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The Heart and Friedreich's Ataxia (FRDA) — A Beginner's Primer and Introduction
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The Heart and Friedreich's Ataxia (FRDA)* — A Beginner's Primer and Introduction
Through our family's personal experience and reading, this information has been compiled to help you in understanding the cardiac problems associated with Friedreich's ataxia, as well as offering tips and advice regarding cardiology appointments and care. Information sources are referenced in the footnotes. The information for the accompanying cardiac problems are frightening. A small percentage of patients never develop cardiac problems. Most do. Some patients remain stable and others' cardiac problems progress rapidly. Sadly, my son's cardiac function has progressively worsened over the years. Research is advancing, but FARA needs your help. 100% of your donations are dedicated to funding research.
* The information provided should NOT be used as a substitute for seeking professional medical diagnosis, treatment, and care. You should NOT rely on any information in these pages to replace consultations with qualified health professionals.
According to the National Institutes of Health (www.nih.gov), "Most people with Friedreich's ataxia die in early adulthood if there is significant heart disease, the most common cause of death." 1 "Subjective symptoms of exertional dyspnea (uncomfortable or labored breathing), palpitations, and anginal pain may be present in moderately advanced disease. Arrhythmias, especially atrial fibrillation, and congestive heart failure frequently occur in the later stages of the disease." 2
My son was genetically confirmed with Friedreich's ataxia at age 11. His GAA repeat lengths are 700 and 1050. He had been exhibiting physical symptoms since he was 9 years old. His primary care physician recommended that he be examined by a cardiologist.
"Most patients will develop a cardiac disease that is called 'left ventricular hypertrophy'" (hypertrophic cardiomyopathy). "This presents itself as an increased thickness of the left ventricular wall and septum. Hypertrophy can either be symmetrical, involving all parts of the heart, or asymmetrical, when mostly the septum becomes hypertrophic without a clear increase in wall thickness of the rest of the heart. A minority of FRDA patients however, do not develop hypertrophy; rather left ventricular dilation occurs."... "As well an important problem in Friedreich's patients are arrhythmias, which can be life threatening." 3
Table of Contents
› What is Hypertrophic Cardiomyopathy (HCM) or left ventricular hypertrophy?
› What are Arrythmias?
› Types of Arrhythmias
› An Appointment with the Cardiologist — Physical Exam
› An Appointment with the Cardiologist — Diagnostic Testing (ECG / Echo / Holter / Event Monitors)
› Preparing for the Cardiology Appointment
› Suggested Questions to Ask the Cardiologist
› A trip to the Emergency Room!
› Warning Signs and Tips
› Genetically speaking, why does FRDA damage the heart?
› Cardiac Function — Different Rates of Progression
› Variations of Cardiac Involvement — Research Abstracts
 › Idebenone or CoQ10 / Vitamin E — Helpful in controlling Cardiac Hypertrophy?
› Participation in the Idebenone Clinical Trial in the US
› Dictionary of Heart Definitions and Terms
› Footnotes — Compilation of Resources
› Common Treatments for Arrhythmias (www.mdausa.org)
What is Hypertrophic cardiomyopathy (HCM)?
"The main feature of hypertrophic cardiomyopathy (HCM) is the muscle mass of the left ventricle enlarges or "hypertrophies." Thickening is seen in the ventricular septal measurement (normal range .08-1.2mm), and in weight. In HCM, septal measurements may be in the range of 1.3mm to 6.0+mm.
In one form of the disease, the wall (septum) between the two ventricles (pumping chamber) becomes enlarged and obstructs the blood flow from the left ventricle. The syndrome is known as hypertrophic obstructive cardiomyopathy (HOCM) or asymmetric septal hypertrophy (ASH). It's also called idiopathic hypertrophic subaortic stenosis (IHSS). Besides obstructing blood flow, the thickened wall sometimes distorts one leaflet of the mitral valve, causing it to leak." 4
At age 11, my son's initial cardiac diagnosis was non-obstructive hypertrophic cardiomyopathy with no arrythmia.
