Yuri Blaauw

“Early” Class III Drugs for the Treatment of Atrial Fibrillation Efficacy and Atrial Selectivity of AVE0118 in Remodeled Atria of the Goat

Background—Currently available antiarrhythmic drugs are only moderately effective against atrial fibrillation (AF) and may cause ventricular proarrhythmia. AVE0118 is a blocker of atrium-specific early K+ currents (IKur/Ito). Methods and Results—Effects of intravenous AVE0118 and dofetilide on atrial effective refractory period (AERP) and inducibility of AF were measured before and after 48-hours of AF-induced electrical remodeling in the goat. During persistent AF (53±19 days), the cardioversion efficacy and effects on atrial wavelength of AVE0118, dofetilide, and ibutilide were evaluated. QT durations were measured during atrial pacing and persistent AF. After 48 hours of AF, the effect of dofetilide on AERP was reduced, and induction of AF was not prevented. In contrast, the class III action of AVE0118 was enhanced, and AF inducibility decreased from 100% to 32% (P<0.001). At 1, 3, and 10 mg · kg−1 · h−1, AVE0118 terminated persistent AF in 1 of 8, 3 of 8, and 5 of 8 goats, respectively. Dofetilide and ibutilide terminated AF in 1 of 5 and 2 of 7 goats. AVE0118 0.5, 1.5, and 5 mg/kg prolonged the AERP during AF and increased the fibrillation wavelength from 6.7±0.6 to 8.5±0.5, 9.7±0.5, and 11.2±0.9 cm (P<0.01). Whereas dofetilide and ibutilide prolonged QT duration, AVE0118 had no appreciable effect. Conclusions—AVE0118 markedly prolongs the AERP during AF without affecting QT duration. Cardioversion of AF was due to an ≈2-fold increase in fibrillation wavelength. Atrium-selective class III drugs like AVE0118 may be a promising new option for safe and effective cardioversion of AF.

Hybrid thoracoscopic surgical and transvenous catheter ablation of atrial fibrillation.

OBJECTIVESnThe purpose of this study was to evaluate the feasibility, safety, and clinical outcomes up to 1 year in patients undergoing combined simultaneous thoracoscopic surgical and transvenous catheter atrial fibrillation (AF) ablation.nnnBACKGROUNDnThe combination of the transvenous endocardial approach with the thoracoscopic epicardial approach in a single AF ablation procedure overcomes the limitations of both techniques and should result in better outcomes.nnnMETHODSnA cohort of 26 consecutive patients with AF who underwent hybrid thoracoscopic surgical and transvenous catheter ablation were followed, with follow-up of up to 1 year.nnnRESULTSnTwenty-six patients (42% with persistent AF) underwent successful hybrid procedures. There were no complications. The mean follow-up period was 470 ± 154 days. In 23% of the patients, the epicardial lesions were not transmural, and endocardial touch-up was necessary. One-year success, defined according to the Heart Rhythm Society, European Heart Rhythm Association, and European Cardiac Arrhythmia Society consensus statement for the catheter and surgical ablation of AF, was 93% for patients with paroxysmal AF and 90% for patients with persistent AF. Two patients underwent catheter ablation for recurrent AF or left atrial flutter after the hybrid procedure.nnnCONCLUSIONSnA combined transvenous endocardial and thoracoscopic epicardial ablation procedure for AF is feasible and safe, with a single-procedure success rate of 83% at 1 year.

Development of a Substrate of Atrial Fibrillation During Chronic Atrioventricular Block in the Goat

Background—Atrial dilatation is an important risk factor for atrial fibrillation (AF). In the present study, we monitored the electrophysiological changes during progressive atrial dilatation in chronically instrumented goats. Methods and Results—In 8 goats, 2 screw-in leads with piezoelectric crystals were implanted transvenously in the right atrium. After 2 weeks, atrial diameter and effective refractory period were measured. AF paroxysms were induced by burst pacing to determine the baseline AF cycle length and stability of AF. After His-bundle ablation, the above measurements were repeated once a week. After 4 weeks of complete AV block, the free wall of the right atrium was mapped and the atrium was fixed in formalin for histological analysis. After His-bundle ablation, the ventricular rate decreased from 113.8±4.8 to 44.6±2.5 bpm. Right atrial diameter increased gradually by 13.5±3.9% during 4 weeks of AV block (P<0.01). The duration of induced AF paroxysms increased from 4.6 seconds to 6.4 minutes (P<0.05). Atrial effective refractory period and AF cycle length remained constant. Spontaneous paroxysms of AF were not observed. Atrial mapping during rapid pacing revealed that slow conduction (<30 cm/s) was present in 3.7±1.0% of the mapped area (control, 0.9±0.5%, P<0.05). Histological analysis showed hypertrophy without atrial fibrosis. Connexin40 and connexin43 expression was unchanged. Conclusions—Chronic AV block in the goat leads to progressive atrial dilatation, prolongation of induced AF paroxysms, and local conduction delays. The increase in AF stability was not a result of a shortening of atrial refractoriness or atrial fibrosis.

EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion

Cardiology, Bern University Hospital, 3010 Bern, Switzerland; Department of Cardiology, Maastricht University Medical Center, 6281 Maastricht, The Netherlands; Isar Medical Centre, 80331 Munich, Germany; Cardiovascular Center Frankfurt, 60389 Frankfurt, Germany; Cardiac Arrhythmia Research Center, Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy; and Davidai Arrhythmia Center, Sheba Medical Center, 52621 Tel Hashomer, Israel

Synergistic Action of Atrial Dilation and Sodium Channel Blockade on Conduction in Rabbit Atria

Introduction: The aim of this study was to investigate the interaction of atrial dilation and blockade of the rapid sodium channel on atrial conduction and degree of anisotropy.

Patients originally diagnosed with idiopathic atrial fibrillation more often suffer from insidious coronary artery disease compared to healthy sinus rhythm controls

BACKGROUNDnIdiopathic atrial fibrillation (AF) refers to a clinically lacking cardiovascular or pulmonary disease generating the pathophysiologic substrate for the arrhythmia. However, because idiopathic AF is associated with an increased event rate, it could be a harbinger of as-yet undetected underlying heart disease.nnnOBJECTIVEnThe purpose of this study was to determine the prevalence of coronary artery disease (CAD) in patients diagnosed with idiopathic paroxysmal AF.nnnMETHODSnOf the 3243 patients who underwent cardiac computed tomographic angiography (CTA) in our center between January 2008 and March 2011, we identified a total of 115 consecutive idiopathic paroxysmal AF patients who underwent CTA before electrophysiologic ablation. Patients were compared with 275 age-, sex-, and PROCAM risk score-matched healthy controls in permanent sinus rhythm. All patients were free of hypertension, diabetes, congestive heart failure, previous known coronary artery and peripheral vascular disease, previous stroke, thyroid, pulmonary, and renal disease, and structural abnormalities on echocardiography.nnnRESULTSnControls more often showed a family history of CAD (38% vs 15%, P <.001), had a higher prevalence of smoking (25% vs 14%, P = .021), higher fasting blood glucose levels (5.5 ± 0.7 mmol/L vs 5.4 ± 0.6 mmol/L, P = .025), and smaller atrial diameters (37 ± 4 mm vs 40 ± 5 mm, P <.001) compared to AF patients. Notwithstanding the above, idiopathic AF patients significantly more often suffered from subclinical CAD compared to controls (49% vs 34%, P = .008). Multivariable regression analysis revealed that beside (as expected) age and gender, a history of AF and left atrial diameter were significant predictors of underlying CAD.nnnCONCLUSIONnHalf of patients originally diagnosed with idiopathic paroxysmal AF show concealed underlying CAD. The detection and treatment of CAD at an early stage could improve the prognosis of these patients.

Left ventricular lead placement in the latest activated region guided by coronary venous electroanatomic mapping.

