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A complication in male patients awaiting heart transplantation: Osteoporosis
Letters to the Editor
205
A complication in male patients awaiting heart transplantation: Osteoporosis Hale Karapolat a,⁎, Sibel Eyigor a , Mehdi Zoghi b , Yeşim Kirazlı a , Sanem Nalbantgil b , B. Durmaz a , and M. Özbaran c a
Ege University Medical Faculty Physical Medicine and Rehabilitation Dept, Turkey b Ege University Medical Faculty Cardiology Department, Turkey c Ege University Medical Faculty Cardiac and Vascular Surgery Department, Turkey
Received 21 May 2008; received in revised form 19 November 2008; accepted 20 November 2008 Available online 6 December 2008
Keywords: Osteoporosis; Heart Failure; Bone metabolism
Since osteoporosis is a disease of bone metabolism which may lead to fractures, this health problem should be deliberated carefully in our country as well as it is done worldwide. Although congestive heart failure (CHF) has not been associated with defined bone disorder, it has been reported that BMD may be low in patients with severe congestive heart failure (CHF) who are candidates for cardiac transplantation [1]. The pathogenesis of disturbed bone turnover in CHF patients is, however, far from clear. Factors associated with congestive heart failure that may contribute to bone loss include cardiac cachexia, low calcium intake, immobility, heparin administration and loop diuretics, low level of 25hydroxyvitamin D (25 OHD), low levels of calcitriol and low circulating sex hormone levels [2,3]. Several studies have reported low bone mineral densities in CHF patients who are candidates for cardiac transplantation [1,4]. However, these studies have limited scientific information and the number of studies comparing BMD measurements of CHF patients with those of age-matched controls are not sufficient. Therefore, this study aims to determine the bone mineral density and assess the relationship among bone mineral density, bone metabolism and the clinical data in end-stage heart failure patients. Heart transplantation candidates due to end-stage heart failure who were followed up by Department of Cardiac and Vascular Surgery of Ege University Medical Faculty between January 2000 and January 2006 were recruited for the study. Study inclusion criteria were to be in the transplant list for at least 6 months, to be free from any psychiatric disease, and to be a volunteer to participate in the study. Patients were excluded if they had cancer, had systemic rheumatologic or connective tissue disorders, had advanced liver or renal ⁎ Corresponding author. Ege University Medical Faculty Physical Medicine and Rehabilitation Dept, 35100 Bornova, Izmir, Turkey. Tel.: +90 2323902406; fax: +90 2323881953 120. E-mail address: [email protected] (H. Karapolat).
disease, primary hyperparatyrodism, thyrotoxicosis or suppressed tyroid stimulating hormone, were unable to ambulate, were New York Heart Association (NYHA) class-IV, had a history of medication that may effect the bone metabolism. Sociodemographic and clinical characteristics were obtained via patient interview and medical record review. Clinical data included NYHA classification, heart failure etiology, ejection fraction, concomitant disease, medication. Control participants were recruited by physician referrals. Exclusion criteria were the same, and controls were sedentary and had no history of CHF. The following assessments were performed for all the subjects: BMD of the lumbar spine (L1–L4) and proximal femur was measured by dual-energy X-ray absorptiometry (DEXA) using a Hologic QDR 4500A apparatus (Hologic, Waltham, MA, USA). According to the WHO criteria, a T-score b −2.5 SD represents osteoporosis and a T-score between −1 SD and −2.5 SD, osteopenia [5]. Blood specimens were analysed for creatinine, creatinine clearance, serum calcium and phosphate, and 24-h urinary calcium and phosphate, follicle-stimulating hormone (FSH), luteinising hormone (LH), free testosterone (fT), serum osteocalcin, urine deoxypyridinoline (DPD), serum-intact parathormopne (PTH). This study was approved by the local ethics committee of our institution and informed consent forms were obtained from all of the patients who participated. All data were analyzed using the SPSS version 14 statistical software package. Mann Whitney U Test And ChiSquare Test were used for statistical analysis. One hundred two end-stage heart failure patients were recruited for the study. Seventy five male patients were eligible, and 61 agreed to participate. Thirty non-HF controls were enrolled into this study. Demographic and clinical characteristics of CHF group is given in Table 1. There was no difference with regard to DEXA measurements between CHF and control groups (p N 0.05), (Table 2). Comparison of blood values between CHF and control groups has shown that 24-hour urine calcium, 24-hour urine
206
Letters to the Editor
phosphate, and fT values were significantly low, while deoxypyridinoline and parathormone values were significantly high (p b 0.05, Table 2). In CHF patients, clinical (NYHA, LVEF, RVEF) and laboratory data did not show any significant correlation with T score and BMD in lumbar spine and femoral region (p N 0.05). No correlation was found also among medications of CHF patients, BMD and T scores of lumbar spine and hip region, and biochemical–hormonal markers (p N 0.05). In our study, no difference was detected between male end-stage heart failure patients and the control group in terms of BMD measurements and T scores in lumbar spine and hip regions. Similarly, in a study carried out with endstage CHF patients with a lower mean age, Shane et al. evaluated the BMD of pretransplant heart failure patients and found normal scores in DEXA [1]. This was because patients in these two studies were young and may not have developed significant bone loss related to HF. In our study, the rate of osteoporosis was higher in the lumbar region, as it was the case for age-matched controls. However, in contrast to our findings, some investigators reported that the greatest decrease in BMD occurred in femoral neck area in CHF patients [1,5]. The discrepancy between femoral neck and lumbar spine BMD have been caused by aortic calcifications, which may elevate lumbar spine BMD. Lower lumbar BMD results of our study may be explained by absence of aortic calcification as the patients are younger in age. Cardiac disease is associated with limited mobility and sedentary lifestyle predispose people to develop vitamin D insufficiency. Shane et al. suggested that low vitamin D metabolite concentrations were associated with PTH concentrations at the upper end of reference range and urinary concentrations of the bone resorption markers above reference range [1]. In accordance to the literature, PTH levels were found higher in our study compared to the control group.
Table 1 Demographic and clinical variables of patients with end stage heart failure. Demographic variables Age (years) (mean ± SD) Time after diagnosis (year) (mean ± SD) BMI (kg/m2) (mean ± SD) Cigarette smoking (pack/years) (mean ± SD)
43.59 ± 11.74 5.20 ± 4.84 26.57 ± 4.34 19.00 ± 20.26
Clinical variables Dilated cardiomyopathy (%) LVEF (%) RVEF (%) NYHA 2/3%
58.5 27.32 ± 10.16 49.05 ± 12.48 82.2/17.8
BMI: Body mass index, LVEF: left ventricular ejection fraction, RVEF: right ventricular ejection fraction.
Table 2 Bone measurement values and blood values of CHF and control groups.
Lumbar BMD (g/cm2) Lumbar T score Femoral neck BMD (g/cm2) Femoral neck T score Femoral trochanter BMD (g/cm2) Femoral trochanter T score 24 hour urine Ca (mg/dl) 24 hour urine P (mg/dl) Free testosterone (pg/ml) Deoxypyridinoline (nM/mM) Parathormone (pg/ml)
CHF group (n: 61)
Control group (n: 30 )
0.96 ± 0.14 − 1.23 ± 1.16 0.85 ± 0.18 −0.41 ± 1.12 0.73 ± 0.13 − 0.40 ± 1.00 129.29 ± 110.87 * 613.58 ± 410.10 * 14.38 ± 7.96 * 6.49 ± 2.76 * 57.96 ± 36.12 *
0.95 ± 0.12 − 1.30 ± 1.08 0.81 ± 0.11 − 0.85 ± 0.82 0.72 ± 0.10 − 0,44 ± 0.82 214.13 ± 103.63 823.57 ± 286.79 19.07 ± 9.34 4.15 ± 1.16 29.47 ± 16.26
CHF: Congestive heart failure, BMD: Bone mineral density, Ca: calcium, P: phosphate. *p b 0.05.
