Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study.

BACKGROUND: Several reports have described Takotsubo syndrome (TTS) secondary to thyrotoxicosis. A complex interaction of central and peripheral catecholamines with thyroid homeostasis has been suggested. In this study, we analysed sequential thyroid hormone profiles during the acute phase of TTS. METHODS: Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at predefined time points in 32 patients presenting with TTS or acute coronary syndrome (ACS, n = 16 in each group) in a 2-year period in two German university hospitals. Data were compared to age- and sex-matched controls (10 samples, each of 16 subjects), and an unsupervised machine learning (ML) algorithm identified patterns in the hormone signature. Subjects with thyroid disease and patients receiving amiodarone were excluded from follow-up. RESULTS: Among patients with TTS, FT4 concentrations were significantly higher when compared to controls or ACS. Four subjects (25%) suffered from subclinical or overt thyrotoxicosis. Two additional patients developed subclinical or overt thyrotoxicosis during stay in hospital. In four subjects (25%), FT4 concentrations were increased, despite nonsuppressed TSH concentration, representing an elevated set point of thyroid homeostasis. The thyroid hormone profile was normal in only six patients (38%) presenting with TTS. CONCLUSION: Abnormal thyroid function is frequent in patients with TTS. Primary hyperthyroidism and an elevated set point of thyroid homeostasis are common in TTS, suggesting a stress-dependent endocrine response or type 2 thyroid allostasis. Thyroid function may be a worthwhile target in treating or preventing TTS.

Correction to: Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

The article Occlusion of left atrial appendage aff ects metabolomic profile:focus on glycolysis, tricarboxylic acid and urea metabolism, written by K. Sattler, M. Behnes, C. Barth, A. Wenke, B. Sartorius, I. El-Battrawy, K. Mashayekhi, J. Kuschyk, U. Hoffmann, T. Papavasiliu, C. Fastner, S. Baumann, S. Lang, X. Zhou, G. Yücel, M. BorggrefeI, Akin, was originally published Online First without open access.

[Dyspnea and skin rash in a 49-year-old male patient]. / Dyspnoe und Hautausschlag bei einem 49-jährigen Patienten.

We report on the case of a 49-year-old man who presented with increasing dyspnea and a skin rash. The community-acquired pneumonia was initially treated with broad spectrum antibiotics. The patient's respiratory condition rapidly worsened and the clinical picture of Waterhouse-Friderichsen syndrome developed with disseminated intravasal coagulopathy and necrosis of the toes. An infection with Capnocytophaga canimorsus, which had been caused by an initially unmentioned dog bite was confirmed. In view of the fulminant course and the high risk of operative treatment of the ubiquitous necroses in all limbs, a joint decision for deescalation of therapy was made together with relatives. The patient died 14 days after admission to hospital.

[Subcutaneous cervical and left thoracic emphysema in a 49-year-old woman on ventilation]. / Zervikales und linksthorakales Weichteilemphysem bei einer 49-jährigen beatmeten Patientin.

We report the case of a 49-year-old woman who was admitted with community-acquired pneumonia. The medical state worsened despite administration of antibiotics. She was intubated and ventilated because of respiratory distress. Several hours after intubation, she developed massive subcutaneous emphysema. The bronchoscopy showed tracheal transmural rupture 3 cm long on the posterior wall of the trachea. The high-risk surgery and massive doses of catecholamine favoured conservative treatment with bilateral endobronchial intubation and veno-venous extracorporeal membrane oxygenation. The patient made a full recovery.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data.

BACKGROUND: Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. METHODS: We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19).Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). RESULTS: 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women.The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%).In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2 < 92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered. CONCLUSION: In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

