Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

A Tale of 2 Morbid Complications in a Patient With Takotsubo Cardiomyopathy.

A 66-year-old female was found hypotensive in ventricular tachycardia (V-tach). Workup confirmed septic shock and takotsubo cardiomyopathy (TCM) with left ventricular (LV) thrombus. Despite the initiation of anticoagulation therapy, she developed an embolic stroke on day 14. Malignant ventricular arrhythmia and LV thrombosis are rare complications of TCM. However, there is no specific guideline regarding prophylactic anticoagulation.

Successful treatment of cardiogenic shock due to Takotsubo syndrome with implantation of a temporary microaxial left ventricular assist device in transaxillary approach.

OBJECTIVES: Cardiogenic shock (CS) can occur in patients with Takotsubo syndrome (TTS). As TTS has received increasing attention and has been more closely researched, several aspects of the pathogenesis have been identified, particularly that an excessive release of catecholamines plays an important role. Nevertheless, evidence on specific therapy concepts is still lacking. As a result, TTS with severe hemodynamic instability and low cardiac output creates unique challenges, and mechanical circulatory support is needed with as few inotropic drugs as possible. METHODS: We present a 77-year-old female patient who underwent minimally invasive surgical mitral valve replacement. After an uneventful course, the patient developed acute heart failure eleven days after surgery. Transthoracic echocardiography (TTE) revealed a new onset of TTS. The patient needed left ventricular venting and full haemodynamic flow. We successfully implanted a microaxial left ventricular assist device (Impella 5.5) using the transaxillary approach. The haemodynamic situation stabilised immediately. The patient was weaned and the Impella 5.5 was explanted after five days. CONCLUSION: We present the first-in-man implantation of a transaxillary Impella 5.5 in a patient with TTS. The patient benefitted from Impella 5.5 therapy with full haemodynamic support and venting of the left ventricle.

Case report: Takotsubo syndrome following percutaneous coronary intervention.

BACKGROUND: Takotsubo syndrome (TTS), which is frequently secondary to severe emotional (fear, anxiety, etc.) or physical stress, is an acute reversible heart failure syndrome characterized by temporary left ventricular regional systolic dysfunction. Nevertheless, TTS after percutaneous coronary intervention (PCI) is rare, and its clinical characteristics are easily confused with complications after PCI. CASE PRESENTATION: This article reports a case of TTS induced by psychological and physical pressure after successful PCI in our institution. The patient had symptoms comparable to complications after PCI, including V1-V5 ST segment elevation and T wave changes of electrocardiogram (ECG) and troponin elevation. Coronary angiogram, left ventricle opacification (LVO), and cardiac magnetic resonance (CMR) were performed to exclude postoperative complications. Diagnosis of TTS was eventually achieved. CONCLUSION: We cannot dismiss the risk of TTS in patients who have unexplained V1-V5 ST segment elevation and T wave changes of ECG and troponin elevation following successful PCI. Meanwhile, medical personnel should provide mental, cultural, and emotional services to patients in addition to essential diagnostic and treatment technical services during the perioperative period.

Relationship between Cardiovascular Risk Factors and Composite Cardiovascular Outcomes in Patients Hospitalized with Takotsubo Syndrome: A Nationwide Analysis.

