Functional and topographic concordance of right atrial neural structures inducing sinus tachycardia.

Cardiorespiratory autonomic control is in tight interaction with an intracardiac neural network modulating sinus node function. To gain novel mechanistical insights and to investigate possible novel targets concerning the treatment of inadequate sinus tachycardia, we aimed to characterize functionally and topographically the right atrial neural network modulating sinus node function. In 16 sheep 3-dimensional electro-anatomical mapping of the right atrium was performed. In five animals additionally magnetically steered remote navigation was used. Selective stimulation of nerve fibers was conducted by applying high frequency (200 Hz) electrical impulses within the atrial refractory period. Histological analysis of whole heart preparations by acetylcholinesterase staining was performed and compared to the acquired neuroanatomical mapping.We found that neural stimulation in the cranial part of the right atrium, within a perimeter around the sinus node area, elicited predominantly shortening of the sinus cycle length of -20.3 ± 10.1 % (n = 80, P < 0.05). Along the course of the crista terminalis atrial premature beats (n = 117) and atrial fibrillation (n = 123) could be induced. Catheter stability was excellent during remote catheter navigation. Histological work-up (n = 4) was in accord with the distribution of neurostimulation sites. Ganglions were mainly innervated by the dorsal right-atrial subplexus, with substantial additional input from the ventral right atrial subplexus. In conclusion, our findings suggest a functional and topographic concordance of right atrial neural structures inducing sinus tachycardia. This might open up new avenues in the treatment of heart rate related disorders.

Super-selective electrical stimulation of the left ventricle via a miniaturized magnetized stimulation wire: proof of concept study.

Cardiac resynchronization therapy provides a treatment option for patients with congestive heart failure. Electrodes are usually advanced via the cardiac venous system (CVS). Placement is often hampered by small vessel diameter or tortuosity. The aim of this study was to develop and test a magnetized stimulation wire (MSW) capable of being navigated into small and tortuous CVS branches. Therefore, a conventional guide wire with a permanent magnet and a single stimulation electrode at its tip was coated with iridium oxide at the distal end and insulated except for the very tip (coating thickness: 500 nm, active uncoated area: 10 mm(2)). The MSW was designed to allow for a remote magnetic steering using a magnetic navigation system (MN) (Stereotaxis™). After in vitro testing of the electrical properties, the MSW was tested in an animal model (n=6 sheep): the MSW was placed in a CVS side branch and navigation characteristics of the MSW were determined. The effective (unipolar) pacing threshold was 4.9±2.4 V (at 2 ms pulse width). The rheobase was 1.89±0.44 V and the chronaxie time was 0.75±0.7 ms. The MSW could be navigated into small CVS branches with reasonable MN properties. This could allow stimulation at CVS sites currently not accessible for conventional stimulation catheters or electrodes.

Augmentation of left ventricular contractility by cardiac sympathetic neural stimulation.

BACKGROUND: Electric stimulation of mediastinal sympathetic cardiac nerves increases cardiac contractility but is not selective for the left ventricle because it elicits sinus tachycardia and enhanced atrioventricular conduction. The aim of this study was to identify sympathetic neural structures inside the heart that selectively control left ventricular inotropy and can be accessed by transvenous catheter stimulation. METHODS AND RESULTS: In 20 sheep, high-frequency stimulation (200 Hz) during the myocardial refractory period with electrode catheters inside the coronary sinus evoked a systolic left ventricular pressure increase from 97+/-20 to 138+/-32 mm Hg (P<0.001) without changes in sinus rate or PR time. Likewise, the rate of systolic pressure development (1143+/-334 versus 1725+/-632 mm Hg/s; P=0.004) and rate of diastolic relaxation (531+/-128 versus 888+/-331 mm Hg/s; P=0.001) increased. The slope of the end-systolic pressure-volume relationship increased (2.3+/-0.8 versus 3.1+/-0.6 mm Hg/mL; P=0.04), as did cardiac output (3.5+/-0.8 versus 4.4+/-0.8 L/min; P<0.001). Systemic vascular resistance and right ventricular pressure remained unchanged. There was a sigmoid dose-response curve. Ultrasound analysis revealed an increase in circumferential and radial strain in all left ventricular segments that was significant for the posterior, lateral, and anterior segments. Pressure effects were maintained for at least 4 hours of continued high-frequency stimulation and abolished by beta1-receptor blockade. Histology showed distinct adrenergic nerve bundles at the high-frequency stimulation site. CONCLUSIONS: Cardiac nerve fibers that innervate the left ventricle are amenable to transvenous electric catheter stimulation. This may permit direct interference with and modulation of the sympathetic tone of the left ventricle.

