Reconciling Differences between Lipid Transfer in Free-Standing and Solid Supported Membranes: A Time-Resolved Small-Angle Neutron Scattering Study.

Maintaining compositional lipid gradients across membranes in animal cells is essential to biological function, but what is the energetic cost to maintain these differences? It has long been recognized that studying the passive movement of lipids in membranes can provide insight into this toll. Confusingly the reported values of inter- and, particularly, intra-lipid transport rates of lipids in membranes show significant differences. To overcome this difficulty, biases introduced by experimental approaches have to be identified. The present study addresses the difference in the reported intramembrane transport rates of dimyristoylphosphatidylcholine (DMPC) on flat solid supports (fast flipping) and in curved free-standing membranes (slow flipping). Two possible scenarios are potentially at play: one is the difference in curvature of the membranes studied and the other the presence (or not) of the support. Using DMPC vesicles and DMPC supported membranes on silica nanoparticles of different radii, we found that an increase in curvature (from a diameter of 30 nm to a diameter of 100 nm) does not change the rates significantly, differing only by factors of order ∼1. Additionally, we found that the exchange rates of DMPC in supported membranes are similar to the ones in vesicles. And as previously reported, we found that the activation energies for exchange on free-standing and supported membranes are similar (84 and 78 kJ/mol, respectively). However, DMPC's flip-flop rates increase significantly when in a supported membrane, surpassing the exchange rates and no longer limiting the exchange process. Although the presence of holes or cracks in supported membranes explains the occurrence of fast lipid flip-flop in many studies, in defect-free supported membranes we find that fast flip-flop is driven by the surface's induced disorder of the bilayer's acyl chain packing as evidenced from their broad melting temperature behavior.

Maximal electrogram attenuation recorded from mini electrodes embedded on 4.5-mm irrigated and 8-mm nonirrigated catheters signifies lesion maturation.

BACKGROUND: The electrograms (EGMs) recorded from mini electrodes (ME) placed on the tip of the ablation electrode allow more precise EGM monitoring during lesion formation. Our objective was to define the lesion boundaries and extracardiac injuries resulting from 60-second RF application versus RF application time titrated to maximal attenuation of the ME EGM in the atria and ventricles using 4.5-mm irrigated and 8-mm catheters. METHODS: RF lesions were placed in both atria and ventricles in 13 (30-35 kg) canines; 6 (4.5-mm OI) and 7 (8 mm). The RF application time was fixed at 60 seconds or terminated at maximal ME EGM amplitude attenuation. RESULTS: Pre/postablation pacing thresholds, EGM amplitudes, and lesion dimensions were not significantly different between maximal EGM attenuation and 60-second RF application using either catheter. Atrial lesion transmurality was also similar for both catheters and groups 91.2% (4.5 mm) and 96% (8 mm) when the RF was titrated to the maximal EGM attenuation and 94.2% (4.5 mm) and 95% (8 mm) with 60-second RF. The 60-second RF ablation, however, presented with significant extracardiac injuries to the lungs and esophagus, along with char formation. Deep ventricular lesions were noted with maximal EGM attenuation that were not different from the 60-second RF ablation. CONCLUSION: Titration of the RF application time to the maximal EGM attenuation based on the ME recordings represents atrial lesion maturation and deep ventricular lesions. Prolonging the RF application results in greater extracardiac injury and char formation without increasing lesion size.

Radiation-associated Arrhythmias: Putative Pathophysiological Mechanisms, Prevalence, Screening and Management Strategies.

Radiation-associated cardiovascular disease, an increasingly recognised disease process, is a significant adverse effect of radiation therapy for common malignancies that involve the chest, and include lymphomas, lung, mediastinal and breast cancers. Two factors contribute to the increasing incidence of radiation-associated cardiovascular disease: advances in malignancy detection and the improved survival of cancer patients, by which many symptoms of radiation-associated cardiovascular disease, specifically radiation-associated arrhythmias, present years and/or decades following initial radiotherapy. We present a focused overview of the currently understood pathophysiology, prevalence and management strategies of radiation-associated arrhythmias, which include bradyarrhythmias, tachyarrhythmias and autonomic dysfunction.

Comparison of quantifiable electrocardiographic changes associated with severe hyperkalemia.

BACKGROUND: Hyperkalemia (HK) is a life-threatening condition that is frequently evaluated by electrocardiogram (ECG). ECG changes in severe HK (≥ 6.3 mEq/L) are not well-characterized. This study sought to compare and correlate ECG metrics in severe HK to baseline normokalemic ECGs and serum potassium. METHODS: A retrospective analysis of 340 severe HK encounters with corresponding normokalemic ECGs was performed. RESULTS: Various ECG metrics were analyzed. P wave amplitude in lead II, QRS duration, T wave slope, ratio of T wave amplitude: duration, and ratios of T wave: QRS amplitudes were significantly different between normokalemic and HK ECGs. P wave amplitude attenuation in lead II correlated better with serum potassium than in V1. T wave metrics that incorporated both T wave and QRS amplitudes correlated better than metrics utilizing T wave metrics alone. CONCLUSION: Multiple statistically significant and quantifiable differences among ECG metrics were observed between normokalemic and HK ECGs and correlated with increasing degrees of serum potassium and along the continuum of serum potassium. When incorporated into a logistic regression model, the ability to distinguish HK versus normokalemia on ECG improved significantly. These findings could be integrated into an ECG acquisition system that can more accurately identify severe HK.

