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ZusammenfassungDas Takotsubo Syndrom (TTS) ist gekennzeichnet durch akut auftretende transiente Wandbewegungsstörungen des linken Ventrikels, denen angiografisch keine signifikanten Koronarstenosen zugrunde liegen. Die Erkrankung tritt überwiegend bei älteren Frauen in der Menopause auf, prinzipiell können jedoch Patienten jeden Alters und beiderlei Geschlechts betroffen sein. Insgesamt wird bei etwa 2% aller Patienten mit dem Verdacht auf ein akutes Koronarsyndrom (ACS) die Diagnose eines TTS gestellt; bei Frauen mit ACS-Verdacht liegt die Inzidenz mit 6–9% deutlich höher. Als Triggerfaktor für ein TTS findet sich bei Frauen häufiger emotionaler Stress und bei Männern physischer Stress. Im Akutstadium der Erkrankung können schwerwiegende Komplikationen auftreten, die Krankenhausmortalität ist vergleichbar mit der beim akuten Myokardinfarkt und bei Männern infolge von Begleiterkrankungen höher als bei Frauen mit einem TTS. Aktuell existiert keine evidenzbasierte Therapie. Um die Prognose des TTS im Akutstadium verbessern und Rezidive verhindern zu können, sind prospektive randomisierte Studien erforderlich.

In randomized trials, direct oral anticoagulants (DOAC) were non-inferior to the vitamin-K-antagonist (VKA) warfarin in preventing stroke/embolism in patients with atrial fibrillation (AF). DOAC are substrates for P-glycoprotein (P-gp), CYP3A4 and CYP2C9. The activity of these enzymes is modulated by several drugs which might induce pharmacokinetic drug-drug interactions (DDI). Drugs affecting platelet function have the potential for pharmacodynamic DDI of DOAC. The literature was searched for: ‘dabigatran,’ ‘rivaroxaban,’ ‘edoxaban,’ or ‘apixaban’ and drugs affecting platelet function, CYP3A4-, CYP2C9- or P-gp-activity. Reports about bleeding and embolic events attributed to DDI with DOAC in AF-patients were found for 43 of 171 drugs with interacting potential (25%), most frequently with antiplatelet and nonsteroidal anti-inflammatory drugs. Whereas a co-medication of platelet-affecting drugs is invariably reported to increase the bleeding risk, the findings regarding P-gp-, CYP3A4- and CYP2C9- activity-affecting drugs are ambiguous. Tests for plasma DOAC-levels and information about DDI of DOAC should be widely available and user-friendly. If advantages and disadvantages of DOAC and VKA can be investigated exhaustively, individualized anticoagulant therapy can be offered to patients, considering co-medication, comorbidities, genetic and geographic factors and the health care system.

Introduction: In patients with cerebral amyloid angiopathy (CAA), intracerebral hemorrhage (ICH) and atrial fibrillation (AF), both antiplatelet and anticoagulant therapy for prevention of embolic stroke increases the risk of recurrent intracerebral hemorrhage. Left atrial appendage closure (LAAC) has, therefore, been suggested as an alternative to antithrombotic therapy in patients with CAA.Case description: A man in his mid-80s suffered from ICH and CAA was diagnosed by magnetic resonance imaging of the brain. He had a history of arterial hypertension, dyslipidemia, monoclonal gammopathy (IgG kappa), and chronic obstructive pulmonary disease. Four months previously, edoxaban 60 mg/d had been prescribed because of permanent AF. Blood pressure at admission was 170/80 mm Hg. The NT-pro-BNP level was 1819 ng/L (reference value: < 486 ng/L). The electrocardiogram showed AF. Echocardiography showed an enlarged left atrium, left ventricular wall thickening, good systolic function and diastolic dysfunction. Edoxaban was stopped and the ICH resolved within 16 days. Interventional LAAC was considered but eventually not performed because of the following reasons: 1. Postinterventional antiplatelet therapy to prevent device-associated thrombus formation would expose him to the risk of recurrent ICH. 2. Aggravation of heart failure may occur due to the missing hemodynamic and endocrine properties of the left atrial appendage. Thus, optimization of antihypertensive therapy without any antiplatelet or anticoagulant therapy was recommended. Thirteen months after ICH, no further hemorrhagic or ischemic events had occurred. Conclusion: In view of the lack of randomized clinical trials in patients with CAA, ICH and AF, neither LAAC nor anticoagulant nor antiplatelet therapy but a healthy lifestyle with a blood-pressure target of < 120/80 mmHg should be recommended to prevent recurrent ICH.

Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding TTS.

The therapeutic effects of music have been known for thousands of years. Recently, studies with music interventions in patients with cardiovascular diseases yielded controversial results. The aim of this review is to provide an overview of the effects of receptive music intervention on the cardiovascular system. We searched in PubMed, SCOPUS and CENTRAL for publications between January 1980 and May 2018. Primary endpoints were heart rate, heart rate variability and blood pressure. Secondary endpoints comprised respiratory rate, anxiety and pain. The quality of the studies was assessed by using the CONSORT statement and the Cochrane risk of bias assessment tool. A meta-analysis and subgroup analyses concerning music style, gender and region were planned. A total of 29 studies comprising 2579 patients were included and 18 studies with 1758 patients investigated the effect of music on patients undergoing coronary angiography or open heart surgery. Other studies applied music to children with congenital heart diseases, pregnant women with hypertension or patients with unstable angina. Due to high methodological study heterogeneity, a meta-analysis was not performed. The study quality was assessed as medium to low. In ten studies with higher quality comprising 1054 patients, music intervention was not associated with significant changes in the cardiovascular endpoints compared to the control group. The subgroup analyses did not demonstrate any relevant results. Currently no definite effect of receptive music intervention on the cardiovascular system can be verified. Further research is needed to assess music as an inexpensive and easy applicable form of therapy.

Using bone‐avid radiotracers, cardiac transthyretin (TTR) amyloidosis can be diagnosed by scintigraphy, thus obviating endomyocardial biopsy. Radiotracer accumulation, however, may also be due to other causes. A 68‐year‐old male with acute myocardial infarction underwent recanalization of the left anterior descending coronary artery (LAD). Postinterventionally, transthoracic echocardiography showed hypokinesia of the septum and anterior wall and a thickened myocardium with granular sparkling appearance. Cardiac amyloidosis was suspected. A 99mTc‐3,3‐diphosphono‐1,2‐propanodicarboxylic acid whole‐body scan 4 days after LAD recanalization showed Perugini 2 myocardial tracer uptake. Monoclonal gammopathy was excluded, and cardiac TTR amyloidosis was diagnosed. Three months later, 99m‐Tc‐hydroxydiphosphate scan showed no myocardial tracer uptake. Cardiac magnetic resonance imaging revealed late gadolinium enhancement within the LAD supply area. No mutation of the TTR gene was found. Suspicion of amyloidosis should consider not only echocardiography but also history and clinical findings. Myocardial oedema due to reperfusion should be acknowledged as a differential diagnosis for cardiac uptake of bone‐avid radiotracers.

This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including β-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:24 issue:2 pages:257-273 ispartof: location:England status: published

As an alternative to oral anticoagulation, percutaneous left atrial appendage (LAA) closure is an increasingly performed procedure to prevent arterial embolism in patients with non‐valvular atrial fibrillation. Besides procedure‐related complications, residual leaks, device‐related thrombus formation, and dislocation of the LAA occluder have been observed during follow‐up. Heart failure as a consequence of interventional LAA closure has not been reported so far. This case report describes a 79‐year‐old lady with permanent non‐valvular atrial fibrillation presenting with New York Heart Association Class IV heart failure. Symptoms had started immediately after attempted LAA closure 11 months before. Transoesophageal echocardiography demonstrated two devices in the LAA, a large peri‐device leak, a mobile LAA thrombus, a right atrial appendage thrombus, and shunting via a patent foramen ovale. Under a maximally tolerated dose of heart failure medication and edoxaban, the patient remains without bleeding or embolism in New York Heart Association Class II. Because of its unique anatomical and endocrine properties, the LAA plays an important role in situations of pressure and volume overload. Interventional LAA closure interacts unfavourably with left atrial compliance and reservoir function. Atrial and brain natriuretic peptide secretion is known to be significantly reduced after LAA closure. Both mechanisms may result in the development of heart failure. Attempted LAA closure—instead of being the solution—may create new serious problems. Development of heart failure should be assessed, and a systematic search for late leaks after LAA closure should be performed in trials investigating safety and efficacy of this intervention.

