Percutaneous left atrial appendage occlusion for stroke prevention in atrial fibrillation: an update.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. One of its most devastating complications is the development of thromboembolism leading to fatal or disabling stroke. Oral anticoagulation (OAC, warfarin) is the standard treatment for stroke prevention in patients with AF with an increased stroke risk. However, there are several obstacles to long-term OAC therapy, including the risk of serious bleeding, several drug-drug interactions and the need for frequent blood testing. Although newer oral anticoagulants have been developed, these drugs also face issues of major bleeding and non-compliance. Therefore, alternative treatment options for stroke prevention in patients with AF with a high stroke risk are needed. Percutaneous left atrial appendage (LAA) occlusion is an evolving therapy, which should be taken into consideration in those patients with non-valvular AF with a high stroke risk and contraindications for OAC. This article aims to discuss the rationale for LAA closure, the available LAA occlusion devices and their clinical evidence until now. Moreover, we discuss the importance of proper patient selection, the role of various imaging techniques and the need for a more tailored postprocedural antithrombotic therapy.

Cardiac remodeling following percutaneous mitral valve repair - initial results assessed by cardiovascular magnetic resonance imaging.

PURPOSE: Percutaneous mitral valve repair with the MitraClip device (Abbott Vascular, Redwood City, California, USA) is a novel therapeutic option in patients with mitral regurgitation. This study evaluated the feasibility of cardiac volume measurements by cardiovascular magnetic resonance imaging (CMR) to assess reverse myocardial remodeling in patients after MitraClip implantation. MATERIALS AND METHODS: 12 patients underwent CMR at baseline (BL) before and at 6 months follow-up (FU) after MitraClip implantation. Cine-CMR was performed in short- and long-axes for the assessment of left ventricular (LV), right ventricular (RV) and left atrial (LA) volumes. RESULTS: Assessment of endocardial contours was not compromised by the device-related artifact. No significant differences in observer variances were observed for LV, RV and LA volume measurements between BL and FU. LV end-diastolic (median 127 [IQR 96 - 150] vs. 112 [86 - 150] ml/m(2); p = 0.03) and LV end-systolic (82 [54 - 91] vs. 69 [48 - 99] ml/m(2); p = 0.03) volume indices decreased significantly from BL to FU. No significant differences were found for RV end-diastolic (94 [75 - 103] vs. 99 [77 - 123] ml/m(2); p = 0.91), RV end-systolic (48 [42 - 80] vs. 51 [40 - 81] ml/m(2); p = 0.48), and LA (87 [55 - 124] vs. 92 [48 - 137] ml/m(2); p = 0.20) volume indices between BL and FU. CONCLUSION: CMR enables the assessment of cardiac volumes in patients after MitraClip implantation. Our CMR findings indicate that percutaneous mitral valve repair results in reverse LV but not in RV or LA remodeling. KEY POINTS: • Volume measurements by cardiovascular magnetic resonance imaging are feasible following percutaneous mitral valve repair despite device-related artifacts.• A significant reduction of left ventricular volume was found in terms of beneficial, reverse left ventricular remodeling after 6-month follow-up.• No significant reduction was found in right ventricular or left atrial volumes after percutaneous mitral valve repair after 6-month follow-up.

Percutaneous interventional mitral regurgitation treatment using the Mitra-Clip system.

The interventional treatment of mitral valve regurgitation by the MitraClip procedure has grown rapidly in Germany and Europe during the past years. The MitraClip procedure has the potential to treat high-risk patients with secondary mitral valve regurgitation and poor left ventricular function. Furthermore, patients with primary mitral valve regurgitation may be treated successfully by the MitraClip procedure in case of high surgical risk or in very old patients. At the same time it has been emphasised that the MitraClip interventional treatment is still at an early stage of clinical development. The largest clinical experience with the MitraClip procedure so far is probably present in some German cardiovascular centers, which here summarise their recommendations on the current indications and procedural steps of the MitraClip treatment. These recommendations of the AGIK and ALKK may present a basis for future development.