ANTECEDENTES: Trabajos previos parecen coincidir en la mayor mortalidad de los pacientes con cáncer y COVID-19. La identificación de posibles factores pronósticos en el momento del ingreso podría ayudar a identificar a los pacientes con mal pronóstico. MÉTODOS: Nos propusimos explorar las características y la evolución de los pacientes con cáncer y COVID-19 ingresados en un registro internacional multicéntrico (HOPE COVID-19).Nuestro objetivo principal es definir aquellas características que nos permitan identificar a los pacientes con cáncer de peor pronóstico (mortalidad en los 30 días siguientes al diagnóstico de COVID-19). RESULTADOS: En este registro se ha recogido a 5.838 pacientes, de los cuales 770 tenían cáncer entre sus antecedentes. La mortalidad hospitalaria alcanzó a 258 pacientes (33,51%). La mediana fue de 75 años (65-82). En cuanto a la distribución por sexo, el 34,55% de los pacientes eran mujeres (266/770).La distribución por tipo de cáncer: genitourinario 238/745 (31,95%), digestivo 124/745 (16,54%) y hematológico 95/745 (12,75%).En el análisis de regresión multivariante, los factores que se asocian de forma independiente con la mortalidad al ingreso son: insuficiencia renal (OR 3,45; IC 97,5%: 1,85-6,58), cardiopatía (2,32; 1,47-3,66), hepatopatía (4,69; 1,94-11,62), dependencia parcial (2,41; 1,34-4,33), dependencia total (7,21; 2,60-21,82), fatiga (1,84, 1;16-2,93), artromialgias (0,45; 0,26-0,78), SatO2 < 92% (4,58; 2,97-7,17), LDH elevada (2,61; 1,51-4,69) y disminución anormal de la presión arterial (3,57; 1,81-7,15). Los parámetros analíticos también están significativamente alterados. CONCLUSIÓN: En los pacientes con cáncer del registro HOPE, la mortalidad a los 30 días por cualquier causa es elevada y se asocia a factores clínicos fácilmente identificables a su llegada al hospital. La identificación de estos pacientes puede ayudar a iniciar tratamientos más intensivos desde el principio y evaluar el pronóstico de estos pacientes.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data.

BACKGROUND: Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. METHODS: We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19). Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). RESULTS: 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women. The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%). In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2<92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered. CONCLUSION: In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

Gender-based comparison of takotsubo syndrome versus myocardial infarction.

BACKGROUND: Takotsubo Syndrome (TTS) is an acute reversible left ventricular dysfunction. Recently published studies have highlighted a similar mortality rate as acute coronary syndrome (ACS). We compared the impact of gender differences on the outcome of TTS patients as compared to ACS patient. DESIGN AND METHODS: We included a collective of 138 patients TTS between 2003 and 2016 at our institution. Patients were divided according to their gender into two groups (Males n=21, 15% and females, n=117, 85%). They were compared with a cohort of 300 patients with a diagnosis of ACS. RESULTS: On the acute phase, in male patients with TTS, a treatment with inotropic was more often required (33.3 vs. 11.5%, P<0.01), were more susceptible to cardiogenic shock (28.6 vs. 12.5%, P<0.04). Concerning the long-term prognosis after the acute event, male patients had higher all-cause mortality over long-term follow-up. A Kaplan-Meier analysis indicated that the mortality of male patients with TTS was significantly higher compared to male patients with ACS (log-rank <0.01), while there was no significant difference between female patients with TTS and ACS (log-rank =0.60, P=0.45). In a multivariate cox regression analysis, male gender (HR 2.7, 95% CI: 1.1-6.5, P=0.02) GFR <60 ml/min (HR 2.8, 95% CI: 1.2-6.0, P=0.01) and history of cancer (HR 3.6, 95% CI 1.4-9.3, P<0.01) were independent predictors of 5-year mortality. CONCLUSIONS: Considerable evidence suggests that TTS compared to ACS implicates more significant clinical short-term events on male patients and it may be associated with poorer long-term prognosis.

Risk stratification in Takotsubo syndrome: a role of mitral annular plane systolic excursion.

AIM: Takotsubo syndrome (TTS) patients have a higher mortality rate than the general population. Our study was conducted to determine the short- and long-term outcome of TTS patients associated with a significantly compromised mitral annular plane systolic excursion (MAPSE) on hospital admission. METHODS AND RESULTS: Our institutional database constituted a collective of 53 patients diagnosed with TTS between 2003 and 2016. The patients were classified into two groups based on the MAPSE, with those presenting with an MAPSE <1 cm on admission categorized into one group (n = 20, 38%) and those presenting with MAPSE ≥1 cm (n = 33, 62%) categorized into another group. Preliminary results indicated that patients with an MAPSE < 1 cm had a greater risk of developing thromboembolic events. The long-term mortality was significantly higher in TTS patients with an MAPSE < 1 cm. In the multivariate Cox regression analysis, cardiogenic shock (hazard ratio 3.5; 95% confidence interval: 1.2-10.7; P = 0.02) and MAPSE < 1 cm (hazard ratio 5.1; 95% confidence interval: 1.3-19.2; P = 0.01) figured as independent predictors of the mortality. CONCLUSION: Although the short-term mortality rates among TTS patients diagnosed with a reduced MAPSE on admission were as similar as without reduced MAPSE, the long-term mortality rates among TTS patients diagnosed with a reduced MAPSE on admission were significantly higher. There is an urgent need for randomized trials, which could help define uniform clinical management strategies for high-risk TTS patients.

Long term outcome of patients suffering from cancer and Takotsubo syndrome or myocardial infarction.

