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The objective of this preclinical study was to evaluate the feasibility and safety of transcatheter endocardial alginate hydrogel injection (TEAi) in a large animal model, utilizing the high-stiffness XDROP® alginate hydrogel in combination with the dedicated EndoWings® catheter-based system. All swine (n = 9) successfully underwent TEAi without complications. Acute results from a subset of animals (n = 5) demonstrated the ability of the catheter to access a wide range of endomyocardial areas and achieve consecutive circumferential hydrogel distribution patterns within the mid-left ventricular wall. Histological examinations at 6 months (n = 4) demonstrated that the XDROP® remained localized within the cardiac tissue. In addition, serial echocardiographic imaging showed that XDROP® had no adverse impacts on LV systolic and diastolic functions. In conclusion, this innovative combination technology has the potential to overcome the translational barriers related to alginate hydrogel delivery to the myocardium. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does left atrial appendage ligation improve catheter ablation treatment of nonparoxysmal atrial fibrillation? Findings: In this randomized clinical trial of 610 adults, primary effectiveness was based on freedom from atrial arrhythmias at 12 months and was not statistically different between those receiving percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation and pulmonary vein isolation alone (64.3% vs 59.9%; difference, 4.3% [bayesian 95% credible interval, −4.2% to 13.2%]). Primary safety was met, with a 30-day serious adverse event rate of 3.4%. At 12 months after pulmonary vein isolation, there was complete closure in 84% of patients who underwent left atrial appendage, and 99% had less than or equal to 5 mm of residual communication with the left atrium. Meaning: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation met prespecified safety criteria, but did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone. Importance: Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation. Objective: To assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation. Design, Setting, and Participants: This multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021. Interventions: Left atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone. Main Outcomes and Measures: A bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation. Results: Overall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, −4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients. Conclusions and Relevance: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT02513797 This multicenter randomized clinical trial examines the effectiveness and safety of left atrial appendage ligation plus pulmonary vein isolation for nonparoxysmal atrial fibrillation treatment. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a growing health problem that increases morbidity and mortality, and in most patients progresses to more advanced diseases over time. Recent research has examined the underlying mechanisms, risk factors, and progression of AF, leading to updated AF disease classification schemes. Although endocardial catheter ablation is effective for early-stage paroxysmal AF, it consistently achieves suboptimal outcomes in patients with advanced AF. Identification of the factors that lead to the increased risk of treatment failure in advanced AF has spurred the development and adoption of hybrid ablation therapies and collaborative heart care teams that result in higher long-term arrhythmia-free survival. Patients with non-paroxysmal AF, atrial remodeling, comorbidities, or AF otherwise deemed difficult to treat may find hybrid treatment to be the most effective option. Future research of hybrid therapies in advanced AF patient populations, including those with dual diagnoses, may provide further evidence establishing the safety and efficacy of hybrid endo-epicardial ablation as a first line treatment. [ABSTRACT FROM AUTHOR]

Left atrial appendage occlusion affects systemic coagulation parameters, leading to additional patient-related benefits. The aim of this study was to investigate the differences in coagulation factor changes 6 months after epicardial left atrial appendage occlusion in patients with different LAA morphometries. This is the first study to analyze these relationships in detail. A prospective study of 22 consecutive patients was performed. Plasminogen, fibrinogen, tPA concentration, PAI-1, TAFI and computed tomography angiograms were performed. Patients were divided into subgroups based on left atrial appendage body and orifice diameter enlargement. The results of blood tests at baseline and six-month follow-up were compared. In a population with normal LAA body size and normal orifice diameter size, a significant decrease in analyzed clotting factors was observed between baseline and follow-up for all parameters except plasminogen. A significant decrease between baseline and follow-up was observed with enlarged LAA body size in all parameters except TAFI, in which it was insignificant and plasminogen, in which a significant increase was observed. Occlusion of the left atrial appendage is beneficial for systemic coagulation. Patients with a small LAA may benefit more from LAA closure in terms of stabilizing their coagulation factors associated with potential thromboembolic events in the future. [ABSTRACT FROM AUTHOR]

Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (−4.18% ± 2.78%, p < 0.001) and free decorin (−3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1−/−) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3–6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct. [ABSTRACT FROM AUTHOR]

