Takotsubo Research Articles

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.

SCARY ECG IN TAKOTSUBO CARDIOMYOPATHY

Abstract Takotsubo cardiomyopathy (TTC) is characterized by a transient ventricular wall motion abnormality and shares common features with acute coronary syndrome (ACS) with a wide spectrum of triggers, such as both emotional or physical, activating common toxic catecholamines–mediated pathways. TTC might be associated with severe clinical complications. We report a case of a 74–year female patient with circulatory shock with mixed phenotype, distributive due to sepsis and cardiogenic due to TTC. The patient presented to the emergency department with severe hypotension, pathological qSOFA score and clinical and laboratory findings consistent with severe sepsis. ECG showed diffuse lambda ST–segment elevation, also called “shark fin”(fig.1). According to hemodynamically unstable scenario and ECG pattern, emergency coronary angiography was performed, showing absence of coronary artery disease(fig. 2). Echocardiography revealed severe LV systolic disfunction (EF 20–25%) with apical ballooning and severe systolic anterior motion (SAM) of the anterior mitral leaflet eliciting dynamic LVOTO with peak gradient greater than 90 mmHg; fig. 3) and severe MR. Patient was treated with cautious fluid administration, hemotrasfusion and empiric large spectrum antibiotic therapy. According to TTC working diagnosis, even if septic state was thought to contribute to cardiogenic shock, norepinephrine was not administered due to concerns for LVOTO and SAM. After overcoming of dramatic first phase and after hemodynamic steadiness was achieved, beta blockade and ACEi were progressively administered. Seriate transthoracic echocardiogram revealed progressive improvement of LV systolic function, regression of apical ballooning, SAM and LVOTO. ECG monitoring showed regression of ischemic ST elevation. ST elevation has been described in about 56% of TTC cases, however with amplitude tipically lower than in STEMI. Lambda–wave ST elevation has been rarely reported. Vasospasm, local intermittent microvascular constriction, catecholamine–induced metabolic toxicity, transmural systolic wall tension and its the mechano–electric feedback can explain scaring ECG–pattern. Despite its rare prevalence in TTC “shark fin” pattern appears to relate to adverse outcome and it should be used as an early marker of potential further clinical deterioration, suggesting more intensive monitoring to avoid delays in possible therapy escalation.

“A BROKEN TRANSPLANTED HEART”: A CASE OF TAKOTSUBO SYNDROME IN A HEART TRANSPLANT RECIPIENT

Abstract 75–year–old female patient went to the emergency department for oppressive chest pain radiating to the left arm and dyspnea, developed after an argument with family members. The patient underwent heart transplant in 2010 because of chronic ischemic heart disease. In history: systemic arterial hypertension, former smoking, dyslipidemia, and chronic renal failure. At blood tests: TnIHS 78.4 ng/L (<29 ng/L), CK–MB 1.9 microg/L, PROBNP–NT 43,000 pg/ml, creatinine 2 mg/dL. ECG showed inverted T waves in DI, AVL and V4 to V6 (fig 1). Transthoracic echocardiography was remarkable for a moderate reduction in systolic function (EF 38%), akinesia of apical portion, mid–segment of the IVS and mid–segment of posterior wall. Coronarography showed epicardial coronaries free of angiographically significant lesions. We decided to not perform ventriculography to avoid worsening renal function. At clinical stabilization, the patient underwent cardiac MRI with evidence of hypokinesia of the mid–ventricular segments with preserved global systolic function and hypo/akinesia of right ventricular apex with endocavitary thrombosis. Tissue characterization images were compatible with the presence of diffuse phlogistic involvement of the left ventricular myocardium (most evident at the mid–ventricular segments), in the absence of areas of myocardial necrosis. On pre–dimission echocardiogram, global left ventricular systolic function appeared markedly improved (auto EF 52%). DISCUSSION Our case is a rare case of Takotsubo syndrome (TS) in a transplanted heart. While TS accounts for 1–2% of all ACS in the general population, there is no precise data on its prevalence in heart transplant recipients. Although the pathophysiological mechanism underlying TS is still debated, there is evidence of hyperactivation of the sympathetic system with excessive catecholamine release. What is particular in our clinical case is that transplanted heart is denervated (because of resection of the post–ganglionic neural axons), although in some patients there is progressive reinnervation starting around the second year. Myocardial scintigraphy with iodine–123 meta iodobenzylguanidine can be used to study reinnervation. In our case, the presence of typical angor may be a clinical indicator of reinnervation, as many transplant patients present with CAV in the absence of chest pain.