While the first part of the scientific statement on the pathophysiology of Takotsubo syndrome was focused on catecholamines and the sympathetic nervous system, in the second part we focus on the vascular pathophysiology including coronary and systemic vascular responses, the role of the central and peripheral nervous systems during the acute phase and abnormalities in the subacute phase, the gender differences and integrated effects of sex hormones, genetics of Takotsubo syndrome including insights from microRNA studies and inducible pluripotent stem cell models of Takotsubo syndrome. We then discuss the chronic abnormalities of cardiovascular physiology in survivors, the limitations of current clinical and preclinical studies, the implications of the knowledge of pathophysiology for clinical management and future perspectives and directions of research. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:24 issue:2 pages:274-286 ispartof: location:England status: published

Takotsubo syndrome was featured in various sessions and posters at the recent Heart Failure Congress and World Congress on Acute Heart Failure 2019 held in Athens. The importance and increasing recognition of this acute heart failure syndrome is reflected by the growing activity at Heart Failure Association congresses over the last 8 years. Two dedicated sessions to Takotsubo syndrome with comprehensive lectures from experts in the field and several posters highlighted new scientific progress, important aspects of epidemiology, pathophysiology, risk stratification, and management of the syndrome and discussed gaps in knowledge of this intriguing entity. This paper will summarize the topics discussed in these sessions including the most recent data from large registries, clinical, and pre‐clinical studies presented at the meeting.

Introduction: Takotsubo syndrome (TTS) may be complicated by left-ventricular (LV) thrombus formation in 1.3–5.3% of patients. Risk factors for thrombi comprise apical TTS, elevated levels of C-reactive protein and troponine, thrombocytosis, persisting ST segment elevation and right-ventricular involvement. Embolic risk appears high, and anticoagulation is recommended. Case Presentation: We present 3 females, aged 60–82 years, with TTS-associated LV thrombi and cerebral embolism despite therapeutic anticoagulation. Two patients showed apical and 1 patient midventricular ballooning. In 2 patients LV thrombi had not been present at the first echocardiographic examination. LV thrombi were multiple and highly mobile in 2 patients; 1 patient had a single immobile thrombus associated with spontaneous echocardiographic contrast (SEC). In each case, 3 of the described risk factors for LV thrombus formation were identified. The embolic stroke occurred 41–120 h after TTS symptom onset and 21–93 h after the initiation of therapeutic anticoagulation. Two patients were discharged with a neurological deficit, and 1 of them eventually died as a consequence of the stroke. LV thrombectomy to prevent embolism, which has been reported in a small number of cases, had not been considered in our patients. Conclusion: At present, the management of patients with TTS-related thrombi is still unclear, and further studies are urgently needed to assess the best methods for imaging and anticoagulation and to determine the role of thrombolysis and cardiac surgery. Until these studies are available, we suggest the following approach: patients with a TTS-related thrombus should be monitored by echocardiography while receiving anticoagulation. In case of highly mobile LV thrombi, the heart team may consider cardiac surgery to prevent systemic embolism. The role of SEC in TTS remains to be determined.

Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding TTS.

Takotsubo syndrome (TTS) occurs predominantly in elderly females but young individuals and children may also be affected. There are no consistent differences between men and women regarding age, symptoms, prehospital delay, or clinical course. Mortality has been reported to be higher in males. The QTc interval may be disproportionately prolonged in male patients in the days after admission predisposing them to ventricular arrhythmias. The higher level of cardiac markers in males with TTS may be related to the greater frequency of physical stress before the onset of TTS. Understanding the pathogenetic background may lead to preventive/therapeutic means against this life-threatening disease.

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed.

