Robotic Ablation of Atrial Fibrillation

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between pulmonary vein (PV) and left atrium (LA) is created. This conduction block prevents AF, which is triggered by irregular electric activity originating from the PV. However, transmural atrial lesions are required which can be challenging. Re-conduction and AF recurrence occur in 20 - 40% of the cases. Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new remote catheter system (RCS), is presented. Objective of this article is to show feasibility of robotic AF ablation with a novel system. Materials and Methods: After interatrial trans-septal puncture is performed using a long sheath and needle under fluoroscopic guidance. The needle is removed and a guide wire is placed in the left superior PV. Then an ablation catheter is positioned in the LA, using the sheath and wire as guide to the LA. LA angiography is performed over the sheath. A circular mapping catheter is positioned via the long sheath into the LA and a three-dimensional (3-D) anatomical reconstruction of the LA is performed. The handle of the ablation catheter is positioned in the robotic arm of the Amigo system and the ablation procedure begins. During the ablation procedure, the operator manipulates the ablation catheter via the robotic arm with the use of a remote control. The ablation is performed by creating point-by-point lesions around the left and right PV ostia. Contact force is measured at the catheter tip to provide feedback of catheter-tissue contact. Conduction block is confirmed by recording the PV potentials on the circular mapping catheter and by pacing maneuvers. The operator stays out of the radiationfield during ablation. Conclusion: The novel catheter system allows ablation with high stability on low operator fluoroscopy exposure.     

Mononucleated and binucleated cardiomyocytes in left atrium and pulmonary vein have different electrical activity and calcium dynamics

Cardiomyocytes consist of single- and bi-nucleus myocytes. However, the electrophysiological characteristics of mononucleated and binucleated myocytes have never been elucidated. Left atrium (LA) and pulmonary veins (PVs) are important substrate and initiators of atrial fibrillation. The purposes of this study were to evaluate the electrical properties and calcium homeostasis in mononucleated and binucleated cardiomyocytes in the LA and PVs. A whole-cell clamp, fluo-4 fluorescence, and immunocytostaining were used to investigated mononucleated and binucleated cardiomyocytes in the LA and PVs. Both mononucleated PV and LA cardiomyocytes had more positive resting membrane potential than respective PV and LA binucleated cardiomyocytes. Additionally, mononucleated PV cardiomyocytes (n = 36) had faster beating rates (2.1 ± 0.2 Hz versus 1.0 ± 0.2 Hz, P < 0.05) than binucleated (n = 10) PV cardiomyocytes. The PV (n = 18) and LA (n = 15) mononucleated cardiomyocytes had larger [Ca2?](i) transients (F/F? 1.64 ± 0.09 versus 1.20 ± 0.03 IU, P < 0.05; 1.52 ± 0.06 versus 1.19 ± 0.05 IU, P < 0.05) than the binucleated PV (n = 10) and LA (n = 10) cardiomyocytes. The immunostaining showed that mononucleated cardiomyocytes had lower Kir 2.3 and higher ryanodine receptor densities than did binucleated cardiomyocytes both in the PV and LA. In conclusions, mononucleated PV and LA cardiomyocytes contain distinctive electrophysiological characteristics with a higher arrhythmogenic activity, which indicates that cell nucleus number may potentially determine the electrical activity and calcium handling in cardiomyocytes.     

Three-dimensional computed tomography overlay for pulmonary vein antrum isolation: Follow-up and clinical outcomes

Background

To facilitate the creation of circumferential lines in pulmonary vein (PV) antrum isolation, three-dimensional (3D) navigation systems are used widely. Alternatively, 3D reconstructions of the left atrium (LA) can be superimposed directly on fluoroscopy to guide ablation catheters and to mark ablation sites.

Methods

In 71 atrial fibrillation patients circumferential PV ablation was performed. 3D reconstructions of the LA were derived from contrast cardiac-computed tomography and circumferential PV isolation was performed. In subsequent ablation procedures, veins were re-isolated, and defragmentation or linear lesions were performed if necessary.

