Physical Trigger Research Articles

Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.

Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course. We retrospectively examined a 10-year (2010-2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients' clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort. Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5years (IQR 62.75-77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King's ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it. TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified.

LONG–TERM FUNCTIONAL LIMITATIONS ON CARDIOPULMONARY EXERCISE TESTING IN A COHORT OF PATIENTS WITH EMOTIONS–TRIGGERED TAKOTSUBO SYNDROME

Abstract Background In patients with prior Takotsubo syndrome (TTS), long lasting functional cardiac limitations were described as compared with normal subjects. Emotions–triggered Takotsubo syndrome (E–TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable factors. The aim of the present study was to assess long–term cardiac functional limitations in a cohort of asymptomatic E–TTS patients. Methods We enrolled n=39 asymptomatic patients with a diagnosis of E–TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 [12–40] months median follow–up from the acute event. A cohort of n=39 individuals matched for age, sex, body mass index and comorbidities served as control. Results Despite recovery of left ventricular ejection fraction, patients with prior E–TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs 22.5 ± 6.5; P < 0.001 and 75.2 ± 14.1 % vs 100.6 ± 17.1%, P <0.001), VO2 at anaerobic threshold (AT) (11.1 [10.1–12.9] vs 14.4 [12.5–18.7]; P <0.001), peak O2 pulse (9.7 ± 2.5 vs 13.1 ± 3.5; P <0.001) and higher VE/VCO2 slope (30.4 ± 3.7 vs 27.2 ± 3.5; P <0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Conclusions Despite their overall favorable outcome, asymptomatic patients with E–TTS were found to have long–term subclinical functional cardiac impairments. CPET proved to be a useful tool in the long–term evaluation of E–TTS patients after recovery of LVEF. Further studies are needed to fully clarify the origin of the detected CPET abnormalities as well as their prognostic relevance in patience with recovered E–TTS.

Impact of Coronary Microvascular Dysfunction in Takotsubo Syndrome: Cause, Consequence or Both?

Takotsubo syndrome (TTS) is an acute cause of heart failure characterized by a reversible left ventricular (LV) impairment usually induced by a physical or emotional trigger. TTS is not always a benign disease since it is associated with a relatively higher risk of life-threatening complications, such as cardiogenic shock, ventricular arrhythmias, respiratory failure, cardiopulmonary resuscitation and death. Despite notable advancements in the management of patients with TTS, physiopathological mechanisms underlying transient LV dysfunction remain largely unknown. Since TTS carries similar prognostic implications than acute myocardial infarction, the identification of mechanisms and predictors of worse prognosis remain key to establish appropriate treatments. The greater prevalence of TTS among post-menopausal women and the activation of the neuro-cardiac axis triggered by physical or emotional stressors paved the way forward to several studies focused on coronary microcirculation and impaired blood flow as the main physiopathological mechanisms of TTS. However, whether microvascular dysfunction is the cause or a consequence of transient LV impairment remains still unsettled. This review provides an up-to-date summary of available evidence supporting the role of microvascular dysfunction in TTS pathogenesis, summarizing contemporary invasive and non-invasive diagnostic techniques for its assessment. We will also discuss novel techniques focused on microvascular dysfunction in TTS which may support clinicians for the implementation of tailored treatments.

