Takotsubo Research Articles

Pediatric takotsubo cardiomyopathy: A review and insights from a National Multicentric Registry.

Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. We included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Patients with pediatric TTS are more commonly male and exhibit a higher prevalence of physical triggers. The left ventricular ejection fraction (LVEF) was significantly lower in the pediatric population (30.5 + 10.4 vs 36.9 + 16.9, p < 0.05), resulting in more than fivefold rates of cardiogenic shock on admission compared to the general adult TTS population (Killip IV 74.1% vs 10.5%, p < 0.001) with similar rates of death and recurrence between groups. TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers, as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscores the necessity for further research in this age group.

Renal impairment and outcome in Takotsubo syndrome: Insights from a national multicentric cohort

IntroductionData on the association between kidney function and Takotsubo syndrome (TTS) outcomes are scarce and conflictive. ObjectiveTo assess the impact of chronic kidney disease (CKD) and acute renal failure (ARF) in patients with TTS. Material and methodsPatients from the prospective nation-wide (RETAKO) registry were included and divided into quartiles of maximum creatinine (Cr) level during hospitalization. ResultsThe prevalence of CKD and ARF in the whole RETAKO cohort was 5.4% and 11.7%, respectively. Compared to Q1 (Cr <0.71), patients within Q4 (Cr > 1.1) had lower left ventricular ejection fraction on admission (38.5 ± 12 vs 43.3 ± 11.3, p = 0.002) and higher bleeding rates during hospitalization (6.7% vs 2%, p = 0.005). In addition, compared to Q1, Q4 patients have a greater incidence of cardiogenic shock (17.3% vs 5.6%, p < 0.001), and a higher rate of 5-year all-cause death and major adverse cardiovascular events (31.5% vs 15.8%, p < 0.001 and 22.5% vs 9.3%, p < 0.001, respectively). ConclusionsTTS patients with CKD have a higher incidence of ARF and exhibit greater Cr on admission, which were linked with higher rates of cardiogenic shock, bleeding during hospitalization as well as major adverse cardiovascular events and all-cause death during a 5-year follow-up.

Gender disparities and predictors of in-hospital mortality with Takotsubo cardiomyopathy

BackgroundTakotsubo cardiomyopathy (TCM) is classically associated with significant gender disparities, such that it is more prevalent in females, but the clinical outcomes are worse for male patients. The goal of this study was to assess contemporary gender disparities in clinical outcomes of TCM hospitalizations and to determine predictors of male in-hospital mortality. MethodsThis was a retrospective analysis involving adult hospitalizations for TCM in the U.S between 2016 and 2020. Multivariable Logistic regression was used to estimate Odds Ratio (OR) for in-hospital mortality between the two genders. Univariable Cox regression was performed to identify predictors associated with in-hospital mortality for male hospitalizations. All factors from the univariable analysis with p < 0.20 were included in a multivariable Cox regression model. ResultsA total of 199,920 patients with TCM were identified. Female patients with TCM had 50% lower risk of in-hospital mortality compared to male patients (Adjusted OR 0.50, 95% CI 0.46–0.55, p < 0.001). Older age, higher Charlson comorbidity index, history of intracranial hemorrhage, cardiac arrest, need for vasopressor agents, mechanical intubation, and cardiogenic shock without the use of temporary mechanical circulatory support (MCS) were associated with higher in-hospital male mortality. ConclusionsAlthough TCM is more prevalent among females, gender disparities exist in the clinical outcomes of TCM patients. Cardiac arrest and cardiogenic shock without the use of temporary MCS were found to be the most significant predictors of male in-hospital mortality. Cardiogenic shock with use of temporary MCS did not lead to higher male in-hospital mortality.

Effects of pharmacological interventions on mortality in patients with Takotsubo syndrome: a report from the SWEDEHEART registry.