IT IS RECOMMENDED THAT CARDIOLOGY APPOINTMENTS BE SCHEDULED EVERY SIX MONTHS UNLESS PROBLEMS OR QUESTIONS ARISE SOONER.
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What are Arrythmias?
"Arrythmias are abnormal heart rhythms. They can cause the heart to pump less effectively. The heart has four chambers. The top two are the atria and the lower two are the ventricles. Normally the heartbeat starts in the right atrium when a special group of cells sends an electrical signal. (These cells are called the sinoatrial or SA node, the sinus node or the heart's "pacemaker.") This signal spreads throughout the atria and to the atrioventricular (A-V) node. The A-V node connects to a group of fibers in the ventricles that conduct the electric signal. The impulse travels down these specialized fibers (the His-Purkinje system) to all parts of the ventricles. The electrical signal must follow this exact route for the heart to pump properly." 4
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Types of Arrhythmias
"Arrhythmias can be diagnosed by electrocardiography and divided into:
- bradycardia, indicating a slow heart rate, mostly based on disease in the sinus node, which is the cardiac pacemaker;
- tachycardias (high heart rates) which can be further divided into
- supraventricular arrhythmias, which in general are not life threatening; and
- ventricular tachycardia, which can be life threatening due to the loss of pump function during high rates.
Symptoms of bradycardia are palpitations, dizziness, and syncope (fainting). The appropriate therapy would involve a pacemaker to correct the slow heart rate.
Tachycardias can be recognised through the increased heart rate. The change from a normal to a fast rate can give rise to syncope and in some cases sudden death can occur.
Supraventricular tachycardias in general can be treated with drugs that control the heart rate, such as digitalis, beta-adrenergic receptor blockade or amiodarone and sotalol.
The effects of these drugs on ventricular tachycardias is less clear and in some cases it may be necessary to implant a device capable of recognising the ventricular arrhythmia and applying the appropriate electrical therapy." 3
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An Appointment with the Cardiologist — Physical Exam
Physical Exam
The physical exam checks height, weight, pulse, respiratory rate, and blood pressure. The cardiologist uses a stethescope to listen to the patient's breathing to determine if the lungs are clear on auscultation (auscultation means the sounds produced by the structures of the lungs during breathing).
The cardiologist listens to the heart with a stethescope to check for normal heart sounds. The heart contracts and relaxes with each heartbeat. The contraction part of this cycle is called systole (S1). The relaxation portion is called diastole (S2). The cardiologist also listens for abnormal sounds such as murmurs or gallops.
A diastolic murmur occurs when the heart muscle relaxes between beats. A systolic murmur occurs when the heart muscle contracts. Systolic murmurs are graded by intensity (loudness) from one to six. A grade 1/6 is very faint, heard only with a special effort. A grade 6/6 is extremely loud.
The term "gallop sounds" refers to the cadence of S1 and S2 along with either an S3 or an S4, or their summation. This nomenclature arose because the trio of sounds simulates the cadence of a galloping horse, especially when the heart rate approaches 100 beats per minute. Gallop sounds are by definition diastolic events.
The cardiologist examines the patient for peripheral edema which is an abnormal build-up of fluids in ankle and leg tissues.
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An Appointment with the Cardiologist — Diagnostic Testing (ECG / Echo / Holter / Event Monitors)
Electrocardiogram
This is a test used to determine if the heart's rate and rhythm are normal or if heart damage has occurred. It's a graphic record of the electrical impulses of the heart.
When an electrocardiogram is done, several wires, or "leads," are usually attached to the arms, legs, and chest. This is called a "12-lead ECG." It allows a doctor to take 12 different recordings at the same time. Each lead records the same electrical impulse, but from a different position in relation to the heart.
Echocardiograph
This is a technique that sends sound waves into the chest to rebound from the heart's walls and valves. The recorded waves show the shape, texture, and movement of the valves on an echocardiogram. They also show the size of the heart chambers and how well they're working.