Results

Adequate 3D reconstructions were formed and registered to fluoroscopy in all patients. All veins, except 2 in one single patient, could be isolated, resulting in freedom of AF in 45 patients (63?%). In 19 patients a second procedure was performed, in which 2.7?±?1.1 PV per patient were re-isolated; in 3 patients a third procedure was performed. After follow-up of 15?±?8?months, 51 (91?%) of patients with paroxysmal and 10 (67?%) with persistent AF were free of AF.

Conclusions

The results of 3D overlay for circumferential PV isolation are good, although the reconduction rate and need for subsequent ablations remains high, and the outcomes of this technique appear to be equivalent to other mapping techniques.     

Increased Ca(2+) sparks and sarcoplasmic reticulum Ca(2+) stores potentially determine the spontaneous activity of pulmonary vein cardiomyocytes

Pulmonary veins (PVs) contain cardiomyocytes with spontaneous activity that may be responsible for PV arrhythmia. Abnormal Ca(2+) regulation is known to contribute to PV arrhythmogenesis. The purpose of this study was to investigate whether PV cardiomyocytes with spontaneous activity have different intracellular Ca(2+) ([Ca(2+)](i)) transients, Ca(2+) sparks and responses to isoproterenol and ryanodine receptor modulators (magnesium and FK506) than do PV cardiomyocytes without spontaneous activity and left atrial (LA) cardiomyocytes. Through fluorescence and confocal microscopy, we evaluated the [Ca(2+)](i) transients and Ca(2+) sparks in isolated rabbit PV and LA cardiomyocytes. PV cardiomyocytes with spontaneous activity had larger [Ca(2+)](i) transients and sarcoplasmic reticulum (SR) Ca(2+) stores than PV cardiomyocytes without spontaneous activity or LA cardiomyocytes. PV cardiomyocytes with spontaneous activity also had a higher incidence and frequency of Ca(2+) sparks, and had Ca(2+) sparks with larger amplitudes than other cardiomyocytes. Magnesium (5.4 mM) reduced the [Ca(2+)](i) transient amplitude and beating rate in PV cardiomyocytes with spontaneous activity. However, in contrast with other cardiomyocytes, low doses (1.8 mM) of magnesium did not reduce the [Ca(2+)](i) transients amplitude in PV cardiomyocytes with spontaneous activity. FK506 (1 muM) diminished the SR Ca(2+) stores in PV cardiomyocytes with spontaneous activity to a lesser extent than that in other cardiomyocytes. Isoproterenol (10 nM) increased the [Ca(2+)](i) transient amplitude to a lesser extent in LA cardiomyocytes than in PV cardiomyocytes with or without spontaneous activity. In conclusion, our results suggest that enhanced [Ca(2+)](i) transients, increased Ca(2+) sparks and SR Ca(2+) stores may contribute to the spontaneous activity of PV cardiomyocytes.     

Usefulness of Contrast Intracardiac Echocardiography in Performing Pulmonary Vein Balloon Occlusion during Cryo-ablation for Atrial Fibrillation

