Durable Physiological Changes and Decreased Syncope Burden 12 Months After Unifocal Right-Sided Ablation Under Computed Tomographic Guidance in Patients With Neurally Mediated Syncope or Functional Sinus Node Dysfunction.

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Unifocal Right-Sided Ablation Treatment for Neurally Mediated Syncope and Functional Sinus Node Dysfunction Under Computed Tomographic Guidance.

Background Biatrial, extensive, and complex ablation strategies have been published for the treatment of neurally mediated syncope, sinus node dysfunction, and functional atrioventricular block. We have developed a less extensive and more specific approach compared with previously published cardioneuroablation strategies, called cardio-neuromodulation. It is based on tailored vagolysis of the sinoatrial node through partial ablation of the anterior right-ganglionated plexus, preferentially through a right-sided approach. Methods Patients with syncope were enrolled between December 2016 and December 2017. They were assigned to group A if they had a positive head-up tilt test and to group B if they presented with a pause ≥3 seconds. The area to target during cardio-neuromodulation was designed offline on a computed tomographic scan. Slow heart rates and pauses were compared during 24-hour rhythm registration at baseline, at 1-month follow-up, and 6-month follow-up. Syncope burden was assessed before the procedure and at 3- and 6-month follow-up. Results Twenty patients underwent cardio-neuromodulation through a right-sided approach (12 in group A, 8 in group B). The first application of radiofrequency energy led to a P-P interval shortening >120 ms in all 20 patients. After a mean±SD ablation time of 7±4 minutes and mean ablated surface area of 11±6 mm2, the P-P interval shortened by 219±160 ms ( P<0.001). The number of beats <50/min during 24-hour rhythm registration was reduced by a median of 100% at 6-month follow-up ( P<0.001). Syncope burden was reduced by 95% at 6-month follow-up ( P<0.001). Conclusions These data indicate that cardio-neuromodulation, through a right-sided and computed tomographic-guided procedure, is safe, fast, and highly reproducible in preventing inappropriate functional sinus bradycardia and syncope recurrence.

Adenosine-induced ventricular asystole or rapid ventricular pacing to enhance three-dimensional rotational imaging during cardiac ablation procedures.

AIMS: Rotational angiography with digital three-dimensional reconstruction (3DRA) allows per-procedural 3D imaging to facilitate cardiac ablation procedures. We developed a new approach that allows per-procedural 3D imaging of the atria and ventricles with a single C-arm rotation, combining higher 3D image quality with a lower contrast and radiation dose. METHODS AND RESULTS: Forty patients underwent 3DRA of the left atrium (LA, n = 26), right atrium (RA, n = 11), left ventricle (LV, n = 2), or right ventricle (RV, n = 1) during ablation procedures performed under general anaesthesia. Contrast agent (60 +/- 12 mL) was diluted and injected directly in the chamber of interest, during adenosine-induced ventricular asystole (n = 31) or rapid RV pacing (n = 9, atrial imaging only) to reduce cardiac motion artefacts and enhance contrast opacification during rotational imaging. Reconstructed 3D data sets were graded according to predefined quality criteria (n = 40) and quantitatively compared with cardiac computed tomography (CT) (LA, n = 14). Adenosine-induced ventricular asystole and rapid pacing both allowed a sustained and homogeneous contrast opacification of target cardiac chambers, resulting in useful 3D data sets in 39 of 40 (98%) patients. Moreover, it was possible to achieve 'good' or 'optimal' 3D image quality in the majority of patients (adenosine: 61%, pacing 78%, P = 0.69). When compared with rapid pacing, the total elimination of cardiac motion artefacts with adenosine more frequently resulted in 'optimal' 3D image quality (42% vs. 11%, P = 0.01) and added the possibility for single-rotation 3D imaging of the ventricles. Quantitative analysis showed an excellent agreement between pulmonary vein diameters measured on cardiac CT and 3DRA images. Integration of 3DRA-based LA surfaces with real-time fluoroscopy was easy and highly accurate. CONCLUSION: Adenosine-induced ventricular asystole or rapid ventricular pacing allow acquisition of 3DRA with an excellent direct contrast opacification of any cardiac chamber and a reduction of cardiac motion artefacts, resulting in high-quality per-procedural 3D imaging with a single C-arm rotation.

Novel mutation in the Per-Arnt-Sim domain of KCNH2 causes a malignant form of long-QT syndrome.

BACKGROUND: It has been proposed that the highest risk for cardiac events in patients with long-QT syndrome subtype 2 (LQT2) is related to mutations in the pore region of the KCNH2 channel. It has also been suggested that a subpopulation of LQT2 patients may benefit from pharmacological therapy with modified KCNH2 channel-blocking drugs. METHODS AND RESULTS: In a large LQT2 family (n=33), we have identified a novel nonpore missense mutation (K28E) in the Per-Arnt-Sim (PAS) domain of the KCNH2 channel associated with a malignant phenotype: One third of the suspected gene carriers experienced a major cardiac event. Wild-type and K28E-KCNH2 channels were transiently transfected in HEK293 cells. For the mutant channel, whole-cell patch-clamp analysis showed a reduced current density, a negative shift of voltage-dependent channel availability, and an increased rate of deactivation. Western blot analysis and confocal imaging revealed a trafficking deficiency for the mutant channel that could be rescued by the K+ channel blocker E-4031. In cells containing both wild-type and mutant channels, deactivation kinetics were normal. In these cells, reduced current density was restored with E-4031. CONCLUSIONS: Our data suggest that besides pore mutations, mutations in the PAS domain may also exhibit a malignant outcome. Pharmacological restoration of current density is promising as a mutation-specific therapy for patients carrying this trafficking-defective mutant.