ADVANCED CARDIAC IMAGING IN LIVER TRANSPLANTATION ECHOCARDIOGRAPHIC VENTRICULAR STRAIN AS PROGNOSTIC TOOLS

Abstract While cardiac involvement in the end–stage liver disease (ESLD) is a known condition, the characteristics of cardiac function in cirrhotic cardiomyopathy and their effects on candidates to liver transplant (LT) are still vague. The evaluation of right ventricular failure (RVF) in liver transplant candidates has been revolutionized by advanced cardiac imaging techniques, particularly echocardiography with global longitudinal strain (GLS) analysis. Aim of the present study is to evaluate RV function indexes in ESLD patients candidate to LT and the potential relationship with the liver disease status and cardiovascular major events on early post–LT phase Forty ESDL adult patients (age 46.8 ± 10 yrs, M/F 33/7) candidate to LT (19 for hepatic failure, 18 for hepatocarcinoma and 3 for other causes) were evaluate. All were submitted to transthoracic echocardiography and coronary CT angiography or coronary angiography. The Model for End–stage Liver Disease (MELD) score in the study population was 19±6.8. The higher values of the MELD score (i.e. the worst liver function condition) were directly correlated with the lower RV–GLS (p<0.02). Cardiac function indexes were LV–EF 62.8±4.5%, RV–GLS –22.9±4.5%, LV–GLS –19.5±4.6% and PAPs 31.8±6.6 mmHg. On 21 day follow–up, 4 patients died (2 with acute RV failure, 1 with Tako–Tsubo syndrome). On CT–angiography the value of calcium score was significantly different between the group of fatal events and the rest (0 vs 567±900), revealing that none of the died patient suffered from coronary atheromatic disease. Our findings identified that specific RV–GLS patterns on echocardiography, indicative of subclinical myocardial dysfunction, were strongly correlated with worst clinical hepatic conditions and reduced survival rates post–transplant. The study highlights the importance of advanced cardiac imaging in identifying liver transplant candidates at higher risk of post–transplant mortality due to RHF.

Takotsubo Syndrome in a Critical COVID-19 Patient: Electrocardiographic and Echocardiographic Evolution

Takotsubo Syndrome in a Critical COVID-19 Patient: Electrocardiographic and Echocardiographic Evolution

A PARTICULAR CASE OF CARDIAC ARREST

Abstract 88–year–old man with arterial hypertension, cognitive impairment, carrier of dual–chamber PM due to sinus node disease. Diagnosis of congenital long QT syndrome (LQT1) approximately 20 years ago during family screening (syncopal episodes in his son positive for LQT1), no history of syncope or major arrhythmias. In home therapy with mirtazapine and norvasc. He arrived in our cardiac intensive care unit for ACC on torsade de pointes trated with two cycles of CPR and 1 DC shock at 200 Joules with ROSC. On arrival ECG evidence of electrically induced ventricular rhythm, QTc 850 msec. On echocardiogram akinesia of the mid–basal segments of all the LV walls (takotsubo–like) with EF 25–30%. On coronary angiography non critical multivessel coronary disease. At laboratory tests increase of WBC, PCR and PCT, slight plateau movement of troponin, normal electrolytes. The patient underwent a chest CT scan with evidence of an inflammatory focus for which antibiotic therapy was started. Congenital long QT syndrome (LQTS) is an inherited condition characterized by prolongation of the QT interval (more than 450 ms in men and 460 ms in women), associated with repolarization abnormalities. There are three main forms transmitted via AD: LQT1, LQT2 and LQT3. The most common variant is LQT1 caused by a loss of function mutation in the KCNQ1 gene which causes a reduction in the outgoing potassium current during phase 3 of the action potential. In these patients, episodes of syncope caused by torsade de pointes, major arrhythmias and sudden cardiac death are frequent. Patients with LQTS should avoid taking drugs that can prolong the QT interval such as some antipsychotics, antidepressants (like mirtazapina that can cause QT prolongation, torsade de pointes, ventricular tachycardia and sudden cardiac death if administered at high doses or in patients with predisposing factors), antibiotics. Furthermore, there are various factors that can influence the QT prolongation: electrolyte alterations, physical stress, cerebrovascular events. The use of mirtazapine for a long period in association with takotsubo syndrome (probably triggered by underlying pneumonia) in a patient with LQTS, may have resulted in massive lengthening of the QT interval causing torsade de pointes and therefore ACC. During the hospitalization, mirtazapine was suspended and nadolol was introduced with a progressive reduction of the QT segment. No new arrhythmic events were recorded.

