Diseases Commons^™

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create …

Clinical Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Surgery In High Surgical Risk Patients With Left Main Or Three-Vessel Coronary Artery Disease, Tonga Nfor, Kambiz Shetabi, Wael Hassan, Quinta Nfor, Jayant Khitha, Anjan Gupta, Tanvir Bajwa, Suhail Allaqaband

Aurora Cardiology Fellows

Purpose Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass graft surgery (CABG) in patients with unprotected left main or three-vessel coronary artery disease (LM-3VD) have excluded patients at high surgical risk. We compared clinical outcomes after PCI with drug-eluting stents to CABG in high surgical risk patients with LM-3VD. Methods Patients with symptomatic LM-3VD who had Society of Thoracic Surgeons (STS)-predicted operative mortality >5% and were undergoing either PCI with drug-eluting stents or CABG at a tertiary care center from January 2009 to December 2010 were enrolled in this nonrandomized prospective study. Results Mean STS score was …

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Nasir Sulemanjee, MD, FACC

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Dianne Zwicke, MD, FACC, FACP, FCCP

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Dianne Zwicke, MD, FACC, FACP, FCCP

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

Echocardiographic Predictors Of Admission Among Patients With Heart Failure With Reduced Ejection Fraction, Chi C. Cho, Yang Shi, Robyn Shearer, Nasir Z. Sulemanjee, Dianne L. Zwicke, T. Edward Hastings, Omar M. Cheema, Vinay Thohan

Dianne Zwicke, MD, FACC, FACP, FCCP

Background: Congestive heart failure afflicts 5.7 million people in the United States with annual incidence of 600,000 and mortality of 280,000. Heart failure accounts for greater than 1 million hospitalizations annually and the single largest inpatient Medicare expense. As the U.S. population ages and greater emphasis is placed on population health as a means to bend projected health care expenditures, large health care organizations will need to develop algorithms to identify patients at high risk with heart failure and possibly preempt hospitalizations. Doppler echocardiography is routinely performed in clinical assessment of severe heart failure.

Purpose: We sought to determine echocardiographic …

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …

Zero-Fluoroscopy Cavotricuspid Isthmus Ablation Using Carto Mapping System As Sole Guiding Method, Wassim Ballany, Indrajit Choudhuri, Mohamed Djelmami-Hani, Ryan L. Cooley

Aurora Electrophysiology Fellows

Background: Catheter ablation of the cavotricuspid isthmus (CTI) is traditionally performed using fluoroscopy and electroanatomical mapping systems. Zero-fluoroscopy approaches have recently been studied, mostly using the EnSite^® mapping system (St. Jude Medical Inc., St. Paul, MN). We studied the feasibility and efficacy of zero-fluoroscopic mapping and ablation of the CTI using the Carto^® 3 system (Biosense Webster Inc., South Diamond Bar, CA).

Purpose: To evaluate the efficacy and safety of a zero-fluoroscopic approach to CTI ablation.

Methods: We included 9 patients with typical atrial flutter for whom mapping and ablation of the CTI was done using Carto mapping …

The Crux Of The Heart –– The Closest Approach Of The Right Atrium To The Left Ventricle, Lynn Erickson, David Krum, Hannah Samuel, Anwer Dhala, Jasbir Sra

Jasbir Sra, MD, FACC, Program Director

Background: Accessory pathways, the source of atrioventricular reentry tachycardia, occasionally connect the left ventricle to the right atrium. This is possible because, in some patients, a portion of the right atrium abuts the left ventricle on the posterior wall of the heart, near the mid-coronary sinus. This anatomic region is known as the “crux” of the heart. These accessory pathways can be difficult to ablate because of the unusual and unexpected substrate. While the presence of these accessory pathways is described in the literature, the prevalence of the underlying anatomic substrate is not currently known.

Purpose: To measure the closest …

Predicting Outcomes In Patients With Atrial Fibrillation And Acute Mesenteric Ischemia, Sanjay Bhandari, Geetanjali Dang, Muhammad Shahreyar, Ahmad Hanif, Vijayadershan Muppidi, Atul Bhatia, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir

Jasbir Sra, MD, FACC, Program Director

Purpose Outcomes in patients with atrial fibrillation who develop acute mesenteric ischemia, and the impact of anticoagulation on complications, are not defined. Methods Patients admitted with acute mesenteric ischemia in the National Inpatient Sample from 2007, with and without atrial fibrillation, were compared for in-hospital outcomes using multivariate regression, and the impact of prior anticoagulation determined. Results Of 48,872 patients with acute mesenteric ischemia, 8,306 had atrial fibrillation, with 680 patients also on anticoagulation. Atrial fibrillation patients were more likely to be older and have hypertension, heart failure, or chronic lung or renal disease. After adjusting for potential confounders, atrial …

Atrial Fibrillation And Stroke In Elderly Patients, Geetanjali Dang, Imaan Jahangir, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir

Jasbir Sra, MD, FACC, Program Director

The increasing prevalence of stroke, with an estimated annual cost of $71.5 billion, has made it a major health problem that increases disability and death, particularly in patients with atrial fibrillation. Although advanced age and atrial fibrillation are recognized as strong risk factors for stroke, the basis for this susceptibility are not well defined. Aging or associated diseases are accompanied by changes in rheostatic, humoral, metabolic and hemodynamic factors that may contribute more to stroke predisposition than rhythm abnormality alone. Several thromboembolism-predisposing clinical characteristics and serum biomarkers with prognostic significance have been identified in patients with atrial fibrillation. Although anticoagulation …

Lead Burden As A Factor For Higher Complication Rate In Patients With Implantable Cardiac Devices, Christopher Kolibash, Naoyo Mori, Jasbir Sra, Masood Akhtar, M. Eyman Mortada

Mohammad Mortada, MD, FACC, FHRS

Purpose Lead revisions have increased over the last decade. Patients who do not undergo lead extraction face an increased lead burden. Consequences of increased lead burden have not been fully defined. We sought to characterize the complication rate and outcomes in patients with sterile redundant leads. Methods We retrospectively reviewed 242 consecutive patients [mean age 74 ± 12 years; 66.9% male] who underwent lead revision that resulted in an abandoned lead from January 2005 to June 2010. Patients were placed in a cohort based on number of leads after last recorded procedure (Group A: ≤2 [n=58]; Group B: 3-4 [n=168]; …