The "echo" measures the ejection fraction and the shortening fraction:
"Ejection fraction. The left ventricle is a chamber which relaxes to fill with blood and then contracts to pump the blood out. Even in a healthy heart, the left ventricle does not pump all of the blood out with each beat. The ejection fraction is defined by the following formula:
The ejection fraction is a useful measure of left ventricular performance. The normal range is 63-77% for males and 55-75% for females (reference: Measurements in Cardiology). If the left ventricle wall is thinned, a decrease in the ejection fraction is seen.
Shortening fraction. The shortening fraction is a slightly different way of measuring left ventricle performance. Instead of measuring and ratio-ing blood volumes, the shortening fraction measures and ratios the change in the diameter of the left ventricle between the contracted and relaxed states:
The normal range is 0.18-0.42, or 18-42% (reference: Measurements in Cardiology). According to the Oeffinger / Keene article, "...above 30% is considered normal, with 26 to 30% representing a mild decrease in function...A decrease in the shortening fraction usually precedes a detectable decrease in the ejection fraction." 8
The "echo" also checks for mitral regurgitation. Mitral regurgitation causes volume overload of the left atrium and subsequently leads to pulmonary edema and congestive heart failure.
Holter Monitor: the cardiologist may order a Holter Monitor. Holter monitoring is a continuous, twenty-four hour electrocardiographic (EKG) recording of the heart's rhythm. A patient wears a small recorder as he or she goes about normal daily life. The machine makes a graphic record of the heart's electrical currents. It is used mainly to document and describe abnormal electrical behavior in the heart. This can be random, spontaneous, sleep-related, or caused by emotion or stress. Capturing and relating symptoms with rhythm disturbances (changes in the normal electrical pattern of the electrocardiogram) during activity requires recording or observing the heart's electrical behavior during that time. This must be done continuously over time as a person goes about normal daily activities.
Our son's cardiologist ordered a Holter Monitor about once per year while he was being monitored by non-obstructive HCM with no arrythmia.
Event Monitor: Intermittent recorders are used for weeks to months to provide brief, intermittent recordings. A patient is able to press the record button to record an "event;" the findings are then sent to the cardiologist for interpretation.
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Preparing for the Cardiology Appointment
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Suggested Questions to Ask the Cardiologist
- After the physical and diagnostic testing, you may ask if there any signficant changes since the last cardiology visit?
- What is the Ejection Fraction?
- What is the Shortening Fraction?
- How do these measurements for the Ejection Fraction and the Shortening Fraction compare to "normal" measurements?
- What is the thickness of the interventricular septum and left ventricular wall?
- Is there any left or right ventricular hypertrophy? Any increase since the last appointment?
- Is there any arrythmia? What type?
- Should my child have any restrictions on physical activity?
- Ask any other questions you have written down to ask the cardiologist.
- Be sure to tell the cardiologist if your child is on any prescription medications OR over-the- counter medications. Some medications, including anti-depressants or cold medicines, can interfere with heart medications.
- Tell the cardiologist of any changes in your child's health or if any surgery (such as spinal fusion) is scheduled.
NOTE: Make appointments to be checked by the cardiologist every 6 months unless problems arise sooner. Some clinics allow you to make the next appointment while checking out from the present appointment.
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A Trip to the Emergency Room!
For over four years my son was examined twice a year by the cardiologist. There was a gradual thickening of the left ventricle, but no appreciable "heart trouble." His last cardiology visit was routine and he was told to return in 6 months. HOWEVER, IN JUST THREE MONTHS HIS CARDIAC FUNCTION DRAMATICALLY DECLINED.
One early morning at 4 a.m., he woke me and asked me to feel his chest. He said it felt like his heart was going too fast. We immediately called our son's cardiologist. The cardiologist referred us to the nearest emergency room. Emergency room testing indicated that my son WAS correct. He did experience arrythmia. The emergency room ECG and Echo test results were forwarded to our cardiologist. His cardiologist performed additional testing including a Holter Monitor.
At age 16 our son's ejection fraction has fallen into the 40th percentile range. Remember, "if your heart manages to pump out 55% or more of the blood in the left ventricle on each beat, you have a strong, healthy heart. When it falls below 55% on each beat, you're slipping." 5 He also was diagnosed with supraventricular tachyardia (SVT). He was prescribed two prescription medications to improve his heart function and help correct the SVT.
