Clinical Briefings™: Clinical Reports from Penn Medicine

Electrophysiology Research and Publications Update

2015-10-23T09:10:00.000-04:00

Under the direction of Francis Marchlinski, MD, researchers with the Electrophysiology (EP) Program at Penn Medicine have been at the forefront of clinical research in the treatment of atrial fibrillation and ventricular tachycardia (VT) for almost two decades.
The publications below are representative of the spectrum of past and present clinical investigations at Penn Electrophysiology.

Acute hemodynamic decompensation during catheter ablation of scar-related ventricular tachycardia: incidence, predictors, and impact on mortality.

Methods: The investigators identified univariate predictors of periprocedural AHD in 193 consecutive patients undergoing radiofrequency catheter ablation of scar-related VT. AHD was defined as persistent hypotension despite vasopressors and requiring mechanical support or procedure discontinuation.
Results: AHD occurred in 22 (11%) patients. Compared with the rest of the population, patients with AHD were older (68.5±10.7 versus 61.6±15.0 years; P=0.037); had a higher prevalence of diabetes mellitus (36% versus 18%; P=0.045), ischemic cardiomyopathy (86% versus 52%; P=0.002), chronic obstructive pulmonary disease (41% versus 13%; P=0.001), and VT storm (77% versus 43%; P=0.002); had more severe heart failure (New York Heart Association class III/IV: 55% versus 15%, P less than 0.001; left ventricular ejection fraction: 26±10% versus 36±16%, P=0.003); and more often received periprocedural general anesthesia (59% versus 29%; P=0.004). At 21±7 months follow-up, the mortality rate was higher in the AHD group compared with the rest of the population (50% versus 11%, log-rank P less than 0.001).
Conclusions: AHD occurs in 11% of patients undergoing radiofrequency catheter ablation of scar-related VT and is associated with increased risk of mortality over follow-up. AHD may be predicted by clinical factors, including advanced age, ischemic cardiomyopathy, more severe heart failure status (New York Heart Association class III/IV, lower ejection fraction), associated comorbidities (diabetes mellitus and chronic obstructive pulmonary disease), presentation with VT storm, and use of general anesthesia.
Source: 2015 Feb;8(1):68-75. Full text available here.

Percutaneous epicardial ablation of ventricular arrhythmias arising from the left ventricular summit: outcomes and electrocardiogram correlates of success.

Methods: Between January 2003 and December 2012, a total of 23 consecutive patients (49 ± 14 years; 39% men) with ventricular arrhythmias arising from the left ventricular summit underwent percutaneous epicardial instrumentation for mapping and ablation because of unsuccessful ablation from the coronary venous system and multiple endocardial LV/right ventricular sites.
Results: Successful epicardial ablation was achieved in 5 (22%) patients. In the remaining 18 (78%) cases, ablation was aborted for either close proximity to major coronary arteries or poor energy delivery over epicardial fat. The Q-wave amplitude ratio in aVL/aVR was higher in the successful group, with a ratio of greater than 1.85 present in 4 (80%) patients in the successful group versus 2 (11%) in the unsuccessful group (P = 0.008). The ratio of R/S wave in V1 was greater in the successful group, with 4 (80%) patients in the successful group having a R/S ratio of greater than 2 in V1 versus 5 (28%) in the unsuccessful group (P = 0.056). None of the patients in the successful group had an initial q wave in lead V1, as opposed to 6 (33%) in the unsuccessful group. The presence of at least 2 of the 3 ECG criteria above predicted successful ablation with 100% sensitivity and 72% specificity.
Conclusions: Epicardial instrumentation for mapping and ablation of ventricular arrhythmias arising from the left ventricular summit is successful only in a minority of patients because of close proximity to major coronary arteries and epicardial fat. A Q-wave ratio of greater than 1.85 in aVL/aVR, a R/S ratio of greater than 2 in V1, and absence of q waves in lead V1 help identify appropriate candidates for epicardial ablation.
Source: 2015 Apr;8(2):337-43. Full text available here.

ECG Criteria to Identify Epicardial Ventricular Tachycardia in Nonischemic Cardiomyopathy

The EP team at HUP compared pace maps and VT-generated QRS complexes from endocardial (ENDO) versus epicardial (EPI) origin in patients with NICM. The study findings showed unequivocally that the ECG morphological criteria (presence of a q wave in Lead 1 (QWL1) appears to be the most specific and sensitive criterion for identifying an EPI site of origin. The study identified new interval criteria that would improve the specificity of identifying an EPI VT origin. A simple multi-step ECG algorithm that incorporates both newly identified morphology and defined interval criteria with the potential to further optimize recognition of an EPI VT site of origin was then established (Fig. 1).
Source: Circ Arrhythmia Electrophysiol. 2010;3:62-71. Full text available here.

