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Biomedical subjects

H U Klein

Publications and source records attributed to H U Klein.

At least 19 recordsLinked to original sources

Cardiac involvement in limb-girdle muscular dystrophy 2I : conventional cardiac diagnostic and cardiovascular magnetic resonance.

BACKGROUND: The C826A mutation in the fukutin-related protein (FKRP) gene is typically associated with autosomal recessive limb-girdle muscular dystrophy 2I (LGMD2I) but oligosymptomatic phenotypes and patients with predominant cardiac involvement are also described. OBJECTIVE: To assess cardiac involvement in patients with LGMD2I. PATIENTS: Nine patients from 5 families (2 female, 7 male) homozygous for the 826C > A FKRP mutation were included. METHODS: Additional to conventional cardiac investigations (electrocardiography and echocardiography) the patients underwent cardiovascular magnetic resonance imaging (CMR). RESULTS/CONCLUSION: Cardiac involvement was detected by CMR in eight of nine patients (reduced left ventricular ejection fraction in 6, enlargement of left ventricular end-diastolic volume in 2 and left ventricular mass in 2) and in four patients by conventional cardiac diagnostic investigations. Two of the nine patients showed no muscle weakness or atrophy but suffered myalgias; both had cardiac manifestation of the disease. CMR is a sensitive method for detecting cardiac abnormalities in patients with LGMD2I and can be used for early detection of mild or subclinical cardiac involvement.

Adolescent↗

Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation.

Atrial tachyarrhythmia (AF) alters intracellular calcium homeostasis and induces cellular hypertrophy of atrial myocytes. The impact of the calcium-dependent calcineurin pathway on the development of AF-induced atrial hypertrophy has not yet been analyzed. In this study, atrial tissue samples from patients with sinus rhythm and chronic persistent atrial fibrillation (CAF) were used to determine changes in expression and activity of calcineurin A (CnA), and its relation to CnA-regulated transcription factors NFATc1-4, and hypertrophic markers ANP, troponin I, and beta-MHC. CnA phosphatase activity and CnAbeta protein contents were significantly upregulated in patients with CAF. Calcineurin activation led to dephosphorylation, redistribution, and subsequent accumulation of NFATc3 in nuclei during CAF, and expression of hypertrophic genes was increased. CAF-dependent changes were reproduced by ex vivo pacing (2-4 Hz) of human atrial tissue slices. FK506 abolished the hypertrophic response induced by electrical-field stimulation. Atrial tachyarrhythmia causes atrial hypertrophy by activation of the CnA signal pathway, which thereby contributes to structural remodeling of human atria.

Aged↗

[Prevention of sudden cardiac death].

The problem of sudden cardiac death (SCD) is complex and many questions concerning the pathophysiologic mechanism are still unanswered. At present the only reliable way of recognizing high risk patients is by means of left ventricular dysfunction, measured as LV-EF<or=35%. The positive predictive accuracy for other non-invasive risk markers is too low. So far, antiarrhythmic drugs have failed to successfully prevent SCD. More than 25 years of clinical experience with the implantable defibrillator (ICD) with its continuous technical improvement has made the ICD the most effective weapon against SCD. Its effectiveness has been demonstrated in many prospective trials and the use of the ICD is fully enclosed within the current guidelines for the prevention of SCD. Guidelines do not, however, replace the physician's judgement and experience to correctly evaluate the patient's status. ICD therapy in the primary and secondary prevention of heart failure, which is often accompanied by a high risk of SCD is, however, not justified without guideline-adjusted therapy.

Age Factors↗

Volume measurement by CARTO compared with cardiac magnetic resonance.