The association of traditional cardiovascular disease (CVD) risk factors with outcomes of Takotsubo syndrome (TTS) is not well-defined. This study examined how modifiable CVD risk factors affect composite cardiovascular outcomes in TTS hospitalizations. TTS admissions were identified using ICD-10 codes and compared for demographics and comorbidities using the 2019 National Inpatient Sample. A multivariable regression examined the association of traditional CVD risk variables with adverse composite cardiovascular outcomes in TTS, controlling for confounders including sociodemographic or hospital-level characteristics and other relevant comorbidities. A total of 16,055 (38.1%) of the 41,855 adult TTS admissions had composite cardiovascular outcomes (TACCO). The TACCO cohort was 81.5% white, 77.3% female, and 72 years old. This group had higher rates of diabetes and peripheral vascular disease (PVD). The results showed that a higher prevalence of diabetes with chronic complications (OR = 1.18) and complicated hypertension (HTN) (OR = 1.1) predicted TACCO, whereas tobacco use disorder (OR = 0.84), hyperlipidemia (OR = 0.76), and uncomplicated HTN (OR = 0.65) (p < 0.001) showed a paradoxical effect with TACCO. TACCO had fewer routine discharges (35.3% vs. 63.4%), longer stays (6 vs. 3 days), and higher median hospital costs (78,309 USD vs. 44,966 USD). This population-based study found that complicated HTN and DM with chronic complications are strongly associated with adverse cardiovascular outcomes in TTS hospitalizations. But still, some risk factors, such as hyperlipidemia and uncomplicated HTN, have counterintuitive effects that require further evaluation. To prevent cardiac events in TTS patients, traditional CVD risk factors must be addressed.

Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

[Takotsubo syndrome with right ventricular involvement in biventricular arrhythmogenic cardiomyopathy]. / Sindrome Takotsubo con interessamento del ventricolo destro nella cardiomiopatia aritmogena biventricolare.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder with fibro-fatty replacement that involves the right ventricle and in the advanced phases could become biventricular. Takotsubo syndrome (TTS) is characterized by reversible systolic dysfunction occurring after a stressful event and independent of the underlying coronary artery disease. A 70-year-old female with family history of sudden cardiac death and a previous diagnosis of biventricular ARVC presented to the emergency department after experiencing chest pain and elevation of myocardial enzymes. The ECG showed sinus bradycardia and negative T-waves from V1-V3. Coronary arteries were free from stenosing atheromatous lesions at coronary angiography. Transthoracic echocardiography showed severe biventricular dysfunction due to left ventricular apical/peri-apical akinesis with apical ballooning pattern. Cardiac magnetic resonance confirmed the presence of transmural biventricular edema in the mid-apical segments in T2 weighted sequences involving both ventricles along with fibro-fatty replacement in post-contrast sequences. At discharge, a cardioverter-defibrillator was implanted. This case report shows that TTS diagnosis is challenging for the clinician due to the presence of structural cardiomyopathy with biventricular involvement. Second-line imaging modalities could be useful to identify the presence of myocardial edema and to recognize those conditions associated with poor prognosis.

[Heart rate disorders in patients with Tako-tsubo syndrome]. / Trastornos del ritmo cardiaco en pacientes con síndrome de Tako-tsubo.

OBJECTIVES: This study sought to evaluate the incidence, prognosis and treatment of heart rhythm disorders (HRD) in Tako-tsubo syndrome (TTS). BACKGROUND: TTS is associated with HRD. The HRD prognostic value is not well characterized in TTS yet. METHODS: The HRD of patients included in the National Registry of Tako-tsubo syndrome, admitted between 2002 and 2018 and coming from 38 hospitals throughout the country, was analyzed. We analyzed any heart rhythm disorder in patients presented before admission, at admission and in long-term follow-up. RESULTS: All types of HRD were described in 259 (23.5%) cases, from a cohort of 1,097 consecutive patients with TTS. HRD was more associated with diabetes mellitus, smoking, hyperuricemia, sleep apnea, anemia with a worse LVEF on admission. The most frequent HRD was a new onset of atrial fibrillation. During hospitalization, patients with HRD showed more complications such as shock on admission, major bleeding, acute renal failure, and combined infections. At follow-up, they presented higher mortality and more major adverse cardiac events, but with a non-significant correlation. CONCLUSIONS: The incidence of HRD in patients with TTS is not infrequent. TTS, when associated with HRD, presents more complications and a worse prognosis both in hospital and in the long term.

Trigger-Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

Background Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German-Italian-Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in-hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long-term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long-term mortality, while chest pain (P=0.035) and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long-term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long-term mortality.