Label noise is omnipresent in the annotations process and has an impact on supervised learning algorithms. This work focuses on the impact of label noise on the performance of learning models by examining the effect of random and class-dependent label noise on a binary classification task: quality assessment for photoplethysmography (PPG). PPG signal is used to detect physiological changes and its quality can have a significant impact on the subsequent tasks, which makes PPG quality assessment a particularly good target for examining the impact of label noise in the field of biomedicine. Random and class-dependent label noise was introduced separately into the training set to emulate the errors associated with fatigue and bias in labeling data samples. We also tested different representations of the PPG, including features defined by domain experts, 1D raw signal and 2D image. Three different classifiers are tested on the noisy training data, including support vector machine (SVM), XGBoost, 1D Resnet and 2D Resnet, which handle three representations, respectively. The results showed that the two deep learning models were more robust than the two traditional machine learning models for both the random and class-dependent label noise. From the representation perspective, the 2D image shows better robustness compared to the 1D raw signal. The logits from three classifiers are also analyzed, the predicted probabilities intend to be more dispersed when more label noise is introduced. From this work, we investigated various factors related to label noise, including representations, label noise type, and data imbalance, which can be a good guidebook for designing more robust methods for label noise in future work. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that epicardial left atrial appendage closure (LAAC) is associated with several short-term neurohormonal effects. However, the long-term effects are currently unknown. Objective: To investigate the effects of percutaneous epicardial left atial appendage (LAA) exclusion using LARIAT on neurohormonal profiles at long-term follow-up. Methods: In a prospective single centre study, 60 patients with long-standing, persistent atrial fibrillation (AF) LARIAT were treated. The major hormones of the adrenergic system, renin-angiotensin-aldosterone system (RAAS), and natriuretic peptides were assessed before the intervention and at regular intervals during the following two years. Results: In patients with epicardial LAAC, atrial natriuretic peptide (ANP) levels were significantly increased from baseline at 24 h and decreased at 7 days, 1 month, and 3 months, while remaining unchanged at 12 and 24 months. Noradrenaline levels were significantly lower at 24 h, 7 days, 1 month, 6 months, 12 months, and 24 months, while epinephrine levels decreased significantly at 1 month, 6 months, 12 months, and 24 months. Plasma renin activity significantly decreased at 7 days, 1 month, 6 months, 12 months, and 24 months, while aldosterone levels significantly decreased at 6 months, 12 months, and 24 months. Endothelin-1 and vasopressin showed a significant increase and decrease, respectively, at 24 h, 7 days, 1 month, 6 months, 12 months, and 24 months. There was also a significant decrease in systolic and diastolic blood pressure at 3 months, 6 months, 1 year, and 2 years after the intervention. Conclusions: Epicardial LAAC in AF patients is associated with persistent neurohormonal changes favouring blood pressure reduction. [ABSTRACT FROM AUTHOR]

Background: Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event.Objective: To objectively ascertain whether alcohol consumption heightens risk for an AF episode.Design: A prospective, case-crossover analysis.Setting: Ambulatory persons in their natural environments.Participants: Consenting patients with paroxysmal AF.Measurements: Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events.Results: Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours.Limitation: Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population.Conclusion: Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur.Primary Funding Source: National Institute on Alcohol Abuse and Alcoholism. [ABSTRACT FROM AUTHOR]

Purpose: The left atrial appendage (LAA) is believed to be a source for thrombus formation and an ancillary structure involved in the initiation and maintenance of atrial fibrillation (AF). LAA ligation has been proposed as adjunctive therapy for the treatment of AF. This study will determine the feasibility of a percutaneous epicardial approach for LAA ligation.Methods: The pericardium of 5 dogs was accessed via percutaneous subxyphoid approach. A 20F epicardial cannula was inserted into the pericardial space and contrast-injected to visualize the LAA. Under fluoroscopic guidance, a suction cup catheter was inserted and attached to the LAA. A 12F snare device was inserted over the vacuum cup to ligate the LAA. The closure of the LAA was verified with LA angiography, in the first 2 dogs, and ICE in all 5 animals. All animals were sacrificed for post hoc assessment of LAA closure.Results: All 5 dogs underwent successful epicardial suture ligation of the LAA. In the first 2 dogs, LA angiography demonstrated complete closure of the LAA. All dogs underwent gross examination of the LAA. Post hoc assessment was notable for a small well-circumscribed hematoma on the LAA, consistent with point of suction cup attachment, as well as complete closure of the entire LAA. No laceration or perforation was noted on the LAA.Conclusions: Exclusion of the LAA via a novel percutaneous epicardial-only approach was successful without complications. This demonstrates the feasibility of this technique in an animal model, and may provide an effective approach for epicardial-only LAA exclusion in humans. [ABSTRACT FROM AUTHOR]

