[Solitary liver tumor as a manifestation of polyarteritis nodosa]. / Solitärer Lebertumor als Manifestation der Panarteriitis nodosa.

HISTORY: A 65-year-old female was admitted with fever of unknown origin. DIAGNOSTIC PROCEDURES: Abdominal computed tomography showed a solid mass (7.5 cm in diameter) with central fluid, located in the right lobe of the liver. Fine-needle aspiration cytology was unremarkable. Further work-up procedures for suspected liver abscess included colonoscopy, which surprisingly revealed adenocarcinoma at 13 cm from the anal orifice. THERAPY AND CLINICAL COURSE: Both lesions in the rectum and liver were resected. While a moderately differentiated (G2) adenocarcinoma of the rectosigmoid junction (stage T3/ N0) was confirmed, histology of the hepatic mass showed liver infarction due to polyarteritis nodosa of the medium-sized arteries. Treatment with 20 mg/d prednisolone was initiated and tapered off over the next three months. The clinical course after discontinuation of corticosteroids was unremarkable over a 6-month follow-up. CONCLUSION: It is suggested that polyarteritis nodosa of the liver occurred in this patient as a paraneoplastic phenomenon and subsided after resection of colorectal cancer and short-term immunosuppression with prednisolone.

[Importance of the history and the utilization of therapy guidelines in patients with arrhythmias]. / Bedeutung der Anamnese und der Umsetzung von Therapieleitlinien bei Rhythmuspatienten.

In this article criteria for taking the history in patients with manifest or potential life threatening arrhythmias are outlined. The importance of a sound (family) history is demonstrated. Besides specific correlates for arrhythmias in the history of a patient, the long term consequences of dyspnoe on exertion and hypertension are outlined. In 80% of patients sudden death is due to myocardial ischemia or interstitial myocardial fibrosis which in turn result from acquired diseases such as coronary artery disease and hypertension. Against this background the importance of the prevention of sudden cardiac death by nonantiarrhythmics drugs is stressed. Examples of under-utilization of therapy guidelines are given with special reference to beta-blocker therapy.

Altered dynamics of action potential restitution and alternans in humans with structural heart disease.

BACKGROUND: Restitution kinetics and alternans of ventricular action potential duration (APD) have been shown to be important determinants of cardiac electrical stability. In this study, we tested the hypothesis that APD restitution and alternans properties differ between normal and diseased human ventricular myocardium. METHODS AND RESULTS: Monophasic action potentials were recorded from the right ventricular septum in 24 patients with structural heart disease (SHD) and in 12 patients without SHD. Standard and dynamic restitution relations were constructed by plotting APD as a function of the preceding diastolic interval. The dynamic restitution relation of both groups showed a steeply sloped segment at short diastolic intervals that was associated with the occurrence of APD alternans. Patients with SHD had a wider diastolic interval range over which APD alternans was present (mean+/-SEM 68+/-11 versus 12+/-2 ms) and showed an earlier onset (168+/-7 versus 225+/-4 bpm) and an increased magnitude (20+/-2 versus 11+/-2 ms) of APD alternans compared with patients without SHD. The occurrence of APD alternans during induced ventricular tachycardia (6 episodes) and during rapid pacing could be derived from the dynamic restitution function. CONCLUSIONS: There are marked differences in the dynamics of APD restitution and alternans in the ventricular myocardium of patients with SHD compared with patients without SHD. These differences may contribute importantly to cardiac electrical instability in diseased human hearts and may represent a promising target for antiarrhythmic substrate modification.

Morphology discrimination: a beat-to-beat algorithm for the discrimination of ventricular from supraventricular tachycardia by implantable cardioverter defibrillators.

