Liu, Xiaoke

BACKGROUND: Radiofrequency (RF) ablation of premature ventricular complexes (PVCs) originating from the left ventricular summit may be unsuccessful, highlighting the need for alternative approaches. We aimed to assess the efficacy and safety of a novel dual-modality focal catheter in treating left ventricular summit PVCs in patients who had failed previous RF ablation. METHODS: Patients were prospectively enrolled and underwent a redo ablation procedure using an irrigated, contact-force sensing, dual-modality focal catheter (TactiFlex Duo, Abbott) under compassionate use indication. The ablation strategy, including the choice of energy modality (monopolar pulsed field [PF], RF, or both), was left to the operator’s discretion. Safety assessments included serial biomarkers, renal function, and CMR within 36 hours. Efficacy was defined as ≥80% reduction in PVC burden with symptom resolution at 3-month follow-up. RESULTS: Six consecutive patients (4 men; mean age, 53.8±15 years) with symptomatic left ventricular summit PVCs and a prior failed RF ablation (range, 1–2) were prospectively enrolled. All PVCs had an inferior axis, with a left bundle V1 morphology observed in 4 of 6 cases (mean burden, 30.1±5.3%). Acute suppression of PVCs was achieved in all cases. Acute suppression with a single PF application in the great cardiac vein-anterior interventricular vein occurred in 2 patients, while 3 patients required additional RF, PF, or combined RF+PF applications at adjacent sites. One patient with an inaccessible great cardiac vein-anterior interventricular vein was successfully treated in the left ventricular outflow tract with RF+PF application. Transient, reversible left anterior descending vasospasm was observed during PF delivery in 2 of 5 cases that underwent PF application adjacent to a coronary artery, despite pretreatment with intracoronary nitroglycerin without ECG or hemodynamic sequelae. All patients had durable suppression of PVCs at follow-up. CONCLUSIONS: In its first human application, dual-modality ablation was feasible and effective for refractory left ventricular summit PVCs. Transient coronary vasospasm occurred, though it was reversible and without acute clinical consequences.

ABSTRACT Background Optimal management in patients presenting with persistent atrial fibrillation, cardiomyopathy, and atrial as well as ventricular dyssynchrony with left bundle branch block is unclear. Results and Methods A 67‐year‐old female patient presented with persistent atrial fibrillation, cardiomyopathy with a newly reduced ejection fraction (EF), increased P wave duration on electrocardiogram (ECG) and left bundle branch block. After shared decision making, the patient elected to proceed with Bachman bundle/left bundle branch area pacing plus atrioventricular (AV) node ablation. At 6‐month follow‐up post procedure, a repeat echocardiogram showed normalized atrial size and EF (65%). Device interrogation demonstrated no recurrent atrial fibrillation with the patient off antiarrhythmic and heart failure medical therapy. Conclusions Integrated atrial and ventricular synchronization through Bachmann bundle and left bundle branch area pacing may help break the cycle of dyssynchrony, remodeling, and arrhythmia. In combination with AV node ablation, it may be considered as an alternative treatment option in certain cases after shared decision making.

Abstract Background Optimal management of checkpoint inhibitor-induced complete heart block is unknown. Previous reports showed relatively high incidence of pacing failure due to the co-existing myocarditis. Case summary A 71-year-old male with a prior history of stage IV metastatic squamous cell lung cancer presents was admitted for dyspnoea and hypotension 10 days after checkpoint inhibitor treatment using pembrolizumab. He was found to have myocarditis, third-degree AV block, severe left ventricular systolic dysfunction with EF 35%, and required pressure support. A dual chamber pacemaker using left bundle branch area pacing (LBBAP) was urgently placed that immediately improved his haemodynamics. Both the cathode and anode were able to capture the ventricle at different pacing outputs. The patient was taken off all intravenous pressors and successfully transferred to a larger centre for further management of the myocarditis with no further arrhythmia or hypotension. Discussion In conclusion, because of the unique ability to capture a large amount of myocardium from both the tip and ring electrodes as well as the ability to deliver cardiac resynchronization therapy, LBBAP may be the preferred pacing strategy in patients who develop complete heart block due to checkpoint inhibitor-induced myocarditis.