Integration of automatic intrathoracic fluid content measurement into clinical decision making in patients with congestive heart failure.

BACKGROUND: Hospitalizations due to decompensation are a frequent problem in treating patients with congestive heart failure (CHF). Continuous impedance measurement via implantable devices may detect pulmonary fluid accumulation due to worsening CHF. An acoustic alert might allow an earlier treatment of impending decompensation. An algorithm that implemented impedance measurement into clinical decision making in treating CHF patients was evaluated. METHODS: Forty-two CHF patients (ejection fraction: 27 +/- 6%; New York Heart Association 2.9 +/- 0.6) with cardiac resynchronization therapy and automatic impedance measurements were included. Upon an alert, a stepped therapy was initiated: category (1) overt decompensation, hospitalization; category (2) worsened CHF, increase of diuretics; category (3) no CHF worsening, brain natriuretic peptide (BNP) measurement, elevated BNP: increase of diuretics, normal BNP: no specific treatment. RESULTS: During 18 +/- 4 months, 45 alerts were treated according to the algorithm. Eleven category 1 alerts led to hospitalization; 21 category 2 and 11 category 3 patients (elevated BNP) were treated conservatively. Two category 3 alerts (normal BNP) received no treatment. CONCLUSIONS: Automatic impedance measurement can be integrated into CHF management. BNP measurement restricted to patients with alert but without clinical signs of worsened CHF may prevent premature therapy escalation.

Imaging of the coronary venous system in patients with congestive heart failure: comparison of 16 slice MSCT and retrograde coronary sinus venography: comparative imaging of coronary venous system.

BACKGROUND: Knowledge of the anatomy of the coronary venous system (CVS) is important for planning of cardiac interventions like cardiac resynchronization therapy or percutaneus mitral annuloplasty. Different methods have been used for preprocedural visualization of the CVS. However, limited data is available comparing invasive retrograde coronary sinus angiography (CSA) and non-invasive multi slice computed tomography (MSCT). Thus, a comparison of retrograde CSA and ECG-gated MSCT for the visualization of the CVS in patients with congestive heart failure (CHF) was performed. METHODS: 20 patients (male: 11) with CHF underwent CSA and MSCT (16 x 0.75 mm collimation, tube voltage: 120 kV, tube current: 550 mAs(eff)). Both methods were compared with respect to vessel diameter and visibility. RESULTS: Vessel visualization was better using retrograde CSA except for middle cardiac vein and small veins which were better seen with MSCT. Overall, there was a trend that MSCT detected more vessels. Vessel diameters were larger measured using retrograde CSA, but only statistically significant for the coronary sinus and middle cardiac vein. CONCLUSION: Whereas MSCT is more suitable for an overview, retrograde CSA offers a more detailed visualization of the CVS including marginal and posterior veins than MSCT. Thus, retrograde CSA allows a better display of target vessels commonly used for cardiac interventions. Overall, these two imaging techniques offer complementary information.

Imaging of the coronary venous system: validation of three-dimensional rotational venous angiography against dual-source computed tomography.