Tako-Tsubo Syndrome Following Pulmonary Vein Isolation for Atrial Fibrillation in a Patient with Primary Aldosteronism.

Tako-tsubo syndrome (TTS) can be triggered by emotional or physical stress and is characterized by transient left ventricular dysfunction with apical ballooning. Some neurologic disorders and pheochromocytoma serve as triggers for TTS, however, its association with primary aldosteronism (PA) is not well known. Pulmonary vein isolation (PVI) with catheter ablation for atrial fibrillation (AF) has been performed worldwide, and TTS following PVI has been reported as a rare complication. Sympathetic stimulation can play an important role in TTS development, however, its mechanism and risk factors are not yet understood.We describe a 72-year-old woman with PA who developed TTS after PVI with radiofrequency catheter ablation (RFCA) for symptomatic paroxysmal AF. Complete isolation of the pulmonary vein was carried out without any complications, however, she complained of epigastric discomfort 7 hours after the procedure. An electrocardiogram showed recurrent AF with a new negative-T wave and prolonged QT interval. Transthoracic echocardiography revealed apical ballooning and basal hypercontraction, characteristic of TTS, and coronary angiography showed no significant stenosis. She was diagnosed with TTS following RFCA for AF and managed well with conservative therapy.The present case suggests that TTS should be recognized as a complication associated with AF ablation. Moreover, PA may be involved in TTS development by increasing sympathetic activity. Further studies on the mechanism and characteristics of TTS are required.

[Left Ventricular Plasty for Left Ventricular Aneurysm Following Takotsubo Cardiomyopathy].

An 82-years-old woman was admitted with sudden chest pain. Coronary angiography did not reveal any significant stenosis, but left ventriculography showed akinesis and ballooning of the apex with a hyperkinetic basal segment, suggestive of takotsubo cardiomyopathy. She suffered intractable heart failure, and laboratory data, electrocardiogram signs of ST-segment elevation and left ventricular( LV) apical dysfunction failed to show improvement. LV plasty was performed on 106th day after the onset because of aneurysmal change of the left ventricular apex myocardium, unremitting sanguineous pericardial effusion, and anemia. She had a good postoperative course and end-diastolic ventricular volume index was remarkably reduced from 144 to 55 ml/m2. She discharged home on the 38th postoperative day.

Can Breaking Heroin Addiction Lead to a Broken Heart? A Case of Reverse Takotsubo Cardiomyopathy in a Patient With Heroin Withdrawal.

Reverse takotsubo cardiomyopathy is triggered by emotional or physical stress and has a presentation similar to that of acute coronary syndrome. A 39-year-old woman with a history of heroin use disorder presented with intractable nausea, vomiting, and diarrhea. She was diagnosed with heroin withdrawal and started on buprenorphine-naloxone. On day 2 of her hospitalization, she developed chest heaviness and had an elevated troponin I level of 3.2 ng/mL (reference range, 0.015-0.045 ng/mL); electrocardiography showed new T-wave inversions in the anterior and inferior leads. Emergent coronary angiography showed patent coronary arteries, and left ventriculography showed basal hypokinesis and apical hyperkinesis, consistent with reverse takotsubo cardiomyopathy secondary to heroin withdrawal. She was started on antihypertensive agents, and her buprenorphine-naloxone dose was increased. At her 3-month follow-up visit, she reported no symptoms consistent with angina or heart failure. This appears to be the first report of heroin withdrawal causing reverse takotsubo cardiomyopathy. Awareness of this association can lead to earlier recognition and treatment of reverse takotsubo cardiomyopathy.

Can Significant Coronary Artery Disease Coexist With Transient Takotsubo Cardiomyopathy, and How Does Spasm Interrelate?