Clinical predictors of late left ventricle recovery in tako-tsubo syndrome

Abstract Funding Acknowledgements None. Introduction Tako-Tsubo syndrome (TTS) or stress cardiomyopathy is characterized by transient dysfunction of the left ventricle (LV) and a clinical presentation that can mimic an acute coronary syndrome. Recovery from contraction abnormalities may occur hours to weeks after the acute event. Although traditionally considered a disease with a favorable prognosis, it has been observed to have a complication rate during hospitalization similar to acute myocardial infarction and a significant mortality rate during follow-up (greater than 5% per patient-year). The recovery time of LV function has demonstrated important prognostic value. Purpose The aim of this work was to determine the clinical predictors of late left ventricular recovery in TTS. Methods Data from the multicenter national registry on Takotsubo Syndrome (RETAKO) were utilized. Clinical, laboratory, echocardiographic, and other imaging test characteristics, as well as events during hospitalization and follow-up, were collected. Recovery within the first days after the acute event was considered early recovery. Patients who died within the first 10 days after the acute event were excluded. Results A total of 1,463 patients were analyzed, of whom 373 (25.5%) had late recovery. The mean age was 71 years, and 86.6% were women. In the late recovery group, factors more common were age over 75 years, male gender, neurological disease, lung disease, peripheral arterial disease, active cancer, physical trigger, initial presentation as dyspnea or syncope, presence of shock, greater left ventricular dysfunction at diagnosis, and higher levels of proBNP. In multivariate analysis, the presence of neurological disease, active cancer, shock during hospitalization, lower initial LV ejection fraction, and physical trigger were associated with late recovery. Conclusions Patients with TTS showing late recovery of LV function have different clinical characteristics and disease presentation compared to those with early recovery. Late recovery was associated with the presence of neurological disease or active cancer, shock during hospitalization, lower initial LV ejection fraction, and physical trigger.

Long-Term Functional Limitations on Cardiopulmonary Exercise Testing in Emotion-Triggered Takotsubo Syndrome.

Background: In patients with prior Takotsubo syndrome (TTS), long-lasting functional cardiac limitations were described as compared with normal subjects. Emotion-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable factors. The aim of the present study was to assess long-term cardiac functional limitations in a cohort of asymptomatic E-TTS patients. Methods: We enrolled n = 40 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 (12-40) months median follow-up from the acute event. A cohort of n = 40 individuals matched for age, sex, body mass index and comorbidities served as control. Results: Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs. 22.1 ± 6.5; p < 0.001 and 75.2 ± 14.1% vs. 100.6 ± 17.1%, p < 0.001), VO2 at anaerobic threshold (AT) (11.5 [10.1-12.9] vs. 14.4 [12.5-18.7]; p < 0.001), peak O2 pulse (9.8 ± 2.5 vs. 12.9 ± 3.5; p < 0.001) and higher VE/VCO2 slope (30.5 ± 3.7 vs. 27.3 ± 3.5; p < 0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Conclusions: Despite its favorable outcome, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry

Background and aimsSeveral studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. MethodsPatients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. ResultsStudy population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin.Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803).At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74–1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04–1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20–2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83–3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68–3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62–3.10, p < 0.001) were associated with increased mortality. ConclusionsStatin therapy after a TTS event was not associated with better prognosis at follow-up.

Abstract 13021: Double-Peaked Trajectory of the Corrected QT Interval and Its Sex Differences During the Clinical Course of Takotsubo Syndrome

Background: In the general population, the normal value of the corrected QT (QTc) interval for women is under 450 ms, which is longer than that of men (under 430 ms). There have been reported several sex differences in characteristics of takotsubo syndrome (TTS). Prolonged QTc interval is a relatively common electrocardiographic finding in TTS. Research Question: Little is known about the sex differences in the trajectory of QTc interval during the clinical course of TTS. Aim: The aim of this study was to determine the change in the QTc interval from the acute onset to one year later by sex. Methods: This study retrospectively included 85 consecutive patients with TTS admitted to our hospital from 2015 to 2023. A total of 848 twelve-lead electrocardiograms (ECG) performed from the date of diagnosis (day 0) within one year were analyzed. Mean QTc intervals were calculated by the day from day 0 to day 16, and after day 17, by defined periods (day 17-30, 31-60, 61-90, 91-180, 181-360). Results: Fifty-eight (68%) patients were women. There were no significant differences between women and men in age (71 ± 13 years vs. 67 ± 10 years, P =0.13), preceding physical trigger (55% vs. 70%, P =0.24), and all-cause mortality within one year (17% vs. 19%, P &gt;0.99). On day 0, the QTc intervals within the normal range were observed both in women and men. The first peak of the QTc interval was observed on day 2 with the mean QTc interval of 475 ± 70 ms in women, and 474 ± 60 ms in men. Once the QTc interval shortened after the first peak, it prolonged again and the second peak was observed around the second week from the onset. In the second peak, the QTc interval was found to be longer in men (503 ± 32 ms) compared to women (471 ± 56 ms). After the second peak, the QTc interval gradually normalized, and never prolonged again until one year. Conclusions: The double-peaked trajectory of the QTc interval was clearly observed during the clinical course of TTS. The variability of the QTc interval was greater in men than in women.

