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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.

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.

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) 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.

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.

Takotsubo cardiomyopathy (TTC) is a distinct clinical entity characterized by the presence of transient left ventricular wall dysfunction without significant culprit obstructive coronary artery disease. Invasive coronary angiography and ventriculography are the 'gold standard' for definitive diagnosis, with an integrated multi-modality imaging approach offering advantages in various clinical scenarios. Echocardiography is a widely available, first-line, non-invasive imaging technique appropriate both in emergency setting to confirm diagnosis, assess for various potential acute complications, and in serial follow-up to track myocardial recovery. Cardiac magnetic resonance (CMR) may be helpful to discriminate TTC from other acute cardiac syndromes with troponin elevation and ventricular dysfunction. Echocardiography, CMR, and nuclear imaging may also provide new insights into possible underlying pathophysiological mechanisms, and myocardial (123)I-metaiodobenzyl-guanidine imaging may have a role for retrospective diagnosis in the subacute phase of late-presenting cases. The potential diagnostic role of coronary computed tomography angiography in the emergency room requires a further study.

Cardiac MRI (CMR) has become an important tool in the diagnosis of cardiomyopathies. CMR is a unique tool for further evaluating and characterizing patients with takotsubo cardiomyopathy (TTC) and studying the underlying causes and pathophysiologic mechanisms of TTC. Using CMR, regional wall motion abnormalities, right ventricular involvement, intraventricular thrombi, and reversible myocardial injury (inflammation or ischemic edema) or irreversible myocardial injury (necrosis or fibrosis) can be detected in patients presenting with TTC. CMR imaging can distinguish between acute myocardial infarction and TTC.

Takotsubo cardiomyopathy (TTC) predominantly occurs in elderly women. Men comprise 10% of the patients, with a similar clinical profile. In contrast to myocardial infarction, age distribution; symptoms, such as angina; and prehospital delay in TTC are not different between genders. In men, physical stress as a triggering event and shock or cardiac arrest on presentation are more frequent. Gender-related differences in TTC need to be carefully investigated at the clinical and experimental levels to explain the evident gender discrepancy in the prevalence of TTC, to clarify the pathogenetic background, and to develop preventive and therapeutic means against this life-threatening disease.

Transesophageal echocardiography (TEE) is accepted as the method of choice for the diagnosis of the patent foramen ovale (PFO). However, direct anatomic confirmation regarding the presence or absence of a PFO on transesophageal imaging has been obtained in only a limited number of patients. Consequently, this study was performed to assess the diagnostic accuracy of contrast and color Doppler TEE for detection of a PFO by comparing the results of TEE with autopsy. The study population comprised 35 consecutive patients (mean age 64 +/- 14 years) who underwent autopsy and prior TEE with examination of the atrial septum. For diagnosis of a PFO, the following criteria were used: (1) no defect in the continuity of the atrial septum on 2-dimensional imaging; (2)or = 1 bright microbubble appearing in left the atrium within 3 heart cycles after opacification of the right atrium during contrast TEE; and (3) turbulent color jet within the atrial septum by color Doppler TEE. For estimating the PFO size, positive contrast studies were graded semiquantitatively (from 1 to 3), and the maximal color Doppler jet width was measured within the atrium septum at the area of maximal turbulence. At autopsy, a PFO was present in 9 of 35 patients (26%). All were correctly diagnosed by color Doppler TEE. The color Doppler jet width correlated well with the PFO diameter determined at autopsy (r=0.99, SEE=0.51 mm, p0.0001). By contrast TEE, 8 of the 9 patients with autopsy-proven PFO were correctly identified. In 1 case with left heart disease and a long interatrial channel, a PFO was missed by contrast TEE but clearly demonstrated by color Doppler TEE. All patients with a PFO diameter10 mm showed intense left atrial opacification of grade 3. With both methods, there were no false-positive results. Sensitivity and specificity for diagnosis of a PFO were 89% and 100% respectively, for contrast TEE, and both 100% for color Doppler TEE. Thus, contrast and color Doppler TEE are complementary and represent a highly sensitive and specific method for diagnosis of a PFO and for estimation of the PFO size.