Inappropriate therapy of SVTs by ICDs remains a major clinical problem despite enhanced detection criteria like "sudden onset" and "rate stability" in third-generation devices. Electrogram morphology discrimination offers an additional approach to improve discrimination of supraventricular tachycardia (SVT) from ventricular tachycardia (VT). In a prospective, multicenter study, patients received an ICD with a beat-to-beat algorithm for morphological analysis of the intracardiac electrogram (Morphology Discrimination, MD). A nominal programmingfor standard enhancement criteria and morphology discrimination was required at implant. Electrogram storage of tachycardia episodes irrespective of delivery of therapy was used to assess sensitivity and specificity of the morphology algorithm alone and in combination with established detection criteria. During a 126 6-month follow-up, 886 episodes of device stored electrograms from 82 of 256patients were evaluated. Atnominal settings, the MD algorithm correctly identified 423 of 551 episodes as VT resulting in sensitivity of 77%. The classification of SVT was met in 239 of 335 episodes resulting in specificity of 71%. In combination with sudden onset, sensitivityincreased to 99.5% at the expense of specificity (48%). In conclusion, SVT-VT discrimination based on morphological analysis alone results in limited sensitivity and specificity. Programming the monitor mode allows individual assessment of the performance of this detection enhancement feature during clinical follow-up without compromising device safety. Only in patients with documented efficacy of morphology discrimination should this feature be subsequently activated.

Breath-to-breath variability correlates with apnea-hypopnea index in obstructive sleep apnea.

BACKGROUND: Breathing in patients with obstructive sleep apnea (OSA) is frequently interrupted by periods of hypopnea and apnea. There is limited information regarding a possible disturbance of breathing outside these periods. STUDY OBJECTIVE: To analyze the degree of breathing disturbance during nonocclusion. DESIGN: Prospective determination of breathing variability during full polysomnographic sleep studies. PATIENTS: Breath-to-breath variation was monitored in 34 patients with OSA and in 9 healthy subjects. MEASUREMENTS AND RESULTS: All breath-to-breath intervals were automatically analyzed from flow signal, displayed, and manually corrected for artifacts. Distribution of all nonapneic breath intervals was analyzed for the extent of difference from a normal distribution pattern by specifying kurtosis. In untreated OSA patients, kurtosis was significantly reduced (0.0 +/- 0.5, mean +/- SD) compared to control subjects (0.8 +/- 0.5), indicating increased variability of nonoccluded breathing. This effect was present in all sleep stages, and the extent depended significantly on the degree of disease. Continuous positive airway pressure breathing was able to normalize kurtosis (1.0 +/- 0.9) immediately. CONCLUSIONS: Breathing in OSA is not only characterized by interruptions of breathing during occlusion, but by a greater variation in the pattern of normal-length breaths.

Independent autonomic modulation of sinus node and ventricular myocardium in healthy young men during sleep.

INTRODUCTION: The aim of this study was to investigate whether autonomic modulation of ventricular repolarization may spontaneously differ from that of the sinoatrial node. METHODS AND RESULTS: Onset of P waves, QRS complexes, and the apex and end of T waves were detected beat to beat in high-resolution ECGs from nine healthy young men during the night. There were time-dependent fluctuations in the QT/RR slopes of consecutive 5-minute segments that could not be explained by the mean RR cycle length of the respective segment. Because the variability found in QT intervals could not be explained by either possible effects of rate dependence or hysteresis, autonomic effects were obvious. Power spectral analysis was performed for consecutive 5-minute segments of PP and QT tachograms. In a given subject, trends in the time course of low-frequency (LF) and high-frequency (HF) power in PP and QT often were similar, but they were quite different at other times. The mean LF/HF ratio for QTend (0.75 +/- 0.1) was different from that of PP (1.8 +/- 0.2; P = 0.002), indicating differences in sympathovagal balance at the different anatomic sites. Furthermore, at a given mean heart rate, averaged QT intervals were different on a time scale of several minutes to hours. The QT/RR slope of 5-minute segments correlated significantly with the HF power of QT variability but not with that of PP variability, indicating effects of the autonomic nervous system on ventricular action potential restitution. CONCLUSION: These differences demonstrate that changes in sinus node automaticity are not necessarily indicative of the autonomic control of ventricular myocardium.