Recurrent episodes of Takotsubo cardiomyopathy in systemic sclerosis

Systemic sclerosis is an autoimmune disease characterized by fibrosis and small vessel vasculopathy, which affects various organ systems, such as the heart. Takotsubo cardiomyopathy is a transient cardiomyopathy in reaction to an emotional or physical trigger. There may be clinical and pathogenetic overlap between Takotsubo cardiomyopathy and primary systemic sclerosis heart disease, and some patients with systemic sclerosis have been diagnosed with recurrent Takotsubo cardiomyopathy. Our large systemic sclerosis clinical cohort was reviewed to identify cases diagnosed with Takotsubo cardiomyopathy. The clinical features, laboratory and imaging results were reviewed and evaluated to perform a comparison between cases. We identified five patients with systemic sclerosis, all female (age 68.6 ± 5.7 years), who were diagnosed with Takotsubo cardiomyopathy. Two of these patients had recurrent episodes: one case with a history of multiple episodes and the other with one recurrence. Typical features included repolarization abnormalities on the electrocardiogram and transient left ventricular dysfunction observed using echocardiography or cardiac magnetic resonance imaging. Our findings build upon previous reports and observations that systemic sclerosis may cause Takotsubo cardiomyopathy. To our knowledge, this is the largest case series of Takotsubo syndrome in patients with systemic sclerosis. This association may provide novel insights into the aetiopathogenesis of Takotsubo cardiomyopathy as part of primary systemic sclerosis heart involvement.

Takotsubo Syndrome, Stressful Triggers, and Risk of Recurrence

The risk of recurrence in takotsubo syndrome (TTS) appears to be low, although previous studies have shown conflicting results and factors associated with recurrences are unclear. The aim of this study is to evaluate the incidence and predictors of TTS recurrences. Adult patients included in the Spanish Multicenter REgistry of TAKOtsubo syndrome (RETAKO) between January 2003 and September 2019 were identified. Patients were categorized based on recurrences during follow-up and a multivariate logistic regression model was used to identify factors associated with recurrences. A total of 1097 patients (mean age 71.0±11.9 years, 87% females) were included, repeated TTS events were documented in 44 patients (4.0%), including 13 patients with prior TTS and 31 patients with recurrent TTS during a median follow-up of 279 days. Two patients (0.02%) had two episodes of recurrence. Compared to patients who had no recurrence of TTS, those with recurrent TTS more frequently had no identifiable stressful trigger in the index admission (20 [64.5%] vs 352 [33.0%], p <0.001). Primary TTS, defined as TTS without physical trigger, was also more common in the recurrence group (93.5% vs 68.3%, p <0.001). The only factor independently associated with recurrences was the absence of an identifiable trigger (odds ratio 3.7 [95% confidence interval 1.8-7.8], p=0.001). In conclusion, our data indicate that for patients presenting with TTS, the rate of early recurrent TTS is approximately 4% per year. Among TTS patients, those who have no identifiable trigger events appear to have a higher rate of recurrence.

