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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Optimizing Cardiac Metabolism: A Novel Strategy in the Treatment of Ischemic Heart Disease


GOAL
To provide cardiologists with information on optimizing cardiac metabolism in patients with ischemic heart disease.

TARGET AUDIENCE
This activity is designed for cardiologists. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Review the prevalence, underlying pathophysiology, and current treatment options for ischemic heart disease.
  • Discuss the role of fatty acid oxidation in cardiac metabolism and reperfusion.
  • Identify strategies for optimizing cardiac metabolism.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  2 hours.

Release date: November 15, 2004. Expiration date: November 15, 2006.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from CV Therapeutics.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:


PROGRAM DIRECTOR

Roger S. Blumenthal, MD, FACC, FCCP, FAHA
Associate Professor of Medicine
Director, Preventive Cardiology
Johns Hopkins Ciccarone Center
for the Prevention of Heart Disease
Johns Hopkins University
School of Medicine
Baltimore, Maryland
Dr Blumenthal reports receiving grants/research support and honoraria from AstraZeneca LP, Kos Pharmaceuticals, Inc, Merck & Co, Inc, and Pfizer Inc.


PARTICIPATING FACULTY

Andrei Damian, MD, FACC
Cardiovascular Consultants, Ltd
Phoenix, Arizona
Dr Damian reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Gary Lopaschuk, PhD
Professor
Departments of Pediatrics and Pharmacology
Cardiovascular Research Group
University of Alberta
Edmonton, Alberta, Canada
Dr Lopaschuk reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Lionel Opie, MD, PhD, DSc, FRCP
Director, Cape Heart Centre
Director, Medical Research
  Council Interuniversity Cape Heart
  Research Group
University of Cape TownMedical School
Cape Town, South Africa
Dr Opie reports receiving honoraria from CV Therapeutics.

Michael Sack, MD, PhD
National Heart, Lung, and Blood Institute
Molecular Biology Section
National Institutes of Health
Bethesda, Maryland
Dr Sack reports having no significant financial or advisory relationships with corporate organizations related to this activity.

David R. Sease, MD, FACC
Cardiovascular Consultants, Ltd
Phoenix, Arizona
Dr Sease reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Marc D. Thames, MD, FACC
Cardiovascular Consultants, Ltd
Phoenix, Arizona
Dr Thames reports serving as a consultant to and receiving honoraria from CV Therapeutics.

Notice: In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. The following faculty members have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs or devices:

Dr Thames—ranolazine, trimetazidine.
Drs Opie and Sack—glucagon-like peptide-1, glucose-insulin-potassium, L-carnitine, perhexiline, propionyl L-carnitine, ranolazine, trimetazidine.
Dr Sack—glucagon-like peptide-1, glucose-insulin potassium, ivabradine, ranolazine, trimetazidine.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.


Optimizing Cardiac Metabolism: A Novel Strategy In The Treatment Of Ischemic Heart Disease
Roger S. Blumenthal, MD, FACC, FCCP, FAHA*

Ischemic heart disease is associated with significant morbidity and mortality. It has been estimated that coronary artery disease (CAD) affects more than 12 million people in the United States and a little under half of these patients will experience angina pectoris. Typically, treatment strategies for CAD include a combination of lifestyle changes, pharmacological, and/or surgical therapies. Therapies that could reverse ischemic heart disease itself would be ideal; unfortunately, such therapies are not available and many patients are refractory to antianginal therapies in use today. Over the past decade, we have increased our understanding of cardiac metabolism in the oxygenated and ischemic state. Patterns of cardiac metabolism are not just theoretically interesting as these patterns are now being transformed into meaningful therapeutic options in the management of ischemic heart disease. In this series, an overview of ischemic heart disease is provided from a biochemical and clinical standpoint. In addition, treatment strategies for optimizing cardiac metabolism are reviewed.