Epicardial Substrate and Outcome with Epicardial Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Thirteen patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and previous failed endocardial ablation referred from across the United States underwent epicardial ablation. All patients were experiencing recurrent VT episodes and were being considered for transplant if VT could not be controlled. Percutaneous pericardial access was successfully and safely obtained using a posterior approach to prevent laceration of the dilated RV. In all patients, the low voltage area with electrogram abnormalities (scar) was more extensive on the epicardium than the endocardium and the origin of epicardial VT was frequently opposite normal areas of endocardium (Fig. 2). Twenty-seven VTs were ablated successfully from the epicardium in 12 of the 13 patients. During an average follow-up of over 18 months, ten of 12 patients (84%) with acute VT elimination had no VT, and two patients had only a single VT episode at two and 38 months respectively without subsequent recurrences. Importantly, since this was a young patient population with an average age of 43 years, elimination of VT also obviated the need for amiodarone therapy in all the patients. The excellent outcome at Penn in this drug refractory group of patients supports an earlier role for ablation therapy in this patient population.
Source: Circulation. 2009;120:366-375. Full text available here.

Team of Faculty
The Hospital of the University of Pennsylvania has the largest electrophysiology program on the East Coast and one of the largest hospital-based programs in the US. Comprised of 14 full-time, board-certified electrophysiologists and more than 20 EP specialized nurse practitioners and physician assistants, the team is dedicated exclusively to treating and eliminating serious and potentially life-threatening heart rhythm disturbances. The team’s leadership in ablative and arrhythmia device therapy is evident in their collective contribution to more than 600 articles to scientific journals in the last 10 years.

Hospital of the University of Pennsylvania
Francis E. Marchlinski, MD
Director, Electrophysiology Professor of Medicine
David J. Callans, MD
Associate Director, Electrophysiology Professor of Medicine

Rajat Deo, MD
Assistant Professor of Medicine
Sanjay Dixit, MD
Associate Professor of Medicine
Andrew Epstein, MD, FAHA, FACC, FHRS
Professor of Medicine
Fermin C. Garcia, MD
Assistant Professor of Medicine

Mathew D. Hutchinson, MD
Associate Professor of Medicine
David Lin, MD
Associate Professor of Medicine

Michael P. Riley, MD, PhD
Assistant Professor of Medicine
Ralph J. Verdino, MD
Associate Professor of Medicine

Access

Inpatient Electrophysiology Locations:

Hospital of the University of Pennsylvania
9 Founders Building
3400 Spruce Street
Philadelphia, PA 19104

Outpatient Electrophysiology Locations:

Penn Heart & Vascular Care
Perelman Center for Advanced Medicine
East Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Medicine Radnor
250 King of Prussia Road
2nd Floor
Radnor, PA 19087

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral

To refer or transfer a patient with VT or other urgent arrhythmia problems, call 215-662-3999. You will be immediately placed in contact with a HUP electrophysiologist.

Enrolling Clinical Trials: The Microcirculation in Claudication and Exercise Rehabilitation

2013-08-06T12:29:00.003-04:00

Penn Heart and Vascular • Vascular Medicine

Researchers at Penn Medicine are investigating the contribution of microvascular dysfunction to claudication and the response of patients with peripheral artery disease (PAD) to supervised exercise rehabilitation.

PAD is common in the United States, affecting almost 30% of individuals older than age 70 and more than 50% of persons with a history of smoking. A condition for which leg pain (claudication) is the chief manifestation, PAD has a significant affect on function and quality of life.

The pathophysiology of PAD, while not completely understood, is thought to involve progressive vascular occlusion, typically in the proximal superficial femoral artery, the popliteal artery at the adductor canal and other susceptible regions where turbulent blood flow occurs.

The treatments for PAD and claudication have the objective of managing symptoms and preventing the progression of occlusion, and range from surgery and angioplasty to exercise rehabilitation and other noninvasive therapeutic strategies; the latter play a significant role in the treatment of mild-tomoderate PAD. Although strategies for surgical interventions have been relatively well elucidated, the foundation for new noninvasive therapies depends upon a greater understanding of the role of microvascular dysfunction and other key contributors to claudication and disease progression.

To investigate these concerns, researchers at Penn Medicine have initiated an NIH-supported clinical study with the major goals of evaluating the contribution of microvascular dysfunction to claudication and the response to supervised exercise rehabilitation among patients with PAD.

The Microcirculation in Claudication and Exercise Rehabilitation (MICRO)

Objectives: 1) To determine the relationship between treadmill peak walking time (PWT) and microvascular blood flow in subjects with moderate PAD; 2) To determine if changes in claudication-limited exercise tolerance correlate with changes in microvascular blood flow following exercise rehabilitation; 3) To determine if the vascular health profile, as measured with endothelial progenitor cells (EPCs) and microparticles (MPs), improves following exercise rehabilitation in patients with PAD.

Methods: (Aim-1) Two hundred and forty subjects with an ankle brachial index (ABI) between 0.4 and 0.8 and with claudication will undergo measurement of the claudication limited PWT using a graded treadmill protocol. A noninvasive technique, pulsed arterial spin labeling (PASL), will be used to measure microvascular blood flow mid-calf within the gastronemius muscle. Near infrared spectroscopy (NIRS) will be performed before, during and after exercise to evaluate the oxygenation level of blood in a targeted vessel and to verify the rate of blood flow. The hypothesis will be tested through a correlation of the PWT with CASL and NIRS measured skeletal muscle microvascular blood flow.

