Clinical effects of long-term cardiac contractility modulation (CCM) in subjects with heart failure caused by left ventricular systolic dysfunction.

INTRODUCTION: Heart failure is a major cause of morbidity and mortality throughout the world. Despite advances in therapy, nearly half of patients receiving guideline-directed medical therapy remain limited by symptoms. Cardiac contractility modulation (CCM) can improve symptoms in this population, but efficacy and safety in prospective studies has been limited to 12 months of follow-up. We report on the first 2 year multi-site evaluation of CCM in patients with heart failure. METHODS: One hundred and forty-three subjects with heart failure and reduced ejection fraction were followed via clinical registry for 24 months recording NYHA class, MLWHFQ score, 6 min walk distance, LVEF, and peak VO2 at baseline and 6 month intervals as clinically indicated. Serious adverse events, and all cause as well as cardiovascular mortality were recorded. Data are presented stratified by LVEF (all subjects, LVEF <35%, LVEF ≥35%). RESULTS: One hundred and six subjects from 24 sites completed the 24 month follow-up. Baseline parameters were similar among LVEF groups. NYHA and MLWHFQ improved in all 3 groups at each time point. LVEF in the entire cohort improved 2.5, 2.9, 5.0, and 4.9% at 6, 12, 18, and 24 months, respectively. Insufficient numbers of subjects had follow-up data for 6 min walk or peak VO2 assessment, precluding comparative analysis. Serious adverse events (n = 193) were observed in 91 subjects and similarly distributed between groups with LVEF <35% and LVEF ≥35%, and similar to other device trials for heart failure. Eighteen deaths (7 cardiovascularly related) over 2 years. Overall survival at 2 years was 86.4% (95% confidence intervals: 79.3, 91.2%). CONCLUSION: Cardiac contractility modulation provides safe and effective long-term symptomatic and functional improvement in heart failure. These benefits were independent of baseline LVEF and were associated with a safety profile similar to published device trials.

[Telemedicine-assisted treatment of a 76-year-old man with heart failure]. / Telemedizingestützte Behandlung eines 76-Jährigen mit Herzinsuffizienz.

The case of a patient with dilated cardiomyopathy and severely impaired left ventricular function is reported. With existing complete left bundle branch block and the patient being on optimal medical therapy, a cardiac resynchronization device with an integrated defibrillator was implanted and the patient was included in our telemonitoring program. During monitoring, an increase in ventricular premature beats with a decrease in biventricular pacing percentage was noticed. Consequently, radiofrequency ablation of the ventricular premature beats which originated in the left ventricle was performed. After ablation we could demonstrate a significant increase in biventricular pacing percentage. This case shows the importance of telemedicine and the complexity in the rhythmological treatment of heart failure patients.

Automatic detection of atrial fibrillation in cardiac vibration signals.

We present a study on the feasibility of the automatic detection of atrial fibrillation (AF) from cardiac vibration signals (ballistocardiograms/BCGs) recorded by unobtrusive bedmounted sensors. The proposed system is intended as a screening and monitoring tool in home-healthcare applications and not as a replacement for ECG-based methods used in clinical environments. Based on BCG data recorded in a study with 10 AF patients, we evaluate and rank seven popular machine learning algorithms (naive Bayes, linear and quadratic discriminant analysis, support vector machines, random forests as well as bagged and boosted trees) for their performance in separating 30 s long BCG epochs into one of three classes: sinus rhythm, atrial fibrillation, and artifact. For each algorithm, feature subsets of a set of statistical time-frequency-domain and time-domain features were selected based on the mutual information between features and class labels as well as first- and second-order interactions among features. The classifiers were evaluated on a set of 856 epochs by means of 10-fold cross-validation. The best algorithm (random forests) achieved a Matthews correlation coefficient, mean sensitivity, and mean specificity of 0.921, 0.938, and 0.982, respectively.

A dedicated cardioversion unit for the treatment of atrial fibrillation. Reducing costs by optimizing processes.

