Case report: Phosphoinositide 3-kinase inhibitor with fulvestrant in a patient with ER+/HER2- metastatic breast carcinoma induced fatal arrhythmias: a preventable event?

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was <500 and <60 ms at baseline) or choose other types of alternative treatment options. This report provided some ideas for clinicians to identify early and prevent the occurrence of fatal arrhythmias during anticancer treatment.

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Bifocal coronary sinus pacing and transcatheter tricuspid valve-in-valve implantation: an innovative combined approach.

One of the most common complications of tricuspid valve replacement is atrioventricular block (AVB), often requiring permanent pacing. The endocardial pacemaker lead, placed in the right ventricle, may sometimes interfere with the implanted prosthesis, causing its early dysfunction and the need for alternative sites of pacing. To the best of our knowledge, we present the first case of a successful combined percutaneous procedure consisting of the implantation of two leads in the coronary sinus for univentricular bifocal pacing and a transcatheter tricuspid valve-in-valve implantation in a young patient with severe dysfunction of the tricuspid bioprosthesis, requiring permanent pacing for a postsurgical complete atrioventricular block.

Tricuspid valve replacement with surgery can often lead to cardiac rhythm disorders requiring a permanent pacemaker. This device may occasionally damage the tricuspid prosthesis. We present the first case of a combined procedure of tricuspid valve replacement and device implantation distant from the prosthesis without the need for a surgical approach in a young patient with severe tricuspid prosthesis malfunctioning and permanent pacing.

Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

BACKGROUND: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes. METHODS AND RESULTS: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression. CONCLUSIONS: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.

A leadless ventricular pacemaker providing atrioventricular synchronous pacing in the real-world setting: 12-Month results from the Micra AV post-approval registry.

BACKGROUND: Advances in leadless pacemaker technology have enabled accelerometer-based atrioventricular (AV) synchronous pacing by sensing atrial mechanical contraction. OBJECTIVE: The purpose of this study was to report the performance of the Micra AV leadless pacemaker from the worldwide Micra AV post-approval registry (PAR) through 12 months. METHODS: The Micra AV PAR is a prospective, single-arm, observational registry designed to assess the safety and effectiveness of Micra AV in a real-world setting. For the present interim analysis, major complications and system revisions through 12 months were summarized and compared to a historical cohort of 2667 transvenous dual-chamber pacing patients. RESULTS: The device was successfully implanted in 796 of 801 patients (99.4%) at 97 centers in 19 countries. Micra AV patients were older (74.1 years vs 71.1 years; P < .0001) with a higher incidence of renal disease (22.3% vs 9.8%; P < .0001) compared with transvenous dual-chamber patients. Through 12 months, the major complication rate was 3.7% in Micra AV patients compared with 8.8% in transvenous dual-chamber patients (hazard ratio 0.42; 95% confidence interval 0.28-0.61; P < .001). The system revision rate was 1.5% in Micra AV patients compared with 5.5% for transvenous dual-chamber patients (hazard ratio 0.25; 95% confidence interval 0.13-0.47; P < .001); this reduction was largely driven by the absence of lead dislodgments requiring revision. The median AV synchrony index was 79.4% (interquartile range 65.2%-86.4%) in patients paced >90%. CONCLUSION: The Micra AV leadless pacemaker was implanted with a high rate of success in patients with multiple comorbidities, with a significantly lower rate of complications and system revisions through 12 months compared to a historical cohort of patients with transvenous dual-chamber pacemakers.

Second-degree atrioventricular block induced by electrical stimulation of transcranial motor-evoked potential: a case report.

BACKGROUND: Although several complications of transcranial motor-evoked potentials (Tc-MEPs) have been reported, reports of arrhythmias during Tc-MEP are very rare. CASE PRESENTATION: A 71-year-old woman underwent transforaminal lumbar interbody fusion under general anesthesia, with intraoperative Tc-MEP monitoring. Preoperative electrocardiography showed an incomplete right bundle branch block but no cardiovascular events in her life. After induction of anesthesia, Tc-MEP was recorded prior to the surgery. During the Tc-MEP monitoring, electrocardiography and arterial blood pressure showed a second-degree atrioventricular block, but it improved rapidly at the end of the stimulation, and the patient was hemodynamically stable. Tc-MEP was recorded seven times during surgery; the incidence of P waves without QRS complexes was significantly higher than before stimulation. The surgery was uneventful, and she was discharged eight days postoperatively without complications. CONCLUSIONS: Our case suggests that electrical stimulation for Tc-MEP can cause arrhythmia. Electrocardiography and blood pressure must be closely monitored during Tc-MEP monitoring.

