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Tim Risius

Publications and source records attributed to Tim Risius.

17 recordsLinked to original sources

Modulation of local Ca2+ release sites by rapid fluid puffing in rat atrial myocytes.

Atrial myocytes that lack t-tubules appear to have two functionally separate sarcoplasmic Ca2+ stores: a peripheral store associated with plasmalemmal L-type calcium channels and a central store with no apparent proximity to L-type calcium channels. Here we describe a set of calcium sparks and waves that are triggered by puffing of pressurized (200-400 mmH2O) bathing solutions onto resting isolated rat atrial myocytes. Puffing of pressurized (200 mmH2O) solutions, identical to those bathing the myocytes from distances of approximately 150 microm onto the surface of a single myocyte triggered or enhanced spontaneously occurring peripheral sparks by five- to six-fold and central Ca2+ sparks by two- to three-fold, without altering the unitary spark properties. Exposure to higher pressure flows (400 mmH2O) often triggered longitudinally spreading Ca2+ waves. These results suggest that pressurized flows may directly modulate Ca2+ signaling of atrial myocytes by activating the intracellular Ca2+ release sites.

Animals↗

Substrate modification combined with pulmonary vein isolation improves outcome of catheter ablation in patients with persistent atrial fibrillation: a prospective randomized comparison.

AIMS: To investigate the effectiveness of additional substrate modification (SM) by left atrial (LA) linear lesions as compared with pulmonary vein isolation (PVI) alone in patients with persistent atrial fibrillation (AF) in a prospective randomized study. Percutaneous PVI has evolved as an accepted treatment for paroxysmal AF but seemed to be less effective in patients with persistent AF. The benefit of PVI alone and additional linear lesions has not been validated in a randomized study so far. METHODS AND RESULTS: Sixty-two patients with persistent AF (median duration 7, range 1-18 months) were randomly assigned to either PVI alone (n = 30) or additional SM (n =32) consisting of a roof line connecting both left superior and right superior PV and LA isthmus ablation between left inferior PV and mitral annulus. Procedures including SM were performed using a three-dimensional mapping system (EnSite NavX, St Jude Medical, St Paul, MN, USA). Anti-arrhythmic drugs were discontinued within 8 weeks after ablation in both groups. Follow-up included daily trans-telephonic ECG transmitted irrespective of the patient's symptoms. PVI was successful in 98% of all targeted veins in both groups. Additional SM did not increase fluoroscopy time (72.1+/-18.7 vs. 72.9+/-17.3 min, P=0.92) because of the use of three-dimensional navigation in the PVI+SM group. AF recurrences within the first 4 weeks following ablation were more common after PVI alone (77%) than additional SM (44%, P=0.002). After a follow-up time of 487 (429-570) days, only 20% of patients undergoing stand alone PVI remained in sinus rhythm when compared with 69% following PVI combined with SM (P=0.0001). Two patients assigned to PVI+SM experienced procedure-related complications (cardiac tamponade and minor stroke) which resolved without sequelae. CONCLUSION: PVI alone is insufficient in the treatment of persistent AF. However, additional left linear lesions increase the success rate significantly. Early AF-relapses are associated with a negative outcome after PVI alone but not following additional SM.

Atrial Fibrillation↗

Heparins increase endothelial nitric oxide bioavailability by liberating vessel-immobilized myeloperoxidase.

BACKGROUND: Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function. METHODS AND RESULTS: Plasma MPO levels before and after heparin administration were assessed by ELISA in 109 patients undergoing coronary angiography. Whereas baseline plasma MPO levels did not differ between patients with or without angiographically detectable coronary artery disease (CAD), the increase in MPO plasma content on bolus heparin administration was higher in patients with CAD (P=0.01). Heparin treatment also improved endothelial NO bioavailability, as evidenced by flow-mediated dilation (P<0.01) and by acetylcholine-induced changes in forearm blood flow (P<0.01). The extent of heparin-induced MPO release was correlated with improvement in endothelial function (r=0.69, P<0.01). Moreover, and consistent with this tenet, ex vivo heparin treatment of extracellular matrix proteins, cultured endothelial cells, and saphenous vein graft specimens from CAD patients decreased MPO burden. CONCLUSIONS: Mobilization of vessel-associated MPO may represent an important mechanism by which heparins exert antiinflammatory effects and increase vascular NO bioavailability. These data add to the growing body of evidence for a causal role of MPO in compromised vascular NO signaling in humans.