TAKOTSUBO SYNDROME PRECEDING THE INDEX EVENT: A DANGEROUS CLINICAL SETTING

Abstract We describe the case of a 68–year–old patient who presented to the Emergency Department following an unwitnessed syncopal episode with slow recovery of consciousness. On admission, the patient had dyspnoea together with physical signs of pulmonary congestion. Cardiac ultrasound showed severe left ventricular dysfunction with an ejection fraction of 30%, and apical and paraapical akinesis. The admission electrocardiogram showed sinus tachycardia and diffuse repolarization abnormalities, hs TnI was elevated and BNP vl blood gas analysis were unremarkable. During observation in the Emergency Department, the patient experienced epileptic seizure, promptly resolved by intravenous Midazolam. Contrast–enhanced chest CT ruled out aortic dissection disclosing a clinically irrelevant subsegmental pulmonary embolism. A non–contrast CT scan of the brain yielded negative results. In consideration of the atypical clinical presentation and scattered evidence of an acute coronary syndrome, the patient was admitted to our Cardiac Intensive Care Unit (CICU) for additional diagnostic workup delaying coronary angiography in the presence of stable TnI elevation. Three hours after admission the patient continued showing altered consciousness and a subsequent brain CT was performed, demonstrating an intraparenchymal hemorrhagic spreading. Repeat ECGs showed precordial T wave inversion and prolongation of the QT interval. These data, together with LV apical dysfunction, raised the suspicion of Takotsubo syndrome secondary to an acute cerebrovascular event. During the hospital stay, recovery of consciousness, spontaneous absorption of the cerebral hemorrhagic spread and complete recovery of left ventricular function at repeat cardiac ultrasound examinations were observed, confirming the almost unequivocal diagnosis of Takotsubo syndrome. The patient was discharged uneventfully and was scheduled for an outpatient coronary CT scan. This case underscores the crucial importance of a thorough clinical assessment in the management of complex patients in the presence of nonunivocal clinical signs and misleading blood test and imaging data. Moreover, Takotsubo syndrome is a protean clinical entity that can precede the index event as in our patient, i.e. cerebral hemorrhage. Misclassification of these patients as having an acute coronary syndrome could have led to the initiation of antithrombotic therapy, with potential fatal outcomes for the patient.