Percutaneous edge-to-edge mitral valve repair. Current clinical evidence with the MitraClip System.

In the past few years, a myriad of technologies have been developed for percutaneous repair of the mitral valve for patients with severe mitral regurgitation (MR) and at high risk for traditional open-heart mitral valve surgery. Among them, MitraClip has emerged as the only clinically safe and effective method for percutaneous mitral valve repair. This device mimics the surgical edge-to-edge mitral valve repair initially described by Dr. Alfieri. In this article, we review the current clinical evidence on the use of the MitraClip--from the randomized control trial EVEREST II to the information derived from expert high-volume centers.

Current state of percutaneous transcatheter mitral valve therapies.

Mitral valve regurgitation (MR) is a frequent condition usually associated with heart failure and reduced survival. Surgery remains the gold standard treatment but a significant number of patients are not optimal candidates due to age, comorbidities or poor left ventricular function. In this subgroup of patients transcatheter mitral interventions have emerged as an alternative to offer improvement of symptoms and increase survival. MitraClip ® is the device with the largest clinical experience and it has been demonstrated to provide clinical benefit in selected patients. However, mitral apparatus is a complex scenario and there are several potential targets for improving mitral regurgitation. The aim of this paper was to review the current trnascatheter technology developed to treat MR.

Transcatheter aortic valve implantation in a heart transplant recipient: a case report.

Transcatheter aortic valve implantation (TAVI) has evolved into a feasible therapeutic option for the management of selected patients with severe aortic stenosis and high or prohibitive risk for standard surgery. Symptomatic severe aortic stenosis occasionally occurs in the allograft long after heart transplantation. Because of specific characteristics and comorbidities of heart transplant recipients, these patients may be considered candidates for this less invasive approach. We report a first case of successful transapical TAVI in a heart transplant recipient with symptomatic severe calcific aortic valvular disease and relevant comorbidities long after heart transplantation.

Assessment of functional anatomy of the mitral valve in patients with mitral regurgitation with cine magnetic resonance imaging: comparison with transesophageal echocardiography and surgical results.

The ability of magnetic resonance imaging (MRI) to accurately define the functional anatomy of mitral regurgitation was assessed. Transesophageal echocardiography (TEE) and cine MRI were performed on 43 patients with mitral regurgitation and were compared for the jet number, location, direction and presence of a prolapse (atrial displacement, malapposition or a flail). In 36 patients, diagnostic accuracy in reference to surgery was assessed. Comparing TEE and MRI the jet number and location were judged in concordance in 86% of patients. Jet location did not show a significant difference (Wilcoxon: P = 0.66) and both modalities correlated strongly (Spearman: r = 0.68, P<0.0001). Jet direction was judged with high concordance (kappa=0.63). Additionally, prolapse evaluation showed high concordance (kappa: valve, 0.63; anterior mitral leaflet, 0.70; posterior mitral leaflet, 0.73). Compared with surgery, the sensitivity for the detection of malapposition of any leaflet or one of both leaflets ranged between 75% and 93% for TEE and 71% and 89% for MRI. Specificities ranged between 88 and 96% for TEE and 88 and 100% for MRI. TEE detected torn chordae in all ten patients, six of which were missed by MRI. MRI is comparable with TEE in prolapse and jet evaluation. MRI is inferior to TEE in depicting anatomical details such as torn chordae.

Coronary artery anomalies Part II: recent insights from clinical investigations.