BackgroundCryoballoon ablation (CBA) has been proven to be very effective for pulmonary vein (PV) isolation (PVI) if complete occlusion is achieved and conventionally assessed by angiographic injection of contrast within PV lumen. The aim of our study was to assess the usefulness of saline contrast intracardiac echocardiography in guiding CBA with respect to PV angiography.MethodsThirty consecutive patients with paroxysmal atrial fibrillation were randomly assigned fluoroscopy plus color-flow Doppler (n = 15; group 1: an iodinated medium as both angiographic and echographic contrast) or contrast intracardiac echocardiography plus color-flow Doppler (n = 15; group 2: saline contrast) for guidance of CBA.ResultsWe evaluated 338 occlusions of 107 PVs. The intracardiac echocontrastography-guided assessment of occlusion, defined as loss of echocontrastographic back-flow to the left atrium after saline injection regardless of the visualization of PV antrum, showed a high level of agreement with the angiographic diagnosis of occlusion. PVI rate was similar in both groups and effectively guided by intracardiac echocontrastography (PVI using ≤ 2 double cryofreezes: 89% of PVs in group 1 vs. 91% in group 2; p=n.s.). Group 2 patients had significantly shorter procedure (127 ± 16 vs. 152 ± 19 minutes; p<0.05) and fluoroscopy times (30 ± 12 vs. 43 ± 9 minutes, p<0.05) and used a lower iodinated contrast (88 ± 26 vs. 190 ± 47 mL, p<0.05).ConclusionsPV occlusion and PVI during cryoablation can be effectively predicted by intracardiac saline echocontrastography. This technique reduces procedural time, radiological exposure and iodinated contrast use.     

What are the post-ablation insular residual electrograms in the posterior left pulmonary veins electrically connected to?

A 67-year-old man underwent a third ablation procedure for a recurrent atrial tachycardia (AT) after an extensive pulmonary vein (PV) isolation, linear ablation along the left atrial (LA) roof and posterolateral mitral isthmus (MI), and defragmentation of persistent atrial fibrillation and an induced perimitral AT. High-resolution mapping during the clinical AT using the Rhythmia system (Boston Scientific) suggested that the AT was a ridge-related reentrant AT and exhibited a reconnection of the left PVs (LPVs). The residual electrograms in the posterior LPVs were surrounded by endocardial scar, which was like an island consisting of residual LPV electrograms. Retrograde venography of the vein of Marshall (VOM) demonstrated that the VOM reached the posterior left superior PV through the ridge between the LA appendage and left inferior PV and then the LPV carina. An ethanol infusion into the VOM resulted in a simultaneous AT termination and complete electrical isolation of the LPVs, that is, the disappearance of the residual LPV electrograms. The insular residual LPV electrograms in the present case did not appear to be endocardially connected to the LA, because the LPV electrograms were surrounded by endocardial scar and there was a large time gap between the earliest activation in the posterior LPVs and activation in the surrounding area. The VOM course on the venography and elimination of the residual LPV electrograms with an ethanol infusion into the VOM suggested that the insular residual LPV electrograms were electrically connected to the posterolateral LA via the VOM and its branches.     

Deceleration time of systolic pulmonary venous flow: a new clinical marker of left atrial pressure and compliance.

The curvilinearity of the atrial pressure-volume curve implies that atrial compliance decreases progressively with increasing left atrial (LA) pressure (LAP). We predicted that reduced LA compliance leads to more rapid deceleration of systolic pulmonary venous (PV) flow. With this rationale, we investigated whether the deceleration time (t dec) of PV systolic flow velocity reflects mean LAP. In eight patients during coronary surgery, before extracorporeal circulation, PV flow by ultrasonic transit time and invasive LAP were recorded during stepwise volume loading. The t dec was calculated using two methods: by drawing a tangent through peak deceleration and by drawing a line from peak systolic flow through the nadir between the systolic and early diastolic flow waves. LA compliance was calculated as the systolic PV flow integral divided by LAP increment. Volume loading increased mean LAP from 11 +/- 3 to 20 +/- 5 mmHg (P < 0.001) (n = 40), reduced LA compliance from 1.16 +/- 0.42 to 0.72 +/- 0.40 ml/mmHg (P < 0.004) (n = 40), and reduced t dec from 320 +/- 50 to 170 +/- 40 ms (P < 0.0005) (n = 40). Mean LAP correlated well with t dec (r = 0.84, P < 0.0005) (n = 40) and LA compliance (r = 0.79, P < 0.0005) (n = 40). Elevated LAP caused a decrease in LA compliance and therefore more rapid deceleration of systolic PV flow. The t dec has potential to become a semiquantitative marker of LAP and an index of LA passive elastic properties.     

