Recurrent Takotsubo Syndrome Resulting From Different Emotional Triggers as Broken and Happy Heart Syndrome.

A postmenopausal woman presented with recurrent takotsubo syndrome on 3 different occasions. The first and second episodes presented as broken heart syndrome and the third as happy heart syndrome. After literature review, the authors believe this is the first recorded case of a patient having broken and happy heart syndrome on separate occasions.

Racial and ethnic disparities in clinical outcomes among patients with takotsubo syndrome; A nation-wide analysis.

BACKGROUND: Takotsubo syndrome (TTS), a stress-induced transient left ventricular dysfunction, remains poorly understood, with an estimated incidence of 1-2 % among acute coronary syndrome cases. This study investigates racial and ethnic disparities in hospital outcomes and clinical characteristics of TTS. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample data from 2016 to 2020, identifying TTS cases through validated ICD-10 codes. Statistical analysis was performed using Stata 18, with logistic regression models adjusting for confounders to identify disparities in outcomes. RESULTS: The study included 32,785 TTS hospitalizations; the majority were White (80.5 %), followed by Black (6.7 %) and Hispanic (5.8 %) patients. Minority groups, mainly Black and Hispanic patients, were younger (average age 63) and predominantly from lower-income brackets, while Asians had the highest income bracket. Length of stay (5.1 days) and Total cost ($22,707.60) were highest among Native Americans. Notable findings include Black patients showing the highest rate of stroke (4.8 %, OR 2.1, 95 % CI 1.2 to 3.4, p = 0.003). The rate of cardiogenic shock was highest among Asians (11 %, OR 2, 95 % CI 1.5 to 2.5, p < 0.001). Mortality rates were elevated in Black (2 %, OR 1.5, 95 % CI 1.3 to 1.7 p < 0.001) and Asian populations (1.8 %, OR 1.97, 95 % CI 1.5 to 2.5, p < 0.001). CONCLUSION: Significant racial and ethnic disparities exist in TTS outcomes, with minority groups having more in-hospital outcomes. These findings highlight the urgent need for targeted interventions and further research to reduce healthcare inequities in TTS management.

Noninvasive Assessment in Takotsubo Syndrome: A Diagnostic Challenge.

Takotsubo syndrome (TTS) is a clinical syndrome characterized by a transient left ventricular dysfunction whose diagnosis can be challenging due to its resemblance to acute myocardial infarction (AMI). Despite the growing recognition of TTS, acute complications and long-term mortality rates are comparable to those observed in AMI patients. In this context, a systematic diagnostic approach is imperative for an accurate patient assessment, with due consideration of the distinctive characteristics and optimal timing of each imaging modality. Coronary angiography with ventriculography may be reserved for cases presenting with ST-segment elevation, whereas in all other cases, the use of multimodality noninvasive imaging allows for a comprehensive evaluation of typical diagnostic features and detection of acute complications while also providing prognostic insights. The aim of this review is to evaluate the current research on non-invasive modalities and to propose a diagnostic algorithm that will facilitate the identification and management of TTS.

Takotsubo syndrome induced by severe hyponatraemia in mineralocorticoid-responsive hyponatraemia of the elderly: a case report.

Background: There are limited reports on mineralocorticoid-responsive hyponatraemia of the elderly (MRHE), a condition that can cause severe hyponatraemia. Case summary: An 85-year-old woman presented with transient loss of consciousness and nausea likely due to untreated severe hyponatraemia (114 mEq/L). Thirty-nine hours after initial admission, she developed sudden cardiac dysfunction and entered a circulatory collapse state. The patient was diagnosed with Takotsubo syndrome. Her hyponatraemia was an essential feature of syndrome of inappropriate antidiuretic hormone secretion. However, she was clinically hypovolaemic. Therefore, the hyponatraemia was diagnosed as MRHE. The serum sodium level was corrected with 3% hypertonic saline administered at a rate of 10 mL per hour, with careful monitoring to avoid overly rapid correction and prevent osmotic demyelination. After 14 days, her serum sodium level, electrocardiogram findings, and cardiac contractions on echocardiography improved. Discussion: To our knowledge, this is the first documented case of Takotsubo syndrome induced by severe hyponatraemia resulting from MRHE. The present report shows that acute cardiomyopathy can develop when severe hyponatraemia is not treated within several hours and at least a day. Since patients with MRHE are hypovolaemia statement, avoidance of diuretic drugs and water restriction for the treatment of hyponatraemia should be carefully considered, especially if they have acute cardiac dysfunction. This report highlights the need for prompt management of severe hyponatraemia in elderly patients and calls for further research on MRHE treatment protocols and its link to cardiomyopathy.

