The aim of this double-blind, randomized, sham-controlled study was to verify the blood pressure (BP)-lowering efficacy of externally delivered focused ultrasound for renal denervation (RDN). Nonrandomized, first proof-of-concept study and experimental evidence suggested that noninvasive techniques of RDN emerged as an alternative approach of RDN to invasive technologies. WAVE IV, an international, randomized (1 : 1) sham-controlled, double-blind prospective clinical study, was prematurely stopped. Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP was at least 135 mmHg, while taking three or more antihypertensive medications. The treatment consisted of bilateral RDN using therapeutic levels of ultrasound energy and the sham consisted of bilateral application of diagnostic levels of ultrasound energy. In the 81 treated patients neither changes in office BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up visit differed between the two groups significantly. Of note, no safety signal was observed. Adherence analysis disclosed full adherence in 77% at baseline and 82% at 6 months’ follow-up visit. Post hoc analysis revealed that stricter criteria for stabilization of BP at baseline were associated with a numerically greater change in 24-h ambulatory BP in the RDN group than in the sham group. Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.

Electro-anatomical mapping may be critical to identify atrial fibrillation (AF) subjects who require substrate modification beyond pulmonary vein isolation (PVI). The objective was to determine correlations between pre-ablation mapping characteristics and 12-month outcomes after a single PVI-only catheter ablation of AF. This study enrolled paroxysmal AF (PAF), early persistent AF (PsAF; 7 days–3 months), and non-early PsAF (>3–12 months) subjects undergoing de novo PVI-only radiofrequency catheter ablation. Sinus rhythm (SR) and AF voltage maps were created with the Advisor HD Grid™ Mapping Catheter, Sensor Enabled™ for each subject, and the presence of low-voltage area (LVA) (low-voltage cutoffs: 0.1–1.5 mV) was investigated. Follow-up visits were at 3, 6, and 12 months, with a 24-h Holter monitor at 12 months. A Cox proportional hazards model identified associations between mapping data and 12-month recurrence after a single PVI procedure. The study enrolled 300 subjects (113 PAF, 86 early PsAF, and 101 non-early PsAF) at 18 centres. At 12 months, 75.5% of subjects were free from AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence. Univariate analysis found that arrhythmia recurrence did not correlate with AF diagnosis, but LVA was significantly correlated. Low-voltage area (28% of the left atrium in SR [hazard ratio (HR): 4.82, 95% confidence interval (CI): 2.08–11.18; P = 0.0003] and >72% in AF (HR: 5.66, 95% CI: 2.34–13.69; P = 0.0001) was associated with a higher risk of AF/AFL/AT recurrence at 12 months. Larger extension of LVA was associated with an increased risk of arrhythmia recurrence. These subjects may benefit from substrate modification beyond PVI.

Introduction: Pulsed field ablation (PFA) exploits the delivery of short high-voltage shocks to induce cells death via irreversible electroporation. The therapy offers a potential paradigm shift for catheter ablation of cardiac arrhythmia. We designed an AC-burst generator and therapeutic strategy, based on the existing knowledge between efficacy and safety among different pulses. We performed a proof-of-concept chronic animal trial to test the feasibility and safety of our method and technology.Methods: We employed 6 female swine – weight 53.75 ± 4.77 kg – in this study. With fluoroscopic and electroanatomical mapping assistance, we performed ECG-gated AC-PFA in the following settings: in the left atrium with a decapolar loop catheter with electrodes connected in bipolar fashion; across the interventricular septum applying energy between the distal electrodes of two tip catheters. After procedure and 4-week follow-up, the animals were euthanized, and the hearts were inspected for tissue changes and characterized. We perform finite element method simulation of our AC-PFA scenarios to corroborate our method and better interpret our findings.Results: We applied square, 50% duty cycle, AC bursts of 100 μs duration, 100 kHz internal frequency, 900 V for 60 pulses in the atrium and 1500 V for 120 pulses in the septum. The inter-burst interval was determined by the native heart rhythm – 69 ± 9 bpm. Acute changes in the atrial and ventricular electrograms were immediately visible at the sites of AC-PFA – signals were elongated and reduced in amplitude (p < 0.0001) and tissue impedance dropped (p = 0.011). No adverse event (e.g., esophageal temperature rises or gas bubble streams) was observed – while twitching was avoided by addition of electrosurgical return electrodes. The implemented numerical simulations confirmed the non-thermal nature of our AC-PFA and provided specific information on the estimated treated area and need of pulse trains. The postmortem chest inspection showed no peripheral damage, but epicardial and endocardial discolorations at sites of ablation. T1-weighted scans revealed specific tissue changes in atria and ventricles, confirmed to be fibrotic scars via trichrome staining. We found isolated, transmural and continuous scars. A surviving cardiomyocyte core was visible in basal ventricular lesions.Conclusion: We proved that our method and technology of AC-PFA is feasible and safe for atrial and ventricular myocardial ablation, supporting their systematic investigation into effectiveness evaluation for the treatment of cardiac arrhythmia. Further optimization, with energy titration or longer follow-up, is required for a robust atrial and ventricular AC-PFA.