(Aim-2) One hundred and twenty of the 240 subjects in Aim-1 will be recruited to participate in a supervised exercise rehabilitation program for 12 weeks. PWT, skeletal muscle microvascular flow (PASL) and volume of oxygenated blood flow to the affected tissue (NIRS) will be measured at 12 weeks following study entry. The hypothesis will be tested through a correlation of changes in PWT with changes in PASL- and NIRS-measured microvascular blood flow. Data collected from the population of subjects not participating in the exercise intervention program will serve as a control.

(Aim-3) The subjects enrolled in Aim-2 will have blood drawn for measurement of EPCs and MPs at baseline 12 weeks following initiation of exercise rehabilitation. The hypothesis will be tested through an analysis of the magnitude and direction of change in the VHP after the intervention of exercise rehabilitation. These data will be evaluated alongside the results of the control population that did not participate in the exercise intervention program. The correlation between changes in the VHP, PWT and microvascular blood flow will also be evaluated.

The principal investigator for this study is Emile Mohler, MD.
For further information about this study, including enrollment guidelines, please contact:

Elizabeth Beothy, BA
Phone: 215-662-7986
Email: eabeothy@mail.med.upenn.edu

Supporting Clinical Research
Exercise-Induced Alterations in Circulating Progenitor Cell Populations

Dr. Mohler and colleagues have published [1] a novel flow cytometry approach for the assessment of multiple cell surface markers
to simultaneously measure the frequency of various subsets of circulating endothelial progenitor cells (EPCs) and mature circulating
endothelial cells at baseline and immediate post-exercise in young healthy patients, older healthy patients and patients with PAD. The
numbers of circulating PCs increased (CD 34+, p< 0.05) 10 minutes after exercise in young healthy subjects, but remained unchanged in PAD subjects and trended downward for older healthy subjects (Figure 2). This is the first published study evaluating the effect of acute exercise on EPCs and mature circulating endothelial cells in patients with claudication from PAD. Interestingly, there was only a slight increase in the progenitor cell subset and no change in EPC subset after exercise for the PAD group. This may be secondary to the relative sedentary lifestyle of patients with claudication as none of the patients we studied were engaged in regular exercise. It remains to be determined if EPC number or function increases after an exercise rehabilitation program and whether this improvement correlates with microvascular flow.

1. Shaffer RG, Greene S, Arshi A, Supple G, Bantly A, Moore JS, Parmacek MS, Mohler ER III. Effect of acute exercise on endothelial progenitor cells in patients with peripheral arterial disease. Vasc Med 2006;11:219-226.

Faculty Team
The specialists in the Penn Vascular Medicine Program offer the most fully integrated and comprehensive care for vascular disease in the Philadelphia region. Treatments include a variety of noninvasive diagnostic methods, lifestyle modification programs, drug therapy, laser therapy and sclerotherapy ablation for varicose and spider veins, as well as balloon angioplasty, stenting and other interventions.

The identification of risk factors that predispose an individual to vascular disease is central to vascular care at Penn. Thus, the Vascular Medicine Program emphasizes prevention and early detection to reduce risk before problems occur. The Program also continues a long tradition
of research and pioneering advances in vascular imaging, minimally invasive stenting, cell therapy to develop new arteries in legs and new medications to help with claudication, among other areas of clinical inquiry.

MICRO Trial Team

Investigators

Emile R. Mohler III, MD
Professor of Medicine

Thomas F. Floyd, MD
Adjunct Assistant Professor of Radiology

Clinical Research Coordinator

Elizabeth Beothy, BA

Download a pdf of this Clinical Briefing.

Biomechanical Modeling to Determine Risk of Aortic Dilatation, Dissection and Rupture

2011-09-30T10:38:00.002-04:00

In collaboration with the Gorman Cardiovascular Research Laboratory at the University of Pennsylvania, surgeons from the Division of Vascular Surgery and Endovascular Therapy, led by Benjamin M. Jackson, MD, are using computational biomechanical models to study the role that mechanical wall stress plays in a variety of aortic pathologies.

Electrocardiogram-gated computed tomography angiography (ECG-gated CTA) scan data were used to create the three dimensional models. Finite element analysis (FEA – a numerical method that subdivides complex structures into small elements with defined material properties to predict the distribution of wall stress in these structures under physiological loading) was then applied to the three dimensional mesh to determine the wall stress distribution of the aorta.

The researchers examined the etiology of thoracic aortic dissection and evaluated the rupture risk of aneurysms of the thoracic aorta. Their findings, which were presented at the 2010 meetings of the American Heart Association, the American College of Surgeons and the Society for Vascular Surgery, are reviewed below.