To the Editor: With interest we read the article of Medi et al about stroke risk and antithrombotic strategies in atrial fibrillation.1 We have several comments on the emerging therapies to prevent stroke that are mentioned in the article: 1. Achieving good control of international normalized ratio (INR) values is a matter of concern in patients undergoing therapy with vitamin K antagonists. A subanalysis of the ACTIVE trial has shown that considerable national differences exist in the quality of oral anticoagulation (OAC).2 Most probably, these differences are caused by organization of the health care system and by differences in the reimbursement of physicians and institutions who take care of patients on vitamin K antagonists. Thus, an improvement in the quality of OAC is a matter of public health, and initiatives …

Transthoracic and transesophageal echocardiography was performed in 40 consecutive adult patients with an atrial septal aneurysm. In 11 (27%) of 40 patients transthoracic echocardiography failed to demonstrate the lesion and the diagnosis was established by the transesophageal approach only. Interatrial shunting, assessed by echocardiographic contrast study and/or color flow mapping, was detected in 13 (54%) of 24 patients on transthoracic imaging and in 29 (76%) of 38 patients during transesophageal echocardiography. Identification of multiple fenestrations (n = 9) and thrombi within the aneurysm (n = 2) could be achieved only by transesophageal ultrasound. A cerebrovascular event of suspected embolic origin occurred in 20 (50%) of 40 patients; 11 (55%) of the 20 patients had repeated cerebral events. Except for mitral valve prolapse in 2 patients and spontaneous left atrial contrast phenomenon in 1 patient no other potential cardiac source of embolism could be identified by transesophageal echocardiography. A marked thickening of the aneurysm was present in 14 (70%) of 20 patients with a cerebrovascular event versus only 4 (20%) of 20 patients without a cerebrovascular event (p less than 0.01). The mechanism of embolization may be both primary thrombus formation within the aneurysm and paradoxical embolization through an interatrial communication as suggested by the findings on transesophageal ultrasound in 2 patients. Although the patients of this study represent a highly selected group it may be concluded that atrial septal aneurysm is a cardiac abnormality with embolic potential. Transesophageal echocardiography has to be regarded the imaging method of choice for evaluation of this lesion.

To the Editor: With great interest we have read the report by Hara et al about patent foramen ovale (PFO) closure using radiofrequency thermal coaptation.1 However, there remain several questions. 1. In the introduction it is stated that the number of indications for PFO closure increases. But, as recently emphasized by the US Food and Drug Administration, at present no randomized trial examining the efficacy of PFO device closure exists.2 2. Different echocardiographic criteria exist for diagnosing a PFO.3 …

To the Editor: With great interest we read the article by Onalan et al about left atrial appendage (LAA) exclusion for stroke prevention in nonrheumatic atrial fibrillation (AF).1 We share the author’s concerns about the hazards of this procedure and would like to emphasize additional arguments. There is no evidence that thromboembolism in AF exclusively derives from LAA thrombi detected by transesophageal echocardiography. The prevalences (4% to 21%) of LAA-thrombi were found in studies of acutely sick patients, patients before cardioversion, cardiac surgery or after recent embolism. Contrarily, when prospectively investigating clinically stable outpatients with AF and no recent embolism by transesophageal echocardiography, the prevalence of LAA thrombi was only …

With interest we read the article by Beyer-Westendorf et al. 1 about drug persistence with rivaroxaban therapy in atrial fibrillation patients—results from the Dresden non-interventional oral anticoagulation registry. In the registry, 1204 rivaroxaban-treated patients with atrial fibrillation were observed during a mean time of 544 days. The discontinuation rate of rivaroxaban was 15% in the first year of treatment, and thus lower than in previous studies investigating patients treated with vitamin K antagonists (VKAs). We have the following questions and concerns: How did the authors ascertain that the patients were indeed taking the drug? Whereas adherence to VKA is easily monitored by measuring the international normalized ratio (INR), a test for rivaroxaban effect is not available. Were …