Acute myocardial infarction or Takotsubo syndrome in a patient with stunned myocardium due to myocardial bridging? A case report of diagnostic dilemma clarified after serial workup.

BACKGROUND: Myocardial bridging is a cardiac anomaly where a segment of epicardial coronary arteries runs through the myocardium and can rarely cause MI. Takotsubo syndrome is a stress-induced cardiomyopathy that can mimic MI. Catecholamine surge during stress can contribute to Takotsubo syndrome, but whether this surge can trigger an inconspicuous myocardial bridging to manifest symptomatically remains unclear, and alternately, whether a myocardial bridge might cause worsening of Takotsubo syndrome is also a matter that needs further research. CASE PRESENTATION: We report the case of a patient who initially presented with features of acute exacerbation of bronchiectasis and subsequently developed symptoms and ECG features suggestive of acute myocardial infarction. Echocardiography revealed features of takotsubo syndrome, and complete myocardial bridging was revealed via coronary angiography. The patient was managed conservatively with pharmacological treatment, and after a few days, echocardiographic features were reversed. As such, the diagnosis shifted toward Takotsubo syndrome with myocardial stunning due to co-existent myocardial bridging. CONCLUSION: We report a rare case of a patient with acute bronchiectasis exacerbation with features suggestive of acute myocardial infarction who had findings of Takotsubo syndrome and complete myocardial bridging. In the beginning, it was difficult to determine whether the symptoms arose due to acute MI resulting from myocardial bridging or were solely due to takotsubo syndrome because of stress from bronchiectasis. Although myocardial bridging is often overlooked as an etiology for acute MI, this case highlights the importance of expanding the differential diagnosis to myocardial bridging in the work-up for the cause of acute MI and how Takotsubo syndrome can mimic acute MI and pose a diagnostic challenge.

Repolarization Injury and Occurrence of Torsades de Pointes During Acute Takotsubo Syndrome.

Background: During takotsubo syndrome (TS), QTc prolongation is common, reflecting repolarization injury and providing the substrate for torsades de pointes (TdP). TdP has been reported sporadically in TS, yet QTc prolongation and TdP risk are often overlooked during management. Objectives: In TS patients, we sought to document TdP incidence, characteristics of patients with TdP, and association of QTc with postdischarge survival. Methods: Among consecutive TS patients at a single institution, we documented admission and discharge QTc, TdP incidence, and postdischarge 1-year mortality from 2006 to 2019. For perspective regarding TdP-TS risk, we characterized all published TdP cases from 2003 to 2022. Results: Of 259 patients, median age was 68 (range: 59-77) years; 92% were female. The QTc interval was prolonged (≥460 ms) on admission in 129 (49.8%) patients and at discharge in 140 (54%) patients. QTc was ≥500 ms either on admission or at discharge in 98 (37.8%) patients. In-hospital TdP incidence was 0.8%. Postdischarge mortality was associated with admission but not discharge, QTc: <460 ms (1.6%); 460-499 ms (12.6%); ≥500 ms (8.8%); P = 0.0056. Among 38 published TdP-TS cases, 80% of TdP events were within 48 hours of hospitalization, 90% of events occurred with QTc ≥500 ms, and 47.5% of events occurred with QTc ≥600 ms. Conditions associated with TdP risk were present in fewer than one-third of patients. Conclusions: During TS, QTc ≥500 ms was frequent. TdP incidence was low, with unpredictable occurrence and observed almost entirely with QTc ≥500 ms. A normal admission QTc was associated with >98% survival at 1-year postdischarge.