A LABILE EQUILIBRIUM: THE CONTROVERSIAL ROLE OF BETA–BLOCKERS IN A CASE OF MID–VENTRICULAR TAKOTSUBO SYNDROME

Abstract Case Report Takotsubo syndrome (TTS) is a non–ischemic heart disease mimicking acute coronary syndrome. The mid–ventricular variant is almost rare (15% of TTS cases). A 62 years old woman was referred to our hospital for oppressive chest pain radiating to the jaw lasting at least 30 minutes after an attempted strangulation by a family member. She denied any conventional cardiovascular risk factor; she was taking beta–blockers (BB) to reduce symptomatic and idiopathic premature ventricular complexes (PVCs) burden. On arrival, the patient was hemodynamically stable, reporting only swallowing difficulties. Physical examination revealed neck bruising and irregular pulse. The initial ECG showed sinus rhythm with a heart rate of 62 bpm, PVCs and a biphasic T wave in lead aVL. Hs–cTnI first dosage was 145 pg/mL. Transthoracic echocardiography (TTE) found moderate left ventricular (LV) dysfunction and severe hypokinesis of mid septal and mid inferior segments. Coronary angiography revealed normal coronary arteries. Left ventriculogram showed hypokinesis of the midventricular section with a hyperdynamic base and apex suggestive of mid–ventricular variant of TTS. After a few hours, she experienced a lipothymic episode and telemetry showed marked sinus bradycardia followed by multiple sinus pauses. A TTE was immediately performed, demonstrating a worsening LV ejection fraction with new development of severe symmetrical akinesia of the LV apex. Successively, psychotherapy was started. Wall motion abnormalities and LV systolic function completely recovered over a few days. At present the patient is in good health status. Discussion domestic violence against women is prevalent, but it is often omitted as a potential stress trigger that affects their hearts. In Italy, it’s reported that 32% of women had experienced physical violence. Strangulation is very uncommon as cause of TTS and psychotherapy may prevent recurrences and recover in a shorter time. Bradycardia due to atrioventricular block and asystole has been described in the acute phase of TTS and it is often attributed to BB therapy. Although BB have been proposed to add further benefit of blunting the effect of catecholamine excess, their use should be used cautiously in the acute phase of TTS. Moreover, beta–adrenoceptor hypersensitivity may generate a parasympathetic drive when on BB infusion, provoking a worsening LV dysfunction and a transient sick sinus syndrome as we described.

TRANSIENT GLOBAL AMNESIA AND CONCOMITANT TAKOTSUBO CARDIOMYOPATHY: A CASE SERIES

Abstract Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of anterograde amnesia, accompanied by repetitive questioning lasting up to 24 hours with whole restoration and without compromise of other neurologic function. Case reports suggest that cardiac dysfunctions may also occur in patients TGA although until now, no study has systematically assessed this phenomenon. Several pathophysiologic mechanisms have been proposed, with particular emphasis on the role of the central and autonomic nervous systems and an increased sympathetic hyperactivity, likewise to Takotsubo Syndrome (TTS). A case series of two cases (one man and one woman) of TGA as a precocious display of concomitant Takotsubo cardiomyopathy was described.

TAKOTSUBO SYNDROME AND SMALL BOWEL OBSTRUCTION: WHEN THE HEART–GUT AXIS GOES HAYWIRE

Abstract Case Report A 66 years old woman was admitted to our emergency department for the onset of intense epigastric pain, nausea and asthenia after breakfast. She had a history of hypertension, dyslipidemia, COPD and deep venous thrombosis with MTHFR gene mutation. Moreover, she had a positive family history for coronary artery disease (CAD). On arrival, she was apyretic, hemodynamically stable, complaining chest and persisting epigastric pain. A mild and diffuse abdominal tenderness was noted without peritoneal signs. The ECG showed sinus tachycardia, ST elevation (STE) in leads D1, aVL, V2 and V3 and ST depression in leads D3, aVR and V1. Blood test revealed a marked increase of PCR with leukocytosis and elevation of Hs–cTnI (840 ng/L) while serum electrolytes were normal. Bed–side echocardiography revealed apical and mid–ventricular akinesia with a severe reduction of left ventricular ejection fraction (LVEF). InterTAK score was 62 (62,6% probability of Takotsubo syndrome – TTS). An urgent coronary angiography (CA) revealed non– obstructive CAD, while ventriculography showed a typical apical ballooning and hyperkinetic base of the LV suggestive of TTS. Subsequently, the CT abdomen showed extra–luminal free fluid and a dilated proximal small bowel (SB) with air–fluid levels and a bubbly pattern of gas in the wall. These radiological findings were consistent with a mechanical SB obstruction, complicated by mesenteric venous thrombosis and intestinal pneumatosis. Exploratory laparotomy revealed SB necrosis as consequence of bridle–mediated obstruction and therefore an ileum resection was performed. The patient clinically improved post–operatively with a complete recovery of the LVEF. Discussion We described a rare presentation of SB obstruction which induced a TTS in a setting of severe psychophysical stress. The management of this emergency situation in which cardiac injury and acute abdomen occurred simultaneously can be challenging. The consulting cardiologist needs to quickly decide whether to prioritize the heart with urgent CA or the gastroenteric condition with surgery. Despite the likelihood of TTS can be high (even calculating InterTak score), new STE and positive troponins can’t be disregarded especially in patients with significant risk factors as seen in our case. Therefore, the strong evidence of a possible acute coronary syndrome may trump a life–saving treatment for SB obstruction.