Marc D. Thames, MD, FACC, David R. Sease, MD, FACC, and Andrei Damian, MD, FACC, from Cardiovascular Consultants, Ltd, have prepared a conceptual framework for understanding angina pectoris. Beginning with a basic definition of angina pectoris including conditions that can provoke or exacerbate this symptom, their discussion turns to an explanation of what actually causes the sensation of anginal discomfort. The idea of coronary flow reserve is presented including important concepts in understanding the flow limiting effects of coronary stenosis. Treatment options for the management of patients with chronic stable angina are presented with a primary objective of returning the patient to normal activities. Pharmacological, nonpharmacological, and alternative therapies are reviewed as therapeutic options.

Gary Lopaschuk, PhD, has provided a biochemical perspective on the role of fatty acid oxidation in cardiac ischemia and reperfusion. The importance of metabolic homeostasis involving adequate oxygen and oxidizable substrates in meeting the energy demands of the heart is explained. Intracellular changes that occur in the heart following ischemia are presented in a manner that assists the reader in understanding the importance of fatty acid reduction after reperfusion. Dr Lopaschuk compares the metabolism of fatty acids and glucose and the associated effects on production of adenosine triphosphate (ATP) and ionic homeostasis. This article concludes with a discussion of myocyte necrosis and resultant reductions in cardiac efficiency associated with ischemia.

The third article is a collaborative effort on the parts of Lionel Opie, MD, PhD, DSc, FRCP, and Michael Sack, MD, PhD. Drs Opie and Sack review several metabolically active agents that act by directly or indirectly stimulating glucose metabolism and glycolysis. Alterations in cardiac metabolism associated with ischemia are explained and related to the rationale behind usefulness of antianginal agents that manipulate cardiac metabolism. The mechanisms involved in the regulation of fatty acid concentrations are reviewed. Included in their discussion of novel agents are glucose-insulin-potassium (GIK), glucose-insulin, glucagon-like peptide-1 (GLP-1), L-carnitine, ranolazine, and trimetazidine.

Dr Sack continues his contribution to this series by providing a review of clinical data of novel antianginal agents as well as clinical implications of these data. Recent clinical data for 2 orally active cardiac metabolism therapies, ranolazine and trimetazidine, are reviewed. Both agents have demonstrated antianginal effects independent from central hemodynamic effects as monotherapy or when combined with traditional drug therapy. Ranolazine is currently under review at the Food and Drug Administration.

Continuous infusions with GIK have provided important data in demonstrating that manipulation of cardiac metabolism may play an important role in the future of antianginal therapy. Preliminary data for GLP-1 and ivabradine suggest these agents may one day be useful in the management of ischemic heart disease. Although promising data are available on novel antianginal therapies, Dr Sack concludes by stating that further data are needed to determine if these novel therapies will actually be able to provide relief for the many angina patients not well controlled with traditional therapies and/or revascularization.

Lastly, an interview with Dr Opie on the future of treating ischemic coronary disease completes this publication. An explanation about the nature of the imbalance between the supply and the use of energy observed in cardiac ischemia is provided. Dr Opie explains that the production of heat consumes a great quantity of the heart's energy while much less ATP is used for contraction and ionic homeostasis. His hypothesis that abnormally increased rates of fatty acid metabolism "waste oxygen" is explained in relationship to a loss of cardiac efficiency in the ischemic heart. Finally, the electrical and mechanical properties of the heart during and after ischemia are discussed.

Traditional pharmacotherapy used in the management of chronic stable angina manipulates the body's need for ATP or the formation of ATP. The fact that many CAD patients continue to suffer from angina despite traditional therapy coupled with our growing understanding that ischemic heart disease is a result of biochemical changes in cardiac metabolism have given rise to the importance of novel antianginal therapy. This series provides the framework for a better understanding of new agents that are able to manipulate cardiac metabolism and may provide for faster functional recovery from an ischemic event.

*Associate Professor of Medicine, Director, Preventive Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address correspondence to: Roger S. Blumenthal, MD, FACC, FCCP, FAHA, Johns Hopkins Ciccarone Center, 600 N Wolfe Street - Blalock 524-C, Baltimore, MD 21287.
E-mail:
rblument@jhmi.edu.





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