Hospital outcomes of patients receiving catheter ablation of atrial fibrillation, left atrial appendage closure, or both.

BACKGROUND: Catheter ablation (CA) and left atrial appendage closure (LAAC) require transseptal access; combining both in a single procedure may have advantages. However, the safety of this approach has not been extensively studied. The objective of this study was to compare in hospital outcomes among patients receiving CA, LAAC, and combination of both treatments on the same day. METHODS: We conducted a retrospective cohort analysis of the National Inpatient Sample database. The primary outcome was the presence of major adverse cardiovascular and cerebrovascular events (MACCE) during index hospitalization. Secondary outcomes included stroke, pericardial effusion, pericardiocentesis, and bleeding. RESULTS: A total of 69,285 hospitalizations with AF were included in the analysis, of which 71.7% received LAAC, 27.8% received CA, and 0.5% received combination of both treatments on the same day. MACEE (OR, 1.63; 95% CI, 0.39-6.70), stroke (OR, 2.98; 95% CI, 0.55-16.01), pericardial effusion (OR, 0.33; 95% CI, 0.07-1.41), pericardiocentesis (OR, 1.00; 95% CI, 0.25-3.86), and bleeding (OR, 3.25; 95% CI, 0.87-12.07) did not differ significantly between CA and combination treatment. Similarly, MACCE (OR, 1.11; 95% CI, 0.28-4.41), stroke (OR, 1.03; 95% CI, 0.24-4.35), pericardial effusion (OR, 0.45; 95% CI, 0.11-1.90), pericardiocentesis (OR, 0.63; 95% CI, 0.14-2.83), and bleeding (OR, 2.04; 95% CI, 0.65-6.39) did not differ significantly between LAAC and combination treatment. CONCLUSIONS: The combined approach is infrequently used in clinical practice (< 1%). However, major life-threatening adverse events did not differ between CA and LAAC when performed in isolation or combined in a single procedural stage on the same day.

Ivabradine toxicity: a case report.

BACKGROUND: We describe a case of symptomatic bradycardia resulting from ivabradine toxicity by measurement of ivabradine levels, of which there are limited reports in the literature. CASE PRESENTATION: A 43-year-old White female presented with several days of near syncope and dizziness accompanied by a drop in her heart rate to 50 beats per minute. She was taking ivabradine for inappropriate sinus tachycardia. After excluding several other causes of bradycardia, we made the diagnosis of ivabradine toxicity by measurement of serum ivabradine levels, an approach that is currently not clinically available. CONCLUSIONS: Measurement of serum ivabradine levels and knowledge of the pharmacokinetic properties of the drug can be utilized to confirm the diagnosis of ivabradine toxicity.

Polymer 3D Printing Review: Materials, Process, and Design Strategies for Medical Applications.

Polymer 3D printing is an emerging technology with recent research translating towards increased use in industry, particularly in medical fields. Polymer printing is advantageous because it enables printing low-cost functional parts with diverse properties and capabilities. Here, we provide a review of recent research advances for polymer 3D printing by investigating research related to materials, processes, and design strategies for medical applications. Research in materials has led to the development of polymers with advantageous characteristics for mechanics and biocompatibility, with tuning of mechanical properties achieved by altering printing process parameters. Suitable polymer printing processes include extrusion, resin, and powder 3D printing, which enable directed material deposition for the design of advantageous and customized architectures. Design strategies, such as hierarchical distribution of materials, enable balancing of conflicting properties, such as mechanical and biological needs for tissue scaffolds. Further medical applications reviewed include safety equipment, dental implants, and drug delivery systems, with findings suggesting a need for improved design methods to navigate the complex decision space enabled by 3D printing. Further research across these areas will lead to continued improvement of 3D-printed design performance that is essential for advancing frontiers across engineering and medicine.

Targeted temperature management for cardiac arrest.

Therapeutic hypothermia, or targeted temperature management (TTM), is a strategy of reducing the core body temperature of survivors of sudden cardiac arrest (SCA) to minimize neurological damage caused by severe hypoxia. Initial clinical trials examining this technique demonstrated significant improvement in neurological function among survivors of out-of-hospital SCA with an initial shockable rhythm. Since then, TTM has become an integral part of the care provided to comatose survivors of SCA. However, multiple questions persist regarding the target cooling temperature, duration of cooling, and utility of TTM in patient populations such as survivors of out-of-hospital SCA with non-shockable rhythms or in-hospital SCA. This review article summarizes the current evidence regarding optimal application of TTM and compares the recommendations for TTM in current guidelines.

How to Prevent, Detect and Manage Complications Caused by Cryoballoon Ablation of Atrial Fibrillation.

Atrial fibrillation is the most common cardiac arrhythmia and the prevalence is increasing every year. Patients who fail to maintain sinus rhythm with use of anti-arrhythmic drug therapy are referred for catheter ablation. Cryoballoon (CB) ablation has emerged as an effective and alternative treatment option to traditional point-by-point radiofrequency ablation, but there can be complications. This article reviews the incidence, presentation, risk factors, management and preventative strategies of three major complications associated with CB ablation: phrenic nerve injury, atrial oesophageal fistula and bronchial injury. Although these complications are rare, electrophysiologists should institute measures to identify high-risk patients, implement best-practice techniques to minimise risks and maintain a high index of suspicion to recognise the complications quickly and implement correct treatment strategies.