Purpose: Optimal stroke prevention strategies for patients with atrial fibrillation (AF) who experience a major bleed are poorly defined. We sought to estimate the effectiveness and safety of oral anticoagulation (OAC) represcription after an OAC contraindication. Methods: TREAT-AF is a retrospective cohort study of patients with newly diagnosed AF (2004–2012), treated in the Veterans Health Administration. From this cohort, we identified patients with a contraindication to OAC after AF diagnoses, defined as incident intracranial bleeding, non-intracranial bleeding requiring hospitalization, or unrepaired cerebral aneurysm or aortic dissection. We used multivariate Cox proportional hazards to estimate the association of OAC prescription in the 90 days following OAC contraindication to ischemic stroke and rebleeding. Results: Among 167,190 patients with newly diagnosed AF (70 ± 11 years, 1.7% female, CHA2DS2-VASc 2.7 ± 1.7), 19,285 patients (11.5%) had an incident bleed (n = 18,342) or an unrepaired cerebral aneurysm or aortic dissection (n = 943). For OAC-contraindicated patients with a CHA2DS2-VASc ≥2 (N = 16,194), OAC was represcribed in 4075 patients (25%) and was associated with a higher risk of non-intracranial bleeding (HR 1.49; 95% CI 1.37–1.61; p < 0.0001) but no difference in intracranial bleeding. There was a trend toward decreased stroke risk (HR 0.85; 95% CI 0.71–1.02; p 0.09). Conclusions: Development of contraindication to OAC after diagnosis of AF is common (11.5%), with most events requiring hospitalization. OAC reinitiation was associated with non-intracranial bleeding risk, with a trend toward reduced stroke risk. These data suggest that stroke prevention approaches after major bleeding events could be beneficial if bleeding risk can be successfully mitigated. [ABSTRACT FROM AUTHOR]

Background: Left atrial appendage closure (LAAC) became an alternative method for stroke prevention in patients with non‐valvular atrial fibrillation (AF) intolerant to long term oral anticoagulation therapy. This study aimed to compare endocardial (Amulet and LAmbere occluders) and epicardial (Lariat) LAAC techniques. Methods: A retrospective, observational case‐control study included 223 consecutive CHA2DS2‐VAS score–matched patients with AF who underwent LAAC in two centers. Results: There were 55 matched cases with the mean CHA2DS2‐VASs score 4.4 ± 1.22 (p = 1). Overall follow‐up was 308.2 patient‐years. The Endocardial group patients were older and more often females with congestive heart failure and peripheral vascular disease. The epicardial group more frequently had a stroke/transient ischemic attack history. There were no differences in hypertension, diabetes mellitus, and indications for procedure between both groups. The mean HAS‐BLED score was significantly higher in the endocardial group than in the epicardial group (4.3 ± 0.9 vs. 3.7 ± 1.3, p =.011). There were no differences in annual rates of thromboembolic events (2.6% vs 0.5%) and annual stroke (0.87% vs. 0%) between the endocardial and epicardial groups. Conclusion: Endocardial and Epicardial LAAC techniques show comparable implantation outcomes and safety profile and stroke prevention in patients with AF. Future randomized studies are needed to corroborate these initial results and assess long term mortality. [ABSTRACT FROM AUTHOR]