How different triggers affect CMR parameters in takotsubo syndrome

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Ospedale Sant'Orsola (Bologna) Background Takotsubo syndrome (TTS) is an acute and transient heart failure syndrome characterized by a temporary wall motion abnormality of the left ventricle. Cardiac magnetic resonance (CMR) has a crucial role to assess ventricles function, regional wall motion abnormalities (RWMA), myocardial edema, late gadolinium enhancement (LGE) and complications. To date, there is a lack of how trigger events impact CMR parameters. Purpose To evaluate the clinical presentation, triggers of TTS and CMR parameters in patients hospitalized for Takotsubo Syndrome (TTS). Methods In our study we evaluated 128 patients hospitalized with TTS between January 2016 and December 2021 in Italy. Diagnosis of Takotsubo syndrome was based on the international Takotsubo diagnostic criteria (InterTAK Diagnostic Criteria). Results The mean age of the study population was 68.7 ± 11.1 years, and 81 % were females. Concerning the event trigger of TTS, 44% of patients experimented with an emotional event and 56% with physical stress. CMR was available in 66 patients, performed 7.5 ± 3.7 days after admission during hospitalization. CMR confirmed that most patients had typical TTS with apical ballooning (87%) while only 4.5% had a midventricular pattern. Left ventricular ejection fraction (LV-EF) mean was 55.3 ± 10.9 %. Mean LV-EF did not significant differ between emotional and physical trigger populations (51±12.5 vs 56.3±7.7; p = 0.12). Myocardial edema was present in 64.2% of patients and the mean number of segments involved was 6.2. ± 5.9. No statistical correlation between TTS trigger and the presence of edema at T2-weighted imaging was noticed. Spotty LGE was observed in 23.1 % of CMR exams, most evidenced in lateral (11.9 %) and inferior segments (10.4 %). LGE was evidenced more frequently in TTS triggered by physical events (38.1% vs 13%; p value=0.04) unlike pericardial effusion (0% vs 14%; p value= 0.04). Moreover, Hs-troponin I peak value was higher in the TTS physical triggered population than TTS with emotional trigger (3413 ± 4457 ng/l vs 2018 ± 2064 ng/l; p value= 0.04). Conclusions Early execution of CMR is essential in suspected TTS because several parameters are relatively time-dependent and derived from dynamic alterations that might resolve over time (such as myocardial edema). In our study patients with a physical trigger had a higher Hs-Troponin I max peak value and, more frequently spotty LGE on CMR. This could be the manifestation of more consistent myocardial damage compared to emotional triggers. However, the physiopathological and prognostic role of LGE in TTS remains unclear.

Triggers, characteristics, and hospital outcome of patients with Takotsubo syndrome: 10 years experience in a large university hospital centre.

A unique clinical feature of Takotsubo syndrome (TTS) is the stress trigger factor. Different types of triggers exist, generally divided into emotional and physical stressor. The aim was to create long-term registry of all consecutive patients with TTS across all disciplines in our large university hospital. We enrolled patients on the basis of meeting the diagnostic criteria of the international InterTAK Registry. We aimed to determine type of triggers, clinical characteristics, and outcome of TTS patients during 10 years period. In our prospective, academic, single centre registry, we enrolled 155 consecutive patients with diagnoses of TTS between October 2013 and October 2022. The patients were divided into three groups, those having unknown (n = 32; 20.6%), emotional (n = 42; 27.1%), or physical (n = 81; 52.3%) triggers. Clinical characteristics, cardiac enzyme levels, echocardiographic findings, including ejection fraction, and TTS type did not differ among the groups. Chest pain was less common in the group of patients with a physical trigger. On the other hand, arrhythmogenic disorders such as prolonged QT intervals, cardiac arrest requiring defibrillation, and atrial fibrillation were more common among the TTS patients with unknown triggers compared with the other groups. The highest in-hospital mortality was observed between patients having physical trigger (16% vs. 3.1% in TTS with emotional trigger and 4.8% in TTS with unknown trigger; P = 0.060). Conclusion: More than half of the patients with TTS diagnosed in a large university hospital had a physical trigger as a stress factor. An essential part of caring for these types of patients is the correct identification of TTS in the context of severe other conditions and the absence of typical cardiac symptoms. Patients with physical trigger have a significantly higher risk of acute heart complications. Interdisciplinary cooperation is essential in the treatment of patients with this diagnosis.