BACKGROUND: Atrial fibrillation (AF) is the most frequent arrhythmia seen in man. Many patients are admitted to the hospital to undergo transesophageal echocardiography (TEE) for thrombus exclusion and subsequent electrical cardioversion (ECV) under deep sedation to restore sinus rhythm. The present study investigated prospectively how workflow optimization can contribute to reducing time and costs in AF patients scheduled for ECV in an outpatient setting. METHODS: A cardioversion unit (CU) was established and equipped to perform all ECV-associated procedures. Between November 2007 and January 2009, ECV was performed in 115 patients in an outpatient setting. Three different settings were tested for ECV: (1) usual care (n = 19): preparation/follow-up in the outpatient clinic, blood testing in the central hospital laboratory (CHL), TEE in the echocardiography laboratory, and ECV in the intensive care unit; (2) optimized process 1 (n = 41): preparation/follow-up, TEE + ECV during one sedation in the CU, blood testing in the CHL; (3) optimized process 2 (n = 55): preparation/follow-up, TEE + ECV and point of care (POC) blood testing in the CU. All procedure-related costs were listed and classified according to material, human resources, and infrastructure. RESULTS: From setting 1 to 3, there was a significant decrease in procedural time from 480 ± 105 min to 205 ± 85 min (p < 0.001). Likewise, ECV-associated costs could be reduced from 683 ± 104  to 299 ± 63  (p < 0.001). CONCLUSION: Establishing a CU for AF enables a more than 50% reduction in procedural time and costs. A combination of TEE and ECV in one sedation and POC testing in the CU were the major contributors to this time and cost reduction.

Sympathetic hyperactivity influences chemosensor function in patients with end-stage renal disease.

BACKGROUND: Autonomic neuropathy is common in patients suffering from end-stage renal disease (ESRD). This may in part explain the high cardiovascular mortality in these patients. Chemosensory function is involved in autonomic cardiovascular control and is mechanistically linked to the sympathetic tone. OBJECTIVE: The aim of the present study was to assess whether sympathetic hyperactivity contributes to an altered chemosensory function in ESRD. MATERIAL AND METHODS: In a randomized, double-masked, placebo controlled crossover design we studied the impact of chemosensory deactivation on heart rate, blood pressure and oxygen saturation in 10 ESRD patients and 10 age and gender matched controls. The difference in the R-R intervals divided by the difference in the oxygen pressures before and after deactivation of the chemoreceptors by 5-min inhalation of 7 L oxygen was calculated as the hyperoxic chemoreflex sensitivity (CHRS). Placebo consisted of breathing room air. Baseline sympathetic activity was characterized by plasma catecholamine levels and 24-h time-domain heart rate variability (HRV) parameters. RESULTS: Plasma norepinephrine levels were increased (1.6 +/- 0.4 vs. 5.8 +/- 0.6; P<0.05) while the SDNN (standard deviation of all normal R-R intervals: 126.4 +/- 19 vs. 100.2 +/- 12 ms), the RMSSD (square root of the mean of the squared differences between adjacent normal R-R intervals: 27.1 +/- 8 vs. 15.7 +/- 2 ms), and the 24-h triangular index (33.6 +/- 4 vs. 25.7 +/- 3; each P<0.05) were decreased in ESRD patients as compared to controls. CHRS was impaired in ESRD patients (2.9 +/- 0.9 ms/mmHg, P<0.05) as compared to controls (7.9 +/- 1.4 ms/mmHg). On multiple regression analysis 24 h-Triangular index, RMSSD, and plasma norepinephrine levels were independent predictors of an impaired hyperoxic CHRS. CONCLUSION: Sympathetic hyperactivity influences chemosensory function in ESRD resulting in an impaired hyperoxic CHRS.

Moderate physical exercise: a simplified approach for ventricular rate control in older patients with atrial fibrillation.

AIMS: This prospective pilot-study was performed to assess whether regular moderate physical activity elevates the parasympathetic tone to the atrio-ventricular node and decreases VR during permanent AF. BACKGROUND: Adequate ventricular rate (VR) control in patients with permanent atrial fibrillation (AF) is not easy to accomplish. METHODS: 10 patients (mean age 59 +/- 10 years) with permanent AF (duration: 10 +/- 8 years) underwent moderate physical exercise adjusted to their individual physical capability (45 min walking/jogging twice a week). To analyze VR control physical exercise tests and Holter-ECG recordings were performed before and after 4 months. In addition, stepwise lactate tests and psycho-pathometric examinations were obtained. RESULTS: After 4 months of training, there was a trend toward a decrease of mean VR in 24 h Holter-ECGs by 12% from 76 +/- 20 to 67 +/- 12 bpm (P = 0.05) while there was no significant decrease of the minimal VR (38 +/- 8 vs. 36.3 +/- 4.5 bpm, P = 0.54). At a lactate threshold of 2 mmol/l there was a trend towards an increase of the running speed from 105 +/- 11 to 116 +/- 12 m/min (P = 0.05). A significant VR decrease of 8% (range 5-10%) was observed at almost all exercise levels during exercise treadmill testing. Increases of exercise capacity and decreases of VR were accompanied by subjective improvements of health perception. CONCLUSION: Regular moderate physical activity decreases VR at rest and during exercise while increasing exercise capacity. Physical training should be taken into account for ventricular rate control during AF.

