Spontaneous episode of polymorphic ventricular tachycardia in a patient with intermittent Brugada syndrome.
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Bundle-Branch Block↗
Biomedical subjects
H U Klein
Publications and source records attributed to H U Klein.
Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans.
BACKGROUND: Previous studies have suggested that atrial fibrillation (AF) is associated with the activation of the atrial angiotensin system. However, it is not known whether the expression of angiotensin II receptors changes during AF. The purpose of this study was to determine the atrial expression of angiotensin II type 1 and type 2 receptors (AT(1)-R and AT(2)-R) in patients with AF. METHODS AND RESULTS: Atrial tissue samples from 30 patients undergoing open heart surgery were examined. Eleven patients had chronic persistent AF (> or =6 months; cAF), 8 patients had paroxysmal AF (pAF), and 11 patients were in sinus rhythm. AT(1)-R and AT(2)-R were localized in the atrial tissue by immunohistochemistry and quantified at the protein and mRNA level by Western blotting and quantitative polymerase chain reaction. Both types of AT-R were predominantly expressed in atrial myocytes in all groups. The amount of AT(1)-R was reduced to 34.9% during cAF (P<0.01) and to 51.7% during pAF (P<0.05) compared with patients in sinus rhythm. In contrast, AT(2)-R was increased during cAF (246%; P=NS) and pAF (505%; P<0.01). AT(1)-R/AT(2)-R mRNA content was similar in all groups. CONCLUSIONS: AF is associated with the down-regulation of atrial AT(1)-R and the up-regulation of AT(2)-R proteins. These findings may help define the pathophysiological role of the angiotensin system in the structural remodeling of the fibrillating atria.
Adult↗
Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.
OBJECTIVES: The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF). BACKGROUND: Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear. METHODS: Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques. RESULTS: Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis. CONCLUSIONS: An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.
Aged↗
The importance of right atrial pacing electrode position and pacing configuration for intra-atrial and inter-atrial conduction times.
Pace prevention of atrial tachyarrhythmias is based in part on the reduction of intra-atrial (IAA) and/or inter-atrial (IEA) conduction. We previously introduced a novel pacing mode using floating atrial ring electrodes on a VDD-lead (BIdirectional MO nophasic impulSe: BIMOS). The effects of BIMOS pacing on IAA and IEA conduction times has not been studied. In nine Merino sheep electrode catheters were placed at the His-Bundle (HBE), high right atrium (HRA), coronary sinus ostium (Cs-Os), and left lateral atrium (LLA). A VDD-lead was introduced with floating electrodes in the high and mid right atrium (Floating). IAA (S/P-HRA, S/P-Cs-Os, S/P-HBE, S/P-Floating), IEA conduction times (S/P-LLA), and P-wave duration (PD) were measured during sinus rhythm (S), during bipolar cathodal pacing (P) in the HRA, in the Cs-Os position, as well as during BIMOS floating pacing. The mean PD during S was significantly shorter than during HRA- (66. 6+/-12.8ms; vs. 116.2+/-11.1ms; p<0.05) and Cs-Os-P (66.6+/-12.8ms vs. 94.4+/-9.0ms; p<0.05). In comparison to HRA-P, BIMOS configuration lead to a significant reduction of the P-wave duration (116.2+/-11.1ms vs. 85. 4+/-8.8ms; p<0.05). During BIMOS pacing, the global atrial conduction time was significantly shorter than during pacing in the HRA and Cs-Os position. The results of this study demonstrate a clear reduction of IAA and IEA conduction times using BIMOS configurations compared to conventional HRA-P. Furthermore, BIMOS pacing produced a more homogeneous atrial activation when compared with conventional HRA- and Cs-Os-P.
Animals↗
The MUSTT study: evaluating testing and treatment.
The multicenter unsustained tachycardia trial (MUSTT) tested the value of electrophysiologically guided antiarrhythmic drug therapy against no therapy in high risk coronary artery disease with poor left ventricular function (LV-EF </= 40%) and nonsustained ventricular tachycardia. Risk assessment was performed by testing inducibility of a sustained ventricular tachycardia. The primary endpoint of the study was sudden arrhythmic death or cardiac arrest. Significant information on risk stratification was gathered by the follow-up of patients that were noninducible. Although MUSTT was not a specific ICD trial for primary prevention of SCD the results of the trial revealed that only with ICD back-upa significant reduction of arrhythmic death or cardiac arrest can be achieved.EP-guided antiarrhythmic drug treatment had a lower incidence of SCD/CA compared to no treatment (12% versus 25%, p = 0.043, hazard ratio 0. 73 after 24 months and 18% versus 32% after 60 months). A subgroup analysis showed that the benefit of antiarrhythmic treatment was only due to ICD implantation. No difference was found between those inducible pts treated exclusively with antiarrhythmic drugs and those who were randomized to no drug treatment. Patients who were not inducible did significantly better than pts who were inducible wether or not treated with antiarrhythmic drugs.MUSTT results strengthen the data of the MADIT study. They confirm the inducibility testing as the most accurate risk stratifier. MUSST demonstrated the poor value of serial EP drug testing as well as the risk of stand alone antiarrhythmic drug treatment.