Aged↗

Simultaneous mapping of activation and motion timing in the healthy and chronically ischemic heart.

BACKGROUND: Experimental data of simultaneous acquired activation and motion (AM) propagation from human subjects are not available. OBJECTIVES: The purpose of this study was to demonstrate the feasibility of a novel mapping technique allowing combined analysis of AM timing in vivo and to delineate the influence of chronically ischemic tissue on cardiac AM propagation. METHODS: Ten patients with remote myocardial infarction and 4 control patients were studied during sinus rhythm using electroanatomic mapping (CARTO). Maps of the left ventricle were obtained via the retrograde aortic approach. Real-time catheter positions were extracted using custom-made software. Catheter motion was analyzed along a static line connecting the catheter tip with the apex. Tissue Doppler measurements in all patients provided data for validation. RESULTS: Four shapes of catheter motion curves were identified and correlated to healthy tissue with variable degrees of preloading, scar tissue and dyskinetic regions, e.g. aneurysms. An analysis of the AM-delay revealed areas of delayed activation in 7, and slow motion onset in 4 patients. Tissue Doppler data correlated well with local onset of motion (correlation coefficient 0,99). CONCLUSION: Activation delays as well as long AM-intervals that can be differentiated with the described mapping technique are responsible for asynchronous contraction in the ischemic heart. Myocardial wall motion abnormalities can be derived from catheter motion curves.

Adult↗

Transient ST-segment-elevation during pulmonary vein ablation using circumferential coiled microelectrodes in a prospective multi-centre study.

AIMS: Paroxysmal atrial fibrillation (PAF) is predominantly triggered by focal ectopies located within the pulmonary veins (PV). The BITMAP Study (Breakthrough and Isolation Trial: Mapping and Ablation of Pulmonary Veins) investigated prospectively the safety and efficacy of a catheter design with circumferential mapping and ablation electrodes. We report the phenomenon of ST-segment-elevation during catheter placement in the left atrium (LA) and superior PVs in this multi-centre study. METHODS AND RESULTS: Forty-three patients (57+/-10 years) with PAF were included in this study. Radiofrequency catheter (RFC) ablation supported by the 4F REVELATION Helix microcatheter (Cardima Inc., Freemont, CA, USA) with eight distal-coiled microelectrodes for bipolar mapping and ablation. RFC was applied at the ostial region of PV (30 W, 45-50 degrees C) with a maximum of four RFC applications per electrode. In four of the 43 patients from three centres, we recorded the occurrence of ST-segment-elevation greater than 0.2 mV and accompanying left thoracic discomfort. The ECG changes and the symptoms started abruptly and lasted for 4.2+/-2.2 min. Pericardial effusion could instantaneously be excluded by echocardiography in all cases. Coronary angiograms were performed in three patients with the longest episodes; no thrombotic material or air emboli were present. The symptoms and the ECG changes resolved completely in all patients. CONCLUSION: The phenomenon of ST-segment-elevation during LA- and PV-mapping in patients with PAF may be a common occurrence. In this prospective multi-centre trial, we demonstrated the reversibility of this phenomenon; no cardiovascular or cerebral damage was reported during both the procedure and the follow-up. Although the mechanism is still unclear, vasospasm may contribute to this phenomenon because of autonomic dysregulation.

Adult↗

Correlation of symptoms to ECG diagnosis following atrial fibrillation ablation.

INTRODUCTION: Currently, definition of success following atrial fibrillation (AF) ablation is commonly based on the lack of symptoms. The purpose of this study was to evaluate the correlation between symptoms and the underlying rhythm after AF ablation. METHODS AND RESULTS: Eighty consecutive patients (pts) were treated for paroxysmal episodes of AF by segmental ostial ablation of all pulmonary veins and right atrial isthmus ablation. For 6 months pts transmitted transtelephonic (T-) ECG recordings in combination with comments daily or in the event of symptoms. Eligible comments were classified as: (1) asymptomatic, (2) symptomatic. Analysis was performed at 1-month intervals, defining an acute (first month) and chronic period (second to sixth month) after ablation. Overall 6,835 T-ECGs were analyzed. Of these 5,437 (79.5%) showed sinus rhythm (SR) and 1,398 (20.5%) showed AF. Pts in SR reported symptoms for 593 (10.9%) episodes, whereas 4,844 (89.1%) episodes were asymptomatic. During AF, 646 (46.2%) episodes were associated with symptoms, and 752 (53.8%) episodes remained asymptomatic. Exclusively asymptomatic were 7 (8.8%) pts. In 30 (52.6%) of 57 pts with AF, arrhythmic events were confined to the acute phase. Of the remaining 27 pts 14 (52%) reported an improvement, 12 (44%) the same, and 1 (4%) worsened symptoms after 3 months. A significant change (P < 0.01) toward more asymptomatic episodes from the acute (43.5%) to the chronic (57.5 +/- 4.5%) period was evident. CONCLUSION: Assessment of success after AF ablation cannot be based on the absence of symptoms due to a high prevalence of asymptomatic episodes.