AIMS: The CARTO electrophysiological mapping system has demonstrated accurate results for end-diastolic ventricular volumes in casts and animals. However, in humans, a comparison with cardiac magnetic resonance (CMR), the non-invasive gold standard for volumetric analysis, has not yet been performed. METHODS AND RESULTS: A total of 34 (29 male) heart failure patients (NYHA class III/IV) underwent an electrophysiological mapping procedure with the CARTO system in the left ventricle (LV) (n = 34) and right ventricle (RV) (n = 12) and CMR for RV and LV end-diastolic volume (RVEDV and LVEDV) measurements another day. Mean LVEDV was comparable between CMR and CARTO (328 +/- 95 and 320 +/- 92 mL, respectively; P = NS), whereas RV volumes measured by CARTO were larger (CMR 140 +/- 48 vs. CARTO 176 +/- 47 mL; P < 0.01). Overall, we found a good correlation between CMR and CARTO measurements for both chambers; however, the Bland-Altman analysis showed a non-interchangeability of these methods. Measurement differences were independent of chamber size, but significantly affected by the number of acquired mapping points. CONCLUSION: Although CMR and CARTO showed a good correlation in the measurement of RVEDV and LVEDV in a group of heart failure patients, the clinical interchangeability of the two methods may be questioned.

Electrophysiologic Techniques, Cardiac↗

[Syncope in the elderly].

Age-related physiologic changes, a higher prevalence of chronic illness, and concomitant (often multiple) medication account for a higher susceptibility of elderly patients to syncope. Although elderly patients are the largest group with syncope, the causes frequently remain unclear. Multifactorial causes, lack of witnesses, overlap with falls, and additional cognitive impairment often confound the assessment of syncope in the elderly. Thus, strategic investigation is often needed to establish the diagnosis and to unmask the cause. In addition to a comprehensive medical history (by both patient and witnesses), a thorough physical examination including supine and standing blood pressure measurements and a standard 12 lead ECG remain the mainstay of diagnosis. The decision whether additional tests are needed depends on indications whether organic heart disease is present or not. Without evidence of structural heart disease, tilt table testing and studies of autonomic function are the next steps. In contrast, additional cardiac investigation (including invasive studies) is needed in patients with suspected or documented cardiac disease. External or implantable loop recorders represent a significant improvement in the diagnosis of rare episodes of (brady- or tachy)-arrhythmias. Prognosis is determined by the underlying (heart) disease.

Aged↗

[Transvenous parasympathetic nerve stimulation in the chronic myocardial infarction phase].

The study describes the electrophysiological effects of transvenous cardiac nerve stimulation in an animal model of myocardial infarction. In ten sheep with recent myocardial infarction, transvenous stimulation of parasympathetic cardiac nerves was achieved from a catheter in the right pulmonary artery. The effects of transvenous cardiac nerve stimulation on sinus rhythm cycle length, ventricular refractory periods and inducibility of monomorphic ventricular tachycardia were evaluated. Sinus rhythm cycle length increased from 620 +/- 24 ms to 723 +/- 30 ms during nerve stimulation with 20 Hz and to 779 +/- 28 ms during stimulation with 40 Hz (p < 0.05). Effective ventricular refractory periods from stimulation sites in non-infarcted right and left ventricular myocardium showed a tendency towards prolongation during cardiac nerve stimulation with shortening after cessation of stimulation. These differences, however, were not significant. In contrast, refractory periods from stimulation sites within the infarcted area remained unchanged during cardiac nerve stimulation. The inducibility of monomorphic ventricular tachycardia by programmed electrical stimulation was reduced during transvenous cardiac nerve stimulation. Pathological examination showed cholinergic nerves in close proximity to the tip of the stimulation catheter in the right pulmonary artery. Transvenous cardiac nerve stimulation in sheep with remote myocardial infarction exhibits electrophysiological effects on the ventricles. Although a parasympathetic effect on the ventricles could not be proven, the observed effects may result from direct stimulation of efferent parasympathetic nerves.

Animals↗

[Molecular biology of the heart atrium. New insights into the pathophysiology of atrial fibrillation as well as its clinical implications].

Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the most important factors for embolic stroke. In recent years, a tremendous amount has been learned about the pathophysiology and molecular biology of AF. Thus, pharmacologic interference with specific signal transduction pathways appears promising as a novel antiarrhythmic approach to maintain sinus rhythm and to prevent atrial clot formation. This review highlights the underlying molecular biology of atrial fibrillation, which may also be relevant for AF therapy.

