Experience with an ICD incorporating biventricular pacing.

Biventricular pacing for cardiac resynchronization is a promising therapy for symptomatic improvement in selected patients with underlying severe congestive heart failure. ICD treatment has been shown to prolong life in patients with life threatening ventricular tachyarrhythmias, but it does not improve quality of life. This review discusses current experience with ICD's incorporating biventricular pacing.

[Visualization of pulmonary vein stenosis after radio frequency ablation for treatment of atrial fibrillation using multidetector computed tomography with retrospective gating]. / Darstellung von Pulmonalvenenstenosen nach Radiofrequenzablation zur Behandlung von Vorhofflimmern unter Verwendung der Multidetektor Computertomographie mit retrospektivem Gating.

PURPOSE: With the number of radio frequency ablations (RFA) for treatment of chronic atrial fibrillation increasing, the diagnostic evaluation for RFA associated pulmonary vein stenosis is getting more important. This study investigates the feasibility of the visualization of pulmonary vein stenosis using non-invasive multidetector computed tomography. MATERIALS AND METHODS: Twenty-eight patients were examined following RFA-treatment. A 4-slice (20 patients) and a 16-slice (8 patients) multidetector CT scanner (SOMATOM Volume Zoom and Sensation 16, Siemens, Forchheim, Germany) with retrospective gating was used to assess the pulmonary veins. Lesion severity was determined on a semi-quantitative scale (< 30 %, 30 - 50 %, > 50 %). RESULTS: CT was performed without any complications in all patients. Diagnostic image quality could be obtained in all examinations. The pulmonary veins showed lesions < 30 % in four patients, lesions of 30 -, 50 % in five patients and a stenosis > 50 % in one patient. Eighteen patients showed no lesions. CONCLUSION: Multidetector CT of the pulmonary veins seems to be able to visualize high-grade and low-grade lesions, but larger catheter-controlled studies are needed for further assessment of the diagnostic accuracy and clinical reliability of this noninvasive method.

Enhanced detection criteria in implantable cardioverter defibrillators: sensitivity and specificity of the stability algorithm at different heart rates.

The lack of specificity in the detection of ventricular tachyarrhythmias remains a major clinical problem in the therapy with ICDs. The stability criterion has been shown to be useful in discriminating ventricular tachyarrhythmias characterized by a small variation in cycle lengths from AF with rapid ventricular response presenting a higher degree of variability of RR intervals. But RR variability decreases with increasing heart rate during AF. Therefore, the aim of the study was to determine if the sensitivity and specificity of the STABILITY algorithm for spontaneous tachyarrhythmias is related to ventricular rate. Forty-two patients who had received an ICD (CPI Ventak Mini I, II, III or Ventak AV) were enrolled in the study. Two hundred ninety-eight episodes of AF with rapid ventricular response and 817 episodes of ventricular tachyarrhythmias were analyzed. Sensitivity and specificity in the detection of ventricular tachyarrhythmias were calculated at different heart rates. When a stability value of 30 ms was programmed the result was a sensitivity of 82.7% and a specificity of 91.4% in the detection of slow ventricular tachyarrhythmias (heart rate < 150 beats/min). When faster ventricular tachyarrhythmias with rates between 150 and 169 beats/min (170-189 beats/min) were analyzed, a stability value of 30 ms provided a sensitivity of 94.5% (94.7%) and a specificity of 76.5% (54.0%). For arrhythmia episodes > or = 190 beats/min, the same stability value resulted in a sensitivity of 78.2% and a specificity of 41.0%. Even when other stability values were taken into consideration, no acceptable sensitivity/specificity values could be obtained in this subgroup. RR variability decreases with increasing heart rate during AF while RR variability remains almost constant at different cycle lengths during ventricular tachyarrhythmias. Thus, acceptable performance of the STABILITY algorithm appears to be limited to ventricular rate zones < 170 beats/min.

[Atrial tachycardia, atrial flutter, atrial fibrillation: curative therapy by focal ablation in a pulmonary vein]. / Atriale Tachykardie, Vorhofflattern, Vorhofflimmern: Kurative Therapie durch fokale Ablation in einer Pulmonalvene.