Objective This study evaluated the frequency, severity and outcome of complications in the clinical course of tako-tsubo cardiomyopathy (TTC). Background TTC is regarded as a benign disease since left ventricular (LV) function returns to normal within a short time. However, severe complications have been reported in selected patients. Methods From 37 hospitals, 209 patients (189 female, age 69±12years) were prospectively included in a TTC registry. Results Complications developed in 108/209 patients (52%); 23 (11%) had >2 complications. Complications occurred median 1day after symptom onset, and 77% were seen within 3days. Arrhythmias were documented in 45/209 patients (22%) including atrial fibrillation in 32 (15%) and ventricular tachycardia in 17 (8%). Of 8 patients resuscitated (4%), 6 survived. Additional complications were right ventricular involvement (24%), pulmonary edema (13%), cardiogenic shock (7%), transient intraventricular pressure gradients (5%), LV thrombi (3%) and stroke (1%). During hospitalization, 5/209 patients (2.5%) died. Patients with complications were older (70±13 vs 67±10years, p=0.012), had a higher heart rate (91±26 vs 83±19/min, p=0.025), more frequently Q\ waves on the admission ECG (36% vs 21%, p=0.019) and a lower LV ejection fraction (47±15 vs 54±14%, p=0.002). Multivariate regression analysis identified Q-waves on admission (OR 2.49, 95% CI 1.23–5.05, p=0.021) and ejection fraction ≤30% (OR 4.03, 95% CI 1.04–15.67, p=0.022) as independent predictors for complications. Conclusions TTC may be associated with severe complications in half of the patients. Since the majority of complications occur up to day 3, monitoring is advisable for this time period.

Objective This study evaluated if there are gender differences in the manifestation of tako-tsubo cardiomyopathy (TTC). Background TTC predominantly occurs in elderly females and mimics acute myocardial infarction (AMI) where men and women are known to have a different clinical profile. Methods 324 patients from 37 hospitals were prospectively included in a TTC registry. Clinical, electrocardiographic, angiographic and outcome data from male and female patients were compared. Results Of 324 patients 296 (91%) were female and 28 (9%) male. Mean age (68±12 vs 66±12years) and prehospital delay were similar. A triggering event preceded TTC onset in 76% of women and 86% of men. Physical stress was more frequent in men (30% vs 57%, p=0.005) whereas more women experienced emotional or no stress. The prevalence of angina and dyspnea did not differ. Fewer females were admitted in cardiogenic shock and/or after out of hospital cardiac arrest (1% vs 14%, p=0.0006), and cardiac troponin was lower (median 7.2 vs 10.7 times the upper limit of normal, p=0.03). The QTc interval was longer in females than in males only on the day of admission (468±52 vs 441±51ms, p=0.047). Overall, complications during the acute course (53% vs 40%) were comparable in both sexes. Conclusions In this large TTC registry, males and females showed a similar clinical profile. In males, physical stress as a trigger event and shock or cardiac arrest as presenting symptoms were more frequent. The QTc interval was longer in females only on admission but similar in males and females during the following days.

With great interest we read the recent European Society of Cardiology (ESC) guidelines for the Management of Atrial Fibrillation.1 We are, however, concerned about the high number of conflicts of interest (COIs) of the authors as listed in the Table 1 . Of 17 authors only 2 (12%) indicated no COI. The chairperson of the task force had the second most COIs ( n = 30). The mean number of COIs of all …

Takotsubo cardiomyopathy is characterized by transient left ventricular dysfunction, electrocardiographic changes, and minimal release of myocardial enzymes that mimic acute myocardial infarction in patients without coronary artery disease. Takotsubo cardiomyopathy is frequently triggered by emotional or physical stress and occurs primarily in post-menopausal women. The pathomechanism of Takotsubo cardiomyopathy is, so far, unknown. Stress-induced amnesia is probably induced by perturbation of the hippocampal function. Assault-induced Takotsubo cardiomyopathy associated with amnesia has not been reported so far. In a 77-year-old Caucasian female, hospitalized because of confusion, anterograde amnesia, and hypertension after she had been assaulted by a female who sneaked up to her when she was unlocking the door of her apartment, Takotsubo cardiomyopathy was diagnosed based on clinical findings, electrocardiography, echocardiography, and coronary angiography. Follow-up after 8 weeks showed a regression of electrocardiographic and echocardiographic abnormalities; the amnesia for the assault, however, remained unchanged. This case shows that Takotsubo cardiomyopathy may be triggered by emotional stress induced during an assault. Assault-induced stress may not only induce Takotsubo cardiomyopathy but also amnesia for some of the events that occurred during the act.

