Publications by authors named "Philipp Krisai"

52 Publications

Vein of Marshall Ethanol Infusion: Feasibility, Pitfalls, and Complications in over 700 Patients.

Circ Arrhythm Electrophysiol 2021 Jul 19. Epub 2021 Jul 19.

Department of Cardiac Pacing and Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, Univ. Bordeaux, Bordeaux University Hospital (CHU), Pessac-Bordeaux, France.

- Vein of Marshall (VOM) ethanol infusion is a relatively new therapeutic option for atrial tachyarrhythmias. We aimed to evaluate the feasibility, pitfalls, and complications associated with this procedure in a large cohort of patients. - Successful ethanol infusion, VOM-related lesion extent, and serious complications were evaluated in 713 consecutive patients treated with VOM ethanol infusion. - While feasible in 88.9% of cases, VOM ethanol infusion failure mainly resulted from non-identification (6.2%), non-cannulation (1.5%), or ethanol infusion in the wrong vein (1.7%). The Vieussens valve was a helpful landmark and was visible in 63.2% of cases. Multivariable analysis identified previous coronary sinus ablation as the only predictor for non-identification. The mean area of VOM-related endocardial scarring was 10.2±5.3 cm. VOM dissection (10.7%), iodine leakage (3.0%), and VOM morphology without visible branches (3.0%) were associated with smaller VOM-related scarring (5.0±3.9 cm, 6.6±3.5 cm and 4.7±2.3 cm, with a p <0.0001, p <0.044, and p <0.0001, respectively). Ethanol infusion in a wrong vein was associated with less mitral line block (72.7% vs. 95.8%, p=0.012). A total of 14 serious complications (2.0%) occurred: 7 tamponades, of which were 6 delayed and treated with pericardiocentesis (2 of these patients had per-procedural VOM perforation), 4 strokes, 1 anaphylactic shock, 1 atrioventricular block, and 1 left appendage isolation. Only 4 of these complications occurred during the procedure. - Although limited by previous coronary sinus ablation, VOM ethanol infusion is a highly feasible treatment for atrial tachyarrhythmia, with a low rate of serious complications.
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http://dx.doi.org/10.1161/CIRCEP.121.010001DOI Listing
July 2021

Sex differences in the origin of Purkinje ectopy initiating idiopathic ventricular fibrillation.

Heart Rhythm 2021 Jul 11. Epub 2021 Jul 11.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Bordeaux, France; Electrophysiology and Ablation Unit, Bordeaux University Hospital (CHU), Pessac, France.

Background: Purkinje ectopics (PurkE) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity.

Objective: To examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF.

Methods: Consecutive patients from four arrhythmia referral centers with PurkE-initiated idiopathic VF were included. We evaluated demographics, medical history and clinical circumstances associated with index VF events, and electrophysiologic characteristics of PurkE. An electrophysiological study was performed in most patients to confirm the Purkinje origin.

Results: Eighty three patients were included (age 38 ± 14 years, 44 women) among whom 32 had a previous history of syncope. Fourty four patients had VF at rest. PurkE originated from the right ventricle (RV) in 41 cases (49%), from the left ventricle (LV) in 36 (44%) and from the both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. Clinical characteristics of patients with RV vs. LV PurkE origins were similar except for sex. RV PurkE were more frequent in men than women (76% vs 24%) whereas LV and biventricular PurkE were more frequent in women (81% vs 19% and 83% vs 17% respectively, p<0.0001).

Conclusion: PurkE triggering idiopathic VF originate dominantly from RV in men and from LV or both ventricles in women adding to other sex-related arrhythmias as Brugada syndrome or long QT. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.
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http://dx.doi.org/10.1016/j.hrthm.2021.07.007DOI Listing
July 2021

Pulsed field ablation prevents chronic atrial fibrotic changes and restrictive mechanics after catheter ablation for atrial fibrillation.

Europace 2021 Jul 8. Epub 2021 Jul 8.

Department of Cardiovascular Imaging, Hôpital Cardiologique du Haut-Lévêque, CHU de Bordeaux, Pessac, France.

Aims: Pulsed field ablation (PFA), a non-thermal ablative modality, may show different effects on the myocardial tissue compared to thermal ablation. Thus, this study aimed to compare the left atrial (LA) structural and mechanical characteristics after PFA vs. thermal ablation.

Methods And Results: Cardiac magnetic resonance was performed pre-ablation, acutely (<3 h), and 3 months post-ablation in 41 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 18) or thermal ablation (n = 23, 16 radiofrequency ablations, 7 cryoablations). Late gadolinium enhancement (LGE), T2-weighted, and cine images were analysed. In the acute stage, LGE volume was 60% larger after PFA vs. thermal ablation (P < 0.001), and oedema on T2 imaging was 20% smaller (P = 0.002). Tissue changes were more homogeneous after PFA than after thermal ablation, with no sign of microvascular damage or intramural haemorrhage. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after thermal ablation. The maximum strain on PV antra, the LA expansion index, and LA active emptying fraction declined acutely after both PFA and thermal ablation but recovered at the chronic stage only with PFA.

Conclusion: Pulsed field ablation induces large acute LGE without microvascular damage or intramural haemorrhage. Most LGE lesions disappear in the chronic stage, suggesting a specific reparative process involving less chronic fibrosis. This process may contribute to a preserved tissue compliance and LA reservoir and booster pump functions.
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http://dx.doi.org/10.1093/europace/euab155DOI Listing
July 2021

Accuracy of automatic abnormal potential annotation for substrate identification in scar-related ventricular tachycardia.