We describe the case of a 50-year-old woman with the clinical diagnosis of cardiomyopathy associated with supraventricular tachycardia refractory to pharmacological treatment. The totally irregular tachyarrhythmia was the result of different episodes of atrial tachycardia, atrial flutter and atrial fibrillation that could be identified in the surface ECG. These findings and the patient's symptoms were all caused by a single focal tachycardia originating from the left upper pulmonary vein. Ablation of this focus represented a curative antiarrhythmic therapy also restoring a normalized ventricular function. Thus, an ablation of the AV node with consecutive pacemaker implantation could be prevented.

Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing.

BACKGROUND: Racemic (R /S)- verapamil is widely used in the management of chronic atrial fibrillation. The negative dromotropic effect is mainly mediated by the S -enantiomer, which is preferentially metabolized. Previous studies report an accumulation of R /S- verapamil during long-term oral treatment of patients with chronic atrial fibrillation. However, the specific disposition of S -verapamil and the pharmacologic effects were not assessed. Therefore uncertainties about the need for dose adjustments remain. METHODS: Using stable isotope technology and a stereospecific assay, we compared the pharmacokinetics and pharmacodynamics of intravenous (10 mg of d(7)-R /S -verapamil) and oral (240 mg of slow release (SR) d(0)-R /S -verapamil) R -verapamil and S -verapamil after the first dose (day 1) and after 3 weeks (day 21) of continuous oral therapy in 8 patients with long-term atrial fibrillation. On both study days, serum samples were obtained for the analysis of d(7)- and d(0)-R -verapamil and S -verapamil. Heart rate (HR) was monitored with electrocardiography (with each blood sample) and Holter electrocardiography (before the study, on day 1, and on day 21). RESULTS: Compared with day 1, clearance of oral R -verapamil and S -verapamil was significantly reduced on day 21 (1007 +/- 380 versus 651 +/- 253 mL/min [-35%] and 5481 +/- 2731 versus 2855 +/- 1097 mL/min [-48%], respectively; P <.05), whereas only a moderate decrease was observed for intravenous R -verapamil and S -verapamil (-23% and -14%, respectively, not significant). Mean HR (89 +/- 11 bpm before verapamil) was effectively reduced, with the same effects on day 1 (68 +/- 8 bpm) and day 21 (68 +/- 8 bpm). Compared with day 1, the HR reduction per ng/mL of S -verapamil (calculated by the area under the curve [from 0-24 hours] ratio of HR reduction and S -verapamil concentration) was significantly lower on day 21 (0.7 +/- 0.4 versus 1.2 +/- 0.7 [bpm]. [ng/mL](-1), for day 21 versus day 1; P <.01). CONCLUSIONS: In patients with chronic atrial fibrillation, clearance of oral, but not intravenous, S -verapamil and R -verapamil is significantly reduced with multiple doses compared with a single dose, thereby indicating predominant impairment of prehepatic rather than hepatic metabolism as the underlying mechanism. However, this kinetic change is clinically compensated by a decrease in the responsiveness to S -verapamil observed with regular dosing. The data suggest that despite accumulation of the drug individual verapamil doses can be maintained during long-term oral rate control therapy.

Comparison of the efficacy of a subcutaneous array electrode with a subcutaneous patch electrode, a prospective randomized study.

The patch electrode and the array electrode are the two types of subcutaneous leads available as an adjunct to a transvenous lead system in patients with high defibrillation thresholds. A prospective randomized study was conducted in 30 consecutive patients comparing the efficacy and the long-term performance of a patch electrode with an array electrode. After determination of the defibrillation threshold for the transvenous lead alone, a subcutaneous patch or an array electrode was implanted in random order. Adding a patch electrode decreased the defibrillation threshold in seven out of 15 patients (47%) from 13.2+/-6.6 to 10.5+/-5.1 J (P<0.05). In 13 out of 15 patients (87%), the implantation of an array electrode caused a significant lowering of the defibrillation threshold from 15.4+/-6.6 to 8.2+/-5.0 J (P<0.0001). The array electrode was significantly more effective in lowering the defibrillation threshold than the patch electrode (P<0.01). Complications during follow-up associated with the subcutaneous patch electrode were observed in four patients whereas no complications were associated with the array electrode (P<0.01). The additional implantation of an array electrode is more effective and associated with fewer complications compared to a patch electrode.

Critical analysis of dual-chamber implantable cardioverter-defibrillator arrhythmia detection : results and technical considerations.