In ihrem Beitrag in DMW 10 / 2015 fassen Hohnloser et al. 6 die Ergebnisse von DOAK-Studien zusammen, deren Autoren mehrheitlich Angestellte der Herstellerfirma waren oder einen Interessenskonflikt angaben 3 4 9 . Inzwischen sind unabhangige Publikationen zu DOAK-assoziierten Nebenwirkungen und Komplikationen erschienen, die von Vitamin-K-Antagonisten (VKA) selten oder gar nicht berichtet wurden 1 10 12 15 16 .

Tako-tsubo-like left ventricular dysfunction phenomenon (TTP) is characterized by transient left ventricular apical ballooning associated with symptoms, electrocardiographic changes and minimal cardiac enzyme release in the absence of coronary artery disease. Initially described in Japan, TTP occurs worldwide, predominantly in women and frequently after emotional or physical stress. Symptoms include anginal chest pain, dyspnea and syncope. Electrocardiographic ST elevations may be present only for several hours, and are followed by negative T waves that persist for months. Arterial hypertension is found in up to 76% of TTP patients, hyperlipidemia in up to 57% and diabetes mellitus in up to 12%. Potential pathophysiological mechanisms for TTP include catecholamine-induced myocardial stunning or hyperkinesis of the basal left ventricular segments, coronary vasospasm, plaque rupture, myocarditis and genetic factors. TTP patients should be monitored similarly to myocardial infarction patients because organ failure, cardiogenic shock, ventricular fibrillation or rupture may occur. Beta-blockers are indicated, whereas catecholamines and nitrates should be avoided. The long-term prognosis is unknown.

Background: Closure of the fibrillating left atrial appendage (LAA) has been recommended during valve surgery to decrease the risk of arterial embolism. However, patients undergoing surgical LAA closure have not systematically been reevaluated for complete LAA obliteration. Methods and Results: During a 12-month period, we studied 6 consecutive patients with paroxysmal (n = 3) or permanent (n = 3) atrial fibrillation who underwent surgical LAA closure at the time of valve surgery. Transesophageal echocardiography (TEE) performed 23–159 days (mean 51) postoperatively demonstrated complete LAA closure in only 1 patient. In 5 patients, incomplete LAA closure was found due to disruption of the closure line. The size of the residual LAA orifice ranged from 3 to 20 mm. There was a high flow velocity at the LAA orifice (0.33–2.2 m/s), whereas flow in the LAA body was low (Conclusion: Surgical LAA closure was incomplete in most patients, resulting in blood stagnation and an increased likelihood of clot formation. Incomplete surgical LAA closure, therefore, may promote rather than reduce the risk of stroke. Intraoperative TEE is mandatory to verify complete LAA obliteration.

To the Editor: Percutaneous left atrial appendage (LAA) transcatheter occlusion (PLAATO) has been suggested to prevent stroke in high-risk patients with atrial fibrillation (AF).1 PLAATO is performed by implanting a novel device via transseptal catheterization into the LAA to seal it.1 Because more than 90% of thrombi are located within the LAA in AF, occlusion of the LAA seems an attractive alternative to oral anticoagulation (OAC), especially in AF patients who are not suitable candidates for OAC. However, performing PLAATO in patients with AF raises several concerns: 1) it is not known whether LAA thrombi are responsible for the increased number of thromboembolic events in patients with AF; atrial, ventricular, or aortic thrombi might also be important sources of arterial embolism; 2) hypercoagulability reported in patients with AF2 will not be treated by the PLAATO technique; 3) it …

The prevalence of a patent foramen ovale (PFO) as assessed by transesophageal contrast echocardiography varies considerably among echocardiographic laboratories (ranging from 8 to 54%). 1–3 This striking difference may be due to several reasons: (1) the population studied (age, healthy persons versus patients, history of embolism); (2) the technique used (contrast agent, provocative maneuvers, ultrasonic instrumentation including transducer frequency); and (3) the criteria applied for diagnosis. The aim of the present study was to clarify some of these factors by assessing the interobserver variability of 2 independent echocardiographic laboratories in diagnosing PFO by transesophageal contrast echocardiography.