BACKGROUND: The pathophysiology of takotsubo syndrome (TTS) is unclear so far. There is strong association of the occurrence of TTS and malignant diseases. An association between malignant diseases and myocardial infarction (MI) was found recently and ascribed to common molecular and lifestyle mechanisms. AIM: To compare the outcome of patients with MI or TTS and malignant diseases in a matched cohort. METHODS: Patients with TTS or with MI (n = 138 per group) were matched for age and sex and assessed retrospectively and prospectively. Occurrence of malignant diseases and clinical outcome was followed up over 4 years. RESULTS: At the time of the index event, 8 (5.8%) MI patients and 17 (12.3%) TTS patients were already diagnosed with cancer. During follow up, the rate of patients who developed cancer was significantly higher in the TTS group than in the MI group (log rank P = 0.01). Mortality was higher in the TTS group, but also in the subgroup of TTS patients with cancer (log rank P < 0.05). In the multivariate analysis, male gender, renal impairment and the history of cancer was associated with an increased risk for death. CONCLUSIONS: Patients with TTS have more often malignant diseases than patients with MI. Cancer patients with TTS have a worse clinical outcome. The underlying mechanism is unclear yet, but the results point at TTS being the syndrome of an extracardiac disease rather than a disease of cardiac origin. Longer and closer follow up of patients with TTS and further studies addressing the mechanism of TTS are needed.

[Bedside implantation of a new temporary vena cava inferior filter : German results from the European ANGEL registry]. / Bettseitige Implantation eines neuen passageren V.-cava-inferior-Filters : Deutsche Daten aus dem europäischen ANGEL-Register.

BACKGROUND: Pulmonary embolism (PE) is a frequently occurring complication in critically ill patients, and the simultaneous occurrence of PE and life-threatening bleeding is a therapeutic dilemma. Inferior vena cava filters (IVCF) may represent an important therapeutic alternative in these cases. The Angel® catheter (Bio2 Medical Inc., San Antonio, TX, USA) is a novel IVCF that provides temporary protection from PE and is implanted at bedside without fluoroscopy. MATERIAL AND METHODS: The European Angel® Catheter Registry is an observational, multicenter study. In our German substudy, we investigated patients from three German hospitals and four intensive care units, who underwent Angel® catheter implantation between February 2016 and December 2016. RESULTS: A total of 23 critically ill patients (68 ± 9 years, 43% male) were included. The main indication for implantation was a high risk for or an established PE, combined with contraindications for prophylactic or therapeutic anticoagulation due to either an increased risk of bleeding (81%) or active bleeding (13%). The Angel® catheter was successfully inserted in all patients at bedside. No PE occurred in patients with an indwelling Angel® catheter. Clots with a diameter larger the 20 mm, indicating clot migration, were detected in 5% of the patients by cavography before filter retrieval. Filter retrieval was uneventful in all of our cases, while filter dislocation occurred in 3% of the patients. CONCLUSION: The German data from the multicenter European Angel® Catheter Registry show that the Angel® catheter is a safe and effective approach for critically ill patients with a high risk for the development of PE or an established PE, when an anticoagulation therapy is contraindicated.

Sex differences of in-hospital outcome and long-term mortality in patients with Takotsubo cardiomyopathy.

BACKGROUND: Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. It is still unclear whether sex differences may influence long-term prognosis of TTC patients. The purpose of this study was to determine whether sex differences do influence the short- and long-term outcomes of TTC. METHODS AND RESULTS: A total of 114 patients with TTC were admitted to the University Medical Centre Mannheim from January 2003 to September 2015 and entered into the TTC database of the University Medical Centre Mannheim, and retrospectively analyzed. Patients were diagnosed by the Mayo Clinic criteria. All-cause mortality over mean follow-up of 1,529±1,121 days was revealed. Significantly more male patients died within long-term follow-up compared to female TTC patients (log-rank test; P=0.01). Most males died of noncardiac causes. In multivariate Cox regression analysis, the male sex (P=0.02, hazard ratio [HR] 2.8, 95% CI 1.1-7.2), the ejection fraction ≤35% (P=0.01, HR 3.3, 95% CI 1.2-9.2) and glomerular filtration rate <60 mL/min (P<0.01, HR 3.1, 95% CI 1.4-7.0) figured out as independent predictors of the adverse outcome. CONCLUSION: This study shows that males suffering from TTC reveal a higher long-term all-cause mortality rate than females over a 5 year follow-up period.

Coincidental coronary artery disease impairs outcome in patients with takotsubo cardiomyopathy.

