Sustained Atrial Fibrillation Research Articles

Postoperative atrial fibrillation: The role of the inflammatory response

ObjectiveAbnormal atrial conduction has been shown to be a substrate for postoperative atrial fibrillation (POAF). This study aimed to determine the relationship between the location of the atrial reentry responsible for POAF, and degree of atrial inflammation. MethodsNormal mongrel dogs (n = 18) were divided into 3 groups: anesthesia alone (anesthesia), lateral right atriotomy (atriotomy), and lateral right atriotomy with anti-inflammatory therapy (steroid). Conduction properties of the right and left atria (RA and LA) were examined 3 days postoperatively by mapping. Activation was observed during burst pacing–induced AF. The RA and LA myeloperoxidase activity was measured to quantitate the degree of inflammation. ResultsSustained AF (>2 minutes) was induced in 5 of 6 animals in the atriotomy group, but in none in the anesthesia or steroid groups. All sustained AF originated from around the RA incision. Three of these animals had an incisional reentrant tachycardia around the right atriotomy and 2 had a focal activation arising from the RA during AF. The LA activations in these animals were passive from the RA activation. The RA activation of the atriotomy group was more inhomogeneous than that of the anesthesia group (inhomogeneity index: 2.0 ± 0.2 vs 1.0 ± 0.1, P < .01). Steroid therapy significantly normalized the RA activation after the atriotomy (1.2 ± 0.1, P < .01). The inhomogeneity of the atrial conduction correlated with the myeloperoxidase activity (r = 0.774, P < .001). ConclusionsReentrant circuits responsible for POAF are dependent on the degree of inflammation and rotate around the atriotomy. Anti-inflammatory therapy decreased the risk of postoperative AF.

Autonomic Tone Activity Before the Onset of Atrial Fibrillation.

The autonomic nervous system has been proven to play a major role in the onset of atrial fibrillation (AF), along with a predisposing substrate and a specific trigger event usually consisting of a premature supraventricular ectopic beat (SVEB). By means of heart rate variability (HRV) analysis, we investigated the activity of the autonomic nervous system before SVEBs nontriggering and triggering AF. We evaluated 28 patients with at least 1 episode of sustained AF (>30 seconds) recorded during 24-hour Holter monitorings. We performed HRV analysis during the hour preceding 35 AF onsets and compared these results with the HRV values before nontriggering SVEBs with similar prematurity. According to the low frequency (LF)/high frequency (HF) ratio in the 5 minutes before the onset, AF episodes were classified as either vagal (LF/HF ratio <1.5) or adrenergic (LF/HF ratio ≥1.5).Vagal episodes (16) showed a decrease in LF (from 50.81 ± 1.67 to 32.73 ± 3.54) and an increase in HF (from 36.00 ± 2.30 to 54.7 ± 3.69) throughout the hour preceding the onset. Adrenergic episodes (19) had opposite changes in LF (from 55.4 ± 4.95 to 67.51 ± 5.24) and HF (from 33.78 ± 5.82 to 27.96 ± 3.51) during the same period. No similar trends were observed before the selected nontriggering SVEBs. Only SVEBs occurring during a phase of hyperactivity of one of the 2 branches of the autonomic nervous system are able to trigger episodes of AF.