AIMnLeft ventricular (LV) lead placement in the latest activated region is an important determinant of response to cardiac resynchronization therapy (CRT). We investigated the feasibility of coronary venous electroanatomic mapping (EAM) to guide LV lead placement to the latest activated region.nnnMETHODS AND RESULTSnTwenty-five consecutive CRT candidates with left bundle-branch block underwent intra-procedural coronary venous EAM using EnSite NavX. A guidewire was used to map the coronary veins during intrinsic activation, and to test for phrenic nerve stimulation (PNS). The latest activated region, defined as the region with an electrical delay >75% of total QRS duration, was located anterolaterally in 18 (basal, n = 10; mid, n = 8) and inferolaterally in 6 (basal, n = 3; mid, n = 3). In one patient, identification of the latest activated region was impeded by limited coronary venous anatomy. In patients with >1 target vein (n = 12), the anatomically targeted inferolateral vein was rarely the vein with maximal electrical delay (n = 3). A concordant LV lead position was achieved in 18 of 25 patients. In six patients, this was hampered by PNS (n = 4), lead instability (n = 1), and coronary vein stenosis (n = 1).nnnCONCLUSIONnCoronary venous EAM can be used intraprocedurally to guide LV lead placement to the latest activated region free of PNS. This approach especially contributes to optimization of LV lead electrical delay in patients with multiple target veins. Conventional anatomical LV lead placement strategy does not target the vein with maximal electrical delay in many of these patients.

Vectorcardiographic QRS area identifies delayed left ventricular lateral wall activation determined by electroanatomic mapping in candidates for cardiac resynchronization therapy

BACKGROUNDnDelayed left ventricular (LV) lateral wall (LVLW) activation is considered the electrical substrate underlying LV dysfunction amenable to cardiac resynchronization therapy (CRT).nnnOBJECTIVEnThe purpose of this study was to assess LVLW activation in CRT candidates using coronary venous electroanatomic mapping (EAM) and to investigate whether the QRS area (QRSAREA) on the vectorcardiogram (VCG) can identify delayed LVLW activation.nnnMETHODSnFifty-one consecutive CRT candidates (29 left bundle branch block [LBBB], 15 intraventricular conduction delay [IVCD], 7 right bundle branch block [RBBB]) underwent intraprocedural coronary venous EAM using EnSite NavX. VCGs were constructed from preprocedural digital 12-lead ECGs using the Kors method. QRSAREA was assessed and compared to QRS duration and 5 different LBBB definitions.nnnRESULTSnDelayed LVLW activation (activation time >75% of QRS duration) occurred in 38 of 51 patients (29/29 LBBB, 8/15 IVCD, 1/7 RBBB). QRSAREA was larger in patients with than in patients without delayed LVLW activation (108 ± 42 µVs vs 51 ± 27 µVs, P < .001), and identified delayed LVLW activation better than QRS duration (area under the curve 0.89 [95% confidence interval 0.79-0.99] vs 0.49 [95% confidence interval 0.33-0.65]). QRSAREA >69 µVs diagnosed delayed LVLW activation with a higher sum of sensitivity (87%) and specificity (92%) than any of the LBBB definitions. Of the different LBBB definitions, the European Society of Cardiology textbook definition performed best with sensitivity of 76% and specificity of 100%.nnnCONCLUSIONnCoronary venous EAM can be used during CRT implantation to determine the presence of delayed LVLW activation. QRSAREA is a noninvasive alternative for intracardiac measurements of electrical activation, which identifies delayed LVLW activation better than QRS duration and LBBB morphology.

A Completely Subcutaneous Implantable Cardioverter Defibrillator in a Patient With Situs Inversus Totalis

A 42-year-old male with a known situs inversus totalis was resuscitated because of ventricular fibrillation. The coronary angiogram showed no abnormalities. An echocardiogram demonstrated apart from the known dextrocardia of the heart a moderate mitral insufficiency but no evidence for an infarcted area. The laboratory results showed only mildly elevated enzymes. Neurological recovery of the patient was unremarkable. An MR scan was not successful because of claustrophobia of the patient. As implantation of transvenous leads in situs inversus can be (1) technically challenging as situs inversus is frequently associated with anomalous venous return, (2) the patient was young, and (3) no pacing indication was present, we opted for a completely subcutaneous implantable cardioverter defibrillator (S-ICD, Cameron Health Inc., San Clemente, CA, USA) that was placed on the right side of the thorax (Fig. 1). Defibrillation of 50 Hz induced ventricular fibrillation during the procedure was successfully performed by the S-ICD.

The role of acute invasive haemodynamic measurements in cardiac resynchronization therapy: looping towards prediction of long-term response and therapy optimization.

This editorial refers to ‘Prediction of long-term outcomeof cardiac resynchronization therapy by acute pressure–volume loop measurements’, by G.J. de Roest et al.doi.10.1093/eurjhf/hfs190Cardiac resynchronization therapy (CRT) has been established asan effective treatment strategy for heart failure patients withsevere LV systolic impairment and electrical dyssynchrony.