LA Compartmentalization for AF Prevention. Introduction: Right atrial compartmentalization has been demonstrated to only reduce the number of atrial fibrillation (AF) episodes: left atrial (LA) fibrillation still occurs. Methods and Results: We report successful LA compartmentalization resulting in isolation of all four pulmonary veins in a 51-year-old woman suffering from paroxysmal AF. Deployment of a complete encircling line resulted in dissociation of electrical activation within the isolated area from the remaining LA. Despite attempts al reinduction by pacing maneuvers inside and outside the isolated area, AF was no longer inducible. During 2l-week follow-up, the patient remained in stable sinus rhythm with rare atrial extrasystoles. Conclusion: If reproducible, this ablation strategy could allow treatment of AF independent of suppression of any triggering event.

An association of atrial septal aneurysm (ASA) with cardiac arrhythmias has been described, and it has been suggested that undulating movements of the aneurysm initiate these arrhythmias, thereby causing arterial embolism. In this prospective study, all available electrocardiograms were reviewed and Holter monitoring was performed in 50 consecutive patients with echocardiographic diagnosis of ASA in order to assess the relationship between the occurrence of arrhythmias, morphologic characteristics of ASA and arterial embolism. Significant arrhythmias were identified in 26 (52%) patients (supraventricular n = 15, ventricular n = 6, both n= 5). Patients with arrhythmias were older (65 ± 12 vs. 54 ± 13 years, p = 0.005), frequently had palpitations (21/26 vs. 1/24, p < 0.0001) and an abnormal resting electrocardiogram (18/26 vs. 5/24, p < 0.001). By echocardiography, patients with arrhythmias had a larger left atrial (42.8 ± 7.4 vs. 35.3 ± 4.6 mm, p < 0.0001) and left ventricular enddiastolic diameter (53.8 ± 5.6 vs. 49.7 ± 4.1, p < 0.01) and a higher prevalence of associated mitral valve prolapse (12/26 vs. 4/24, p = 0.05). Potential cardiovascular causes for arrhythmia other than ASA were present in the great majority of patients with documented arrhythmias (24/26 vs. 7/24, p < 0.0001). The base diameter of ASA was larger in patients with arrhythmias (25.5 ± 6.2 vs. 21.4 ± 3.4, p < 0.01) and correlated with a larger left atrial diameter (r = 0.72, p < 0.0001). Concerning the mobility of ASA (maximal protrusion or phasic excursion), there was no significant difference between the two patient groups. Arterial embolism, however, predominantly occurred in ASA patients without arrhythmias (16/24 vs. 9/26, p < 0.05). In conclusion, the majority of patients with ASA and arrhythmias has underlying structural heart disease other than ASA which may be responsible for the arrhythmias observed. Arrhythmias in association with ASA do not play a major role as a mechanism for arterial embolism.

Left atrial appendage (LAA) elimination is regarded to protect patients with atrial fibrillation (AF) from stroke or embolism. The Watchman occluder is a device for percutaneous LAA occlusion and is at present investigated in the PROTECT AF trial. In a 78-year-old man, embolization of the Watchman device occurred 10 minutes after implantation. At emergency cardiac surgery, the device was removed from the aortic valve and an aortic bioprosthesis and a pacemaker had to be implanted. One year postoperatively, he still suffers from heart failure. This case shows that percutaneous LAA occlusion may result in serious complications.