The role of intracardiac echocardiography in interventional electrophysiology.

Visualization of the cardiac anatomy becomes more and more important as the complexity of interventions increases. Intracardiac echocardiography (ICE) provides good depiction of cardiac soft tissue structures and has become an important tool in today's cardiology. It has been shown to be valuable during many ablation procedures for supraventricular and ventricular arrhythmias. ICE has been used for monitoring catheter placement, observing catheter-tissue contact and lesion formation as well as titrating ablation energy. The rate of complications could be reduced, outcome of procedures improved and radiation exposure decreased. Even more, new therapy strategies have been evaluated based on ICE and it has also been used in the setting of three- dimensional imaging and image integration.

Magnetic versus manual guidewire manipulation in neuroradiology: in vitro results.

INTRODUCTION: Standard microguidewires used in interventional neuroradiology have a predefined shape of the tip that cannot be changed while the guidewire is in the vessel. We evaluated a novel magnetic navigation system (MNS) that generates a magnetic field to control the deflection of a microguidewire that can be used to reshape the guidewire tip in vivo without removing the wire from the body, thereby potentially facilitating navigation along tortuous paths or multiple acute curves. METHOD: The MNS consists of two permanent magnets positioned on either side of the fluoroscopy table that create a constant precisely controlled magnetic field in the defined region of interest. This field enables omnidirectional rotation of a 0.014-inch magnetic microguidewire (MG). Speed of navigation, accuracy in a tortuous vessel anatomy and the potential for navigating into in vitro aneurysms were tested by four investigators with differing experience in neurointervention and compared to navigation with a standard, manually controlled microguidewire (SG). RESULTS: Navigation using MG was faster (P=0.0056) and more accurate (0.2 mistakes per trial vs. 2.6 mistakes per trial) only in less-experienced investigators. There were no statistically significant differences between the MG and the SG in the hands of experienced investigators. One aneurysm with an acute angulation from the carrier vessel could be navigated only with the MG while the SG failed, even after multiple reshaping manoeuvres. CONCLUSION: Our findings suggest that magnetic navigation seems to be easier, more accurate and faster in the hands of less-experienced investigators. We consider that the features of the MNS may improve the efficacy and safety of challenging neurointerventional procedures.

Impact of ECG gating in contrast-enhanced MR angiography for the assessment of the pulmonary veins and the left atrium anatomy.

PURPOSE: Implementation of ECG gating in contrast-enhanced MR angiography (ceMRA) for improved visualization of the pulmonary veins, the left atrium, and the thoracic vessels. MATERIALS AND METHODS: CeMRA was performed on twelve patients with a history of recurrent atrial fibrillation for the purpose of an intra-individual comparison with and without ECG gating on a 1.5 Tesla MR system (Gyroscan Intera, Philips Medical Systems, Best, NL). Objective image quality parameters such as the signal-to-noise ratio (SNR) of the blood and the contrast-to-noise ratio (CNR) between the blood and myocardium or lung parenchyma were analyzed. The contour sharpness of the pulmonary veins, left atrium, ascending aorta, and pulmonary trunk was also measured. In addition, the artifact level was subjectively assessed by two observers blinded with respect to the sequence parameters. Statistically significant differences (p < 0.05) between the procedures were analyzed using the Wilcoxon test and Pearson Chi-square test. RESULTS: The use of ECG gating in ceMRA significantly reduced artifacts caused by cardiac motion and vessel pulsation. This in turn lead to a significant increase in the contour sharpness of the left atrium and the thoracic vessels. In addition, higher SNR and CNR were found using ECG-gated ceMRA compared to standard ceMRA. CONCLUSION: The use of ECG gating in ceMRA results in artifact-free and sharper delineation of the structures of the heart and thoracic vessels.

Telephonic transmission of 12-lead electrocardiograms during acute myocardial infarction.