Atrial Fibrillation↗

Impact of amiodarone on electrophysiologic properties of pulmonary veins in patients with paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary veins (PVs) are the predominant location of triggers for atrial fibrillation (AF), but little is known about the electrophysiologic properties of PVs. In addition, the influence of amiodarone on the electrophysiologic properties of PVs has not been elucidated. METHODS AND RESULTS: Fifty-five patients with symptomatic and drug-resistant AF were divided into two groups: group 1 patients (n=29) without antiarrhythmic drug therapy at the time of electrophysiologic study (EPS), and group 2 patients (n=26) undergoing continuous long-term treatment with amiodarone. EPS including programmed stimulation of both atria and within the PVs was performed in both groups. In group 1, the effective refractory period (ERP) of all PVs (174 +/- 62 msec) was significantly shorter than the ERP of the left atrium ([LA] 254 +/- 30 msec, P=0.0001) and right atrium ([RA] 221 +/- 29 msec, P=0.0001). The same pattern was observed in group 2 (PV: 210 +/- 58 msec; LA: 259 +/- 35 msec, P=0.0001; RA: 246 +/- 37 msec, P=0.0255). The ERP of all stimulated PVs was significantly lower in group 1 (174 +/- 62 msec) than in group 2 (210 +/- 58 msec; P=0.0001). The ERP of the left superior and right superior PVs and RA but not the left inferior PV and LA were significantly increased in patients treated with amiodarone. Decremental conduction properties were observed in all stimulated PVs, and there were no significantly differences between the maximal decrement of both groups. CONCLUSION: The distinctive electrophysiologic properties of PVs are emphasized by amiodarone therapy. Long-term amiodarone treatment is responsible for heterogeneous alteration of the PV electrophysiology, which may account for the individual antiarrhythmic responses in a subset of patients with paroxysmal AF.

Amiodarone↗

Efficacy and safety of radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia in the elderly.

INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common regular supraventricular tachycardia in the general population as well as in elderly patients. The purpose of the study was to investigate the success and complication rate particularly regarding the induction of an atrioventricular (AV) block by radiofrequency (RF) ablation in elderly patients with and without a preexisting AV block. METHODS AND RESULTS: Between February 1998 and July 2004, all patients with symptomatic AVNRT referred for slow-pathway ablation in our institution were included and divided into two groups: group 1 patients younger than 75 years (n = 508) and group 2 patients > or =75 years (n = 70). A preexisting prolonged PR interval was present in 17 (3.3%) patients of group 1 and in 26 (37%, P < 0.0001) patients of group 2. Following successful slow-pathway ablation (follow-up time group 1: 37 +/- 22, group 2: 37 +/- 24 months) no induction of an AV block was observed in group 2 but in four patients of group 1 (0.79%) a complete heart block was induced requiring a pacemaker implantation. In group 1, 15 (2.95%) patients with a recurrence of AVNRT were readmitted for a repeat ablation procedure. No recurrences occurred in group 2. CONCLUSION: Despite a higher incidence of preexisting prolonged PR intervals slow-pathway ablation in elderly patients is both effective and safe and should be considered as the first line therapy also in this patient population.

Age Factors↗

Multimodality of Ca2+ signaling in rat atrial myocytes.