J Cardiovasc Electrophysiol 2021 Jul 5. Epub 2021 Jul 5.

Department of Cardiac Pacing and Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, University Hospital (CHU), University of Bordeaux, Bordeaux, France.

Introduction: Ultrahigh-density mapping for ventricular tachycardia (VT) is increasingly used. However, manual annotation of local abnormal ventricular activities (LAVAs) is challenging in this setting. Therefore, we assessed the accuracy of the automatic annotation of LAVAs with the Lumipoint algorithm of the Rhythmia system (Boston Scientific).

Methods And Results: One hundred consecutive patients undergoing catheter ablation of scar-related VT were studied. Areas with LAVAs and ablation sites were manually annotated during the procedure and compared with automatically annotated areas using the Lumipoint features for detecting late potentials (LP), fragmented potentials (FP), and double potentials (DP). The accuracy of each automatic annotation feature was assessed by re-evaluating local potentials within automatically annotated areas. Automatically annotated areas matched with manually annotated areas in 64 cases (64%), identified an area with LAVAs missed during manual annotation in 15 cases (15%), and did not highlight areas identified with manual annotation in 18 cases (18%). Automatic FP annotation accurately detected LAVAs regardless of the cardiac rhythm or scar location; automatic LP annotation accurately detected LAVAs in sinus rhythm, but was affected by the scar location during ventricular pacing; automatic DP annotation was not affected by the mapping rhythm, but its accuracy was suboptimal when the scar was located on the right ventricle or epicardium.

Conclusion: The Lumipoint algorithm was as/more accurate than manual annotation in 79% of patients. FP annotation detected LAVAs most accurately regardless of mapping rhythm and scar location. The accuracy of LP and DP annotations varied depending on mapping rhythm or scar location.
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http://dx.doi.org/10.1111/jce.15148DOI Listing
July 2021

Epicardial Course of the Musculature Related to the Great Cardiac Vein: Anatomical Considerations and Clinical Implications for Mitral Isthmus Block after Vein of Marshall Ethanol Infusion.

Heart Rhythm 2021 Jul 1. Epub 2021 Jul 1.

Unité d'électrophysiologie cardiaque, Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, L'Institut de RYthmologie et modélisation Cardiaque (LIRYC), Univ. Bordeaux, France.

Background: Mitral isthmus gaps have been ascribed to an epicardial musculature anatomically related to the great cardiac vein (GCV) and the vein of Marshall (VOM). Their lumen offers an access for radiofrequency application or ethanol infusion, respectively.

Objective: To evaluate the frequency of mitral isthmus gaps accessible via the GCV lumen, to assess their location around the GCV circumference, and to propose an efficient ablation strategy when present.

Methods: One hundred consecutive patients underwent VOM ethanol infusion (step 1) and endocardial linear ablation from the mitral annulus to the left inferior pulmonary vein (step 2). In cases of mitral isthmus gap, endovascular ablation of the GCV anchored wall facing the left atrium was systematically performed (step 3), while the opposite GCV free wall was targeted in case of block failure only (step 4).

Results: After VOM ethanol infusion and endocardial ablation, mitral isthmus block occurred in 51 patients (51%). Pacing maneuvers and activation sequences demonstrated an epicardial gap via the VOM in 2 patients (2%), and via the GCV in 47 patients (47%). In the latter case, block was achieved at the GCV anchored wall in 42 patients (89%), and the GCV free wall in 5 patients (11%). Global success rate of mitral isthmus block was 98%. No tamponade occurred.

Conclusion: With the advent of VOM ethanol infusion, residual mitral isthmus gaps are mostly eliminated within the first centimeter of the GCV. Thorough mapping of the entire circumference of the GCV wall can help identify these epicardial gaps.
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http://dx.doi.org/10.1016/j.hrthm.2021.06.1202DOI Listing
July 2021

Role of endocardial ablation in eliminating an epicardial arrhythmogenic substrate in patients with Brugada syndrome.

Heart Rhythm 2021 Jun 26. Epub 2021 Jun 26.

Department of Cardiac Pacing and Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, University of Bordeaux, Bordeaux University Hospital (CHU), Pessac-Bordeaux, France. Electronic address:

Background: Epicardial ablation is occasionally limited by coronary artery (CA) injuries or epicardial fat (EF).

Objective: The purpose of this study was to evaluate the anatomic obstacles that prevent ablation of epicardial abnormal potentials (EAPs) in patients with Brugada syndrome (BrS) and to investigate the feasibility of EAP elimination by endocardial right ventricular (RV) ablation.

Methods: This study included 16 BrS patients with previous ventricular fibrillation (VF), including 10 with an electrical storm. Data from multidetector computed tomography were assessed, and the proximity of the CA and EF was correlated with EAPs.

Results: EAPs were present in the epicardial RV outflow tract and RV inferior wall in all patients and 12 patients (75%), respectively. These EAPs were present within 5 mm of the main body and branches of the right CA in 14 patients (87.5%). However, only 1.4% ± 2.9% of the EAP area was covered with thick EF (≥8 mm). Partial EAP elimination by endocardial RV ablation was feasible in all 10 patients, with 53.3% successful endocardial RV radiofrequency applications for eliminating EAPs. After the procedure, VF remained inducible in 37.5% of the patients. During the 25.1 ± 29.1 months of follow-up, no patients experienced an electrical storm, and VF burden significantly decreased (median VF episodes before and after ablation: 7 and 0, respectively).