[A new ICD morphology criterion for differentiating supraventricular and ventricular tachycardia]. / Neues ICD-Morphologie-Kriterium zur Differenzierung supraventrikulärer und ventrikulärer Tachykardien.

The high incidence of inappropriate therapies due to supraventricular tachycardia remains a major unsolved problem of the implantable cardioverter defibrillator. A new morphology discrimination (MD) algorithm has been introduced to improve specificity of ICD therapy without loss of sensitivity. It was the aim of this study to systematically analyze sensitivity and specificity of the MD criterion in combination with the enhanced detection criteria sudden onset and rate stability in the detection of ventricular and supraventricular tachycardia. After ICD implantation in 259 patients, 787 detected episodes in 74 patients with available stored electrograms were documented during a follow-up period of 359 +/- 214 days. With a nominal programming of the MD algorithm at > or = 60%, sensitivity and specificity for all episodes were 82.6%/77.2%. For sinus tachycardia, atrial fibrillation and atrial flutter the specificities were 80.6%, 69.6% and 75%, respectively. In patients with primarily appropriate MD detection, sensitivity and specificity significantly improved to 95.8%/91.7%. Programming the sudden onset criterion with < 100 ms and the stability criterion with < 50 ms, sensitivity and stability of the combined application of the MD algorithm and sudden onset and MD algorithm and stability were 96.2%/52.2% and 94.4%/63.8%, respectively. The MD criterion in combination with other enhanced detection criteria might significantly improve specificity of tachyarrythmia detection of ICD therapy.

[Neurocardiogenic convulsive syncope--differential diagnosis, pathophysiology and therapy based on a case report]. / Die neurokardiogene konvulsive Synkope--Differentialdiagnose, Pathophysiologie und Therapie anhand eines Fallberichts.

Neurocardiogenic convulsive syncope as a disease at the border between cardiovascular and neurologic dysfunction can pose considerable diagnostic challenges. We report on the case of a 19 year-old female patient with recurrent neurocardiogenic convulsive syncope where the time from the onset of symptoms to the correct diagnosis and initiation of an effective therapy spanned more than three years. Based on this case report, we discuss differential diagnosis, pathophysiology and therapy of this disorder of autonomic cardiovascular regulation. Neurocardiogenic convulsive syncope should be considered whenever a patient has both syncope that exhibits a typical cardiovascular pattern (e.g., fainting of short duration with rapid reorientation phase) and prolonged loss of consciousness with characteristic neurological features (e.g., cerebral seizures with postictal state of confusion). Head-up tilt testing, introduced into clinical practice in 1986, is an efficient tool to diagnose neurocardiogenic syncope with comparatively high sensitivity in patients with recurrent syncope of unknown origin. Besides orthostatic training and pharmacotherapy, permanent dual-chamber cardiac pacing has gained increasing importance as treatment for cardioinhibitory forms of neurocardiogenic syncope.

Receiver operating characteristics of perceptrons: influence of sample size and prevalence.

In many practical classification problems it is important to distinguish false positive from false negative results when evaluating the performance of the classifier. This is of particular importance for medical diagnostic tests. In this context, receiver operating characteristic (ROC) curves have become a standard tool. Here we apply this concept to characterize the performance of a simple neural network. Investigating the binary classification of a perceptron we calculate analytically the shape of the corresponding ROC curves. The influence of the size of the training set and the prevalence of the quality considered are studied by means of a statistical-mechanics analysis.

Demonstration of nonlinear components in heart rate variability of healthy persons.

We present a systematic approach for detecting nonlinear components in heart rate variability (HRV). The analysis is based on twenty-three 48-h Holter recordings in healthy persons during sinus rhythm. Although many segments of 1,024 R-R intervals are stationary, only few stationary segments of 8,192-32,768 R-R intervals can be found using a test of Isliker and Kurths (Int. J. Bifurcation Chaos 3:1573-1579, 1993.). By comparing the correlation integrals from these segments and corresponding surrogate data sets, we reject the null hypothesis that these time series are realization of linear processes. On the basis of a test statistic exploring the differences of consecutive R-R intervals, we reject the hypothesis that the R-R intervals represent a static transformation of a linear process using optimized surrogate data. Furthermore, time irreversibility of the heartbeat data is demonstrated. We interpret these results as a strong evidence for nonlinear components in HRV. Thus R-R intervals from healthy persons contain more information than can be extracted by linear analysis in the time and frequency domain.