Aims: We report the collective European experience of percutaneous left atrial appendage (LAA) suture ligation using the recent generation LARIAT+ suture delivery device.Methods and Results: A total of 141 patients with non-valvular atrial fibrillation and contraindication to oral anticoagulation (OAC), thrombo-embolic events despite OAC or electrical LAA isolation were enrolled at seven European hospitals to undergo LAA ligation. Patients were followed up by clinical visits and transoesophageal echocardiography (TOE) following LAA closure. Left atrial appendage ligation was completed in 138/141 patients (97.8%). Three patients did not undergo attempted deployment of the LARIAT device due to pericardial adhesion after previous epicardial ventricular tachycardia ablation (n = 1), a pericardial access-related complication (n = 1), and multiple posterior LAA lobes (n = 1). Serious 30-day procedural adverse events occurred in 4/141 patients (2.8%). There were two device-related LAA perforations (1.4%) not resulting in any corrective intervention as the LAA was completely sealed with the LARIAT. Minor adverse events occurred in 19 patients (13.5%), including two pericardial effusions due to procedure-related pericarditis requiring pericardiocentesis. Transoesophageal echocardiography was performed after LAA ligation in 103/138 patients (74.6%) after a mean of 181 ± 72 days. Complete LAA closure was documented in 100 patients (97.1%). Two patients (1.8% of patients with follow-up) experienced a transient ischaemic attack at 4 and 7 months follow-up, although there was no leak observed with TOE. There were two deaths during long-term follow-up which were both not device related.Conclusion: Initial experience with the LARIAT+ device demonstrates feasibility of LAA exclusion. Further larger prospective studies with longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a cardiac rhythm disorder associated with increased morbidity and mortality. It is the leading risk factor for cardioembolic stroke and its early detection is crucial in both primary and secondary stroke prevention. Continuous monitoring of cardiac rhythm is today possible thanks to consumer-grade wearable devices, enabling transformative diagnostic and patient management tools. Such monitoring is possible using low-cost easy-to-implement optical sensors that today equip the majority of wearables. These sensors record blood volume variations—a technology known as photoplethysmography (PPG)—from which the heart rate and other physiological parameters can be extracted to inform about user activity, fitness, sleep, and health. Recently, new wearable devices were introduced as being capable of AF detection, evidenced by large prospective trials in some cases. Such devices would allow for early screening of AF and initiation of therapy to prevent stroke. This review is a summary of a body of work on AF detection using PPG. A thorough account of the signal processing, machine learning, and deep learning approaches used in these studies is presented, followed by a discussion of their limitations and challenges towards clinical applications. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart. Methods: Young adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-β1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells. Results: ECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role. Conclusions: ECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Human adipose-derived stem cells (hASCs) can differentiate into multiple lineages and be harvested abundantly. However, the expression of pluripotency markers, which is important for the renewal and differentiation capabilities of hASCs, decreases during monolayer culture. Increasing evidence has proven that cells aggregated to form cell spheroids in 3D cell cultures better mimic the in vivo microenvironment and can enhance the expression of stemness markers. In this study, uniform hASC spheroids were formed by seeding cells in agarose microwell plates, and the size of the spheroids could be adjusted. Most importantly, the stemness expression of the spheroids increased significantly. Additionally, we utilized microbial transglutaminase (mTG), which is an enzyme that exhibits highly specific activity over a wide range of temperature and pH, to crosslink gelatin. The enzymatic crosslinking reaction is milder than physical and chemical methods, which may lead to cell death. The properties of the gelatin/mTG hydrogel were evaluated in detail. In addition, the spheroids were encapsulated in the 3D hydrogel successfully. The results showed that the hydrogel has low toxicity to the cells, which significantly proliferated in the 3D hydrogel. Moreover, the analysis of the differentiation potential indicated that the cell spheroids in the 3D hydrogel exhibited good activity, especially adipogenesis and chondrogenesis, compared to the cell suspension group. Furthermore, the in vivo data confirmed the excellent injectability and biocompatibility of the 3D hydrogel. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial appendage closure (LAAC) with LARIAT offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation. The aim of this study was to present long-term clinical outcomes of LAAC in these patients (AF). Material and methods: A prospective, single-center study was performed in 139 patients undergoing LAAC with Lariat. Thromboembolic events, severe bleeding and mortality rate were recorded. The reduction in risk of thromboembolism and bleeding after LAAC was calculated. Results: The mean CHADS2-score was 1.8 ± 1.0, mean CHA2DS2-VASc score was 2.9 ± 1.6 and HAS-BLED score was 3.1 ± 1.1. After 428.4 patient-years of follow-up (mean 4.2±1.0 years), the thromboembolism rate was 0.6% with a calculated thromboembolism risk reduction of 81%. The severe bleeding rate was 0.8%; calculated bleeding risk reduction was 78%. The overall mortality rate was 1.6%. Conclusions: Long-term outcomes show that LAAC with Lariat is a safe and effective treatment for stroke prevention and bleeding risk reduction in AF patients with a high level of underlying risk. [ABSTRACT FROM AUTHOR]

We report the case of a 60-year-old patient who underwent orthotopic heart transplant 14 years earlier. Routine echocardiography showed giant masses in the left atrium. There were no symptoms or thromboembolic events in the past. Magnetic resonance imaging study revealed very enlarged left atrium (8.7 × 10.6 cm) occupied by irregular smooth mass (7 × 5 × 6.1 cm) with a stalk that was attached to the posterior left atrial wall in the area of graft suture lines. Intraoperative examination revealed a massive thrombus (12 × 10 cm) that filled almost the entire left atrial area. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The incidence of AF increases with age and is associated with increased stroke, heart failure and mortality. Persistent and long standing persistent AF is difficult to treat and often refractory to medical therapy and catheter ablation. Areas covered: This article reviews the historical development of the surgical Cox-MAZE procedure and current hybrid and minimally invasive surgical approaches for the treatment of persistent and long standing persistent AF. The role of concomitant pulmonary vein isolation and left atrial appendage (LAA) exclusion will also be reviewed. Expert commentary: An ablation pattern emulating the Cox-Maze surgical procedure is commonly needed to obtain maintenance of sinus rhythm in patients with persistent and long standing persistent atrial fibrillation. Minimally invasive bilateral thorascopic surgical procedures can achieve a similar Cox-Maze lesion set, but are associated with increased adverse events compared to catheter ablation. Future prospective randomized studies are required to confirm whether the recently developed hybrid subxyphoid epicardial/endocardial procedure and percutaneous LAA ligation and catheter ablation are indeed as effective as surgical options with less adverse events. [ABSTRACT FROM AUTHOR]