Takotsubo syndrome (TS) is a heart condition mimicking acute myocardial infarction. TS is characterized by a sudden weakening of the heart muscle, usually triggered by physical or emotional stress. In this study, we aimed to investigate the effect of pharmacological interventions on short- and long-term mortality in patients with TS. We analysed data from the SWEDEHEART (the Swedish Web System for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry, which included patients who underwent coronary angiography between 2009 and 2016. In total, we identified 1724 patients with TS among 228263 individuals in the registry. The average age was 66±14years, and 77% were female. Nearly half of the TS patients (49.4%) presented with non-ST-elevation acute coronary syndrome, and a quarter (25.9%) presented with ST-elevation myocardial infarction. Most patients (79.1%) had non-obstructive coronary artery disease on angiography, while 11.7% had a single-vessel disease and 9.2% had a multivessel disease. All patients received at least one pharmacological intervention; most of them used beta-blockers (77.8% orally and 8.3% intravenously) or antiplatelet agents [aspirin (66.7%) and P2Y12 inhibitors (43.6%)]. According to the Kaplan-Meier estimator, the probability of all-cause mortality was 2.5% after 30days and 16.6% after 6years. The median follow-up time was 877days. Intravenous use of inotropes and diuretics was associated with increased 30day mortality in TS [hazard ratio (HR)=9.92 (P<0.001) and HR=3.22 (P=0.001), respectively], while angiotensin-converting enzyme inhibitors and statins were associated with decreased long-term mortality [HR=0.60 (P=0.025) and HR=0.62 (P=0.040), respectively]. Unfractionated and low-molecular-weight heparins were associated with reduced 30day mortality [HR=0.63 (P=0.01)]. Angiotensin receptor blockers, oral anticoagulants, P2Y12 antagonists, aspirin, and beta-blockers did not statistically correlate with mortality. Our findings suggest that some medications commonly used to treat TS are associated with higher mortality, while others have lower mortality. These results could inform clinical decision-making and improve patient outcomes in TS. Further research is warranted to validate these findings and to identify optimal pharmacological interventions for patients with TS.

Takotsubo syndrome after bilateral simultaneous total knee arthroplasty - A case report

IntroductionCardiac complications represents a major cause of morbidity and mortality especially after bilateral simultaneous total knee arthroplasty (BS-TKA). Takotsubo syndrome after BS-TKA has not been described in the literature. Case presentationA 60 years-old women underwent BS- TKA and she suddenly developed bradycardia and hypotension after second knee wound closure. The electrocardiography revealed ST elevation and echocardiography showed apical hypokinesia of left ventricle. Coronary angiography revealed normal epicardial coronaries and a provisional diagnosis of Takotsubo cardiomyopathy was made. Serial ECGs revealed resolution of ST elevation and normal LV function within 5 days. On one-year follow up, she was able to do all her normal activities, and 12-lead electrocardiography were back to normal. ConclusionCardiac complications represents a major cause of morbidity and mortality especially after BS-TKA. Surgeons must be vigilant in the postoperative period for any likely precipitating factors of stress induced cardiomyopathy. Takotsubo syndrome should be considered as a differential diagnosis with features of acute coronary syndrome in elderly post-menopausal patients.

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.

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

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

Recurrent Takotsubo Syndrome: How Frequent, and How Does It Present?

Recurrent Takotsubo syndrome (TS) is not uncommon but experience with TS recurrence is inherently limited by the infrequency of the condition itself and incomplete long-term follow-up. There is limited published data on the clinical features and outcomes of patients with recurrent TS. We aimed to describe the clinical characteristics and outcomes of patients with recurrent TS in a large Auckland cohort. The clinical profile, in-hospital, and long-term outcomes were prospectively assessed in consecutive patients with recurrent TS presenting to Auckland's three major hospitals between January 2006 and January2023. During the study period, 472 TS patients were identified. Of the 467 patients discharged alive after the index event, 45 (9.6%) patients (mean age 62.3±11.0 years), all women, experienced recurrent TS. Median time interval from index event to the first recurrence was 3.14 years (range 27 days to 13.8 years). In 27 (60%) of the 45 patients, the subsequent events involved a stressor (physical triggers, n=8; emotional triggers, n=19). The stressor type differed between the index and recurrent event in 18 (40%) of the 45 patients. Thirteen (28.9%) had a different echocardiographic variant of TS at first recurrence. All patients with recurrent TS were discharged alive. Four patients died late after discharge from the first recurrence, all but one from a non-cardiac cause. One in 10 patients with TS experience recurrent events. These may occur many years later, and both the stressor type and the echocardiographic variant may be different at the recurrent event.