Information on the anatomy of the cardiac venous system (CVS) is increasingly important for cardiac resynchronization therapy or percutaneous transvenous mitral valve annuloplasty. Three-dimensional (3D) imaging can further improve the understanding of the relationship of cardiac structures. This study was performed to validate the accuracy of rotational coronary sinus angiography (CSA) displaying the 3D anatomy of the CVS compared to ECG-gated, contrast-enhanced, cardiac dual-source computed tomography (DSCT). Five domestic pigs (60 kg) underwent DSCT using a standardized examination protocol. Using a standard C-arm for fluoroscopy, a rotational CSA was obtained and 3D-image reconstructions performed. Side branches were identified using both methods and enumerated. Vessel visibility was estimated for each side branch and great cardiac vein/anterior interventricular vein. Also, vessel diameters were measured at distinct landmarks, i.e., side branching. The amount of contrast medium was determined and the effective radiation exposure of both methods was calculated. There was no significant difference regarding the vessel diameter of the great cardiac vein/anterior interventricular vein or its side branches. Also, estimation of vessel visibility was not different between the two imaging modalities. Estimated radiation exposure and amount of contrast medium were lower for rotational CSA. In conclusion, a 3D reconstruction of rotational CSA images is possible. All parts of the CVS are well depicted, allowing a 3D overview of the CVS anatomy. On-site 3D visualization might improve decision making during cardiac interventions. In contrast to DSCT, rotational CSA does not demonstrate the anatomy of the mitral annulus or the course of the left circumflex artery.

Association of echocardiographic atrial size and atrial fibrosis in a sequential model of congestive heart failure and atrial fibrillation.

BACKGROUND: Cardioversion (CV) success of atrial fibrillation (AF) inversely correlates to the size of the left atrium (LA). Atrial fibrillation and its most important risk factor, congestive heart failure (CHF), both induce atrial structural enlargement and fibrosis. To investigate the effect of AF and CHF on atrial dilatation and fibrosis, and to estimate whether echocardiographically determined atrial size may be used as a marker for atrial fibrosis. METHODS: In six dogs, pacemakers were implanted followed by HIS bundle ablation. After 4 weeks of rapid ventricular stimulation (185 bpm) for CHF induction, additional rapid atrial stimulation (500 bpm) was maintained for 7 weeks to induce AF. Serial determinations of echocardiographic atrial size were performed. Seven dogs with sinus rhythm served as histological controls. Postmortem tissue was obtained to determine the degree and composition of atrial fibrosis. RESULTS: While the ejection fraction of the AF/CHF dogs decreased significantly from 57+/-5% to 19+/-7% (P<.01), an increased degree of atrial fibrosis was found (right atrium [RA], 4.9+/-2.0% to 19.9+/-5.4%; LA, 4.4+/-1.6% to 22.2+/-3.2%; P<.01), accompanied by a significant increase of atrial volumes (LA: 21+/-4 to 44+/-4 mm3; P<.01; RA: 10+/-3 to 18+/-6 mm3; P<.05) and LA diameters (34+/-4 to 43+/-2 mm, P<.05). Atrial fibrosis and size significantly correlated. CONCLUSIONS: Atrial fibrillation/CHF leads to a significant atrial fibrosis and dilation. The increased echocardiographic size correlates to the degree of atrial fibrosis and may be used as clinical marker for atrial fibrosis. The fibrosis accompanying atrial dilatation may also explain why LA size, as determined by echocardiography, is a strong predictor of CV success.

Efficacy of transesophageal defibrillation in ventricular fibrillation of long duration.

INTRODUCTION: Increasing duration of ventricular fibrillation (VF) is associated with a higher risk of ineffective resuscitation. In addition, precountershock chest compression can influence defibrillation success. Transesophageal defibrillation may increase defibrillation success because of the proximity of the esophagus to the heart. We evaluated the efficacy of transesophageal defibrillation compared with standard transthoracic defibrillation after long episodes of VF. METHODS: Defibrillation success after 10 minutes of untreated VF was evaluated in 12 sheep randomized into 2 groups: (group A) in 6 sheep, up to 3 transthoracic shocks were applied, followed by up to 3 transesophageal shocks (first shock: 150 J, second and third shocks: 200 J). (group B) In 6 sheep, 2 minutes of precountershock chest compression preceded the defibrillation shocks. Truncated biphasic shocks were delivered between a sternal and an apical patch electrode for transthoracic defibrillation and between an esophageal and a cutaneous patch electrode for transesophageal defibrillation. RESULTS: In group A with no precountershock chest compression, external defibrillation failed despite shocks with maximum energy (200 J) in all 6 sheep. Transesophageal defibrillation was successful in 3 sheep (50%). In group B with precountershock chest compression, external defibrillation failed in all 6 sheep. Transesophageal defibrillation was successful with the first shock in all 6 sheep. CONCLUSIONS: Transesophageal defibrillation may terminate VF of long duration that is refractory to standard defibrillation. Precountershock chest compression may increase transesophageal defibrillation success.

