© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Reply to Letter to the Editor
aDipartimento di Medicina Clinica e Biotecnologia Applicata "D. Campanacci", Universita* di Bologna, Bologna, Italy
bMRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry University of Oxford and Oxford Radcliffe Hospital, Oxford, UK
cUniversity Department of Clinical Neurosciences, Royal Free and University College School of Medicine, UCL, London, UK
* Corresponding author. Tel.: 0039-5130-5993; fax: 0039-5130-3962 lodi{at}med.unibo.it
Received 19 March 2002; accepted 19 March 2002
We thank Dr Osterziel and his colleagues for their comments. As pointed out by Dr Osterziel and colleagues, the main finding of our work [1] is that a deficit of cardiac bioenergetics (i.e. low PCr to ATP ratio) is present in Friedreich Ataxia patients (FRDA) without cardiomyopathy as demonstrated by septal (IVSd) and posterior wall (PWd) thickness <1.1 cm and normal end-diastolic and end-systolic dimensions as well as fractional shortening. In our patients, PWd ranged from 0.7 to 1.59 cm and IVSd from 0.74 to 1.70. When we divided our FRDA patients into two groups based on a cut-off value of 1.1 cm of PWd and/or IVSd thickness, we found no difference in cardiac PCr/ATP ratios between patients with wall thickness <1.1 and those with wall thickness=1.1. Dr Osterziel and his colleagues argue about the cut-off values we used to define LVH and suggest a higher value of 1.3 cm as used in other studies [2–4]. We used a cut-off value of 1.1 cm to define LVH as this is the value commonly used in clinical practice [6,7]. Although reference ranges vary, particularly for septal wall thickness, a higher value of 1.3 cm has been more specifically applied to patients with familial hypertrophic cardiomyopathy (HCM) (see Refs. [2–4]). This has been particularly valuable in the pre-genetic era in deciding whether subjects in affected families had clinical evidence of HCM or not. Had we used 1.3 cm as the cut off point, even more of our patients (16 out of 18) would have fallen into the category with a "normal heart" associated with abnormal metabolite ratios. Independently of the cut-off value chosen to define LVH, the point we wanted to make (see Fig. 2 in Ref. [1]) was that the reduced cardiac PCr/ATP found in most of our 18 FRDA did not correlate with IVSd nor PWd thickness.
To avoid making any assumptions about hypertrophy criteria we have now analysed the relation between wall thickness and impaired bioenergetics (Fig. 1). These findings show that i) the bioenergetic impairment in the heart of FRDA patients is not secondary to LVH but is rather a direct effect of the underlying genetic abnormality and, ii) at least in this group of FRDA patients, increased wall thickness in the absence of failing heart did not contribute to further impairment of cardiac bioenergetics.
|
Virtually all previous phosphorus MR spectroscopy studies of the heart showing abnormal PCr to ATP ratios were performed on patients with some form of structural or functional abnormality. Our study shows that a mitochondrial lesion can cause metabolic abnormalities in the absence of structural or functional abnormalities, so that the biochemical changes could trigger the eventual muscle change that leads to hypertrophy. We used raw data from echo measurements to avoid possible bias. We accept that various derived indices related to body surface area, height, etc. have been proposed, but these have been primarily for epidemiological studies. Nevertheless, we have re-classified our FRDA patients according to their LV wall thickness (=IVSd+PWd thickness) taking into account their height and sex [5]. Confirming our findings obtained using uncorrected echocardiographic values, cardiac PCr/ATP in the 10 FRDA patients with LVH (1.38±0.60 cm) was similar to those found in the 8 FRDA patients without LVH (1.55±0.46; p=0.52).
 |
References |
|---|
 Top References |
|---|
- Lodi R., Rajagopalan B., Blaimire A.M., et al. Cardiac energetics are abnormal in Friedreich ataxia patients in the absence of cardiac dysfunction and hypertrophy; an in vivo 31P magnetic resonance spectroscopy study. Cardiovasc Res (2001) 52:111–119.
[Abstract/Free Full Text] - Charron P., Dubourg O., Desnos M., et al. Diagnostic value of electrocardiography and echocardiography for familial hypertrophic cardiomyopathy in a genotyped adult population. Circulation (1997) 96:214–219.
[Abstract/Free Full Text] - Maron B.J., Moller J.H., Seidman C.E., et al. Impact of laboratory molecular diagnosis on contemporary diagnostic criteria for genetically transmitted cardiovascular diseases: hypertrophic cardiomyopathy, long-Q T syndrome, and Marfan syndrome. Circulation (1998) 98:1460–1471.
[Free Full Text] - McKenna W.J., Spirito P., Desnos M., et al. Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. Heart (1997) 77:130–132.
[Abstract/Free Full Text] - Vasan R.C., Larson M.G., Levy D., et al. Distribution and categorization of echocardiographic measurements in relation to reference limits. The Framingham Heart Study: formulation of a Height- and Sex-specific classification and its prospective Validation. Circulation (1997) 96:1863–1873.
[Abstract/Free Full Text] - Salcedo S. Atlas of echocardiography. W.B. Saunders, 1985. p. 14.
- Arvan S. Echocardiography: an integrated approach. Churchill Livingstone 1984:503.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||