Ultramarathon induces metabolite changes associated with the pathophysiology of cardiovascular diseases- in silico and in vivo analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre (NCN) and Internal source of Medical University of Warsaw. Introduction Regular physical exercise is analogous to improved cardiovascular health and increased longevity. However, if in excess it can act as a double edged sword. Acute bouts of extreme physical activity trigger complex molecular responses reflected by changes in inflammatory markers and metabolic pathways that are believed to yield detrimental effects on the cardiovascular system (CVS)[1]. Purpose We aimed to assess the effects of high-intensity and long-lasting exercise prototype (100km run) on the metabolomic changes in a unique population of high-level long-term ultra-marathon runners. Methods Plasma samples were collected from ultramarathon runners (n=22) with 2-time points: before and after the run (Completion (100 km) or exhaustion (52 - 91 km, median 74 km)). For untargeted metabolomic analysis we used ultra-high resolution Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry with an electrospray ion source in direct injection. Mass spectra were analyzed by T-Rex2D algorithm in the MetaboScape5.0. Identified compounds were ontologically analyzed using MetaboAnalystR. MetscapeCytoscape plugin was used for metabolite-gene interaction analysis and gene lists were obtained from Biomart and DisGeNet. Results Mann-Whitney test (FDR&amp;lt;0.05) identified 1601 up and 1030 downregulated metabolites with a at least 2 fold of difference after high-intensity run. Enrichment analysis showed that the top pathways affected by analyzed metabolites were the TCA cycle (FDR=0.0442), metabolism of; Sphingolipids (p=0.00774), Glyoxylate and dicarboxylate (p=0.0249) and Butanoate (p=0.0352). Top disease phenotypes associated with differentially regulated metabolites were critical illness (major trauma, severe septic shock, or cardiogenic shock) (p=0.00154) and multiple CVS-related diseases (Fig1). Top after the run up-regulated metabolites identified in the study included heart failure associated acetylcarnitines[2] CAR(14:2) (log2FC=11.57; AUC=0.97), Dodecanoylcarnitine (2.00;0.960), 9-Decenoylcarnitine (1.78;0.95), CAR(DC8:0) (14.99;0.94), but also 2-Carboxy-5,7-dimethyl-4-octanolide (8.04;0.98), Methylmalonic acid (9.33;0.96) and cardiotoxic Cyclophosphamide (16.29;0.940)[3]. Top down-regulated metabolites after the run included potentially cardio-protective Gamma Glutamylglutamic acid (log2FC=-1.81; AUC=0.85), Fructose 1,6-bisphosphate (-2.42;0.88)[4], Oleamide (-1.82;0.86) and gamma-Glutamylglycine (-7.98;0.85). Interaction network analysis focused on genes associated with CVS identified atherosclerosis/ obesity-related Phospholipase A2 Group IB (PLA2G1B) as potentially the most affected gene by analyzed metabolites (Fig2). Conclusion Results show a twofold post run increase in metabolites that are both potential markers for acute exercise and that are strongly associated with CV diseases. This calls for consideration of the detrimental effects of excessive exercise and implementation of monitoring in amateur athletes.

P436 ASSOCIATION BETWEEN REVERSE–TAKO–TSUBO E NEUROLOGICAL DISORDER

Abstract Reverse–Tako–tsubo (r–TTC) is a rare variant of Tako–tsubo syndrome (TTC). TTC is characterized by transient and reversible left ventricular systolic dysfunction, for which an emotional or physical stressful trigger can usually be identified. Clinically, it mimics an acute myocardial infarction, with elevation of myocardial cytonecrosis enzymes and no obstractive coronary artery stenosis. On imaging, r–TTC is characterized by hypokinesia of the mid–basal regions associated with hyperkinesia of the apical region that resolves spontaneously. Case report: 78–year–old female affected by cerebral atrophy, leukoencephalopathy, cognitive impairment, behavior disorders. Reported episode of loss of consciousness lasting several minutes, associated with spontaneously resolving tremors and left hemisome hyposthenia. When she arrived in the emergency room, the haematological tests found high troponin values. On CT brain without contrast, no evidence of alterations of the encephalic tissues referable to acute lesions, but it showed of diffuse supratentorial leukoaraiosis and widening of the cerebrospinal fluid spaces on an atrophic basis. The neurological evaluation excludes the presence of a seizure. The electrocardiogram showed diffuse negative T waves and QTc 636 ms. The coronary angiography didn’t show significant coronary arteries stenosis and the ventriculography showed normal ventricular dimensions with total akinesia of the mid segments and normokinesia of the apical region with an ejection fraction of 50%. With these findings a diagnosis of mid left ventricular Tako–tsubo (r–TTC) was made. Transthoracic color Doppler echocardiography confirmed the alterations of the left ventricular kinetics observed by ventriculography. Conclusions compared to CTT, r–TTC is associated with a lower decline in global systolic function and, as reported in the literature, there is a greater connection to neurological insults as triggering factors, such as episodes of aneurysmal subarachnoid hemorrhage, brain surgery, ischemic stroke seizures and traumatic brain injury. The underlying mechanisms are still unknown, a crucial role in catecholamine–induced cardiotoxicity, coronary microvascular dysfunction or coronary vasospasm and/or estrogen deficiency is hypothesized.