A simple device to apply equibiaxial strain to cells cultured on flexible membranes.

The biomechanical environment to which cells are exposed is important to their normal growth, development, interaction, and function. Accordingly, there has been much interest in studying the role of biomechanical forces in cell biology and pathophysiology. This has led to the introduction and even commercialization of many experimental devices. Many of the early devices were limited by the heterogeneity of deformation of cells cultivated in different locations of the culture plate membranes and were also attached with complicated technical/electronic efforts resulting in a restriction of the reproducibility of these devices. The objective of this study was to design and build a simple device to allow the application of dose-dependent homogeneous equibiaxial static stretch to cells cultured on flexible silicone membranes to investigate biological and biomedical questions. In addition, cultured neonatal rat atrial cardiomyocytes were stretched with the proposed device with different strain gradients. For the first time with this study we could demonstrate that stretch up to 21% caused dose-dependent changes in biological markers such as the calcineurin activity, modulatory calcineurin-interacting protein-1, voltage-gated potassium channel isoform 4.2, and voltage-gated K(+) channel-interacting proteins-2 gene expression and transient outward potassium current densities but not the protein-to-DNA ratio and atrial natriuretic peptide mRNA. With both markers mentioned last, dose-dependent stretch alterations could only be achieved with stretch up to 13%. The simple and low-cost device presented here might be applied to a wide range of experimental settings in different fields of research.

Decreased plasminogen activator inhibitor and tissue metalloproteinase inhibitor expression may promote increased metalloproteinase activity with increasing duration of human atrial fibrillation.

INTRODUCTION: Atrial fibrosis has been shown to concur with the persistence of atrial fibrillation (AF) and is only incompletely reversible, thus counteracting attempts to restore and maintain sinus rhythm (SR). Besides the angiotensin system, the matrix metalloproteinases (MMP) play a major role in the pathogenesis of fibrosis. Thus, the present study investigated changes of the MMP system during the development of human AF. METHODS AND RESULTS: Right atrial appendages of 146 patients were excised during heart surgery and grouped according to rhythm (SR vs AF) and AF duration. Hydroxyproline as a surrogate for collagen content and morphometrically determined collagen content increased significantly from SR (14.3 +/- 7.7%) to chronic permanent AF (CAF) of 6-24 months (21.2 +/- 9.2%, P = 0.02), and CAF of > 60 months (25.3 +/- 4.7%, P < 0.01). From SR to paroxysmal and chronic persistent AF (CPAF) and to CAF MMP-2 and MMP-9 activity rose, while their mRNA and protein levels were not altered significantly. Plasminogen activator inhibitor (PAI), an inhibitor of a potent activator of many MMPs, was significantly decreased with increasing duration of AF. In parallel, the mRNA levels of the tissue inhibitors of MMPs TIMP-1 and -2 decreased significantly. CONCLUSION: Human atrial fibrogenesis is enhanced with increasing duration of AF: a longer AF duration is associated with elevated atrial interstitial MMP activity, but decreased PAI and TIMP expression.

Single-step atrial thrombus exclusion and transesophageal cardioversion in atrial fibrillation.

Atrial fibrillation (AF), the most common arrhythmia, has a major impact on both patient morbidity and healthcare economics. Hospital admissions due to AF have risen by two-thirds in the last 20 years. This is due mainly to an aging population and an increasing prevalence of chronic heart disease. Strategies for the management of AF include prevention of thromboembolism, rate control and correction of the arrhythmia. Electrical cardioversion as one component of the treatment of AF requires the absence of atrial thrombi. Transesophageal echocardiography is used routinely for exclusion of atrial thrombi prior to cardioversion in many hospitals. This review presents preliminary data on the clinical use of devices for simultaneous transesophageal echocardiography and transesophageal cardioversion.

Simultaneous transesophageal cardioversion and echocardiography: feasibility and safety.

