[CRT in atrial fibrillation--methodical and apparatus options in decision-making]. / CRT bei Vorhofflimmern. Methodische und apparative Optionen zur Entscheidungsfindung.

Heart failure and atrial fibrillation often coexist, especially with increasing degree of heart failure severity. Under this constellation, the advantage of cardiac resynchronization therapy (CRT) is still under discussion and displayed as an unresolved problem in the guidelines for cardiac stimulation and resynchronization. If ventricular desynchronization can be documented and response to CRT can be expected, the challenge is to interoperatively seek the best left ventricular electrode position and to postoperatively optimize the device in order to achieve the best therapy performance. This situation encourages the development of individualized methods and to utilize innovative apparatus features in order to consolidate individual decisions and to optimize CRT in heart failure with atrial fibrillation.

Cross-modal integration of intranasal stimuli: a functional magnetic resonance imaging study.

Most odorants, in addition to the olfactory system, also activate the intranasal trigeminal system. Recent studies have shown that pure trigeminal stimulation activates somatosensory regions as well as regions traditionally thought of as primary olfactory areas. As a main aim of this study we wished to a) ascertain which brain regions are responsive to an "artificially" bimodal odor composed of a trigeminal (CO(2)) and an olfactory stimulant (phenyl ethyl alcohol, PEA) and b) determine if presenting CO(2) and PEA simultaneously activates different brain regions than when presenting them individually. Fifteen men were scanned using functional magnetic resonance imaging while smelling PEA, CO(2), and a mixture of both stimuli (CO(2)PEA) presented simultaneously. Odors were presented monorhinally to the right nostril in a block design. The contrast between CO(2)PEA and baseline revealed areas implicated in the processing of both olfactory and trigeminal stimuli. When the mixture was contrasted with the sum of its single components (CO(2)PEA-{CO(2)+PEA}), activations in integration centers (left superior temporal and right intraparietal sulcus) and in orbitofrontal areas (left medial and lateral orbitofrontal cortex) were detected. The opposite contrast ({CO(2)+PEA}-CO(2)PEA) did not reveal any significant activation. In contrast to studies which have used natural mixed olfactory/trigeminal stimuli, we have shown that the perception of an artificial mixed olfactory/trigeminal stimulus activates, as opposed to inhibiting the olfactory cortex. Further, we also conclude that a mixed olfactory/trigeminal stimulus appears to lead to higher cortical activations than the sum of its parts.

[Implantation of a re-synchronization device in a patient with persistent left superior vena cava-a case report]. / Implantation eines Resynchronisationssystems bei persistierender oberer Hohlvene Ein Fallbericht.

We report an implantation of a cardiac re-synchronization system in a patient with persistent left superior vena cava. This anomaly occurs in 0.3 to 0.5% of healthy individuals and remains usually asymptomatic. Variations of the superior vena cava should be considered in venous catheterization and other procedures such as implantation of pacemaker and ICD systems as well as port catheter insertion. In re-synchronization systems, persistent left superior vena cava can be an obstacle for cannulation of the coronary sinus and placement of a transvenous left ventricular lead.

Heart failure and apoptosis: electrophoretic methods support data from micro- and macro-arrays. A critical review of genomics and proteomics.

The multiple causes and multiple consequences of mammalian heart failure make it an attractive proposition for analysis using gene array technology, especially where the failure is idiopathic in nature. However, gene arrays also hold potential artefacts, particularly when gene expression levels are low, and where changes in expression levels are modest. Also, at present, the number of genes available on arrays is not large enough to prevent potential sampling deficiencies. Thus, it may not be wise to place too much reliance on quantitative interpretations of gene array data. Also, recently doubts were raised about the qualitative reliability of array genes. Electrophoretic methods are slow, cumbersome and complex but they can provide confirmation that the trends and numbers arising from the new gene arrays are reliable. In this overview, we compare gene array data with data from protein activity assays such as zymograms, Western blots, two-dimensional electrophoresis, and immunohistochemistry. Similar or complementary data from the same heart tissues analyzed by either microarrays or macroarrays can be reassuring to those interested in reliable molecular analyses of normal and failing hearts. Similar principles will apply to other tissues and cells.

