Comparison of troponin and natriuretic peptides in Takotsubo syndrome and acute coronary syndrome: a meta-analysis.

OBJECTIVE: Takotsubo syndrome (TTS) is an acute heart failure syndrome which resembles acute coronary syndrome (ACS) at presentation. Differentiation requires coronary angiography, but where this does not occur immediately, cardiac biomarkers may provide additional utility. We performed a meta-analysis to compare troponin and natriuretic peptides (NPs) in TTS and ACS to determine if differences in biomarker profile can aid diagnosis. METHODS: We searched five literature databases for studies reporting NPs (Brain NP (BNP)/NT-pro-BNP) or troponin I/T in TTS and ACS, identifying 28 studies for troponin/NPs (5618 and 1145 patients, respectively). RESULTS: Troponin was significantly lower in TTS than ACS (standardised mean difference (SMD) -0.86; 95% CI, -1.08 to -0.64; p<0.00001), with an absolute difference of 75 times the upper limit of normal (×ULN) higher in ACS than TTS. Conversely, NPs were significantly higher in TTS (SMD 0.62; 95% CI, 0.44 to 0.80; p<0.00001) and 5.8×ULN greater absolutely. Area under the curve (AUC) for troponin in ACS versus TTS was 0.82 (95% CI, 0.70 to 0.93), and 0.92 (95% CI, 0.80 to 1.00) for ST-segment elevation myocardial infarction versus TTS. For NPs, AUC was 0.69 (95% CI, 0.48 to 0.89). Combination of troponin and NPs with logistic regression did not improve AUC. Recursive Partitioning and Regression Tree analysis calculated a troponin threshold ≥26×ULN that identified 95% cases as ACS where and specificity for ACS were 85.71% and 53.57%, respectively, with 94.32% positive predictive value and 29.40% negative predictive value. CONCLUSIONS: Troponin is lower and NPs higher in TTS versus ACS. Troponin had greater power than NPs at discriminating TTS and ACS, and with troponin ≥26×ULN patients are far more likely to have ACS.

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.

Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review.

Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry.

BACKGROUND: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. METHODS: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). FINDINGS: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). INTERPRETATION: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. FUNDING: This research was not funded by any public, commercial, or not-for-profit agencies.

Prognostic Utility of Society for Cardiovascular Angiography and Interventions Shock Stage Approach for Classifying Cardiogenic Shock Severity in Takotsubo Syndrome.

BACKGROUND: Cardiogenic shock (CS) is a significant complication of Takotsubo syndrome (TTS), contributing to heightened mortality and morbidity. Despite this, the Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks validation in patients with TTS and CS. This study aimed to characterize a patient cohort with TTS using the SCAI staging system and assess its utility in cases of TTS complicated by CS. METHODS AND RESULTS: From a TTS national registry, 1591 consecutive patients were initially enrolled and stratified into 5 SCAI stages (A through E). Primary outcome was all-cause in-hospital mortality; secondary end points were TTS-related in-hospital complications and 1-year all-cause mortality. After exclusions, the final cohort comprised 1163 patients, mean age 71.0±11.8 years, and 87% were female. Patients were categorized across SCAI shock stages as follows: A 72.1%, B 12.2%, C 11.2%, D 2.7%, and E 1.8%. Significant variations in baseline demographics, comorbidities, clinical presentations, and in-hospital courses were observed across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage showed a significant association with increased in-hospital mortality (adjusted odds ratio: 1.77-29.31) compared with SCAI shock stage A. Higher SCAI shock stages were also associated with increased 1-year mortality. CONCLUSIONS: In a large multicenter patient cohort with TTS, the functional SCAI shock stage classification effectively stratified mortality risk, revealing a continuum of escalating shock severity with higher stages correlating with increased in-hospital mortality. This study highlights the applicability and prognostic value of the SCAI staging system in TTS-related CS.

Can a "broken heart" successfully be transplanted? A brief report.

A 59-year-old woman, with dilated ischemic cardiomyopathy, was urgently admitted to our Intensive Care Unit for cardiogenic shock. ECMO VA was implanted and placed on the national emergency waitlist for transplantation. A potential donation was identified ten days later. The donor was a 58-year-old woman, with no cardiovascular risk factors, had died of a rupture of a cerebral aneurysm with left ventricle dysfunction due to Takotsubo syndrome. Brain injuries such as hemorrhage, trauma and stroke have been extensively documented in literature to cause a surge in stress hormones, such as catecholamines. Such a surge can have a direct effect on the heart, resulting in a transient myocardial dysfunction commonly referred to as "Takotsubo cardiomyopathy" or "broken heart syndrome". Many studies have shown that hearts that are dysfunctional at the start of transplant screening, with normal contractile function at the time of organ retrieval, have similar outcomes to hearts that do not have dysfunction. In our case, the transplanted heart, at the time of sampling, still had moderate dysfunction (EF 40%) which completely disappeared after the transplant.

Is Takotsubo syndrome induced by patent ductus arteriosus occlusion?

Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.

Frequent POCUS and auscultation for an earlier diagnosis of takotsubo syndrome and unraveling of its pathophysiology: The possible crucial role of LVOTO.

There is ample literature associating LVOTO with hypertension, AMI, LV hypertrophy, sigmoid septum, HCM, and TTS, particularly in midde aged/elderly/postmenopausal women, suggestive of a causal role for LVOTO in the pathophysiology of TTS. Although there is significant evidence that TTS is triggered by a sudden autonomic sympathetic nervous system surge and/or elevated blood-ridden catecholamines, the exact pathophysiologic trajectory leading to the clinical expression of the disease is still being debated. This review expounds on the possibility that LVOTO is a causal early component of this trajectory, and proposes that TTS is a malady within the broad spectrum of the myocardial ischemic injury/stunned myocardium states. The postulated underlying mechanism by which LVOTO causes TTS is a sudden abterload rise, with resultant oxygen/energy supply/demand mismatch, leading to a transient myocardial ischemia/injury myocardial stunning state. This needs to be explored painstakingly, and this review includes some suggestions for such undertaking. Ellucidation of the pathophysiology of TTS, and possible proof about a mechanistic role of LVOTO, may ensure that our current pharmacological and device panoply is adequate for the management of TTS.