It has been suggested that the multiplicity of Ca(2+) signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca(2+) signaling cascade initiated by mechanical forces induced by "puffing" of solution onto the myocytes. Ca(i) transients were measured in fura-2 acetoxymethyl (AM) loaded cells using alternating 340- and 410-nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied by an electronically controlled micro-barrel system, activated slowly (approximately 300 ms) developing Ca(i) transients that lasted 1,693 +/- 68 ms at room temperature. Subsequent second and third puffs, applied at approximately 20 s intervals activated significantly smaller or no Ca(i) transients. Puff-triggered Ca(i) transients could be reactivated once again following caffeine (10 mM)-induced release of Ca(2+) from sarcoplasmic reticulum (SR). Puff-triggered Ca(i) transients were independent of [Ca(2+)](o), and activation of voltage-gated Ca(2+) or cationic stretch channels or influx of Ca(2+) on Na(+)/Ca(2+)exchanger, because puffing solution containing no Ca(2+), 10 microM diltiazem, 1 mM Cd(2+), 5 mM Ni(2+), or 100 microM Gd(3+) failed to suppress them. Puff-triggered Ca(i) transients were enhanced in paced compared to quiescent myocytes. Electrically activated Ca(i) transients triggered during the time course of puff-induced transients were unaltered, suggesting functionally separate Ca(2+) pools. Contribution of inositol 1,4,5-triphosphate (IP(3))-gated or mitochondrial Ca(2+) pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 microM 2-aminoethoxydiphenyl borate (2-APB) and 0.1 to 1 microM carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and 1 mM Nomega-Nitro-L-arginine methyl ester (L-NAME) and 7-nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff-triggered Ca(i) transients. It was concluded that neither Ca(2+) influx nor depolarization was required for activation of this signaling pathway. These studies suggest that pressurized puffs of solutions activate a mechanically sensitive receptor, which signals in turn the release of Ca(2+) from a limited Ca(2+) store of mitochondria. How mechanical forces are sensed and transmitted to mitochondria to induce Ca(2+) release and what role such a Ca(2+) signaling pathway plays in the physiology or pathophysiology of the heart remain to be worked out.

Animals↗

Sub-threshold stimulation in variants of atrioventricular nodal re-entrant tachycardia: electrophysiological effects and impact for guidance of slow pathway ablation.

AIM: Sub-threshold stimulation (STS) applied during atrioventricular nodal re-entrant tachycardia (AVNRT) of the common (slow-fast) type has been shown to effectively characterise target sites suitable for slow pathway (SP) ablation but has not been investigated in the setting of fast-slow and slow-slow variants. METHODS AND RESULTS: Seventeen consecutive patients (52+/-16 years, 12 female) with sustained uncommon type AVNRT (fast-slow: n = 13, slow-slow: n = 4) were investigated. Mapping of the SP was started postero-septally close to the coronary sinus ostium and continued toward mid-septal sites, if required. Target sites for STS were selected according to established criteria including the recording of the earliest retrograde atrial activation during AVNRT. Long duration (5 s) constant current STS during AVNRT variants was performed in a stepwise manner (max 5 mA) at each site eligible for SP ablation until termination or capture occurred. Radiofrequency current (RFC) was delivered following successful STS termination of tachycardia (65 degrees C, 60 s) and exclusion of catheter dislodgement. Uncommon AVNRT with a mean cycle length of 405+/-70 ms was induced without spontaneous termination in all patients. Interruption of AVNRT variants due to selective STS-induced block of the retrograde (n = 12) or anterograde (n =2) SP occurred without capture in 14/17 (82%) patients. This was exclusively observed at sites with successful subsequent RFC application. AVNRT was rendered non-inducible in all patients after a median of 1 (1-11) RFC pulses without complications. CONCLUSIONS: Uncommon AVNRT can be interrupted by STS delivered at subsequently successful target sites for SP ablation in most patients (82%). The high positive and negative concordance between the effects of STS and following RFC application indicates that STS-mapping is also useful in the setting of AVNRT variants.

Adult↗

Radiofrequency catheter ablation of a macroreentrant ventricular tachycardia late after surgical repair of tetralogy of Fallot using the electroanatomic mapping (CARTO).

This case report describes a patient with a sustained monomorphic VT after surgical repair of a tetralogy of Fallot (TOF). In combination with the three-dimensional electroanatomic mapping system, CARTO, and conventional mapping techniques the VT was identified as a macro-reentrant tachycardia circling around the border between pulmonary graft and right ventricular outflow tract (RVOT). A y-shaped ablation line crossing this zone was created. The VT terminated during RF application and was not inducible again. This case underlines the use of a combined conventional and three-dimensional electroanatomic mapping technique can be helpful for catheter ablation of ventricular arrhythmias in TOF patients.

Adult↗

Large tip electrodes for successful elimination of atrial flutter resistant to conventional catheter ablation.