Congenital anomalies of the coronary arteries occur in 0.2-1.2% of the general population; they cause 12% of sports-related sudden cardiac deaths and 1.2% of non-sports-related deaths. We review some of the substantial advances that have been made both, in the understanding of the embryonic development of the coronary arteries and in the clinical diagnosis and management of their anomalies. In this second part of our review we elucidate recent approaches to defining coronary anomalies and provide information on their incidence and prognosis. In addition, we discuss the options for screening large populations for potentially lethal coronary malformations and elucidate the role of invasive diagnostic modalities such as intravascular ultrasound, flow wire and pressure wire. The clinical relevance of coronary anomalies is discussed particularly for the ill-defined group of anomalies that only occasionally cause severe clinical events comprising anomalous origination of a coronary artery from the opposite sinus (ACAOS), coronary artery fistulae and myocardial bridging. Finally, we provide an update on current diagnostic and therapeutic recommendations.

[Improved analysis of left ventricular function using three-dimensional echocardiography]. / Verbesserte Beurteilung der linksventrikulären Funktion mittels 3D-Echokardiographie.

Left ventricular geometry and function are important pathophysiologic and prognostic parameters. However, especially in patients with cardiac pathologies left ventricular geometry can be complex. Quantification of left ventricular volumes using conventional two-dimensional echocardiography is only possible when simplifying assumptions of left ventricular geometry are made. In contrast three-dimensional echocardiography allows direct quantification of left ventricular volumes even in complex distortions of left ventricular shape. The availability of real-time three-dimensional echocardiography has brought this technique into clinical practice. Three-dimensional echocardiography is a technique that may be used as a routine echocardiographic method in the near future.

Coronary artery anomalies. Part I: Recent insights from molecular embryology.

Congenital anomalies of the coronary arteries occur in 0.2-1.2% of the general population and may cause substantial cardiovascular morbidity and mortality. We review some of the advances that have been made both, in the understanding of the embryonic development of the coronary arteries (part I) and in the clinical diagnosis and management of their anomalies (part II). In this first part of our review we elucidate basic mechanisms of coronary vasculogenesis, angiogenesis and embryonic arteriogenesis. Moreover, we review the role of cellular progenitors such as epicardium-derived cells, cardiac neural crest cells and cells of the peripheral conduction system. Then we discuss the role of growths factors (such as FGV, HIF 1, PDGF B, TGFbeta1, VEGF, and VEGFR-2) and genes (such as FOG-2, VCAM-1, Bves, and RALDH2) at different states of coronary development. and we discuss the role of the cardiac neural crest in the concurrence of coronary anomalies with aortic root malformations. This part of the article is designed to review major determinants of coronary vascular development to provide a better understanding of the multiplicity of options and mechanisms that may give rise to coronary anomaly. To this end, we highlight results from experiments that provide insight in mechanisms of coronary malformation.

Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia.

Learning in neuronal networks occurs by instructions to the neurons to change their synaptic weights (i.e., efficacies). According to the present model a molecular mechanism that can contribute to change synaptic weights may be represented by multiple interactions between membrane receptors forming aggregates (receptor mosaics) via oligomerization at both pre- and post-synaptic level. These assemblies of receptors together with inter alia single receptors, adapter proteins, G-proteins and ion channels form the membrane bound part of a complex three-dimensional (3D) molecular circuit, the cytoplasmic part of which consists especially of protein kinases, protein phosphatases and phosphoproteins. It is suggested that this molecular circuit has the capability to learn and store information. Thus, engram formation will depend on the resetting of 3D molecular circuits via the formation of new receptor mosaics capable of addressing the transduction of the chemical messages impinging on the cell membrane to certain sets of G-proteins. Short-term memory occurs by a transient stabilization of the receptor mosaics producing the appropriate change in the synaptic weight. Engram consolidation (long-term memory) may involve intracellular signals that translocate to the nucleus to cause the activation of immediate early genes and subsequent formation of postulated adapter proteins which stabilize the receptor mosaics with the formation of long-lived heteromeric receptor complexes. The receptor mosaic hypothesis of the engram formation has been formulated in agreement with the Hebbian rule and gives a novel molecular basis for it by postulating that the pre-synaptic activity change in transmitter and modulator release reorganizes the receptor mosaics at post-synaptic level and subsequently at pre-synaptic level with the formation of novel 3D molecular circuits leading to a different integration of chemical signals impinging on pre- and post-synaptic membranes hence leading to a new value of the synaptic weight. Engram retrieval is brought about by the scanning of the target networks by the highly divergent arousal systems. Hence, a continuous reverberating process occurs both at the level of the neural networks as well as at the level of the 3D molecular circuits within each neuron of the network until the appropriate tuning of the synaptic weights is obtained and, subsequently, the reappearance of the engram occurs. Learning and memory in the basal ganglia is discussed in the frame of the present hypothesis. It is proposed that formation of long-term memories (consolidated receptor mosaics) in the plasma membranes of the striosomal GABA neurons may play a major role in the motivational learning of motor skills of relevance for survival. In conclusion, long-lived heteromeric receptor complexes of high order may be crucial for learning, memory and retrieval processes, where extensive reciprocal feedback loops give rise to coherent synchronized neural activity (binding) essential for a sophisticated information handling by the central nervous system.