CLINICAL MASKS OF AMYLOIDOSIS WITH THE HEART INVOLVEMENT: MODERN DIAGNOSTIC ISSUES

In amyloidosis AL-type the heart involvement is most common; this type is specific with predecessor proteins of light immunoglobulin chains, transthyretin (TTR), mutant and wild (senile) types. Most common clinical form is restriction cardiomyopathy. Aim. To assess the recent specifics of diagnostics, due to broader abilities of novel methods. Material and methods. Five 40-79-year old patients with various morpho￾functional variants of heart involvement and typical ECG signs (low QRS voltage, QS, non-sufficient R increase, absence of left ventricle (LV) hypertrophy signs) to verify the suspected amyloidosis, underwent EchoCG, immunohistochemistry of blood and urine for light chains of immunoglobulines, biopsy of subcutaneous fat and mucose of the gum/gut; MDCT of the heart (n=3), MRI (n=1), scintigraphy with 99Tc-pyrophosphate with assessment in 1 hour after indicator injection (n=1), endomyocardial biopsy (n=2), titer of anticardial antibodies assessment (n=2), DNA-diagnostics (n=1). Results. The diagnosis of amyloidosis was confirmed in all cases. Its morpho-functional types were RSMP with LV hypertrophy, hypertrophic cardiomyopathy (HCMP) with no restriction but progressing fall of ejection fraction (EF), dilation cardiomyopathy (DCMP), severe hypertrophy with low EF, minimal hypertrophy with no restriction and systolic dysfunction. There was AL-type diagnosed (n=2, one case with myopathy mimicking “dermatomyositis”), mutant TTR (n=1, novel mutation Thr40Asn) and wild TTR (n=2) types. The leading clinical signs were biventricular heart failure and atrial rhythm disorders: sustained atrial fibrillation in 3 patients (in one, before amyloidosis verification, the RF-modification was done as “labyrinth” surgery, isthmus block with no established efficacy) and frequent supraventricular extrasystoly in one another. To the patient with mutant ATTR the ICD was implanted with further replacement by CRT-D, and increase of EF from 24% to 31% was achieved (patient is followed-up for 8 years). As the morphological equivalent of severe systolic dysfunction in this patient the amyloid deposition in myocardial arteries could be suspected. MDCT revealed typical subendocardial delayed deposition in 2 from 3 patients, in one case there was also diffuse deposition of 99Tc-pyrophosphate in myocardium. Antibodies to the nuclei of cardiomyocytes (specific ANF) was found in a female patient with AL-type and DCMP, which made not to rule out myocarditis. Conclusion. Cardiac amyloidosis might present as any structural and functional variant of cardiomyopathy, including DCMP. The most specific is diffuse hypertrophy with restriction and EF decrease, but with no LV dilation. Early fall of contractility, ischemia symptoms and LV dilation might be the result of amyloid lesion of small arteries. In the presence of any systemic presentations together with “HCMP”, “RCMP”, “DCMP” there must be amyloidosis ruled out. Myocardial scintigraphy with 99Tc-pyrophosphate is a method of use for the diagnosis of ATTR; MDCT of the heart — for any type of amyloidosis. Cardiac amyloidosis might be followed by significant type of the titer of specific ANF (secondary reaction or concomitance with myocarditis?).

Dronedarone attenuates the duration of atrial fibrillation in a dog model of sustained atrial fibrillation.

Atrial fibrillation (AF) is a supraventricular arrhythmia that leads to a decrease in cardiac output and impairs cardiac function and quality of life. Dronedarone has an atrial-selective property and has been used for management of AF in humans, but limited information is available in dogs. This study was designed to evaluate efficacy of dronedarone in attenuating the duration of AF in dog model of sustained AF. Six beagle dogs were anesthetized with isoflurane and instrumented to measure atrial action potential duration (aAPD) and atrial effective refractory period (AERP). Then AF was induced by rapid right atrial pacing (20 V, 40 Hz) simultaneously with infusion of phenylephrine (2 µg/kg/min, intravenously) for 20 min. The duration of sustained AF was recorded, and the animals were allowed to recover. Dronedarone was given at a dose of 20 mg/kg, BID, orally for 7 days. On the last day, the dogs were anesthetized again to record aAPD and AERP, and AF was induced with the same procedure as described above. The results showed that after dronedarone administration the aAPD was lengthened significantly from 76.4 ± 4.2 ms to 91.2 ± 3.9 ms (P<0.05) and AERP was prolonged significantly from 97.5 ± 2.8 ms to 120 ± 4.8 ms (P<0.05). The duration of sustained AF was also significantly attenuated after receipt of dronedarone (P<0.05). It can be suggested that oral dronedarone attenuates the duration of sustained AF in a dog model of AF by extending the AERP more than the aAPD, causing post-repolarization refractoriness. Hence, dronedarone may be useful for management of AF in dogs.