Clinical Study Review

Increased Ascending Aortic Wall Stress in Patients with Bicuspid Aortic Valves[1]
Objective: This study sought to determine why patients with bicuspid aortic valves (BAV) are at increased risk of ascending aortic dilatation, dissection, and rupture compared to patients with normal tricuspid aortic valves (TAV). BAV is a defect of the aortic valve that results in the formation of two leaflets or cusps instead of the normal three.
Methods: The investigators hypothesized that ascending aortic wall stress may be increased in BAV compared to TAV. Biomechanical models of the aorta were created using BAV/TAV pairs matched for diameter. Finite element analysis was then performed to predict wall stress in the ascending aorta using a systolic pressure load of 120 mm Hg and a uniform aortic wall thickness of 1.7 mm.
Results: When normalized by radius, the wall stress was greater in the ascending aorta of patients in the BAV group [0.31 ± 0.06 MPa/cm] than in those of the TAV group [0.27 ± 0.03 MPa/cm, P=0.013] (Figure 1). Thus, increased ascending aortic wall stress may account in part for the increased propensity to aortic dilatation, rupture and dissection in patients with BAV.
[1] Ann Thorac Surg. 2011;92:1384-1389.

Rupture Risk of Saccular Descending Thoracic Aortic Aneurysms by Stress Modeling
Objective: To investigate the rupture risk of saccular descending thoracic aortic aneurysms (DTA) by comparing wall stress in patients with saccular DTAs to that found in patients with fusiform DTA.
Methods: Three-dimensional meshes of the aorta were created from computed tomography angiography scan data of subjects with fusiform and saccular DTAs. Finite element analysis was then performed to determine wall stress using a systolic pressure load of 120 mm Hg and a uniform aortic
wall thickness of 3.2 mm.
Results: The normalized wall stress for saccular DTA was found to be greater than that for fusiform DTA (Figure 2), indicating that geometric factors (such as aneurysm shape) influence wall stress and rupture risk. The finding that saccular aneurysms have a higher wall stress than fusiform aneurysms of similar diameter provides a rationale for the repair of saccular DTA at a smaller diameter and suggests a role for biomechanical modeling
in surgical decision-making.

Pathogenesis of Acute Aortic Dissection: A Finite Element Stress Analysis[2]
Objectives: This study was performed to determine whether type A and B aortic wall dissections are caused by elevated pressure-induced regional wall stress.
Methods: The researchers created a three-dimensional mesh of the aorta. Finite element analysis using a systolic pressure load of 120 mm Hg was then performed to predict regional thoracic aortic wall stress.
Results: The researchers identified local maxima of wall stress above the sinotubular junction in the ascending aorta and distal to the left subclavian artery. No local maximum of wall stress was found in the remainder of the descending thoracic aorta. This stress distribution may contribute to the pathogenesis of aortic dissections, given their co-localization. Future investigations to determine the utility of image-derived biomechanical calculations in predicting aortic dissection are warranted, and therapies designed to reduce the pressure load-induced wall stress in the thoracic aorta are rational.
[2] Ann Thorac Surg. 2011;91:458-463.
Faculty Team
The Division of Vascular Surgery and Endovascular Therapy at Penn provides comprehensive therapy for arterial vascular disorders and Paget-Schroetter syndrome, including treatment of cerebrovascular disease, aneurysmal disease of the aorta, iliac, and peripheral arteries and treatment of occlusive disease of the aorta and its branches. The Division is also among a select group of research centers involved in FDA trials investigating new, advanced ways to treat thoracoabdominal aortic aneurysms.

Division of Vascular Surgery and Endovascular Therapy

Ronald M. Fairman, MD
Chief, Division of Vascular Surgery and Endovascular Therapy
Clyde F. Barker-William Maul Measey Professor of Surgery

Benjamin M. Jackson, MD
Assistant Professor of Surgery

Grace J. Wang, MD
Assistant Professor of Surgery

Gorman Cardiovascular Research Group

Joseph H. Gorman, III, MD
Professor of Surgery

Robert C. Gorman, MD
Professor of Surgery

Access
Perelman Center for Advanced Medicine
Penn Heart and Vascular Center
East Pavilion, 2nd Floor
3400 Civic Center Boulevard

To refer a patient to Penn Medicine, please contact Penn PhysicianLink^TM here or at 877-937-7366.

Download a pdf of this Clinical Briefing.

Comprehensive Care at Every Stage of Heart Failure

2010-08-09T08:20:00.002-04:00

The Heart Failure and Transplantation Program at the Hospital of the University of Pennsylvania (HUP) has developed a multidisciplinary algorithm for heart failure management that reflects the chronic, progressive nature of the disease. Thus, the program provides a seamless continuum of care to address heart failure, its effects and comorbidities from its earliest stages onward.

Case Study
Mr. W, a 58-year-old male with a two-year history of non-ischemic cardiomyopathy, was referred to the Penn Heart and Vascular Center. At presentation, his medications included carvedilol 25 mg BID, lasix 40 mg BID, enalapril 20 mg BID, and spironolactone 25 mg QD. Despite good compliance with this regimen, Mr. W was increasingly symptomatic, requiring an increase in his daily diuretic dose.

After consultation at Penn, Mr. W was electively scheduled for right heart catheterization, which revealed a markedly abnormal cardiac performance, with a cardiac index of only 1.4L/min/m2 and an elevated pulmonary capillary wedge pressure (35mmHg) with normal systemic vascular resistance. Milrinone was initiated following admission to the inpatient heart failure unit, with improvement in cardiac index.