Takotsubo syndrome: getting closer to its causes.

Takotsubo syndrome (TTS) accounts for between 1 and 4% of cases presenting clinically as an acute coronary syndrome. It typically presents as a transient cardiac phenotype of left ventricular dysfunction with spontaneous recovery. More dramatic presentations may include cardiogenic shock or cardiac arrest. Despite progress in the understanding of the condition since its first description in 1990, considerable questions remain into understanding underlying pathomechanisms. In this review article, we describe the current published data on potential underlying mechanisms associated with the onset of TTS including sympathetic nervous system over-stimulation, structural and functional alterations in the central nervous system, catecholamine secretion, alterations in the balance and distribution of adrenergic receptors, the additive impact of hormones including oestrogen, epicardial coronary or microvascular spasm, endothelial dysfunction, and genetics as potentially contributing to the cascade of events leading to the onset. These pathomechanisms provide suggestions for novel potential therapeutic strategies in patients with TTS including the role of cognitive behavioural therapy, beta-blockers, and endothelin-A antagonists. The underlying mechanism of TTS remains elusive. In reality, physical or emotional stressors likely trigger through the amygdala and hippocampus a central neurohumoral activation with the local and systemic secretion of excess catecholamine and other neurohormones, which exert its effect on the myocardium through a metabolic switch, altered cellular signalling, and endothelial dysfunction. These complex pathways exert a regional activation in the myocardium through the altered distribution of adrenoceptors and density of autonomic innervation as a protective mechanism from myocardial apoptosis. More research is needed to understand how these different complex mechanisms interact with each other to bring on the TTS phenotype.

Takotsubo syndrome: more frequent in women, more dangerous in men.

Takotsubo syndrome (TTS) is an acute myocardial disease characterized by reversible left ventricular dysfunction, in the absence of obstructive coronary artery disease, caused by adrenergic overactivity and associated with non-negligible morbidity and mortality. Takotsubo syndrome, by far more frequent in women, who account for 9 out of 10 cases, is generally triggered by intense psychoemotional stress. In men, TTS has different, though not yet fully defined, characteristics and clinical course. In fact, men have a higher prevalence of a physical trigger and comorbidities, such as bronchopulmonary or cerebral pathologies, diabetes mellitus, and malignant neoplasms. The hospital course is burdened by a higher rate of cardiogenic shock and mortality. The long-term prognosis is also less favourable in men. Takotsubo syndrome in men characterizes a higher-risk phenotype, which requires close monitoring during hospitalization and careful surveillance during follow-up.

Cluster-Analytic Identification of Clinically Meaningful Subtypes in MCAS: The Relevance of Heat and Cold