Association between anti-SSA autoantibodies and conduction disturbances in heart failure.

BACKGROUND: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack the conduction system. However, whether autoantibodies are associated with conduction disturbances in patients with HF is unclear. OBJECTIVE: The purpose of this study was to assess whether anti-SSA, anti-Ro/Sjögren syndrome-related antigen A antibodies known for congenital atrioventricular block (AVB), is associated with conduction disturbances in patients with HF. METHODS: This retrospective observational study used data from patients with HF who were admitted to Beijing Anzhen Hospital between January 2018 and June 2022. Patients who were tested for anti-SSA and had undergone electrocardiographic examination during hospitalization were included. Conduction disturbances, including AVB, bundle branch block (BBB), and intraventricular conduction delay, were confirmed by a cardiologist blinded to anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances. RESULTS: A total of 766 patients were included in this study, of whom 70 (9.1%) were anti-SSA positive. Subjects who were anti-SSA positive showed a higher prevalence of AVB (20% vs 10.6%) and BBB (27.3 % vs 10.9 %), including both left BBB and right BBB (all P <.05). After adjusting for known risk factors, anti-SSA was independently associated with AVB (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.18-5.43; P = .03) and BBB (OR 3.15; 95% CI 1.68-5.89; P <.001). CONCLUSION: Anti-SSA is independently associated with AVB and BBB in patients with HF. Further study of the role of autoantibodies in the development of conduction abnormalities in patients with HF to generate possible targeted treatments is required.

Third-Degree Atrioventricular Block And Asystole After Lung Resection: A Rare Complication.

Surgical resection remains the optimal therapeutic option for early-stage operable NSCLC. Despite significant advances in recent years related to anesthetic and surgical techniques, cardiopulmonary complications remain major causes for postoperative morbimortality. In this paper we present a case of a patient who developed complete AV block followed by asystole after lung resection surgery. The patient underwent surgery via right VATS and the procedure was uneventful.  On the first post-operative day patient developed a third-degree atrioventricular block followed by 6 seconds asystole. Pharmacological treatment was instituted and implementation of a permanent pacemaker occurred on the third post-operative day, without complications. The remaining postoperative course was uneventful and the patient was discharged home on the sixth post-operative day. It is the objective of the authors to report and highlight this rare and potencial fatal complication of lung resection.

Comparison of Global Longitudinal Strain in Dual-chamber versus Ventricular Pacemaker in Complete Heart Block.

Context: Bradycardia caused by total atrioventricular block (TAVB) is treated by implantation of permanent pacemakers (PPMs) in either dual-chamber (DDD) versus ventricular (VVI) pacing modes. DDD is considered a more physiological pacing mode than VVI as it avoids atrioventricular dyssynchrony. However, previous trials have failed to demonstrate the superiority of DDD in improving quality of life and morbidity. Aims: This study aims to provide postpacemaker function of the left ventricle (LV) measured with global longitudinal strain (GLS), in TAVB patients. Settings and Design: This is a comparative study; samples included in the study are adult TAVB patients undergoing PPM implantation, without significant heart function, and structural abnormality. Echocardiographic parameters are obtained before, after 1 month, and after 3 months post-PPM. Subjects and Methods: A total of 98 TAVB patients undergoes PPM implantation during the study period, 55 patients were excluded, and in the end, only 43 patients fulfill the inclusion criteria. Statistical Analysis Used: Baseline data between DDD and VVI are compared using unpaired t-test. Statistical significance 1 month post-PPM and 3 months post-PPM is analyzed using paired t-test. Results: There were no significant differences between both groups at baseline. However, significant GLS changes are observed 1 month after PPM in the VVI group (P = 0.002), but no significant change was observed in the DDD group even after 3 months (P = 0.055). Conclusions: In our study, we conclude that DDD is superior in maintaining LV function in the short term in TAVB patients after PPM implantation.

Clinical analysis of temporary pacemaker implantation in 6 children with fulminant myocarditis.