For Emergency Room Visits: REMEMBER TO BRING YOUR CHILD'S FILE OF PREVIOUS CARDIOLOGY REPORTS; it serves as a guide to the on-call physician in determining a change in your child's cardiac function.
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Warning Signs and Tips:
NOTE: ANY TIME A FRIEDREICH'S ATAXIA PATIENT REPORTS UNUSUAL HEART SYMPTOMS, CALL HIS OR HER DOCTOR OR CARDIOLOGIST OR GO IMMEDIATELY TO THE HOSPITAL EMERGENCY ROOM.
Some of the symptoms could include shortness of breath on exertion, dizziness, fainting, chest pain or discomfort, or abnormal heart rhythms.
Children may describe a heart symptom as my heart feels "funny" or "different". Examples: It feels like horses galloping. It feels like it's racing real fast. It feels heavy. My heart feels like it's flip flopping. Abnormal heart rhythms in some cases can lead to sudden death.
Encourage your child with FRDA to alert you if his or her heart feels "funny" or "different" than usual.
Periodically ask how his or her heart is "feeling."
You can check the pulse rate at http://www.drkoop.com/ency/93/003399.html
Praise your child for alerting you that some thing was wrong — it's vitally important. In our son's case, there were no outward signs we could've observed.
Check with your cardiologist before your child participates in strenuous physical activities. Because of the lack of coordination and general weakening of the muscles, our son does not engage in strenuous activities now. However, some patients do.
Ask your cardiologist if there are specific activities he or she would recommend be restricted.
Any activity that includes a warning for "heart patients" such as hot tubs or amusement park rides should be taken seriously. Check with your cardiologist before these activities.
Avoid caffeinated beverages and tobacco that can cause arrythmia.
For Emergency Room Visits: REMEMBER TO BRING YOUR CHILD'S CARDIOLOGY MEDICAL RECORDS CONTAINING PREVIOUS CARDIOLOGY REPORTS; it serves as a guide to the on-call physician in determining a change in your child's cardiac function.
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Genetically speaking, why does FRDA damage the heart?
"Studies have revealed that frataxin, a protein that should normally be present in the nervous system, the heart, and the pancreas, is severely reduced in patients with Friedreich's ataxia. Studies have shown that patients have abnormally high levels of iron in their heart tissue. It is believed that the nervous system, heart, and pancreas may be particularly susceptible to damage from free radicals (produced when the excess iron reacts with oxygen) because once certain cells in these tissues are destroyed by free radicals they cannot be replaced. Nerve and muscle cells also have metabolic needs that may make them particularly vulnerable to free radical damage. The discovery of the genetic mutation that causes Friedreich's ataxia has added new impetus to research efforts on this disease." 1
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Cardiac Function — Different Rates of Progression
The progression of Friedreich's ataxia varies with each patient. The patients who develop cardiomyopathy have varying presentations and differing rates of progression compared to other FRDA patients.
Let the cardiologist determine the best treatment based on the patient's cardiac problems related to FRDA! "What works for Johnnie's heart, doesn't necessarily work for Suzie's heart." Each case is different.
Cardiomyopathy is more frequently seen with longer GAA repeat alleles [Durr et al 199, Filla et al 1996, Monros et al 1997]. Significant correlation is seen between the length of the GAA expansion and the thickness of the interventricular septum and left ventricular wall [Isnard et al 1997, Dutka et al 1999, Bit-Avragim et al 2001]. Isnard et al [1997] found echocardiographic evidence of left ventricular hypertrophy in 81% of patients with FRDA with repeat lengths greater than 770 triplets and in only 14% of those with repeat lengths less than 770 triplets. Montermini, Richter et al (1996) and Delatycki, Paris et al (1999) showed that the presence of cardiomyopathy correlated with the severity of disease as assessed by earlier age of onset. 2
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Variations of Cardiac Involvement - Research Abstracts
Variations of cardiac involvement - Pubmed Research Abstracts 6
- Am J Cardiol 1996 Apr 15;77
The varying evolution of Friedreich's ataxia cardiomyopathy.