BACKGROUND: One of the perceived benefits of dual-chamber implantable cardioverter-defibrillators (ICDs) is the reduction in inappropriate therapy due to new detection algorithms. It was the purpose of the present investigation to propose methods to minimize bias during such comparisons and to report the arrhythmia detection clinical results of the PR Logic dual-chamber detection algorithm in the GEM DR ICD in the context of these methods. METHODS AND RESULTS: Between November 1997 and October 1998, 933 patients received the GEM DR ICD in this prospective multicenter study. A total of 4856 sustained arrhythmia episodes (n=311) with stored electrogram and marker channel were classified by the investigators; 3488 episodes (n=232) were ventricular tachycardia (VT)/ventricular fibrillation (VF), and 1368 episodes (n=149) were supraventricular tachycardia (SVT). The overall detection results were corrected for multiple episodes within a patient with the generalized estimating equations (GEE) method with an exchangeable correlation structure between episodes. The relative sensitivity for detection of sustained VT and/or VF was 100.0% (3488 of 3488, n=232; 95% CI 98.3% to 100%), the VT/VF positive predictivity was 88.4% uncorrected (3488 of 3945, n=278) and 78.1% corrected (95% CI 73.3% to 82.3%) with the GEE method, and the SVT positive predictivity was 100.0% (911 of 911, n=101; 95% CI 96% to 100%). CONCLUSIONS: A structured approach to analysis limits the bias inherent in the evaluation of tachycardia discrimination algorithms through the use of relative VT/VF sensitivity, VT/VF positive predictivity, and SVT positive predictivity along with corrections for multiple tachycardia episodes in a single patient.

Atrial L-type Ca2+-channel, beta-adrenorecptor, and 5-hydroxytryptamine type 4 receptor mRNAs in human atrial fibrillation.

Molecular and electrical remodeling of ion channels determining action potential duration has been proposed as a major mechanism in chronic atrial fibrillation. We investigated the mRNA expression of the cardiac L-type Ca2+-channel subunits alpha1c, alpha2/delta1, beta1a, and beta1b/c in atrial tissue of patients with chronic atrial fibrillation compared to patients in sinus rhythm. In addition, the mRNA expression of the 5-hydroxytryptamine type 4-, beta1-, and beta2-adrenergic receptors, which are known to stimulate the L-type Ca2+-current in human atrium, was analyzed and the effect of chronic beta-blocker treatment on the mRNA expression of these receptors and of the L-type Ca2+-channel subunits was assessed. Total RNA was isolated from right atrial appendages of patients in sinus rhythm and of patients with chronic atrial fibrillation. Then, semiquantitative RT-PCR using 18S RNA as the "housekeeping gene" was performed. In patients with chronic atrial fibrillation, there were only mild reductions in mRNA expression of the alpha1c-subunit (-15.5 %, p = 0.13), and of the beta1-subunit isoforms a and c (-13.3 %, p = 0.14 and -16.6%, p = 0.18, respectively). However, mRNA expression of the alpha2/delta1-subunit (-31.5 %, p < 0.01) and of the beta1-subunit isoform b (-39.9 %, p < 0.0005) was significantly reduced in patients with chronic AF. Taken together, the mRNA expression of the beta1-subunit isoforms b and c, which are splice variants, was significantly down-regulated by 26.5 % (p < 0.05) in these patients. The analysis of the beta1c/beta1b ratio resulted in a significant shift by 39.2 % (p < 0.0001) in favor of beta1c in patients with chronic atrial fibrillation. In the AF patients, the abundance of the 5-HT4-receptor transcript was significantly reduced by 36 % (p < 0.05). The beta-adrenoreceptor transcription was unchanged. In both SR and AF patients, chronic beta-blocker treatment did neither significantly effect the mRNA expression of the L-type Ca2+-channel subunits, the beta-adrenoreceptor subtypes 1 and 2, nor that of the 5-HT4-receptor. Our data show that chronic AF is associated with a decrease in the atrial mRNA amount of auxiliary subunits of the L-type Ca2+-channel and of the 5-HT4-receptor. This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4-receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia.

A priori expectancy bias and its relation to shock experience and anxiety: a naturalistic study in patients with an automatic implantable cardioverter defibrillator.