Causes and Prevention of Inappropriate Implantable Cardioverter-Defibrillator Shocks.

Use of implantable cardioverter-defibrillators as a primary prevention therapy has been shown to reduce mortality in patients after cardiac arrest and also with left ventricular systolic dysfunction. Yet, inappropriate shocks are variably reported and associated with a reduction in quality of life. Inappropriate shocks are the result of environmental causes leading to electromagnetic interference and inappropriate sensing of external noise, device-related causes from inappropriate sensing of physiologic or pathologic signals, and supraventricular arrhythmias. Strategies to reduce inappropriate shocks include aggressive treatment of supraventricular tachycardia, changes in device programming including prolonged detection time, programming antitachycardic pacing and using discriminator algorithms, and cardiac rehabilitation.

His-Bundle Pacing for Identifying Optimal Ablation Sites in Patients Undergoing Atrioventricular Junction Ablation: Teaching an Old Dog a New Trick.

BACKGROUND: Atrioventricular (AV) junction (AVJ) ablation is conventionally performed by localizing the His-bundle electrogram (HBE). Identification of HBE in the presence of atrial fibrillation (AF) can be difficult, and can make this simple procedure challenging. In this study, we describe our experience with an alternative approach to localize optimal ablation sites using His-bundle pacing (HBP). METHODS: Between 1/1/2014 and 12/31/2015, we performed 13 AVJ ablations using the standard electrogram-guided approach and 11 ablations using HBP. All cases utilized a long femoral guiding sheath and an 8-mm-tip electrode radiofrequency (RF) energy ablation catheter. Pacing was performed at high output (10 mA at 2 ms) to initially achieve right bundle branch capture. The catheter was withdrawn until a narrow QRS morphology and increased stim-to-QRS time were observed. HBP was confirmed when paced and native QRS were identical in morphology. RF energy was applied at the site of HBP capture until AV block was observed. RESULTS: Baseline characteristics of patients in each arm were not significantly different. Compared with the standard approach, HBP was associated with trends toward lower RF applications (3 vs. 2, P = 0.16) and shorter mean RF time (208 seconds vs. 128 seconds, P = 0.19). CONCLUSION: HBP is an effective technique to identify optimal ablation sites during AVJ ablation and may shorten procedure time. HBP can be used to identify the AV node during AF without recording the His potential. Future studies with larger sample size are needed to better characterize the utility of this technique.

The tetraspanin CD63 is required for efficient IgE-mediated mast cell degranulation and anaphylaxis.

Mast cell (MC) activation through the high-affinity IgE receptor FcεRI leads to the release of mediators involved in immediate-type allergic reactions. Although Abs against the tetraspanins CD63 and CD81 inhibit FcεRI-induced MC degranulation, the intrinsic role of these molecules in FcεRI-induced MC activation is unknown. In MCs, CD63 is expressed at the cell surface and in lysosomes (particularly secretory lysosomes that contain allergic mediators). In this study, we investigated the role of CD63 in MC using a CD63 knockout mouse model. CD63-deficiency did not affect in vivo MC numbers and tissue distribution. Bone marrow-derived MC developed normally in the absence of CD63 protein. However, CD63-deficient bone marrow-derived MC showed a significant decrease in FcεRI-mediated degranulation, but not PMA/ionomycin-induced degranulation, as shown by ß-hexosaminidase release assays. The secretion of TNF-α, which is both released from granules and synthesized de novo upon MC activation, was also decreased. IL-6 secretion and production of the lipid mediator leukotriene C4 were unaffected. There were no ultrastructural differences in granule content and morphology, late endosomal/lysosomal marker expression, FcεRI-induced global tyrosine phosphorylation, and Akt phosphorylation. Finally, local reconstitution in genetically MC-deficient Kit(w/w-v) mice was unaffected by the absence of CD63. However, the sites reconstituted with CD63-deficient MC developed significantly attenuated cutaneous anaphylactic reactions. These findings demonstrate that the absence of CD63 results in a significant decrease of MC degranulation, which translates into a reduction of acute allergic reactions in vivo, thus identifying CD63 as an important component of allergic inflammation.

A2B adenosine receptor promotes mesenchymal stem cell differentiation to osteoblasts and bone formation in vivo.

