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In 1988 the United States Centers for Disease Control in Atlanta, Georgia sponsored a meeting of academic physicians who defined a syndrome called the Chronic Fatigue Syndrome (CFS).  The physician-scientists described a syndrome – that is, a group of symptoms not understood by doctors – in which previously healthy young adults in their late 30’s to 40’s (typically) became ill with an unexplained, ongoing fatigue which ultimately was so severe that it disrupted the ordinary life of the affected patients.  Exercise worsened the fatigue.  A non-rotational lightheadedness was common.  Multiple aches were common, and ultimately, the patients with the newly named Chronic Fatigue Syndrome could not work, shop or engage in ordinary activities of everyday life.  There was no understanding as to cause, and some physicians thought this was really a psychiatric illness.  But anyone experiencing such a drastic change in her/his life would become depressed.

I was unaware of their work at this time. However, the doctors assembled in Atlanta concluded that CFS was a physical illness of unknown cause.  CFS offered a great challenge to physicians, because understanding the cause of an illness determines its treatment.  There was no understanding of the cause of the overwhelming, incapacitating fatigue of CFS.

After a satisfying professorial career of over 20 years, I left academic life in 1982.  I looked forward to practicing Internal Medicine and Infectious Diseases.  My background was Infectious Diseases, particularly viral diseases.  I was aware of virus induced heart disease, having studied this in my university research.  This research resulted in articles as well as textbook chapters regarding cardiomyopathy.

Ultimately I became aware that the symptoms of CFS resembled a prolonged infectious mononucleosis.  Infectious mononucleosis is an illness usually occurring in adolescence.  Infectious mononucleosis may be caused by one of two herpesviruses: the Epstein-Barr virus (EBV) or the Human Cytomegalovirus (HCMV).  These two mononucleosis syndromes are self-limited; that is, patients recover.

Fairly soon, I asked myself  - Could Chronic Fatigue Syndrome be a prolonged mononucleosis syndrome?  There isn’t anyone who has any kind of a heart condition who isn’t fatigued.  Could Chronic Fatigue Syndrome also involve the heart?



I began to look at patients with CFS for evidence of involvement of the heart, and experience (by tests of blood for antibodies) with the two mononucleosis viruses, EBV and HCMV.  The findings have been remarkable!

Abnormal Holter Monitoring

Abnormal T-wave flattenings and inversions are found in patients with the US Centers for Disease Control defined CFS.  This finding has been tested statistically, and we can now say that 90% of patients with CFS have abnormal 24-hour monitoring.  This is a biomarker.  The absence of abnormal Holter monitoring leads us to believe that CFS as the cause of fatigue is less likely.  The T-wave of the electrocardiogram records repolarization (electrical recovery) of the left ventricle after every heartbeat in preparation for the next heartbeat.  The normal T-wave is upright.  With increased heart rates the abnormal T-waves occur.  Abnormal oscillating T-waves occur with exercise.  The symptoms of CFS are worsened by exercise, a striking coincidence.

Abnormal Contraction of the Heart

Patients with CFS who have been ill for months may have abnormal cardiac dynamics.  This means that the rhythmic, symmetrical, wonderful symphonic-like harmonious closure of the left ventricle is now asymmetric.  This indicates that there is some weakening of the left ventricular muscle.  (Patients with coronary artery disease may also have abnormal left ventricular dynamics.)  We have found that approximately 1 in 4 patients with CFS who has been ill for one year or more has abnormal asymmetric abnormal cardiac dynamics.  It is indeed frightening to hear of weakening of the heart muscle.  Therefore, at this time and out of context, I report that the treatment with anti-viral medicines, which we use, may reverse this heart muscle weakness, and return it toward normal!

