Anand D. Shah

Mechanisms of Reactive Oxygen Species–Dependent Downregulation of Insulin Receptor Substrate-1 by Angiotensin II

Objective—Angiotensin II has been implicated in the pathogenesis of the vascular complications of insulin resistance. Recently, serine phosphorylation and degradation of insulin receptor substrate-1 (IRS-1) were shown to inhibit Akt activation and reduce glucose uptake. Therefore, we examined the effects of chronic angiotensin II treatment on IRS-1 phosphorylation and protein expression in vascular smooth muscle cells (VSMCs). Methods and Results—Using Western analysis, we found that angiotensin II (100 nmol/L; 18 hours) caused a 61±5% degradation of IRS-1 and abolished insulin-induced activation of Akt. Phosphorylation of IRS-1 on Ser307, which leads to subsequent IRS-1 degradation, was stimulated by angiotensin II. This phosphorylation was blocked by the Src inhibitor PP1 and by the antioxidants N-acetylcysteine and ebselen. Stable overexpression of catalase abrogated angiotensin II–induced IRS-1 phosphorylation and IRS-1 degradation. Similarly, a mutant phosphoinositide-dependent kinase-1 (PDK1) that cannot associate with Src abolished IRS-1 phosphorylation and degradation induced by angiotensin II. Proteasome inhibitors also prevented IRS-1 degradation. Conclusions—Thus, angiotensin II decreases IRS-1 protein levels in VSMCs via Src, PDK1, and reactive oxygen species–mediated phosphorylation of IRS-1 on Ser307 and subsequent proteasome-dependent degradation. These events impair insulin signaling and provide a molecular basis for understanding the clinical observation that angiotensin II type 1 receptor antagonists improve insulin resistance and its associated vasculopathies.

Safety and Quality of 1.5-T MRI in Patients With Conventional and MRI-Conditional Cardiac Implantable Electronic Devices After Implementation of a Standardized Protocol

OBJECTIVE The purpose of this study was to evaluate the safety and diagnostic utility of 1.5-T MRI examinations of individuals with conventional and MRI-conditional cardiac implantable electronic devices (CIEDs). SUBJECTS AND METHODS Patients with a CIED who were referred for MRI were evaluated by radiologists and cardiac electrophysiologists for study participation. CIED interrogation was performed immediately before and after MRI, and cardiac telemetry monitoring was performed during MRI. CIED programming changes, malfunctions, and intraprocedural events were documented. Whether diagnostic questions were answered and whether artifacts related to the CIED were present and negatively affected image interpretation were recorded. RESULTS One hundred thirteen MRI examinations were performed for 104 patients with CIEDs (74 pacemakers [60 conventional, 14 MRI conditional]; 39 implantable cardiac defibrillators). Device reprogramming was required before MRI for 62.8% of studies (71/113). No significant changes in lead parameters were noted during or after MRI. Electromagnetic noise was detected on at least one lead in 7.1% of studies. Three patients reported transient symptoms (one case each of heating at the pocket site, tingling at the pocket site, and palpitations). All images were considered diagnostic for the original clinical query. Artifacts related to CIEDs were described in 3.5% of MRI reports (4/113) and were present only when the pulse generator was included in the FOV. CIED-related artifacts limited evaluation of tissues immediately adjacent to the pulse generator. CONCLUSION Establishment of a multidisciplinary work flow allows individuals with conventional and MRI-conditional CIEDs to safely undergo 1.5-T MRI with diagnostic questions consistently answered.

Clinical Performance of Magnetic Resonance Imaging Conditional and Nonconditional Cardiac Implantable Electronic Devices: CLINICAL OUTCOMES: MRI AND CIED

This study compared risks associated with magnetic resonance imaging (MRI) in patients with non‐MRI conditional and MRI conditional pacing and defibrillator systems with particular attention to clinically actionable outcomes.

Electrogram Characteristics of Ablated and Non-Ablated Myocardium in Humans: A Comparison of Miniaturized Embedded Electrodes and Conventional Ablation Electrodes

Intracardiac electrogram voltage remains an important metric for radiofrequency lesion application. Embedded micro‐electrodes within ablation catheters are now approved for use in humans.