[Diagnosis and therapy of infectious endocarditis. What measures are required?]. / Diagnostik und Therapie der infektiösen Endokarditis. Welche Massnahmen sind erforderlich?

Infectious endocarditis remains a potentially life-threatening disease, the outcome of which can be substantially influenced by rapid diagnosis and initiation of suitable treatment. Leading clinical features are fever, a new sound suggestive of valvular insufficiency and, when the course is subacute, anemia. The main diagnostic procedures are transthoracic and transesophageal echocardiography that reliably identify vegetation, valvular insufficiency and abscess. Of decisive importance for treatment and prognosis is the rapid identification of the pathogen by means of blood culture and, if necessary, serologic and molecular-biologic measures. Antimicrobial treatment is applied in accordance with the recommendations of the American Heart Association. Surgical treatment is indicated in the event of refractory infection, severe valvular insufficiency with heart failure, valve avulsion, recurrent emboli or large floating vegetation with an elevated risk of embolism.

Oscillation of pain intensity during adenosine infusion. Relationship to beta-endorphin and sympathetic tone.

Adenosine is a neuromodulator with both excitatory and inhibitory effects dependent in part upon preconditions; it can act as an algesic or an analgesic agent. Previously we found variations of pain intensity during constant infusion of adenosine. We therefore quantified pain intensity during constant infusion of adenosine at a rate of 140 microg/kg/min intravenously in healthy volunteers, placebo controlled, double blind, and the relation to hemodynamic, vasomotor and sudomotor responses of the sympathetic nervous system and to the role of peripheral beta-endorphin response. The perceived chest pain during adenosine infusion showed an oscillatory pattern. Painful periods of about 30s were interrupted by painfree periods, and pain was always preceded by an increase in vasomotor sympathetic activity and by increased sudomotor activity. Plasma beta-endorphin values were heterogenous but exhibited an increase during infusion.

Pulpal ischemia in man: effects on detection threshold, A-delta neural response and sharp dental pain.

Preferential blocks of peripheral nerves have shown that myelinated nerves are more susceptible to local compression and less resistant to asphyxia than unmyelinated fibers. Since two groups of functionally different nociceptors exist in the dental pulp, it is of theoretical and clinical interest to determine the influence of ischemia on the sensitivity of human dental pulp, using standard means for testing tooth vitality and at the same time investigating the intensity coding in one pathway of the afferent trigeminal system. Adrenaline was used to study the differential effect of adrenaline-induced ischemia on intradental A-delta nerve activity (INA) and the concomitant sharp pain, as well as on the detection threshold for monopolar electrical stimulation. Cold (ethyl chloride) and heat (heated gutta-percha) stimulation was applied to the tooth surface. In accordance with the hydrodynamic theory of dentin sensitivity the rapid fluid flow induced in the dentinal tubuli by these thermal stimuli is an adequate stimulus for selectively activating the A-delta nerves in healthy pulps. Consistency plots of the magnitude of the perceptual experience of sharp pain against the neural population response in linear coordinates yielded a high product-moment correlation, implying linearity for the intensity coding relationship. In contrast to the significant reduction of INA and its perceptual correlate of sharp pain after adrenaline administration, the electrical detection threshold remained constant during the full test period, suggesting that electrical threshold measurements have their limitations as a diagnostic tool or criterion for assessing the sensitivity of the dental pulp. The absence of A-delta activity was parallelled by no sensation of sharp pain. These findings suggested that the integrated neural A-delta activity constituted the underlying peripheral neurophysiological mechanism of the sensory intensity of sharp dental pain.

