Scintigraphic Evidence for a Specific Long-Chain Fatty Acid Transporting System Deficit and the Genetic Background in a Patient With Hypertrophic Cardiomyopathy

Nakata, Tomoaki; Nakahara, Norifumi; Sohmiya, Koichi; Okamoto, F; Tanaka, Takao; Kawamura, Keishiro; Shimamoto, Kazuaki

doi:10.1253/jcj.63.319

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…That is to say, we consider that slight ischemia, not detectable with 99m Tc tetrofosmin myocardial scintigraphy, was present and that the abnormal fatty acid metabolism was caused by the ischemia. There is a close relationship between CD36 deficiency and reduced myocardial uptake of 123 I-BMIPP in HCM, 14 but in the present case flowcytometric analysis showed that the CD36 molecule expression was positive on both platelets and monocytes.…”

Section: Discussioncontrasting

confidence: 67%

Effective Disopyramide Treatment in a Boy With Mid-Ventricular Hypertrophic Obstructive Cardiomyopathy.

Teraguchi

Ikemoto

Kobayashi

2002

Circ J

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alicov et al first reported in 1976 a subtype of hypertrophic obstructive cardiomyopathy (HOCM) with mid-ventricular obstruction, 1 which is a rare subtype of HOCM, comprising 1% of hypertrophic cardiomyopathies. 2 We present an unusual, pediatric case of mid-ventricular hypertrophic obstructive cardiomyopathy (MVHOCM). Case ReportAt the age of 10 years, the patient first presented to hospital with severe chest pain, which occurred early in the morning and disappeared spontaneously with bed rest. The family history was not significant. Based on the echocardiographic findings, he was diagnosed as having hypertrophic cardiomyopathy (HCM) and was prescribed 30 mg of propranolol daily. Four months later, he was admitted for further evaluation: blood pressure was 118/78 mmHg, pulse rate 80 beats/min and respiratory rate 20 breaths/min; grade 3/6 harsh systolic murmur at the lower left sternal border. Electrocardiogram showed a mean frontal QRS axis of -60°and a deep S wave in V1; chest X-ray showed neither cardiomegaly nor pulmonary venous congestion. Two-dimensional echocardiography showed asymmetric septal hypertrophy, most marked at the mid-ventricular level, and papillary muscles coming into contact at the mid-ventricular level during systole. The thickness of the interventricular septum and of the left ventricular posterior wall was 15 and 10 mm, respectively. There was no evidence of systolic anterior motion of the mitral valve. Color Doppler echocardiography showed formation of a stenotic jet into the body of the left ventricle, and a peak systolic gradient of 100 mmHg was recorded by continuous-wave Doppler echocardiography. MVHOCM was suspected, and (Fig 1). The coronary angiogram was normal. A right ventricular endomyocardial biopsy specimen showed hypertrophic cardiomyocytes and augmentation of interstitial collagen fiber. Plasma -galactosidase activity was 13.8 nmol·h -1 ·ml -1 (normal, 4.8-17.6). The patient did not have the characteristic skin manifestation of Fabry's disease. An exercise stress 99m Tc tetrofosmin myocardial scintigram disclosed no obvious perfusion defect, but the first 123 I--methyl iodophenyl pentadecanoic acid (BMIPP) myocardial scintigram (Fig 2A, at the age of 11 years and 11 months) showed a reduced uptake by the septal and inferior walls. He was put on restricted exercise with 30 mg/day of propranolol and continued for approximately 2 years without complaint.The chest pain and dyspnea on exertion re-appeared at the age of 12 years and 3 months. He sometimes became pale, which was considered to be indicative of presyncope. The second 123 I-BMIPP myocardial scintigram (Fig 2B, A 14-year-old boy with mid-ventricular hypertrophic obstructive cardiomyopathy (MVHOCM) first presented at the age of 10 years with severe chest pain. Two-dimensional echocardiography disclosed marked hypertrophy at the mid-portion of the ventricular septum, and left ventriculography showed an hourglass appearance at systole. He was initially treated with propranolol, but the chest pain and dyspnea on exer...

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Section: Discussioncontrasting

confidence: 67%

Effective Disopyramide Treatment in a Boy With Mid-Ventricular Hypertrophic Obstructive Cardiomyopathy.

Teraguchi

Ikemoto

Kobayashi

2002

Circ J

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“…27 Observations in CD36 deficient humans and rodents have suggested the possible pathological involvement of CD36 deficiency in cardiomyopathy 8,23,24,[28][29][30] and altered lipid and carbohydrate handling 31,32 in humans, and spontaneous hypertension, hypertriglyceridemia, abdominal obesity, insulin resistance, 26,33,34 cardiac hypertrophy, 35 and dyslipidemia 27 in rodents.…”

Section: Circulation Journal Vol66 September 2002mentioning

confidence: 99%

CD36 Genotype and Long-Chain Fatty Acid Uptake in the Heart.