Echocardiographic changes and heart failure hospitalizations following rhythm control for arrhythmia-induced cardiomyopathy: results from a multicenter, retrospective study.

BACKGROUND: The incidence and prevalence of arrhythmia-induced cardiomyopathy (AIC) are unclear but likely underrecognized. LV dysfunction is common among patients with atrial fibrillation (AF), atrial flutter (AFL), and frequent premature ventricular contractions (PVC). The hallmark of AIC is the improvement of left ventricular ejection fraction (LVEF) following arrhythmia treatment. Changes in echocardiographic parameters and their effect on outcomes after rhythm control for AIC are not well understood. We aimed to study echocardiographic parameters and outcomes following rhythm control for AIC. METHODS: A multicenter, retrospective study was conducted at 4 different medical centers involving patients with AIC. Clinical, echocardiographic, and outcome (mortality and heart failure hospitalizations [HFH]) parameters were extracted from the medical record. RESULTS: Two hundred fifty-five patients (age 66 ± 11 years, 73% male) with AIC caused by AF (51%), atrial tachycardia/AFL (20%), and PVCs (29%) were included and followed for a median period of 6 months after successful rhythm control. Significant improvements in left ventricular (LV) ejection fraction (P < 0.0001), LV end-systolic volume (ml) (90 ± 48 to 58 ± 30; P < 0.0001), LV internal diameter end diastole (cm) (5.5 ± 0.78 to 5.3 ± 0.64; P = 0.0001) and end systole (4.7 ± 0.95 to 4.3 ± 1.02; P < 0.0001), right atrial pressure (mmHg) (11.3 ± 5.0 to 7.4 ± 3.2; P = 0.0001), and right ventricular function (n (%)) (42 (44) to 9 (11); P < 0.0001) were noted following arrhythmia treatment. No deaths occurred during follow-up. HFH occurred in 7 patients. Arrhythmia recurrence rate was 50.5%. Neither echocardiographic parameters nor recurrence of arrhythmia correlated with HFH. CONCLUSION: Arrhythmia treatment significantly improved echocardiographic LV dimensions, LVEF, and RAP in this multicenter AIC cohort, underscoring the need for early recognition and aggressive rhythm control in suspected AIC patients. The event rate was too low to assess for outcome predictors.

Drug Interactions Affecting Antiarrhythmic Drug Use.

Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.

Percutaneous repair of post-myocardial infarction ventricular septal rupture presenting with cardiogenic shock.

Ventricular septal rupture (VSR) is an uncommon and devastating complication with a high mortality rate due to limited available interventions required by expert hands in a small window of opportunity. Most commonly seen following delayed myocardial infarctions (MI), the rate of VSR has decreased partly from protocol driven reperfusion therapy; however, cases are still present, particularly when diagnosis is delayed. We present a case of a critically ill patient in cardiogenic shock following a large anterolateral wall ST-elevation MI complicated by a large VSR whom was transferred to our academic institution for percutaneous repair. Of note, such intervention was initially performed by Lock in 1988 and a comprehensive review published in 2016 noted only 273 such cases. This review noted patient cases since that initial percutaneous closure by Lock with a majority of cases utilizing an Amplatzer system; others being Clamshell and CardioSEAL. Our patient underwent the percutaneous VSR closure utilizing an Amplatzer Occluder delivery system with successful insertion of an 18 mm muscular VSD Amplatzer closure device. Although the rarely performed procedure was successful and provided invaluable insights into the treatment and management of VSR, the patient succumbed to multiple critical disease processes in the following days post intervention. Patient consent and ethics committee approval for publication, as per Saint Louis University case publication guidelines, were confirmed and approved.

Relationship between lesion formation and electrophysiological responses using catheters equipped with mini-electrodes in chronic atrial fibrillation.

BACKGROUND: The study focuses on the electrophysiological changes associated with lesion formation using 4.5-mm irrigated and 8-mm standard catheters equipped with mini-electrodes (MEs) positioned circumferentially on the tip. OBJECTIVE: The aim of the study was to test the relationship between the maximal electrogram (EGM) reduction, frequency spectrum shift, and their impact on atrial lesion formation in the atrial fibrillation (AF) model. Furthermore, we hypothesize that the high fidelity recording from the MEs allows improved discrimination of ablated tissues from nonablated tissues. METHODS: Under fluoroscopic and NavX guidance, atrial ablation lesions were placed in 4 canines in chronic AF (>12 months in AF) to achieve intercaval, cavotricuspid isthmus, and left atrial contiguous lesions. Lesion times were titrated to the maximal loss of EGM amplitude as recorded from the MEs. Radiofrequency (RF) lesions were sequentially connected on the basis of the ME recordings of tissue viability. RESULTS: In lesions formed using a 4.5-mm irrigated catheter (172 lesions) and in those formed using an 8-mm catheter (155 lesions), the time to nadir of the EGM reduction was 22 ± 12 and 22 ± 9 seconds (NS:p>0.05). Contiguous transmural lesions were successfully placed and guided by the ME EGMs and confirmed by frequency spectra. CONCLUSION: In the chronic AF model, EGM reduction and frequency spectrum shift recorded from the MEs are twice the reduction recorded using the 4.5mm and 8mm tip to ring electrodes. RF titration based on the maximal EGM diminution is an effective approach to monitor lesion formation and may improve safety by preventing unnecessarily prolonged RF application. The ME EGM recording greatly facilitates placement of contiguous transmural linear lesions.