To test the feasibility of a small and simple system for telephonic transmission of 12-lead electrocardiograms (ECGs), 70 patients with acute coronary syndrome admitted to the cardiac care unit (CCU) were included in a feasibility study. The transmission system consisted of a belt with multiple electrodes, which was positioned around the chest. The ECG signal was sent to a call centre via a standard telephone line. In parallel, a standard 12-lead ECG was recorded on site. In a retrospective analysis, each lead of the transmitted ECG was compared with the on-site 12-lead ECG with regard to ST-segment changes and final diagnosis. In all 37 patients with acute ST-elevation myocardial infarction, the diagnosis was correctly established on the basis of telephone-transmitted ECGs. In 96% of limb and 88% of chest leads, ST elevations which were visible in standard ECGs were correctly displayed on telephonically transmitted ECGs. In the remaining 33 patients no false-positive diagnosis was made using transtelephonic ECG analysis. A control group of 31 patients without apparent heart disease showed high concordance between standard ECGs and telephonically transmitted ECGs. Telephonically transmitted 12-lead ECGs interpreted by a hospital-based internist/cardiologist might allow a rapid and accurate diagnosis of ST-elevation myocardial infarction and may increase diagnostic safety for the emergency staff during prehospital decision making and treatment of acute myocardial infarction.

Steroid-eluting and fractally coated electrodes in children with high pacing thresholds.

High pacing thresholds in epicardially implanted leads are a frequent issue in children after cardiac surgery. In 2 infants, repeated revisions of non-steroid-eluting leads were necessary. To avoid further frequent replacements, two epicardial ventricular leads, one steroid-eluting and an additional fractally coated electrode as a pacing "backup" were connected to the atrial and ventricular outlet of a DDD pacemaker, allowing a comparison between two both electrodes. Showing no differences in long-term measurements, both electrodes seem to provide a comparably high level of safety.

Differential effects of atropine and isoproterenol on inducibility of atrioventricular nodal reentrant tachycardia.

BACKGROUND: Radiofrequency ablation of the "slow pathway" in atrioventricular nodal reentrant tachycardia (AVNRT) relies on tachycardia non-inducibility after ablation as success criterion. However, AVNRT is frequently non-inducible at baseline. Thus, autonomic enhancement using either atropine or isoproterenol is frequently used for arrhythmia induction before ablation. METHODS: 80 patients (57 women, 23 men, age 50+/-14 years) undergoing slow pathway ablation for recurrent AVNRT were randomized to receive either 0.01 mg/kg atropine or 0.5-1.0 microg/kg/min isoproterenol before ablation after baseline assessment of AV conduction. The effects of either drug on ante- and retrograde conduction was assessed by measuring sinus cycle length, PR and AH interval, antegrade and retrograde Wenckebach cycle length (WBCL), antegrade effective refractory period (ERP) of slow and fast pathway and maximal stimulus-to-H interval during slow and fast pathway conduction. RESULTS: Inducibility of AVNRT at baseline was not different between patients randomized to atropine (73%) and isoproterenol (58%) but was reduced after atropine (45%) compared to isoproterenol (93%, P<0.001). Of the 28 patients non-inducible at baseline isoproterenol rendered AVNRT inducible in 21, atropine in 4 patients. Dual AV nodal pathway physiology was present in 88% before and 50% after atropine compared to 83% before and 73% after isoproterenol. Whereas both drugs exerted similar effects on ante- and retrograde fast pathway conduction maximal SH interval during slow pathway conduction was significantly shorter after isoproterenol (300+/-48 ms vs. 374+/-113 ms, P=0.012). CONCLUSION: Isoproterenol yields higher AVNRT inducibility than atropine in patients non-inducible at baseline. This may be caused by a more pronounced effect on antegrade slow pathway conduction.

Catheter stimulation of cardiac parasympathetic nerves in humans: a novel approach to the cardiac autonomic nervous system.

BACKGROUND: Cardiac parasympathetic nerves run alongside the superior vena cava (SVC) and accumulate particularly epicardially adjacent to the orifice of the coronary sinus (CS). In animals, these nerves can be electrically stimulated inside the SVC or CS, which results in negative chronotropic/dromotropic effects and negative inotropic effects in the atria but not the ventricles. Parasympathetic nerve stimulation (PS) with 20 Hz in the CS, however, also excites the atria, thereby inducing atrial fibrillation. The present study overcomes this limitation by applying high-frequency nerve stimuli within the atrial refractory period. Using this technique, we investigated for the first time whether neurophysiological effects similar to those in animals can be obtained in humans. METHODS AND RESULTS: In 25 patients, parasympathetic nerves were stimulated via a multipolar electrode catheter placed in the SVC (stimulation with 20 Hz; n=14) or CS (pulsed 200-Hz stimuli; n=11). A significant sinus rate decrease and prolongation of the antegrade Wenckebach period was achieved during PS in the SVC. During PS in the CS, a graded-response prolongation of the antegrade Wenckebach interval was observed with increasing PS voltage until third-degree AV block occurred in 8 of 11 patients. The negative chronotropic/dromotropic effects started and terminated immediately after the onset and termination of PS, respectively. Atropine abolished these effects (n=11). CONCLUSIONS: Human parasympathetic efferent nerve stimulation induces reversible negative chronotropic and dromotropic effects. PS may serve as an adjunctive tool for the diagnosis/treatment of supraventricular tachycardias and may be beneficial for ventricular rate slowing during tachycardic atrial fibrillation in patients with congestive heart failure.

