Takotsubo Cardiomyopathy With Inconspicuous Initial Electrocardiogram: A Potentially Serious Cardiac Pathology Related to Emotional Stress

Introduction: Takotsubo cardiomyopathy (TCM) is frequently associated with emotional or physical stress. Thus, patients with TCM might present primarily at a psychiatric clinic. Appropriate diagnosis and therapy may thus be delayed.Case report: A 43-year-old female patient presented as an emergency to the psychiatric outpatient clinic after experiencing severe work-related bullying. On admission, she complained of acute left thoracic chest pain as well as depressed mood, low energy, anhedonia, generalized anxiety, and sleep difficulties, present for several weeks. The initial electrocardiogram (ECG) was unremarkable; serum troponin levels, however, were markedly elevated. The patient was transferred to the department of cardiology. Via cardiac catheterization and MRI, an acute coronary syndrome was excluded and apical ballooning and left ventricular dysfunction, compatible with TCM, was found.Conclusion: Patients with acute psychopathology, recent emotional or physical stress, and acute cardiothoracic symptoms should receive immediate cardiological investigations. As the ECG may be normal in patients with TCM, concurrent measurement of the troponin serum level is recommended. Psychiatrists should consider TCM in patients who report recent stressful events accompanied by cardiothoracic symptoms

Cardiac magnetic resonance imaging for preprocedural planning of percutaneous left atrial appendage closure

IntroductionPercutaneous closure of the left atrial appendage (LAA) facilitates stroke prevention in patients with atrial fibrillation. Optimal device selection and positioning are often challenging due to highly variable LAA shape and dimension and thus require accurate assessment of the respective anatomy. Transesophageal echocardiography (TEE) and x-ray fluoroscopy (XR) represent the gold standard imaging techniques. However, device underestimation has frequently been observed. Assessment based on 3-dimensional computer tomography (CTA) has been reported as more accurate but increases radiation and contrast agent burden. In this study, the use of non-contrast-enhanced cardiac magnetic resonance imaging (CMR) to support preprocedural planning for LAA closure (LAAc) was investigated.MethodsCMR was performed in thirteen patients prior to LAAc. Based on the 3-dimensional CMR image data, the dimensions of the LAA were quantified and optimal C-arm angulations were determined and compared to periprocedural data. Quantitative figures used for evaluation of the technique comprised the maximum diameter, the diameter derived from perimeter and the area of the landing zone of the LAA.ResultsPerimeter- and area-based diameters derived from preprocedural CMR showed excellent congruency compared to those measured periprocedurally by XR, whereas the respective maximum diameter resulted in significant overestimation (p < 0.05). Compared to TEE assessment, CMR-derived diameters resulted in significantly larger dimensions (p < 0.05). The deviation of the maximum diameter to the diameters measured by XR and TEE correlated well with the ovality of the LAA. C-arm angulations used during the procedures were in agreement with those determined by CMR in case of circular LAA.DiscussionThis small pilot study demonstrates the potential of non-contrast-enhanced CMR to support preprocedural planning of LAAc. Diameter measurements based on LAA area and perimeter correlated well with the actual device selection parameters. CMR-derived determination of landing zones facilitated accurate C-arm angulation for optimal device positioning

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BackgroundCryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce.MethodsThe YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible.ResultsA total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months.ConclusionsThe incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article

Cryo-balloon catheter localization in X-Ray fluoroscopy using U-net

Purpose!#!Automatic identification of interventional devices in X-ray (XR) fluoroscopy offers the potential of improved navigation during transcatheter endovascular procedures. This paper presents a prototype implementation of fully automatic 3D reconstruction of a cryo-balloon catheter during pulmonary vein isolation (PVI) procedures by deep learning approaches.!##!Methods!#!We employ convolutional neural networks (CNN) to automatically identify the cryo-balloon XR marker and catheter shaft in 2D fluoroscopy during PVI. Training data are generated exploiting established semiautomatic techniques, including template-matching and analytical graph building. A first network of U-net architecture uses a single grayscale XR image as input and yields the mask of the XR marker. A second network of the similar architecture is trained using the mask of the XR marker as additional input to the grayscale XR image for the segmentation of the cryo-balloon catheter shaft mask. The structures automatically identified in two 2D images with different angulations are then used to reconstruct the cryo-balloon in 3D.!##!Results!#!Automatic identification of the XR marker was successful in 78% of test cases and in 100% for the catheter shaft. Training of the model for prediction of the XR marker mask was successful with 3426 training samples. Incorporation of the XR marker mask as additional input for the model predicting the catheter shaft allowed to achieve good training result with only 805 training samples. The average prediction time per frame was 14.47 ms for the XR marker and 78.22 ms for the catheter shaft. Localization accuracy for the XR marker yielded on average 1.52 pixels or 0.56 mm.!##!Conclusions!#!In this paper, we report a novel method for automatic detection and 3D reconstruction of the cryo-balloon catheter shaft and marker from 2D fluoroscopic images. Initial evaluation yields promising results thus indicating the high potential of CNNs as alternatives to the current state-of-the-art solutions