IS IT REALLY A CASE OF TAKOTSUBO? SOMETIMES APPEARENCES CAN BE DECEPTIVE

Abstract We report the case of a 22–year–old female with a history of David procedure and mechanical valve replacement (ATS 22 mm) due to bicuspid aortic valve and severe AR with ascending aorta aneurysm in 2015. Regular annual clinical follow–up (EKG and ultrasound) was always normal. Since 2022 the patient suffered from episodes of dyspnea, chest pain and sadness diagnosed as Panic Disorder. Home–therapy: Warfarin, estroprogestinic pill. At the latest outpatient visit she was asymptomatic and in good overall condition, but her EKG showed novel alterations (T wave inversion in antero–lateral leads and QT prolongation). She was then sent to the ED. LAB: troponin levels were normal (6.8 ng/ml) with an elevated Nt–proBNP (425 ng/ml) and a low INR (1.53). Questioned about recent events she reported a road trauma which occurred two weeks prior. She was then admitted to Cardiology clinic. Ultrasound: apical akinesia with reduced wall thickness, EF 48%, E/E‘ 10, and normal right ventricular function. The aortic valve prosthesis was functional without pathological regurgitation, and other echocardiographic parameters were within normal limits. EKG and ultrasound abnormalities along with a recent history of trauma supported Takotsubo Syndrome diagnosis (InterTAK score = 79.8% – 67pt), even though troponin levels were normal. Throughout hospitalization there were no changes in the EKG or pathological increases in troponin, and the patient remained asymptomatic. The patient was treated with LMWH to achieve adequate INR levels and initiated on B–blocker, ACEi, and SGLT2i for HFmrEF. Cardiac MRI revealed apical segment akinesia with dilation and reduced wall thickness (EDV 97 ml/m²), EF 41%, transmural ischemic LGE in the apical region and a ventricular thrombus (16x4 mm). The patient underwent coronary angiography which showed normal epicardial coronary arteries. Upon careful history–taking, the patient admitted irregular intake of VKA in the previous months. Given this information, the MRI and angiographic findings the diagnosis of unrecognized prior acute coronary syndrome, likely due to coronary thromboembolism in a patient with PHV and suboptimal compliance with VKA, was established. The patient was discharged home upon achieving a persistently therapeutic INR, with instructions to discontinue contraceptive therapy. Conclusion: coronary thromboembolism is a rare complication of PHV with inadequate anticoagulation leading, in this case, to an unrecognized MI.

The Science Behind Stress: From Theory to Clinic, Is Basal Septal Hypertrophy the Missing Link between Hypertension and Takotsubo Cardiomyopathy?