Angiotensin II↗

[The Wearable Cardioverter Defibrillator (WCD) for the prevention of sudden cardiac death -- a single center experience].

The Wearable Cardioverter Defibrillator (WCD) is an external defibrillator that automatically detects and treats ventricular tachyarrhythmias without the need for assistance from a bystander while at the same time allowing the patient to ambulate freely. The main components of the system are the defibrillator unit and a chest belt with electrodes for arrhythmia detection and therapy delivery. Between December 1998 and October 2001, 84 patients used the device at our institution. The majority of patients had a history of acute myocardial infarction or coronary artery bypass surgery with an increased risk for sudden cardiac death or were awaiting heart transplantation. During a mean follow-up of 116+/-90 days, 7 episodes of ventricular tachyarrhythmias were detected and terminated successfully by the WCD in 5 patients. In 9720 days, there was one inappropriate shock due to oversensing of electrical noise. Four patients died during follow-up; none of them had a cardiac arrest while wearing the device. Five patients were excluded because of irregularities in device use. An ICD was implanted in 24 patients at the end of the follow-up period. The WCD is effective in detecting and treating ventricular tachyarrhythmias in patients with an intermittently increased risk for sudden cardiac death. Further use of the system in larger patient populations is needed to confirm its safety and cost effectiveness.

Aged↗

Expression and activity of ectopeptidases in fibrillating human atria.

Recent studies have demonstrated that atrial fibrillation (AF) occurs in the presence of degenerative changes of atrial tissue. In contrast, bradykinin (BK) appears to have cardioprotective effects diminishing myocardial hypertrophy and fibrosis. It is unknown, however, whether AF has direct effects on BK metabolism. Therefore, the purpose of this study was to determine the atrial expression of the membrane-bound peptidases, also referred to as ectopeptidases, carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPIV), and alanyl-aminopeptidase (APN) in patients with and without AF. Atrial tissue samples of 35 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or = 6 months; CAF), the remaining 18 patients (controls) had no history of AF. Peptidase expression was analyzed at the mRNA (quantitative RT-PCR) level and apparent changes were confirmed at the protein level. In case of unaltered mRNA levels, enzyme activity was determined. Reduced amounts of CPM-mRNA were found in patients with CAF (41.3+/-9.7 U nu controls: 86.1+/-17.5 U P<0.05). CPM protein was decreased to 47.5% in patients with CAF compared with controls (P<0.01). DPIV and APN mRNA amounts were similar in both groups. DPIV activity, however, was increased during CAF (219.6+/-30 pkat/mg protein v controls: 195.8+/-21.8 pkat/mg P<0.05). APN activity was unchanged. In conclusion, atrial bradykinin metabolizing activities are significantly altered during AF in humans. The observed alterations in ectopeptidase expression/activity may play a role in the structural remodeling of fibrillating atria.

Atrial Fibrillation↗

Case report: severe skin burn at the site of the indifferent electrode after radiofrequency catheter ablation of typical atrial flutter.

Although radiofrequency (RF) catheter ablation has been shown to be an effective treatment strategy in patients with supraventricular tachycardia, RF ablation may lead to potentially serious complications. We describe a case of a 65-year old man who was transferred for catheter ablation of typical atrial flutter. 21 RF applications (mean energy: 81+/-9 watts) were applied in the temperature-controlled mode (70 degrees C) between a 8-mm tip electrode and an indifferent electrode using a high-power RF generator (100 watts) until bi-directional atrial isthmus block was achieved. After the procedure, a third-degree skin burn (10x2 cm) was observed at the lateral edge of the adhesive indifferent electrode whereas the medial edge of the electrode was not fully attached to the skin surface. This case is one out of 1128 ablation procedures (0.09 %) at our institution using a high-power RF generator. The present study demonstrates a severe skin burn induced by mal-attachment of an indifferent electrode during RF ablation. Long RF energy application times, high-power settings, and heavy sedation may have contributed to the observed severity of skin damage.

Aged↗

Response of atrial fibrillatory activity to carotid sinus massage in patients with atrial fibrillation.