BACKGROUND: Transesophageal echocardiography (TEE) is routinely used to exclude atrial thrombus prior to cardioversion of atrial fibrillation (AF). Because the TEE probe lies adjacent to the atria, cardioversion using an electrode attached to the TEE probe should allow for immediate low-energy transesophageal cardioversion. OBJECTIVE: The purpose of this study was to evaluate a cardioversion electrode sheath that can be affixed to conventional TEE probes for simultaneous thrombus exclusion and cardioversion of AF. METHODS: A thin electrode was integrated into a latex or polyurethane sheath covering a conventional TEE probe. TEE thrombus exclusion and biphasic transesophageal cardioversion using a step-up protocol were performed during deep sedation. Esophagoscopy was performed immediately after cardioversion and after 1 week. RESULTS: TEE was performed in 27 patients. One patient showed left atrial thrombi. Transesophageal cardioversion was successful in 25 of the remaining 26 patients. Mean atrial cardioversion threshold was 63 +/- 48 J. Transesophageal cardioversion restored sinus rhythm in two patients with unsuccessful transthoracic cardioversion. Transesophageal cardioversion in deep sedation was well tolerated. Esophagoscopy revealed slight mucosal damage in three patients at the site of shock application; two of these patients showed signs of gastroesophageal reflux disease. Mucosal damage unrelated to the site of shock delivery was noted in three patients. CONCLUSION: Atrial thrombus exclusion and transesophageal cardioversion of AF via a disposable cardioversion sheath offers the opportunity to perform transesophageal cardioversion and TEE thrombus exclusion during one sedation. It may not be suitable for use in patients with gastroesophageal reflux disease. Transesophageal cardioversion may establish sinus rhythm in selected patients refractory to transthoracic cardioversion.

Imaging of the coronary venous system: retrograde coronary sinus angiography versus venous phase coronary angiograms.

BACKGROUND: Left ventricular lead implantation for cardiac resynchronization therapy (CRT) usually requires a pre- or intraprocedural occlusion contrast venography of the coronary sinus (CS) in order to identify tributaries to the lateral wall. As many patients undergo a preprocedural coronary angiogram, we investigated the diagnostic accuracy of venous phase imaging of the CS in patients prior to CRT implantation. The aim of this study was to assess the quality of venous phase coronary sinus angiography. METHODS: In 24 CRT patients retrograde occlusion venography and venous phase coronary sinus angiography obtained during coronary angiography were compared with respect to image quality, vessel diameters and the ability to identify a coronary sinus side branch suitable for left ventricular lead placement. RESULTS: Suitable target vessels for left ventricular lead implantation were identified in all patients irrespective of the method (retrograde occlusion venography or venous phase coronary sinus angiography). There was a high concordance in vessel diameters between venous phase and retrograde angiography. Visibility was superior in retrograde venography. CONCLUSIONS: In heart failure patients who are scheduled for coronary angiograms venous phase coronary sinus angiography is a time-saving and easy to perform alternative imaging modality. Radiation exposure and the amount of contrast medium needed is reduced as compared to coronary sinus occlusion angiography. The information obtained thereby may be used to plan subsequent CRT implantation without the need for retrograde coronary sinus angiography.

Ventricular fibrillation due to severe mitral valve prolapse.

Mitral valve prolapse usually has a good prognosis. However, an association between mitral valve prolapse and atrial and ventricular arrhythmias has been described. This case presents a patient who was admitted after cardiac resuscitation due to ventricular fibrillation. A severe mitral valve prolapse was the only pathology found.

Semi-automated 3-dimensional intracardiac echocardiography: development and initial clinical experience of a new system to guide ablation procedures.

BACKGROUND: Pre-interventional three-dimensional (3D) reconstruction of the heart by CT or MRI provides important information on cardiac anatomy for electrophysiological interventions. However, updates of 3D-imaging modalities with high soft-tissue contrast are not available during ablation procedures. OBJECTIVE: We describe the development and first clinical testing of a close to real-time visualization of cardiac anatomy by intracardiac echocardiography (ICE). METHODS: An electronic phased-array 5-10 MHz ICE-catheter (AcuNav/Siemens/64 elements) was inserted via a straightened femoral vein sheath (12F) and placed in the right atrium in 5 pigs. A custom-made prototype stepper motor allowed automatic rotation around the longitudinal axis from 90 degrees to 360 degrees in 2-5 degrees steps. For every plane 2D images of a complete cardiac cycle were acquired, triggered by respiration and ECG. The ultrasound images were digitized and 3D-reconstruction was performed by a prototype software. After experimental validation the system was tested in 6 patients during electrophysiological studies. RESULTS: From a single location in the right atrium, 3D-acquisition and reconstruction of both atria and ventricles with good image quality were achieved within 3-5 minutes. Doppler-mode facilitated identification of the great vessels including the pulmonary veins and their entry into the heart. 3D-visualization of ablation catheters was also possible in all patients and pigs. CONCLUSION: Semi-automated 3D intracardiac echocardiography from a single site inside the right atrium provides the electrophysiologist with a detailed image of both atria and ventricles with repeated updates of the cardiac anatomy.