Effects of procainamide on electrical activity in thoracic veins and atria in canine model of sustained atrial fibrillation

Focal discharges (FDs) are present in thoracic veins during atrial fibrillation (AF). We hypothesize that procainamide exerts its anti-AF action by suppressing FDs in the thoracic veins. We studied six mongrel dogs (22-27 kg) with sustained (>6 h) AF induced by 47 +/- 20 days of chronic rapid LA appendage (LAA) or pulmonary vein (PV) pacing. Procainamide was infused intravenously until AF was terminated or a cumulative dose of 20 mg/kg was reached. High-resolution mapping during AF showed FDs in the vein of Marshall, PVs, and the LAA. Procainamide significantly (P < 0.05) reduced the frequency of these FDs and suppressed the interactions of wave fronts between PVs and LA. The cumulative dose of PA needed to terminate AF correlated negatively (r =-0.9, P < 0.05) with the baseline effective refractory period (ERP) of PV and positively (r = 0.8, P < 0.05) with the baseline maximum dominant frequency (DF) of AF. In four of five dogs, AF converted to atrial tachycardia originating from the PVs before termination. Attempts to reinduce sustained AF were unsuccessful in these five dogs. AF was resistant to procainamide in the sixth dog. In conclusion, procainamide reduced the rate of FDs in the thoracic veins and the LA and suppressed the interaction between PVs and LA. Second, FDs in the PV are more resistant to procainamide's action than FDs in the atria. Third, inherent PV ERP is important in determining the antifibrillatory efficacy of procainamide.     

Hydrogen sulphide increases pulmonary veins and atrial arrhythmogenesis with activation of protein kinase C

Hydrogen sulphide (H₂S), one of the most common toxic air pollutants, is an important aetiology of atrial fibrillation (AF). Pulmonary veins (PVs) and left atrium (LA) are the most important AF trigger and substrate. We investigated whether H₂S may modulate the arrhythmogenesis of PVs and atria. Conventional microelectrodes and whole‐cell patch clamp were performed in rabbit PV, sinoatrial node (SAN) or atrial cardiomyocytes before and after the perfusion of NaHS with or without chelerythrine (a selective PKC inhibitor), rottlerin (a specific PKC δ inhibitor) or KB‐R7943 (a NCX inhibitor). NaHS reduced spontaneous beating rates, but increased the occurrences of delayed afterdepolarizations and burst firing in PVs and SANs. NaHS (100 μmol/L) increased I_KATP and I_NCX in PV and LA cardiomyocytes, which were attenuated by chelerythrine (3 μmol/L). Chelerythrine, rottlerin (10 μmol/L) or KB‐R7943 (10 μmol/L) attenuated the arrhythmogenic effects of NaHS on PVs or SANs. NaHS shortened the action potential duration in LA, but not in right atrium or in the presence of chelerythrine. NaHS increased PKC activity, but did not translocate PKC isoforms α, ε to membrane in LA. In conclusion, through protein kinase C signalling, H₂S increases PV and atrial arrhythmogenesis, which may contribute to air pollution‐induced AF.     

Left atrial conduit volume is generated by deviation from the constant-volume state of the left heart: a combined MRI-echocardiographic study

