Long-term QT prolongation in monkeys after doxorubicin administration at doses similar to breast cancer therapy.

Background: Studies in small animals and human patients have suggested that anthracyclines may prolong cardiac repolarization, or at least inhibit repolarization reserve, predisposing to QT prolongation and dangerous arrhythmias such as Torsades de pointes. This association in humans is difficult to confirm due to multiple confounding variables such as the presence of other medications and concurrent illness. Objectives: Identify a long-term association between anthracycline administration and repolarization prolongation in nonhuman primates, which can be measured as prolonged QT/QTc intervals on surface electrocardiogram. Methods: Five female African Green monkeys (AGMs) aged 13 ± 1 years received Doxorubicin (Dox) at doses similar to women treated for breast cancer (30-60 mg/m2/biweekly IV, total cumulative dose: 240 mg/m2) and underwent 12-lead electrocardiogram (ECG) before and 15 weeks after the final dose of Dox treatment. A blinded paired analysis was performed on ECG derived heart rate (HR), QRS, QT and QT corrected for HR (QTc) interval durations. Results: After Dox, all monkeys exhibited increased QT (BL: 323.2 ± 27.4 ms vs. Post-Dox: 366.4 ± 18.7 ms, p = 0.002) and QTc (BL: 440.2 ± 22.8 ms vs. Post-Dox: 500.8 ± 22.0 ms, p = 0.009) intervals, without any significant changes in HR or QRS duration (p = 0.92 and p = 0.47 respectively). Conclusions: AGMs treated with Dox exhibited long-term QT and QTc prolongation, along with the expected cardiotoxicity (LVEF decrease). While similar findings were shown in small animal studies, confounders make human association difficult to prove. Our finding provides a valuable intermediary step, showing direct effect of Dox on repolarization in nonhuman primates.

Direct oral anticoagulants (DOAC) versus vitamin K antagonist in left ventricular thrombus: An updated meta-analysis.

Background and Aims: Current clinical guidelines for treating left ventricular thrombus (LVT) are limited by inadequate evidence to inform the comparative efficacy of oral anticoagulants. In this meta-analysis, we aimed to compare the efficacy and safety of direct oral anticoagulants (DOAC) to vitamin K antagonists (VKA) in patients with LVT. Methods: Four standard databases were searched for relevant literature comparing the efficacy and safety between DOAC and VKA for LVT treatment, published before August 19, 2023. Both the randomized controlled trials and observational studies were included in the analysis. The outcomes of interest were the resolution of LVT, all-cause mortality, stroke, systemic embolism, and bleeding. Data from the selected studies were extracted and analyzed using RevMan 5.4 using odds ratio. Results: Among 3959 studies from the database search and bibliography review, 33 were included in the analysis. LVT resolution was observed in 72.59% in the DOAC group versus 67.49% in the VKA group (odds ratio [OR]: 1.28, confidence interval [CI]: 1.07-1.53). Mortality was lower in the DOAC group (11.71% vs. 18.56%) (OR: 0.60, CI: 0.36-1.00; borderline statistical significance). Likewise, bleeding events (9.60% vs. 13.19%) (OR: 0.65, CI: 0.52-0.81) and stroke (7.54% vs. 11.04%) (OR: 0.71, CI: 0.53-0.96) were also significantly lower in the DOAC group. Conclusion: DOAC use for LVT showed better thrombus resolution and reduced risk of bleeding and stroke compared to VKA. Likewise, DOAC use was associated with lower mortality with borderline statistical significance.

Rapid atrial pacing above the maximum sensor rate: a case report.

Background: While ventricular-based timing modes are known to cause elevated atrial pacing above the lower rate when intrinsic atrioventricular (AV) conduction is shorter than programmed AV delay, there is one case report in 2015 by Jafri et al. where rapid atrial pacing was induced in an Abbott device set DDI with a lower rate of 90 by an unsensed premature atrial complex and slow intrinsic AV conduction allowing pacemaker 'crossover.' Case summary: We present a very unusual case of rapid atrial pacing at >180 b.p.m. due to a perfect storm of events that we believe has not been previously reported. A patient with a St. Jude Abbott DCPPM set DDDR had an atrial tachyarrhythmia causing a mode switch to DDIR, which uses ventricular-based timing. This was followed by a period of rapid atrial pacing that terminated spontaneously. Discussion: This phenomenon depended on an initial atrial tachyarrhythmia causing a mode switch to DDIR. In addition, the set lower rate would not have led to a short enough calculated ventriculo-atrial interval (VAI), but because rate responsive pacing was enabled, the calculated VAI was short enough to promote the crossover in setting of slow AV conduction and allow the rapid atrial pacing. Understanding this unique mechanism requires careful attention to pacemaker timing cycles and appreciation of the limitations of device programming. While it appears that a similar phenomenon was reported once in the literature, we believe that this episode of rapid atrial pacing was even more serendipitous due to the unlikely series of events required for its inception.

Arrhythmia Following Pulse Generator Change: What Is the Mechanism?

We present an unusual case of a "reverse" pacemaker-mediated endless loop arrhythmia with native atrioventricular conduction serving as the anterograde limb of the tachycardia circuit and the atrial depolarization stimulated by the pacemaker in response to the sensed ventricular QRS. The electrocardiogram findings can be explained by lead reversal in the header during pulse generator change, with the ventricular lead connected to the atrial port and the atrial lead connected to the ventricular port. Careful examination of the electrocardiogram with attention to the 2 closely spaced pacing stimuli separated by the paced atrioventricular delay provided an important clue for diagnosis this case.

Prevention and Treatment of Atrioesophageal Fistula Related to Catheter Ablation for Atrial Fibrillation.

Atrioesophageal fistula (AEF) is an uncommon but devastating complication of catheter ablation for atrial fibrillation. Even with appropriate recognition and treatment, mortality is greater than 30% in most studies. If AEF is suspected, it is essential to avoid endoscopy and to order immediate cross-sectional imaging. If the diagnosis is confirmed, a thoracic surgeon should be promptly notified and must assess the patient urgently. The prognosis for AEF is poor even if it is appropriately recognized and addressed, so prevention must be a high priority. Prevention of AEF should involve the use of low-risk and cost-effective measures during ablation, which may increase safety, efficacy, or both. These strategies may include conscious sedation (as opposed to general anesthesia), low-power ablation, low-flow irrigation, short-duration lesions, esophageal temperature measurement, esophageal deviation, and pharmacologic prophylaxis with proton pump inhibitors or histamine H2 receptor blockers. Multiple new technologies are now becoming available, which may further reduce esophageal injury. Proceduralists should be aware of the available techniques and equipment that may help to reduce the risk of AEF, while simultaneously considering the possibility of unintended consequences.