Pediatric Cardiology

, Volume 26, Issue 5, pp 727–730

High-Dose Beta-Blocker Hypertrophic Cardiomyopathy Therapy in a Patient with Friedreich Ataxia


    • Department of Pediatric CardiologyMother and Child Health Institute
  • D. Zamurovic
    • Department of Pediatric NeurologyMother and Child Health Institute
Case Report

DOI: 10.1007/s00246-005-0930-7

Cite this article as:
Kosutic, J. & Zamurovic, D. Pediatr Cardiol (2005) 26: 727. doi:10.1007/s00246-005-0930-7


Heart involvement in patients with Friedreich ataxia (FRDA) is a condition marked by inevitable progressive deterioration, with premature death. There is currently no specific treatment for FRDA. Recently, a therapy with idebenone, a short-chain coenzyme Q10 analogue, was reported to reduce left ventricular mass by 20% in about half of FRDA patients, but a double-blind placebo-controlled study did not fully confirm these results. In this case report, we present a 5-year follow-up of symmetrical concentric hypertrophic cardiomyopathy (HCM) in an FRDA patient treated with high-dose propranolol. The therapy resulted in a reduction in the thickness of the septal and posterior left ventricular walls and complete normalization of diffuse electrocardiographic repolarization abnormalities. To the best of our knowledge, this is the first such case to be reported in the literature, demonstrating the positive effects of high-dose beta-blocker treatment on heart involvement in patients with FRDA.


Friedreich ataxiaHypertrophic cardiomyopathyHigh-dose beta-blocker therapy

Although high-dose beta-blocker (HDβB) therapy has been used to treat patients with familial hypertrophic cardiomyopathy (HCM) [10], there are no published reports regarding the possible role of HDβB therapy in the treatment of heart abnormalities in patients with Friedreich ataxia (FRDA). We report the effects of high-dose propranolol therapy on heart abnormalities in a single patient with FRDA.

Case Report

In February 1999, a 12.5-year-old girl (weight, 25 kg; height, 135 cm) was admitted to our institution for the first time. The disease had commenced in 1994 with clumsiness in the girl’s gait. Personal and family history were negative for FRDA. The ataxia was progressive, and in 1996 scoliosis was noted as well. Echocardiographic examination showed moderate symmetrical concentric left ventricular HCM. Based on these findings, a clinical diagnosis of FRDA was established. Between 1994 and 1999, the patient was treated intermittently with propranolol (1 mg/kg/24 hours), verapamil (1 mg/kg/24 hours), and tocoferol (10 mg t.i.d.).

On admission to our institution, the girl had severe limb and gait ataxia, absent lower tendon reflexes, pes cavus, and severe scoliosis, but she was still capable of making a few steps on her own. On auscultation, she had a grade 3/6 apical systolic murmur. An electrocardiogram (ECG) demonstrated a sinus rhythm, frequency of 89/min, PQ 0.12 seconds, and no voltage signs of left ventricular hypertrophy but deep negative T waves in the inferior limb and left precordial leads. An echocardiogram revealed moderate symmetrical concentric left ventricular hypertrophy with septal and posterior left ventricular wall thickness of 9 mm each. Genetic testing definitively confirmed the clinical diagnosis of FRDA (820 GAA repeats on the small allele). The patient was treated with amantadin (50 mg b.i.d.), tocoferol (10 mg t.i.d.), and verapamil (10 mg t.i.d.) for 8 months (April – December 1999). Because no improvement was noted, amantadin was discontinued.

By the end of 1999, she began to suffer from attacks of precordial pain with shortness of breath. An echocardiogram, done 11 months after the initial one, demonstrated further increase in her septal (11–12 mm) and posterior (10 mm) left ventricular wall thickness, as well as hyperrefractile and thickened papillary muscles. All ECGs done in 1998 through 2000 consistently showed diffuse repolarization abnormalities with deep negative T waves in the inferior limb and left precordial leads (Fig. 1A). There was no doubt that despite continuous treatment with tocoferol and verapamil and intermittent treatment with low-dose propranolol (1 mg/kg/24 hours), our patient’s heart condition was progressively deteriorating.
Fig. 1

A March 1999, June 1999, and January 2000: electrocardiogram (ECG) strips consistently demonstrating deep negative T waves in V4–V6. B April 2000: last EGG with diffuse repolarization abnormalities (negative T waves in II, III, aVF, and V4–V6).

At the beginning of 2000, we initiated a continuous moderate-dose (2.4 mg/kg/24 hours) propranolol treatment. Three months later (April 2000), the girl reported feeling much better. Her episodes of chest pain and shortness of breath fully disappeared, and they have not been observed since that time. However, her control ECG remained unchanged in comparison to the previous ones, with negative T waves in the inferior limb (II, III, AVF) and left precordial leads (V4–V6) (Fig. 1B). No side effects of the propranolol treatment were observed. At that checkup, the dosage of propranolol was increased from 2.4 mg/kg/24 hours to a high dose of 4.8 mg/kg/24 hours (from 60 mg to 120 mg/24 hours). Three months later (July 2000), an ECG showed no repolarization abnormalities, with positive T waves in both the inferior limb and left precordial leads (Fig. 2A). This condition has remained unchanged during the 4.5-year follow-up period (Fig. 2B), Six months after initiation of the HDβB treatment, an echocardiogram showed a small but clinically significant reduction in the girl’s septal and posterior left ventricular wall thickness (9–10 mm each). Subsequent echo scans confirmed further reduction in the thickness of her septal and posterior left ventricular walls.
Fig. 2

A July 2000: first electrocardiogram (ECG) without repolarization abnormalities (positive T waves in II, III, aVF, and V4–V6). B EGG done in 2001–2004 confirming normal repolarization sequence in the left precordial leads (positive T waves in V4–V6).