Takotsubo Syndrome or Peripartum Cardiomyopathy? Depends on Who You Are Talking to.

Takotsubo syndrome (otherwise known as broken-heart syndrome or left ventricular apical ballooning) is a rare cause of reversible heart failure that predominantly affects postmenopausal women. It was first described by Japanese researchers in the 1990s and has become established as a differential for heart failure following a physically or psychologically stressful event. This was popularised by a spike in cases following natural disasters in Japan. As the recognition of takotsubo syndrome in the differential diagnosis for sudden, onset heart failure in a previously healthy individual has grown, so has the discussion concerning takotsubo in the peripartum period. Peripartum cardiomyopathy is a rare cause of reversible heart failure in the latter weeks of pregnancy and the postpartum period. Morbidity and mortality for both cardiomyopathies can be highly variable, ranging from complete recovery of cardiac function to life threatening arrhythmias and even death. This rapid review highlights the similarities between both cardiomyopathies and challenges the hitherto assumption that both takotsubo and peripartum cardiomyopathies are distinct entities that can easily be distinguished from one another. The implications of this are significant within the context of the behavioural aspects of diagnosis, treatment, and outcome.

Temporal Trends in Takotsubo Syndrome: Results From the International Takotsubo Registry.

BACKGROUND: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. OBJECTIVES: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. METHODS: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. RESULTS: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). CONCLUSIONS: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

Recovery of Left Ventricular Function and Long-Term Outcomes in Patients With Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a form of transient left ventricular (LV) dysfunction that usually resolves within days to weeks. OBJECTIVES: We aimed to assess the predictors and prognostic impact of time-to-LV recovery after TTS. METHODS: Prospective serial imaging data from the nationwide, multicenter RETAKO (REgistry on TAKOtsubo Syndrome) were comprehensively reviewed to assess the timing of LV recovery. Multivariable logistic regression was used to assess factors associated with late (≥10 days) vs early (<10 days) recovery. The long-term risk of all-cause mortality was compared between the late and early recovery groups using fully adjusted Cox models, and using flexible parametric survival models with recovery time included as a continuous variable. RESULTS: Of 1,463 patients included (median age 73 years, 13% men), 373 (25%) had late and 1,090 (75%) had early LV recovery. Older age, history of neurological disorders, bystander coronary artery disease, active cancer, physical triggers, elevated inflammatory biomarkers, cardiogenic shock, and lower LV ejection fraction at admission were independent predictors of late recovery. At 4-year follow-up, the adjusted risk of death was significantly higher in patients with late recovery compared with those with early recovery (16.0% vs 8.6%, adjusted HR: 1.31; 95% CI: 1.12-1.60), with the risk of death increasing by 8% for every additional 10-day delay in time-to-LV recovery (adjusted HR: 1.08; 95% CI: 1.04-1.13). CONCLUSIONS: Late recovery of LV function after TTS is associated with reduced short- and long-term survival. In TTS patients without early LV recovery, closer clinical follow-up might be considered.

Evaluation of Recurrent Takotsubo Syndrome.