Background The cornerstone of atrial fibrillation (AF) ablation is isolation of the pulmonary veins (PVs). Patients with recurrent AF undergoing repeat ablation usually have PV reconnection (PVr). The ablation strategy and outcome of patients undergoing repeat ablation who have persistent isolation of all PVs (PVi) at the time of repeat ablation is unknown. Methods and results We studied consecutive patients with recurrent AF undergoing repeat ablation and compared patients with PVi to those with PVr. One hundred fifty-two patients underwent repeat ablation, and of these, 25 patients (16.4%) had PVi. Patients with PVi underwent ablation targeting any isoproterenol induced AF triggers, atrial substrate, or inducible atrial tachycardias or flutters. Patients with PVi compared to PVr were more likely to have a history of persistent AF (64% vs. 26%; P < 0.0001), obesity (BMI 30.4 vs. 28.2; P = 0.05), and prior use of contact force sensing catheters (28% vs. 0.8%, P < 0.0001). After a mean follow-up of 19 ± 15 months, 56% of PVi patients remained in sinus rhythm compared to 76.3% of PVr patients (P = 0.036). In a multivariable model, PVi patients and those with cardiomyopathy had a higher risk of recurrent atrial tachyarrhythmias (HR = 3.6 95%, CI 1.6-8.3, P = 0.002 and HR = 6.2, 95% CI 2.3-16.3, P < 0.0001, respectively). Conclusion In patients who have all PVs isolated at the time of the redo AF ablation, a strategy of targeting non-PV AF triggers and inducible flutters can still lead to AF freedom in more than half of patients. Patients with PVr, however, have a better long-term outcome. [ABSTRACT FROM AUTHOR]

Background Atrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP). Methods In paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1-S2 coupling interval without atrial capture using a 600-ms drive cycle length. Results In 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP. Conclusions The QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aims: AUGMENT-HF was an international, multicentre, prospective, open-label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow-up. This report presents the results from 1 year of extended follow up for this clinical trial. Methods and Results: We enrolled 78 patients with advanced HF, randomized (1:1), to Algisyl with SMT or SMT alone as previously reported. Patient inclusion criteria were LVEF ≤35%, peak VO2 of 9.0-14.5 mL/min/kg and LV end-diastolic diameter (LVEDD) index 30-40 mm/m(2) (LVEDD/body surface area). Patients must have been on stable, evidence-based therapy for HF. A total of 58 patients, mean age 62.3 ± 9.6 years, with ischaemic (57.7%) or non-ischaemic (42.3%) HF completed 12 months of follow-up. Treatment with Algisyl was associated with improved peak VO2 at 12 months; treatment effect vs. control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P < 0.001). Statistically significant improvements were observed for VO2 at anaerobic threshold, 6-min walk test distance, and NYHA functional class (all P < 0.001). Through 12 months of follow-up there were 4 (10.5%) deaths in the control group and 9 (22.5%) deaths in the Algisyl group. Conclusions: Algisyl in addition to SMT was more effective than SMT alone for providing sustained 1-year benefits in exercise capacity, symptoms, and clinical status for patients with advanced HF. These data support larger clinical evaluations of this novel therapy. [ABSTRACT FROM AUTHOR]

Periprocedural Colchicine for Epicardial Access Procedures Introduction Left atrial appendage (LAA) can be effectively and safely excluded using a novel percutaneous LARIAT ligation system. However, due to pericardial catheter manipulation and LAA ligation and subsequent necrosis, postprocedural course is complicated by pericarditis. We intended to evaluate the preprocedural use of colchicine on the incidence of postprocedural pericardial complications. Methods and Results In this multicenter observational study, we included all consecutive patients who underwent LARIAT procedure at the participating centers. Many patients received periprocedural colchicine at the discretion of the physician. We compared the postprocedural outcomes of patients who received prophylactic periprocedural colchicine (colchicine group) with those who did not receive colchicine (standard group). A total of 344 consecutive patients, 243 in the 'colchicine group' and 101 in the 'standard group,' were included. The mean age, median CHADS2VASc score, and HASBLED scores were 70 ± 11 years, 3 ± 1.7, and 3 ± 1.1, respectively. There were no significant differences in major baseline characteristics between the two groups. Severe pericarditis was significantly lower in the 'colchicine group' compared to the 'standard group' (10 [4%] vs. 16 [16%] P<0.0001). The colchicine group, compared to the standard group, had lesser pericardial drain output (186 ± 84 mL vs. 351 ± 83, P<0.001), shorter pericardial drain duration (16 ± 4 vs. 23 ± 19 hours, P<0.04), and similar incidence of delayed pericardial effusion (4 [1.6%] to 3 [3%], P = 0.42) when compared to the standard group. Conclusion Use of colchicine periprocedurally was associated with significant reduction in postprocedural pericarditis and associated complications. [ABSTRACT FROM AUTHOR]