Although modeling the four-chambered heart as a constant-volume pump successfully predicts causal physiological relationships between cardiac indexes previously deemed unrelated, the real four-chambered heart slightly deviates from the constant-volume state by ventricular end systole. This deviation has consequences that affect chamber function, specifically, left atrial (LA) function. LA attributes have been characterized as booster pump, reservoir, and conduit functions, yet characterization of their temporal occurrence or their causal relationship to global heart function has been lacking. We investigated LA function in the context of the constant-volume attribute of the left heart in 10 normal subjects using cardiac magnetic resonance imaging (MRI) and contemporaneous Doppler echocardiography synchronized via ECG. Left ventricular (LV) and LA volumes as a function of time were determined via MRI. Transmitral flow, pulmonary vein (PV) flow, and lateral mitral annular velocity were recorded via echocardiography. The relationship between the MRI-determined diastolic LA conduit-volume (LACV) filling rate and systolic LA filling rate correlate well with the relationship between the echocardiographically determined average flow rate during the early portion of the PV D wave and the average flow rate during the PV S wave (r = 0.76). We conclude that the end-systolic deviation from constant volume for the left heart requires the generation of the LACV during diastole. Because early rapid filling of the left ventricle is the driving force for LACV generation while the left atrium remains passive, it may be more appropriate to consider LACV to be a property of ventricular diastolic rather than atrial function.     

High-density mapping of pulmonary veins and left atrium during ibutilide administration in a canine model of sustained atrial fibrillation

Ibutilide can prolong refractory period and terminate reentry. Whether ibutilide has the same effects on pulmonary vein (PV) focal discharge (FD) is unclear. We induced sustained atrial fibrillation (AF) in seven dogs by rapid left atrial (LA) pacing for 74 +/- 46 days. Ibutilide was repeatedly infused until it terminated AF (0.02 +/- 0.01 mg/kg) or when a cumulative dose was reached (0.04 mg/kg). High-resolution computerized epicardial mapping was performed. We found intermittent FD at the PVs and reentry at the PV-LA junction during AF. Ibutilide increased the cycle length of consecutive reentry from 97 +/- 13 to 112 +/- 18 ms and increased FD from 96 +/- 7 to 113 +/- 9 ms. In four dogs with both FD and reentry at the PVs, the incidence of reentry decreased from 3.5 +/- 1.9/s at baseline to 2.2 +/- 1.8/s after ibutilide administration. However, the incidence of FD remained unchanged. The conducted wave fronts between PV and LA were significantly reduced by ibutilide (10.4 +/- 2.0/s vs. 8.0 +/- 1.6/s). The ibutilide dose needed to terminate AF correlated negatively with the baseline effective refractory period of PV and LA. We conclude that ibutilide reduces reentrant wave fronts but not PV FD in a canine model of pacing-induced sustained AF. These findings suggest that the PV FD during AF is due to nonreentrant mechanisms. High doses of ibutilide may completely terminate all reentrant activity, converting AF to PV tachycardia before the resumption of sinus rhythm.     

Direct Pressure Monitoring Accurately Predicts Pulmonary Vein Occlusion During Cryoballoon Ablation

Cryoballoon ablation (CBA) is an established therapy for atrial fibrillation (AF). Pulmonary vein (PV) occlusion is essential for achieving antral contact and PV isolation and is typically assessed by contrast injection. We present a novel method of direct pressure monitoring for assessment of PV occlusion.Transcatheter pressure is monitored during balloon advancement to the PV antrum. Pressure is recorded via a single pressure transducer connected to the inner lumen of the cryoballoon. Pressure curve characteristics are used to assess occlusion in conjunction with fluoroscopic or intracardiac echocardiography (ICE) guidance. PV occlusion is confirmed when loss of typical left atrial (LA) pressure waveform is observed with recordings of PA pressure characteristics (no A wave and rapid V wave upstroke). Complete pulmonary vein occlusion as assessed with this technique has been confirmed with concurrent contrast utilization during the initial testing of the technique and has been shown to be highly accurate and readily reproducible.We evaluated the efficacy of this novel technique in 35 patients. A total of 128 veins were assessed for occlusion with the cryoballoon utilizing the pressure monitoring technique; occlusive pressure was demonstrated in 113 veins with resultant successful pulmonary vein isolation in 111 veins (98.2%). Occlusion was confirmed with subsequent contrast injection during the initial ten procedures, after which contrast utilization was rapidly reduced or eliminated given the highly accurate identification of occlusive pressure waveform with limited initial training.Verification of PV occlusive pressure during CBA is a novel approach to assessing effective PV occlusion and it accurately predicts electrical isolation. Utilization of this method results in significant decrease in fluoroscopy time and volume of contrast.     