Background: After an initial Takotsubo syndrome (TTS) event, there is growing recognition of adverse long-term outcomes, including recurrent TTS events. Recurrent events have been incompletely evaluated. Objectives: The objective of this study was to characterize recurrent TTS events and evaluate variables associated with recurrence. Methods: We studied 88 consecutive participants in the Cedars-Sinai Smidt Heart Institute Takotsubo Registry, an observational registry collecting retrospective and prospective data in TTS survivors. Detailed medical records are adjudicated. Standardized psychosocial questionnaires are administered remotely. Results: Of 88 participants with adjudicated TTS, 15 (17%) experienced at least 1 recurrent TTS event (median 3.30 years to first recurrent event, range 0.13-18.56 years). In 9 of these 15 participants, there were different patterns of wall motion abnormalities observed between events. The recurrence-free survival significantly differed based on the pattern of wall motion abnormalities at the index TTS event. Clinical, electrocardiographic, echocardiographic, and invasive data obtained at the index TTS event were similar between participants who went on to have at least 1 recurrent event and those who did not. Conclusions: Recurrent TTS episodes occurred in a significant proportion of cases, a median of 3.30 years after the index event. The recurrent episodes often had distinct triggers and different wall motion abnormalities compared to the index event. The wall motion pattern at the index event impacted the recurrence-free survival, though confirmatory studies are needed. TTS participants had a high rate of adverse psychosocial stress characteristics based on detailed questionnaires. (The Cedars-Sinai Smidt Heart Institute Takotsubo Registry & Proteomic Study; NCT03910569).

Cardiohistological Findings in Refeeding Syndrome.

Severe eating disorders may develop refeeding syndrome, which sometimes resembles severe cardiac dysfunction. A woman in her thirties was admitted to our hospital because of cardiogenic shock. Transthoracic echocardiography showed reduced left ventricular systolic function. In her medical history, she had been diagnosed with refeeding syndrome. A ventricular endocardial biopsy was performed to exclude other cardiac diseases. A histological examination showed conspicuously atrophied cardiomyocytes with nuclear swelling and irregularities; the myocardial sequence was disturbed with fibrosis. Immunostaining revealed that lipid droplet markers, adipose triglyceride lipase, and perilipin 2 were poorly observed in the cardiomyocytes, while expression of both proteins was attenuated in fibroblasts within the myocardial layer. The abnormal metabolism of fatty acids was the presumed cause of cardiac dysfunction.

Intraoperative Takotsubo Syndrome.

Takotsubo cardiomyopathy is a rare condition that presents a diagnostic challenge due to its close resemblance to acute myocardial ischemia and other cardiac disorders. The excessive production of catecholamines triggers abnormal and severe changes in the myocardium, typically resulting in significant dyskinesia of the left ventricle's apex, reduced ejection fraction, hypotension, and pulmonary edema. Recent reports suggest that potential risk factors may include postmenopausal syndrome and intense, unexpected stress, whether related to life events or medical conditions. Complications such as heart failure, thrombosis, and severe arrhythmias are infrequent and more likely to occur in patients with pre-existing cardiac conditions. We present the case of a 22-year-old woman who developed intraoperative Takotsubo cardiomyopathy during a transsphenoidal resection of a prolactin-secreting pituitary tumor under general anesthesia. Perioperative combination of cabergoline and oxymetazoline induced intraoperative hypertension, pulmonary edema, and Takotsubo stress cardiomyopathy. To our knowledge, this is the first reported case in the literature of intraoperative Takotsubo cardiomyopathy, potentially linked to the specific combination of intraoperative cabergoline and oxymetazoline.

Racial disparities in trend, clinical characteristics and outcomes in Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute transient nonischemic cardiomyopathy often characterized by its hallmark feature of left ventricular apical ballooning. The correlation between racial backgrounds and the prognosis of individuals with TTS remains poorly defined. Our study aimed to explore the influence of race on the trends, clinical presentations, and outcomes in patients diagnosed with TTS. METHODS: We queried the National Inpatient Sample (NIS) database from 2016 to 2020 and identified hospitalizations with TTS. We compared the clinical features and outcomes across three different races - non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic population. The primary outcome was in-hospital mortality. RESULTS: 76,505 weighted hospitalizations for TTS were identified, of which 65,495 (85.6%) were non-Hispanic White, 5,830 (7.6%) were non-Hispanic Black, and 5,180 (6.8%) were Hispanics. After propensity-score matching, NHB patients had higher odds of acute kidney injury (OR: 1.49, 95% CI: 1.21-1.84, p < 0.001) and mechanical ventilation (OR: 1.33, 95% CI: 1.04-1.68, p = 0.02). Hispanic patients had a higher incidence of acute kidney injury requiring dialysis when compared to NHW patients (OR: 2.53, 95% CI: 1.11-5.77, p = 0.027). There was no significant difference in terms of in-hospital mortality between NHB and Hispanic patients when compared to NHW patients. Notably, Hispanic populations experienced a higher mortality rate during the COVID-19 period. CONCLUSION: Our study suggested significant differences in the outcomes of TTS across different racial groups. Hispanic populations experienced a higher mortality rate with TTS during the COVID-19 era. Further research should emphasize discovering the factors contributing to the observed disparities.