The modern theory of stress, initially proposed by Hans Selye in 1956, signifies an important development in our understanding of this phenomenon. Selye’s The Stress of Life serves as a foundational book for subsequent scientific questions. In this article, we focus on a comprehensive look at stress and use a literature review to explain its theoretical foundations as well as its clinical equivalent. Our research focuses on the complex mechanisms of stress, with a particular emphasis on the consequences of cardiac remodeling and adaptation processes. Myocardial remodeling might be seen as a response to increased stress in acute or chronic situations. Stressed heart morphology (SHM) is a very interesting description representing basal septal hypertrophy (BSH), which is detectable in both acute emotional stress and chronic stress due to increased afterload in hypertension. Acute stress cardiomyopathy (ASC) and hypertension in the same individuals could be clinically linked. Also, in this report, we mention the geometric and functional similarity of the left ventricle (LV) septal base in both acute and chronic clinical situations. Therefore, cardiac imaging methods are crucial to assessing LV segmental aspects in ASC patients. We propose a new paradigm that ASC may develop in hypertensive patients with SHM. We document the segmental progression of microscopic LV remodeling using a third-generation microscopic ultrasound and note that BSH takes a longer time to occur morphologically than an acutely developed syndrome. However, the majority of ASC events have a predominant base, and the absence of segmental remodeling details, including BSH and cardiac decompensation with apical ballooning, on echocardiographic reports may mask the possible underlying hypertensive disease. In fact, beyond ASC cases, previously undiagnosed hypertension is very common, even in developed countries, and is associated with masked target organ damage.

Perspectives on Resolving Diagnostic Challenges between Myocardial Infarction and Takotsubo Cardiomyopathy Leveraging Artificial Intelligence

Background: cardiovascular diseases, including acute myocardial infarction (AMI) and takotsubo cardiomyopathy (TTC), are significant causes of morbidity and mortality worldwide. Timely differentiation of these conditions is essential for effective patient management and improved outcomes. Methods: We conducted a review focusing on studies that applied artificial intelligence (AI) techniques to differentiate between acute myocardial infarction (AMI) and takotsubo cardiomyopathy (TTC). Inclusion criteria comprised studies utilizing various AI modalities, such as deep learning, ensemble methods, or other machine learning techniques, for discrimination between AMI and TTC. Additionally, studies employing imaging techniques, including echocardiography, cardiac magnetic resonance imaging, and coronary angiography, for cardiac disease diagnosis were considered. Publications included were limited to those available in peer-reviewed journals. Exclusion criteria were applied to studies not relevant to the discrimination between AMI and TTC, lacking detailed methodology or results pertinent to the AI application in cardiac disease diagnosis, not utilizing AI modalities or relying solely on invasive techniques for differentiation between AMI and TTC, and non-English publications. Results: The strengths and limitations of AI-based approaches are critically evaluated, including factors affecting performance, such as reliability and generalizability. The review delves into challenges associated with model interpretability, ethical implications, patient perspectives, and inconsistent image quality due to manual dependency, highlighting the need for further research. Conclusions: This review article highlights the promising advantages of AI technologies in distinguishing AMI from TTC, enabling early diagnosis and personalized treatments. However, extensive validation and real-world implementation are necessary before integrating AI tools into routine clinical practice. It is vital to emphasize that while AI can efficiently assist, it cannot entirely replace physicians. Collaborative efforts among clinicians, researchers, and AI experts are essential to unlock the potential of these transformative technologies fully.

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.

Pediatric Takotsubo cardiomyopathy: a review and insights from a national multicentric registry

Abstract Funding Acknowledgements None. Background 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. Objectives We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. Methods 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. Results Comparison between the RETAKO general population is detailed in Table 1. Pediatric patients with TTS had a median age of 11 years (IQR = 4-14). When compared to the RETAKO general population, they were more often male (51.9% vs 23.3%, p<0.001), and displayed a higher prevalence of secondary forms (90.7% vs 35.6% in adults, p<0.001). Regarding race, 11 cases (20.4%) were from Asia and 42 (77.8%) were Caucasian; whereas in RETAKO 1420 (94.9%) were Caucasians, with under 5 cases (<0.1%) being Asian. Pediatric patients presented less commonly with angina (11.1% vs 64.1%, p<0.001) or dyspnea (30% vs 41.7%, p<0.001), compared to the general RETAKO cohort. Nevertheless, pediatric patients with TTS exhibited a higher Killip status on admission (Killip IV 74.1% vs 10.5%, p<0.001), and higher needs of vasoactive and mechanical ventilatory support during hospitalization. Regarding complementary exams, pediatric patients presented with lower LVEF on admission (30.5+10.4 vs 36.9+16.9, p = 0.014) together with greater prevalence of atypical (basal or midventricular) TTS patterns on echocardiography (30.2% vs 15.8%, p = 0.006). Additionally, there were significantly less ST-segment alterations in the pediatric population (either ST-segment elevation or depression), without differences on T wave inversion in the admission ECG. During follow-up, all-cause deaths (11.1% vs 12,5%, p = 0.761) and TTS recurrences (3.8% vs 3,8%, p = 0.863) were similar between groups. Conclusions 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 underscored the necessity for further research in this age group.Table 1

