title: Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene: a positron emission tomography study.
abstract: BACKGROUND
  The relationship between myocardial metabolic changes and the severity of left ventricular (LV) hypertrophy in patients with hypertrophic cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities in patients with a genetically identical cause for HCM but with variable LV hypertrophy.
  
  
  RESULTS
  Eight patients with HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene underwent myocardial perfusion, oxidative, and free fatty acid (FFA) metabolism measurements via positron emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine 14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA). LV mass, work, and efficiency were assessed by echocardiography. Thirty-six healthy volunteers served as control subjects. Compared with control subjects, HCM patients had increased myocardial oxidative metabolism and FFA uptake (P < .05). However, in patients, LV mass was inversely related to global myocardial perfusion, oxidative metabolism, and FFA uptake (all P < .03), and regional wall thickness was inversely related to regional perfusion (P < .01), oxidative metabolism (P < .001), and FFA uptake (P < .01). Therefore patients with mild (LV mass less than median of 177 g) but not advanced LV hypertrophy were characterized by increased perfusion, oxidative metabolism, and LV efficiency as compared with control subjects (P < .05).
  
  
  CONCLUSIONS
  In HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism are increased and inversely related to LV hypertrophy at both the whole heart and regional level. Increased metabolism and efficiency characterize patients with mild myocardial hypertrophy. These hypermetabolic alterations regress with advanced hypertrophy.
authors.affiliation: Turku PET Centre, Turku, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Tuunanen
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Jyri
authors.initials: J
authors.lastname: Toikka
authors.forename: Pertti
authors.initials: P
authors.lastname: Jääskeläinen
authors.forename: Päivi
authors.initials: P
authors.lastname: Marjamäki
authors.forename: Keijo
authors.initials: K
authors.lastname: Peuhkurinen
authors.forename: Tapio
authors.initials: T
authors.lastname: Viljanen
authors.forename: Petri
authors.initials: P
authors.lastname: Sipola
authors.forename: Kira Q
authors.initials: KQ
authors.lastname: Stolen
authors.forename: Jarna
authors.initials: J
authors.lastname: Hannukainen
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods*; D014335:Tropomyosin / Q000235:genetics*
chemical_list: D005230:Fatty Acids, Nonesterified; C490775:TPM1 protein, human; D014335:Tropomyosin; D010100:Oxygen