Preserved autonomic modulation of the sinus and atrioventricular nodes following posteroseptal ablation for treatment of atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Following radiofrequency catheter ablation of AV nodal reentrant tachycardia (AVNRT), inappropriate sinus tachycardia may occur, possibly due to damage to autonomic cardiac nerve fibers. Furthermore, inducibility of AVNRT is often critically dependent on the autonomic balance. We investigated whether successful ablation of AVNRT is associated with an alteration of autonomic input to the sinus and AV nodes. METHODS AND RESULTS: To estimate changes in the autonomic modulation of the sinus and AV nodes, power spectra of beat-to-beat PP and PR intervals were analyzed from high-quality nighttime ECG recordings of 11 patients before and after radiofrequency application. Normalized HF power (nHF) of PP and PR intervals was used as an index of efferent vagal modulation and the LF/HF ratio as an index of sympathovagal balance of the sinus node (PP) and AV node (PR). Before ablation, LF/HF(PP) was 3.2 and nHF(PP) was 0.3 in the sinus node. For the AV node, LF/HF(PR) was 1.2 and nHF(PR) was 0.5. Following ablation, LF/HF(PP) (3.5) and nHF(PP) (0.3) of the PP intervals did not change. Similarly to the sinus node, there were no changes in the autonomic modulation of the AV node, as both LF/HF(PR) (1.2) and nHF(PR) (0.5) remained unchanged. CONCLUSION: Our results indicate that autonomic control of the sinus and AV nodes is preserved following successful radiofrequency ablation of AVNRT. The effects of posteroseptal radiofrequency current application are not necessarily mediated by changes in the autonomic input to the AV node.

Body surface potentials during discharge of the implantable cardioverter defibrillator.

INTRODUCTION: Little is known about the hazard for persons in contact with patients experiencing a high-voltage discharge of their implantable cardioverter defibrillator (ICD). Compared to epicardial systems, this risk may be increased with transvenous electrode systems and particularly in active can configurations. METHODS AND RESULTS: In 23 patients with a transvenous active can ICD system, body surface potentials Vs and current through an external resistance were measured during 35 discharges. Vs was detected using skin electrodes positioned over the left subpectorally implanted pulse generator [C], apex of the heart [A], and the right pectoral region [RP]. Mean Vs during discharges without an external shunt resistance ranged between 13 and 63.8 V [C to A] and 12.5 to 47.3 V [C to RP] (ICD peak stored/output voltage Vcap = 183 to 606 V, n = 20). Mean current flow [C to A] was 8.2 to 46.8 mA (Vcap = 288 to 633 V, n = 10) and 42 to 120.7 mA (Vcap = 447 to 579 V, n = 5) across a resistance of 1,696 and 797 omega, respectively. CONCLUSION: During high-output shocks, a considerable potential difference is present on the body surface of ICD patients that, according to the literature, may induce a single cardiac response in a bystander. Analogous to spontaneous extrasystoles, there is only a minimal chance of triggering a tachyarrhythmia by this stimulated extra beat. Direct induction of ventricular fibrillation is unlikely, since reported fibrillation threshold values are much higher than the observed magnitudes of current and voltage.

Inappropriate discharge of an implantable cardioverter defibrillator during atrial flutter and intermittent ventricular antibradycardia pacing.

