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(Circulation. 2000;101:e121.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Differences in Cardiac Energetics Between Patients With Familial and Nonfamilial Hypertrophic Cardiomyopathy

Wulf-Ingo Jung, PhD; Thomas Hoess, MS; Michael Bunse, PhD; Stefan Widmaier, PhD

Hypertension and Diabetes Research Unit, Max Grundig Clinic, Bühl, Germany, Physikalisches Institut, University of Tübingen, Tübingen, Germany

Ludger Sieverding, MD; Johannes Breuer, MD; Jürgen Apitz, MD

Division of Pediatric Cardiology, University of Tübingen, Tübingen, Germany

Oliver Schmidt, MS

Division of Pediatric Cardiology University of Tübingen, Tübingen, Germany, Physikalisches Institut, University of Tübingen, Tübingen, Germany

Franz van Erckelens, MD; Guenther J. Dietze, MD

Hypertension and Diabetes Research Unit, Max Grundig Clinic, Bühl, Germany

Otto Lutz, PhD

Physikalisches Institut University of Tübingen, Tübingen, Germany

	Introduction

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To the Editor:

We have recently shown by ³¹P NMR spectroscopy that abnormalities in the myocardial metabolism occur in asymptomatic patients with hypertrophic cardiomyopathy (HCM).¹ HCM is inherited in about half of the patients (familial hypertrophic cardiomyopathy, FHC). Among the most lethal genetic defects is the Arg403Gln mutation in the ß-cardiac myosin heavy chain.² Using a mouse model of this missense mutation, Spindler et al² showed a possible link between the clinical syndrome of FHC and myocardial energetics by demonstrating decreased phosphocreatine (PCr) and increased inorganic phosphate (P_i) concentrations.

Stimulated by this report, we reanalyzed our data published in this journal¹ for possible differences between FHC and patients without a known family history of HCM (nonfamilial hypertrophic cardiomyopathy, NFHC). The spectroscopic results (mean±SD) for controls (n=11, aged 27±3 years), patients with NFHC (n=8, aged 15±5 years), and patients with FHC (n=6, aged 18±10 years) were as follows: PCr/ATP: 2.46±0.53, 2.10±0.39, and 1.81±0.28 (P=0.01 versus controls); PME (phosphomonoester) · 100/PCr: 8.4±6.7, 14.1±6.2, and 18.9±15.9; P_i · 100/PCr: 9.7±7.2 (n=9), 12.3±4.5 (n=8), and 22.9±8.6 (n=5, P<0.02 versus NFHC, P<0.05 versus controls); and maximum end-diastolic interventricular septum thickness: 10±1, 23±12, and 27±11 mm. The intracellular pH was 7.08±0.03 for all groups.

These new analyses suggest that the severity of metabolic abnormalities is different in FHC and NFHC. This can be concluded from the significantly increased P_i/PCr ratio and from trends toward a greater PME/PCr and a smaller PCr/ATP ratio in FHC. Reduced PCr/ATP and increased P_i/PCr ratios may be due to increased cardiac work under resting conditions arising from the increased myocardial mass. However, FHC and NFHC showed no significant difference in the extent of hypertrophy. Alterations in energy metabolism may also occur in the absence of myocardial ischemia,³ as manifested in glucose metabolism.¹ Results by others⁴ also support such a hypothesis. Moreover, in the MHC^403/+ mouse model of FHC,² the increased P_i and decreased PCr concentrations compared with wild-type mice are thought to be due to the myosin mutation and not to be a simple consequence of myocardial hypertrophy.

FHC and NFHC show striking differences in metabolite ratios. Since we have no explanation why ischemia or hypoxia should affect the FHC group while the NFHC group remains much less affected, the results from Spindler et al² may also apply to our patients. In fact, the reanalyzed data provide some evidence that the changes in metabolite ratios in the myocardium of FHC patients show a relation to their inherited gene mutations. Since the 6 patients with FHC belong to 5 different families, even the retrospective determination of their genetic defects will not be sufficient. More extensive examinations of different families with several affected members will be necessary before genotype/phenotype correlations can be made.

	References

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1. Jung W-I, Sieverding L, Breuer J, Hoess T, Widmaier S, Schmidt O, Bunse M, van Erckelens F, Apitz J, Lutz O, Dietze GJ. ³¹P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy. Circulation. 1998;97:2536–2542.[Abstract/Free Full Text]
   
2. Spindler M, Saupe KW, Christe ME, Sweeney HL, Seidman CE, Seidman JG, Ingwall JS. Diastolic dysfunction and altered energetics in the MHC^403/+ mouse model of familial hypertrophic cardiomyopathy. J Clin Invest. 1998;101:1775–1783.[Medline] [Order article via Infotrieve]
   
3. Grover-McKay M, Schwaiger M, Krivokapich J, Perloff JK, Phelps ME, Schelbert HR. Regional myocardial blood flow and metabolism at rest in mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1989;13:317–324.[Abstract]
   
4. Zhang J, Zhang Y, Murakami Y, From AH, Ugurbil K, Bache RJ. Myocardial oxygenation and bioenergetics at high work states in hearts with left ventricular hypertrophy. Circulation. 1997;96(suppl I):I-413. Abstract.
   

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