Adult↗
Perspectives: does amiodarone increase non-sudden deaths? If so, why?
Despite the antiarrhythmic efficacy of amiodarone, a definitive correlation between amiodarone treatment and increased non-arrhythmic mortality in patients with heart failure and depressed ventricular function has been reported. Results from research in the field of cardiac resynchronization therapy in heart failure may provide some explanations to this observation. We discussed the hypothetical link between amiodarone and non-arrhythmic mortality, which might have a cause--effect relationship, based on cardiac electromechanical disarrangement provoked by electrophysiological properties of amiodarone.
Amiodarone↗
Incidence of cutaneous vasoactivity in patients with anemia and pulmonary hypoxia.
BACKGROUND: In cutaneous laser Doppler flow (LDF)-recordings, various forms of flowmotion or vasoactivity can be observed. It is still a matter of dispute, whether flowmotion is a phenomenon of physiological or pathophysiological conditions. Therefore, we tested the hypothesis of increased vasoactivity being typical for patients with various degrees of acute and chronic anemia as well as with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We examined 12 healthy controls, 14 patients with COPD with a PO2 below 60 mmHg, 16 patients with chronic and 7 patients with acute anemia with an Hb below 12 g/dl. We used a simple LDF-technique on the dorsum of the forefoot. The regularity of blood flow frequencies was determined by calculation of the coefficient of variation. RESULTS: Periods without vasoactivity (i.e. constant flow pattern) were 21% in normal controls, 7% in patients with COPD and 2% in patients with acute or chronic anemia. Mean frequencies in the four groups varied between 3.8 and 4.8 cpm, with significant changes only in the group with acute blood loss. However, vasoactivity was significantly more regular in the COPD- and anemia-groups as compared to normal controls, with coefficients of variation of 47.4% for controls, 31.8% for COPD- and 29.3% for chronic and 35.1% for acute anemia-patients. CONCLUSIONS: The present paper shows that cutaneous vasoactivity is more regular in the three examined clinical entities of systemic tissue hypo-oxygenation, i.e. chronic and acute anemia and severe COPD as compared to healthy control subjects. Therefore, we hypothesize that increased vasoactivity constitutes a regulatory defense mechanism in cases of reduced oxygenation, by improving microcirculatory blood flow distribution.
Adult↗
Changes in AV node conduction curves following slow pathway modification.
Dual AV node physiology often persists after successful slow pathway (SP) ablation, and the mechanism of tachycardia elimination is unresolved. Therefore, AV node conduction curves were analyzed following successful ablation (4 +/- 1 energy applications) in 85 consecutive patients (58 women, age 50 +/- 2 years) with typical AVNRT. Twenty-seven patients (32%) had complete elimination (group 1) whereas 58 (68%) patients had persistence (group 2) of dual AV node physiology. A significant increase in the AV node Wenckebach cycle length (WB-CL) was observed in both groups (310 +/- 9 to 351 +/- 15 ms in group 1, and 325 +/- 8 to 369 +/- 9 ms in group 2, P < 0.05). A decrease in the fast pathway (FP) ERP (339 +/- 15 to 279 +/- 12 ms) and an increase in the maximum FP AH interval (141 +/- 5 to 171 +/- 7) were observed only in group 1 (P < 0.05). In group 2, no change in the SP ERP (267 +/- 7 to 280 +/- 10 ms) was observed, and the change in the maximum SP-AH following ablation showed a significant inverse relation to the maximum SP-AH at baseline in group 2. In conclusion, (1) an increase in the WB-CL is observed independent of the persistence or elimination of dual physiology after successful ablation; (2) when dual physiology is eliminated, significant changes in the FP ERP and the maximum FP-AH occur; (3) when dual physiology persists, FP physiology and the SP ERP remain unchanged, and a significant inverse relation between the change in the maximum SP-AH following ablation and the maximum baseline SP-AH is observed.
Atrioventricular Node↗
Circadian variations in atrial fibrillatory frequency in persistent human atrial fibrillation.