The differentiation of osteoblasts from their precursors, mesenchymal stem cells, is an important component of bone homeostasis as well as fracture healing. The A2B adenosine receptor (A2BAR) is a Gα(s)/α(q)-protein-coupled receptor that signals via cAMP. cAMP-mediated signaling has been demonstrated to regulate the differentiation of mesenchymal stem cells (MSCs) into various skeletal tissue lineages. Here, we studied the role of this receptor in the differentiation of MSCs to osteoblasts. In vitro differentiation of bone marrow-derived MSCs from A2BAR KO mice resulted in lower expression of osteoblast differentiation transcription factors and the development of fewer mineralized nodules, as compared with WT mice. The mechanism of effect involves, at least partially, cAMP as indicated by experiments involving activation of the A2BAR or addition of a cAMP analog during differentiation. Intriguingly, in vivo, microcomputed tomography analysis of adult femurs showed lower bone density in A2BAR KO mice as compared with WT. Furthermore, A2BAR KO mice display a delay in normal fracture physiology with lower expression of osteoblast differentiation genes. Thus, our study identified the A2BAR as a new regulator of osteoblast differentiation, bone formation, and fracture repair.

Urine matrix metalloproteinases (MMPs) as biomarkers for the progression of fracture healing.

Whilst the majority of fractures heal normally, it is estimated that ∼10% of fractures exhibit some level of delayed or impaired healing. Although radiography is the primary diagnostic tool to assess the progression of fracture healing, radiographic features only qualitatively correlate with tissue level increases in mineral content and do not quantitatively measure underlying biological processes that are associated with the progression of healing. Specific metaloproteinases have been shown to be essential to processes of both angiogenesis and mineralised cartilage resorption and bone remodelling at different phases of fracture healing. The aim of this study was to determine the potential of using a simple urine based assay of the activity of two MMPs as a means of assessing the biological progression of fracture healing through the endochondral phase of healing. Using a standard mid-diaphyseal murine model of femoral fracture, MMP9 and MMP13 proteins and enzymatic activity levels were quantified in the urine of mice across the time-course of fracture healing and compared to the mRNA and protein expression profiles in the calluses. Both urinary MMP9 and MMP13 protein and enzymatic activity levels, assessed by Western blot, zymogram and specific MMP fluorometric substrate assays, corresponded to mRNA expression and immunohistologic assays of the proteins within callus tissues. These studies suggest that urinary levels of MMP9 and MMP13 may have potential as metabolic markers to monitor the progression of fracture healing.

Chronic Kidney Disease and Atrial Fibrillation: A Contemporary Overview.

Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity, including myocardial infarction, heart failure and stroke. Similar to CKD, atrial fibrillation (AF) is a prevalent arrhythmia that increases risk for both stroke and overall mortality. Recent studies demonstrate that both prevalence and incidence of AF is higher in patient with versus without renal impairment and risk for developing AF increases as renal function worsens. Potential mechanisms for the higher burden of AF in CKD patients include but are not limited to augmented sympathetic tone, activation of the renin-angiotensin-aldosterone system and myocardial remodeling. Similar to the general population, AF confers an increased risk for both stroke and overall mortality in the CKD population. The safety and efficacy of antithrombotic therapy across the spectrum of CKD remains unknown, however, as patients with advanced renal failure are frequently excluded from randomized trials. While treatment with vitamin K antagonists appears to reduce ischemic complications without significant bleeding harm in patients with mild to moderate CKD and AF, the risk benefit ratio of anticoagulation among thosewith advanced renal failure on dialysis requires further investigation. Prospective, randomized trials are war ranted to define the impact of antithrombotic therapy on reducing stroke risk in patients with both AF and CKD.

Comparison of high efficiency CZT SPECT MPI to coronary angiography.

BACKGROUND: The recently introduced cadmium zinc telluride (CZT) SPECT cameras have the potential to reduce radiation exposure to patients and shorten imaging time. So far, there has been only one small study comparing the results of high efficiency CZT SPECT myocardial perfusion imaging (MPI) to invasive coronary angiography. METHODS: All patients who had either a Tc-99m sestamibi or Tl-201 SPECT MPI study using a CZT camera (GE Discovery NM 530c) over a 1-year period followed by a coronary angiogram within 2 months were included. Only patients with a history of CABG surgery were excluded. Standard stress protocols were employed. Rest images were acquired for 5 min and stress supine and prone images for 3 min each. Both MPI studies and coronary angiograms were interpreted by blinded readers. A standard 17-segment model was employed for MPI interpretation, and coronary angiograms were interpreted for the presence of obstructive epicardial coronary artery disease (CAD) defined as ≥70% luminal narrowing. Correlation was based on the ability to diagnose obstructive epicardial CAD. RESULTS: Of the 3,111 patients who underwent SPECT imaging using the CZT camera during this time period, 230 patients qualified for the correlation study (mean age 64.2 ± 11.0 years old, 69% male, and 49% had a history of intracoronary stenting). Tc-99m was used in 76% vs Tl-201 in 24% of the studies. Exercise stress was performed in 60% of patients and vasodilator pharmacologic stress in 40%. Sensitivity was 95%, normalcy rate was 97%, and accuracy was 69% for detecting obstructive CAD. CONCLUSIONS: In this so far largest correlation study between coronary angiography and high efficiency CZT SPECT imaging, a high sensitivity and accuracy for detecting obstructive epicardial CAD was found for this new SPECT camera technology.