An inpatient heart transplant evaluation was begun with the transplant team, including the nurse coordinator for transplant assessment and education, a social worker to address potential psycho-social concerns pre- and post-transplant, and a financial counselor to verify insurance and prescription coverage. A battery of lab tests was performed to more accurately determine Mr. W’s risk at the time of transplant and to aid in individualization of his post-transplant immunosuppression.

Mr. W felt much better on inotropic support, although he developed significant ventricular dysrhythmias. At the weekly multidisciplinary transplant meeting, the cardiac surgeons decided to evaluate Mr. W for a ventricular assist device (VAD) as a bridge to transplant. Subsequently, he underwent successful implantation of the HeartMate® II. His recovery was uneventful. To ensure that he would be in optimal condition for his transplant, he was followed closely by the nutritionists and physical therapists on the transplant team.

After successfully completing 6 weekly outpatient appointments with the VAD coordinators and HUP transplant cardiologists, Mr. W underwent heart transplant surgery. He has done remarkably well post-transplant. He eagerly talks about his experience and serves as an inspiration to those who are waiting on the list. He now comes in on a routine basis for his cardiac biopsies and is scheduled to start cardiac rehabilitation soon.

Our Team of Faculty
The Penn Heart and Vascular Center is comprised of a multidisciplinary team of specialists and clinicians whose experience spans the breadth and depth of heart failure care. The team includes some of the nation's finest cardiologists, cardiovascular surgeons, nurses, transplant and VAD coordinators, as well as social workers and specialists in cardiac imaging, arrhythmia management, cardiac anesthesia, infectious disease, immunology and rehabilitation medicine. Together, this team is dedicated to the management of patients with complex heart failure.

Heart Failure
Susan C. Brozena, MD
Associate Professor of Medicine
Thomas C. Cappola, MD, ScM
Herbert C. Rorer Associate Professor in Medical Sciences
Stephen M. Chrzanowski, MD
Brian M. Drachman, MD
Clinical Assistant Professor of Medicine

Lee R. Goldberg, MD, MPH
Associate Professor of Medicine

Mariell L. Jessup, MD
Professor of Medicine
Kenneth B. Margulies, MD
Professor of Medicine
Rhondalyn McLean, MD
Assistant Professor of Medicine
Anjali Tiku Owens, MD
Assistant Professor of Medicine
J. Eduardo Rame, MD
Assistant Professor of Medicine
Anjali Vaidya, MD
Assistant Professor of Medicine
Joyce W. Wald, DO
Assistant Professor of Clinical Medicine
Ross. R. Zimmer, MD
Clinical Assistant Professor of Medicine

Cardiovascular Surgery
Michael A. Acker, MD
William Maul Measey Professor of Surgery
Pavan Atluri, MD
Edward Cantu III, MD

Heart Failure Nurse Specialists
Eileen Baxter, BSN, RN
Sarah Fontana, MSN, RN, CHFN
Lauren McDevitt, BSN, RN
Patricia McGurl, MSN, RN
Judie Shilling, RN
Joann Treacy, BSN, RN
Linda Wells, MA, RN, CHFN
Mechanical Circulatory Support Device (MSD) Coordinators
Mary Lou O’Hara, MSN, RN, CCRN

Judy Marble, RN, BSN

Heart Transplant Clinical Practitioners
Susan Chambers, MSN, CRNP
Wilhelmina Maslanek, MSN, CRNP
Maria Molina, MSN, CRNP
Patricia Curry-Stutman, MSN, CRNP
Mary Williams, MSN, CRNP

Heart Transplant Nurse Coordinators
William Wynne, BSN, RN
Patricia Poderis RN

Pre-Transplant Coordinator
Nicole Hornsby, MSN, CRNP

Social Workers
Deborah L. Gordon, MSS, LCSW
Sallie Blair Smith, MSW
Julia Bruno, MSW, LSW

Financial Coordinator
Cammy McCaskill

Clinical Operations Director
Donna Chojnowski, MSN, CRNP

For more information on Heart Failure, Mechanical Assist Device and Transplantation programs and services.

To refer a patient and/or consult with a doctor: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral or http://PennMedicine.org/heart.

Importance of Evaluation for Obstructive Sleep Apnea in Obese Patients with Type 2 Diabetes

2010-06-17T10:51:00.002-04:00

Specialists at the Penn Sleep Centers are encouraging physicians treating obese patients with diabetes, particularly those with higher waist circumferences (truncal obesity), to be evaluated for obstructive sleep apnea (OSA). Data from epidemiologic and clinical studies now suggests that OSA places patients at increased risk for the development of altered glucose metabolism, and could thus be a contributing cause of type 2 diabetes.¹ In studies comparing obese OSA patients with weight matched non-OSA controls, the combination of OSA and obesity was found to increase insulin resistance.² According to a recent report,3 the prevalence of undiagnosed OSA among obese patients with type 2 diabetes is greater than 85% (Figure 1). Importantly, many of the patients in the study had no symptoms of sleepiness or snoring, and reported symptoms (such as sleepiness and snoring) did not predict which patients were likely to have sleep apnea. More than half of the patients with OSA had moderate or severe sleep apnea, a factor shown in recent population-based and longitudinal studies to be an independent risk factor for all cause mortality. Some studies ^4,5 have shown that diabetic patients with OSA who receive sustained, regular treatment with continuous positive airway pressure (CPAP) can improve insulin sensitivity and glycaemic control. CPAP treatment has been demonstrated to reduce systolic blood pressure and heart rate and to improve left ventricular ejection fraction in patients with OSA.