Focal impulse and rotor modulation: Acute procedural observations and extended clinical follow-up

Focal impulse and rotor modulation (FIRM) was based on the premise that atrial fibrillation (AF) is sustained by rotors that are sufficiently stable to be eliminated by targeted ablation. Early experience reported high success as compared to conventional strategies. The purpose of this study was to report on a single-center experience with extended follow-up by using FIRM in a variety of patients with AF. All FIRM-guided ablation procedures were included. During spontaneous or induced AF, FIRM software constructed phase maps to identify putative AF sources, then targeted for radiofrequency ablation, with adjunctive pulmonary vein isolation (PVI), if needed. All mapped rotors and/or sources were eliminated on the basis of repeated FIRM mapping. Of 47 patients, sustained AF was not present or induced in 4 patients who did not undergo FIRM ablation. Of the remaining 43 patients, prior AF was paroxysmal in 9 (21%) and 72% had a median of 1 prior PVI. Spontaneous AF (n = 22, 52%) and induced AF (n = 21, 49%) were mapped, and all patients had rotors identified (1.8 ± 0.8 per patient; 70% in the left atrium). AF termination occurred in 2 patients (5%) and none organized to atrial tachycardia. Touch-up redo PVI was also performed in 31 patients (72%). At 16.0 ± 10.7 months (range 1-34 months), only 9 patients (21%) were free of recurrent AF; and only 5 patients (12%) were free of AF and off antiarrhythmic drugs. Long-term clinical results after FIRM ablation in this diverse challenging cohort showed poor efficacy. Randomized clinical trials are needed to evaluate the efficacy and clinical utility of the FIRM ablation approach for treating AF.

Anatomical dilatation of the superior vena cava associated with an arrhythmogenic response induced by SVC scan pacing after atrial fibrillation ablation

BackgroundThe relationship between pulmonary vein (PV) arrhythmogenicity and its anatomy has been reported. However, that of the superior vena cava (SVC) has not been well discussed. Arrhythmogenic response induced by pacing stimulation at SVC might help with identifying SVC arrhythmogenicity. The purpose of this study was to investigate the relationship between the anatomical dilatation of SVC and the arrhythmogenic response induced by pacing at SVC. MethodsForty-three patients who underwent atrial fibrillation (AF) ablation were enrolled in this study. After PV isolation, scan pacing (up to triple extra stimulation following intrinsic sinus beats) was performed at SVC. The arrhythmogenic response was defined as following: (1) repetitive atrial responses, (2) non-sustained, and (3) sustained AF/ atrial tachycardia. To assess the dilatation of SVC, we measured the cross-sectional area of the SVC (SVC-area) using multi-planar reconstruction CT imaging. ResultsArrhythmogenic responses were documented in 24 patients (Group 1). No arrhythmogenic responses were documented in the remaining 19 patients (Group 2). The SVC-area was significantly larger in Group 1 than Group 2 (3.1±0.9 vs. 2.2±0.8cm2, P=0.004). A multivariate analysis revealed only SVC-area was associated with arrhythmogenic responses (odds ratio=2.87, CI 1.05–7.82, P=0.04). Furthermore, AF recurrence rate was significantly higher in patients with SVC-area>2.56cm2 than those with SVC-area <2.56cm2 (9 [42.9%] of 21 vs. 3 [13.6%] of 22, P=0.026). ConclusionDilatation of SVC was associated with an arrhythmogenic response, and the AF recurrence rate was significantly higher in patients with large SVC-area. Adjunctive catheter intervention for the SVC might be indicated in patients with a dilated SVC and an arrhythmogenic response.

Dronedarone prevents atrial fibrillation in dog model of sustained atrial fibrillation

Dronedarone prevents atrial fibrillation in dog model of sustained atrial fibrillation

Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm.