An 86-year-old woman being treated for metastatic breast cancer developed severe chest pain at rest during a follow-up visit at a hospital's outpatient oncology clinic. An electrocardiogram showed severe ST-segment elevation. The patient was given sublingual nitroglycerin and was transferred to the emergency department. Diagnostic coronary angiography revealed moderate coronary artery disease with calcific stenoses and transient spastic occlusion of the left anterior descending coronary artery. For this patient, sublingual nitroglycerin aborted the spastic event and apparent transient takotsubo cardiomyopathy. Chemotherapy can potentially cause endothelial dysfunction and increased coronary spasticity, which could result in takotsubo cardiomyopathy.

Neutrophil-to-lymphocyte ratio as a predictor of in-hospital complications and overall mortality in Takotsubo syndrome preceded by physical triggers.

BACKGROUND: Takotsubo syndrome (TTS) with physical triggers has worse short- and long-term clinical courses than those with emotional triggers. However, predictive factors associated with poor outcomes of TTS with physical triggers are unknown. METHODS: We included 231 patients identified as TTS preceded by physical triggers at two tertiary referral hospitals from 2010 to 2019. In-hospital complications (IHC)-a composite of malignant arrhythmia, need for mechanical circulatory support or mechanical ventilation, and in-hospital death-and overall mortality were retrospectively reviewed. The associations with clinical features were evaluated by multivariable logistic and Cox regression analyses. RESULTS: The mean age was 69.3 ± 11.6 years, and 85 (36.8%) were male. The in-hospital complications rate was 46.8%. During a median follow-up of 883 days, 96 (41.6%) had died, and overall mortality was 13.6% per patient-year. Higher neutrophil-to-lymphocyte ratio (NLR) was associated with a higher risk of IHC (area under the receiver operating characteristic curve = 0.73; positive and negative predictive value = 60.9% and 67.2% for NLR ≤ 12); odds ratio (OR) with 95% confidence interval (CI) was 1.03 (1.01-1.05), p = 0.010. Subsequently, higher NLR was also related to a greater risk of overall mortality; patients with high NLR (NLR > 12) exhibited poor long-term survival than those with low NLR (NLR ≤ 5): hazard ratio (95% CI), 3.70 (1.72-7.94) with p < 0.001. CONCLUSIONS: A high NLR at initial presentation is associated with an increased risk of IHC and overall mortality in TTS preceded by physical triggers. Given that the treatment of TTS is mainly supportive, intensive monitoring with careful follow-up would be warranted in patients with high NLR.

Rationale and design of BROKEN-SWEDEHEART: a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome.

BACKGROUND: Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome without any evidence-based treatment options. No treatment for TS has been examined in a randomized trial. STUDY DESIGN AND OBJECTIVES: BROKEN-SWEDEHEART is a multicenter, randomized, open-label, registry-based 2 × 2 factorial clinical trial in patients with TS designed to test whether treatment with adenosine and dipyridamole accelerates cardiac recovery and improves clinical outcomes compared to standard care (study 1); and apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs (study 2). The trial will enroll 1,000 patients. Study 1 (adenosine hypothesis) will evaluate 2 coprimary end points: (1) wall motion score index at 48 to 96 hours (evaluated in the first 200 patients); and (2) the composite of death, cardiac arrest, need for mechanical assist device or heart failure hospitalization within 30 days or left ventricular ejection fraction <50% at 48 to 96 hours (evaluated in 1,000 patients). The primary end point in study 2 (apixaban hypothesis) is the composite of death or thromboembolic events within 30 days or the presence of intraventricular thrombus on echocardiography at 48 to 96 hours. CONCLUSIONS: BROKEN-SWEDEHEART will be the first prospective randomized multicenter trial in patients with TS. It is designed as 2 parallel studies to evaluate whether adenosine accelerates cardiac recovery and improves cardiac function in the acute phase and the efficacy of anticoagulation therapy for preventing thromboembolic complications in TS. If either of its component studies is successful, the trial will provide the first evidence-based treatment recommendation in TS. CLINICAL TRIALS IDENTIFIER: The trial has been approved by the Swedish Medicinal Product Agency and the Swedish Ethical Board and is registered at ClinicalTrials.gov (NCT04666454).