Conclusion: EAPs are near the CA in most BrS patients, thereby requiring caution during epicardial ablation, whereas EF is less of an issue. Endocardial ablation is feasible to eliminate some EAPs and may be combined with epicardial ablation.
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http://dx.doi.org/10.1016/j.hrthm.2021.06.1188DOI Listing
June 2021

Association of Heart Rate Variability With Silent Brain Infarcts in Patients With Atrial Fibrillation.

Front Cardiovasc Med 2021 21;8:684461. Epub 2021 May 21.

Department of Cardiology, University Hospital Basel, Basel, Switzerland.

Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, = 816) or AF (AF-group, = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group ( < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03-2.70; = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) -0.47 (-0.84; -0.09), = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI ( = 0.017). Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment. NCT02105844.
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http://dx.doi.org/10.3389/fcvm.2021.684461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175975PMC
May 2021

Local abnormal ventricular activity detection in scar-related VT: Microelectrode versus conventional bipolar electrode.

Pacing Clin Electrophysiol 2021 Jun 12;44(6):1075-1084. Epub 2021 May 12.

Department of Cardiac Pacing and Electrophysiology, Univ. Bordeaux, Bordeaux University Hospital (CHU), Pessac-Bordeaux, France.

Background: Conventional bipolar electrodes (CBE) may be suboptimal to detect local abnormal ventricular activities (LAVAs). Microelectrodes (ME) may improve the detection of LAVAs. This study sought to elucidate the detectability of LAVAs using ME compared with CBE in patients with scar-related ventricular tachycardia (VT).

Methods: We included consecutive patients with structural heart disease who underwent radiofrequency catheter ablation for scar-related VT using either of the following catheters equipped with ME: QDOTTM or IntellaTip MIFITM. Detection field of LAVA potentials were classified as three types: Type 1 (both CBE and ME detected LAVA), Type 2 (CBE did not detect LAVA while ME did), and Type 3 (CBE detected LAVA while ME did not).

Results: In 16 patients (68 ± 16 years; 14 males), 260 LAVAs electrograms (QDOT = 72; MIFI = 188) were analyzed. Type 1, type 2, and type 3 detections were 70.8% (QDOT, 69.4%; MIFI, 71.3%), 20.0% (QDOT, 23.6%; MIFI, 18.6%) and 9.2% (QDOT, 6.9%; MIFI, 10.1%), respectively. The LAVAs amplitudes detected by ME were higher than those detected by CBE in both catheters (QDOT: ME 0.79 ± 0.50 mV vs. CBE 0.41 ± 0.42 mV, p = .001; MIFI: ME 0.73 ± 0.64 mV vs. CBE 0.38 ± 0.36 mV, p < .001).

Conclusions: ME allow to identify 20% of LAVAs missed by CBE. ME showed higher amplitude LAVAs than CBE. However, 9.2% of LAVAs can still be missed by ME.
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http://dx.doi.org/10.1111/pace.14253DOI Listing
June 2021

Reply to the Editor-Omissions and misconceptions on vein of Marshall ethanol infusion.

Heart Rhythm 2021 Jul 20;18(7):1251-1252. Epub 2021 Apr 20.

Electrophysiology and Ablation Unit and LIRYC, CHU de Bordeaux, Bordeaux-Pessac, France. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2021.04.009DOI Listing
July 2021

Biomarkers of Inflammation and Risk of Hospitalization for Heart Failure in Patients With Atrial Fibrillation.

J Am Heart Assoc 2021 Apr 10;10(8):e019168. Epub 2021 Apr 10.

Population Health Research Institute McMaster University Hamilton Canada.

Background Hospitalization for heart failure (HF) is very common in patients with atrial fibrillation (AF). We hypothesized that biomarkers of inflammation can identify patients with AF at increased risk of this important complication. Methods and Results Patients with established AF were prospectively enrolled. Levels of hs-CRP (high-sensitivity C-reactive protein) and interleukin-6 were measured from plasma samples obtained at baseline. We calculated an inflammation score ranging from 0 to 4 (1 point for each biomarker between the 50th and 75th percentile, 2 points for each biomarker above the 75th percentile). Individual associations of biomarkers and the inflammation score with HF hospitalization were obtained from multivariable Cox proportional hazards models. A total of 3784 patients with AF (median age 72 years, 24% prior HF) were followed for a median of 4.0 years. The median (interquartile range) plasma levels of hs-CRP and interleukin-6 were 1.64 (0.81-3.69) mg/L and 3.42 (2.14-5.60) pg/mL, respectively. The overall incidence of HF hospitalization was 3.04 per 100 person-years and increased from 1.34 to 7.31 per 100 person-years across inflammation score categories. After multivariable adjustment, both biomarkers were significantly associated with the risk of HF hospitalization (per increase in 1 SD, adjusted hazard ratio [HR], 1.22; 95% CI, 1.11-1.34 for log-transformed hs-CRP; adjusted HR, 1.48; 95% CI, 1.35-1.62 for log-transformed interleukin-6). Similar results were obtained for the inflammation score (highest versus lowest score, adjusted HR, 2.43; 95% CI, 1.80-3.30; value for trend <0.001). Conclusions Biomarkers of inflammation strongly predicted HF hospitalization in a large, contemporary sample of patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.
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http://dx.doi.org/10.1161/JAHA.120.019168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174180PMC
April 2021

Persistent atrial fibrillation ablation in cardiac laminopathy: Electrophysiological findings and clinical outcomes.

Heart Rhythm 2021 Jul 31;18(7):1115-1121. Epub 2021 Mar 31.