Hypogonadism in adult men is associated almost constantly with a BMD lower than normal [6,7] and in adult young men hypogonadism is a frequent cause of secondary osteoporosis [8]. Supporting our results, previous studies have shown testosterone deficiency in men with CHF are consistently reported to be low in proportion to the severity of heart failure [9,10]. Bone markers may be helpful in the prediction of future bone loss [11]. Pérez-Castrillon et al. found no relationship between bone turnover markers [osteoprotogerin (OPG)/ receptor activator of nuclear factor-KB ligand (RANKL)] and BMD in patients with acute coronary syndrome [12]. In addition elevated serum levels of osteocalcin, a marker of bone turnover, presented by their coronary patients with osteoporosis [12]. In accordance with other studies, deoxypyridinoline, one of the bone resorption markers, was found significantly high in our study [13,14]. Elevated deoxypyridinoline levels in CHF patients were also associated in the literature with secondary causes of osteoporosis such as renal function impairment, vitamin D insufficiency (secondary PTH elevation), and hypogonadism. It is thought that elevated deoxypyridinoline levels in our study might also be associated with increased PTH or hypogonadism. Our study results have pointed to an increase in bone resorption markers in end-stage male CHF patients although BMD was not different from that of the health control group. Bone markers reflect early changes in bone metabolism. Therefore, the assessment of bone turnover may reflect ongoing bone remodelling more accurately than bone mass measurements [11]. Identification of risky groups for osteoporosis before transplant and taking preventive and therapeutic measures is crucial in this respect. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [15].
Letters to the Editor
References [1] Shane E, Mancini D, Aaronson K, et al. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 1997;103:197–207. [2] Pisani M, Mullen M. Prevention of osteoporosis in cardiac transplant recipients. Curr Opin Cardiol 2001;17:160–4. [3] Christ E, Linka A, Junga G, et al. Bone density and laboratory parameters of bone metabolism in patients with terminal heart disease. Schweiz Med Wochenschr 1996;126:1553–9. [4] Van Cleemput J, Daenen W, Nijs J, Geusens P, Dequeker J, Vanhaecke J. Timing and quantification of bone loss in cardiac transplant recipients. Transpl Int 1995;8:196–200. [5] Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. Bone Miner Res 1994;9:1137–41. [6] Finkelstein JS, Klibanski A, Neer RM. A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty. J Clin Endocrinol Metab 1996;81:1152–5. [7] Benito M, Gomberg B, Wehrli RH, et al. Deterioration of trabecular architecture in hypogonadal men. J Clin Endocrinol Metab 2003;88:1497–502.
207
[8] Orwoll ES, Klein RF. Osteoporosis in men. Endocr Rev 1995;16:87–116. [9] Kontoleon PE, Anastasiou-Nana MI, Papapetrou PD, et al. Hormonal profile in patients with congestive heart failure. Int J Cardiol 2003;87:179–83. [10] Moriyama Y, Yasue H, Yoshimura M, et al. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab 2000;85:1834–40. [11] Zittermann A, Schleithoff SS, Koerfer R. Markers of bone metabolism in congestive heart failure. Clin Chim Acta 2006;366:27–36. [12] Pérez-Castrillon JL, Abad L, Vega G, et al. Bone mineral density, bone remodeling and osteoprotegerin in patients with acute coronary syndrome. Int J Cardiol 2008;129:144–5. [13] Cohen N, Gorelik O, Almoznino-Sarafian D, et al. Renal dysfunction in congestive heart failure, pathophysiological and prognostic significance. Clin Nephrol 2004;61:177–84. [14] Silverberg DS, Wexler D, Blum M, et al. The interaction between heart failure, renal failure and anemia — the cardio-renal anemia syndrome. Blood Purif 2004;22:277–84. [15] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.11.091
Author's reply: What is a true definition of MELAS? Nobuyuki Takahashi and Toshio Shimada ⁎ Division of Cardiovascular Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo City, Shimane 693-8501, Japan Received 12 June 2008; accepted 20 November 2008 Available online 6 December 2008
We would like to thank Prof. Finsterer for your very insightful comments [1] to our article [2]. Firstly, we are sorry for insufficient description or information about the patient in our article. On admission, the patient's right grip strength was 11 kg and left grip strength was 9 kg, his muscular strength deteriorated remarkably for his age. The cataract was confirmed on the ophthalmological examination. Cerebral computerized tomographic scan revealed bilateral basal ganglia calcifications and diffuse atrophy. In our case, the lactate level of cerebrospinal fluid was 46 mg/dl. We don't have precise reference levels of lactate in cerebrospinal fluid. In the other article, Koga et al. mentioned ⁎ Corresponding author. Tel.: +81 853 20 2249; fax: +81 853 20 2204. E-mail address: [email protected] (T. Shimada).