Introduction There are several methods to induce ventricular fibrillation (VF) during defibrillation threshold (DFT) testing. Delivering a shock at a critical time during the T wave (T-shock) is the conventional approach, while delivering a constant direct current voltage (DC stim) from the implantable cardioverter defibrillator is an alternative method. Only a few reports compare VF induction methods. The purpose of this study was to evaluate the effects and safety of DC stim versus T-shock. Methods We retrospectively investigated 414 consecutive patients undergoing DFT testing. We compared the two groups (DC stim and T-shock) with respect to clinical characteristics, electrocardiogram (ECG) changes, and complications. Results Ventricular arrhythmia, including ventricular tachycardia (VT) and VF, was induced by DC stim in 93 patients or T-shock in 321 patients. No more than three attempts were performed during one procedure. There was no significant difference in the baseline ECG, induced tachycardia cycle length (TCL), or complications between the two groups. However, the induced TCL was significantly shorter than the clinical TCL regardless of induction method (P = 0.001). Five patients suffered major complications (i.e., electromechanical dissociation or incessant VT). A history of atrial fibrillation was significantly greater in patients with major complications than the others (80% vs 24%, P = 0.004), and was an independent predictor on multivariate analysis. Conclusions There is no significant difference in induced TCL or complications between the DC stim and T-shock. The induced TCL is significantly shorter than clinical TCL regardless of induction method. [ABSTRACT FROM AUTHOR]

Aims AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. Methods Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. Results Enrolled patients were 63±10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26±5% and a mean peak VVO2 of 12.2±1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months--treatment effect vs. Control: +1.24 mL/kg/min (95% confidence interval 0.26-2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). Conclusion Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. [ABSTRACT FROM AUTHOR]

The most severe consequence of atrial fibrillation (AF) is a cardioembolic stroke. The incidence of cardioembolic stroke increases significantly in patients with AF. Although warfarin has been the mainstay of the prevention of cardioembolic stroke, there are several limitations to the use of warfarin that hinder its effectiveness. This article provides the historical development of devices that exclude the left atrial appendage, their effectiveness and potential patient selection, as an alternative to warfarin and the novel oral anticoagulation therapy for the prevention of cardioembolic stroke in patients with AF. [ABSTRACT FROM AUTHOR]

Despite the controversy in mechanism, rodent and clinical studies have demonstrated beneficial effects of stem/progenitor cell therapy after myocardial infarction ( MI). In a rat ischaemic reperfusion MI model, we investigated the effects of immunomodification of CD 34+ cells on heart function and myocardial conduction. Bispecific antibody (BiAb), consisting of an anti-myosin light chain antibody and anti- CD45 antibody, injected intravenously was used to direct human CD34+ cells to injured myocardium. Results were compared to echocardiography guided intramyocardial ( IM) injection of CD34+ cells and PBS injected intravenously. Treatment was administered 2 days post MI. Echocardiography was performed at 5 weeks and 3 months which demonstrated LV dilatation prevention and fractional shortening improvement in both the BiAb and IM injection approaches, with BiAb achieving better results. Histological analyses demonstrated a decrease in infarct size and increase in arteriogenesis in both BiAb and IM injection. Electrophysiological properties were studied 5 weeks after treatments by optical mapping. Conduction velocity ( CV), action potential duration ( APD) and rise time were significantly altered in the MI area. The BiAb treated group demonstrated a more normalized activation pattern of conduction and normalization of CV at shorter pacing cycle lengths. The ventricular tachycardia inducibility was lowest in the BiAb treatment group. Intravenous administration of BiAb offers an effective means of stem cell delivery for myocardial repair post-acute MI. Such non-invasive approach was shown to offer a distinct advantage to more invasive direct IM delivery. [ABSTRACT FROM AUTHOR]