Casazza F, Morpurgo M.; Division of Cardiology, San Carlo Hospital, Milan, Italy.
During a mean follow-up period of 8 years, 17% of 66 patients with Friedreich's ataxia developed hypokinetic-dilated cardiomyopathy; most patients originally had a hypertrophic left ventricle. The presence of pathologic Q waves identifies a subgroup of patients with wall motion abnormalities; these patients are more likely to develop a hypokinetic left ventricle, and the prognosis is ostensibly poorer. PMID: 8623752 [PubMed - indexed for MEDLINE] Neurosci Lett 2001 Jun 29;306(3):169-72
- Progression of cardiopathology in Friedreich ataxia: clinico-instrumental study Cardiologia. 1990 May;35(5):423-31. Italian.
Casazza F, Ferrari F, Piccone U, Maggiolini S, Capozi A, Morpurgo M. Divisione di Cardiologia, Ospedale S Carlo Borromeo, Milano.
Clinical, electrocardiographic and echocardiographic 5-year follow-up was performed in our institution on 61 patients with Friedreich's ataxia. Cardiac failure was evident in 5% of the patients, and was the most common cause of death. Cardiac arrhythmias, most commonly supraventricular in origin, usually occurred together with the onset of cardiac failure and in 1 case resulted in sudden death. ST-T abnormalities were present in 91% of the cases, and were independent from other clinical parameters. On the contrary, pseudonecrotic (5%) and right ventricular hypertrophy pattern were associated with a poor prognosis. Left ventricular hypertrophy was evident at the echocardiogram in 75% of cases and remained unchanged throughout the entire follow-up period. In 1 case left ventricular hypertrophy turned to dilative cardiomyopathy. Autopsy was performed in 2 out of 4 decreased patients and revealed massive interstitial fibrosis with cellular degeneration in the absence of coronary lesions.
PMID: 2148503 [PubMed - indexed for MEDLINE]
- Am J Cardiol 1986 Sep 1;58(6):518-24
Spectrum of cardiac involvement in Friedreich's ataxia: clinical, electrocardiographic, and echocardiographic observations.
Alboliras ET, Shub C, Gomez MR, Edwards WD, Hagler DJ, Reeder GS, Seward JB, Tajik AJ.
Combined 2-dimensional and M-mode echocardiography was used to assess the cardiac status of 22 patients with Friedreich's ataxia, and the findings were correlated with the clinical and electrocardiographic (ECG) data. Mean age at onset of Friedreich's ataxia was 8 years (range 3 to 18); mean age at echocardiography was 18 years (range 8 to 39). Echocardiographic findings were abnormal in 19 patients (86%). The 3 patients with normal echocardiographic findings did not have cardiac symptoms, but 1 had ECG repolarization abnormalities. Concentric left ventricular (LV) thickening, the most common echocardiographic finding, was found in 15 patients (68%) and in all 15 the papillary muscles were thickened. These 15 patients had ECG repolarization abnormalities and 5 had left-axis deviation; however, only 3 satisfied ECG criteria for LV or right ventricular hypertrophy. Two of the 15 patients (9%) had symptoms of heart failure. Two patients had asymmetric septal thickening without clinical evidence of LV outflow tract obstruction; neither had cardiac symptoms, but both had ECG repolarization abnormalities. Two patients showed a dilated cardiomyopathy pattern; both had heart failure and atrial flutter. One of these patients died, and necropsy revealed 4-chamber cardiac dilatation, biventricular hypertrophy, and histologic findings of diffuse interstitial fibrosis, myocellular hypertrophy, and necrosis. This study revealed a wide spectrum of cardiac abnormalities in patients with Friedreich's ataxia. PMID: 2944367 [PubMed - indexed for MEDLINE]
- Progression of hypertrophic into a dilated left ventricle in Friedreich's ataxia.
G Ital Cardiol. 1988 Jul;18(7):615-8.
Casazza F, Morpurgo M.; Department of Cardiology, S. Carlo Hospital, Milan.