Unité d'électrophysiologie, Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, L'Institut de RYthmologie et modélisation Cardiaque (LIRYC), Université Bordeaux, Bordeaux-Pessac, France. Electronic address:

Background: Little is known about persistent atrial fibrillation (AF) ablation in patients with cardiac laminopathy (CLMNA).

Objectives: We aimed to characterize atrial electrophysiological properties and to assess the long-term outcomes of persistent AF ablation in patients with CLMNA.

Methods: All patients with CLMNA referred in our center for persistent AF ablation were retrospectively included. Left atrial (LA) volume, left atrial appendage (LAA) cycle length, interatrial conduction delay, and LA voltage amplitude were analyzed during the ablation procedure. Sinus rhythm maintenance and LA contractile function were assessed during long-term follow-up.

Results: From 2011 to 2020, 8 patients were included. The mean age was 47 ± 14 years, and 3 patients (38%) were women. The LA volume was 205.8 ± 43.7 mL; the LAA AF cycle length was 250.7 ± 85.6 ms; and the interatrial conduction delay was 296.5 ± 110.1 ms. Large low-voltage areas (>50% of the LA surface; <0.5 mV electrogram) were recorded in all 8 patients. Two patients had inadvertent LAA disconnection during ablation. All A waves recorded by pulsed Doppler in sinus rhythm were <30 cm/s before and after AF ablation. Early arrhythmia recurrence was recorded in 7 patients (87%) (time to recurrence 4 ± 4 months; 1.5 procedures per patient). After a mean follow-up of 4.4 ± 3.2 years, 4 patients underwent implantable cardioverter-defibrillator therapy for life-threatening ventricular arrhythmia and 3 patients finally underwent heart transplantation.

Conclusion: Patients with persistent AF afflicted by CLMNA exhibit severe LA impairment because of large low-voltage areas, prolonged conduction velocity, and reduced contractile function. Ablation procedures have a limited effect with a high recurrence rate.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.040DOI Listing
July 2021

Significance of manifest localized staining during ethanol infusion into the vein of Marshall.

Heart Rhythm 2021 Jul 16;18(7):1057-1063. Epub 2021 Mar 16.

Electrophysiology and Ablation Unit, Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, L'Institut de RYthmologie et Modélisation Cardiaque (LIRYC), Université Bordeaux, Bordeaux, France.

Background: Localized staining due to venule injury is attributable to ethanol infusion into the vein of Marshall (Et-VOM).

Objective: The purpose of this study was to investigate adverse outcomes of localized staining during Et-VOM in patients undergoing ablation for atrial fibrillation.

Methods: Two hundred four patients (age 64 ± 10 years; 153 male) were sorted based on the aspect of localized staining. Staining of atrial myocardium that spread uniformly along the VOM vascular tree following selective VOM venography was considered normal, in contrast to predominantly localized staining that spread concentrically from a focal point due to vascular injury. Outcomes between the 2 groups were compared.

Results: Localized staining was observed in 27% of patients. No patients developed clinically significant pericardial effusions during Et-VOM; however, 7 patients developed pericardial effusions on the first postprocedural day (3.6% in patients with vs 3.4% in patients without localized staining). No significant difference was found in achievement of acute mitral isthmus (MI) block (96% vs 98%) and size of the endocardial low-voltage area (8.5 ± 4.1 cm vs 9.3 ± 5.3 cm) in patients with and without localized staining, respectively. Long-term follow-up was not impacted by localized staining. Freedom from recurrent atrial tachyarrhythmias (66% vs 76%) and durability of MI block (57% vs 54%) were not significantly different with and without localized staining. There were no cases of rehospitalization for pericarditis, chronic pericardial effusion, or heart failure.

Conclusion: In our study, localized staining was frequent but was not associated with clinically relevant impact or disadvantages.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.023DOI Listing
July 2021

Ligament of Marshall ablation for persistent atrial fibrillation.

Pacing Clin Electrophysiol 2021 May 5;44(5):782-791. Epub 2021 Apr 5.

LIRYC, University of Bordeaux, CHU de Bordeaux, Bordeaux France, Service de Rhythmologie, Hôpital Cardiologique du Haut-Lévêque (Centre Hospitalier Universtaire de Bordeaux), Talence, Aquitaine, France.

Beyond pulmonary vein isolation, the two main additional strategies: Cox-Maze procedure or targeting of electrical signatures (focal bursts, rotational activities, meandering wavelets), remain controversial. High-density mapping of these arrhythmias has demonstrated firstly that a patchy lesion set is highly proarrhythmogenic, favoring macro-re-entry through conduction slowing and providing pivots for localized re-entry. Secondly, discrete anatomical structures such as the Vein or Ligament of Marshall (VOM/LOM) and the coronary sinus (CS) have epicardial muscular bundles that are more frequently involved in re-entry than previously thought. The Marshall Bundle can be ablated at any point along its course from the mid-to-distal coronary sinus to the left atrial appendage. If necessary, the VOM may be directly ablated using ethanol infusion to eliminate PV contributions and produce conduction block across the mistral isthmus. Ethanol ablation of the VOM, supplemented with RF ablation, may be more effective in producing conduction block at the mitral isthmus than repeat RF ablation alone.
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http://dx.doi.org/10.1111/pace.14208DOI Listing
May 2021

Use of high-density activation and voltage mapping in combination with entrainment to delineate gap-related atrial tachycardias post atrial fibrillation ablation.

Europace 2021 Jul;23(7):1052-1062

Electrophysiology and Ablation Unit, Hôpital Cardiologique du Haut Lévêque, Avenue de Magellan, 33604 Pessac Cedex, France.