that the reference level is less than 1.2 mmol/L [3]. Our measured value recalculated to mmol/L was equal to 5.1 mmol/L with high value in your reference level [4]. As Prof. Finsterer pointed, it is very difficult to exclude hypertrophic cardiomyopathy completely without myocardial biopsy. As a cause of left ventricular hypertrophy, we also doubted Fabry disease, but his α-galactosidase activity of peripheral blood was within the normal range. Cardiac echocardiogram didn't demonstrate the findings of left ventricular hypertrabeculation/noncompaction. In this case, we identified the mitochondrial A3243G mutation in the patient's both skeletal muscle and leukocyte. However, we measured the heteroplasmy rate only in the patient's skeletal muscle. Additionally, repeated measurement of heteroplasmy rate has not been performed and we couldn't measure the activities of respiratory chain complexes.
205
A complication in male patients awaiting heart transplantation: Osteoporosis Hale Karapolat a,⁎, Sibel Eyigor a , Mehdi Zoghi b , Yeşim Kirazlı a , Sanem Nalbantgil b , B. Durmaz a , and M. Özbaran c a
Ege University Medical Faculty Physical Medicine and Rehabilitation Dept, Turkey b Ege University Medical Faculty Cardiology Department, Turkey c Ege University Medical Faculty Cardiac and Vascular Surgery Department, Turkey
Received 21 May 2008; received in revised form 19 November 2008; accepted 20 November 2008 Available online 6 December 2008
Keywords: Osteoporosis; Heart Failure; Bone metabolism
Since osteoporosis is a disease of bone metabolism which may lead to fractures, this health problem should be deliberated carefully in our country as well as it is done worldwide. Although congestive heart failure (CHF) has not been associated with defined bone disorder, it has been reported that BMD may be low in patients with severe congestive heart failure (CHF) who are candidates for cardiac transplantation [1]. The pathogenesis of disturbed bone turnover in CHF patients is, however, far from clear. Factors associated with congestive heart failure that may contribute to bone loss include cardiac cachexia, low calcium intake, immobility, heparin administration and loop diuretics, low level of 25hydroxyvitamin D (25 OHD), low levels of calcitriol and low circulating sex hormone levels [2,3]. Several studies have reported low bone mineral densities in CHF patients who are candidates for cardiac transplantation [1,4]. However, these studies have limited scientific information and the number of studies comparing BMD measurements of CHF patients with those of age-matched controls are not sufficient. Therefore, this study aims to determine the bone mineral density and assess the relationship among bone mineral density, bone metabolism and the clinical data in end-stage heart failure patients. Heart transplantation candidates due to end-stage heart failure who were followed up by Department of Cardiac and Vascular Surgery of Ege University Medical Faculty between January 2000 and January 2006 were recruited for the study. Study inclusion criteria were to be in the transplant list for at least 6 months, to be free from any psychiatric disease, and to be a volunteer to participate in the study. Patients were excluded if they had cancer, had systemic rheumatologic or connective tissue disorders, had advanced liver or renal ⁎ Corresponding author. Ege University Medical Faculty Physical Medicine and Rehabilitation Dept, 35100 Bornova, Izmir, Turkey. Tel.: +90 2323902406; fax: +90 2323881953 120. E-mail address: [email protected] (H. Karapolat).