Chronobiological variation in takotsubo syndrome: an updated systematic review and meta-analysis.

Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year. The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR). The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified. The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05). TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.

Takotsubo syndrome in a cancer patient treated with a combination of anti-cancer drugs including immune checkpoint inhibitors: a case report.

Background: Takotsubo syndrome (TTS) is characterized by transient regional left ventricular (LV) dysfunction occurring in individuals exposed to physical or emotional stress. Various stressors are triggers for TTS in cancer patients, and anti-cancer drugs have recently been proposed as a trigger. Therefore, further studies are needed to clarify these triggers and avoid the unnecessary interruption of anti-cancer treatment. Case summary: A 66-year-old woman presented with dyspnoea 10 days after the initiation of atezolizumab in combination with bevacizumab. She had previously received osimertinib as first-line therapy for recurrent lung cancer after primary resection and atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin as second-line therapy. She was admitted due to electrocardiography abnormalities and elevated troponin I and brain natriuretic peptide levels. Echocardiography revealed circumferential severe LV hypokinesis at the mid-ventricular level, with preserved wall motion at the base and apex. Cardiac catheterization performed after the attenuation of symptoms with 20 mg of intravenous furosemide showed normal coronary arteries. Cardiac magnetic resonance imaging on Day 4 revealed increases in T1 and T2 values and extracellular volume fraction; however, neither myocardial infiltration of inflammatory cells or myocardial necrosis was observed in endomyocardial samples obtained on the day of her arrival. Atypical TTS was suspected, and she was treated with perindopril, bisoprolol, and spironolactone. Magnetic resonance imaging 1.5 months after the onset of TTS showed improvements in LV contractility, T1 and T2 values, and the extracellular volume fraction. Discussion: A more detailed understanding of the relationship between anti-cancer drugs and TTS is crucial for preventing interruptions to anti-cancer therapy.

[Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors].

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2-8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2-0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

Roles and Mechanisms of Dopamine Receptor Signaling in Catecholamine Excess Induced Endothelial Dysfunctions.

Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 µM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. Patch clamp, FACS, ELISA, PCR, western blot and immunostaining analyses were performed in the study. Epi enhanced small conductance calcium-activated potassium channel current (ISK1-3) without influencing the channel expression and the effect was attenuated by D1/D5 receptor blocker. D1/D5 agonists mimicked the Epi effect, suggesting involvement of D1/D5 receptors in Epi effects. The enhancement of ISK1-3 caused by D1/D5 activation involved roles of PKA, ROS and NADPH oxidases. Activation of D1/D5 and SK1-3 channels caused a hyperpolarization, reduced NO production and increased ROS production. The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.

Takotsubo Syndrome Development Immediately Following Hemodialysis Initiation: A Case Report.

We herein report a case of Takotsubo syndrome in an 80-year-old woman with end-stage renal disease who hesitated to initiate hemodialysis for pulmonary edema. On hospital day 2, the patient experienced cardiac arrest. Coronary angiography after spontaneous return of circulation showed no substantial stenosis. Takotsubo syndrome was diagnosed based on echocardiography findings. On hospital day 3, she developed ventricular fibrillation but was spontaneously resuscitated. Patients with chronic kidney disease and those who postpone dialysis initiation may be at an increased risk of developing Takotsubo syndrome. Early and careful monitoring and adequate shared decision-making are essential for seamless initiation of dialysis.