Apoptosis of ventricular and atrial myocytes from pacing-induced canine heart failure.

OBJECTIVE: Rapid ventricular pacing in dogs results in a low output cardiomyopathic state similar to idiopathic dilated cardiomyopathy in man. Cell death by apoptosis may play an important role in the loss of cardiac function. This study investigates the molecular pathways involved in the regulation of apoptosis in dogs with pacing-induced heart failure. METHODS: Apoptosis was identified by terminal transferase nick end-labelling (TUNEL) in the ventricles and atria of dog hearts affected by rapid-ventricular pacing. Western blots were used to determine expression of the components involved in the initiation (Fas, Fas-Ligand, FADD), regulation (Bcl-2, Bax) and execution (caspase-2 and caspase-3) of apoptosis. RESULTS: Pacing-induced heart failure resulted in a significant increase in the number of ventricular and atrial myocyte nuclei undergoing apoptosis as measured by TUNEL. Compared to the samples from control hearts (n=6) the expression of Bcl-2, an inhibitor of apoptosis, was significantly reduced in ventricles from five dogs with pacing-induced heart failure. No change in the expression of the apoptotic inducer Bax was detected. Fas and FADD were significantly elevated in all paced ventricles, and Fas-L was only detected in the paced hearts. Both caspase-2 and caspase-3 were elevated following ventricular pacing. CONCLUSIONS: We have identified components of the signalling pathways along which apoptosis proceeds following the induction of heart failure in dogs. Apoptosis was also detected in the atria raising the possibility that, like human dilated cardiomyopathy, the molecular changes are global.

[Late fields in magnetcardiography and late potentials in electrocardiography after acute myocardial infarction]. / Vergleich magnetokardiographischer Spätfelder mit elektrokardiographischen Spätpotentialen bei Postinfarktpatienten.

UNLABELLED: A high specificity and a high positive prediction has been reached in risk stratification for a sudden cardiac death after acute myocardial infarction (AMI) by combining multiple methods. But sensitivity and negative prediction are still not satisfying. There are the same physiological processes underlying magnetocardiography (MCG) and electrocardiography (ECG). Nevertheless, the signals in each method contain different information. METHODS: We studied the cardiac magnetic fields in 50 patients after AMI and in 32 probands and calculated the magnetic late field (LF), according to Simsons late potential (LP) analysis. We defined normal values, according to the 95% confidence interval of the probands (QRS < =97 ms, RMS > = 0. 6, LAS < 25 ms). RESULTS: We compared the results of LF and LP analysis regarding pathologic-nonpathologic and found 76% of the patients with the same results in both methods. Four patients had magnetic signals with low amplitude in the ST segment in contrast to the ECG result, while 6 patients with a "LP positive" diagnosis based on RMS and LAS only, did not show LF. In addition, we have found the magnetic QRS complex to be shorter than the electrical one. DISCUSSION: In general, the results of LF measurement are similar to the ones of LP measurement. Presumably, there are intracardial currents, which are not detectable by ECG. Further studies are needed to evaluate the prognostic value in patients at high risk for cardiac arrhythmias.

Changes in myocardial protein expression in pacing-induced canine heart failure.

Canine rapid ventricular pacing produces a low output cardiomyopathic state which is similar to dilated cardiomyopathy. In this study dogs were paced at 245 beats per minute (bpm) for 3-4 weeks until signs of heart failure were apparent. Unpaced dogs were used as controls. A previous study identified myocardial protein changes in the pH region 4-7 following ventricular pacing by using two-dimensional electrophoresis (2-DE) (Heinke et al., Electrophoresis 1998 19, 2021-2030). Many of these proteins were associated with mitochondria, energy metabolism within the cardiomyocyte, the cytoskeleton and calcium cycling. The present study aimed to examine the proteins migrating in the more basic region of the 2-DE pattern using immobilised pH gradient 3-10 strips to separate myocardial proteins. The expression of 31 proteins was altered in the paced myocardium: 21 were decreased and 10 increased. Following the identification of 23 of these spots by either amino acid compositional analysis or peptide mass fingerprinting or a combination of both, we confirm that many of the proteins whose expression is altered following ventricular pacing are associated with the mitochondria and energy production within the cardiomyocyte, including creatine kinase M, triosephosphate isomerase, phosphoglycerate mutase, cytochrome c oxidase, cytochrome b5, hydroxymethyl glutaryl CoA synthase, myoglobin, and 3,2-trans-enoyl-CoA transferase. Additionally, the cytoskeletal protein actin was increased in the paced hearts. These results strongly support the notion that energy production is impaired and mitochondrial dysfunction is involved in the development of heart failure in the paced dog.