BACKGROUND AND AIM: Takotsubo cardiomyopathy (TC) is an important differential diagnosis of coronary artery disease (CAD), mimicking acute coronary syndrome in clinical symptoms, biomarker profiles and ST-elevation in ECG. Absence of occlusive coronary disease is an essential criterion distinguishing both diseases. The aim of the study was to explore the influence of co-existing incidental CAD on poorer clinical outcomes and all-cause mortality in TC. DESIGN, METHODS AND RESULTS: Our mono-centric study cohort constituted 114 consecutive patients diagnosed with TC between 2003 and 2015. The primary endpoint was the all-cause mortality. Additionally, we compared the incidence of thromboembolic events, life-threatening arrhythmias, cardiogenic shock and in-hospital death. There was no significant difference in gender distribution or mean age in both groups. Patients diagnosed with a co-existing CAD (n = 22), had a more pronounced cardiovascular risk profile. The all-cause mortality among patients with co-existing CAD after a 2-year follow-up was higher than those diagnosed with lone TC (22.7 vs. 5.4 %, P = 0.07). In a multivariate cox regression analysis CAD (HR 3.5, 95 %CI 1.0-11.6; P = 0.04), LVEF ≤ 35% (HR 3.8, 95% CI 0.0-0.6, P = 0.01) and cardiogenic shock (HR 3.8, 95% CI 1.2-11.3; P = 0.01) were independent predictors of the primary endpoint. CONCLUSION: Our study reveals that co-existing CAD impairs the outcome in patients with TC. The diagnostic work-up for TC should therefore not necessarily hinge on ruling out CAD.

Prevalence of cancer in Takotsubo cardiomyopathy: Short and long-term outcome.

BACKGROUND: Takotsubo Cardiomyopathy (TTC) is a transient disorder of ventricular wall dysfunction, mostly induced by physical or emotional stress. TTC may be associated with adverse cardiac events. The association of cancer and its clinical impact in TTC patients has not been described yet. METHODS: In 114 consecutive patients presenting with TTC between January 2003 and September 2015, we studied the frequency of cancer diagnosis, and compared the clinical course and the occurrence of a clinical endpoint of cancer and non-cancer patients during a follow up of 4.2years. RESULTS: Of the 114 patients, 16 (14.0%) had a malignancy already diagnosed at TTC, and further 11 patients received the diagnosis during follow up. Cancer patients had higher frequency of atrial fibrillation and lower hemoglobin levels at admission than patients without cancer. While the occurrence of in-hospital events was comparable, the diagnosis of cancer at TTC event or during follow up was predictive for a higher rate of the composite endpoint. In the Kaplan-Meier analysis, malignant diseases were strongly associated not only with overall mortality but also with worsened time of event-free survival during the long-term outcome. CONCLUSIONS: Prevalence of malignant diseases is high in TTC patients, and is a risk factor for worse outcome. Screening for malignancies should be recommended in all patients presenting with TTC. Further studies are needed to define the association on molecular levels.

Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

BACKGROUND: Left atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet. OBJECTIVES: We aimed to study the effects of interventional LAAC on systemic metabolism. METHODS: Products of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1). RESULTS: During follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta -0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01). CONCLUSIONS: Successful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.

Comparison and outcome analysis of patients with apical and non-apical takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is a relevant differential diagnosis in patients presenting with signs of an acute coronary syndrome. Although recent literature has highlighted some salient features of this disorder, there has been little information elucidating the differences in clinical features, electrocardiographic findings, echocardiographic data and TTC-related complications associated with the different variants of TTC. METHODS AND RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC between 2003 and 2015 and these patients were subsequently divided into two groups based on the presence (n = 82, 72%) or absence (n = 32, 28%) of the apical form of TTC. The protocol for our proposed study was approved by the Ethics Committee of the University Medical Centre in Mannheim. It was noticed that the patients presenting with the apical form of TTC belonged to an older age group as compared to those presenting with the non-apical form (61.1 ± 8.9 years vs. 69.5 ± 11.2; P < 0.01). The QTc interval prolongation at index-event was observed to be quantifiably greater in the 'apical variant' patients group (484.8 ± 57 ms vs. 464 ± 34.1 ms; P = 0.06). With respect to cardiovascular risk factors, patients with arterial hypertension did have a higher predilection to present with the apical form (63.4% vs. 43.7%; P = 0.06), however, the impact of smoking was less pronounced in this patient group (24.4% vs. 50%, P = 0.01). Furthermore, our study highlighted a significant impact on ejection fraction (EF), with a compromised left ventricular function (36 ± 9% vs. 42.4 ± 9.7%, P < 0.01) and greater involvement of the right ventricle in the apical variant patients group (23% vs. 3%, P = 0.04). Patients with the apical form also showed a greater tendency to develop TTC-related complications such as cardiogenic shock and required longer monitoring and care in comparison. CONCLUSIONS: The apical and non-apical variants of TTC are manifestations of the same syndrome. They differ significantly, however, in their clinical presentation, related complications and prognosis.