Cath Lab Digest - May 2008 - (Page 8)

8 ON THE HORIZON MAY 2008 continued from page 1 Cell Therapy in the Cath Lab for Heart Failure: A look at MyoCell® Therapy and the SEISMIC Trial Interestingly, it no longer resembles a pure skeletal muscle cell, nor does it achieve a full cardiac muscle cell phenotype. Instead, it functions somewhere in between. In doing so, these myoblast cells convert from a fast-twitch to a slow-twitch phenotype and are then able to contribute to the cardiac workload. After a large number of confirming preclinical studies, the first series of human studies with autologous skeletal myoblasts were conducted in early 2000-2001. Among them was the first study in which a catheter was used to implant the cells. Many of the early studies with either stem cells or other biologic agents involved cardiac surgery (frequently still the case today), with the surgeon injecting cells, genes or other investigational biologic About the SEISMIC [Safety and Effects of Implanted (Autologous) Skeletal Myoblasts (MyoCell®) using an Injection Catheter] Trial The SEISMIC trial, a 40-patient, randomized, multicenter, controlled, Phase II-a study conducted in Europe, evaluated the catheter application of autologous skeletal myoblasts in patients with congestive heart failure (CHF). Proprietary cell (MyoCell®) and endoventricular needleinjection catheter (MyoCath®) products of Bioheart, Inc. were used in this study. Patients were required to be stable on standard medical therapy for CHF, as well as previously fitted with implanted cardiac defibrillators (ICDs). On admission to the trial, patients were randomized at a 2:1 ratio into the treatment versus control groups with 26 patients receiving MyoCell therapy and 14 patients randomized to the control group and receiving optimal medical therapy alone. “The results from the SEISMIC Trial are encouraging,” said Prof. Patrick W. Serruys, MD, PhD, Principal Investigator and Chief, Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center – Rotterdam, the Netherlands. Final six-month, follow-up patient data were presented by Prof. Serruys during the late-breaking clinical trial sessions at the April 2008 American College of Cardiology Scientific Session. “While the study was specifically designed to show safety, the findings also suggest positive trends in clinical benefits when evaluating the treated group versus the control group at six months.” Patients in both groups were evaluated at three- and six-month intervals using a variety of tests, including digital imaging and standard quality-of-life measurement such as the six-minute walking test, New York Heart Association (NYHA) heart failure classification and Minnesota Living with Heart Failure (MLHF) questionnaire. Final six-month results observed in the SEISMIC trial include: • Average left ventricular ejection fraction for patients in the cell therapy and control arms remained essentially unchanged. For the treatment arm, ejection fraction slightly increased from 30.9% at baseline to 31.2% at six months, while patients in the control arm under standard medical therapy essentially remained unchanged (32.6% and 32.5%, respectively). At six months, however, the end systolic diameter of the left ventricle was smaller in the cell-therapy treated patients (54.6 mm vs. 51.7 mm), suggesting a trend toward positive remodeling. • 84% of treated patients experienced improved or unchanged sixminute walking test scores compared to 31% of the control group, while 69 percent of the control group's results worsened, versus only 16% of the treated group. • 94% of treated patients experienced improved or unchanged NYHA classification compared to 58% of the control group, while 42% of the control group’s results worsened versus only 6% of the treated group. Prof. Serruys also noted that reports of arrhythmia among the patients evaluated in SEISMIC, both in terms of total number of episodes as well as timing of episodes, were no different between the treatment and control arms in the study. This suggests that MyoCell is not associated with a higher prevalence of arrhythmias; rather, that arrhythmias are an expected occurrence for this subset of heart failure patients. “These data support the need for a randomized, double-blind, placebo-controlled study involving the MyoCell technology,” said Prof. Serruys. “We look forward to applying our learning from this trial to the larger, more comprehensive MARVEL trial currently underway in the U.S. and Europe.” MARVEL is a phase II/III, double-blind, randomized, placebo-controlled multicenter study to assess the safety and cardiovascular effects of MyoCell implantation by a catheter delivery system in congestive heat failure patients post-myocardial infarction(s). of cells having the same capabilities of differentiation and division. While “resident” stem cells have been identified in the heart, they seem unable to effectively repair the myocardium in the way that skeletal myoblasts can repair skeletal muscle. The catheter is placed in the left ventricle and the interventional cardiologist navigates it to the region where a previous heart attack has occurred (target area). A needle is extended at the distal tip of the catheter, through which cells are injected. When this began in the 1990’s, the thought was to see whether implanting skeletal myoblasts into the heart could somehow take over or replace some of the function lost by patients having previous heart attacks or those suffering other forms of cardiac injury, even though skeletal myoblasts are programmed to do a different kind of work than heart muscle. Animal studies leading up to human studies, both in the U.S. and in Europe, indicated that when a skeletal myoblast is implanted into a cardiac environment, it can take on a hybrid form of function. products when a patient was undergoing bypass surgery. The first catheter-based delivery of a myoblast was in 2001, in Prof. Patrick Serruys’ cath lab at the Erasmus University Thoraxcenter, in The Netherlands. I was fortuntate to be working along with other investigators on the Bioheart team, including Prof. Serruys. We treated the first series of patients using a catheter to implant these cells. The results from this early work were published in the Journal of the American College of Cardiology in 2003 (Smits et al., JACC, Vol. 42, No. 12, 2003: 2063-2069). Disclosure statement: Dr. Sherman is a member of the Bioheart Scientific Advisory Board. He reports no conflicts of interest regarding the content herein.

Table of Contents Feed for the Digital Edition of Cath Lab Digest - May 2008

Cath Lab Digest - May 2008 The King Faisal Specialist Hospital and Research Centre Cell Therapy in the Cath Lab for Heart Failure: A Look at MyoCell® Therapy and the SEISMIC Trial Performance Improvement Strategies Speed Up Treatment Times in the Management of ST-Elevation Myocardial Infarction (STEMI) Patients Contents Clinical Editor’s Corner Commentary: Performance Improvement Strategies Speed Up Treatment Times in the Management of ST-Elevation Myocardial Infarction (STEMI) Patients Ask the STEMI Expert Comparing Drug-Eluting Stents and Bare-Metal Stents SICP: The Ten-Minute Interview with… Christopher Kambak, RT(R) Cardiac Cath Lab Economics in a Public Hospital of a Developing Country Keeping Your Heart & Vascular Employees: Proven Ideas for an Effective Retention Plan Unspoken Words Ask the Clinical Instructor Society of Invasive Cardiovascular Professionals Meetings Calendar Education Center What Do You Think? Clinical & Industry News Classifieds Advertisers Index

Cath Lab Digest - May 2008

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