At present, her septum is 8.5 mm and her posterior wall is 8 mm thick, with preserved systolic and diastolic left ventricular functions. The HDβB treatment (≤200 mg/24 hours) is administered regularly and has not been changed for the past 4.5 years. Unfortunately, the therapy had no effect on the progression of the girl’s neurological condition, and since 2002 she has been confined to a wheelchair.


The clinical course of heart disease in patients with FRDA is one of inevitable progressive deterioration and, ultimately, most of them die from cardiac causes. Electrocardiographic abnormalities are found in ≤90% of patients, and they progress in relation to the duration of the disease. Repolarization abnormalities, manifesting as diffuse T-wave inversion in the inferior limb and left precordial leads, are the most commonly reported findings and the most consistent ECG marker of cardiac involvement in patients with FRDA [1, 4, 5]. Echocardiography detects cardiac involvement in 60% to 100% of patients, most commonly in a form of symmetrical, concentric, and slowly progressive HCM [4, 5]. There is no specific treatment, and until recently supportive therapy was all that was available [4, 5, 12]. Thus, any therapeutic approach capable of inducing even a small reversal of cardiac pathology and a decrease in cardiac hypertrophy should be considered highly significant.

Recently, a reduction of >20% of left ventricular mass was demonstrated in about half of the FRDA patients treated by antioxidant idebenone, a short-chain analogue of coenzyme Q10. However, a double-blind placebo-controlled study did not fully confirm the results [6, 9]. To the best of our knowledge, the use of HDβB treatment in an attempt to relieve the cardiac symptoms and to stop the progress of cardiomyopathy in a patient with FRDA has not been reported heretofore.

Drawing on the positive experience of Ostman-Smith et al. [10] with patients who had familial HCM, we started a high-dose propranolol therapy. We were aware that the histology of HCM in patients with FRDA is very much different from the one in patients with dominantly inherited familial HCM [4]. However, Ostman-Smith et al. [10] had suggested that positive effect of HDβB treatment was probably independent of the genetic mechanism underlying the HCM because it was present in HCM both with and without Noonan syndrome. Moreover, Marian et al. [8] suggested that cardiac hypertrophy is a compensatory phenomenon rather than a direct consequence of mutations.

Three months after we instituted the HDβB treatment (July 2000), a control ECG showed no repolarization abnormalities, with positive T waves in both the inferior limb and left precordial leads (Fig. 2A). Prior to administration of the HDβB therapy, our patient had received the same medications for months and her cardiac condition had deteriorated progressively, albeit slowly. Thus, dramatic improvement of her ECG repolarization abnormalities can be attributed only to the HDβB treatment. Furthermore, 6 months after this therapy was initiated, a small but significant reduction of the thickness of the girl’s septal and posterior left ventricular walls was observed, which is in agreement with the results of Ostman-Smith et al. [10]. It is possible that the normalization of the sequence of repolarization is a consequence of reduced hypertrophy. However, considering that the normalization of the sequence of repolarization was observed well before a reduction in left ventricular wall thickness was seen, it is more likely that it occurred as a result of decreased myocardial metabolic demands and improved myocardial perfusion [2]. Hence, we believe that the HDβB treatment resulted in a reduction of energy demand and that it favorably changed the myocardial energy demand–supply mismatch, thereby inducing the regression of cardiac hypertrophy.

Cardiac involvement in patients with FRDA is due to a partial deficit of mitochondrial protein frataxin. Ristow et al. found that frataxin is a key activator of oxidative phosphorylation and mitochondrial energy conversion and suggested that reduced levels of frataxin in FRDA patients primarily result in a disease of ATP deficiency [11]. Lodi et al. confirmed that decreased levels of frataxin lead to a reduction of mitochondrial ATP generation in tissues with high metabolic activities, inducing compensatory responses such as hypertrophy in the heart, a high energy-dependent organ [7]. Finally, Blair et al. proposed that an inability to maintain adequate levels of ATP is the unifying abnormality in familial HCM and related phenotypes [3]. If abnormalities of ATP homeostasis do play a central role in any form of HCM, irrespective of the type of mutation or the pathohistology, and if HDβB treatment is capable of inducing the regression of left ventricular hypertrophy in patients with familial HCM [10], then there is every reason to believe that the same effect can be achieved in any patient with myocardial hypertrophy including FRDA patients. The clinical course of our FRDA patient treated with high-dose propranolol seems to support this hypothesis. However, more patients with HCM should be submitted to HDβB treatment before any definitive conclusions can be drawn. A therapy protocol combining idebenone (increases mitochondrial ATP production) and high-dose beta-blocker (decreases ATP demand) might prove to be a promising alternative.

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© Springer Science+Business Media, Inc. 2005