Fishing for the genetic basis of cardiovascular disease

Cardiovascular disease (CVD) has recently overtaken infectious disease to become the biggest global killer. Genetic factors have emerged as being of major importance in the pathogenesis of CVD. Owing to disease heterogeneity, variable penetrance and high mortality, human genetic studies alone are not sufficient to elucidate the genetic basis of CVD. Animal models are needed to identify novel genes that are involved in cardiovascular pathology and to verify the effect of suspected disease genes on cardiovascular function. An intriguing model organism is the zebrafish danio rerio. Several features of the zebrafish, such as a closed cardiovascular system, transparency at embryonal stages, rapid and external development, and easily tractable genetics make it ideal for cardiovascular research. Moreover, zebrafish are suitable for forward genetics approaches, which allow the unbiased identification of novel and unanticipated cardiovascular genes. Zebrafish mutants with various cardiovascular phenotypes that closely correlate with human disease, such as congenital heart disease, cardiomyopathies and arrhythmias, have been isolated. The pool of zebrafish mutants, for which the causal gene mutation has been identified, is constantly growing. The human orthologues of several of these zebrafish genes have been shown to be involved in the pathogenesis of human CVD. Cardiovascular zebrafish models also provide the opportunity to develop and test novel therapeutic strategies, using innovative technologies such as high throughput in vivo small molecule screens

Paxillin and Focal Adhesion Kinase (FAK) Regulate Cardiac Contractility in the Zebrafish Heart.

An orchestrated interplay of adaptor and signaling proteins at mechano-sensitive sites is essential to maintain cardiac contractility and when defective leads to heart failure. We recently showed that Integrin-linked Kinase (ILK), ß-Parvin and PINCH form the IPP-complex to grant tuned Protein Kinase B (PKB) signaling in the heart. Loss of one of the IPP-complex components results in destabilization of the whole complex, defective PKB signaling and finally heart failure. Two components of IPP, ILK and ß-Parvin directly bind to Paxillin; however, the impact of this direct interaction on the maintenance of heart function is not known yet. Here, we show that targeted gene inactivation of Paxillin results in progressive decrease of cardiac contractility and heart failure in zebrafish without affecting IPP-complex stability and PKB phosphorylation. However, we found that Paxillin deficiency leads to the destabilization of its known binding partner Focal Adhesion Kinase (FAK) and vice versa resulting in degradation of Vinculin and thereby heart failure. Our findings highlight an essential role of Paxillin and FAK in controlling cardiac contractility via the recruitment of Vinculin to mechano-sensitive sites in cardiomyocytes

Impact of re-definition of paroxysmal and persistent atrial fibrillation in the 2012 and 2016 European Society of Cardiology atrial fibrillation guidelines on outcomes after pulmonary vein isolation

Purpose!#!In the 2016 European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation (AF), the definition of AF type has been modified compared with the 2010 guidelines and its 2012 focused update. We compared the difference of single procedure outcomes using the definitions before and after 2016 on a cohort of patients with AF undergoing AF ablation.!##!Methods!#!Consecutive AF ablation patients with paroxysmal or persistent AF were retrospectively reclassified applying the 2010, 2012, and 2016 ESC definitions on AF type.!##!Results!#!We included a total of 628 patients. Applying the 2010 ESC AF guidelines definition, 68% of patients were paroxysmal while according to the 2016 ESC AF guidelines, the proportion increased to 87%. Applying the 2010 ESC guidelines definition, recurrence rates of paroxysmal and persistent AF patients differ significantly (log-rank p < 0.001). Applying the 2012 focused update and the 2016 ESC AF guidelines, recurrence rates do not differ significantly. In a cox regression model applying the 2010 guidelines, persistent AF is the only independent predictor of AF recurrence in our cohort. However, when applying the 2016 guidelines, persistent AF is no longer a predictor of AF recurrence.!##!Conclusions!#!The revised definition of AF types in the 2016 ESC AF guidelines leads to a marked shift from persistent to paroxysmal AF. It appears that the old definition provided a better separator to predict rhythm outcome after AF ablation