Potential benefit of transesophageal defibrillation: an experimental evaluation.

INTRODUCTION: Because of the proximity of the esophagus to the heart, transesophageal defibrillation might increase defibrillation success. We assessed the defibrillation threshold (DFT) of transesophageal defibrillation compared with standard transthoracic defibrillation. METHODS: Defibrillation success and DFTs were determined in 22 female pigs with high (68+/-4 kg, n=12) or low body weight (39+/-1 kg, n=10). After induction of ventricular fibrillation, biphasic shocks were delivered between two cutaneous patch electrodes (sternal and apical position) or between an esophageal and two cutaneous patch electrodes in a sternal and apical position. The esophageal electrode was integrated into a latex sheath covering a standard transesophageal echocardiography probe. RESULTS: In 5 of 12 pigs with high body weight, external defibrillation failed despite 3 consecutive 200-J shocks, whereas subsequent transesophageal defibrillation was successful with the first shock. In the remaining 7 pigs, a more than 50% reduction in DFT was obtained with transesophageal defibrillation compared with standard biphasic external defibrillation (67+/-27 vs 164+/-23 J, P<.001). Pigs with lower body weight were successfully defibrillated by both transthoracic and transesophageal shocks. The DFT in pigs with low body weight was significantly lower using transesophageal defibrillation compared with transthoracic shocks (65+/-15 vs 99+/-38 J, P<.05). CONCLUSIONS: In this animal model, nonresponders to standard external defibrillation could successfully be defibrillated via an esophageal-cutaneous electrode configuration. Overall, an almost 50% DFT reduction was achieved by transesophageal defibrillation. Transesophageal defibrillation may provide an additional tool for terminating VF, which is refractory to external defibrillation, eg, in patients with very high body weight.

[Morphology and function of the intrinsic cardiac nervous system]. / Morphologie und Funktion des intrinsischen kardialen Nervensystems.

Access to the intrinsic cardiac autonomic nervous system can now be achieved via percutaneous catheter stimulation techniques. Thereby, cardiac functions like atrioventricular nodal conduction, sinus cycle length and ventricular inotropy can be dynamically regulated. The present article provides examples of this new technique in acute and chronic models but also first human applications.

Selective increase of cardiac neuronal sympathetic tone: a catheter-based access to modulate left ventricular contractility.

OBJECTIVES: This study was designed to develop a technique to selectively increase the sympathetic tone to the heart by cardiac sympathetic nerve stimulation (SNS). BACKGROUND: Access to the cardiac sympathetic neurons may allow modulating the adrenergic tone of the heart while avoiding systemic side effects. METHODS: Cardiac sympathetic nerves course within neural sleeves along the subclavian artery. Because of this proximity, transvascular SNS was attempted with electrode catheters inside the subclavian artery in 16 pigs. RESULTS: Right/left (R-/L-) SNS (20 Hz) during ventricular pacing at 200/min evoked a >100% increase of left ventricular systolic pressure (baseline: 51 +/- 1 mm Hg; L-SNS: 118 +/- 26 mm Hg; R-SNS: 116 +/- 33 mm Hg; p < 0.001) while systemic vascular resistance remained unchanged. There was a sigmoid dose-response curve with rapid on- and offset of the effect during SNS initiation/cessation. Positive inotropic effects persisted for 12 h of continued SNS (n = 4). Besides positive dromotropic effects, L-SNS/R-SNS yielded a 41% and 77% sinus rate increase, respectively. CONCLUSIONS: The neural adrenergic tone to the heart can be selectively increased by catheter stimulation of cardiac efferent sympathetic nerves.