Aims: An incomplete understanding of the mechanism of atrial tachycardia (AT) is a major determinant of ablation failure. We systematically evaluated the mechanisms of AT using ultra-high-resolution mapping in a large cohort of patients.

Methods And Results: We included 107 consecutive patients (mean age: 65.7 ± 9.2 years, males: 81 patients) with documented endocardial gap-related AT after left atrial ablation for persistent atrial fibrillation (AF). We analysed the mechanism of 134 AT (94 macro-re-entries and 40 localized re-entries) using high-resolution activation mapping in combination with high-density voltage and entrainment mapping. Voltage in the conducting channels may be extremely low, even <0.1 mV (0.14 ± 0.095 mV, 51 of 134 AT, 41%), and almost always <0.5 mV (0.03-0.5 mV, 133 of 134 AT, 99.3%). The use of multipolar Orion, HDGrid, and Pentaray catheters improved our accuracy in delineating ultra-low-voltage areas critical for maintenance of the circuit of endocardial gap-related AT. Conventional ablation catheters often do not detect any signal (noise level) even using adequate contact force, and only multipolar catheters of small electrodes and shorter interelectrode space can detect clear fractionated low-amplitude and high frequency signals, critical for re-entry maintenance. We performed a diagnosis in 112 out of 134 AT (83.6%) using only activation mapping and in 134 out of 134 AT (100%) using the combination of activation and entrainment mapping.

Conclusion : High-resolution activation mapping in combination with high-density voltage and entrainment mapping is the ideal strategy to delineate the critical part of the circuit in endocardial gap-related re-entrant AT after AF ablation.
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http://dx.doi.org/10.1093/europace/euaa394DOI Listing
July 2021

Association of the CHAD(S)-VASc Score and Its Components With Overt and Silent Ischemic Brain Lesions in Patients With Atrial Fibrillation.

Front Neurol 2020 12;11:609234. Epub 2021 Jan 12.

Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Basel, Switzerland.

Silent and overt ischemic brain lesions are common and associated with adverse outcome. Whether the CHADS-VASc score and its components predict magnetic resonance imaging (MRI)-detected ischemic silent and overt brain lesions in patients with atrial fibrillation (AF) is unclear. In this cross-sectional analysis, patients with AF were enrolled in a multicenter cohort study in Switzerland. Outcomes were clinically overt, silent [in the absence of a history of stroke/transient ischemic attack (TIA)] and any MRI-detected ischemic brain lesions. Logistic regression analyses were performed to assess the relationship of the CHADS-VASc score and its components with ischemic brain lesions. An adapted CHAD-VASc score (excluding history of stroke/TIA) for the analyses of clinically overt and silent ischemic brain lesions was used. Overall, 1,741 patients were included in the analysis (age 73 ± 8 years, 27.4% female). At least one ischemic brain lesion was observed in 36.8% (clinically overt: 10.5%; silent: 22.9%; transient ischemic attack: 3.4%). The CHAD-VASc score was strongly associated with clinically overt and silent ischemic brain lesions {odds ratio (OR) [95% confidence interval (CI)] 1.32 (1.17-1.49), < 0.001 and 1.20 (1.10-1.30), < 0.001, respectively}. Age 65-74 years (OR 2.58; 95%CI 1.29-5.90; = 0.013), age ≥75 years (4.13; 2.07-9.43; < 0.001), hypertension (1.90; 1.28-2.88; = 0.002) and diabetes (1.48; 1.00-2.18; = 0.047) were associated with clinically overt brain lesions, whereas age 65-74 years (1.95; 1.26-3.10; = 0.004), age ≥75 years (3.06; 1.98-4.89; < 0.001) and vascular disease (1.39; 1.07-1.79; = 0.012) were associated with silent ischemic brain lesions. A higher CHAD-VASc score was associated with a higher risk of both overt and silent ischemic brain lesions. www.ClinicalTrials.gov, identifier: NCT02105844.
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http://dx.doi.org/10.3389/fneur.2020.609234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835704PMC
January 2021

Ventricular tachycardia in a patient with repaired d-transposition of the great arteries.

HeartRhythm Case Rep 2021 Jan 17;7(1):26-29. Epub 2020 Oct 17.

Department of Cardiac Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, Univ. Bordeaux, Bordeaux University Hospital (CHU), Pessac-Bordeaux, France.

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http://dx.doi.org/10.1016/j.hrcr.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813791PMC
January 2021

Improved agreement and diagnostic accuracy of a cuffless 24-h blood pressure measurement device in clinical practice.

Sci Rep 2021 Jan 13;11(1):1143. Epub 2021 Jan 13.

Medical Outpatient and Hypertension Clinic, ESH Hypertension Centre of Excellence, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

A cuffless blood pressure (BP) device (TestBP) using pulse transit time is in clinical use, but leads to higher BP values compared to a cuff-based 24 h-BP reference device (RefBP). We evaluated the impact of a recent software update on BP results and TestBP's ability to differentiate between normo- and hypertension. 71 individuals had TestBP (Somnotouch-NIBP) and RefBP measurements simultaneously performed on either arm. TestBP results with software version V1.5 were compared to V1.4 and RefBP. Mean 24 h (± SD) BP for the RefBP, TestBP-V1.4 and TestBP-V1.5 were systolic 134.0 (± 17.3), 140.8 (± 20) and 139.1 (± 20) mmHg, and diastolic 79.3 (± 11.7), 85.8 (± 14.1) and 83.5 (± 13.0) mmHg, respectively (p-values < 0.001). TestBP-V1.5 area under the curve (95% confidence interval) versus RefBP for hypertension detection was 0.92 (0.86; 0.99), 0.94 (0.88; 0.99) and 0.77 (0.66; 0.88) for systolic and 0.92 (0.86; 0.99), 0.92 (0.85; 0.99) and 0.84 (0.74; 0.94) for diastolic 24 h, awake and asleep BP respectively. TestBP-V1.5 detected elevated systolic/diastolic mean 24 h-BP with a 95%/90% sensitivity and 65%/70% specificity. Highest Youden's Index was systolic 133 (sensitivity 95%/specificity 80%) and diastolic 87 mmHg (sensitivity 81%/specificity 98%). The update improved the agreement to RefBP. TestBP was excellent for detecting 24 h and awake hypertensive BP values but not for asleep BP values.
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http://dx.doi.org/10.1038/s41598-020-80905-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806663PMC
January 2021