BACKGROUND: There is little literature on the use of temporary pacemakers in children with fulminant myocarditis. Therefore, we summarized the use of temporary cardiac pacemakers in children with fulminant myocarditis in our hospital. METHODS: The clinical data of children with fulminant myocarditis treated with temporary pacemakers in Wuhan Children's Hospital from January 2017 to May 2022 were retrospectively analyzed. RESULTS: A total of 6 children were enrolled in the study, including 4 boys and 2 girls, with a median age of 50 months and a median weight of 15 kg. The average time from admission to pacemaker placement was 2.75 ± 0.4 h. The electrocardiogram showed that all 6 children had third-degree atrioventricular block (III°AVB). The initial pacing voltage, the sensory sensitivity of the ventricle and the pacing frequency were set to 5-10 mV, 5 V and 100-120 bpm respectively. The sinus rhythm was recovered in 5 patients within 61 h (17-134) h, and the median time of using temporary pacemaker was 132 h (63-445) h. One of the children had persistent III°AVB after the temporary pacemaker. With parental consent, the child was fitted with a permanent pacemaker on the 12th day of his illness. CONCLUSIONS: When fulminant myocarditis leads to severe bradycardia or atrioventricular block in children, temporary pacemakers have the characteristics of high safety to improve the heart function.

Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Clinical/electrophysiologic characteristics of infranodal Wenckebach in patients with indication for permanent ventricular pacing: A prospective study.

BACKGROUND: Infranodal Wenckebach is rare and not well characterized. OBJECTIVE: We prospectively studied clinical and electrophysiologic characteristics of patients with atrioventricular (AV) Wenckebach with an indication for permanent ventricular pacing. METHODS: During a 2-year period, all patients with an indication for permanent ventricular pacing underwent targeted preimplantation electrophysiologic study. Clinical and electrophysiologic characteristics at presentation and ventricular pacing percentage at 6-month follow-up were evaluated. RESULTS: A total of 163 patients (median age, 68 [interquartile range, 60-74] years; male, 59%; median QRS duration, 110 [90-130] ms; complete AV block in 123 [75.5%]) were included. AV Wenckebach was noted in 22 (13.4%) patients (median age, 70 [63-76.5] years; male, 54%; median QRS duration, 120 [110-140] ms) and classified as infranodal (12/163 [7.3%]) vs AV nodal (10/163 [6.1%]). Patients with infranodal Wenckebach (infrahisian in all), compared with AV nodal Wenckebach, demonstrated higher frequency with left ventricular ejection fraction ≤40% (41.7% vs 0%; P = .04), longer median HV interval (90 vs 49 ms; P = .005), lower frequency of isolated first-degree AV block (8.3% vs 60%; P = .02), higher frequency of right bundle branch block with left anterior fascicular block (75% vs 10%; P = .003), lesser PR increment at onset of AV Wenckebach (20.5 vs 80 ms; P = .002), and onset of 2:1 AV block at longer cycle lengths (91.7% vs 20%; P = .002). CONCLUSION: Of patients referred for pacemaker implantation, infranodal Wenckebach was present in 27.5% (11/40) without complete AV block. It was as frequent as AV nodal Wenckebach and associated with characteristic electrophysiologic findings.

New-onset atrial high-rate episodes in left bundle branch area pacing versus right ventricular pacing for patients with atrioventricular block.

BACKGROUND: Left bundle branch area pacing (LBBAP) demonstrated beneficial effects on clinical outcomes. Comparative data on the risk of atrial high-rate episodes (AHREs) between LBBAP and right ventricular pacing (RVP) are lacking. AIMS: This study aimed to investigate whether LBBAP can reduce the risk of new-onset AHREs compared with RVP in patients with atrioventricular block (AVB). METHODS: We enrolled 175 consecutive AVB patients with no history of atrial fibrillation undergoing dual-chamber pacemaker implantation (LBBAP or RVP). Propensity score matching for baseline characteristics yielded 43 matched pairs. The primary outcome was new-onset AHREs detected on a scheduled device follow-up. Changes in echocardiographic measurements were also compared between the groups. RESULTS: New-onset AHREs occurred in 42 (24.0%) of all enrolled patients (follow-up 14.1 [7.5] months) and the incidence of new-onset AHREs in the LBBAP group was lower than in the RVP group (19.8% vs. 34.7%; P = 0.04). After propensity score matching, LBBAP still resulted in a lower incidence of new-onset AHREs (11.6% vs. 32.6%; P = 0.02), and a lower hazard ratio for new-onset AHREs compared with RVP (HR, 0.274; 95% CI, 0.113-0.692). At 1 year, LBBAP achieved preserved left ventricular ejection fraction (LVEF) (63.0 [3.2]% to 63.1 [3.1]%; P = 0.56), while RVP resulted in reduced LVEF (63.4 [4.9]% to 60.5 [7.3]%; P = 0.01]). Changes in LVEF were significantly different between the 2 groups (by 2.6% [0.2 to 5.0]%; P = 0.03). CONCLUSION: LBBAP demonstrated a reduced risk of new-onset AHREs compared with RVP in patients with AVB.