Cardiac rhythm is extremely robust, generating 2 billion contraction cycles during the average human life span. Transcriptional control of cardiac rhythm is poorly understood. We found that removal of the transcription factor gene Tbx5 from the adult mouse caused primary spontaneous and sustained atrial fibrillation (AF). Atrial cardiomyocytes from the Tbx5-mutant mice exhibited action potential abnormalities, including spontaneous depolarizations, which were rescued by chelating free calcium. We identified a multitiered transcriptional network that linked seven previously defined AF risk loci: TBX5 directly activated PITX2, and TBX5 and PITX2 antagonistically regulated membrane effector genes Scn5a, Gja1, Ryr2, Dsp, and Atp2a2 In addition, reduced Tbx5 dose by adult-specific haploinsufficiency caused decreased target gene expression, myocardial automaticity, and AF inducibility, which were all rescued by Pitx2 haploinsufficiency in mice. These results defined a transcriptional architecture for atrial rhythm control organized as an incoherent feed-forward loop, driven by TBX5 and modulated by PITX2. TBX5/PITX2 interplay provides tight control of atrial rhythm effector gene expression, and perturbation of the co-regulated network caused AF susceptibility. This work provides a model for the molecular mechanisms underpinning the genetic implication of multiple AF genome-wide association studies loci and will contribute to future efforts to stratify patients for AF risk by genotype.

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1.

Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12 months of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas none of 6 controls displayed sustained AF (P < 0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687 ± 212.02 seconds vs. 2.50 ± 0.88 seconds, P < 0.0001), but no persistent or permanent AF was observed. A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility.

Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Than Those With Paroxysmal Atrial Fibrillation.

The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08). Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502.

Low-level carotid baroreflex stimulation suppresses atrial fibrillation by inhibiting left stellate ganglion activity in an acute canine model

Low-level carotid baroreflex stimulation (LL-CBS) appears to have a potential antiarrhythmogenic effect. The purpose of this study was to investigate effects of short-term LL-CBS on an atrial fibrillation (AF) canine model. Group 1 (LL-CBS in the 6 hour-rapid atrial pacing model): Anesthetized dogs underwent 6 hours of rapid atrial pacing (RAP) with concomitant LL-CBS in last 3 hours (LL-CBS group; n = 7) or without (control group; n = 6). Effective refractory period (ERP), ERP dispersion, and window of vulnerability to AF were determined. Left stellate ganglion (LSG) neural activity and heart rate variability were analyzed. Group 2 (LL-CBS on electrically or mechanically induced AF with acetylcholine): In subgroup 1, sustained AF was induced by injecting acetylcholine (Ach; 10 mM) into the anterior right ganglionated plexus at baseline and after 3-hour LL-CBS (n = 7) or sham operation (n = 6). In subgroup 2, Ach was applied onto the right atrial appendage. The time of duration of AF and the average AF cycle length were determined in both subgroups. Group 1: LL-CBS reversed the RAP-induced ERP shortening and increase in ERP dispersion and window of vulnerability (P < .05). The activation of LSG, decrease in high frequency, and increase in low frequency and low frequency/high frequency ratio induced by RAP were also reversed by LL-CBS (P < .05). After 6-hour RAP, plasma norepinephrine and angiotensin II concentrations were significantly lower in the LL-CBS group than in the control group (P < .05). Group 2: The AF duration was shortened and the average AF cycle length was prolonged markedly in both subgroups (P < .01) by LL-CBS. LL-CBS can reverse RAP-induced atrial electrical remodeling and suppress electrically or mechanically induced AF with Ach, and the anti-AF effect is attributed to attenuation of autonomic nerve remodeling, including inhibition of the LSG activity.

Adenosine-Induced Atrial Fibrillation: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart.

Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor and its downstream GIRK (G protein-coupled inwardly rectifying potassium channels) channels (IK,Ado). We applied biatrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and nonfailing human hearts (n=37). Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10-100 µmol/L) produced more significant shortening of action potential durations in RA (from 290±45 to 239±41 ms, 17.3±10.4%; P<0.01) than LA (from 307±24 to 286±23 ms, 6.7±6.6%; P<0.01). In 10 hearts, adenosine induced AF (317±116 s) that, when sustained (≥2 minutes), was primarily maintained by 1 to 2 localized reentrant drivers in lateral RA. Tertiapin (10-100 nmol/L), a selective GIRK channel blocker, counteracted adenosine-induced action potential duration shortening and prevented AF induction. Immunoblotting showed that the superior/middle lateral RA had significantly higher adenosine A1 receptor (2.7±1.7-fold; P<0.01) and GIRK4 (1.7±0.8-fold; P<0.05) protein expression than lateral/posterior LA. This study revealed a 3-fold RA-to-LA adenosine A1 receptor protein expression gradient in the human heart, leading to significantly greater RA versus LA repolarization sensitivity in response to adenosine. Sustained adenosine-induced AF is maintained by reentrant drivers localized in lateral RA regions with the highest adenosine A1 receptor/GIRK4 expression. Selective atrial GIRK channel blockade may effectively treat AF during conditions with increased endogenous adenosine.

Spatiotemporal characteristics of atrial fibrillation electrograms: A novel marker for arrhythmia stability and termination

BackgroundSequentially mapped complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) sites have been targeted during catheter ablation for atrial fibrillation (AF). However, these strategies have yielded variable success and have not been shown to correlate consistently with AF dynamics. Here, we evaluated whether the spatiotemporal stability of CFAE and DF may be a better marker of AF sustenance and termination. MethodsEighteen sheep with 12 weeks of “one-kidney, one-clip” hypertension underwent open-chest studies. A total of 42 self-terminating (28–100s) and 6 sustained (>15min) AF episodes were mapped using a custom epicardial plaque and analyzed in 4-s epochs for CFAE, using the NavX CFE-m algorithm, and DF, using a Fast Fourier Transform. The spatiotemporal stability index (STSI) was calculated using the intraclass correlation coefficient of consecutive AF epochs. ResultsA total of 67,733 AF epochs were analyzed. During AF initiation, mean CFE-m and the STSI of CFE-m/DF were similar between sustained and self-terminating episodes, although median DF was higher in sustained AF (p=0.001). During sustained AF, the STSI of CFE-m increased significantly (p=0.02), whereas mean CFE-m (p=0.5), median DF (p=0.07), and the STSI of DF remained unchanged (p=0.5). Prior to AF termination, the STSI of CFE-m was significantly lower (p<0.001), with a physiologically non-significant decrease in median DF (−0.3Hz, p=0.006) and no significant changes in mean CFE-m (p=0.14) or the STSI of DF (p=0.06). ConclusionsSpatiotemporal stabilization of CFAE favors AF sustenance and its destabilization heralds AF termination. The STSI of CFE-m is more representative of AF dynamics than are the STSI of DF, sequential mean CFE-m, or median DF.

Class I Histone Deacetylase Inhibition for the Treatment of Sustained Atrial Fibrillation.

Current therapies are less effective for treating sustained/permanent versus paroxysmal atrial fibrillation (AF). We and others have previously shown that histone deacetylase (HDAC) inhibition reverses structural and electrical atrial remodeling in mice with inducible, paroxysmal-like AF. Here, we hypothesize an important, specific role for class I HDACs in determining structural atrial alterations during sustained AF. The class I HDAC inhibitor N-acetyldinaline [4-(acetylamino)-N-(2-amino-phenyl) benzamide] (CI-994) was administered for 2 weeks (1 mg/kg/day) to Hopx transgenic mice with atrial remodeling and inducible AF and to dogs with atrial tachypacing-induced sustained AF. Class I HDAC inhibition prevented atrial fibrosis and arrhythmia inducibility in mice. Dogs were divided into three groups: 1) sinus rhythm, 2) sustained AF plus vehicle, and 3) sustained AF plus CI-994. In group 3, the time in AF over 2 weeks was reduced by 30% compared with group 2, along with attenuated atrial fibrosis and intra-atrial adipocyte infiltration. Moreover, group 2 dogs had higher atrial and serum inflammatory cytokines, adipokines, and atrial immune cells and adipocytes compared with groups 1 and 3. On the other hand, groups 2 and 3 displayed similar left atrial size, ventricular function, and mitral regurgitation. Importantly, the same histologic alterations found in dogs with sustained AF and reversed by CI-994 were also present in atrial tissue from transplanted patients with chronic AF. This is the first evidence that, in sustained AF, class I HDAC inhibition can reduce the total time of fibrillation, atrial fibrosis, intra-atrial adipocytes, and immune cell infiltration without significant effects on cardiac function.

Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing.

BackgroundAccumulating evidence suggests that myeloperoxidase (MPO) is involved in atrial remodeling of atrial fibrillation (AF). Statins could reduce the MPO levels in patients with cardiovascular diseases. This study evaluated the effects of atorvastatin on MPO level and atrial remodeling in a rabbit model of pacing-induced AF.MethodsEighteen rabbits were randomly divided into sham, control and atorvastatin groups. Rabbits in the control and atorvastatin groups were subjected to rapid atrial pacing (RAP) at 600 bpm for 3 weeks, and treated with placebo or atorvastatin (2.5 mg/kg/d), respectively. Rabbits in the sham group did not receive RAP. After 3 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, atrial effective refractory period (AERP) and AF inducibility were measured by atrial electrophysiological examination, and histological changes were evaluated by Masson trichrome-staining. The L-type calcium channel α1c (Cav1.2), collagen I and III, MPO, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by real time polymerase chain reaction and/or western blot.ResultsAll rabbits were found to have maintained sinus rhythm after 3 weeks of RAP. Atrial burst stimulation induced sustained AF (>30 min) in 5, 4, and no rabbits in the control, atorvastatin, and sham groups, respectively. The AERP shortened and Cav1.2 mRNA level decreased in the control group, but these changes were suppressed in the atorvastatin group. Obvious left atrial enlargement and dysfunction was found in both control and atorvastatin groups. Compared with the control group, these echocardiograhic indices of left atrium did not differ in the atorvastatin group. Prominent atrial fibrosis and increased levels of collagen I and III were observed in the control group but not in the atorvastatin group. The mRNA and protein levels of MPO, MMP-2 and MMP-9 significantly increased in the control group, but these changes were prevented in the atorvastatin group.ConclusionTreatment with atorvastatin prevented atrial remodeling in a rabbit model of RAP-induced AF. The reduction of levels of atrial MPO, MMP-2 and MMP-9 may contribute to the prevention of atorvastatin on atrial remodeling.

Patient with non-valvular atrial fibrillation on ineffective anticoagulant therapy

Migotanie przedsionków jest czynnikiem ryzyka wystąpienia udaru mózgu. W celu zmniejszenia tego ryzyka powszechnie stosuje się terapię przeciwzakrzepową. Poniżej przedstawiono przypadek chorego z utrwalonym migotaniem przedsionków i licznymi obciążeniami kardiologicznymi, u którego miesiąc wcześniej implantowano CRT-D. W okresie okołozabiegowym odstawiono leki przeciwzakrzepowe. W pierwszym tygodniu leczenia przeciwkrzepliwego riwaroksabanem pacjent doznał niedokrwiennego udaru mózgu, a podczas hospitalizacji na Oddziale Neurologii wystąpiła gorączka, którą wiązano z wkłuciem dożylnym na lewej kończynie górnej, dlatego też zastosowano antybiotykoterapię. Wobec braku poprawy wysunięto podejrzenie infekcyjnego zapalenia wsierdzia i chory został przyjęty do Kliniki Kardiologii. W przezprzełykowym badaniu echokardiograficznym nie uwidoczniono wegetacji, jednocześnie stwierdzono skrzeplinę w uszku lewego przedsionka. Usunięto układ CRT-D, stosując w okresie okołozabiegowym heparynę niefrakcjonowaną. Nieskuteczna terapia przeciwkrzepliwa może się wiązać ze zwiększonym ryzykiem powikłań zakrzepowo-zatorowych. Obecność infekcyjnego zapalenia wsierdzia związanego z implantowanym CRT-D (CDRIE — cardiac device-related infective endocarditis ) stanowi dodatkowy, nieujęty w skalach, czynnik ryzyka wystąpienia epizodu zakrzepowo-zatorowego, ale również krwawienia wewnątrzczaszkowego.

