TCM were identified in the current update. Of them, 3 (16.7%) have been previously identified, and 15 (83.3%) are different from the previous reports. Thus, the list of drugs as possible triggers of TCM updated in 2022 includes 72 drugs. CONCLUSION: There are new case reports that link drugs with the development of TCM. The current list is principally made up of drugs that generate sympathetic overstimulation. However, some of the listed drugs do not have a clear link with sympathetic activation.

Mitochondrial damage in a Takotsubo syndrome-like mouse model mediated by activation of ß-adrenoceptor-Hippo signaling pathway.

Takotsubo syndrome (TTS) is characterized by short-term contractile dysfunction with its mechanism undefined. We showed that activation of cardiac Hippo pathway mediates mitochondrial dysfunction and that stimulation of ß-adrenoceptors (ßAR) activates Hippo pathway. Here, we investigated the role of ßAR-Hippo signaling in mediating mitochondrial dysfunction in isoproterenol (Iso)-induced TTS-like mouse model. Elderly postmenopausal female mice were administered with Iso (1.25 mg/kg/h for 23 h). Cardiac function was determined by serially echocardiography. At days 1 and 7 post-Iso exposure, mitochondrial ultrastructure and function were examined by electron microscopy and various assays. Alterations in cardiac Hippo pathway and effects of genetic inactivation of Hippo kinase (Mst1) on mitochondrial damage and dysfunction in the acute phase of TTS were investigated. Isoproterenol exposure induced acute increase in biomarkers of cardiac damage and ventricular contractile dysfunction and dilation. At day 1 post-Iso, we observed extensive abnormalities in mitochondrial ultrastructure, downregulation of mitochondrial marker proteins, and mitochondrial dysfunction evidenced by lower ATP content, increased lipid droplets, higher contents of lactate, and augmented reactive oxygen species (ROS). All changes were reversed by day 7. ßAR stimulation led to activation of cardiac Hippo pathway with enhanced expression of Hippo kinase Mst1 and inhibitory YAP phosphorylation, as well as reduced nuclear YAP-TEAD1 interaction. In mice with cardiac expression of inactive mutant Mst1 gene, acute mitochondrial damage and dysfunction were mitigated. Stimulation of cardiac ßAR activates Hippo pathway that mediates mitochondrial dysfunction with energy insufficiency and enhanced ROS, promoting acute but short-term ventricular dysfunction.NEW & NOTEWORTHY Takotsubo syndrome (TTS) is featured by activation of sympatho-ß-adrenoceptor (ßAR) system leading to acute loss of ventricular contractile performance. However, the molecular mechanism remains undefined. We demonstrated, in an isoproterenol-induced murine TTS-like model, extensive mitochondrial damage, metabolic dysfunction, and downregulated mitochondrial marker proteins, changes temporarily associated with cardiac dysfunction. Mechanistically, stimulation of ßAR activated Hippo signaling pathway and genetic inactivation of Mst1 kinase ameliorated mitochondrial damage and metabolic dysfunction at the acute phase of TTS.

Pediatric Takotsubo cardiomyopathy resulting from clonidine overdose.

Takotsubo cardiomyopathy is a syndrome characterized by localized apical dysfunction of the left ventricle. It is rarely seen in pediatric patients, but can carry significant morbidity and mortality. While most commonly associated with psychosocial stressors or physical exertion, a growing number of cases are being attributed to medications. We describe a case of a six-month-old male diagnosed with Takotsubo cardiomyopathy in the setting of an accidental clonidine overdose. The patient presented with altered mental status and hypertension. In the course of his broad workup, cardiac dysfunction was indicated by bedside ultrasound in the Emergency Department. The classic apical dyskinesis was seen on a follow-up, cardiology-based echocardiogram. The patient responded to high-dose naloxone and only briefly required an epinephrine infusion. His symptoms resolved in a few days and serial echocardiograms showed a return to normal LV function. Rates of pediatric clonidine overdoses are increasing in the setting of changing prescribing practices. Our case illustrates some key features of the clinical presentation, as well as demonstrates a rare sequelae to this common toxic exposure. To our knowledge, this is the first reported pediatric case of Takotsubo cardiomyopathy secondary to a clonidine overdose.

Dobutamine-induced Takotsubo syndrome in a paediatric heart transplant patient.

Takotsubo syndrome is a potentially reversible cause of acute systolic dysfunction. Takotsubo syndrome is rare in children, with no reported dobutamine-induced cases to date. We present a 14-year-old male with prior history of heart transplantation, who developed Takotsubo syndrome during dobutamine stress echocardiography. We highlight the importance of its early recognition to ensure supportive measures with avoidance of inotropic medications.

Iatrogenic adrenaline induced mid-ventricular Takotsubo cardiomyopathy: a case-based review.

Takotsubo cardiomyopathy (TCM) is regarded as an acute and often reversible cardiac syndrome characterised by apical ballooning of the left ventricle that occurs in the absence of coronary artery obstruction and myocarditis. The underlying pathophysiology remains largely unknown, but the most widely accepted theory is catecholamine toxicity.More recently, atypical variants of TCM have been described, and are characterised by the regional wall motion abnormalities that are observed. Mid-ventricular Takotsubo cardiomyopathy (MVTCM) is characterised by hypokinesia/akinesia of the mid left ventricular wall segments with hyperdynamic basal and apical function. This report describes the first documented case of a patient who developed MVTCM after receiving a dose of intravenous adrenaline. This case provides further evidence to support the notion that catecholamine toxicity is implicated in the pathogenesis of TCM.