Focal atrial fibrillation: experimental evidence for a pathophysiologic role of the autonomic nervous system.

INTRODUCTION: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. METHODS AND RESULTS: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing high-frequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13+/-8 V and AT/AF at 15+/-9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19+/-6 V and AT/AF at 26+/-6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89+/-35 msec to 60+/-22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolar-izations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. CONCLUSION: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation.

PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.

Inogranic pyrophosphate (PPi) inhibits hydroxyapatite deposition, and mice deficient in the PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) Plasma cell membrane glycoprotein-1 (PC-1) develop peri-articular and arterial calcification in early life. In idiopathic infantile arterial calcification (IIAC), hydroxyapatite deposition and smooth muscle cell (SMC) proliferation occur, sometimes associated with peri-articular calcification. Thus, we assessed PC-1 expression and PPi metabolism in a 25-month-old boy with IIAC and peri-articular calcifications. Plasma PC-1 was <1 ng/ml by enzyme-linked immunosorbent assay in the proband, but 10 to 30 ng/ml in unaffected family members and controls. PC-1 functioned to raise extracellular PPi in cultured aortic SMCs. However, PC-1 was sparse in temporal artery lesion SMCs in the proband, unlike the case for SMCs in atherosclerotic carotid artery lesions of unrelated adults. Proband plasma and explant-cultured dermal fibroblast NTPPPH and PPi were markedly decreased. The proband was heterozygous at the PC-1 locus, and sizes of PC-1 mRNA and polypeptide, and the PC-1 mRNA-coding region sequence were normal in proband fibroblasts. However, immunoreactive PC-1 protein was relatively sparse in proband fibroblasts. In conclusion, deficient extracellular PPi and a deficiency of PC-1 NTPPPH activity can be associated with human infantile arterial and peri-articular calcification, and may help explain the sharing of certain phenotypic features between some IIAC patients and PC-1-deficient mice.

Catheter ablation of cardiac autonomic nerves for prevention of vagal atrial fibrillation.

BACKGROUND: Vagal stimulation shortens the atrial effective refractory period (AERP) and maintains atrial fibrillation (AF). This study investigated whether the parasympathetic pathways that innervate the atria can be identified and ablated by use of transvenous catheter stimulation and radiofrequency current catheter ablation (RFCA) techniques. METHODS AND RESULTS: In 11 dogs, AERPs were determined at 7 atrial sites during bilateral cervical vagal nerve stimulation (VNS) and electrical stimulation of the third fat pad (20 Hz) in the right pulmonary artery (RPA). VNS shortened the AERP at all sites (from 123+/-4 to 39+/-4 ms, P<0.001) and increased the covariance of AERP (COV-AERP) (from 9+/-3% to 27+/-13%, P<0.001). RPA stimulation shortened the AERP at all sites from 123+/-4 to 66+/-13 ms (P<0.001) and increased the COV-AERP from 9+/-3% to 30+/-12% (P<0.001). In 7 dogs, transvascular RFCA of the parasympathetic pathways along the RPA was performed, and in 3 dogs, additional RFCA of parasympathetic fibers along the inferior (n=2) or superior (n=1) vena cava was performed. RFCA blunted the AERP shortening at all sites during VNS (114+/-4 ms after RFCA), abolished the increase of COV-AERP during VNS (12+/-7% after RFCA), and led to an increase of the baseline AERP (123+/-4 ms before versus 127+/-3 ms after RFCA, P=0.002). Before RFCA, AF could be induced and maintained as long as VNS was continued, whereas after RFCA, AF was no longer inducible during VNS. CONCLUSIONS: -Transvascular atrial parasympathetic nerve system modification by RFCA abolishes vagally mediated AF. This antifibrillatory procedure may provide a foundation for investigating the usefulness of neural ablation in chronic animal models of AF and eventually in patients with AF and high vagal tone.