Percutaneous closure of secundum atrial septal defect with a new self centering device ("angel wings").

OBJECTIVE: To investigate the safety, efficacy, and clinical application of a new self centering device ("angel wings") for closure of secundum atrial septal defects (ASD II) and persistent foramen ovale in all age groups. DESIGN: Multicentre, prospective, nonrandomised study. INCLUSION CRITERIA: defects with an occlusive diameter of < or = 20 mm and a surrounding rim of > 4 mm; body weight > 10 kg; and an indication for surgical closure of secundum atrial septal defect. Additionally, there were compassionate indications for closure in patients with persistent foramen ovale. INTERVENTIONS: Defects were closed by a transcatheter device consisting of two square frames made of superelastic nitinol wire. The frames are covered by elastic polyester fabric, which is sewn together at a central circle. All procedures, except for three interventions that were carried out under sedation, were performed under general anaesthesia using transoesophageal echocardiography and fluoroscopy to monitor intervention. RESULTS: Closure was attempted in 75 (71%) of 105 patients. An ASD II was present in 35 children and 15 adults. A persistent foramen ovale was present in 25 adults with suspected paradoxical embolism. Transcatheter closure was unsuccessful in three children and crossover to surgery was required. Residual shunts were found in 20 patients (27%) immediately after the procedure. A transient atrioventricular third degree block occurred in three patients (4%) and the right atrial disk was not fully deployed in three. A minor shunt (< 3 mm) was present in only three (4%) of 72 patients during follow up of 1-17 months. Blood clots on the right atrial disks in two patients (one required lysis) were seen during follow up transoesophageal echocardiography. Serious complications demanding surgical removal of the device occurred in three patients. One patient had haemopericardial tamponade because of an aortic lesion. Left atrial thrombus formation due to an unfolded right atrial disk was found in a second patient and dislodgement of the left atrial disk resulted in a large residual shunt in a third. CONCLUSIONS: Percutaneous closure of a central ASD with a diameter < or = 20 mm in paediatric and adult patients is feasible and effective with this new device. It is a promising alternative to surgical closure. Modifications of the design, however, seem to be mandatory as 4% of patients developed serious complications.

Reduced activity in the extrastriate visual cortex of individuals with strabismic amblyopia.

In order to examine the relationship between reduced visual acuity in human strabismic amblyopia and the cortical activation pattern, we studied, by use of positron emission tomography (PET) and the H2(15)O bolus technique, changes in the regional cerebral blood flow (rCBF) induced by monocular visual stimulation of 8 individuals with this disorder. Individual amblyopic thresholds for monocular detection of the checkerboard pattern were employed as stimuli for both eyes during PET scans. Statistical analysis of subtracted images showed significant increases in rCBF (P < 0.05) by the stimulation of the sound eye localized bilaterally to Brodmann's areas (BAs) 17-19. The cortical response evoked by the amblyopic eye was significantly reduced (P < 0.05) in the ipsilateral BAs 18, 19. These results suggest that the reduction in contrast sensitivity (pattern vision) in amblyopia is coupled with deactivation in identifiable regions of occipital visual areas, including ipsilateral BAs 18,19.