96-17: Atrial tachycardias in patients with long-standing persistent atrial fibrillation undergoing thoracoscopic epicardial RF ablation

Introduction: Surgical epicardial thoracoscopic RF ablation (SETA) was shown to be more effective in terms of clinical results than catheter based procedures in patients with atrial fibrillation (AF). However, neither surgery nor catheter ablation alone can achieve 100% complete and durable transmural lesions. The aim of this study was to determine mechanisms and localization of atrial tachycardias found after epicardial ablation. Methods: Patients with long-standing persistent AF underwent SETA with aim to create circumferential lesions around the ipsilateral pulmonary veins (PVs) using bipolar RF clamps, to complete linear connecting lesions and to ablate ganglionated plexi using linear pen. As a second step, a detailed 3D electroanatomical mapping (EAM) of both atria using CARTO3 system was performed within 6-8 weeks following surgical procedure. All spontaneous or induced atrial tachycardias (ATs) were mapped and ablated. Results: Sixty patients (mean age 62 years, LA diameter 49 ± 6 mm) were studied. Forty-five patients (75%) had sinus rhythm in the beginning of EAM. Six patients (10%) had typical CTI-dependent right atrial flutter; two patients (5.1%) had right atrial (RA) tachycardia, one patient (2.6%) had focal tachycardia arising from the middle CS, three patients (5%) had perimitral left atrial (LA) flutter, and finally, four patients (6.7%) had AF. All spontaneous ATs were successfully mapped and ablated. As a part of protocol, incremental atrial pacing was performed after finalization of all lines and PV isolations at the end of procedure. In 46 patients (76.7%), no sustained AF and/or AT was induced, in three patients (5%), AF lasting > 30 s was induced, but spontaneously terminated. Non self-terminating AF was induced in two patients (3.3%). In the remaining 9 patients (15%), 13 ATs were induced: 6 arising from the RA and 7 arising from the LA. All but 2 ATs were successfully abolished by RF ablation. Mean procedure and fluoroscopic times of the whole procedure reached 132 ± 37 min and 8 ± 2 min, respectively. 84% of patients maintained stable SR off antiarrhythmic therapy at 12-month follow-up. Reasonable arrhythmia control was achieved in 94% of patients. Conclusion: At least one quarter of patients are suffering from spontaneous ATs and/or AF after SETA. Catheter ablation of ATs following surgery is safe and highly effective. Sequential hybrid approach seems to achieve normal SR in vast majority of patients with previously long-standing persistent AF.

176-57: Impact of Detected Arrhythmias on further Therapy Decision in Patients with Wearable Cardioverter Defibrillators

Background: Patients (pts) with reduced left ventricular function often suffer from fatal cardiac arrhythmias. Cardioverter Defibrillator implantation (ICD) is recommended after risk stratification and/ or a period of optimized pharmacological and/ or coronary interventional treatment. Wearable cardioverter defibrillator (WCD) have been invented to bridge this period, providing both, cardiac rhythm monitoring and defibrillation therapy delivery. As there are only few data about further therapy decision in WCD pts, we present a single centre experience. Methods: 84 pts (64 male, 64 ± 14 years) with reduced left ventricular function (EF 33.5 ± 12.9 %) received a WCD (LifeVest®, ZOLL, Pittsburgh, PA, USA). 46 pts suffered from dilative cardiomyopathy or non-ischemic cardiomyopathy, 21 pts from ischemic heart disease post coronary intervention or from CABG operation (n = 3), 6 pts from acute myocarditis, 4 pts from ICD explantation, and 4 from other reasons. Results: Pts wore WCD 48.5 ± 32.6 days and 20.3 ± 3.8 hours per day. During that time, 2065 events were registered, ranging from 1 to 222 events per pt. 1592 events were automatically detected, 366 events were manually activated and 99 were due to initiating the system. Out of the automatically detected events, 1586 were tachycardia and 6 were bradycardia or asystole. The latter was in all patients due to disconnected systems. Out of the manually detected events, only 8 arrhythmias were “true”, i.e. sustained VT (n = 2), non-sustained VT (n = 2), bradycardia (n = 1), and atrial fibrillation (n = 3). In 3 pts. arrhythmia detection led to an adequate and successful shock delivery. Non of these patients showed VT/VF before or after this event. All data were transferred automatically by the device remote system. After WCD therapy, 33 pts (39.3%) received an ICD due to persistence of left ventricular EF reduction and/or persistence of high degree of ventricular ectopy. In 51 pts (60.7%), an ICD implantation could be avoided. Conclusion: Among patients with reduced left ventricular function and high risk of ventricular arrhythmia, the use of WCD was feasible and showed a high acceptance rate. In these pts, WCD allowed a high detection rate and shock application, if necessary. As decision for ICD implantation was based on arrhythmias detected by WCD only in few patients, the impact of arrhythmias on ICD implantation seems to be low in these patients.