The role of capacitance in the water balance of Andean giant rosette species

Abstract Pith water storage capacity and its role in plant-water relations were studied in seven giant rosette species of the genus Espeletia from the Venezuelan Andes. Readily available water from the pith was calculated to be capable of sustaining mean transpiration for up to 2.5 h. The relative importance of water stored in the pith, however, differed among species. The species that grow in the higher and colder environments tended to have a greater capacitance than the species that grow in the lower and less extreme environments. The pith volume per unit leaf area (PV/LA) was found to be a good indicator of the relative water storage capacity of the adult individuals of each species. Diurnal fluctuations in leaf water potential were not as pronounced in the species with higher PV/LA values. The species-specific PV/LA was highly correlated with the leaf turgor loss point and with the total resistance to water flow from soil to leaves. These results suggested that species-specific capacitance in the genus Espeletia is a response to temperature-limited soil water availability and that cold tropical environments with frequent subfreezing temperatures tend to select for high water storage capacity in giant rosette plants.     

Impact of surface tension on the conversion rate of large to small surfactant aggregates

The extracellular alveolar surfactant can be separated into the highly surface active large surfactant aggregates (LA) and the less active small surfactant aggregates (SA). Conversion of LA to SA is encountered upon cyclic surface area changes and demands the presence of enzymatic activity. In the present study we investigated the influence of surface tension on the conversion of LA to SA. Bronchoalveolar lavage fluid (BALF) obtained from healthy rabbits was cycled for various time periods in absence or presence of increasing amounts of serum proteins or oleic acid. LA were isolated, quantified and the minimum surface tension (gamma(min)) of uncycled or cycled LA was assessed in absence or presence of increasing amounts of serum proteins or oleic acid. In additional experiments, already cycled LA with a gamma(min) of approximately 20 mN/m were pooled, diluted to a similar PL concentration as original BALF and cycled a second time. Serum proteins and oleic acid dose-dependently: (i) increased the gamma(min) values of LA when added to the isolated LA; and (ii) decreased the LA to SA conversion when added to BALF. These events were directly correlated, suggesting inhibition of LA to SA conversion by increase in gamma(min) of the LA fraction. In line with this suggestion, already cycled LA displaying poor surface activity showed no further conversion in a second cycling maneuver, whereas LA being similarly prepared from uncycled BALF did. We conclude that LA to SA conversion is inversely correlated with the surface tension of the LA fraction. An increase in gamma(min) of the LA fraction during the cycling procedure blocks further LA to SA conversion and may thus represent a negative feedback mechanism.     

Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation

Repetitive rapid activities are present in the pulmonary veins (PVs) in dogs with pacing-induced sustained atrial fibrillation (AF). The mechanisms are unclear. We induced sustained (>48 h) AF by rapidly pacing the left atrium (LA) in six dogs. High-density computerized mapping was done in the PVs and atria. Results show repetitive focal activations in all dogs and in 12 of 18 mapped PVs. Activation originated from the middle of the PV and then propagated to the LA and distal PV with conduction blocks. The right atrium (RA) was usually activated by a single large wavefront. Mean AF cycle length in the PVs (left superior, 82 +/- 6 ms; left inferior, 83 +/- 6 ms; right inferior, 83 +/- 4 ms) and LA posterior wall (87 +/- 5 ms) were significantly (P < 0.05) shorter than those in the LA anterior wall (92 +/- 4 ms) and RA (107 +/- 5 ms). PVs in normal dogs did not have focal activations during induced AF. No reentrant wavefronts were demonstrated in the PVs. We conclude that nonreentrant focal activations are present in the PVs in a canine model of pacing-induced sustained AF.     