Atrioventricular block with coronary sinus potential dissociation after lateral mitral isthmus block: What is the mechanism?

J Cardiovasc Electrophysiol 2021 Mar 23;32(3):874-877. Epub 2021 Jan 23.

Department of Cardiac Pacing and Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, Bordeaux University Hospital (CHU), Pessac-Bordeaux, France.

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http://dx.doi.org/10.1111/jce.14877DOI Listing
March 2021

High-risk atrioventricular block in Brugada syndrome patients with a history of syncope.

J Cardiovasc Electrophysiol 2021 Mar 19;32(3):772-781. Epub 2021 Jan 19.

Department of Cardiovascular Medicine, Division of Arrhythmia and Electrophysiology, National Cerebral and Cardiovascular Center, Osaka, Japan.

Background: Determining the etiology of syncope is challenging in Brugada syndrome (BrS) patients. Implantable cardioverter defibrillator placement is recommended in BrS patients who are presumed to have arrhythmic syncope. However, arrhythmic syncope in BrS patients can occur in the setting of atrioventricular block (AVB), which should be managed by cardiac pacing. The clinical characteristics of BrS patients with high-risk AVB remain unknown.

Methods: This study included 223 BrS patients with a history of syncope from two centers. The clinical characteristics of patients with high-risk AVB (Mobitz type II second-degree AVB, high-degree AVB, or third-degree AVB) were investigated.

Results: During the 99 ± 78 months of follow-up, we identified six BrS patients (2.7%) with high-risk AVB. Three of the six patients (50%) with AVB presented with syncope associated with prodromes or specific triggers. Four patients (67%) were found to have paroxysmal third-degree AVB during the initial evaluation for BrS and syncope, while two patients developed third-degree AVB during the follow-up period. The incidence of first-degree AVB was significantly higher in AVB patients than in non-AVB patients (83% vs. 15%; p = .0005). There was no significant difference in the incidence of ventricular fibrillation between AVB and non-AVB patients (AVB [17%], non-AVB [12%]; p = .56).

Conclusion: High-risk AVB can occur in BrS patients with various clinical presentations. Although rare, the incidence is worth considering, especially in BrS patients with first-degree AVB.
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http://dx.doi.org/10.1111/jce.14876DOI Listing
March 2021

Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation (Marshall-PLAN): Prospective, single-center study.

Heart Rhythm 2021 Apr 29;18(4):529-537. Epub 2020 Dec 29.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Pessac-Bordeaux, France; Bordeaux University Hospital (CHU), Cardio-Thoracic Unit, Pessac, France.

Background: Beyond pulmonary vein isolation (PVI), the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined.

Objective: The purpose of this study was to examine a novel comprehensive ablation strategy (Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation [Marshall-PLAN]) strictly based on anatomical considerations.

Methods: Left atrial (LA) sites were sequentially targeted as follows: (1) coronary sinus and vein of Marshall (CS-VOM) musculature; (2) PVI; and (3) anatomical isthmuses (mitral, roof, and cavotricuspid isthmus [CTI]). The primary endpoint was 12-month freedom from AF/atrial tachycardia (AT).

Results: Seventy-five consecutive patients were included (age 61 ± 9 years; 10 women; AF duration 9 ± 11 months; mean LA volume 197 ± 43 mL). VOM ethanol infusion was completed in 69 patients (92%). The full Marshall-PLAN lesion set (VOM, PVI, mitral, roof, and CTI with block) was successfully completed in 68 patients (91%). At 12 months, 54 of 75 patients (72%) were free from AF/AT after a single procedure (no antiarrhythmic drugs) in the overall cohort. In the subset of patients with a complete Marshall-PLAN lesion set (n = 68), the single procedure success rate was 79%. After 1 or 2 procedures, 67 of 75 patients (89%) remained free from AF/AT (no antiarrhythmic drugs). After 1 or 2 procedures, VOM ethanol infusion was complete in 72 of 75 patients (96%).

Conclusion: A novel ablation strategy that systematically targets anatomical atrial structures (VOM ethanol infusion, PVI, and prespecified linear lesions) is feasible, safe, and associated with a high rate of freedom from arrhythmia recurrence at 12 months in patients with persistent AF.
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http://dx.doi.org/10.1016/j.hrthm.2020.12.023DOI Listing
April 2021

Impact of Vein of Marshall Ethanol Infusion on Mitral Isthmus Block: Efficacy and Durability.

Circ Arrhythm Electrophysiol 2020 12 16;13(12):e008884. Epub 2020 Nov 16.