Kintaka

Tanaka

Imai

et al. 2002

Circ J

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lthough the heart preferentially uses long-chain fatty acids (LCFAs) as its main energy substrate, alteration in LCFA utilization is well known in pathological hearts 1 and in such cases, assessment of the LCFA metabolism is of clinical importance in determining etiology and developing therapeutic strategies.LCFA metabolism in the heart has been clinically evaluated by scintigraphy using iodine-123-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP), a radioactive LCFA analog. Regional defects of myocardial LCFA uptake are often revealed in patients with coronary artery disease 2-5 and have been interpreted as follows: (1) dissociation between BMIPP and flow-tracer activity (ie, reduced BMIPP uptake but less reduced flow-tracer accumulation) may indicate ischemic but still viable myocardium (ie, the 'mismatch of blood flow and metabolism'); or (2) diminished accumulation of BMIPP together with reduced flowtracer radioactivity related to necrotic or fibrotic tissue.However, despite the increase of flow tracer accumulation in the heart, defects of BMIPP uptake have been noticed in patients with hypertrophic cardiomyopathy and interestingly, an almost negative depiction of the heart by BMIPP scintigraphy has been occasionally observed in patients without discernible defects of coronary perfusion. [6][7][8] The underlying mechanism of this discrepancy (ie, decreased uptake of LCFA in the heart despite rather increased uptake of flow-tracer) has not been fully elucidated. Circulation Journal Vol.66, September 2002The first step of cellular LCFA metabolism is a transverse process of LCFA in the plasma membrane. Although this process is still in dispute, several lines of evidence suggest a protein-mediated process in addition to a simple diffusive process. Among the putative proteins involved, CD36 is a potential candidate. [8][9][10][11] In fact, CD36 knock-out mice have severe defects of LCFA uptake in the heart, 10 and homozygous and compound heterozygous mutation of the CD36 gene (hereafter referred to as CD36 -/-) in humans also causes severe defects of myocardial LCFA uptake, with an almost negative depiction of the heart by BMIPP scintigraphy. 8 In addition to the effects of CD36 -/-on the LCFA uptake in the heart, CD36 -/-resulted in a lack of CD36 expression in platelets and monocytes, referred to as type I CD36 deficiency. 12 We recently found a strong association between the genotype in the coding region of CD36 and the expression level of CD36. Heterozygous mutations in the coding region of this gene (hereafter referred to as CD36 +/-) resulted in the reduced expression of CD36 in monocytes, approximately half that observed in the wild-type gene (hereafter referred to as WT). 13 Accordingly, we hypothesized that not only CD36 -/-but also CD36 +/-might lead to the defects of LCFA uptake in the heart.The effects of CD36 -/-on the LCFA uptake in the heart have been characterized, so far, only qualitatively; that is, an almost negative depiction of the heart by BMIPP scintigraphy. The quantitative evaluat...

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“…Studies utilizing a nonmetabolizable fatty acid analogue, BMIPP, suggest that FAT/CD36 accounts for 50% to 80% of the total fatty acid uptake by the heart. 6 Polymorphisms in human FAT/CD36 occur in Asian and African populations at a relatively high frequency, and there have been reports that these deficient individuals have reduced cardiac fatty acid uptake [7][8][9][10][11][12][13][14] and cardiac abnormalities. However, considerable controversy exists with regard to the potential involvement of FAT/CD36 deficiency in the development of hypertrophic cardiomyopathy, 7,[15][16][17][18][19] and it has not been directly proven whether patients with FAT/ CD36 deficiency have reduced cardiac fatty acid oxidation rates or energetically compromised hearts.…”

mentioning

confidence: 99%

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

et al. 2004

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Background-Evidence from humans suggests that fatty acid translocase (FAT)/CD36 deficiency can lead to functionally and/or energetically compromised hearts, but the data are equivocal, and the subject remains controversial. In this report we assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in the intact heart and determined the effect of FAT/CD36 on energy metabolism during reperfusion of ischemic hearts. Methods and Results-Isolated working hearts from wild-type and FAT/CD36-knockout (KO) mice were perfused with Krebs-Henseleit solution containing 0..5 mmol/L calcium, and 100 U/mL insulin at a preload pressure of 11.5 mm Hg and afterload pressure of 50 mm Hg. Hearts were aerobically perfused for 30 minutes or aerobically perfused for 30 minutes, followed by 18 minutes of global no-flow ischemia and 40 minutes of aerobic reperfusion. Rates of fatty acid oxidation in FAT/CD36-KO hearts were significantly lower than in wild-type hearts at both concentrations of palmitate (0.4 or 1.2 mmol/L). In addition, hearts from FAT/CD36-KO mice displayed a compensatory increase in glucose oxidation rates. On aerobic reperfusion after ischemia, cardiac work of FAT/CD36-KO hearts recovered to the same extent as wild-type hearts. Conclusions-FAT/CD36-deficient

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Scintigraphic Evidence for a Specific Long-Chain Fatty Acid Transporting System Deficit and the Genetic Background in a Patient With Hypertrophic Cardiomyopathy

Cited by 12 publications

References 18 publications

Effective Disopyramide Treatment in a Boy With Mid-Ventricular Hypertrophic Obstructive Cardiomyopathy.

Effective Disopyramide Treatment in a Boy With Mid-Ventricular Hypertrophic Obstructive Cardiomyopathy.

CD36 Genotype and Long-Chain Fatty Acid Uptake in the Heart.

Fatty Acid Translocase/CD36 Deficiency Does Not Energetically or Functionally Compromise Hearts Before or After Ischemia

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