A systematic cohort review of pheochromocytoma-induced typical versus atypical Takotsubo cardiomyopathy.

BACKGROUND: A rare presentation of pheochromocytoma (PCC) is catecholamine-induced-cardiomyopathy, or Takotsubo cardiomyopathy (TCM). PCC-induced TCM(PCC-TCM) can present as a typical or atypical type, based on the location of cardiac wall motion abnormalities. In this review, we sought to assess features and outcomes for PCC-TCM, and to compare typical and atypical subtypes. METHODS: A search was conducted on two databases (PubMed and Embase) for case series or reports on PCC-TCM from 2006 to 2020. RESULTS: One-hundred-and-two papers with a total of 104 cases of PCC-TCM were retrieved: 67(64.4%) typical and 37(35.6%) atypical subtypes. Overall median age was 50[range:23-86] years, the atypical group about a decade younger(p < 0.001). A female preponderance was seen for either subtype (∼75%). The most common presentations were chest pain(n = 60;58%), dyspnoea(n = 46;44%), and headache(n = 41;39.4%). Those with atypical subtype more often presented with fluid overload (typical:3% versus atypical:60%); acute pulmonary oedema (35% versus 60%); and cardiogenic shock (22% versus 43%) (all p < 0.05). Six patients (6%) died pre-operatively (typical:8% versus atypical:3%; p = 0.32). Non-fatal pre-operative complications occurred more among those with atypical TCM(p < 0.001), specifically cardiac arrest (typical:5% versus atypical:32%) and respiratory failure (9% versus 24%; both p < 0.05). Overall, 98 underwent surgery, majority undergoing laparoscopic adrenalectomy (81%); similar among the subtypes(p = 0.71). No robust data was provided on short-term outcomes, although two patients suffered from post-operative complications. CONCLUSION: Although quite similar in presentation to either standalone TCM or PCC, PCC-TCM seems to be associated with a higher degree of morbidity and mortality. The atypical PCC-TCM subgroup seems to have a more severe course with possibly a poorer outcome. Further research is needed to make more reliable inferences.

Takotsubo Cardiomyopathy and ß-Blocker Poisoning: A Case Report.

ß-blocker poisoning is frequently observed because of its primary use for the treatment of cardiovascular diseases. The management of ß-blocker toxicity is dependent on the cardiovascular response and the severity of presentation. The present study describes the case of a patient with combined drug intoxication, ß-blocker, digoxin, benzodiazepines, acetaminophen and opiates in a suicidal attempt. A 63-year-old female was found somnolent and in a confused state at her residence following intentional poly-drug ingestion. Upon presentation, she was found to be hemodynamically unstable and was thus treated with vasopressors. The toxicological screening performed upon presentation was positive for polydrug ingestion. On day 3, the patient developed chest pain and ST-segment elevation in anterior leads, while transthoracic echocardiographic assessment disclosed a non-dilated left ventricle with moderate dysfunction and akinesia of the apex. Coronary angiogram revealed normal coronary arteries and, subsequently, the diagnosis of Takotsubo cardiomyopathy (TTC) was suspected. Supportive treatment was initiated with favorable evolution and left ventricular ejection fraction normalization. The management of hemodynamic instability with vasopressors should be judiciously administered in the treatment of ß-blocker poisoning, in view of the adverse effects on cardiac functions, including stress cardiomyopathy.

Takotsubo syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab plus axitinib.

We report the case of a patient with metastatic renal cell carcinoma who developed Takotsubo syndrome (TTS) 6 days after starting pembrolizumab plus axitinib as first-line treatment. Coronary angiogram was negative for obstructive coronary artery disease and echocardiogram revealed a depressed left ventricular ejection fraction with apical akinesis. Axitinib was discontinued and myocardial contractile function fully recovered 23 days after the initial presentation. The treatment was safely resumed and granted a partial response of disease. A literature review regarding TTS in patients receiving VEGFR tyrosine kinase inhibitors and/or immune checkpoint inhibitors was performed. TTS is reported as a rare adverse event and the possible causal relationship between TTS and antineoplastic therapy is still unclear. Further research is warranted to better understand cardiotoxicity mechanisms and their management.

We report the case of a patient with metastatic renal cell carcinoma who developed a rare cardiac adverse event called Takotsubo syndrome 6 days after starting antineoplastic therapy with pembrolizumab plus axitinib. Axitinib was discontinued and cardiac function fully recovered 23 days after the initial presentation. The treatment was safely resumed and granted a partial response of disease. Takotsubo syndrome is reported as a rare adverse event and the possible causal relationship with antineoplastic therapy is still unclear. Further research is warranted to better understand cardiotoxicity mechanisms and their management.

Takotsubo Syndrome in a Rheumatoid Arthritis Patient Under Tofacitinib: A Case Report.

We describe a case of a 57-year-old white woman treated for rheumatoid arthritis (RA) with tofacitinib 10mg daily (started one year ago) and prednisolone 5mg daily. She presented to the emergency department with a tight squeezing chest pain and shortness of breath for 7h and the clinical evaluation revealed regional systolic dysfunction of the left ventricle, mimicking a myocardial infarction, in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. All changes were transient and resolved completely within 4 days. The diagnosis of Takotsubo cardiomyopathy (TKM) was established. This is, as far as we know, the first report of a case of TKM in a RA patient taking tofacitinib. Although the association has not been previously described and the precise cause cannot be identified in this patient, the association with tofacitinib should be considered given the etiopathogenic rationale and the absence of any other identifiable cause.