Procedural outcomes and long-term survival following trans-venous defibrillator lead extraction in patients with end-stage renal disease

Aims End-stage renal disease (ESRD) increases the risk of implantable cardioverter-defibrillator (ICD) infection. We sought to define outcomes of lead extraction in patients with ESRD. Methods and results Implantable cardioverter-defibrillator lead extractions at our institution from January 2006 to March 2014 were stratified by absence (Control-Ex, n = 465) or presence (ESRD-Ex, n = 43) of ESRD. Procedural outcomes and survival were determined by medical records review. Survival in the ESRD-Ex group was compared with a contemporaneous cohort with ESRD undergoing ICD lead implantation (ESRD-I, n = 127). Among extraction patients, those with ESRD were more likely to be extracted for infection (74.4% vs. 28.6%, P < 0.001). Extraction procedure success (Control-Ex: 97% vs. ESRD-Ex: 93%, P = 0.17) and procedural deaths (Control-Ex: 1.1% vs. ESRD-Ex: 2.3%, P = 0.413) were similar. Survival 1 year following extraction was worse in the ESRD-Ex group compared with the Control-Ex, with a survival rate of 65.6% vs. 92.6% (P < 0.001); these curves continued to diverge through year 3. One-year survival in the ESRD-Ex group was worse than among ESRD patients undergoing ICD implant (ESRD-I), but these curves converged and survival was similar by year 3. Conclusions Implantable cardioverter-defibrillator lead extraction can be performed safely and effectively in patients with ESRD. However, despite high rates of procedural success, long-term mortality following extraction in ESRD patients is substantial. Much of the long-term mortality risk appears to be accounted for by the presence of ESRD and an indication for an ICD.

Magnetic resonance imaging safety in nonconditional pacemaker and defibrillator recipients: A meta-analysis and systematic review

BACKGROUND Recommendations regarding performance of magnetic resonance imaging (MRI) in non-MRI conditional pacemaker and defibrillator recipients are evolving. Previous studies have suggested low adverse event rates with MRI in nonconditional cardiac implantable electronic device (CIED) recipients, but low power limits optimal characterization of risk. OBJECTIVE The purpose of this study was to perform a systematic review and meta-analysis to characterize the clinical risk associated with MRI in CIED recipients in order to improve power. METHODS PubMed and CINAHL indexed articles from 1990 to 2017 were queried. A random effects model was used for meta-analysis of continuous variables. Safety outcomes were evaluated with descriptive statistics. RESULTS Seventy studies of non-MRI conditional devices undergoing MRI were identified, allowing for analysis of 5099 patients who underwent a total of 5908 MRI studies. Heterogeneity in lead parameter changes was observed within studies, although smaller variances were noted between studies. All lead characteristics and battery voltages showed very small, clinically insignificant changes when assessed as a pooled cohort, although cases of clinically relevant outcomes were also noted (lead failure 3, implantable cardioverter-defibrillator shock 1, electrical reset 94). Electrical resets were found only in older devices. Defibrillator function was unchanged, and inappropriate shocks were avoided with pre-MRI programming changes. CONCLUSION This review demonstrated low lead failure and clinical event rates in non-MRI conditional pacemaker and defibrillator recipients undergoing MRI. Observed changes were small and interstudy variance was low, suggesting that the composite event rates offer a reasonable estimate of true effect. The observed adverse events reinforce the need for ongoing vigilance and caution, particularly with older devices.

ELECTROGRAM CHARACTERISTICS OF ABLATED AND NON-ABLATED MYOCARDIUM IN HUMANS WITH MINIATURIZED EMBEDDED ELECTRODES COMPARED TO CONVENTIONAL ELECTRODES

Intracardiac electrogram voltage remains an important metric for the monitoring and assessment of radiofrequency lesion application. Embedded micro-electrodes within ablation catheters are now approved for use in humans (Mifi, Boston Scientific). This study examined electrogram characteristics of

Hemodynamic Findings of Effusive-Constrictive Pericarditis.

A 64-year-old man with rheumatoid arthritis presented with progressive abdominal and leg swelling, anorexia, and dyspnea for several years. Physical examination was notable for a pericardial knock, pulsatile hepatomegaly, and lower extremity edema. The jugular vein was distended past the angle of

Failure of an Implantable Defibrillator to detect transition from sinus tachycardia to slow ventricular tachycardia with 'Onset' discrimination algorithm activated.

A 74-year-old male with inotrope-dependent congestive heart failure (CHF) had recurrence of slow ventricular tachycardia (VT) ( Panel A ). Although this VT exceeded the programmed rate cutoff ( Panel B ), therapy was inhibited, because it did not exceed the change in rate criterion specified by …

THE SIGNIFICANCE OF INCOMPLETE AND COMPLETE RIGHT BUNDLE BRANCH BLOCKS IN YOUNG ADULTS

Incomplete right bundle branch block (IRBBB) and right bundle branch block (RBBB) are typically thought to be benign findings in young adults. However, this has not been validated with current diagnostic criteria for IRBBB and RBBB. We assessed the hypothesis that in patients 18-40 years old without