COVID-19 vaccines-associated Takotsubo cardiomyopathy: A narrative review.

Takotsubo cardiomyopathy (TTC) is a severe, acute, reversible, and self-limited cardiac dysfunction. It usually affects postmenopausal women and is mostly triggered by physical or emotional stressors. Following the COVID-19 pandemic, millions of doses of different types of COVID-19 vaccines are being administered globally. There have been reports of different cardiac complications after receiving COVID-19 vaccines. To our knowledge, there have been 16 reported cases of COVID-19 vaccination-associated TTC. In this study, we first provide a brief overview of TTC and then an overview of selected reported TTC cases following COVID-19 vaccinations. It is crucial to highlight that the occurrence of TTC after vaccination does not establish a direct cause-and-effect relationship between immunization and TTC. Further investigations are necessary to examine any potential association between COVID-19 vaccines and the incidence of TTC. Additionally, the benefits of receiving COVID-19 vaccines significantly outweigh the potential risks of developing adverse events.

Tiempo de realización de la resonancia magnética cardiaca y valor diagnóstico en pacientes con infarto de miocardio sin obstrucción de arterias coronarias

Introduction and objectivesThe present study sought to establish the diagnostic yield of cardiovascular magnetic resonance (CMR) in a large cohort of patients admitted with myocardial infarction (MI) with nonobstructive coronary artery disease (MINOCA) based on the timing of referral to CMR. MethodsConsecutive patients referred to CMR from January 2009 to February 2022 with a working diagnosis of MINOCA were retrospectively evaluated. Cine, T2-weighted, early, and late gadolinium-enhanced images were acquired and analyzed. The frequency of the underlying diagnosis and the association between timing of CMR and relative frequency of each diagnosis were assessed. ResultsWe included 207 patients (median age 50 years, 60% men). Final diagnosis after CMR was achieved in 91% of the patients (myocarditis in 45%, MI in 20%, tako-tsubo cardiomyopathy in 19%, and other cardiomyopathies in 7%). The performance of CMR within 7 days of admission with MINOCA (median, 5 days; 117 patients) allowed a higher diagnostic yield compared with CMR performed later (median, 10 days; 88 patients) (96% vs 86%, P=.02). Although myocarditis was the most frequent diagnosis in both groups according to time to CMR, its frequency was higher among patients with a CMR performed within the first 7 days (53% vs 35%, P=.02). The frequency of other underlying diagnoses was not influenced by CMR timing. ConclusionsCMR led to an underlying diagnosis of MINOCA in 91% of patients and its diagnostic yield increased to 96% when CMR was performed within 7 days of admission. The most frequent diagnosis was myocarditis.

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

ObjectiveTakotsubo 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...

Identifying the trigger of Takotsubo syndrome is challenging when several of them are present

Identifying the trigger of Takotsubo syndrome is challenging when several of them are present

‘Wilt Break My Heart?’ Takotsubo Syndrome and Shakespeare’s Discourse of Heartbreak in Antony and Cleopatra and King Lear

ABSTRACT Shakespeare’s characters knew well the dangers and causes of an overcharged heart. This article places representations of heartbreak in Shakespeare’s canon in dialogue with twenty-first-century medical understanding of heartbreak or Takotsubo syndrome (TTS). Over thirty years since its coinage in cardiac medicine, heartbreak syndrome or TTS remains poorly understood. In response to this dearth of information around TTS, this article turns to early modern accounts of heartbreak – particularly its dramatic representation in King Lear and Antony and Cleopatra – and examines these alongside unfolding research into TTS. The essay illuminates a contagious inter-heart dynamic at play in King Lear and analyses best practice treatments for supportive management of stress-induced cardiomyopathy in Antony and Cleopatra. This comparative analysis of broken hearts in Shakespeare and in twenty-first century medical knowledge of TTS aims to offer mutual enlightenment across Shakespeare studies and cardiac medicine.