Patients with an automatic implantable cardioverter defibrillator (AICD) may offer an unique naturalistic opportunity to study whether expectancy biases develop because of precipitating aversive or traumatic experiences and/or because of elevated anxiety. An expectancy bias and its associations with AICD discharge and anxiety was examined in 24 AICD patients with a thought experiment. While patients without AICD discharge exhibited no expectancy bias, patients with discharge experiences were found to expect that stimuli depicting medical emergency situations will be followed by an aversive consequence. The magnitude of their expectancy bias was positively correlated with their anxiety level. In the group with AICD discharge, patients with low anxiety levels exhibited no bias, while patients with high anxiety levels exhibited a rather strong bias. It seems that the experience of an aversive or traumatic event, here an AICD discharge, is a necessary (but not sufficient) precipitating event for the development of an expectancy bias. If such an event happens, trait anxiety level presumably determines if and how strong the expectancy bias will be.

Variable responsiveness of anterograde and retrograde fast pathway conduction to adenosine in patients with typical AV-nodal reentry tachycardia.

Adenosine is known as a substance which depresses predominantly the slow pathway of the av-node. However, the effect of adenosine on the anterograde and retrograde fast pathway (FP) has not been studied in a large patient population. Ninety-one patients with inducible typical av-nodal reentrant tachycardias (AVNRT) were included. The clinically used dosage of 12 mg adenosine was administered subsequently as bolus injection during a constant atrial and ventricular pacing (500 ms) in all patients. Electrophysiological av-nodal parameters were determined. A higher responsiveness of the anterograde compared to the retrograde FP was observed: the majority of patients (76%) blocked anterogradely and 55% blocked retrogradely within the FP after the administration of 12 mg adenosine. Thirty-six percent of all patients revealed a differential behaviour to adenosine. Sixteen percent of all patients were completely resistant to adenosine (P=0.012). Electrophysiological parameters did not predict the responsiveness of the FP to adenosine. In patients with typical AVNRT the anterograde FP shows a higher sensitivity than the retrograde FP to adenosine. This might reflect an anatomical and/or functional distinction between anterograde and retrograde FP. The variable response to adenosine could be due to individual anatomical and electrophysiological heterogenity of the perinodal tissue and the av-node.

[Electrical remodeling in atrial fibrillation--cellular and molecular mechanisms]. / Elektrisches Remodeling bei Vorhofflimmern--Zelluläre und molekulare Mechanismen.

Atrial fibrillation is associated with changes in atrial electrophysiology that facilitate the initiation and persistence of the arrhythmia. The underlying cellular and molecular mechanisms are diverse; they have intensively been investigated over the past few years. The results, that have substantially improved the understanding of the pathophysiology of atrial fibrillation are reviewed. On the cellular level, atrial fibrillation leads to a strong shortening and an impaired rate adaptation of the action potential as well as changes in action potential morphology. Atrial fibrillation is associated with an altered gene expression of the L-type calcium channel (ICa,L) and of potassium channels (Ito, IK1, IKACh). The molecular mechanisms of intraatrial conduction slowing are less well understood; changes in the expression or distribution of gap junction proteins or a decrease of the fast sodium inward channel (INa) seem to be involved. A trigger for many of the observations is an overload of the myocyte cytoplasm with Ca2+ and a consecutive decrease of the systolic calcium gradient, furthermore changes in calcium-handling proteins are detectable in atrial fibrillation. In the last part, the clinical relevance and potential new therapeutic approaches are discussed.

[Administration of adenosine for termination of atrioventricular nodal reentry tachycardia: induction of atrial fibrillation with rapid conduction over an accessory pathway and unmasking of concomitant Wolff-Parkinson-White syndrome]. / Adenosingabe zur Terminierung einer atrio-ventrikulär-nodalen-Reentry-Tachykardie: Induktion von Vorhofflimmern mit schneller Uberleitung bei Demaskierung eines konkomitierenden Wolff-Parkinson-White-Syndroms.

The antiarrhythmic properties of adenosine, its ultra-short half-life and the absence of frequent serious side effects make it a front-line agent in arrhythmia management, especially in the treatment of atrioventricular nodal reentrant tachycardia. Due to a shortening of atrial refractoriness, adenosine can facilitate the induction of atrial fibrillation. Life threatening tachycardias may result from a potential rapid conduction of atrial fibrillation over an accessory pathway especially if the latter one has a short antegrade refractory period. We report a case of a 59 year old female patient in which intravenous administration of adenosine during typical atrioventricular nodal reentrant tachycardia was followed by atrial fibrillation with rapid conduction over a hitherto unknown accessory pathway. After intravenous administration of adenosine the tachycardia was terminated successfully within 38 s. After a short period of asystole, spontaneous atrial fibrillation developed unmasking an antegrade preexcitation with subsequent rapid ventricular response (210 b/min). The three-lead ECG showed a narrow QRS complex tachycardia. Because of spontaneous conversion to sinus rhythm and the absence of hemodynamic compromise there was no need for external cardioversion. During electrophysiological study an antidromic atrioventricular reentrant tachycardia was recorded over a left posteroseptal accessory pathway including antegrade conduction properties only. Because of its ultrashort half-life, serious side effects after adenosine administration are rare. The possibility of life threatening proarrhythmias after intravenous adenosine administration should be taken into consideration if the etiology of a paroxysmal supraventricular tachycardia is not clear and a concomitant Wolff-Parkinson-White syndrome cannot be excluded. As with application of all intravenous antiarrhythmic agents, the administration of adenosine should only be performed if continuous ECG monitoring and cardioversion facilities are available and possible.