Comparing clinical profiles, in-hospital complications and one-year cerebrovascular events in typical and midventricular TTS-results from a retrospective study between two third-level centers

Abstract Funding Acknowledgements None. Background Apical ballooning is considered the typical form of Takotsubo syndrome (TTS) and occurs in about 75-80% of cases. Midventricular (MV) is the most frequent atypical variant and represents about 15% of TTS. Clinical and analytical characteristics, early complications and the risk of cerebrovascular events (CVEs) between these two specific groups are poorly studied. Purpose of the study To investigate the clinical profile, laboratory variables, in-hospital complications and one-year CVEs between typical and MV variants of TTS. Methods we retrospectively examined the patients admitted to two third-level hospitals with a diagnosis of TTS. A total of 248 TTS met InterTAK diagnostic criteria. Clinical features, myocardial enzymes, echocardiographic variables, early complications and one-year CVEs were assessed. Results Of 248 patients diagnosed with TTS, a total of 205 (83%) patients presented with typical and 43 (17%) with MV variant of TTS. Patients with MV form were younger (age mean ± SD 68 ± 12 vs 74 ± 11 years, p value = 0.002) and had a lower incidence of hypertension (46% vs 73%; p value < 0.001) than those with apical variant. On admission, patients with MV form presented a lower degree of left ventricular dysfunction (EF mean ± SD, 44 ± 9% vs 41 ± 9%, p value = 0.018) and a tendence not to present left ventricular outflow tract obstruction (LVOTO) (0 vs 9%, p value = 0.049). Lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels on admission (median [IQR], 881 [99 – 3049] pg/mL vs 3466 [677 - 9067] pg/mL, p value <0.001) and at peak (3150 [947- 4437] pg/mL vs 4622 [1886 - 13163] pg/mL, p value = 0.005) were observed in MV group compared to the typical form. In-hospital cardiovascular (CV) complications were frequently observed (46% in the overall population) and appeared to be more frequent in the typical variant (51% vs 33%, p value= 0.035); in particular, we reported a higher prevalence of AF (16% vs 2%, p value = 0.022). The number of CS and VT cases is remarkable in both the subgroups (13% vs 7%; 5% vs 2%), with a higher prevalence in the typical form, even if not reaching a statistically significant difference between the two groups (p= 0.437; p= 0.695). No significant differences were observed in LV thrombosis, and in on admission and one-year CVEs between the two groups, although with a higher prevalence in the typical variant (respectively 3 vs 0, 10 vs 1 and 5 vs 0). Conclusions MV TTS presents some differences in clinical characteristics, analytical values and echocardiographic parameters compared to the typical variant. In-hospital CV complications are remarkable, and more frequently observed in typical variant, although not reaching a statistically significant difference in CS and VT. Similarly, more CVE were observed in the typical TTS group, although in the absence of a statistical significance. The importance of close monitoring in the acute phase is confirmed for both variants under study.

Exploring biomarkers as predictors of left ventricular recovery in a national registry of takotsubo syndrome patients (RETAKO)