LAA Ligation and Pulmonary Vein Isolation Introduction Left atrial appendage (LAA) ligation results in LAA electrical isolation and a decrease in atrial fibrillation (AF) burden. This study assessed the feasibility of combined percutaneous LAA ligation and pulmonary vein isolation (PVI) in patients with persistent AF. Methods and Results A total of 22 patients with persistent AF underwent LAA ligation with the LARIAT device followed by PVI. PVI was confirmed with the demonstration of both entrance and exit block. Patients (n = 10) in sinus rhythm pre- and post-LAA ligation underwent P-wave analysis. Monitoring for AF was performed at 1, 3, and 6 months postablation. LAA ligation was successful in 21 of 22 (95%) patients. The procedure was aborted in one patient due to pericardial adhesions. PVI was performed in 20 of 21 patients. One patient converted to atrial flutter with a controlled ventricular response after LAA ligation and refused subsequent PVI. Demonstration of entrance and exit block was achieved in 19 of 20 patients. At 3 months, 13 of 19 (68.4%) patients were in sinus rhythm. Four patients underwent a second PVI. At 6 months, 15 of 20 (75%) patients were in sinus rhythm. There was a significant decrease in P-wave duration and P-wave dispersion after LAA ligation. Complications with LAA ligation included pericarditis, a delayed pleural effusion, and a late pericardial effusion. Conclusions Staged LAA ligation and PVI is feasible and decreases P-wave dispersion. Randomized studies are needed to assess the efficacy of LAA ligation as adjunctive therapy to PVI for maintaining sinus rhythm in patients with persistent AF. [ABSTRACT FROM AUTHOR]

Predictors of LV Dysfunction with Idiopathic PVC Introduction Patients with frequent premature ventricular complexes (PVCs) might be at risk for the developing or exacerbation of left ventricular (LV) dysfunction. However, some patients with a high-PVC burden do not develop cardiomyopathy, while other patients with low-PVC burden can develop cardiomyopathy. The purpose of this study was to evaluate the positive predictors of idiopathic PVCs-induced cardiomyopathy. Methods and Results We investigated 214 patients undergoing successful ablation of PVCs who had no other causes of cardiomyopathy. We divided the study cohort into 2 groups: ejection fraction (EF) ≥ 50% (normal LV) and EF < 50% (LV dysfunction). We analyzed the clinical characteristics, including the electrocardiogram and findings at electrophysiology study. Among these patients, 51 (24%) had reduced LVEF and 163 (76%) had normal LV function. Patients with LV dysfunction had significantly longer coupling interval (CI) dispersion (maximum-CI-minimum-CI) and had significantly higher PVC burden compared to those with normal LV function (CI-dispersion: 115 ± 25 milliseconds vs. 94 ± 19 milliseconds; P < 0.001; PVC burden: 19% vs. 15%; P = 0.04). Furthermore, patients with LV dysfunction had significantly higher body mass index (BMI) compared to those with normal LV function (BMI > 30 kg/m2; 37% vs. 13%; P = 0.001). Logistic regression analysis showed that CI-dispersion, PVC burden, and BMI (>30 kg/m2) are independent predictors of PVC-induced cardiomyopathy. Conclusions In addition to the PVC burden, the CI-dispersion and BMI are associated with PVC-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background Aging is associated with higher incidence of heart failure and death following myocardial infarction ( MI). The molecular and cellular changes that lead to these worse outcomes are not known. Methods and Results Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac- DEVD- CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice ( P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/ Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition. Conclusions Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI. [ABSTRACT FROM AUTHOR]

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model. [ABSTRACT FROM AUTHOR]

Background: The axillary vein is a commonly used extrathoracic access site for cardiac rhythm device lead implantation. We sought to describe variation in axillary vein location and identify predictors of a more cranial or caudal radiographic location to facilitate blind venous cannulation. Methods: This was a single-center, retrospective study of patients undergoing lead implantation between 2006 and 2010. The cranial-caudal location of the axillary vein lateral and medial to the rib cage border was determined by reviewing peripheral contrast venograms. Multivariate linear regression was performed. Results: Of 155 patients, the majority were men (62%) and White (53%). The most frequent position of the lateral and medial axillary vein was over the third rib (40%) and top of the third rib (15%), respectively. In multivariate analysis, whites had a more caudal location of both the lateral (0.56 rib spaces lower, 95% confidence interval [CI] 0.22-0.91, P = 0.002) and medial axillary vein (0.50 rib spaces lower, 95% CI 0.85-0.91, P = 0.019). Other independent predictors included an approximate 3-4% higher rib space location for every digit increase in body mass index (BMI) (P = 0.049 for the lateral location and P = 0.016 for the medial location) and an approximate half rib space higher location for males (P = 0.015 for the lateral location and P = 0.013 for the medial location). Conclusions: The most common radiographic position of the axillary vein was over the third rib. Whites have a more caudal axillary vein location while men and patients with higher BMI have a more cranial position of the axillary vein. (PACE 2011; 34:1585-1592) [ABSTRACT FROM AUTHOR]