High variability of retrograde fast pathway sensitivity to adenosine.

BACKGROUND: Adenosine is widely used as a tool to assess the effectiveness of radiofrequency ablation of concealed accessory pathways. HYPOTHESIS: The goal of this study was to determine the reliability of this test by studying the retrograde fast pathway sensibility in a large patient population with typical atrioventricular (AV) nodal reentry tachycardias. We sought also to determine whether AV nodal properties were predictive of a retrograde fast pathway sensitivity to adenosine. METHODS: In all, 124 patients with inducible AV nodal reentrant tachycardia were included in this study. All patients received a clinically used standard dose of 12 mg adenosine during ventricular pacing, with 500 ms and a constant ventriculoatrial (VA) conduction via the fast pathway. Electrophysiologic parameters of the AV node were determined in all patients in order to correlate them with the adenosine sensitivity of the retrograde pathway. RESULTS: In 74 patients, the injection of 12 mg adenosine resulted in a transient VA block, whereas no VA block occurred in the remaining 50 patients. In two patients, concealed accessory pathways were unmasked after the injection of adenosine. The adenosine sensitivity of the retrograde fast pathway was associated with longer retrograde conduction times and cycle lengths during AV nodal reentrant tachycardias. CONCLUSION: This study shows a high variability of retrograde fast pathway sensitivity to adenosine. Thus, in 40% of patients the lack of VA block after adenosine injection is not specific for persistent accessory pathway function after radiofrequency ablation. Electrophysiologic properties of patients with AV nodal reentrant tachycardias were different in patients with and without adenosine-sensitive retrograde fast pathways, possibly indicating differential patterns of penetration of the retrograde fast pathway into the compact AV node.

Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The primary objective of the present study was to assess the efficacy of metoprolol CR/XL to reduce the risk of relapse after cardioversion of persistent atrial fibrillation to sinus rhythm. BACKGROUND: Indirect data from studies with d,l sotalol provide evidence that the beta-blocking effects of the compound are important in maintaining sinus rhythm after cardioversion of atrial fibrillation. METHODS: After successful conversion to sinus rhythm, 394 patients with a history of persistent atrial fibrillation were randomly assigned to treatment with metoprolol CR/XL or placebo. The two treatment groups were similar with respect to all pretreatment characteristics. Patients were seen on an outpatient basis for recording of resting electrocardiogram (ECG) after one week, one, three and six months of follow-up or whenever they felt that they had a relapse into atrial fibrillation or experienced an adverse event. RESULTS: In the metoprolol CR/XL group, 96 patients (48.7%) had a relapse into atrial fibrillation compared with 118 patients (59.9%) in the placebo group (p = 0.005). Heart rate in patients after a relapse into atrial fibrillation was significantly lower in the metoprolol group (98 +/- 23 beats/min) than in the placebo group (107 +/- 27 beats/min). The rate of adverse events reported was similar in both groups when the difference in follow-up time was taken into account. CONCLUSIONS: The results of this double-blind, placebo-controlled study in patients after cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter.

[Ventricular fibrillation in intra-atrial cardioversion of atrial fibrillation]. / Kammerflimmern bei intraatrialer Kardioversion von Vorhofflimmern.