Atrial fibrillatory frequency reflects the atrial refractory period during AF. This study was conducted to investigate noninvasively the diurnal fluctuations of fibrillatory frequency in persistent human atrial fibrillation and to determine the relationship between changes in ventricular rate and fibrillatory frequency. Ambulatory ECGs were recorded in 30 patients (18 men, 12 women, mean age 60 +/- 11 years) with persistent AF (> 24 hours). AF frequency was measured in 1-minute ECG segments by subtracting averaged QRST complexes and applying Fourier analysis to the resulting signals at 4 PM, 10 PM, 4 AM, and 10 AM. Peak frequency was determined in the 3-12 Hz frequency band. Mean fibrillatory frequency measured 6.6 +/- 0.6 Hz (range 5.0-7.8 Hz). Two different frequency patterns were distinguished comparing maximal diurnal versus nocturnal fibrillatory frequency. In six (20%) patients an increase (P = 0.045) in nocturnal fibrillatory frequency (type I) was found. In the remaining 24 (80%) patients a decrease (P < 0.001) in fibrillatory frequency occurred (type II). Type I AF showed a strong inverse correlation between relative changes (percent) in ventricular rate and fibrillatory frequency obtained from two consecutive measurement points (r = -0.88 to -.97, P < 0.01), whereas in type II AF a moderate positive correlation (r = 0.36 to 0.41, P < 0.05) was detected. These data indicate a circadian pattern in AF frequency that concurs with ventricular rate changes suggesting a modulating influence of the autonomic nervous system on atrial electrophysiology in persistent human AF.
Adult↗
Persistent T-wave changes after radiofrequency catheter ablation of an accessory connection (Wolff-parkinson-white syndrome) are caused by "cardiac memory".
BACKGROUND: The purpose of this study was to determine the incidence and origin of T-wave changes after ablation of an accessory atrioventricular connection (AC), which could either be a sign of damage to the coronary circulation or a result of persistent abnormal repolarization secondary to previously abnormal ventricular activation ("cardiac memory"). METHODS AND RESULTS: Ninety of 107 consecutive patients (33 women and 57 men, mean age 36 +/- 5 years) undergoing successful catheter ablation of an AC were studied. Patients with bundle branch block or more than 1 AC were excluded. Sixty-four patients had manifest preexcitation (group 1) and 26 had a concealed AC (group 2). Immediately after loss of preexcitation, 38 (59%) patients with a manifest AC showed T-wave abnormalities. In contrast, none of the patients with a concealed AC had T-wave abnormalities after ablation (P <.05). The T-wave changes (1) did not correlate with the number or duration of energy applications or with markers of tissue injury; (2) correlated with the location of the AC and the degree of preexcitation, respectively; and (3) completely resolved over a period of weeks to months. None of the patients had recurrence of preexcitation or tachycardia during a mean follow-up of 16 +/- 7 months. CONCLUSIONS: T-wave changes after ablation are most likely caused by "cardiac memory" and are not a sign of myocardial or coronary injury.
Adult↗
Non-invasive assessment of fibrillatory activity in patients with paroxysmal and persistent atrial fibrillation using the Holter ECG.
OBJECTIVE: Automatic analysis of the frequency content of the fibrillatory baseline on the surface ECG accurately reflects the average rate of atrial fibrillation (AF). This frequency measurement correlates with the behavior of AF and predicts the response to administration of ibutilide, a new antiarrhythmic drug. Neither the temporal pattern of fibrillatory frequency in spontaneous paroxysmal or persistent AF, nor its response to chronic antiarrhythmic medication has been studied so far. METHODS AND RESULTS: Holter ECG recordings were made in 20 patients during AF. One minute ECG segments were selected for analysis. The frequency content of the fibrillatory baseline was then quantified using digital signal processing. After high-pass filtering, the QRST complexes were subtracted using a template matching algorithm. The resulting fibrillatory baseline signal was subjected to Fourier transformation, displayed as a frequency power spectrum and the peak frequency (f) was determined. In 11 patients (7 male, 4 female, age 62 +/- 10 years) 31 paroxysmal AF episodes were analyzed. Duration ranged from 1 min to 665 min (115 +/- 175 min). Initial mean peak f measured 5.1 +/- 0.7 Hz (range 3.9 to 6.9 Hz). There was a positive correlation between f and AF duration (R = 0.53, p = 0.002). AF of less than 15 min duration (n = 13) showed a lower f (4.8 +/- 0.6 Hz) when compared with longer lasting episodes (n = 18, 5.3 +/- 0.7 Hz, p = 0.03). In short AF episodes f was constant, whereas in longer-lasting episodes f increased to 5.8 +/- 0.5 Hz (p < 0.001) within 5 min. In 9 patients (9 male, age 58 +/- 8 years) with persistent AF oral antiarrhythmic drugs (amiodarone n = 5, sotalol n = 3, flecainide n = 1) were given prior to electrical cardioversion for prophylaxis of AF recurrence. Frequency measurements were obtained at baseline and 3 to 5 days after initiation of drug administration. At baseline mean f measured 6.9 +/- 0.4 Hz. Frequency was reduced by antiarrhythmic drugs to 5.8 +/- 0.4 Hz (p < 0.001). CONCLUSIONS: (1) The duration of paroxysmal AF episodes can be predicted using spectral analysis of ECG recordings of AF episodes. (2) An increase in fibrillatory frequency is associated with AF persistence. (3) This technique can be used to monitor the response to antiarrhythmic medication.