Use of three-dimensional computed tomography overlay for real-time cryoballoon ablation in atrial fibrillation reduces radiation dose and contrast dye

Aims

Cryoballoon pulmonary vein (PV) isolation in patients with atrial fibrillation has proven to be effective in short-term and long-term follow-up. To visualise the PV anatomy, pre-ablation contrast pulmonary venography is commonly performed. Three-dimensional (3D) computed tomography (CT) overlay is a new technique creating a live 3D image of the left atrium by integrating a previously obtained CT scan during fluoroscopy. To evaluate the benefits of 3D CT overlay during cryoballoon ablation, we studied the use of 3D CT overlay versus contrast pulmonary venography in a randomised fashion in patients with paroxysmal atrial fibrillation undergoing cryoballoon PV isolation.

Methods and results

Between October 2012 and June 2013, 30 patients accepted for PV isolation were randomised to cryoballoon PV isolation using either 3D CT overlay or contrast pulmonary venography. All patients underwent a pre-procedural cardiac CT for evaluation of the anatomy of the left atrium (LA) and the PVs. In the 3D CT overlay group, a 3D reconstruction of the LA and PVs was made. An overlay of the CT reconstruction was then projected over live fluoroscopy. Patients in the contrast pulmonary venography group received significantly more contrast agent (77.1 ± 21.2 cc vs 40.1 ± 17.6 cc, p < 0.001) and radiation (43.0 ± 21.9?Gy.cm2 vs 28.41 ± 11.7?Gy.cm2, p = 0.04) than subjects in the 3D CT overlay group. There was no difference in total procedure time, fluoroscopy time and the amount of cryoapplications between the two groups.

Conclusion

The use of 3D CT overlay decreases radiation and contrast dye exposure and can assist in guiding cryoballoon-based PV isolation.

     

Early mitral deceleration and left atrial stiffness

Left ventricular (LV) filling deceleration time (DT) is determined by the sum of atrial and ventricular stiffnesses (KLA + KLV). If KLA, however, is close to zero, then DT would reflect KLV only. The purpose of this study was to quantify KLA during DT. In 15 patients, KLV was assessed, immediately after cardiopulmonary bypass, from E wave DT as derived from mitral tracings obtained by transesophageal echocardiography and computed according to a validated formula. In each patient, a left atrial (LA) volume curve was also obtained combining mitral and pulmonary vein (PV) cumulative flow plus LA volume measured at end diastole. Time-adjusted LA pressure was measured simultaneously with Doppler data in all patients. KLA was then calculated during the ascending limb of the V loop and during DT. LA volume decreased by 7.3 +/- 6.5 ml/m2 during the first of mitral DT, whereas LV volume increased 9.4 +/- 8.4 ml/m2 (both P < 0.001). There was a small amount of blood coming from the PV during the same time interval, with the cumulative flow averaging 3.2 +/- 2.4 ml/m(2) (P < 0.001). Mean LA pressure was 10.0 +/- 5.1 mmHg, and it did not change during DT [from 7.8 +/- 4.3 to 8.0 +/- 4.3 mmHg, not significant (NS)], making KLA, which averaged 0.46 +/- 0.39 mmHg/ml during the V loop, close to zero during DT [KLA(DT): from -0.002 +/- 0.08 to -0.001 +/- 0.031 mmHg/ml, NS]. KLV, as assessed noninvasively from DT, averaged 0.25 +/- 0.32 mmHg/ml. In conclusion, notwithstanding the significant decrement in LA volume, KLA does not change and can be considered not different from zero during DT. Thus KLA does not affect the estimation of KLV from Doppler parameters.     