Bordeaux University Hospital (CHU), Cardiac Electrophysiology and Cardiac Stimulation Team, CHU Bordeaux, IHU Lyric, Université de Bordeaux, France (T.N., T.P., K.V., C.G., C.A., P.K., F.D.R., T. Kamakura, T.T., Y.N., T. Kitamura, M.T., G.C., R.T., R.C., N.W., J.D., F.S., H.C., M. Hocini, M. Haïssaguerre, P.J., N.D.).

Background: Achieving bidirectional mitral isthmus (MI) block using radiofrequency catheter ablation (RFCA) alone is challenging, and MI reconnection is common. Adjunctive vein of Marshall (VOM) ethanol infusion (VOM-Et) can facilitate acute MI block. However, little is known about its long-term success. This study sought to evaluate the impact of adjunctive VOM-Et on MI block achievement and durability compared with RFCA alone.

Methods: Patients undergoing the first attempt of posterior MI ablation were grouped according to their MI block index strategy: adjunctive VOM-Et and RFCA alone. Rates of acute MI block and MI reconnection observed during repeat procedures were compared between the 2 groups.

Results: The VOM-Et group consisted of 152 patients (63.8±9.4 years) undergoing adjunctive VOM-Et for MI block. The RFCA group consisted of 110 patients (60.9±9.2 years) undergoing MI ablation using RFCA alone. Acute MI block was more frequently achieved in the VOM-Et group (98.7% [150/152] versus 63.6% [70/110]; <0.001) with shorter RFCA duration (5.00 [3.00-7.00] versus 19.0 [13.6-22.0] minutes; <0.001). Of the 220 patients with MI block achieved during the index procedure, 81 underwent a repeat procedure during follow-up (VOM-Et group: 23.3% [35/150] versus RFCA group: 65.7% [46/70], respectively; <0.001). A significantly greater number of patients exhibited durable MI block in the VOM-Et group (62.9% [22/35] versus 32.6% [15/46], respectively; =0.008).

Conclusions: Beyond facilitating acute MI block, VOM-Et is associated with greater lesion durability as evidenced by higher rates of MI block during repeat procedures.
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http://dx.doi.org/10.1161/CIRCEP.120.008884DOI Listing
December 2020

Epicardial course of the septopulmonary bundle: Anatomical considerations and clinical implications for roof line completion.

Heart Rhythm 2021 Mar 11;18(3):349-357. Epub 2020 Nov 11.

Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, L'Institut de RYthmologie et modélisation Cardiaque (LIRYC), Université Bordeaux, Bordeaux, France.

Background: Gaps in the roof line have been ascribed to epicardial conduction using the septopulmonary bundle.

Objectives: We sought to evaluate the frequency of septopulmonary bundle bypass during roof line ablation, to describe anatomical conditions favoring this epicardial gap, and to propose an alternative strategy when present.

Methods: One hundred consecutive patients underwent atrial fibrillation ablation. A de novo roof line was created between the superior pulmonary veins. In cases of residual gaps, a floor line was created between the inferior pulmonary veins. Microtomography imaging and histological analyses of 5 human donor hearts were performed: a specific focus was made on the dome and the posterior wall.

Results: Residual gaps were more frequent in roof lines than floor lines (33% vs 15%; P = .049). Electrogram morphologies, activation sequences, and pacing maneuvers indicated an epicardial bypass of the roof line in all cases. Conduction block was obtained in 67 roof lines and 28 floor lines, resulting in a 95% success rate of linear block, without "box" isolation. Between the superior pulmonary veins, the atrial myocardium was thicker and consistently displayed adipose tissue separating the septopulmonary bundle from the septoatrial bundle.

Conclusion: Epicardial conduction across the roof line is common and requires careful electrogram analysis to detect. In such cases, a floor line can be an effective alternative strategy, with clear validation criteria. Myocardial thickness and fat interposition may explain difficulties in achieving lesion transmurality during roof line ablation.
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http://dx.doi.org/10.1016/j.hrthm.2020.11.008DOI Listing
March 2021

Letter by Krisai et al Regarding Article, "Preventive or Deferred Ablation of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy and Implantable Defibrillator (BERLIN VT): A Multicenter Randomized Trial".

Circulation 2020 Sep 21;142(12):e184-e185. Epub 2020 Sep 21.

Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047003DOI Listing
September 2020

Heart Rate Variability Triangular Index as a Predictor of Cardiovascular Mortality in Patients With Atrial Fibrillation.

J Am Heart Assoc 2020 08 28;9(15):e016075. Epub 2020 Jul 28.

Department of Cardiology University Hospital Basel Basel Switzerland.

Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5-minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal-to-normal intervals, square root of the mean squared differences of successive normal-to-normal intervals and mean heart rate) were calculated. During follow-up, an end point committee adjudicated each cause of death. During a mean follow-up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including β blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1-2.6; =0.01) and all-cause death (hazard ratio, 1.42; 95% CI, 1.02-1.98; =0.04). Conclusions The HRV index measured in a single 5-minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.
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http://dx.doi.org/10.1161/JAHA.120.016075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792265PMC
August 2020

Evaluation of the QT interval in patients with drug-induced QT prolongation and torsades de pointes.

J Cardiovasc Electrophysiol 2020 10 28;31(10):2696-2701. Epub 2020 Jul 28.

Department of Cardiology, Electrophysiology and Ablation Unit, Bordeaux University Hospital (CHU), Pessac, France.

Background: Data on the optimal location of the electrocardiogram (ECG) leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking.

Methods: We systematically reviewed the literature for the ECGs of patients with diLQTS and subsequent TdP. We assessed T wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion.