disease, primary hyperparatyrodism, thyrotoxicosis or suppressed tyroid stimulating hormone, were unable to ambulate, were New York Heart Association (NYHA) class-IV, had a history of medication that may effect the bone metabolism. Sociodemographic and clinical characteristics were obtained via patient interview and medical record review. Clinical data included NYHA classification, heart failure etiology, ejection fraction, concomitant disease, medication. Control participants were recruited by physician referrals. Exclusion criteria were the same, and controls were sedentary and had no history of CHF. The following assessments were performed for all the subjects: BMD of the lumbar spine (L1–L4) and proximal femur was measured by dual-energy X-ray absorptiometry (DEXA) using a Hologic QDR 4500A apparatus (Hologic, Waltham, MA, USA). According to the WHO criteria, a T-score b −2.5 SD represents osteoporosis and a T-score between −1 SD and −2.5 SD, osteopenia [5]. Blood specimens were analysed for creatinine, creatinine clearance, serum calcium and phosphate, and 24-h urinary calcium and phosphate, follicle-stimulating hormone (FSH), luteinising hormone (LH), free testosterone (fT), serum osteocalcin, urine deoxypyridinoline (DPD), serum-intact parathormopne (PTH). This study was approved by the local ethics committee of our institution and informed consent forms were obtained from all of the patients who participated. All data were analyzed using the SPSS version 14 statistical software package. Mann Whitney U Test And ChiSquare Test were used for statistical analysis. One hundred two end-stage heart failure patients were recruited for the study. Seventy five male patients were eligible, and 61 agreed to participate. Thirty non-HF controls were enrolled into this study. Demographic and clinical characteristics of CHF group is given in Table 1. There was no difference with regard to DEXA measurements between CHF and control groups (p N 0.05), (Table 2). Comparison of blood values between CHF and control groups has shown that 24-hour urine calcium, 24-hour urine
206
Letters to the Editor
phosphate, and fT values were significantly low, while deoxypyridinoline and parathormone values were significantly high (p b 0.05, Table 2). In CHF patients, clinical (NYHA, LVEF, RVEF) and laboratory data did not show any significant correlation with T score and BMD in lumbar spine and femoral region (p N 0.05). No correlation was found also among medications of CHF patients, BMD and T scores of lumbar spine and hip region, and biochemical–hormonal markers (p N 0.05). In our study, no difference was detected between male end-stage heart failure patients and the control group in terms of BMD measurements and T scores in lumbar spine and hip regions. Similarly, in a study carried out with endstage CHF patients with a lower mean age, Shane et al. evaluated the BMD of pretransplant heart failure patients and found normal scores in DEXA [1]. This was because patients in these two studies were young and may not have developed significant bone loss related to HF. In our study, the rate of osteoporosis was higher in the lumbar region, as it was the case for age-matched controls. However, in contrast to our findings, some investigators reported that the greatest decrease in BMD occurred in femoral neck area in CHF patients [1,5]. The discrepancy between femoral neck and lumbar spine BMD have been caused by aortic calcifications, which may elevate lumbar spine BMD. Lower lumbar BMD results of our study may be explained by absence of aortic calcification as the patients are younger in age. Cardiac disease is associated with limited mobility and sedentary lifestyle predispose people to develop vitamin D insufficiency. Shane et al. suggested that low vitamin D metabolite concentrations were associated with PTH concentrations at the upper end of reference range and urinary concentrations of the bone resorption markers above reference range [1]. In accordance to the literature, PTH levels were found higher in our study compared to the control group.
Table 1 Demographic and clinical variables of patients with end stage heart failure. Demographic variables Age (years) (mean ± SD) Time after diagnosis (year) (mean ± SD) BMI (kg/m2) (mean ± SD) Cigarette smoking (pack/years) (mean ± SD)
43.59 ± 11.74 5.20 ± 4.84 26.57 ± 4.34 19.00 ± 20.26
Clinical variables Dilated cardiomyopathy (%) LVEF (%) RVEF (%) NYHA 2/3%
58.5 27.32 ± 10.16 49.05 ± 12.48 82.2/17.8
BMI: Body mass index, LVEF: left ventricular ejection fraction, RVEF: right ventricular ejection fraction.
Table 2 Bone measurement values and blood values of CHF and control groups.
Lumbar BMD (g/cm2) Lumbar T score Femoral neck BMD (g/cm2) Femoral neck T score Femoral trochanter BMD (g/cm2) Femoral trochanter T score 24 hour urine Ca (mg/dl) 24 hour urine P (mg/dl) Free testosterone (pg/ml) Deoxypyridinoline (nM/mM) Parathormone (pg/ml)
CHF group (n: 61)
Control group (n: 30 )
0.96 ± 0.14 − 1.23 ± 1.16 0.85 ± 0.18 −0.41 ± 1.12 0.73 ± 0.13 − 0.40 ± 1.00 129.29 ± 110.87 * 613.58 ± 410.10 * 14.38 ± 7.96 * 6.49 ± 2.76 * 57.96 ± 36.12 *
0.95 ± 0.12 − 1.30 ± 1.08 0.81 ± 0.11 − 0.85 ± 0.82 0.72 ± 0.10 − 0,44 ± 0.82 214.13 ± 103.63 823.57 ± 286.79 19.07 ± 9.34 4.15 ± 1.16 29.47 ± 16.26
CHF: Congestive heart failure, BMD: Bone mineral density, Ca: calcium, P: phosphate. *p b 0.05.