Background: Left bundle branch area pacing (LBBAP) has rapidly emerged as a promising modality of physiologic pacing and has demonstrated excellent lead stability. In this retrospective study, we evaluate whether this pacing modality can allow concomitant atrioventricular node (AVN) ablation and same-day dismissal. Methods: Twenty-four consecutive patients (female 63%, male 37%) with an average age of 78 ± 5 years were admitted for pacemaker (75%)/defibrillator (25%) implantations and concomitant AVN ablation. Device implantation with LBBAP was performed first, followed by concomitant AVN ablation through left axillary vein access to allow for quicker post-procedure ambulation. The patients were discharged on the same day after satisfactory post-ambulation device checks. Results: LBBAP was successful in 22 patients (92% in total, 20 patients had an LBBP and two patients had a likely LBBP), followed by AVN ablation from left axillary vein access (21/24, 88%). All patients had successful post-op chest x-rays, post-ambulation device checks, and were discharged on the same day. After a mean follow up of three months, no major complications occurred, such as LBBA lead dislodgement requiring a lead revision. The LBBA lead pacing parameters immediately after implantation vs. three-month follow up were a capture threshold of 0.8 ± 0.3 V@0.4 ms vs. 0.6 ± 0.3 V@0.4 ms, sensing 9.9 ± 3.9 mV vs. 10.4 ± 4.1 mV, and impedance of 710 ± 216 ohm vs. 544 ± 110 ohm. The QRS duration before and after AVN ablation was 117 ± 32 ms vs. 123 ± 14 ms. Mean LVEF before and three months after the implantation was 44 ± 14% vs. 46 ± 12%. Conclusion: LBBA pacing not only offers physiologic pacing, but also allows for a concomitant AVN ablation approach from the left axillary vein and safe same-day hospital dismissal.

Abstract Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional KATP channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is found at the end of this article.

Metabolic-sensing ATP-sensitive K+ channels (KATP channels) adjust membrane excitability to match cellular energetic demand. In the heart, KATP channel activity has been linked to homeostatic shortening of the action potential under stress, yet the requirement of channel function in securing cardiac electrical stability is only partially understood. Here, upon catecholamine challenge, disruption of KATP channels, by genetic deletion of the pore-forming Kir6.2 subunit, produced defective cardiac action potential shortening, predisposing the myocardium to early afterdepolarizations. This deficit in repolarization reserve, demonstrated in Kir6.2-knockout hearts, translated into a high risk for induction of triggered activity and ventricular dysrhythmia. Thus, intact KATP channel function is mandatory for adequate repolarization under sympathetic stress providing electrical tolerance against triggered arrhythmia.

Sepsis, the systemic inflammatory response to infection, imposes a high demand for bodily adaptation, with the cardiovascular response a key determinant of outcome. The homeostatic elements that secure cardiac tolerance in the setting of the sepsis syndrome are poorly understood. Here, in a model of acute septic shock induced by endotoxin challenge with Escherichia coli lipopolysaccharide (LPS), knockout of the KCNJ8 gene encoding the vascular Kir6.1 K ATP channel pore predisposed to an early and profound survival disadvantage. The exaggerated susceptibility provoked by disruption of this stress‐responsive sensor of cellular metabolism was linked to progressive deterioration in cardiac activity, ischemic myocardial damage, and contractile dysfunction. Deletion of KCNJ8 blunted the responsiveness of coronary vessels to cytokine‐ or metabolic‐mediated vasodilation necessary to support myocardial perfusion in the wild‐type (WT), creating a deficit in adaptive response in the Kir6.1 knockout. Application of a K ATP channel opener drug improved survival in the endotoxic WT but had no effect in the Kir6.1 knockout. Restoration of the dilatory capacity of coronary vessels was required to rescue the Kir6.1 knockout phenotype and reverse survival disadvantage in lethal endotoxemia. Thus, the Kir6.1containing K ATP channel, by coupling vasoreactivity with metabolic demand, provides a vital feedback element for cardiovascular tolerance in endotoxic shock.—Kane, G. C., Lam, C‐F., O'Cochlain, F., Hodgson, D. M., Reyes, S., Liu, X‐K., Miki, T., Seino, S., Katusic, Z. S., Terzic, A. Gene knockout of the KCNJ8encoded Kir6.1 KATP channel imparts fatal susceptibility to endotoxemia. FASEB J. 20, 2271–2280 (2006)