Results: Of 84 patients, 61.9% were female and the mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (SD) 671 (102) vs. 655 (97) ms, p = .02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were noninterpretable: 10 (11.9%) due to too flat T waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were noninterpretable in nine (10.7%) patients: six (7.1%) due to frequent, early PVCs, one (1.2%) due to insufficient ECG quality, two (2.4%) due to missing chest leads but none due to too flat T waves. The most common T wave morphologies in the limb leads were flat (51.0%), broad (14.3%), and late peaking (12.6%) T waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%), and biphasic (15.2%) T waves.

Conclusions: Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG.
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http://dx.doi.org/10.1111/jce.14687DOI Listing
October 2020

Canakinumab After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation: A Pilot Randomized Trial.

Circ Arrhythm Electrophysiol 2020 07 14;13(7):e008197. Epub 2020 Jun 14.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Canada (D.C.).

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http://dx.doi.org/10.1161/CIRCEP.119.008197DOI Listing
July 2020

Analyzing 24-Hour Blood Pressure Measurements with a Novel Cuffless Pulse Transit Time Device in Clinical Practice-Does the Software for Heartbeat Detection Matter?

Diagnostics (Basel) 2020 May 31;10(6). Epub 2020 May 31.

Medical Outpatient and Hypertension Clinic, ESH Hypertension Centre of Excellence, University Hospital Basel, 4031 Basel, Switzerland.

Background: The Somnotouch-Non-Invasive-Blood-Pressure (NIBP) device delivers raw data consisting of electrocardiography and photoplethysmography for estimating blood pressure (BP) over 24 hours using pulse-transit-time. The study's aim was to analyze the impact on 24-hour BP results when processing raw data by two different software solutions delivered with the device.

Methods: We used data from 234 participants. The Somnotouch-NIBP measurements were analyzed using the Domino-light and Schiller software and compared. BP values differing > 5 mmHg were regarded as relevant and explored for their impact on BP classification (normotension vs. hypertension).

Results: Mean (±standard deviation) absolute systolic/diastolic differences for 24-hour mean BP were 1.5 (±1.7)/1.1 (±1.3) mm Hg. Besides awake systolic BP ( = 0.022), there were no statistically significant differences in systolic/diastolic 24-hour mean, awake, and asleep BP. Twenty four-hour mean BP agreement (number (%)) between the software solutions within 5, 10, and 15 mmHg were 222 (94.8%), 231 (98.7%), 234 (100%) for systolic and 228 (97.4%), 232 (99.1%), 233 (99.5%) for diastolic measurements, respectively. A BP difference of >5 mmHg was present in 24 (10.3%) participants leading to discordant classification in 4-17%.

Conclusion: By comparing the two software solutions, differences in BP are negligible at the population level. However, at the individual level there are, in a minority of cases, differences that lead to different BP classifications, which can influence the therapeutic decision.
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http://dx.doi.org/10.3390/diagnostics10060361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345122PMC
May 2020

Increased heart rate due to supra-ventricular tachycardia triggering premature ventricular contraction.

J Cardiovasc Electrophysiol 2020 Jun 15;31(6):1544-1546. Epub 2020 May 15.

LIRYC, University of Bordeaux, CHU de Bordeaux, Bordeaux, France.

We describe a case wherein the presence of premature ventricular contractions was related to an increased heart rate that occurred due to supra-ventricular tachycardia: atrial tachycardia or atrioventricular nodal reentry tachycardia.
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http://dx.doi.org/10.1111/jce.14533DOI Listing
June 2020

Change in Atrial Fibrillation Burden over Time in Patients with Nonpermanent Atrial Fibrillation.

Cardiol Res Pract 2020 17;2020:9583409. Epub 2020 Apr 17.

Cardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland.

Introduction: The natural course of atrial fibrillation (AF) is not well defined. We aimed to investigate the change in AF burden over time and its associated risk factors among AF patients.

Methods: Fifty-four participants with recently documented paroxysmal or persistent AF were enrolled. Main exclusion criteria were permanent AF or previous catheter ablation for AF. AF burden was calculated as time in AF divided by total recording time using yearly continuous 7-day Holter-ECG recordings. A relative change ≥10% or an absolute change >0.5% in AF burden between two yearly Holter-ECG recordings was considered significant.

Results: Mean age was 67 years, 72% were men. The proportion of patients with no recorded AF increased from 53.7% at baseline to 78.6% (=0.1) after 4 years of follow-up. In 7-day Holter-ECG recordings performed after baseline, 23.7% of participants had a decrease and 23.7% an increase in AF burden. In separate mixed effect models, AF burden over time was associated with prior stroke ( 42.59, 95% CI (23.40; 61.77); < 0.0001), BNP ( 0.05, CI (0.02; 0.09); =0.005) end-diastolic ( 0.49, CI (0.23; 0.74); =0.0003) as well as end-systolic ( 0.25, CI (0.05; 0.46); =0.02) left atrial volume, left atrial ejection fraction ( -0.43, CI (-0.76;-0.10); =0.01), -wave ( 36.67, CI (12.96; 60.38); =0.003), and deceleration time ( -0.1, CI (-0.16; -0.05); =0.002). In a multivariable model, a history of prior stroke ( 29.87, CI (2.61; 57.13); =0.03) and BNP levels ( 0.05, CI (0.01; 0.08); =0.007) remained significantly associated with AF burden.

Conclusions: Few patients with paroxysmal or persistent AF have AF episodes on yearly 7-day Holter-ECG recordings, and AF progression is rare. AF burden was independently associated with a history of prior stroke and BNP levels.
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http://dx.doi.org/10.1155/2020/9583409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183533PMC
April 2020