Exploring the Role of Psychological Stress in Takotsubo Cardiomyopathy a.k.a Broken-Heart Syndrome

This comprehensive review delves into the multifaceted aspects of Takotsubo Cardiomyopathy (TCM), commonly known as Broken Heart Syndrome, exploring its intricate connection with psychological stress. Beginning with an introduction and historical context, the discussion progresses to elucidate the significance of understanding the link between psychological stress and TCM, emphasizing its impact on symptomatology, quality of life, treatment approaches, and psychological well-being. Further, the review unravels the underlying mechanisms and complex pathophysiology of TCM, categorizing its triggers and stressors while exploring the intricate relationship between psychological stress and TCM onset. Additionally, it discusses the implications of war-related stressors on TCM development, underscoring the need for effective stress management strategies tailored to individuals with TCM. Overall, this review offers a comprehensive exploration of TCM, shedding light on its nuanced relationship with psychological stress and advocating for tailored treatment approaches to address the unique needs of affected individuals.

Takotsubo syndrome: left atrial and ventricular myocardial strain impairment in the subacute and convalescent phases assessed by CMR.

We investigated the differences in impairment of left ventricle (LV) and left atrium (LA) contractile dysfunction between subacute and convalescent takotsubo syndrome (TTS), using myocardial strain analysis by cardiac magnetic resonance (CMR) feature-tracking technique. We retrospectively selected 50 patients with TTS clinical-radiological diagnosis who underwent CMR within 30days since symptoms onset: 19 studied during the early subacute phase (sTTS, ≤ 7days) and 31 during the convalescence (cTTS, 8-30days). We measured the following: LV global longitudinal, circumferential, and radial strain (lvGLS, lvGCS, lvGRS) and strain rate (SR) and LA reservoir (laS_r), conduit (laS_cd), and booster pump strain (laS_bp) and strain rate (laSR_r, laSR_cd, laSR_bp). Patients were compared with 30 age- and sex-matched controls. All patients were women (mean age 63years). TTS patients showed altered LV- and LA-strain features, compared to controls. sTTS was associated with increased laS_bp (12.7% versus 9.8%) and reduced lvEF (47.4% versus 54.8%), lvGLS (-12.2% versus 14.6%), and laS_cd (7.0% versus 9.5%) compared to cTTS (p ≤ 0.029). The interval between symptoms onset and CMR was correlated with laS_bp (r = -0.49) and lvGLS (r = 0.47) (p = 0.001 for both). At receiver operating characteristics analysis, laS_bp was the best discriminator between sTTS and cTTS (area under the curve [AUC] 0.815), followed by lvGLS (AUC 0.670). LA dysfunction persists during the subacute and convalescence of TTS. laS_bp increases in subacute phase with progressive decrease during convalescence, representing a compensatory mechanism of LV dysfunction and thus a useful index of functional recovery. Atrial strain has the potential to enhance the delineation of cardiac injury and functional impairment in TTS patients, assisting in the identification of individuals at higher risk and facilitating the implementation of more targeted and personalized medical therapies. • In TTS, after ventricular recovery, atrial dysfunction persists assessable with CMR feature tracking. • Quantitative assessment of atrial strain discriminates atrial functions: reservoir, conduit, and booster pump. • Atrial booster pump changes after acute TTS, regardless of ventricular function. • Atrial strain may serve as a temporal marker in TTS.

Immunotherapy-associated cardiovascular toxicities: insights from preclinical and clinical studies.