BACKGROUND AND OBJECTIVE: Transient left ventricular (LV) apical ballooning (AB) is characterized by chest pain, electrocardiographic (ECG) changes and LV apical akinesia mimicking anterior myocardial infarction (AMI) in the absence of coronary artery disease. This study aimed to assess if the ECG could reliably differentiate between these two syndromes with a similar clinical presentation. PATIENTS AND METHODS: Among 2086 patients with an acute coronary syndrome (ACS) undergoing coronary angiography over a 6.5-year period, 33 patients (1.6 %) with apical ballooning (AB) were identified (29 f, 4 m, median age 77 [68 - 80] years). AB patients were compared to 28 consecutive age and sex matched AMI patients (23 f, 5 m; 68 [56 - 76] years) undergoing successful PCI of the LAD with similar findings on LV angiography. We compared the ECG on admission, at the time of maximal T-wave inversion, before discharge and the longest QTc-interval. RESULTS: The number of leads showing ST-segment elevation (4 [3 - 6] vs. 5 [5 - 7]; p = 0,005) and the sum of the level of ST-segment elevation (0,7 [0,5 - 0,9] mV vs. 0,9 [0,7 - 1,5] mV; p = 0,002) was significantly greater in AMI. An abnormal Q wave at presentation was more frequent in AMI (21 % vs 79 %, p > 0.001) and persisted in half of AMI patients whereas the Q wave disappeared in all AB patients during follow-up (0 % vs. 61 %, p > 0.001). The QTc interval was significantly longer in AB (568 [521 - 614] ms vs. 471 [438 - 513] ms; p > 0,001). During follow-up, AB patients displayed significantly more leads with T-wave inversion (8 [8 - 9] vs. 6 [5 - 8]; p > 0,001), and the sum of the level of T-wave inversion (2,9 [2,2 - 4,6] mV vs. 1,4 [0,9 - 2,3] mV; p > 0,001) was significantly larger than in AMI. A formula considering ST-segment elevation on admission and T-wave inversion as well as Q waves during follow-up allowed discrimination between AB and AMI (sensitivity 93 %, specificity 86 %). CONCLUSION: ECG findings in AB patients are significantly different from those in AMI patients. At initial presentation, the extent of ST-segment elevation and the number of abnormal Q waves are greater in AMI. During follow-up, no Q wave, a longer QTc interval and a greater extent of T-wave inversion are typical findings in AB patients.

Transoesophageal ultrasound imaging of the spinal canal through an intervertebral disc was successfully achieved in 44 of 50 adults (18 women and 32 men; mean age 56 years, range 22-79) who, for cardiological indications had transoesophageal echocardiography. On average, five (range 1-11), usually sequential, segments were visualized. In 37 patients pulse-synchronous sagittal displacement of the spinal cord was noted, presumably caused by cerebrospinal fluid pulsation. In one woman, with known syringomyelia, the spinal cord cavity was well shown. Real-time demonstration of dynamic events in the spinal canal opens up new possibilities for the diagnosis and follow-up monitoring of spinal diseases.

Background Transesophageal echocardiography (TEE) is regarded as the method of choice for imaging left atrial appendage thrombi (LAAT). However, the interobserver variability among 2 independent echocardiographic laboratories in diagnosing LAAT by multiplane TEE has not yet been assessed. Methods and Results The videorecordings of 50 patients in atrial fibrillation (25 from each laboratory) were blindly reviewed by 1 experienced observer from each institution. LAAT were assessed as present, absent or questionable. Indications for TEE were: cardioversion (n=17), valve disease (n=13), endocarditis (n=12), or embolism (n=8). The prevalence of LAAT was 10% (observer 1) vs 12% (observer 2). A questionable LAAT was assessed in 6% vs 12% and a LAAT was excluded in 84% vs 76%, respectively. By head-to-head comparison, disagreement occurred in 11 cases (22%, kappa =0.5). Discrepant results were not related to the echocardiographic equipment. Problems occurred because of reverberation artifacts of the ridge between the left atrial appendage and left upper pulmonary vein (n=5), and in differentiating LAAT from spontaneous echocardiographic contrast (n=4) or an echogenic atrioventricular groove (n=1). The differentiation of pectinate muscles from LAAT was the reason for disagreement in only 1 case. Eliminating the category of questionable thrombi increased the kappa value to 0.65. In 5 patients undergoing cardiac surgery, both observers had agreed on the presence (n=1) or absence (n=4) of LAAT, and intraoperatively the results of TEE were confirmed. Conclusion Even with multiplane TEE, interobserver variability among 2 independent echocardiographic laboratories for diagnosing LAAT remains high because of problems in differentiating LAAT from spontaneous echocardiographic contrast and reverberation artifacts. (Circ J 2007; 71: 122 - 125)