Case Study
Mr. E, a 35-year-old man, presented to his primary care physician for routine follow up care. His medical history was significant for type 2 diabetes, hypertension and obesity. Outpatient medications included metformin 1000mg twice daily, lisinopril 10mg once daily and amlodipine 10mg once daily. The patient had no specific complaints during the visit but, when asked by his physician, admitted that his wife had urged him to visit because she could no longer tolerate his snoring. He denied excessive daytime sleepiness. Clinical examination was significant only for obesity (body mass index = 37.2kg/m2) and an elevated blood pressure of 145/94, despite antihypertensive medications. An outpatient sleep study was ordered to investigate for obstructive sleep apnea (OSA). The polysomnogram revealed severe obstructive sleep apnea with an apnea hypopnea index of 42 events per hour and an oxyhemoglobin nadir of 80%. The patient was referred for a titration polysomnogram, which established a CPAP pressure of 10 cm of water as the optimal pressure needed to treat Mr. E’s severe OSA. CPAP therapy was initiated using a nasal mask interface. Mr. E returned to his primary care provider three months later. His blood pressure was within optimal range (128/74) without change in his antihypertensive regimen. His wife reported his snoring had been abolished with the use of his CPAP unit. In addition, Mr. E noted that he now feels more energized and rested on waking in the morning. "Given that OSA may complicate diabetes in the obese, it’s important that physicians treating obese patients with type 2 diabetes consider the possibility of OSA, even in the absence of symptoms. This is especially true of those with higher waist circumference and higher BMI levels." -Allan I. Pack, MB, ChB, PhD Chief, Division of Sleep Medicine Professor of Medicine

References

Tasali E, Mokhlesi B, Van Cauter E. Chest. 2008;133:496506.
Tassone F, Lanfranco F, Gianotti L, et al. Clin Endocrinol (Oxf). 2003;59:374379.
Foster GD, Sanders MH, Millman R, et al. In press. Diabetes Care. 2009.
Schachin SP, Nechanitzky T, Dittel C, et al. Med Sci Monit. 2008;14: CR117CR121.
Harsch IA, Schahin SP, RadespielTröger M, et al. Am J Resp Crit Care Med. 2004;169:156162.

Team of Faculty
Penn Sleep Center is comprised of a multidisciplinary team of clinicians from the departments of medicine, neurology, psychiatry, otorhinolaryngology and oral and maxillofacial surgery—a concentration of expertise that permits a comprehensive approach to the diagnosis and treatment of sleep disorders and their comorbidities. One of only three sleep centers in the United States designated by the National Institutes of Health as a specialized center for research in sleep, the Penn Sleep Center is fully accredited by the American Academy of Sleep Medicine. With seven locations in the Philadelphia area, the Sleep Center currently performs more than 5,000 sleep studies each year.

Allan I. Pack, MD, Phd Assistant Professor of Urology in Surgery
Charles R. Cantor, MD, DABSM Medical Director, Penn Sleep Centers Clinical Associate Professor of Neurology
Maria Antoniou, MD, DABSM Assistant Professor of Clinical Medicine
Philip R. Gehrman, PhD, CBSM Assistant Professor of Psychiatry
Nalaka S. Gooneratne, MD, DABSM Assistant Professor of Medicine
Indira Gurubhagavatula, MD, MPH Assistant Professor of Medicine
Grace W. Pien, MD, MSCE, DABSM Assistant Professor of Medicine
David M. Raizen, MD, PhD, DABSM Assistant Professor of Neurology
Ilene M. Rosen, MD, DABSM Assistant Professor of Clinical Medicine
Sharon L. Schutte-Rodin, MD, DASBSM, CBSM Clinical Associate Professor of Medicine
Richard J. Schwab, MD, DABSM Professor of Medicine
Sigrid C. Veasey, MD, DABSM Associate Professor of Medicine

Access
Patient appointments are available at:

Penn Sleep Centers
Hospital of the University of Pennsylvania*†
3624 Market Street
Suite 201
Philadelphia, PA 19104

Penn Sleep Center**†
3624 Market Street
Suite 201 Philadelphia, PA

Pennsylvania Hospital**
800 Spruce Street
Philadelphia, PA 19107

Penn Medicine Radnor ***†
250 King of Prussia Road
2nd Floor
Radnor, PA 19087

Penn Sleep Center at the Sheraton University City Hotel*† 3
6th and Chestnut Streets
Philadelphia, PA 19104

Penn Sleep Center at the Pavilion at Doylestown Hospital*
599 West State Street
Suite 101
Doylestown, PA 18901

Penn Sleep Center at Audubon Homewood Suites Hotel*†
681 Shannondell Blvd
Audubon, PA 19403

† Indicates a facility of the Hospital of the University of Pennsylvania
* Indicates overnight sleep study site
** Indicates overnight sleep study site and sleep specialist site
*** Indicates sleep specialist site

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral

Continuous Positive Airway Pressure Therapy for Patients with Obstructive Sleep Apnea and Atrial Fibrillation

2010-06-16T08:45:00.002-04:00

The Penn Sleep Centers are currently using continuous positive airway pressure (CPAP) to treat patients with obstructive sleep apnea (OSA) who have atrial fibrillation.