The most widely accepted criterion for successful radiofrequency catheter (RFC) ablation of typical atrial flutter is the development of bi-directional isthmus block. In a subset of patients, conventional RFC ablation fails to achieve this endpoint because deeper and wider lesions are required. We investigated the efficacy of a long 8-mm tip catheter in these cases. One hundred and seventy-four consecutive patients (137 male; 61 +/- 9 years) with recurrent typical atrial flutter underwent conventional RFC ablation first with a standard 4 mm tip catheter. In resistant cases (n = 52), ablation was continued using a large tip 8-mm catheter when the 4-mm tip catheter failed. Resistant atrial flutter was identified when 21 RFC pulses failed to reach the selected endpoint of bi-directional isthmus block or in cases of transient bi- directional block (at least 3 episodes). In 122 of the 174 patients (70%) conventional atrial flutter ablation was successfully performed with 13 +/- 5 RFC applications. In the remaining 52 subjects (30%), the ablation procedure was completed using the large tip electrode catheter. In 30 of these 52 patients (58%), the catheter was changed because of persistent intra-atrial conduction after 21 RFC pulses and in 22 (42%) because of intermittent conduction block after 11 +/- 5 applications. Using the large tip electrode catheter, the selected endpoint was achieved in all patients of both groups with 3 +/- 2 RFC pulses (power output of 50-60 W, pulse duration of 60 sec). No post-procedure complications were observed. After 15 +/- 5 months of follow-up, 16 patients (9%) had recurrence of atrial flutter. Five of the patients had been in the resistant group. In patients with atrial flutter resistant to conventional ablation therapy, the long tip (8-mm) catheter appears to be a safe and effective alternative to use of the conventional 4-mm tip catheter.

Atrial Flutter↗

Dissociated activity and pulmonary vein fibrillation following functional disconnection: impact for the arrhythmogenesis of focal atrial fibrillation.

The present study sought to investigate the electrophysiological properties of isolated pulmonary veins following successful radiofrequency (RF) catheter ablation in patients with paroxysmal atrial fibrillation (PAF). Overall, 71 pulmonary veins in 37 consecutive patients (age: 56 +/- 9 years) with recurrent PAF were targeted for RF ablation at the ostial region in order to achieve a complete functional block. Following disconnection, the incidence of dissociated pulmonary vein (PV) activity and its response to orciprenalin were studied. RF ablation abolished conduction in 67 (94%) of 71 potentially arrhythmogenic PVs after a mean of 10.7 +/- 6.4 RF applications for each PV. After ablation, spontaneous dissociated automatic activity (9 to 52 beats/min, median 27) was found in 6 out of 67 isolated PVs (left superior: n = 1, left inferior: n = 1, right superior: n = 2, common left PV: n = 2). Slight acceleration (13 to 68 beats/min, median 29) of dissociated PV activity was observed during infusion of orciprenalin. Following isolation, initiation of sustained or nonsustained local fibrillation was recorded in only two cases of the common left sided PV with preceding automatic activity. In one patient PV fibrillation occurred during orciprenalin infusion following a repetitive response to a dissociated automatic rhythm with increasing duration as well as destabilization. In the other patient, PV fibrillation occurred immediately after the occurrence of PV automaticity. Slow dissociated automatic rhythms are detectable within 9% of disconnected PVs. The unique anatomic substrate of common left PVs seem to favor the occurrence of local fibrillation following isolation. The initiation pattern of fibrillation within the isolated PV has pathophysiological implications and underlines the contribution of multiple factors to the onset and sustenance of PAF.

Aged↗

Electrical disconnection of an arrhythmogenic superior vena cava with discrete radiofrequency current lesions guided by noncontact mapping.

This case describes a 54-year-old patient with paroxysmal atrial fibrillation and atrial flutter. Conventionally recorded local electrogram demonstrated a cycle length of 245 ms in the SVC which was conducted to the right atrium in a 2:1 fashion. The analysis of the virtual unipolar local electrogram from the noncontact mapping system demonstrated slow conduction between SVC and right atrium orthogonal to the atrial breakthrough in the upper part of the crista terminalis. RF ablation at the atrial breakthrough induced the electrical disconnection between the CVC and the right atrium.

Atrial Fibrillation↗

Functional disconnection of arrhythmogenic pulmonary veins in patients with paroxysmal atrial fibrillation guided by combined electroanatomical (CARTO) and conventional mapping.