The authors describe the case of a girl who developed Friedreich's ataxia at, approximately, the age of 7, with evidence of cardiac involvement being detected by electrocardiography and echocardiography at a later date. Cardiac function was moderately impaired and remained unchanged for a number of years, during which a picture of hypertrophic left ventricle seemed to be firmly established. Later still, however, the cardiac situation shifted gradually toward a hypokinetic form of the disease, with a progressive thinning of the interventricular septum and posterior wall of the left ventricle, associated enlargement of the ventricular chambers and increasingly severe hypokinesia leading to repeated episodes of heart failure.
PMID: 3234661 [PubMed - indexed for MEDLINE]
- Cardiology 1988;75(5):321-7
Noninvasive assessment of systolic and diastolic function in 50 patients with Friedreich's ataxia.
Giunta A, Maione S, Biagini R, Filla A, De Michele G, Campanella G.; Department of Internal Medicine, 2nd School of Medicine, University of Naples, Italy.
Fifty consecutive patients with Friedreich's ataxia were examined to characterize their cardiac diastolic function. Electrocardiographic abnormalities were detected in 42 (80%) of the 50 patients. Echocardiography showed left ventricular hypertrophy in 14 patients (28%): concentric in 12 and asymmetric in 2. Left ventricular percent fractional shortening was normal in all except 2 patients. Diastolic filling characteristics measured from Doppler mitral flow velocity traces were not statistically different from those of 18 healthy control subjects. No abnormal diastolic flow pattern was observed in patients with left ventricular hypertrophy, whether concentric or asymmetric. PMID: 3233613 [PubMed - indexed for MEDLINE]
Idebenone or CoQ10 / Vitamin E - Helpful in controlling Cardiac Hypertrophy?
"Deficiency of frataxin results in defective mitochondrial respiration, abnormal accumulation of iron in the mitochondria, and production of oxygen free radicals. Antioxidant therapy by free radical scavengers such as idebenone, coenzyme Q10, vitamin E has been considered for slowing the progression of FRDA.
Enlargement of the left ventricle (the large pumping chamber of the heart) is common in this disease. In studies in France and Canada, patients with Friedrich's ataxia who were given idebenone, an antioxidant similar to the dietary supplement coenzyme Q, had a decrease in the size of their left ventricle. Rustin et al (1999) presented preliminary evidence of the ability of idebenone to reverse the cardiac hypertrophy in three patients with FRDA.
Pubmed Abstract on Rustin findings:
Idebenone is effective at controlling cardiac hypertrophy in Friedreich's ataxia. As the drug has no serious side effects, there is a good case for giving it continuously in a dose of 5-10 mg/kg/day in patients with Friedreich's ataxia at the onset of hypertrophic cardiomyopathy. Heart 2002 Apr;87(4):346-9; Comment in: Heart. 2002 Apr;87(4):316-7. Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia; Hausse AO, Aggoun Y, Bonnet D, Sidi D, Munnich A, Rotig A, Rustin P.
Schols et al (2001) were unable to reproduce the beneficial effects of idebenone in a larger cohort.
Pubmed Abstract on Schols findings:
Friedreich ataxia, the most common form of degenerative ataxia, is thought to be caused by respiratory deficiency due to mitochondrial iron accumulation and oxidative stress. Idebenone, a free-radical scavenger, protects mitochondrial function in in vitro models of FA. In a placebo-controlled crossover trial we studied the effect of idebenone on respiratory function in nine ambulant FA patients. (31)P magnetic resonance spectroscopy demonstrated mitochondrial impairment in vivo in skeletal muscle of all FA patients, but no recovery with idebenone. No effects were seen in clinical scores. Echocardiography did not confirm a preliminary study reporting improvement of FA-associated cardiomyopathy with idebenone.
Idebenone in patients with Friedreich ataxia; Schols L, Vorgerd M, Schillings M, Skipka G, Zange J.; Department of Neurology, St. Josef Hospital, Ruhr-University, Bochum, Germany. Neurosci Lett 2001 Jun 29;306(3):169-72
Schulz et al (2000) showed the idebenone treatment reduced the higher urinary levels of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative DNA damage) in patients with FRDA.