Immune checkpoint inhibitors (ICIs) have become a widely accepted and effective treatment for various types of solid tumors. Recent studies suggest that cardiovascular immune-related adverse events (irAEs) specifically have an incidence rate ranging from 1.14% to more than 5%. Myocarditis is the most common observed cardiovascular irAE. Others include arrhythmias, pericardial diseases, vasculitis, and a condition resembling takotsubo cardiomyopathy. Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway, and the recently discovered lymphocyte-activation gene 3 (LAG-3) pathway, play a critical role in boosting the body's natural immune response against cancer cells. While ICIs offer significant benefits in terms of augmenting immune function, they can also give rise to unwanted inflammatory side effects known as irAEs. The occurrence of irAEs can vary in severity, ranging from mild to severe, and can impact the overall clinical efficacy of these agents. This review aims to summarize the underlying mechanisms of cardiovascular irAE from both preclinical and clinical studies for a better understanding of cardiovascular irAE in clinical application.

Focal Takotsubo Cardiomyopathy: A Case Report and Literature Review

Focal Takotsubo Cardiomyopathy: A Case Report and Literature Review

Management of cardiac emergencies in women: a clinical consensus statement of the Association for Acute CardioVascular Care (ACVC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the Heart Failure Association (HFA), and the European Heart Rhythm Association (EHRA) of the ESC, and the ESC Working Group on Cardiovascular Pharmacotherapy.

Cardiac emergencies in women, such as acute coronary syndromes, acute heart failure, and cardiac arrest, are associated with a high risk of adverse outcomes and mortality. Although women historically have been significantly underrepresented in clinical studies of these diseases, the guideline-recommended treatment for these emergencies is generally the same for both sexes. Still, women are less likely to receive evidence-based treatment compared to men. Furthermore, specific diseases affecting predominantly or exclusively women, such as spontaneous coronary dissection, myocardial infarction with non-obstructive coronary arteries, takotsubo cardiomyopathy, and peripartum cardiomyopathy, require specialized attention in terms of both diagnosis and management. In this clinical consensus statement, we summarize current knowledge on therapeutic management of these emergencies in women. Key statements and specific quality indicators are suggested to achieve equal and specific care for both sexes. Finally, we discuss several gaps in evidence and encourage further studies designed and powered with adequate attention for sex-specific analysis.

Role of cardiac magnetic resonance imaging in identifying infarct related artery and non-ischemic pathogenesis in patients presenting with non ST elevation myocardial infarction

IntroductionIdentifying an Infarct-related artery (IRA)in Non-STEMI is sometimes tricky. Besides, myocardial infarction with non-obstructive coronary arteries (MINOCA) mimickers are often labeled as myocardial infarction. Late Gadolinium enhancement (LGE) on cardiac MRI can help in identifying IRA besides MINOCA mimickers. AimsTo study the role of LGE on cardiac MRI(CMR) in NSTEMI. Material MethodsIt was a prospective observational, double-blinded study. 70 NSTEMI patients were prospectively enrolled over two years. CMR was done before coronary angiography (CAG) during the index hospitalization. Matching was done between IRA selected by CAG and IRA as determined by LGE on MRI. ResultsMean age was 58 ± 15 years. CAG could not identify IRA in 38.6% (n = 27) patients. In this patient group, LGE-CMR identified IRA in 48.1% (n = 13) & a new non-CAD diagnosis was identified in 18.5% (n = 5) patients. IRA was identified in 61.4% (n = 43) by CAG & in this patient group, LGE-CMR identified a different IRA in 6.9% (n = 3) patients. LGE-CMR also identified a new non-CAD diagnosis in 11.6% (n = 5) of patients from this group. Overall, LGE-CMR led to a new IRA diagnosis in 23% (n = 16) patients & a diagnosis of non-ischemic pathogenesis in 14% (n = 10) patients. Non-Ischemic diagnosis on CMR included stress cardiomyopathy in 3, myocarditis in 6, and infiltrative disorder in 1 patient. ConclusionCMR leads to new IRA diagnoses or non-ischemic pathogenesis in one-third of the cohort.

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

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. 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). 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.