Feasibility of digital atrial fibrillation screening in an elderly population:The Ulm heart rhythm weeks

AIMS: Atrial fibrillation (AF) screening in risk populations has the potential to prevent strokes. The authors tested the feasibility of a digital program with initial photoplethysmographic (PPG) self-screening and cardiologist-attended electrocardiographic (ECG) confirmation of screen-positive cases. METHODS: Inhabitants of the city of Ulm aged ≥ 65 years were invited to participate. After digital consent, participants were given access to a smartphone application for 14 days of self-screening (two recordings per day recommended). Screen-positive participants without known AF were invited to present to a cardiologist for AF confirmation with a 14-day ECG event recorder. PPG recordings were first analyzed by algorithm using a combination of linear and non-linear methods. The quality of pathological (classified by algorithm) PPG and all ECG recordings were checked by a telecare service. Primary outcomes included adherence to the screening protocol defined as the proportion of participants performing at least 14 PPG recordings (or until documentation of absolute arrhythmia) and the proportion of pathological PPG and all ECG recordings rejected by the telecare center. RESULTS: A total of 215 participants registered. Of these, 204 (95%) performed at least one recording and 169 (79%) reached the performance target of two sufficient measurements per day; 75 PPG recordings were automatically classified as pathological by algorithm; 14 (19%) were rejected by the telecare service due to poor quality. Of the 12 participants with a suspected first diagnosis of AF, five visited a cardiologist as part of the study. Of 1090 ECG recordings obtained, 390 (36%) were qualified as non-diagnostic. AF was confirmed in three cases. CONCLUSIONS: A digital AF screening program with initial self-screening and referral of screen-positive cases to a cardiologist-attended ECG-confirmation service is feasible with meaningful results in an elderly risk population. However, the availability of the target population of persons > 65 years of age for such a digital screening program appears to be limited despite extensive public relations activities

Safety of conscious sedation in electroanatomical mapping procedures and cryoballoon pulmonary vein isolation

Immobilization of patients during electrophysiological procedures, to avoid complications by patients' unexpected bodily motion, is achieved by moderate to deep conscious sedation using benzodiazepines and propofol for sedation and opioids for analgesia. Our aim was to compare respiratory and hemodynamic safety endpoints of cryoballoon pulmonary vein isolation (PVI) and electroanatomical mapping (EAM) procedures. Included patients underwent either cryoballoon PVI or EAM procedures. Sedation monitoring included non-invasive blood pressure measurements, transcutaneous oxygen saturation (tSp

Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart

The vertebrate heart possesses autoregulatory mechanisms enabling it first to sense and then to adapt its force of contraction to continually changing demands. The molecular components of the cardiac mechanical stretch sensor are mostly unknown but of immense medical importance, since dysfunction of this sensing machinery is suspected to be responsible for a significant proportion of human heart failure. In the hearts of the ethylnitros-urea (ENU)-induced, recessive embryonic lethal zebrafish heart failure mutant main squeeze (msq), we find stretch-responsive genes such as atrial natriuretic factor (anf) and vascular endothelial growth factor (vegf) severely down-regulated. We demonstrate through positional cloning that heart failure in msq mutants is due to a mutation in the integrin-linked kinase (ilk) gene. ILK specifically localizes to costameres and sarcomeric Z-discs. The msq mutation (L308P) reduces ILK kinase activity and disrupts binding of ILK to the Z-disc adaptor protein β-parvin (Affixin). Accordingly, in msq mutant embryos, heart failure can be suppressed by expression of ILK, and also of a constitutively active form of Protein Kinase B (PKB), and VEGF. Furthermore, antisense-mediated abrogation of zebrafish β-parvin phenocopies the msq phenotype. Thus, we provide evidence that the heart uses the Integrin–ILK–β-parvin network to sense mechanical stretch and respond with increased expression of ANF and VEGF, the latter of which was recently shown to augment cardiac force by increasing the heart's calcium transients