The Clinical Manifestations, Diagnosis and Management of Takotsubo Syndrome

The Takotsubo syndrome (TTS) is a transient cardiac dysfunction characterised by a variety of ventricular wall-motion abnormalities. Alternative nomenclatures for this disorder include stress-induced cardiomyopathy, apical ballooning syndrome and ‘broken heart syndrome’. TTS bears stark resemblance to an acute coronary syndrome, wherein patients present with acute chest pain and initial diagnostic workup correlates to abnormalities suggesting significant coronary stenosis. Interestingly, the distinguishing factor in TTS is the absence of an occlusive coronary vascular disease, which could correlate with these changes. The underlying pathophysiology explaining the evolution of TTS is still debatable; however, results from various recent studies and registers have shed more light on this obscure clinical entity. The detailed description of a criterion which demonstrably includes most patients with probable TTS has helped tune management strategies in ensuring necessary supportive care and early therapeutic interventions of complications, which could arise in course of the disease

Comparison and Outcome Analysis of Patients with Takotsubo Cardiomyopathy Triggered by Emotional Stress or Physical Stress

Background: Previous studies revealed that takotsubo cardiomyopathy (TTC) is triggered by physical and emotional stresses. This study was performed to determine the short- and long-term prognostic impact of emotional- and physical stress associated with TTC.Methods and results: Our institutional database constituted a collective of 84 patients diagnosed with TTC between 2003 and 2015. The patients were divided into two groups as per the presence of emotional stress (n = 24, 21%) or physical stress (n = 60, 52.6%). The endpoint was a composite of in-hospital events (thromboembolic events and life-threatening arrhythmias), myocardial infarction, all-cause of mortality, re-hospitalization due to heart failure, stroke, and recurrence of TTC. A Kaplan–Meier analysis indicated a significantly lower event-free survival rate over a mean follow-up of 5 years in the emotional group than the physical stress group (log-rank, p < 0.01). Multivariate Cox regression analysis revealed only emotional stress (HR 0.4, 95% CI: 0.2–0.9, p < 0.05) as a negative independent predictor of the primary endpoint.Conclusion: Rates of in-hospital events and short- as well as long-term events were significantly lower in TTC patients suffering from emotional stress as compared to patients with physical stress

Interventional Left Atrial Appendage Closure: Focus on Practical Implications

Catheter-based left atrial appendage closure is an evolving therapy for the prophylaxis of thromboembolic complications in nonvalvular atrial fibrillation patients, which are ineligible for long-term oral anticoagulation. For this indication, it is recommended by the current European guidelines. This review of the existing literature should facilitate the understanding of the therapy’s practical implications. It presents a clinical approach toward a correct patient selection, gives an overview of the different devices and the procedural aspects, reflects differences and benefits between several postprocedural regimens for device surveillance as well as antithrombotic medication and rounds off with a summary of the relevant studies concerning efficacy and safety outcome measures

Clinical outcomes associated with catecholamine use in patients diagnosed with Takotsubo cardiomyopathy

Background: Recent hypotheses have suggested the pathophysiological role of catecholamines in the evolution of the Takotsubo syndrome (TTS). The extent of cardiac and circulatory compromise dictates the use of some form of supportive therapy. This study was designed to investigate the clinical outcomes associated with catecholamine use in TTS patients. Methods: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The study-patients were subsequently classified into two groups based on the need for catecholamine support during hospital stay (catecholamine group n = 93; 81%, non-catecholamine group = 21; 19%). The primary end-point of our study was all-cause mortality. Results: Patients receiving catecholamine support showed higher grades of circulatory and cardiac compromise (left ventricular ejection fraction (LVEF) 39.6% vs. 32.7%, p-value < 0.01) and the course of disease was often complicated by the occurrence of different TTS-associated complications. The in-hospital mortality (3.2% vs. 28.5%, p < 0.01), 30-day mortality (17.2% vs. 51.4%, p < 0.01) as well as long-term mortality (38.7% vs. 80.9%, p < 0.01) was significantly higher in the group of patients receiving catecholamine support. A multivariate Cox regression analysis attributed EF ≤ 35% (HR 3.6, 95% CI 1.6–8.1; p < 0.01) and use of positive inotropic agents (HR 2.2, 95% CI 1.0–4.8; p 0.04) as independent predictors of the adverse outcome. Conclusion: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTS patients receiving catecholamine support as compared to the other study-patients. These results need further evaluation in pre-clinical and clinical trials to determine if external catecholamines contribute to an adverse clinical outcome already compromised by the initial insult

- LAA Occluder View for post-implantation Evaluation (LOVE) - standardized imaging proposal evaluating implanted left atrial appendage occlusion devices by cardiac computed tomography

Background: A standardized imaging proposal evaluating implanted left atrial appendage (LAA) occlusion devices by cardiac computed tomography angiography (cCTA) has never been investigated. Methods: cCTA datasets were acquired on a 3rd generation dual-source CT system and reconstructed with a slice thickness of 0.5 mm. An interdisciplinary evaluation was performed by two interventional cardiologists and one radiologist on a 3D multi-planar workstation. A standardized multi-planar reconstruction algorithm was developed in order to assess relevant clinical aspects of implanted LAA occlusion devices being outlined within a pictorial essay. Results: The following clinical aspects of implanted LAA occlusion devices were evaluated within the most appropriate cCTA multi-planar reconstruction: (1) topography to neighboring structures, (2) peri-device leaks, (3) coverage of LAA lobes, (4) indirect signs of neo-endothelialization. These are illustrated within concise CT imaging examples emphasizing the potential value of the proposed cCTA imaging algorithm: Starting from anatomical cCTA planes and stepwise angulation planes perpendicular to the base of the LAA devices generates an optimal LAA Occluder View for post-implantation Evaluation (LOVE). Aligned true axial, sagittal and coronal LOVE planes offer a standardized and detailed evaluation of LAA occlusion devices after percutaneous implantation. Conclusions: This pictorial essay presents a standardized imaging proposal by cCTA using multi-planar reconstructions that enables systematical follow-up and comparison of patients after LAA occlusion device implantation