Heart Biopsies Show Cardiomyopathy

Biopsies of the heart from CFS patients indicate that there is cardiac involvement.  I have been fortunate to attract a very talented group of physicians interested in studying CFS with me.  They are Dr. Howard Dworkin, formerly Head of Nuclear Medicine at William Beaumont Hospital (WBH); Dr. William O’Neill, formerly Head of Cardiology ,WBH, and presently Clinical Dean, University of Miami School of Medicine; Dr. James Goldstein, Academic Cardiologist, WBH,  and Dr. Marcus Zervos, formerly Head of Infectious Diseases Research, WBH, now Chief, Infectious Diseases, Henry Ford Hospital, Detroit.  Thomas Fitzgerald, Ph.D., Statistician on the faculty of the University of Michigan Hospital has been and is a continuing important collaborator.  Sio Beqaj, Ph.D, molecular biologist, currently Director of Path Group Laboratory, Nashville, TN, has been and remains an active collaborator.  He is also Director of the laboratory at the Treatment Center for CFS, Beverly Hills, MI.  Robert G. Deeter, Ph.D., formerly of Anti-Infectives, GlaxoWelcome Co., now at AmGen Laboratory, California, was an active collaborator.  In addition, Dr. C.H. Chang, Anatomic Pathology, WBH, has done special staining and electron microscopic studies of cardiac biopsies of CFS patients.


There is firm evidence in CFS patients that active Epstein-Barr virus (EBV), active cytomegalovirus (HCMV), active Human Herpesvirus 6 or a combination of these viruses, are common findings in patients with CFS.  In 1997, Dr. Lerner hypothesized CFS is caused by 3 herpesviruses: EBV, HCMV and/or HHV6. These three viruses establish “latent” infection in B-lymphocytes, monocyte-macrophage precursors, or T-lymphocytes respectively.  Virus reactivation, and both abortive and complete virus multiplication occur.  Therefore CFS patients have been described with continuing primary or reactivated infections.


In a controlled pilot study (random and blinded) the antiviral drug valacyclovir (Valtrex) is shown effective in reducing the fatigue of single virus EBV CFS.  A blinded trial of valacyclovir has been completed and confirms the original study.  Initial studies involving subsets including HCMV and HHV6, utilizing the antiviral drug valgancyclovir (Valcyte), are also successful and exciting.  When patients are treated with appropriate antiviral medicines after specific proof of EBV, HCMV and/or HHV6 virus active infection (subset classification), research has shown significant improvement in cardiac and CFS symptoms. 



  1. Any new infection (such as the common cold or bronchitis, or sinusitis, or a urinary tract infection) will worsen the symptoms of CFS.  These common infections must be treated vigorously.
  2. Exercise must be avoided, but living within the parameters of doing what you can do without ensuing exhaustion is encouraged.  In other words, activities that increase your heart rate must be avoided.
  3. Alcohol may be a cardiac toxin.  I ask that CFS patients not drink alcohol.
  4. Other conditions also may be chronic and may worsen or accompany CFS, for instance, chronic Lyme disease.  Other co-existing conditions must be found and treated (e.g. high blood pressure, diabetes mellitus). 
  5. Of course, we want CFS patients to be well; we want CFS patients to live normally.  We want CFS patients to be able to exercise, but I ask our patients not to exercise until her/his Energy Index Point Score® (EIPS®) improves to 8.  A CFS patient has an EIPS® of zero if bedridden.  An EIPS® of 5 allows a CFS patient to keep a sedentary job, but do little else.  A CFS patient with an EIPS® point score 7 does not need to nap during the day.


Having a life changing illness like CFS is disruptive to one’s self and family.  In order to improve, a family support system is necessary.


We now understand the cause of CFS.  What this means is that we are able to treat cause rather than only treat symptoms.  For instance, the treatment of pneumonia was unsuccessful until it was discovered that pneumonia is a bacterial infection, and the bacterium, the pneumococcus, is treatable with penicillin.  Similarly, the treatment of CFS requires etiologic causal understanding.  This treatment is now present.


Energy Index Point Score® (EIPS®) is a registered trademark, U.S. Patent and Trademark Office.

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