Background Surgical closure of patent foramen ovale (PFO) has been considered definitive and the gold standard for preventing recurrent paradoxical embolism. However, in contrast to transcatheter PFO closure, patients undergoing operation have not systematically been re-evaluated for residual shunting. This study aimed to assess the efficacy of surgical PFO closure during follow-up by transesophageal echocardiography (TEE). Methods Eleven adult patients with diagnosis of a PFO by contrast and/or color Doppler TEE underwent PFO closure by thoracotomy and direct suturing because of paradoxical embolism (n = 4), because of impending paradoxical embolism (n = 1), or during valve operation (n = 6). Results TEE performed 5 days to 7 months after PFO closure revealed residual shunting in 8 of 11 patients (73%). The shunt size was unchanged in two patients. According to the color Doppler jet width across the atrial septum, the postoperative PFO diameter was smaller in 5 of the remaining 6 patients. Right-to-left shunting by contrast TEE, however, had newly developed (n = 1) or increased (n = 2) for patients with concomitant valve operation. Despite therapeutic anticoagulation a cerebrovascular event occurred in one patient 4 weeks after attempted PFO closure. The mechanism for persistent shunting was incomplete sealing of septum primum and septum secundum by the suture line (n = 6) or a new iatrogenic defect of the fossa ovalis caused by surgical manipulation (n = 2). In two patients a second TEE after 12 and 41 months revealed enlargement of the PFO diameter. Conclusions Surgical PFO closure can not be regarded as the gold standard for definitive treatment of interatrial shunts. Residual shunting present in a high proportion of patients may partly explain the recurrence of embolic events.

The "elimination" of the left atrial appendage (LAA) seems to be an attractive alternative to oral anticoagulation in the treatment of atrial fibrillation, especially in patients with contraindications to oral anticoagulation therapy. The LAA, however, plays an important role in the maintenance and regulation of the cardiac function, in arterial hypertension, atrial fibrillation, coronary heart disease, valvular heart disease, and heart failure. Data, mainly from animal studies, indicate that elimination of the LAA may impede thirst in patients with hypovolemia, may impair hemodynamic response to volume or pressure overload, may decrease cardiac output, and may promote heart failure. It may have adverse effects in humans as well. Further studies on the hemodynamic and neurohumoral consequences of left atrial appendage elimination are required to advance our understanding of LAA physiology and pathophysiology.

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed.

Echocardiography is frequently the initial noninvasive imaging modality used to assess patients with takotsubo cardiomyopathy (TTC). Standard transthoracic echocardiography can provide, even in the acute care setting, useful information about left ventricular (LV) morphology as well as regional and global systolic or diastolic function. It allows the differentiation of different LV morphologic patterns according to the localization of wall motion abnormalities. A "circumferential pattern" of LV myocardial dysfunction characterized by symmetric wall motion abnormalities involving the midventricular segments of the anterior, inferior, and lateral walls should be considered suggestive of TTC and included in the differential diagnosis of acute coronary syndromes. Moreover, advanced echocardiographic techniques, including speckle-tracking, myocardial contrast, and coronary flow studies, are providing mechanistic and pathophysiologic insights into this unique syndrome. Early identification of any potential complications (i.e., LV outflow tract obstruction, reversible moderate to severe mitral regurgitation, right ventricular involvement, thrombus formation, and cardiac rupture) are crucial for the management, risk stratification, and follow-up of patients with TTC. Because of the dynamic evolution of the syndrome, comprehensive serial echocardiographic examinations should be systematically performed. This review focuses on these aspects of imaging and the increasing understanding of the clinical and prognostic utility of echocardiography in TTC.