INTRODUCTION: Inappropriate discharges of an implantable cardioverter defibrillator (ICD) are troublesome to the patient and sometimes a difficult task for the physician trying to identify and treat the cause. METHODS AND RESULTS: For the first time, we report a mechanism of inappropriate ICD discharges during episodes of atrial flutter with a slow ventricular response and intermittent antibradycardia pacing. The episodes occurred in two patients and were triggered by the unique sensing algorithm of the Ventritex Cadence V-100 in combination with the tripolar CPI Endotak 072 transvenous defibrillation lead, which provides integrated bipolar sensing. CONCLUSION: Besides treatment of the underlying arrhythmia, reprogramming of the device, an electrode position far away from the atria, and true bipolar sensing will enhance the performance of ICD systems with respect to the episodes described here. In addition, more flexible sensing algorithms may, in the future, prevent this overall rare complication.

[Implantation of a transvenous defibrillation system in isolated persistent left superior vena cava]. / Implantation eines transvenösen Defibrillationssystems bei isoliert persistierender linker oberer Hohlvene.

HISTORY AND CLINICAL FINDINGS: A 49-year-old man, an alcoholic for the past 7 years, complained of dizziness, palpitations and exertional dyspnoea (NYHA stage III). Physical examination revealed peripheral cyanosis, slightly raised jugular venous pressure, râles in the lung bases, a loud systolic murmur, maximal over the apex, and an enlarged palpable liver. INVESTIGATIONS: Results of biochemical tests were unremarkable. The ECG showed sinus rhythm, 1 degree AV block and signs of left ventricular hypertrophy. Chest radiogram demonstrated cardiac dilatation and probably absent right superior vena cava (SVC). Long-term ECG monitoring during episodes of dizziness and one syncope revealed self-limited periods of unifocal ventricular tachycardia. Echocardiography and angiography showed bilateral ventricular dilatation with an ejection fraction reduced to 20%, as well as mild mitral and moderate tricuspid regurgitation but normal cardiac valves, suggesting a dilated cardiomyopathy. Coronary angiography was normal. No myocarditis was revealed on myocardial biopsy. The patient declined electrophysiological investigation. TREATMENT AND COURSE: Amiodarone caused higher degree AV block. A temporary pacemaker lead was inserted via the persistent left SVC, amiodarone discontinued and later a pacemaker-defibrillator system (ICD) implanted, previous digital subtraction angiography having demonstrated a left SVC and absent right SVC. The transvenous electrode had been placed via the left subclavian vein, left SVC (anode), coronary sinus, right atrium into the right ventricle (cathode), and the pacemaker-defibrillator implanted subpectorally. Stable electrode position and correct ICD function has been documented over 2 years. 4 months after implantation bursts of ventricular tachycardia recurred every few minutes that responded to renewed amiodarone administration. CONCLUSION: Good long-term results can be obtained with ICD electrodes implanted via a persistent LSVC.

Evolution of late potentials during the first 8 hours of myocardial infarction treated with thrombolysis.

It has been demonstrated that successful thrombolytic therapy is associated with a reduction of late potentials in the signal-averaged electrocardiogram (SAECG) recorded within 48 hours after hospital admission. This study extends these observations, using for the first time a longitudinal design investigating whether ischemia and its potential reversal by thrombolytic therapy are associated with dynamic changes in SAECG recordings obtained continuously for 8 hours after the start of therapy in patients with acute myocardial infarction (MI). SAECGs were obtained from 12 patients (2 women and 10 men; ages 63 +/- 13 years) with acute MI. The SAECG (X2 + Y2 + Z2)1/2 was generated with a high pass filter of 40 Hz, noise < or = 0.3 microV. Comparing the SAECG recordings during the first and eighth hours, there was a significant decrease in filtered QRS duration (fQRS; 119.5 +/- 17.1 vs 106.3 +/- 15.3 ms) and duration of the low amplitude signals < or = 40 microV of the terminal QRS (LAS40; 48.8 +/- 18 vs 34.2 +/- 14.2 ms), and increase of root mean square voltage of the last 40 ms of the QRS (t-RMS; 14.8 +/- 9.3 vs 37.8 +/- 34.4 microV) (rank test, P < or = 0.05). In this patient series, there was a significant improvement of fQRS, t-RMS, and LAS40 during the first 8 hours of acute MI, perhaps indicating reversal of ischemia with thrombolysis. Even during acute MI, these markers of delayed conduction allow investigation of intervention induced changes in myocardial conduction and possibly prediction of the patency of the infarct related artery using signal-averaging techniques.

