Cryoballoon Catheter Ablation in Atrial Fibrillation

Pulmonary vein isolation with catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation refractory or intolerant to antiarrhythmic medications. The cryoballoon catheter was recently approved for this procedure. In this paper, the basics of cryothermal energy ablation are reviewed including its ability of creating homogenous lesion formation, minimal destruction to surrounding vasculature, preserved tissue integrity, and lower risk of thrombus formation. Also summarized here are the publications describing the clinical experience with the cryoballoon catheter ablation in both paroxysmal and persistent atrial fibrillation, its safety and efficacy, and discussions on the technical aspect of the cryoballoon ablation procedure

Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice

Obstructive sleep apnea (OSA) is a common breathing disorder that affects a significant portion of the adult population. In addition to causing excessive daytime sleepiness and neurocognitive effects, OSA is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not completely understood. Using exposure to intermittent hypoxia (IH) to mimic OSA, we have recently reported that mice exposed to IH exhibit endothelial cell (EC) activation, which is an early process preceding the development of cardiovascular disease. Although widely used, IH models have several limitations such as the severity of hypoxia, which does not occur in most patients with OSA. Recent studies reported that mice with deletion of hemeoxygenase 2 (Hmox2-/-), which plays a key role in oxygen sensing in the carotid body, exhibit spontaneous apneas during sleep and elevated levels of catecholamines. Here, using RNA-sequencing we investigated the transcriptomic changes in aortic ECs and heart tissue to understand the changes that occur in Hmox2-/- mice. In addition, we evaluated cardiac structure, function, and electrical properties by using echocardiogram and electrocardiogram in these mice. We found that Hmox2-/- mice exhibited aortic EC activation. Transcriptomic analysis in aortic ECs showed differentially expressed genes enriched in blood coagulation, cell adhesion, cellular respiration and cardiac muscle development and contraction. Similarly, transcriptomic analysis in heart tissue showed a differentially expressed gene set enriched in mitochondrial translation, oxidative phosphorylation and cardiac muscle development. Analysis of transcriptomic data from aortic ECs and heart tissue showed loss of Hmox2 gene might have common cellular network footprints on aortic endothelial cells and heart tissue. Echocardiographic evaluation showed that Hmox2-/- mice develop progressive dilated cardiomyopathy and conduction abnormalities compared to Hmox2+/+ mice. In conclusion, we found that Hmox2-/- mice, which spontaneously develop apneas exhibit EC activation and transcriptomic and functional changes consistent with heart failure

Symptomatic Long Pauses and Bradycardia due to Massive Multinodular Goiter

Sinus node dysfunction with symptomatic bradycardia or chronotropic incompetence is generally an indication for pacemaker implantation. However, in patients with symptomatic sinus bradycardia, the identification and treatment of underlying pathologies may avoid the need for permanent pacemaker implantation. We present a case of carotid sinus syndrome and severe obstructive sleep apnea due to a massive multinodular goiter in a patient who presented with recurrent sinus pauses and syncope. The patient was managed without pacemaker implantation but instead with thyroidectomy resulting in decompression of the carotid sinus and airway and resolution of bradycardic episodes

Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets

Product transfer from lab-scale to pilot-scale of quetiapine fumarate orodispersible films using quality by design approach

In this study, transfer from lab-scale non-continuous production to pilot-scale continuous production of orodispersible films was provided using solvent casting method under the framework of quality by design. Non-continuous production was carried out with petri dishes and continuous production was carried out with a coating machine. Films containing hydroxypropyl methylcellulose E5 as film forming polymer, polyethylene glycol 400 and propylene glycol as plasticizers, quetiapine fumarate as drug were formulated. Viscosity of the polymer dispersions, weight, thickness and disintegration time of the films were compared for the transfer of production. pH, moisture content, mechanical properties, folding endurance, uniformity of dosage units, dissolution, stability studies were also performed in pilot-scale orodispersible films. Finally, cytotoxicity studies were performed to determine cell viability. The study showed the possibility of producing F2-p-65/70 (pilot-scale film formulation containing 10 mg propylene glycol, dried at 65 degrees C and 70 degrees C) and F4-p-65/70 (pilot-scale film formulation containing 15 mg propylene glycol, dried at 65 degrees C and 70 degrees C), as the most suitable for further studies. Thus, a promising improvement has been achieved for schizophrenic patients by the production of quetiapine fumarate loaded orodispersible films and the process of scale-up in films has been demonstrated