Multicenter experience with andexanet alfa for refractory pericardial bleeding during catheter ablation of atrial fibrillation.

INTRODUCTION: Pericardial bleeding is a rare but life-threatening complication of atrial fibrillation (AF) ablation. Patients taking uninterrupted oral anticoagulation (AC) may be at increased risk for refractory bleeding despite pericardiocentesis and administration of protamine. In such cases, andexanet alfa can be given to reverse rivaroxaban or apixaban. In this study, we aim to describe the rate of acute hemostasis and thromboembolic complications with andexanet for refractory pericardial bleeding during AF ablation. METHODS AND RESULTS: In this multicenter, case series, participating centers identified patients who received a dose of apixaban or rivaroxaban within 24 h of AF ablation, developed refractory pericardial bleeding during the procedure despite pericardiocentesis and administration of protamine and received andexanet. Eleven patients met inclusion criteria, with mean age of 73.5 ± 5.3 years and median CHA2 DS2 -VASc score 4 [3-5]. All patients received protamine and pericardiocentesis, and 9 (82%) received blood products. All patients received a bolus of andexanet followed, in all but one, by a 2-h infusion. Acute hemostasis was achieved in eight patients (73%) while three required emergent surgery. One patient (9%) experienced acute ST-elevation myocardial infarction after receiving andexanet. Therapeutic AC was restarted after a mean of 2.2 ± 1.9 days and oral AC was restarted after a mean of 2.9 ± 1.6 days, with no recurrent bleeding. CONCLUSION: In patients on uninterrupted apixaban or rivaroxaban, who develop refractory pericardial bleeding during AF ablation, andexanet can achieve hemostasis thereby avoiding the need for emergent surgery. However, there is a risk of thromboembolism following administration.

Determinants of Response to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a well-established treatment modality for ambulatory patients with heart failure (HF) who have prolonged QRS, left bundle branch block, reduced left ventricular (LV) ejection fraction, and New York Heart Association class II-IV. CRT has been shown to induce reverse LV remodeling and improve HF symptoms and clinical outcomes. About one-third of CRT recipients are considered non-responders. Patient selection, LV lead location, LV lead selection, multipoint pacing, and optimization of the atrioventricular and ventriculo-ventricular intervals were all shown to be associated with a better CRT response rate. Herein, we review the determinants of CRT response.

Focal Atrial Tachycardia Arising From the Posterior Wall of the Left Atrium.

Potential foci for atrial tachycardia have been previously described in various locations including crista terminalis, tricuspid annulus, coronary sinus ostium, pulmonary vein ostia. In this report, we present a case of a focal atrial tachycardia arising from the posterior wall of the left atrium which has not been described before. (Level of Difficulty: Advanced.).

Novel Use of a Rotating Mechanical Dilator Sheath for S-ICD Lead Extraction.

A 53-year-old man with a subcutaneous implantable cardioverter-defibrillator (S-ICD) presented with inappropriate shocks. He underwent device extraction, and the lead was freed using a rotating mechanical dilator sheath. As patients with S-ICDs get older, extractions will become more complicated and more common. We have described a novel method of S-ICD lead extraction. (Level of Difficulty: Advanced.).

Various Manifestations of 5-Fluorouracil Cardiotoxicity: A Multicenter Case Series and Review of Literature.

5-Fluorouracil is a key element to the treatment of colon cancer. But it is also one of the most cardiotoxic chemotherapies, and the management of those that experience cardiotoxicity can be challenging. We present three cases of 5-FU cardiac toxicity that manifested as myocardial infarction, cardiogenic shock, and ventricular fibrillation. Additionally, we discuss the current literature regarding 5-fluorouracil cardiotoxicity mechanisms as well as management.

Correlation of right atrial enlargement on ECG to right atrial volume by echocardiography in patients with pulmonary hypertension.

Previous attempts to validate ECG criteria for right atrial (RA) enlargement (RAE) have been limited by sample sizes and lack of accepted standards for measuring RA size. New guidelines have recommended that RA volume (RAV) be used to determine RA size. Since these guidelines were released, no studies have been published that correlate RAE by ECG to RAV using the new standards. We aimed to validate previously proposed ECG criteria for RAE, commonly called P pulmonale, and to establish whether a correlation exists between P wave amplitudes and RAV as determined by echocardiogram in patients from the pulmonary hypertension (PHT) clinic. We identified patients from the PHT clinic that had an echocardiogram and ECG done at most 30days apart. We defined increased P wave amplitude as ≥2mm in lead II and ≥1mm in lead V1. The RA was determined to be enlarged if the RAV index (RAVI) was ≥39mL/m2 for men and ≥33mL/m2 for women. Patients were stratified into four groups: those with P II≥2mm, those with P V1≥1mm, those that met both criteria, and those that met neither. Right atrial volumes were then compared. Sixty-three patients were included in the study (7 men, 56 women). Three men and 36 women had an ECG that met criteria for P pulmonale. Five men and 28 women had an enlarged RA on echocardiogram. Sixty-nine percent of ECGs that met criteria for RAE were associated with increased RAV by echocardiogram. The specificity of each of the ECG criteria for P pulmonale at detecting RAE was 100% for men. The criterion with the highest specificity among women was P II≥2mm AND P V1≥1mm (94%). The least specific criterion for women was P II≥2mm (70%). The sensitivity of each criterion was much lower. The most sensitive criteria for men and women were P V1≥1mm (66.6%) and P II≥2mm (48%), respectively. The correlation of P wave amplitude in leads II and V1 and RAVI was not statistically significant for any of the ECG criteria for P pulmonale. In patients from the PHT clinic, the specificity of P pulmonale for detecting RAE is high, but the sensitivity is relatively low. These results suggest that in PHT, P pulmonale can be used to confirm that the RA is enlarged, but it is not a reliable test for diagnosing RAE.