Anti-Arrhythmia Agents↗
An increase in sinus rate following radiofrequency energy application in the posteroseptal space.
An increase in sinus rate has been previously described in patients with AV node reentry (AVNRT) following successful AV node modification. This increase could either be a specific sign of elimination of slow pathway conduction or it could be a consequence of energy application in the posteroseptal area. Thus, we compared the changes in sinus cycle length following successful slow pathway ablation (defined as complete elimination of dual AV node physiology) in patients having AVNRT with those in patients undergoing successful ablation of a posteroseptal atrioventricular accessory connection. Twenty five patients (16 women and 9 men, mean age 41 +/- 4 years) with typical AVNRT (cycle length 378 +/- 12 ms) and 29 patients (16 women and 13 men, age 34 +/- 5 years) with an accessory connection (17 manifest and 12 concealed) were studied. The electrophysiology study was performed during sedation with Fentanyl and Midazolam. The mean number of energy applications was 3 +/- 1 for successful slow pathway ablation and 4 +/- 1 for successful ablation of the accessory connection (p:NS). Following the successful energy application, the sinus cycle length decreased significantly 776 ms at baseline to 691 ms in patients with AVNRT. Following successful ablation of the posteroseptal AC, sinus cycle length decreased from 755 ms at baseline to 664 ms (p < 0.05 in both groups [difference between groups not significant]). The decrease in sinus cycle length did not correlate with the number of RF energy applications required for successful ablation or the total energy delivered. In conclusion, ablation of the AV node slow pathway and a posteroseptal accessory connection results in similar increases in the sinus rate. Thus, the increase in sinus rate is probably due to energy application in the posteroseptal space, possibly due to concomitant destruction of vagal inputs, and it is not specific for elimination of slow pathway conduction.
Adult↗
Can catheter ablation in cardiac arrest survivors prevent ventricular fibrillation recurrence?
Ventricular tachyarrhythmias are the most common cause for sudden cardiac death. The success of catheter ablation for supraventricular tachycardias led to the supposition that ablation could also be used in the treatment of ventricular tachycardias. Despite the promising results in bundle branch reentry and some forms of idiopathic ventricular tachycardia, the success rate in patients with coronary artery disease is still low. There is hope that new approaches to reliably localize the critical region of the tachycardia and new ablation techniques to create larger areas of injury may lead to a wider application of ablation therapy in the treatment of ventricular tachycardia. Survivors of cardiac arrest typically have more rapid and unstable arrhythmias than patients with sustained ventricular tachycardia, and these rapid arrhythmias frequently degenerate into ventricular fibrillation. The instability of the arrhythmia makes it impossible to localize the arrhythmia origin with current mapping techniques. Experimental and clinical data, however, suggest that these arrhythmias also frequently start from a localized area of electrical activation. With developments in mapping techniques and energy delivery, catheter ablation may soon become a feasible therapeutic approach in some patients with unstable arrhythmias. The article discusses the prerequisites for this approach and suggests the patients who may be appropriate candidates for this technique.
Arrhythmias, Cardiac↗
Prolongation of monophasic action potential duration and the refractory period in the human heart by tedisamil, a new potassium-blocking agent.
The effect of intravenous tedisamil (0.3 mg.kg-1), a newly developed potassium-blocking agent, on ventricular repolarization was studied in 10 patients (three women, seven men; mean age 53 +/- 8 years) with coronary artery disease (stenoses < or = 60%). Left ventricular monophasic action potentials, effective refractory periods and surface electrocardiograms were recorded during sinus rhythm and during constant atrial pacing at cycle lengths of 600, 500 and 400 ms. Under tedisamil there was a 12% reduction of heart rate and in parallel a prolongation of QTc interval (+10%) and left ventricular monophasic action potential duration (+16% at 90% repolarization). QRS duration remained unchanged. Tedisamil increased the duration of monophasic action potentials during constant atrial pacing, indicating a direct prolongation effect on left ventricular repolarization independent of sinus node activity. By increasing the atrial pacing rate this prolonging effect diminished. Left ventricular effective refractory periods also increased in a frequency-dependent fashion with a greater prolongation effect at long cycle lengths as compared to short cycle lengths. The ratio between effective refractory period and monophasic action potential duration, however, remained constant, independent of heart rate. We conclude that tedisamil is bradycardiac at the dose tested and has a reverse use dependent prolongation effect on left ventricular repolarization and refractoriness. The electrophysiologic profile is consistent with a class III antiarrhythmic classification.
Action Potentials↗