Takotsubo Like Cardiomyopathy with Concomitant Pheochromocytoma: A Rare Presentation.

Pheochromocytoma classically presents with headache, diaphoresis, palpitations and, raised blood pressure. Rarely, it manifests as cardiomyopathy. Herein, we present a case of a 42-year woman who presented with heart failure and on work-up was found to have pheochromocytoma leading to Takotsubo-like cardiomyopathy. The biochemical profile revealed raised serum metanephrines and normetanephrines. CT abdomen showed a left adrenal mass. Within two weeks of presentation and before surgical excision of the mass, she recovered from cardiomyopathy. After medical optimisation, the patient underwent elective adrenalectomy, which on histological evaluation revealed pheochromocytoma. Key Words: Cardiomyopathy, Pheochromocytoma, Adrenal mass.

A myasthenic crisis of broken hearts (reverse takotsubo): Case report and review of literature.

Myasthenic crisis (MC) is rarely associated with takotsubo cardiomyopathy (TTC), but embolic complications of MC-associated reverse TTC are yet to be documented. We present a case of a 70-year-old Caucasian female with MC-associated reverse TTC, developing acute cerebral infarcts. Following aggressive treatment with immunoglobulins and anticholinergics, cardiac function normalised. TTC is an important differential diagnosis in acute deteriorations of cardiac function, particularly in intensive care, not only due to frequent use of inotropes and embolic complications but also because cardiac function is reversible with good medical care. Early specialist neurologist and cardiologist input should be sought in such cases.

Pheochromocytoma with Takotsubo Syndrome and acute heart failure: a case report.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor that can overproduce catecholamines. Heart failure and Takotsubo Syndrome (TTS) caused by excessive catecholamines are uncommon pheochromocytoma complications. CASE PRESENTATION: A 27-year-old woman was referred to our center for further preoperative assessment and adrenalectomy. She came to the emergency ward with the typical symptoms of acute coronary syndrome and heart failure, including chest stuffiness, dyspnea, epigastric pain, and diaphoresis. The high level of 24-hour urinary vanillylmandelic acid and abdominal computed tomography findings supported the diagnosis of pheochromocytoma. Transthoracic echocardiography showed diffuse hypokinesis of the left ventricular wall with an ejection fraction of 23%. All symptoms and left ventricular function recovered rapidly after left laparoscopic adrenalectomy. Histopathology findings confirmed the diagnosis of pheochromocytoma. Based on the above findings, we eventually diagnosed her with pheochromocytoma-induced TTS. CONCLUSIONS: This is a rare case of pheochromocytoma without hypertension complicated by TTS and acute heart failure. A diagnosis of pheochromocytoma-induced TTS should be considered for patients presenting with uncommon heart failure, even in patients without hypertension. Standard treatment is the surgical removal of the adrenal mass.

Takotsubo cardiomyopathy in the setting of thyroid storm.

A woman in her 50s with a background of chronic obstructive pulmonary disease secondary to smoking presented with intermittent chest tightness, dyspnoea and vomiting for 4 days. A presumed diagnosis of acute coronary syndrome (ACS) was made based on dynamic ischaemic ECG changes and elevation in high-sensitivity cardiac troponin T levels. She underwent emergent coronary angiography which demonstrated mild coronary artery disease with left ventriculography suggestive of mid-wall variant Takotsubo cardiomyopathy. Thyroid function tests performed to investigate sinus tachycardia were consistent with hyperthyroidism, and her thyroid-stimulating hormone receptor antibody was elevated. A diagnosis of thyroid storm was made in the setting of a newly diagnosed Graves' disease and the patient was subsequently commenced on guideline-based therapy. This case demonstrates that Takotsubo cardiomyopathy, a mimic of ACS, is a possible complication of thyroid storm and therefore hyperthyroidism should be considered in the list of differentials in patients presenting with Takotsubo cardiomyopathy.