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.

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.

Pheochromocytoma leading to Takotsubo and Ogilvie syndrome, a pathophysiological triad.

Takotsubo syndrome (TTS) is a transient left ventricle dysfunction usually caused by a stressful trigger (emotional or physical). We report the case of a 77 year-old female patient who presented with TTS caused by a pheochromocytoma, a catecholamine-producing neuroendocrine tumour. Diagnosis was facilitated by acute kidney injury prompting renal ultrasound, recurrence of TTS and symptoms of episodic palpitations, profuse sweating and labile blood pressure. Furthermore, during her hospitalisation the patient also developed an Ogilvie syndrome, an acute colonic pseudo-obstruction, due to the catecholamine-excess. Treatment consisted of betablocker and angiotensin-converting enzyme inhibitor for TTS, neostigmine for Ogilvie syndrome, in combination with alpha-blocker and surgical removal of the tumour after recuperation of left ventricular function and colonic pseudo-obstruction. To our knowledge, this is the first case report of the pathophysiological triad of pheochromocytoma leading to Takotsubo and Ogilvie syndrome in a single patient.

Takotsubo syndrome during treatment with 5-fluorouracil. / Takotsubosyndrom under behandling med fluorouracil.

BACKGROUND: Fluoropyrimidines have been linked to cardiovascular toxicity. CASE PRESENTATION: A woman in her forties with locally advanced rectal cancer received curative-intent treatment according to the RAPIDO protocol. Shortly after starting the first 5-fluorouracil infusion she developed chest/epigastric pain, nausea and vomiting. Electrocardiogram showed mild ST elevation in multiple contiguous leads. Troponin I was elevated. Transthoracic echocardiogram (TTE) displayed signs suggestive of myocardial infarction. Coronary angiogram indicated no obstructive coronary artery disease. Ventriculography demonstrated apical hypokinesia and basal hyperkinesia. MRI revealed no signs of myocardial infarction or myocarditis. The patient was diagnosed with Takotsubo syndrome, possibly induced by 5-fluorouracil. Follow-up TTE three weeks later was normal. Subsequently, she received treatment with tegafur/gimeracil/oteracil (Teysuno®) in place of 5-fluorouracil, combined with oxaliplatin. No further cardiotoxicity was observed during three cycles. INTERPRETATION: The patient was diagnosed with Takotsubo syndrome following 5-fluorouracil infusion, likely to represent 5-fluorouracil-induced cardiotoxicity. Following replacement of 5-fluorouracil with Teysuno®, she experienced no signs of cardiotoxicity.

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.

[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.

Pheochromocytoma crisis with refractory Acute Respiratory Distress Syndrome (ARDS), Takotsubo syndrome, emergency adrenalectomy, and need for Extracorporeal Membrane Oxygenation (ECMO) in a previously undiagnosed and asymptomatic patient, due to the use of metoclopramide.

BACKGROUND: Pheochromocytoma (PCC) crisis is a rare life-threatening endocrine emergency. The diagnosis and treatment of PCC crisis, with acute respiratory distress syndrome (ARDS) as the first manifestation, is highly challenging, and traditional PCC management strategies are no longer suitable for these patients. CASE PRESENTATION: A 46-year-old female patient was admitted to the Intensive Care Unit (ICU) following sudden-onset acute respiratory distress and subsequent initiation of mechanical ventilation via endotracheal intubation. She was initially suspected of having a PCC crisis through the bedside critical care ultrasonic examination protocol. The computed tomography examination revealed a left adrenal neoplasm of 6.5cm × 5.9cm. The plasma-free metanephrine level was 100 times higher than the reference value. These findings were compatible with her PCC diagnosis. Alpha-blockers and fluid intake were started immediately. The endotracheal intubation was removed on the 11th day after admission to the ICU. The patient progressed to severe ARDS again, and invasive ventilation and continuous renal replacement therapy were needed. Despite aggressive therapy, her condition deteriorated. Therefore, she underwent veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-assisted emergency adrenalectomy after multidisciplinary discussion. Postoperatively, the patient was supported by VA-ECMO for 7days. She was discharged from the hospital on day 30 after tumor resection. CONCLUSIONS: This case highlighted the challenges in diagnosing and managing ARDS associated with PCC crisis. The traditional preoperative preparation protocol and optimal operation timing for patients with PCC are not suitable for patients with PCC crisis. Patients with life-threatening PCC crisis may benefit from early tumor removal, and VA-ECMO could maintain hemodynamic stability during and after surgery.