BackgroundMast cell activation syndrome (MCAS) is a clinically heterogeneous disease with allergy-like symptoms and abdominal complaints. Its etiology is only partially understood and it is often overlooked.AimsThe aim of this study was to identify subgroups of MCAS patients to facilitate diagnosis and allow a personalized therapy.MethodsBased on data from 250 MCAS patients, hierarchical and two-step cluster analyses as well as association analyses were performed. The data used included data from a MCAS checklist asking about symptoms and triggers and a set of diagnostically relevant laboratory parameters.ResultsUsing a two-step cluster analysis, MCAS patients could be divided into three clusters. Physical trigger factors were particularly decisive for the classification as they showed remarkable differences between the three clusters. Cluster 1, labeled high responders, showed high values for the triggers heat and cold, whereas cluster 2, labeled intermediate responders, presented with high values for the trigger heat and low values for cold. The third cluster, labeled low responders, did not react to thermal triggers. The first two clusters showed more divers clinical symptoms especially with regard to dermatological and cardiological complaints. Subsequent association analyses revealed relationships between triggers and clinical complaints: Abdominal discomfort is mainly triggered by histamine consumption, dermatological discomfort by exercise, and neurological symptoms are related to physical exertion and periods of starvation. The reasons for the occurrence of cardiological complaints are manifold and triggers for respiratory complaints still need better identification.ConclusionOur study identified three distinct clusters on the basis of physical triggers, which also differ significantly in their clinical symptoms. A trigger-related classification can be helpful in clinical practice for diagnosis and therapy. Longitudinal studies should be conducted to further understand the relationship between triggers and symptoms.

On the rotation of melting ice disks

This investigation was inspired by the work of Dorbolo et al. (Phys Rev E 93(3):15, 2016), which was the first to study, at a laboratory scale, the phenomenon observed in the natural world of floating disks of ice rotating. They conclude that, in controlled conditions, ice disks are able to induce their own rotation. Whilst their work successfully exposes multiple aspects of the kinematics of such disks, and the buoyancy-driven flow generated beneath them as they melt, the mechanism by which rotation is triggered remains unsubstantiated. We therefore return in this work to the study of floating ice disks, focusing specifically on the importance of experimental technique in obtaining reliable measurements of disk behaviour. Our investigation reveals that the motion of ice disks placed on a nominally quiescent body of fresh water is unpredictable, with some disks remaining motionless, and others rotating clockwise or anticlockwise. For those in motion, the average rate of rotation observed was less than half of that recorded by Dorbolo et al., a discrepancy possibly explained by residual background motions in the nominally quiescent surrounding body of water. However, given our observation that non-melting disks of high-density polyethylene (HDPE) cooled to the same temperature as the ice (comparable HDPE and ice disks differing by only sim 4% in mass) consistently rotated at rates less than those made of ice, it is hypothesised that, within the confines of the freshwater environment, the motion of the turbulent meltwater plume that forms beneath an ice disk amplifies the effect of residual background motions. From our observations, it is concluded that residual motions are an underlying physical trigger for disk rotation.

598 PREVALANCE AND PREDICTORS OF LONG-TERM CARDIAC SYMPTOMS IN PATIENTS WITH TAKOTSUBO SYNDROME

Abstract Background Takotsubo syndrome (TTS) is characterized by an acute and transient left ventricular dysfunction, usually involving the apical and midventricular segments, associated with troponin elevation and often triggered by either emotional or physical stressors. Once considered a benign condition, it is now clear that TTS patients have increased long-term mortality compared with the general population. Prevalence and the determinants of long-term cardiac symptoms in TTS patients have been scarcely investigated. Methods We enrolled consecutive patients admitted to our Centre with a diagnosis of TTS . All patients underwent invasive coronary angiography with left ventriculography at admission and only those fulfilling both the Mayo Clinic and Heart Failure Association criteria for a TTS diagnosis were selected for this study. Clinical, biochemical, and instrumental data were collected at admission and before discharge, and patients were followed-up for: symptoms recurrence (i.e., presence of effort angina and/or dyspnoea in the absence of other obvious causes) and all-cause mortality. The prevalence of long-term symptoms was further compared with a control group of unselected patients admitted for acute coronary syndromes (ACS) in the same period, matched for sex, age, and left ventricular ejection fraction (LVEF) at discharge. Results We eventually enrolled 118 patients (aged 73±10 years, 91% of whom were female). Acute chest pain was the most common presenting symptom (73%), followed by dyspnoea (32%), acute heart failure (16%), cardiogenic shock (9%), and syncope (8%). Most of cases (82%) were classified as having a typical (apical) LV dysfunction. Either a physical or an emotional stressor was identified in 37 (31%) and 31 (26%) of the patients, respectively. At admission, patients showed moderate systolic dysfunction (LVEF 40±9%), which was often improved at discharge (LVEF 52±8%). Over a median follow-up of 21 (interquartile interval 11-53) months, 35% of patients complained of some cardiac symptom: 32% of patients complained of effort dyspnoea and 7% (partially overlapping with the former) complained of effort angina. When compared with ACS patients (n=55, aged 71±10 years, 94% women, LVEF 53±9%), TTS patients featured a similar mortality rate, a lower (non-significant) prevalence of angina, and a significantly higher prevalence of dyspnoea (p=0.02). Notably, while a lower age at presentation (p=0.017) and a physical trigger (p=0.015) were significantly associated with the risk of recurrent angina, the absence of chest pain (p=0.044), a lower LVEF at admission (p=0.019), and a higher troponin T concentration at discharge (p=0.018) were associated with the presence of dyspnoea at follow-up. Finally, older age, male sex, renal dysfunction, cardiogenic shock, and concomitant coronary artery disease were all associated with a higher risk of death. Prescription of ACE-inhibitors and/or beta-blockers were associated with reduced risk (p&amp;lt;0.05, for all), in line with previous reports. Conclusion TTS is associated with a high risk of recurrent cardiac symptoms, mostly dyspnoea, over time. Selected clinical, biochemical, and instrumental characteristics may help identify patients more at risk, who may deserve a closer follow-up and potentially tailored therapies, to be investigated in future studies.