BACKGROUND: Isolation of arrhythmogenic pulmonary veins (PVs) by radiofrequency current (RF) application has been introduced as a curative treatment for patients (pts) with paroxysmal atrial fibrillation (AF). The present study sought to investigate the feasibility and efficacy of this approach guided by conventional and electroanatomical mapping (CARTO). METHODS: Twenty pts (13 male; 57 +/- 8 years) with recurrent documented focally triggered idiopathic AF refractory to multiple antiarrhythmic drugs were prospectively included. Atrial premature beats were present at baseline in 9 pts and could be provoked in further 8 pts. Empirical ablation of both superior PVs was performed in 3 pts with no focal activity. After transseptal puncture selective angiography of all PVs was obtained. Thirty-six PVs (left superior: n = 18, right superior: n = 10, left inferior: n = 8) were targeted for RF ablation. A complete left atrial CARTO-map including the left atrial (LA) to pulmonary vein (PV) junction was obtained during sinus rhythm and/or coronary sinus pacing. RF was initially applied at the PV-LA junction at areas with the shortest left atrial- to PV potential interval (target 50 degrees C, max. 30 W, duration 60 sec). Isolation was confirmed by the complete disappearance of specific PV potentials. RF lesions were analyzed with respect to the number of segment-quarters covering the PV ostium. RESULTS: Functional isolation could be achieved in 35 out of 36 PVs following 10 +/- 5 RF applications for each PV. RF applications covered 2 or less quarter segments of the overall PV circumference in 29 (80%) PVs. Total session duration was 6.5 +/- 1.6 h with a mean fluoro-time of 54 +/- 18 minutes. For CARTO mapping and ablation a mean fluoro time of 34 +/- 6 min was required. During a mean follow up period of 8.3 +/- 2.5 months AF relapsed in 9 pts (46%). A second approach was performed in 5 pts. and demonstrated either new foci (n = 2) or recurrence of previously isolated PV (n = 8). The second RF ablation procedure led to stable sinus rhythm in 3 out 5 pts. Thus, the overall success rate including the second procedure was 70%. CONCLUSIONS: CARTO guided functional isolation of presumed arrhythmogenic PVs by RF lesions covering 2 or less segments of the PV ostium in most patients is feasible. However, repeat procedures are often warranted to permanently treat paroxysmal atrial fibrillation.

Adult↗

Impact of the distribution and structure of myocardium in the pulmonary veins for radiofrequency ablation of atrial fibrillation.

Focal AF is frequently triggered by ectopic beats mostly originating from the pulmonary veins (PVs). So far, the morphological substrate for this entity is not well defined. Therefore, the distribution of myocardial cells within the PV were examined as potential target sites for RF application. The PVs (118) of 30 human autopsied hearts (age of death 63 +/- 13 years, 17 men) were dissected in their complete circumference starting 1 cm from the ostium. Tissue sections of the PV were stained with hematoxylin-eosin and with Masson's trichrome. To characterize the developmental state of the myocardial tissue in the PV, immunohistochemistry was performed with antibodies reacting with antigens which are stage specifically expressed during cardiac development (HNK1/Leu7, alpha-SMA, calponin and desmin). Furthermore, proliferative activity was assessed using antibodies against the Ki-67 antigen (MIB-1). In two hearts a left-sided common PV ostium was found. The other hearts showed four separated PV ostia. The ostium diameter of the right inferior PV (1.2 +/- 0.3 cm) was significantly smaller (P < 0.05) than remaining PV ostia (right superior 1.5 +/- 0.2, left superior, 1.5 +/- 0.3 and left inferior 1.4 +/- 0.3 cm) of the 118 specimen. There was no significant difference in the presence of myocardium in the PV 1-cm distant from the ostium comparing the right superior (78%), the right inferior (81 %), the left superior (81%), and the left inferior (81%) PV. In 54% of cases the myocardial bundles covered the complete PV circumference. In up to 38% of the small extensions of the myocardial bundles myocardial cells, characterized by distinct cross-striations and spindle shape were found. However, since these cells could not be labeled for other markers than desmin, their immature state seems unlikely. The anatomic distribution of myocardium in the PV suggests that RF applied to the entire circumference may be frequently required for its electrical isolation. Whether spindle-shaped myocytes have different electrophysiological behavior has to be further investigated.

Atrial Fibrillation↗