Abstract Funding Acknowledgements None. Introduction Tako-Tsubo Syndrome (TTS) is characterized by transient dysfunction of the left ventricle (LV) of uncertain etiology, although considered a benign entity, TTS has a mortality rate and complications similar to STEMI patients (1). Late LV recovery (>10 days) has been associated with a worse prognosis. Currently, there is no data on biomarkers that can predict the disease's progression. Purpose We aim to correlate different biomarkers with LV recovery in TTS patients. Method We used data from the National Multicenter Registry on Tako-Tsubo Syndrome (RETAKO). Information on biomarkers, including NT-proBNP, C-reactive protein (CRP), leukocytes, and platelets, was collected both upon admission and at peak values. Early recovery was considered when it occurred within the first 10 days after the index event. A non-parametric correlation analysis was conducted to assess the predictive capacity of different biomarkers on LV recovery. Results Out of a total of 1,463 patients, 373 (25.5%) experienced late LV recovery. The average age was around 73 years, with the majority of the sample being women (86%). Significant differences were observed between the groups in NT-proBNP, CRP, and peak values of leukocytes and platelets, with higher levels in the late recovery group. In the linear correlation analysis, a significant association was found between late recovery and higher levels of NT-proBNP, peak leukocytes and platelets, however it was not statistically significant for the levels of CRP. Conclusions In a large national cohort of TTS patients, higher levels of NT-proBNP, peak of leukocytes and platelets during the hospital stay were significantly associated with late LV recovery. This recovery appears to depend on the degree of LV dysfunction and the inflammatory response.Biomarkers table 1

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.

Transient Left Ventricular Dysfunction from Cardiomyopathies to Myocardial Viability: When and Why Cardiac Function Recovers.

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.

Gender-based differences in clinical profile, management and mortality in cardiogenic shock. Prognostic accuracy of CardShock vs IABP Score, the Shock-CAT study

Abstract Funding Acknowledgements None. Background Mortality in cardiogenic shock (CS) remains very high. Gender could influence in aetiology, management, outcomes and risk stratification predictors. Purpose The aim is to analyse differences in clinical profile, management, in-hospital prognosis and mortality risk in CS patients depending on sex and compare the prognostic accuracy of CardShock and IABP scores between sexes in a Mediterranean cohort. Method Shock-CAT study was a multicentre, prospective, observational study conducted between December 2018 and December 2019 in eight public University hospitals in Spain, including CS patients of different aetiologies. Data on clinical presentation, biomarkers, management, including mechanical cardiac/circulatory support (MCS) were analysed comparing women and men. Cardshock and IABP score have been compared to assess 90-days mortality risk between sexes. Results A total of 382 CS patients (p) were included: women 24.9% (n=95 p) and men 75.1% (n=287p). Women were older than men (68.9 vs 64.1 years, P=0.004). CS due to acute coronary syndrome (ACS) was more frequent in men (66.6% vs 43.2%), and myocarditis (1.7 vs 6.3%), stress cardiomyopathy (0.3% vs 8.4%) and severe aortic stenosis (2.4% vs 6.3%) were more prevalent in women, all p<0.001. Cardiac arrest was more prevalent in men than women (38.4% vs 25.3%, p=0.020). MCS was implanted in 35.3% of patients, without gender differences (men 36.6%, women 31.6%, p=0.376). Even though there was a non-significant trend to lower use in women of IABP (31.1% vs 26.5%), Impella (13.5% vs 7.4%) or ECMO (10.4% vs 7.4%). Risk scores were similar between sexes: Cardshock (men:4.32 vs 4.40 women, p=0.674) and IABP score (men: 2.31 vs 2.04 women, p=0.190). There were no differences between men and women in in-hospital mortality (32.4% vs 34.7%, p=0.675) or 6-months mortality (41.5% vs 40%, p=0.989). Receiver-operating characteristic curves demonstrated that IABP shock score had superior prognostic power for predicting 90-days mortality when compared with Cardshock score in men (area under the curve -AUC- 0.72 vs 0.64) respectively, p=0.009, although both scores were similar in women (AUC 0.70 vs 0.72, p=0.635), Figures 1-2. Conclusions Women with CS were older than men and had less ACS and cardiac arrest at admission. There is a non-significant lower use of mechanical assistance devices in women, although in-hospital or 6-months mortality were similar in both sexes. IABP score provided better 90-days mortality risk prediction than CardShock score in men, but both scores were similar in women with cardiogenic shock.Men ROC Curves 90-days MortalityWomen ROC Curves 90-days Mortality