A novel behavioral paradigm to assess multisensory processing in mice.

Human psychophysical and animal behavioral studies have illustrated the benefits that can be conferred from having information available from multiple senses. Given the central role of multisensory integration for perceptual and cognitive function, it is important to design behavioral paradigms for animal models to provide mechanistic insights into the neural bases of these multisensory processes. Prior studies have focused on large mammals, yet the mouse offers a host of advantages, most importantly the wealth of available genetic manipulations relevant to human disease. To begin to employ this model species for multisensory research it is necessary to first establish and validate a robust behavioral assay for the mouse. Two common mouse strains (C57BL/6J and 129S6/SvEv) were first trained to respond to unisensory (visual and auditory) stimuli separately. Once trained, performance with paired audiovisual stimuli was then examined with a focus on response accuracy and behavioral gain. Stimulus durations varied from 50 ms to 1 s in order to modulate the effectiveness of the stimuli and to determine if the well-established "principle of inverse effectiveness" held in this model. Response accuracy in the multisensory condition was greater than for either unisensory condition for all stimulus durations, with significant gains observed at the 300 ms and 100 ms durations. Main effects of stimulus duration, stimulus modality and a significant interaction between these factors were observed. The greatest behavioral gain was seen for the 100 ms duration condition, with a trend observed that as the stimuli became less effective, larger behavioral gains were observed upon their pairing (i.e., inverse effectiveness). These results are the first to validate the mouse as a species that shows demonstrable behavioral facilitations under multisensory conditions and provides a platform for future mechanistically directed studies to examine the neural bases of multisensory integration.

Impaired spatial memory in APP-overexpressing mice on a homocysteinemia-inducing diet.

Consumption of a diet that significantly elevates homocysteine (homocysteinemia) induces cell death in the CA3 hippocampal subfield in amyloid precursor protein (APP) over-expressing transgenic mice but not in wild-type controls. We assessed behavioral and other neuropathological effects of a homocysteinemia-inducing diet in aged APP-overexpressing mice. Starting at 16-18 months of age, mice were fed either a treatment diet lacking folate, choline, and methionine, and supplemented with homocysteine, or a control diet containing normal amounts of folate, choline and methionine but no homocysteine. After 5 months on the experimental diets, performance on a delayed non-matching-to-position working-memory task was unimpaired. In contrast, spatial reference memory in the water maze was impaired in transgenic mice on the treatment diet. Transgenic mice had higher homocysteine levels than wild-type mice even when fed the control diet, suggesting an effect of genotype on homocysteine metabolism. Methyl-donor deficiency did not alter amyloid deposition in the transgenic mice. These results suggest that disrupted homocysteine metabolism may induce Abeta-associated memory impairments and neurodegeneration in APP overexpressing mice.

Cooperative synchronized assemblies enhance orientation discrimination.

There is no clear link between the broad tuning of single neurons and the fine behavioral capabilities of orientation discrimination. We recorded from populations of cells in the cat visual cortex (area 17) to examine whether the joint activity of cells can support finer discrimination than found in individual responses. Analysis of joint firing yields a substantial advantage (i.e., cooperation) in fine-angle discrimination. This cooperation increases to more considerable levels as the population of an assembly is increased. The cooperation in a population of six cells provides encoding of orientation with an information advantage that is at least 2-fold in terms of requiring either fewer cells or less time than independent coding. This cooperation suggests that correlated or synchronized activity can increase information.

Cooperation between area 17 neuron pairs enhances fine discrimination of orientation.

We examined 66 complex cells in area 17 of cats that were paralyzed and anesthetized with propofol and N2O. We studied changes in ensemble responses for small (<10 degrees ) and large (>10 degrees ) differences in orientation. Examination of temporal resolution and discharge history revealed advantages in discrimination from both dependent (e.g., synchronization) and independent (e.g., bursting) interspike interval properties. For 27 pairs of neurons, we found that the average cooperation (the advantage gained from the joint activity) was 57.6% for fine discrimination of orientation but <5% for gross discrimination. Dependency (probabilistic quantification of the interaction between the cells) was measured between 29 pairs of neurons while varying orientation. On average, the dependency tuning for orientation was 35.5% narrower than the average firing rate tuning. The changes in dependency around the peak orientation (at which the firing rate remains relatively constant) lead to substantial cooperation that can improve discrimination in this region. The narrow tuning of dependency and the cooperation provide evidence to support a population-encoding scheme that is based on biologically plausible mechanisms and that could account for hyperacuities.