Pubmed Abstract on Schulz findings:
Increased generation of reactive oxygen species may underlie the pathophysiology of Friedreich ataxia (FRDA). The authors measured concentrations of 8-hydroxy-2'-deoxyguanosine (8OH2'dG), a marker of oxidative DNA damage, in urine and of dihydroxybenzoic acid (DHBA), a marker of hydroxyl radical attack, in plasma of 33 patients with FRDA. They found a 2.6-fold increase in normalized urinary 8OH2'dG but no change in plasma DHBA as compared with controls. Oral treatment with 5 mg/kg/day of the antioxidant idebenone for 8 weeks significantly decreased urinary 8OH2'dG concentrations, indicating that 8OH2'dG may be useful in monitoring therapeutic interventions in patients with FRDA.-1721
Oxidative stress in patients with Friedreich ataxia.;Schulz JB, Dehmer T, Schols L, Mende H, Hardt C, Vorgerd M, Burk K, Matson W, Dichgans J, Beal MF, Bogdanov MB.; Department of Neurology, University of Tubingen, Germany. PMID: 11113228
[PubMed - indexed for MEDLINE]
CoQ10 and Vitamin E
Lodi et al (2001) showed improved ATP production in the heart and skeletal muscle of patients with FRDA following 3-6 months treatment with coenzyme Q10 and vitamin E.
Pub Med Abstract on Lodi CoQ10 and Vitamin E findings
The researchers used 31P-MRS to evaluate the effect of 6 months of antioxidant treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports the evaluation of such therapy as a disease-modifying strategy in this neurodegenerative disorder.
"Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia. Lodi R, Hart PE, Rajagopalan B, Taylor DJ, Crilley JG, Bradley JL, Blamire AM, Manners D, Styles P, Schapira AH, Cooper JM.; Department of Biochemistry, University of Oxford, United Kingdom. Ann Neurol 2001 May;49(5):590-6;
PMID: 11357949 [PubMed - indexed for MEDLINE] "
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Participation in the Idebenone Clinical Trial in the US
Largely because of the promise being shown in the French and Canadian clinical trials, we are working hard here in the United States to prepare a multi-center, multinational trial of Idebenone. The purpose of the trial will be to establish, to FDA standards, first the safety of the drug in FRDA patients of all ages (Phase 1), and then the efficacy of the drug against FRDA symptoms, including the optimum dose of the drug for achieving maximum effect. If the trial is successful in those two objectives, the drug will be eligible for FDA approval for FRDA patients and can then be prescribed by physicians for FRDA patients and covered by medical insurance (based on an individual's healthcare policy terms).
Genetically confirmed FRDA patients are eligible to enroll in a Clinical Study (clinicalstudies.info.nih.gov) underway at the National Institutes of Neurological Disorders and Stroke at NIH (US) to determine the highest dose of idebonone that can safely be given to patients with Friedreich's ataxia.
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Dictionary of Heart Definitions and Terms
American Heart Associate Heart and Stroke Encyclopedia (www.americanheart.org)
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Footnotes — Compilation of Resources
(1) NIH National Institute of Neurological Disorders and Stroke Friedreich's Ataxia Fact Sheet (www.ninds.nih.gov)
(2) Gene Clinics (www.geneclinics.org)
(3) European Federation of Hereditary Ataxias Euro-Ataxia Newsletter January 1998
Caradiac Problems in Friedreich's Ataxia; Pieter A. Doevendans, University Hospital Maastricht, Netherlands (www.euro-ataxia.org)
(4) American Heart Association Heart and Stroke Encyclopedia (www.americanheart.org)
(5) CHF Patients.com
› FAQ - Ejection Fraction
› Glossary
(6) PubMed / National Library of Medicine (www.pubmed.gov)
(7) Muscular Dystrophy Association — The Heart is a Muscle Too; Frequently Asked Questions About Cardiac Problems in Neuromuscular Disease; by Margaret Wahl (www.mdausa.org)
(8) Pediatric Oncology Resource Center Definitions of Ejection Fraction and Shortening Fraction (www.acor.org)
Thank you to the above sources for Internet access to the valuable information necessary to produce this document.
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