Trigger‐Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry

Stress‐induced cardiomyopathy; Takotsubo syndromeMiocardiopatía inducida por estrés; Síndrome de takotsuboMiocardiopatia induïda per l'estrès; Síndrome de takotsuboBackground Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German‐Italian‐Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in‐hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long‐term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long‐term mortality, while chest pain (P=0.035) and treatment with angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long‐term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long‐term mortality

Follow-up of iatrogenic aorto-coronary "Dunning" dissections by cardiac computed tomography imaging

Background: Iatrogenic aorto-coronary dissections following percutaneous coronary interventions (PCI) represent a rare but potentially life threatening complication. This restrospective and observational study aims to describe our in-house experience for timely diagnostics and therapy including cardiovascular imaging to follow-up securely high-risk patients with Dunning dissections. Methods: Dunning dissections (DD) occurred during clinical routine PCIs, which were indicated according to current ESC guidelines. Diagnostic assessment, treatment and follow-up were based on coronary angiography with PCI or conservative treatment and cardiac computed tomography (cCTA) imaging. Results: A total of eight patients with iatrogenic DD were included. Median age was 69 years (IQR 65.8–74.5). Patients revealed a coronary multi-vessel-disease in 75% with a median SYNTAX-II-score of 35.3 (IQR 30.2–41.2). The most common type of DD was type III (50%), followed by type I (38%) and type II (13%). In most patients (88%) the DD involved the right coronary arterial ostium. 63% were treated by PCI, the remaining patients were treated conservatively. 88% of patients received at least one cCTA within 2 days, 50% were additionally followed-up by cCTA within a median of 6 months (range: 4–8 months) without any residual. Conclusion: Independently of the type of DD (I-III) it was demonstrated that cCTA represents a valuable imaging modality for detection and follow-up of patients with DDs

Real life experience with the wearable cardioverter-defibrillator in an international multicenter Registry

Patients at high risk for sudden cardiac death (SCD) may benefit from wearable cardioverter defibrillators (WCD) by avoiding immediate implantable cardioverter defibrillator (ICD) implantation. Different factors play an important role including patient selection, compliance and optimal drug treatment. We aimed to present real world data from 4 centers from Germany and Switzerland. Between 04/2012 and 03/2019, 708 patients were included in this registry. Patients were followed up over a mean time of 28 ± 35.5 months. Outcome data including gender differences and different etiologies of cardiomyopathy were analyzed. Out of 708 patients (81.8% males, mean age 61.0 ± 14.6), 44.6% of patients had non-ischemic cardiomyopathy, 39.8% ischemic cardiomyopathy, 7.9% myocarditis, 5.4% prior need for ICD explantation and 2.1% channelopathy. The mean wear time of WCD was 21.2 ± 4.3 h per day. In 46% of patients, left ventricular ejection fraction (LVEF) was > 35% during follow-up. The younger the patient was, the higher the LVEF and the lower the wear hours per day were. The total shock rate during follow-up was 2.7%. Whereas an appropriate WCD shock was documented in 16 patients (2.2%), 3 patients received an inappropriate ICD shock (0.5%). During follow-up, implantation of a cardiac implantable electronic device was carried out in 34.5% of patients. When comparing German patients (n = 516) to Swiss patients (n = 192), Swiss patients presented with longer wear days (70.72 ± 49.47 days versus 58.06 ± 40.45 days; p = 0.001) and a higher ICD implantation rate compared to German patients (48.4% versus 29.3%; p = 0.001), although LVEF at follow-up was similar between both groups. Young age is a negative independent predictor for the compliance in this large registry. The most common indication for WCD was non-ischemic cardiomyopathy followed by ischemic cardiomyopathy. The compliance rate was generally high with a decrease of wear hours per day at younger age. Slight differences were found between Swiss and German patients, which might be related to differences in mentality for ICD implantation

Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats

Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting with an ejection fraction (EF) of greater than 50% along with different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understanding of HFpEF, effective treatments are still limited. In the current study we attempted to unravel the molecular basis of sex-dependent differences in HFpEF pathology. We analyzed left ventricular samples from 1-year-old female and male transgenic (TG) rats homozygous for the rat Ren-2 renin gene (mRen2) characterized with hypertension and diastolic dysfunction and compared it to age-matched female and male wild type rats (WT) served as control. Cardiomyocytes from female and male TG rats exhibited an elevated titin-based stiffness (Fpassive), which was corrected to control level upon treatment with reduced glutathione indicating titin oxidation. This was accompanied with high levels of oxidative stress in TG rats with more prominent effects in female group. In vitro supplementation with heat shock proteins (HSPs) reversed the elevated Fpassive indicating restoration of their cytoprotective function. Furthermore, the TG group exhibited high levels of proinflammatory cytokines with significant alterations in apoptotic and autophagy pathways in both sexes. Distinct alterations in the expression of several proteins between both sexes suggest their differential impact on disease development and necessitate distinct treatment options. Hence, our data suggested that oxidative stress and inflammation distinctly drive diastolic dysfunction and remodeling in female and male rats with HFpEF and that the sex-dependent mechanisms contribute to HF pathology