Background: An unusual 12-lead electrocardiographic pattern may be present in patients with cavotricuspid isthmus (CTI)-dependent flutter. Objective: Using baseline patient characteristics and echocardiography, we sought to study predictors of unusual electrocardiogram (ECG) characteristics in patients with CTI-dependent atrial flutter. Methods: This was a dual-center, retrospective cohort study of 147 patients undergoing electrophysiology study and ablation for CTI-dependent atrial flutter. Results: Among this cohort, 23 patients (16%) had unusual 12-lead ECG characteristics. Using multivariate logistic regression, we found two clinical predictors for having an unusual ECG pattern. A clockwise (CW) pattern at time of electrophysiology study was the strongest predictor of an unusual ECG pattern (odds ratio 15.3, 95% confidence interval [CI] 4.0-59.4, P < 0.005). In addition, patients with decreased systolic function had a 3.5 greater odds (95% CI 1.1-11.5, P = 0.037) of having an unusual ECG pattern. Conclusions: Our data demonstrate that among patients suffering from CTI-dependent atrial flutter who are referred for ablation, 16% will have unusual ECG patterns. Patients with CW atrial activation and left ventricle dysfunction have greater odds of manifesting unusual patterns by surface electrocardiogram. (PACE 2011; 34:1251-1257) [ABSTRACT FROM AUTHOR]

Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease. [ABSTRACT FROM AUTHOR]

ECG and EGM of IIR. Introduction: Intra-isthmus reentry (IIR) is a circuit within the cavotricuspid isthmus (CTI). The purpose of this study is to prospectively define the electrogram and surface ECG characteristics of IIR, and its clinical implications. Methods and Results: Fourteen patients underwent electrophysiological studies and were found to have IIR. Detailed electrogram mapping of the CTI was available in all, electroanatomic mapping (EAM) in 8 of 14 (57%) patients. In all, entrainment mapping during tachycardia proved reentry, and showed that the anteroinferior CTI was out of the circuit and the septal CTI was in the circuit in 12 of 14 patients, whereas in 2, the circuit was confined within the mid and/or anteroinferior CTI. Fractionated potentials (FPs) spanning 34-71% of the tachycardia cycle length were recorded within the CTI in all, and double potentials were inscribed in 10 of 14 (71%). Analysis of the tricuspid annulus electrograms showed spontaneous shifts from a counterclockwise (CCW) to clockwise or fusion patterns. Surface ECGs showed either typical CCW pattern (12 patients) or atypical patterns (3 patients). The EAMs showed a focal pattern in 3, a CCW pattern in 5. The successful ablation site always occurred at the area with maximal FP duration. Over the same period, 33 of 384 (9%) patients who underwent ablation for CTI-dependent flutter had prior successful CTI ablation, 7 of 33 (21%) were found to have IIR during the redo procedure. Conclusions: (1) Electrogram and ECG patterns of IIR frequently show atypical flutter. (2) IIR was successfully ablated in an area of the CTI associated with maximal duration of FPs. (3) IIR is a significant cause of 'recurrent flutter' in patients with prior CTI ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1099-1106) [ABSTRACT FROM AUTHOR]

Background: Ventricular tachycardia (VT) is a common cause of mortality in post-myocardial infarction (MI) patients, even in the current era of coronary revascularization treatment. We report a reproducible VT model in rats with chronic MI induced by ischemia-reperfusion and describe its electrophysiological characteristics using high-resolution optical mapping. Methods: An MI was generated by left anterior descending coronary ligation (25 minutes) followed by reperfusion in 20 rats. Electrophysiology study and optical mapping were performed 5 weeks later using a Langendorff-perfused preparation and compared to normal rats. Results: The conduction velocity of the MI border zone was decreased to 53% of the normal areas remote from the infarct (0.37 ± 0.16 m/sec vs 0.70 ± 0.09 m/sec, P < 0.0001). The rate of VT inducibility in MI rats was significantly greater than in normal control rats (70% vs 0%, P = 0.00002). VT circuits involving the infarct area were identified with optical mapping in 83% MI rats. In addition, fixed and functional conduction block were observed in the infarct border zone. Conclusion: This ischemia-reperfusion MI rat model is a reliable VT model, which simulates clinical revascularization treatment. High-resolution optical mapping in this model is useful to study the mechanism of VT and evaluate the effects of therapies. (PACE 2010; 33:687–695) [ABSTRACT FROM AUTHOR]

Background: The extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair. Methodology/Principal Findings: Four peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides-Hep I, Hep III, RGD-were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment. Conclusions/Significance: We demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology. [ABSTRACT FROM AUTHOR]

We report a case of a 45-year-old man with incessant supraventricular tachycardia (SVT) in the setting of intrahepatic inferior vena cava thrombus and a left upper extremity arteriovenous fistula. A diagnostic electrophysiology study (EPS) was performed via the right internal jugular and right subclavian veins. After confirming the mechanism of SVT was atrial tachycardia (AT), mapping, and successful ablation was performed using remote catheter navigation. This case demonstrates that remote navigation can facilitate the therapy of complex arrhythmias in challenging clinical situations. [ABSTRACT FROM AUTHOR]