Different vagal modulation of the sinoatrial node and AV node in patients with congestive heart failure.

1. We have previously shown that in healthy young men autonomic control of the sinoatrial (SA) and AV node may be independent during sleep. It is conceivable, that this independence is lost in patients with high sympathetic activity. This would be in analogy to exercise in normal subjects, where an increase in sinus rate is associated with a shortening of the PR interval. 2. The aim of this study was to investigate whether this independence of SA and AV nodal autonomic modulation is maintained in patients with congestive heart failure. 3. For analysis of heart rate variability (HRV) the ECG was online digitized from 10 pm to 6 am in six patients with congestive heart failure (EF < 40%). The onset of P-waves and QRS-complexes was recognized by a computer algorithm with an accuracy of +/-1 ms. Power spectra of PR intervals and PP intervals were calculated for consecutive 256 second segments. The power in the high frequency component. (HF, 0.15 - 0.4 Hz) of PP intervals was used as an index of vagal drive to the SA node. The vagal input to the AV node was determined by the spectral power of the corresponding PR intervals. 4. All patients showed the typical spectral peak in the HF band, both in PP and PR. The power spectral density of HF varied over time with different patterns for PP and PR. The ratio of the HF power derived from PP and PR was calculated for each segment. This ratio was not constant, but showed a distinct time course. 5. Congestive heart failure did not abolish the independence of vagal modulation of SA and AV node, as assessed by the HF power derived from PP and PR intervals. Thus, the difference in vagal traffic to the SA and AV node was maintained even in the setting of high background sympathetic activity. Further investigation is needed to analyze potential factors responsible for this difference in patterns and the clinical relevance of this finding.

Independent autonomic modulation of the human sinus and AV nodes: evidence from beat-to-beat measurements of PR and PP intervals during sleep.

INTRODUCTION: Evidence from animal experiments indicates that the autonomic nervous system may influence the sinus (SA) and atrioventricular (AV) nodes differently. We investigated, therefore, whether there are spontaneous functional differences in the innervation of the SA and AV nodes in man. METHODS AND RESULTS: This study was performed in 10 healthy males (ages 21 to 26 years) during strict bed rest from 10 pm to 6 am. Three ECG leads were digitized on-line. PR and PP intervals were determined on a beat-to-beat basis off-line using a correlation algorithm with an accuracy of +/- 2 msec and were verified visually. During major body movements, there were sudden decreases in PP intervals of 36 to 827 msec (mean 335) for periods of 6 to 265 seconds (mean 24). During these phases of heart rate (HR) acceleration, PR intervals showed either concomitant shortening (9 to 30 msec), no change, or lengthening (6 to 25 msec). Furthermore, tonic changes in the PR interval occurred over 15-minute periods during which the range of PP intervals was constant. Additionally, recovery-adjusted PR interval (PR-b2/RP) and cycle length were negatively correlated for some periods, which confirmed independent autonomic effects on SA node and AV node. CONCLUSION: Beat-to-beat measurement of PR intervals allows for evaluation of autonomic effects on the human AV node. The different patterns in PR intervals during sudden spontaneous increases in HR and the tonic changes in PR interval indicate that the autonomic inputs to the SA and AV nodes are, in principle, independent of each other.

General relation between variance-time curve and power spectral density for point processes exhibiting 1/f beta-fluctuations, with special reference to heart rate variability.

Counting statistics in the form of the variance-time curve provides an alternative to spectral analysis for point processes exhibiting 1/f beta-fluctuations, such as the heart beat. However, this is true only for beta < 1. Here, the case of general beta is considered. To that end, the mathematical relation between the variance-time curve and power spectral density in the presence of 1/f beta-noise is worked out in detail. A modified version of the variance-time curve is presented, which allows us to deal also with the case beta > or = 1. Some applications to the analysis of heart rate variability are given.