Intermittent drivers anchoring to structural heterogeneities as a major pathophysiological mechanism of human persistent atrial fibrillation.

The mechanisms responsible for perpetuation of human persistent atrial fibrillation (AF) are controversial and probably vary between individuals. A wide spectrum of mechanisms have been described in experimental studies, ranging from a single localized stable (focal/reentrant) source, to multiple sources, up to diffuse bi-atrial wavelets. We characterized AF drivers in patients with persistent AF (lasting less than 1year) using novel high resolution mapping, imaging and modelling approaches with the objective of evaluating their relationship to atrial structural heterogeneities. Using panoramic non-invasive mapping in humans, focal or reentrant sources driving AF waves were identified, originating from multiple distinct regions and exhibiting short lifespans and periodic recurrences in the same locations. The reentrant driver regions harboured long, fractionated electrograms covering most of the fibrillatory cycle lengths with varying beat-to-beat sequences suggestive of unstable trajectories attached to slow conducting heterogeneous tissue. MRI atrial imaging demonstrated that such drivers preferentially clustered at the borders of fibrotic atrial regions. In patient-specific computer simulations, sustained AF was shown to be driven by meandering transitory reentries attached to fibrosis borders expressing specific metrics in density and extent. Finally, random microstructural alterations devoid of cellular electrical changes were modelled, showing that a percolation mechanism could also explain atrial reentries and complex fractionated electrograms. These data from clinical, imaging and computational studies strongly suggest that intermittent and spatially unstable drivers anchoring to structural heterogeneities are a major pathophysiological mechanism in human persistent atrial fibrillation.

Focal impulse and rotor modulation as a stand-alone procedure for the treatment of paroxysmal atrial fibrillation: A within-patient controlled study with implanted cardiac monitoring

Focal impulse and rotor modulation (FIRM) has been proposed as a novel approach for the treatment of atrial fibrillation (AF). This study aimed to investigate the efficacy of FIRM as a stand-alone procedure for the treatment of paroxysmal AF. A total of 27 patients with paroxysmal AF underwent sequential biatrial computational mapping. Sites with repetitive centrifugal or spiral reentry-like activity were considered to be AF-sustaining sources and targeted by irrigated radiofrequency (RF) ablation. All patients were seen in the outpatient clinic after 1, 3, and 6 months and thereafter every 6 months. Cardiac monitors were implanted 3 months before ablation in 17 patients (63%). Repetitive activity interpreted as sustained AF sources was found in all patients, with an average of 3.0 ± 1.1 sources located in the left atrium and 0.6 ± 0.6 sources in the right atrium. The majority of sources were rotors (95%). The total source-ablation radiofrequency time was 20.0 ± 9.0 minutes. At 15.2 ± 3.9 months of follow-up, the prespecified end point of <1% AF burden (outside a 3-month blanking period) was achieved in 2 of the 17 continuously monitored patients (12%). Of all the 27 patients who underwent FIRM, AF episodes of ≥30 minutes were recorded in 23 (85%), while AF episodes ≥60 minutes were recorded in 21 patients (78%). This study suggest that biatrial ablation of localized patient-specific sources alone, as detected by this method, is not sufficient to reduce paroxysmal AF burden in the majority of patients.