Pregnancy-associated takotsubo cardiomyopathy hospitalizations in the United States.

Takotsubo cardiomyopathy (TCM) is most common not only in postmenopausal women aged ≥50 yr but also in pregnant individuals. However, there are no national estimates on the prevalence, timing of occurrence, correlates, and outcomes of pregnancy-associated TCM. Using the Nationwide Inpatient Sample (NIS: 2016-2020), we describe rates of pregnancy-associated TCM hospitalizations among 13- to 49-yr-old pregnant individuals in the United States by selected demographic, behavioral, hospital, and clinical characteristics. Joinpoint regression was used to describe the annual average percent change of pregnancy-associated TCM hospitalizations. Survey logistic regression was used to measure the association of pregnancy-associated TCM hospitalizations with maternal outcomes. Of the 19,754,535 pregnancy-associated hospitalizations, 590 were TCM associated. The overall trend in pregnancy-associated TCM hospitalizations remained stable during the study period. The majority of TCM occurred during the postpartum, followed by antepartum and delivery-associated hospitalizations. When compared with pregnancy hospitalizations without TCM, those with TCM were more likely to be over the age of 35 yr and use tobacco and opioids. Comorbidities during TCM-associated pregnancy hospitalizations included heart failure, coronary artery disease, hemorrhagic stroke, and hypertension. After controlling for potential confounders, the odds of pregnancy-associated TCM hospitalizations were 98.7 times [adjusted odds ratio (aOR) = 98.66, 95% confidence interval (CI) 31.23-311.64] and 14.7 times (aOR = 14.75, 95% CI 9.99-21.76) higher for experiencing in-hospital mortality and a prolonged hospital stay, respectively, than those without TCM. Although rare, pregnancy-associated TCM hospitalization is more likely to occur during the postpartum period and is associated with in-hospital mortality and prolonged hospital stay.NEW & NOTEWORTHY Although rare, pregnancy-associated takotsubo cardiomyopathy hospitalizations are more likely to occur during the postpartum period and are associated with in-hospital mortality and prolonged hospital stay.

Meta-Analysis and Clinical Features of Perioperative Takotsubo Cardiomyopathy in Noncardiac Surgery.

Perioperative takotsubo cardiomyopathy (pTCM) is an increasing condition defined as cardiomyopathy in the setting of emotional and physiologic stressors imposed by surgery. We aimed to classify and understand the presentation, management, and prognosis of noncardiac surgery pTCM in published cases. As such, a review of previous studies using the PubMed, Embase, Cochrane, and Web of Science databases was conducted to obtain case reports and series reporting noncardiac pTCM from inception to September 2022, and a crude analysis was conducted to classify the clinical features. Of the 1,002 studies, 96 met our inclusion criteria, of which 101 cases were extracted and included in the final systematic review. A total of 29.7% of cases occurred during general surgery and 20.8% during transplant procedures. The median age at presentation was 55 years, with a 42 to 65 interquartile range. The prevalence of hypertension and mood disorders were 22.8% and 9.9%, respectively. Before the procedures, physiologic stressors occurred more commonly than emotional stressors (20.8% and 11%, respectively). Objective findings, including ST-T-wave changes, new arrhythmias, and hypotension, were the most common initial presenting symptoms. Most cases occurred during emergence from surgery or on the first postoperative day. Mechanical circulatory support was required in 15.8% of the cases, and the all-cause in-hospital mortality was 6.9%. The ejection fraction and symptoms improved within a median of 2 weeks after diagnosis (interquartile range 1 to 6). In conclusion, the risk factors, triggers, and outcomes of pTCM appear to differ from those of classic nonperioperative TCM presentations. Future studies will help shed light on this more frequently diagnosed condition complicating some noncardiac surgical cases.

Hemodynamic Assessment in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology. OBJECTIVES: This study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms. METHODS: Left ventricular (LV) pressure-volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases. RESULTS: TTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL [P = 0.024]; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s [P = 0.031]; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL [P = 0.002]); and a shortened systolic period (286 ms vs 343 ms [P < 0.001]). In response, the pressure-volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms [P < 0.001]; minimal rate of change in diastolic pressure -1,457 mm Hg/s vs -2,192 mm Hg/s [P < 0.001]), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL [P = 0.942]). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure-volume area compared with that of control subjects (P = 0.357). CONCLUSIONS: TTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops [OCTOPUS]; NCT03726528).

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.