In some cases carotid sinus massage (CSM) may induce AF, whereas it may terminate AF in others. The purpose of this study was to investigate the influence of CSM on atrial fibrillatory frequency using spectral analysis of the surface ECG. Continuous ECG recordings were made in 19 patients (12 men, 7 women, mean age 61 +/- 11 years) with AF. Unilateral CSM was performed in the standard fashion to one randomized bifurcation of the carotid artery at a time. Ventricular rate and fibrillatory frequency were assessed in 30-second ECG segments at baseline and during CSM. The frequency content of the fibrillatory baseline was quantified using digital signal processing (filtering, subtraction of averaged QRST complexes, and Fourier transformation). CSM resulted in a relative change in fibrillatory frequency of 4.5 +/- 3.9% (range 0%-13%). In 8 (42%) patients an increase in fibrillatory frequency was found (6.4 +/- 0.5 vs 6.8 +/- 0.5 Hz, P = 0.012). In 9 (47%) patients a decrease in fibrillatory frequency occurred (6.5 +/- 0.8 vs 6.1 +/- 0.8 Hz, P = 0.008) without AF termination. The remaining two patients showed no change in fibrillatory frequency. CSM on the contralateral side after 2 minutes produced fibrillatory frequency changes in the same direction in all patients with a good reproducibility in its magnitude (r = 0.59, P = 0.05). Calcium channel blockers were more frequently used (78% vs 25%, P = 0.044) in patients with a decrease in fibrillatory frequency compared to patients with a frequency increase. There were no significant changes in ventricular rate during CSM. In conclusion, two different responses of atrial fibrillatory frequency to CSM were found. This might explain why CSM may facilitate AF induction in some cases and AF termination in others. Calcium channel blocker treatment may prevent an increase in fibrillatory frequency provoked by CSM suggesting a blunted electrical remodeling process.

Adult↗

Electrocardiographic characteristics in patients with nonrheumatic atrial fibrillation and their relation to echocardiographic parameters.

The aim of this study was to determine the relation between (1) ECG fibrillatory wave amplitude and left atrial diameter and left atrial appendage (LAA) flow velocity using different ECG recording techniques, and (2) ECG fibrillatory frequency and frequency of LAA contractions in patients with nonrheumatic AF. In 36 patients (22 men, 14 women, mean age 61 +/- 11 years) with persistent AF, ECG recordings were performed using a standard 12-lead EGG and an orthogonal EGG lead system using a high gain, high resolution ECG. AF was classified as coarse (fibrillatory amplitude > or = 1 mm) orfine (fibrillatory amplitude < 1 mm) in leads I, aVF, V1 and corresponding leads X, Y, and Z. Fibrillatory frequency from the ECG was determined by subtracting averaged QRST complexes and applying a Fourier analysis to the resulting signal. Doppler flow was obtained from LAA during transesophageal echocardiography and LAA emptying velocity was determined. Fourier analysis was also applied to the Doppler signal generating the frequency of LAA contractions. Coarse AF was observed in 0, 9, and 18 patients in leads I, aVF, and V, respectively. It was more often (P < 0.05) detected in corresponding leads X (n = 13), Y (n = 31), and Z (n = 23). Fine AF in lead X was associated with a reduced LAA velocity (33 +/- 16 cm/s in coarse AF vs 22 +/- 13 cm/s in fine AF, P = 0.05). There was neither a relation between AF coarseness in any other ECG lead and LAA flow velocity, left atrial diameter, or echo contrast. In 25 patients with an active LAA flow, the mean frequency of LAA contractions was 6.8 +/- 0.8 Hz. The corresponding mean frequency obtainedfrom the EGG was 6.7 +/- 0.7 Hz (r = 0.85, P < 0.001). The mean difference between these two measures was 0.04 Hz, and the 95% confidence limits were 0.90 and- 0.82 Hz using the Bland-Altman method. In conclusion, AF coarseness and its relation to LAA flow velocity depend on the ECG recording technique used. LAA contractions represent one mechanical correlate of the electrical fibrillatory activity in AF.

Atrial Fibrillation↗