The primary therapy for OSA, CPAP has known antihypertensive and antisympathetic effects, and has been demonstrated to reduce the risk of recurrent atrial fibrillation.

Obstructive sleep apnea is characterized by repetitive pharyngeal collapse during sleep resulting in blockage of the airway, hypoxia and sleep disruption. OSA is very common in the US population— recent data suggests that approximately 20 percent of the population is affected.

Multiple studies have demonstrated a strong association between atrial fibrillation and OSA. Patients with OSA are more likely to have atrial fibrillation than patients without OSA. Furthermore, in patients that undergo cardioversion for atrial fibrillation, OSA—if present—has been associated with a high rate of atrial fibrillation recurrence.

Emerging data continues to elucidate the pathophysiological relationship between OSA and atrial fibrillation. The hypoxemia and hypercapnea that occur in OSA are known to be arrhythmogenic. Other effects of the disorder, including increased sympathetic drive and elevated Creactive protein levels, are associated with the pathogenesis of atrial fibrillation.

The Penn Sleep Centers have been using new CPAP technology to improve patient adherence to therapy and allow physicians to track information on patient’s sleeping patterns. In addition to alerting the patient and Sleep Center staff when there is a mask leak, the new technology provides information on whether apnea has been eliminated and whether the machine is being used on a nightly basis.

Case Study

Mr. J, a 49-year-old man, presented to the Emergency Department (ED) with palpitations, lightheadedness and shortness of breath. He denied chest pain. His symptoms had started 2 hours prior, during the night (at approximately 11pm) and woke him from sleep. His medical history was significant only for paroxysmal atrial fibrillation and hypertension for which the patient was taking HCTZ 25mg once daily.

In the past, he had one episode of atrial fibrillation confirmed by EKG at his primary physician’s office. The episode was self-limited and resolved without specific intervention within 24 hours of onset. At that time, nuclear stress testing was negative for ischemia and echocardiogram revealed left ventricular hypertrophy and mildly elevated pulmonary artery pressure.

Thyroid functions were within normal limits. Examination in the ED revealed an obese man, in respiratory distress with blood pressure of 77/45 and a heart rate of 165/minute. EKG confirmed atrial fibrillation with rapid ventricular response; ST segments appeared normal. Cardiac enzymes were within normal limits.

Cardioversion with 100J successfully converted the patient to sinus rhythm. A review of the patient’s history found excessive daytime somnolence and loud snoring. Focused upper airway examination revealed macroglossia, tongue ridging and a crowded oropharynx
(Fig. 1).

Mr. J had an overnight polysomnogram (Fig. 2) as an outpatient, which confirmed severe obstructive sleep apnea associated with severe oxyhemoglobin desaturation (oxyhemoglobin nadir = 75%). The apnea/hypopnea index equaled 37 events per hour. CPAP therapy was commenced.

One year later, Mr. J continued to be compliant with CPAP therapy. His excessive daytime somnolence had markedly improved, his BMI had decreased after having initiated a regular exercise routine and no further episodes of atrial fibrillation had occurred.

Team of Faculty

Comprised of a consortium of clinicians from the departments of medicine, neurology, psychiatry, otorhinolaryngology and oral and maxillofacial surgery, the Penn Sleep Center is one of only three sleep centers in the United States designated by the National Institutes of Health as a specialized center for research in sleep. This concentration of physicians from different departments permits a comprehensive approach to the diagnosis and treatment of sleep disorders and their comorbidities.

Allan I. Pack, MD, PhD
Chief, Division of Sleep Medicine Professor of Medicine

Charles R. Cantor, MD, DABSM
Director, Penn Sleep Centers Clinical Associate Professor of Neurology

Maria Antoniou, MD, DABSM
Assistant Professor of Clinical Medicine

Philip R. Gehrman, PhD, CBSM
Assistant Professor of Psychiatry

Nalaka S. Gooneratne, MD, DABSM
Assistant Professor of Medicine

Indira Gurubhagavatula, MD, MPH
Assistant Professor of Medicine

Grace W. Pien, MD, MSCE, DABSM
Assistant Professor of Medicine

David M. Raizen, MD, PhD, DABSM
Assistant Professor of Neurology

Ilene M. Rosen, MD,DABSM
Assistant Professor of Clinical Medicine

Sharon L. Schutte-Rodin, MD, DABSM, CBSM
Clinical Associate Professor of Medicine

