Zoltán Csanádi

Transcranial Measurement of Cerebral Microembolic Signals During Pulmonary Vein Isolation A Comparison of Two Ablation Techniques

Background—Pulmonary vein isolation has increasingly been used to cure atrial fibrillation, but concerns have recently been raised that subclinical brain damage may occur because of microembolization during these procedures. We compared the occurrence of bubble formation seen on intracardiac echocardiography and the microembolic signals (MESs) detected by transcranial Doppler on the use of different ablation techniques and anticoagulation strategies. Methods and Results—This prospective study included 35 procedures in 34 consecutive patients (age, 52; SD, 12.8 years; female:male 9:25). Pulmonary vein isolation was performed with a cryoballoon and the conventional anticoagulation protocol (activated clotting time >250 s) in 10 procedures (group 1), with a multipolar duty-cycled radiofrequency pulmonary group 2), and with regime a pulmonary vein ablation catheter with an aggressive anticoagulation (activated clotting time >320 s) in 13 procedures (group 3). The mean total numbers of MESs detected during the procedures were 833.7 (SD, 727.4) in group 1, 3142.6 (SD, 1736.4) in group 2, and 2204.6 (SD, 1078.1) in group 3 (P=0.0005). MESs were detected mostly during energy delivery in the pulmonary vein ablation catheter groups, whereas a relatively even distribution of emboli formation was seen during cryoballoon ablations. A significant correlation was found in all groups between the degree of bubble formation on intracardiac echocardiography and the number of MESs (P=0.0000). Conclusions—Duty-cycled radiofrequency ablation is associated with significantly more MESs, even when more aggressive anticoagulation is applied. With both techniques most of these microemboli are gaseous in nature.

Cerebral microembolization during atrial fibrillation ablation: Comparison of different single-shot ablation techniques

BACKGROUND Clinically silent cerebral ischemia (SCI) detected by diffusion-weighted MRI has been reported in 5-40% of patients undergoing pulmonary vein isolation (PVI). Although initial reports suggested a high rate of SCI with phased radiofrequency (RF) ablation on use of the pulmonary vein ablation catheter (PVAC), the incidence was subsequently markedly reduced in consequence of procedural modifications in recent studies. We analyzed cerebral microembolization as assessed with transcranial Doppler during phased RF ablation and with two other single-shot AF ablation technologies: the cryoballoon (CB) and the nMARQ™ multipolar irrigated RF ablation system. METHODS AND RESULTS A total of 89 patients (mean age: 57, SD: 12years; 62 males) with paroxysmal or persistent AF underwent PVI. Phased RF was used according to the initial protocol in 7 patients (PVAC Group I), with procedural modifications and a newer (14.4) version of the RF generator in 37 patients (PVAC Group II) and with the most recent (version 15.1) generator in 18 patients (PVAC Group III). Ablation was performed with the CB in 13 and with the nMARQ system in 14 patients. The number of microemboli (mean+(SD)) detected in the middle cerebral arteries was 2703 (918) in PVAC Group I, 1087 (542) in PVAC Group II, 719 (469) in PVAC Group III, 1057 (784) with CB and 2166 (1047) with nMARQ (p<0.01). CONCLUSION Significant decreases in MES counts were observed thanks to the procedural modifications and newer RF generator with phased RF. High MES counts comparable to those with the initial phased RF resulted from the use of nMARQ.

Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial

Abstract Aims This prospective, multicentre study (PRECISION GOLD) evaluated the incidence of asymptomatic cerebral embolism (ACE) after pulmonary vein isolation (PVI) using a new gold multi-electrode radiofrequency (RF) ablation catheter, pulmonary vein ablation catheter (PVAC) GOLD. Also, procedural efficiency of PVAC GOLD was compared with ERACE. The ERACE study demonstrated that a low incidence of ACE can be achieved with a platinum multi-electrode RF catheter (PVAC) combined with procedural manoeuvres to reduce emboli. Methods and results A total of 51 patients with paroxysmal atrial fibrillation (AF) (age 57 ± 9 years, CHA2DS2-VASc score 1.4 ± 1.4) underwent AF ablation with PVAC GOLD. Continuous oral anticoagulation using vitamin K antagonists, submerged catheter introduction, and heparinization (ACT ≥ 350 s prior to ablation) were applied. Cerebral magnetic resonance imaging (MRI) scans were performed within 48 h before and 16–72 h post-ablation. Cognitive function assessed by the Mini-Mental State Exam at baseline and 30 days post-ablation. New post-procedural ACE occurred in only 1 of 48 patients (2.1%) and was not detectable on MRI after 30 days. The average number of RF applications per patient to achieve PVI was lower in PRECISION GOLD (20.3 ± 10.0) than in ERACE (28.8 ± 16.1; P = 0.001). Further, PVAC GOLD ablations resulted in significantly fewer low-power (<3 W) ablations (15 vs. 23%, 5 vs. 10% and 2 vs. 7% in 4:1, 2:1, and 1:1 bipolar:unipolar energy modes, respectively). Mini-Mental State Exam was unchanged in all patients. Conclusion Atrial fibrillation ablation with PVAC GOLD in combination with established embolic lowering manoeuvres results in a low incidence of ACE. Pulmonary vein ablation catheter GOLD demonstrates improved biophysical efficiency compared with platinum PVAC. Trial registration ClinicalTrials.gov NCT01767558.