Protein changes observed in pacing-induced heart failure using two-dimensional electrophoresis.

Rapid ventricular pacing in dogs results in a low output cardiomyopathic state which is similar to idiopathic dilated cardiomyopathy in man. However, the pathophysiological mechanisms which cause this failure following pacing are unknown. Five dogs underwent rapid ventricular pacing. Hearts were stimulated at 245 beats per min (bpm) for four weeks and then reduced to 190 bpm to stabilize the failure. Six unoperated dogs were used as controls. This paper compares the two-dimensional gel electrophoresis (2-DE) protein patterns of left ventricular samples from the paced myocardium with the control dogs. Changes in protein expression were analyzed qualitatively and semi-quantitatively. In the paced dog samples 69 protein spots were significantly altered of which 42 were decreased and 27 were elevated. One qualitative change was observed: elongation factor Tu was present only the control hearts. Of these proteins, 20 have been identified by a combination of N-terminal protein microsequencing, peptide mass profiling by mass spectrometry, amino acid compositional analysis, and by comparison with databases of canine and human ventricular proteins. Ten of these are associated with mitochondria and energy production, including: pyruvate dehydrogenase E1 component, isocitrate dehydrogenase subunit alpha, HSP60 and HSP70, creatine kinase M and fatty acid binding protein. The cytoskeletal protein desmin was detected in reduced quantities and a spot corresponding to a fragment of desmin was increased. These results indicate that the development of heart failure in the paced dog involves alterations in mitochondrial energy production, the cytoskeleton and calcium activation.

Different electrophoretic techniques produce conflicting data in the analysis of myocardial samples from dilated cardiomyopathy patients: protein levels do not necessarily reflect mRNA levels.

A variety of electrophoretic techniques were used to search for potential causes of human dilated cardiomyopathy (DCM). Northern blots were used to quantify alpha-cardiac and alpha-skeletal muscle actins, and beta-myosin heavy chain mRNAs which are the predominant expressed isoform species. We found a wide range of mRNA levels expressed in both DCM and nondiseased (ND) samples of left ventricles. However, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels of the same heart samples revealed a stable and constant ratio of actin and myosin. Dystrophin deficiency might account for the DCM symptoms and so dystrophin levels of DCM and ND samples were evaluated using Western blots probed with monoclonal antibodies for the N-, C- and mid-rod portions of this protein. We found that dystrophin levels were constant in all 29 DCM and 5 ND samples suggesting that dystrophin deficiency is probably not a contributing cause. We explored the possibility that terminal failure may be due to an apoptotic-like event in the cardiomyocytes. Zymograms of DCM and ND samples revealed a significant increase in DNase I activity in the DCM group compared to the ND samples. These data raise the possibility that end-stage failure may be associated with apoptosis.

Esophageal balloon electrode catheter for transthoracic recording of His-bundle potential with transesophageal atrial pacing.

To evaluate the influence of transesophageal atrial pacing of the transthoracic His potential identification, we combined signal-averaged ECG with transesophageal atrial pacing with low threshold for pacing averaging ECG recording. A tripolar 10 French esophageal balloon electrode catheter, with one cylindrical electrode on the tip of the catheter and two balloon electrodes on the cardiac side of the catheter, used in 53 patients, allowed a painless transesophageal atrial pacing and a high signal to noise distance in the signal-averaged ECG. Transesophageal atrial pacing allowed in 37 of 53 patients an identification of His potential by increasing the distance between the end of the atrial potential and the onset of the His potential in the pacing averaging ECG. The esophageal balloon electrode catheter allowed a painless transesophageal atrial pacing with low threshold for atrial capture during a long pacing time and a high signal to noise distance in the pacing averaging ECG. The increasing of the heart rate with transesophageal atrial pacing allowed the transthoracic identification of the His potential in the pacing averaging ECG.