Recently intra-atrial defibrillation has become an interesting alternative to external defibrillation and drug therapy for the treatment of atrial fibrillation. Low-energy intra-atrial defibrillation can be used to restore sinus rhythm f.ex. after a failed external cardioversion or during an electrophysiologic study when the administration of antiarrhythmic drugs should be avoided. Additionally this new technique has led to the development of implantable atrial defibrillators for the treatment of selected patients suffering from chronic atrial fibrillation. Intra-atrial defibrillation seems to be a highly effective and safe method, but little experience exists concerning the outcome so far. Especially the potential risk of inducing ventricular pro-arrhythmia is subject of current controversy. We report the case of a 79-year-old patient suffering from WPW syndrome with a concealed bypass tract who was subject to an intra-atrial defibrillation during an electrophysiologic study. At the beginning of the study atrial fibrillation could be converted to sinus rhythm by a single low-energy atrial defibrillation (3 J.). After a short period of time a second intra-atrial defibrillation had to be performed in the same way because of recurrent atrial fibrillation. By this atrial shock ventricular fibrillation was induced, so that high energy external defibrillation became necessary. Analyzing the ECG a correct R-wave synchronization was found, but a rather short preceding RR interval (252 ms). In conclusion, low energy atrial defibrillation is gaining importance as a highly effective new technique to restore sinus rhythm in patients suffering from atrial fibrillation resistant to conventional therapies. Nevertheless potential risks have to be considered such as the induction of ventricular pro-arrhythmia. Therefore, a correct R-wave synchronization is obligatory and shock delivery should be withheld after short RR intervals. Future prospective randomized studies will have to show whether this new technique is really safe enough and superior to the conventional methods for restoring sinus rhythm in patients suffering from atrial fibrillation.

Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is associated with important alterations in cardiac ion channels that cause shortening and impaired rate adaptation of atrial repolarization. The mechanisms underlying potassium current remodeling in human AF are not clear. We investigated the effects of AF on the gene expression of the Kv4.3, Kv1.4, and Kv1.5 potassium channel subunits and correlated the findings with the transient outward (Ito) and the sustained outward (Isus or I(Kur)) potassium current. METHODS AND RESULTS: Semiquantitative reverse transcription-polymerase chain reaction was used to evaluate mRNA expression, and ion currents were studied with the patch clamp technique in right atrial appendages from patients in AF and compared with those from patients in stable sinus rhythm (SR). The presence of AF was associated with a 61% reduction in Kv4.3 mRNA expression (P < 0.001 vs SR), which was paralleled by a reduction in Ito current densities in this group of patients (i.e., at +50 mV: 7.44+/-0.76 pA/pF in SR and 1.24+/-0.28 pA/pF in AF; P < 0.001 vs SR). mRNA levels of Kv1.4 were identical in the two groups. AF did not affect either the gene expression of Kv1.5 or the current densities of Isus. CONCLUSION: Chronic AF in humans reduces Ito by transcriptional down-regulation of the Kv4.3 potassium channel. Altered gene expression is an important component of the electrical remodeling process and may contribute to repolarization abnormalities in AF.

Molecular and electrophysiological evidence for "remodeling" of the L-type Ca2+ channel in persistent atrial fibrillation in humans.

Persistent atrial fibrillation (AF) is associated with shortened action potential duration (APD) and reduced atrial refractoriness. Remodeling of ion currents responsible for AP morphology has been proposed as a major mechanism in persistent AF. In the present study we investigated the activity of the cardiac L-type Ca2+ channel and the mRNA transcription of the cardiac L-type Ca2+ channel subunits in patients with persistent AF compared to patients in sinus rhythm (SR). Right atrial appendages of 10 patients in SR and of 5 patients with AF were used for myocyte isolations to record L-type Ca2+ currents (ICa,L) by the patch-clamp technique. Right atrial appendages of 16 patients in Sr and of 5 patients with AF served as sources for determining the mRNA expression of the L-type Ca2+ channel alpha 1c-, alpha 2/delta-, beta a-, and beta b/beta c-subunits by semiquantitative RT-PCR. ICa,L density was reduced by 70% (p < 0.001) in AF patients compared to the sinus rhythm group. Cell sizes, expressed as cell capacitance, were identical in both groups. mRNA expressions of the alpha 1c-subunit and the beta b/beta c-subunits were reduced in AF patients by 18.9% (p < 0.05) and 77.7% (p < 0.005), respectively, while mRNA transcriptions of the alpha 2/delta- and the beta a-subunits were not significantly different between SR and AF patients. A decrease in the availability of functional L-type Ca2+ channels in AF patients, due to reduced alpha 1c-subunit and substantial lack of beta b/beta c-subunit transcription seems to contribute to the shortening of APD and refractory periods in AF, thereby favoring increased atrial excitation rate and perpetuation of AF.