Attraction of Rotors to the Pulmonary Veins in Paroxysmal Atrial Fibrillation: A Modeling Study

Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors in the left atrium (LA) or at the pulmonary veins (PVs) is not fully understood. To gain insight into this dynamic and complex process, we studied the role of the heterogeneous distribution of transmembrane currents in the PVs and LA junction (PV-LAJ) in the localization of rotors in the PVs. We also investigated whether simple pacing protocols could be used to predict rotor drift in the PV-LAJ. Experimentally observed heterogeneities in I_K1, I_Ks, I_Kr, I_to, and I_CaL in the PV-LAJ were incorporated into two- and pseudo three-dimensional models of Courtemanche-Ramirez-Nattel-Kneller human atrial kinetics to simulate various conditions and investigate rotor drifting mechanisms. Spatial gradients in the currents resulted in shorter action potential duration, minimum diastolic potential that was less negative, and slower upstroke and conduction velocity for rotors in the PV region than in the LA. Rotors under such conditions drifted toward the PV and stabilized at the shortest action potential duration and less-excitable region, consistent with drift direction under intercellular coupling heterogeneities and regardless of the geometrical constraint in the PVs. Simulations with various I_K1 gradient conditions and current-voltage relationships substantiated its major role in the rotor drift. In our 1:1 pacing protocol, we found that among various action potential properties, only the minimum diastolic potential gradient was a rate-independent predictor of rotor drift direction. Consistent with experimental and clinical AF studies, simulations in an electrophysiologically heterogeneous model of the PV-LAJ showed rotor attraction toward the PV. Our simulations suggest that I_K1 heterogeneity is dominant compared to other currents in determining the drift direction through its impact on the excitability gradient. These results provide a believed novel framework for understanding the complex dynamics of rotors in AF.     

山羊房颤模型中左心房与肺静脉外膜碎裂电位的动态比较

目的: 比较在持续性房颤发生、发展过程中,房颤模型山羊左心房与肺静脉外膜碎裂电位(CFAEs)的变化,以期探讨肺静脉外膜碎裂电位(CFAEs)在持续性房颤中的作用。方法: 选取10只雌性山羊,使用左心房快速刺激,发送输出电压为6 V、周长为20 ms的脉冲1 s,间隔2 s后重复发放,以此方法建立持续性房颤模型(房颤持续＞24 h),平均刺激时间为(9.5±2.3)d。在整个房颤发生、发展过程中,记录并比较刺激前后左心房及肺静脉外膜CFAEs的动态变化。结果: 随着刺激时间延长,心房不应期(AERP)逐渐缩短,房颤持续时间逐渐延长,左心房及肺静脉外膜的CFAEs逐渐增多,肺静脉外膜CFAEs的比例始终多于左心房。当房颤持续24 h,肺静脉外膜CFAEs几乎持续存在(房颤初发与房颤持续24 h相比,2.7%±3.6% vs 92.6%±6.4%,P＜0.05),肺静脉外膜CFAEs比例明显高于左心房(P＜0.05)。结论: 心外膜CFAEs具有位置特异性,与电重构相关联。房颤发生发展中心外膜CFAEs逐渐增多,可能在房颤的维持中起重要作用。     

Technique of pulmonary vein isolation by catheter ablation

In selected patients with atrial fibrillation, the fibrillation episodes may be initiated by single or short bursts of ectopy often originating from one or more pulmonary veins (PVs). Therefore, electrical isolation of these veins by catheter ablation is currently being explored as a treatment modality for patients with paroxysmal and even more permanent types of atrial fibrillation. At present, two different techniques are used: 1) selective ablation of electrical connections between left atrium and myocardial sleeves inside the PVs; and 2) contiguous encircling lesions around and outside the PV ostia. With both techniques, moderate to high success rates have been reported with a limited follow-up duration. Both types of procedure are very complex and require a highly skilful team. With the variable anatomy of the PVs, non-invasively acquired angiographic images may serve as a roadmap for catheter manipulation. Modern three-dimensional catheter navigation techniques can be applied to facilitate accurate catheter positioning with limited fluoroscopic exposure. Experimental and clinical research is needed to define patient selection criteria.