[Clinical-electrophysiologic studies on the actions of the anti-arrhythmic substance AWD-G256 in man]. / Klinisch-elektrophysiologische Untersuchungzen zur Wirkung der antiarrhythmischen Substanz AWD-G256 beim Menschen.

The effects of the new antiarrhythmic drug AWD-G256 (1) were investigated by clinical electrophysiology (His bundle electrography, programmed electrical stimulation) in 19 patients with supraventricular tachycardias but without structural heart disease. In a maximal dosage of 0.45 mg/kg body mass 1 only minimally affects electrophysiological parameters of the impulse formation and conduction. At this time the therapeutic value of 1 is not clear.

Balloon electrode catheter for transesophageal atrial pacing and transesophageal ECG recording.

A new balloon electrode catheter (10 French) with five or six balloon electrodes placed on the cardiac side was developed for transesophageal atrial pacing and bipolar ECG recording. The diameter of the hemispheric electrodes is 6 mm and the length of the esophageal balloon is 10 cm. The transesophageal atrial pacing threshold was measured with the balloon electrode catheter by transesophageal programmed atrial stimulation (TPS) (n = 54). At the onset of TPS, the feeling, capture (n = 54), and pain voltage threshold (n = 6) were measured by increasing the amplitude of the pacing voltage during high rate bipolar atrial pacing and bipolar atrial ECG recording. In 38 TPS, the capture threshold was lower than the feeling threshold (n = 28). In 16 TPS, the capture threshold was higher than the feeling threshold. In conclusion, painless atrial pacing and excellent ECG recording can be achieved with a multipolar esophageal balloon electrode catheter with a low pacing voltage amplitude and a high P wave amplitude.

Termination of tachycardias by transesophageal electrical pacing.

To evaluate the therapeutic significance of noninvasive transesophageal pacing for termination of tachycardias the method of rapid atrial or ventricular transesophageal pacing was used in 233 patients with different tachycardiac arrhythmias. We were able to terminate atrial flutter in 136 of 162 patients by transesophageal rapid atrial stimulation (conversion to sinus rhythm in 75 cases, induction of atrial fibrillation in 61 cases). Atrial tachycardias were interrupted in 17 of 23 patients (sinus rhythm in 11 cases, atrial fibrillation in six cases). AV reciprocating/AV nodal supraventricular reentry tachycardias were terminated in 62 of 63 patients (sinus rhythm in 58 cases, atrial fibrillation in four cases). By transesophageal rapid ventricular pacing ventricular tachycardias could be terminated in ten of 15 patients. The success rate of transesophageal pacing was influenced by the pacing rate, by the type of tachycardiac arrhythmia inclusive by the type of atrial flutter and by the tachycardia's cycle length. Because the success rates are comparable with invasive technique and the procedure is simpler, the noninvasive transesophageal antitachycardiac pacing should be respected as the method of the first choice in patients with supraventricular tachycardias.

[Electrophysiological anti-arrhythmia effects of tiracizine in ventricular tachycardia]. / Elektrophysiologische und antiarrhythmische Effekte von Tiracizin bei ventrikulären Tachykardien.

The electrophysiologic effects and antiarrhythmic efficacy of tiracizine, a new class I antiarrhythmic drug, were studied in 16 patients with documented sustained ventricular tachycardia (VT) after intravenous drug application and in 6 patients after oral drug administration by means of programmed ventricular stimulation (PVS). After intravenous tiracizine (0.3 mg/kg) the VT was no longer inducible by PVS in 3 of 16 patients and became nonsustained in another patient. In 11 of 13 patients with further inducible VT the cycle duration of VT increased after tiracizine (mean 29 ms). After oral tiracizine (150-225 mg/day) the VT induction was suppressed in one patient. In a second patient the VT became nonsustained. Cycle length of VT in 4 patients with persistent induction of VT was longer after therapy (mean 88 ms). Antiarrhythmic efficacy of intravenous or oral tiracizine can be expected in at least one third of patients with VT.