Exploratory Review of the Takotsubo Syndrome and the Possible Role of the Psychosocial Stress Response and Inflammaging.

Takotsubo syndrome (TTS) is a cardiomyopathy that clinically presents as a transient and reversible left ventricular wall motion abnormality (LVWMA). Recovery can occur spontaneously within hours or weeks. Studies have shown that it mainly affects older people. In particular, there is a higher prevalence in postmenopausal women. Physical and emotional stress factors are widely discussed and generally recognized triggers. In addition, the hypothalamic-pituitary-adrenal (HPA) axis and the associated glucocorticoid-dependent negative feedback play an important role in the resulting immune response. This review aims to highlight the unstudied aspects of the trigger factors of TTS. The focus is on emotional stress/chronic unpredictable mild stress (CUMS), which is influenced by estrogen concentration and noradrenaline, for example, and can lead to changes in the behavioral, hormonal, and autonomic systems. Age- and gender-specific aspects, as well as psychological effects, must also be considered. We hypothesize that this leads to a stronger corticosteroid response and altered feedback of the HPA axis. This may trigger proinflammatory markers and thus immunosuppression, inflammaging, and sympathetic overactivation, which contributes significantly to the development of TTS. The aim is to highlight the importance of CUMS and psychological triggers as risk factors and to make an exploratory proposal based on the new knowledge. Based on the imbalance between the sympathetic and parasympathetic nervous systems, transcutaneous vagus nerve stimulation (tVNS) is presented as a possible new therapeutic approach.

Takotsubo cardiomyopathy and psychiatric illness- insight from National Inpatient Sample (NIS) and National Re-admission Database (NRD) 2016 to 2018.

BACKGROUND: Emotional stress is a common precipitating cause of takotsubo cardiomyopathy (TC). Preexisting psychiatric disorder (PD) was linked to worsening outcomes in patients with TC1,2. However, there is limited data in literature to support this. This study aimed to determine the differences in outcomes in TC patients with and without PD. METHODS: We identified all patients with a diagnosis of TC using the National Inpatient Sample (NIS) and the National Readmission Database (NRD) data from 2016 to 2018. The patients were separated into TC with PD group and TC without PD group. Multiple variable logistic regression was then performed. RESULTS: Using NIS 2016-2018, we identified 23,220 patients with TC, and 43.11% had PD. The mean age was 66.73 ± 12.74 years, with 90.42% being female sex. The TC with PD group had a higher 30-readmission rate 1.25 (95% CI:1.06-1.47), Cardiogenic shock [aOR = 7.3 (95%CI 3.97-13.6), Mechanical ventilation [aOR = 4.2 (95%CI 2.4-7.5), Cardiac arrest [aOR = 2.6 (95%CI 1.1-6.3), than TC without PD group. CONCLUSION: Psychiatric disorders were found in up to 43% of patients with TC. The concomitant PD in TC patients was not associated with increased mortality, AKI, but had higher rates of cardiogenic shock, use of mechanical ventilation and cardiac arrest. The TC group with PD was also associated with increased 30-day readmission, LOS and total charges compared to TC patients without PD.

Albumin Levels and Risk of Early Cardiovascular Complications After Ischemic Stroke: A Propensity-Matched Analysis of a Global Federated Health Network.

BACKGROUND: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke. METHODS: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records (International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching. RESULTS: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels. CONCLUSIONS: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation.

Takotsubo syndrome : A cause of reversible microvascular coronary dysfunction.

Since the first description of takotsubo syndrome 30 years ago, only a little is known on the underlying physiopathology leading to peculiar left ventricular function alteration and myocardial damage related to acute emotional or physical stress. In the present case, we used continuous invasive thermodilution to evaluate coronary microvascular function at the acute phase of takotsubo and after recovery. The acute phase of takotsubo was characterized by a reduced coronary output and altered reserved flow with persistently high resistance during hyperaemia. At 6 weeks, we described a complete recovery of microvascular function, concomitant to LVEF recovery.

Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients With Takotsubo Cardiomyopathy.

BACKGROUND: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TC), but there is no well-established tool for risk stratification. This study sought to evaluate the prognostic value of several artificial intelligence-augmented ECG (AI-ECG) algorithms in patients with TC. METHODS AND RESULTS: This study examined consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. Several previously validated AI-ECG algorithms were used for the estimation of ECG- age, probability of low ejection fraction, and probability of atrial fibrillation. Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events, defined as cardiovascular death, recurrence of TC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. In the final analysis, 305 patients with TC were studied over a median follow-up of 4.8 years. Patients with future major adverse cardiac events were more likely to be older, have a history of hypertension, congestive heart failure, worse renal function, as well as high-risk AI-ECG findings compared with those without. Multivariable Cox proportional hazards analysis indicated that the presence of 2 or 3 high-risk findings detected by AI-ECG remained a significant predictor of major adverse cardiac events in patients with TC after adjustment by conventional risk factors (hazard ratio, 4.419 [95% CI, 1.833-10.66], P=0.001). CONCLUSIONS: The combined use of AI-ECG algorithms derived from a single 12-lead ECG might detect subtle underlying patterns associated with worse outcomes in patients with TC. This approach might be beneficial for stratifying high-risk patients with TC.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

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.