Electrical Storm in the Brain and in the Heart: Epilepsy and Brugada Syndrome

We describe a patient with the coincidence of 2 ion channel disorders with autosomal dominant inheritance: Brugada syndrome, a potentially fatal cardiac condition, and cryptogenic focal epilepsy, likely due to a neurologic channelopathy. Although Brugada syndrome was discovered incidentally, most of the clinical features of epilepsy in this patient shared the risk factor characteristics of sudden unexplained death in epilepsy syndrome. This case provides additional information on the potential interaction between ion channel abnormalities in the heart and in the brain. Furthermore, it may suggest that patients with epilepsy at increased risk for sudden unexplained death in epilepsy syndrome should undergo a careful cardiac evaluation.

New perspectives in the renin-angiotensin-aldosterone system (RAAS) IV: circulating ACE2 as a biomarker of systolic dysfunction in human hypertension and heart failure.

Background Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling. Methods, Findings Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured. sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patients populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters. Conclusions Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF.

Predictors of cerebral microembolization during phased radiofrequency ablation of atrial fibrillation: Analysis of biophysical parameters from the ablation generator

BACKGROUND Pulmonary vein isolation with phased radiofrequency current and use of a pulmonary vein ablation catheter (PVAC) has recently been associated with a high incidence of clinically silent brain infarcts on diffusion-weighted magnetic resonance imaging and a high microembolic signal (MES) count detected by transcranial Doppler. OBJECTIVE The purpose of this study was to investigate the potential correlation between different biophysical parameters of energy delivery (ED) and MES generation during PVAC ablation. METHODS MES counts during consecutive PVAC ablations were recorded for each ED and time stamped for correlation with temperature, power, and impedance data from the GENius 14.4 generator. Additionally, catheter-tissue contact was characterized by the template deviation score, calculated by comparing the temperature curve with an ideal template representing good contact, and by the respiratory contact failure score, to quantify temperature variations indicative of intermittent contact due to respiration. RESULTS A total of 834 EDs during 48 PVAC ablations were analyzed. A significant increase in MES count was associated with a lower average temperature, a temperature integral over 62°C, a higher average power, the total energy delivered, higher respiration and template deviation scores (P <.0001), and simultaneous ED to the most proximal and distal poles of the PVAC (P <.0001). CONCLUSION MES generation during ablation is related to different indicators of poor electrode-tissue contact, the total power delivered, and the interaction between the most distal and the most proximal electrodes.

Pacemaker‐Mediated Tachycardia over the Upper Rate Limit in a Biventricular Pacemaker System: What is the Mechanism?

Case Presentation A 51-year-old man with nonischemic dilated cardiomyopathy, a low ejection fraction (25%), and New York Heart Association class III heart failure was referred to our Department for cardiac resynchronization therapy. His electrocardiogram (ECG) showed an atypical right bundle branch block and left posterior hemiblock morphology, with a QRS duration of 160 ms (Fig. 1), and with intraand inter-ventricular dyssynchrony. A biventricular pacemaker (Stratos LV, Biotronik, Berlin, Germany) was implanted with a bipolar left ventricular (LV) lead positioned in the proximal segment of the anterior vein in the absence of an appropriate lateral or posterior branch. The LV threshold was 3.5 V at 1 ms and the output was programmed to 6 V at 1 ms. One week later, the patient was admitted with sustained regular wide QRS complex tachycardia at 167 beats/min, an almost identical QRS axis in the frontal plane and similar QRS complexes as compared with the baseline nonpaced ECG (Fig. 1). Intracardiac signals during the tachycardia through device interrogation are presented in Figure 2 (left). Prompt termination of the tachycardia was achieved with an iv bolus of adenosine (6 mg). At testing, the atrial and right ventricular (RV) leads showed excellent sensing and capture parameters, with a further increase in the LV threshold, since the implantation and only intermittent capture at the programmed values. Tachycardia with identical morphology to the presenting arrhythmia was reinitiated during the LV capture threshold test (Fig. 3, left). What is the mechanism of this tachycardia?

Potential Biological Markers of Atrial Fibrillation: A Chance to Prevent Cryptogenic Stroke

Stroke affects millions of people all over the world, causing death and disability. The most frequent type of this disease is ischemic stroke, which can be caused by different factors. In approximately 25 percent of cases, no obvious cause can be found. Recent observations have shown that paroxysmal atrial fibrillation could be responsible for a significant number of cryptogenic stroke events. Short- or long-lasting ECG monitoring could help with the diagnosis of transient arrhythmias. Unfortunately, these techniques either are expensive or require good patient compliance. An alternative option is the identification of biological markers that are specific for atrial fibrillation and can be used to predict arrhythmia. In this review, we give a summary of the recent advances in the research of arrhythmia markers. Based on their structure and function, we differentiated four groups of biomarkers: markers of inflammation, markers of fibrosis, markers with hormonal activity, and other markers. In spite of intensive researches, the optimal biological marker is still not available, but there are some promising markers, like NT-proBNP/BNP.

Cerebrovascular Complications Related to Atrial Fibrillation Ablation and Strategies for Periprocedural Stroke Prevention

Transcatheter treatment of atrial fibrillation (AF) is a complex intervention performed in patients who are at inherently increased risk of a thromboembolic complication, including stroke. It is therefore not surprising that cerebrovascular accidents have been among the most feared complications since the inception of AF ablation. While improvements have been made to limit the incidence of thromboembolic events during catheter ablation of AF, the optimal strategy to minimize such complications has yet to be determined. It is hoped that larger trials using periprocedural anticoagulation strategies can be undertaken to definitively address these important concerns.

Intracardiac Hemostasis and Fibrinolysis Parameters in Patients with Atrial Fibrillation

Aims To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. Patients and Methods Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. Results Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. Conclusions None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level.