391 NEUROLOGICAL DISORDERS AND TAKOTSUBO SYNDROME: CLINICAL FEATURES AND OUTCOMES. RESULTS FROM A MULTICENTER PROSPECTIVE EUROPEAN REGISTRY OF 2300 PATIENTS.

Abstract Background and aims Takotsubo syndrome (TTS) is an acute heart failure syndrome featured by a reversible left ventricular systolic dysfunction. However, few data have been reported about prevalence of non-cardiovascular comorbidities as chronic neurological disorders in TTS patients. Aim of this study was to compare clinical features, short- and long-term outcome among TTS patients with history of neurological disorder. Methods 2301 patients with TTS were enrolled in a multicenter prospective European registry from July 2002 to November 2021. Clinical features, in- and out-of-hospital MACE, laboratory and imaging data were collected and a long-term follow-up was performed. Results Prevalence of history of neurological disorder was 17% (n= 400 pts). Most represented neurological conditions were previous cerebrovascular disorders (ischemic stroke and transient ischemic attack, 36.2%), followed by neurodegenerative disorders (30.7%, including cognitive disorders and motion disorders), tensive migraine (10%) and epilepsy (9.5%). Neurological Patients developed TTS more frequently after a physical trigger (46.2% vs 33.8%, p&amp;lt;0.01). Sepsis (10%), acute neurological trigger (9.5%) and extreme activity/trauma (8.5%) where the type of physical trigger more prevalent. During hospitalization neurological patients had longer in-hospital stay (10±11 days vs 8±8 days, p&amp;lt;0.01) and experienced more often in-hospital complications (27% vs 16%, p=0.0001) mainly driven by cardiogenic shock and in-hospital death (12% vs 7.6%; 6.5% vs 2.8%, respectively p&amp;lt;0.01). Long-term mortality was higher in patients with history of neurological disorders (23.5% vs 10%, p&amp;lt;0.01), with a mean follow up of 2.5 ± 5.8 years. Conclusions Patients with history of neurological disorders and TTS have different clinical features and worse prognosis with higher short-term and long-term mortality.

Das Takotsubo-Syndrom

TTS is an acute heart failure syndrome that usually affects postmenopausal women. The Syndrome is often preceded by an emotional or physical trigger. TTS strongly resembles acute myocardial infarction from a clinical standpoint and also exhibits ECG changes in the same proportion. There are specific patterns of wall motion abnormalities, based on which, the syndrome can be divided into four types. Neurological and/or psychiatric comorbidities are common in TTS patients. Therapy is based on the hemodynamic state and the presence of left ventricular outflow tract obstruction or cardiogenic shock. TTS has a comparable mortality to acute myocardial infarction. Pathophysiologically, the activation of the brain-heart axis with acute catecholamine storm seems to inherit a central role.