Richard J. Schwab, MD, DABSM
Professor of Medicine

Sigrid C. Veasey, MD, DABSM
Associate Professor of Medicine

Access

With seven locations in the Philadelphia area, the Sleep Center currently performs more than 5,000 sleep studies each year. Patient appointments are available at:

Penn Sleep Centers
Hospital of the University of Pennsylvania***†
3624 Market Street Suite 201
Philadelphia, PA 19104

Penn Sleep Center*†
3624 Market Street,
Suite 201 Philadelphia, PA

Pennsylvania Hospital*
800 Spruce Street
Philadelphia, PA 19107

Penn Medicine Radnor **†
250 King of Prussia Road
2nd Floor
Radnor, PA 19087

Penn Sleep Center at the Sheraton University City Hotel***†
36th and Chestnut Streets
Philadelphia, PA 19104

Penn Sleep Center at the Pavilion at Doylestown Hospital***
599 West State Street Suite 101
Doylestown, PA 18901

Penn Sleep Center at Audubon Homewood Suites Hotel***†
681 Shannondell Blvd
Audubon, PA 19403 †

* Indicates a facility of the Hospital of the University of Pennsylvania
** Indicates overnight sleep study site and sleep specialist site
*** Indicates sleep specialist site
***† Indicates overnight sleep study site

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral

Endovascular Stent Grafts for Thoracic and Aortic Aneurysm Repair: Clinical Developments 2009

2009-12-08T12:22:00.002-05:00

The Division of Vascular Surgery and Endovascular Therapy at Penn Medicine has been at the forefront of clinical research in endovascular devices to treat abdominal aortic aneurysms AAAs) for almost two decades. As a result, Penn endovascular surgeons were among the first in the nation to use minimally invasive endovascular stent grafts to repair abdominal and thoracic aortic aneurysms. Penn is currently one of a small number of research centers in the United States involved in studies to further refine existing endograft devices as well as to develop new devices for endovascular repair.

Ongoing Endovascular Clinical Trials The Endurant Stent Graft System Trial
The Endurant Stent Graft System features the newest iteration of an FDA-approved device that has been enhanced with flexible components and a lower delivery profile to permit better access to blood vessels in patients with challenging anatomies, including tortuous or highly angulated aortas, small iliacs or aneurysms with short necks (a proximal neck of 15 mm length is usually required to allow endovascular AAA repair). These patients are currently treated with open surgery. The Endurant graft system has improved migration resistance, a smaller profile and suprarenal anchoring pins designed to permit slow, controlled deployment at the renal arteries, and is thus well suited to infrarenal implantation. Ronald M. Fairman, MD, is the principal investigator at the Hospital of the University of Pennsylvania (HUP); Edward Y. Woo, MD, is the co-principal investigator.

The Zenith® Fenestrated AAA Endovascular Stent Graft Trial
This Phase 1 trial is investigating the safety and efficacy of the Zenith Fenestrated AAA Endovascular Stent Graft. The device was developed to treat complex abdominal aortic aneurysms, and incorporates scallops called fenestrations in the top section, permitting it to treat aortic and aorto-iliac aneurysms extending close to the renal and superior mesenteric arteries. This reduces the risk of restricting or blocking critical blood flow to the kidneys and bowel. This device has been approved in Europe. Ronald M. Fairman, MD, is the principal investigator at HUP.

The Zenith® Low-Profile AAA Endovascular Graft Trial
This trial is investigating the efficacy and safety of a smaller delivery system and new nitinol version of the Zenith AAA endograft. The device is designed for patients with smaller vascular access vessels who might not otherwise be candidates for endograft treatment. Advantages include a reduced need for surgical cut down to access the femoral artery for device insertion. Ronald M. Fairman, MD, is the national principal investigator; Edward Y. Woo, MD, is the principal investigator at HUP.

Team of Faculty
The Division of Vascular Surgery and Endovascular Therapy at Penn performs more carotid, aortic, and peripheral arterial repairs than any other medical center in the region, and is involved in advanced FDA trials to investigate new ways to treat abdominal and thoracic aortic aneurysms.

Hospital of the University of Pennsylvania
Ronald M. Fairman, MD Chief, Division of Vascular Surgery and Endovascular Therapy, Clyde F. Barker-William Maul Measey Professor of Surgery
Clyde F. Barker, MD Donald Guthrie Professor of Surgery
Benjamin M. Jackson, MD Assistant Professor of Surgery
Edward Y. Woo, MD Assistant Professor of Surgery
Grace Wang, MD Assistant Professor of Surgery

Patient appointments are available at:

Hospital of the University of Pennsylvania
3400 Spruce Street
4 Silverstein Pavilion
Philadelphia, PA 19104

Perelman Center for Advanced Medicine
Penn Heart and Vascular Center
East Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Presbyterian Medical Center
Department of Surgery
266 Wright Saunders Building
39th & Market Streets
Philadelphia, PA 19104

To refer a patient and/or consult with a doctor: Call 800-789-PENN (7366) or visit PennMedicine.org/referral