Hypogonadism in adult men is associated almost constantly with a BMD lower than normal [6,7] and in adult young men hypogonadism is a frequent cause of secondary osteoporosis [8]. Supporting our results, previous studies have shown testosterone deficiency in men with CHF are consistently reported to be low in proportion to the severity of heart failure [9,10]. Bone markers may be helpful in the prediction of future bone loss [11]. Pérez-Castrillon et al. found no relationship between bone turnover markers [osteoprotogerin (OPG)/ receptor activator of nuclear factor-KB ligand (RANKL)] and BMD in patients with acute coronary syndrome [12]. In addition elevated serum levels of osteocalcin, a marker of bone turnover, presented by their coronary patients with osteoporosis [12]. In accordance with other studies, deoxypyridinoline, one of the bone resorption markers, was found significantly high in our study [13,14]. Elevated deoxypyridinoline levels in CHF patients were also associated in the literature with secondary causes of osteoporosis such as renal function impairment, vitamin D insufficiency (secondary PTH elevation), and hypogonadism. It is thought that elevated deoxypyridinoline levels in our study might also be associated with increased PTH or hypogonadism. Our study results have pointed to an increase in bone resorption markers in end-stage male CHF patients although BMD was not different from that of the health control group. Bone markers reflect early changes in bone metabolism. Therefore, the assessment of bone turnover may reflect ongoing bone remodelling more accurately than bone mass measurements [11]. Identification of risky groups for osteoporosis before transplant and taking preventive and therapeutic measures is crucial in this respect. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [15].
Letters to the Editor
References [1] Shane E, Mancini D, Aaronson K, et al. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 1997;103:197–207. [2] Pisani M, Mullen M. Prevention of osteoporosis in cardiac transplant recipients. Curr Opin Cardiol 2001;17:160–4. [3] Christ E, Linka A, Junga G, et al. Bone density and laboratory parameters of bone metabolism in patients with terminal heart disease. Schweiz Med Wochenschr 1996;126:1553–9. [4] Van Cleemput J, Daenen W, Nijs J, Geusens P, Dequeker J, Vanhaecke J. Timing and quantification of bone loss in cardiac transplant recipients. Transpl Int 1995;8:196–200. [5] Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. Bone Miner Res 1994;9:1137–41. [6] Finkelstein JS, Klibanski A, Neer RM. A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty. J Clin Endocrinol Metab 1996;81:1152–5. [7] Benito M, Gomberg B, Wehrli RH, et al. Deterioration of trabecular architecture in hypogonadal men. J Clin Endocrinol Metab 2003;88:1497–502.
207
[8] Orwoll ES, Klein RF. Osteoporosis in men. Endocr Rev 1995;16:87–116. [9] Kontoleon PE, Anastasiou-Nana MI, Papapetrou PD, et al. Hormonal profile in patients with congestive heart failure. Int J Cardiol 2003;87:179–83. [10] Moriyama Y, Yasue H, Yoshimura M, et al. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab 2000;85:1834–40. [11] Zittermann A, Schleithoff SS, Koerfer R. Markers of bone metabolism in congestive heart failure. Clin Chim Acta 2006;366:27–36. [12] Pérez-Castrillon JL, Abad L, Vega G, et al. Bone mineral density, bone remodeling and osteoprotegerin in patients with acute coronary syndrome. Int J Cardiol 2008;129:144–5. [13] Cohen N, Gorelik O, Almoznino-Sarafian D, et al. Renal dysfunction in congestive heart failure, pathophysiological and prognostic significance. Clin Nephrol 2004;61:177–84. [14] Silverberg DS, Wexler D, Blum M, et al. The interaction between heart failure, renal failure and anemia — the cardio-renal anemia syndrome. Blood Purif 2004;22:277–84. [15] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.11.091
Author's reply: What is a true definition of MELAS? Nobuyuki Takahashi and Toshio Shimada ⁎ Division of Cardiovascular Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo City, Shimane 693-8501, Japan Received 12 June 2008; accepted 20 November 2008 Available online 6 December 2008
We would like to thank Prof. Finsterer for your very insightful comments [1] to our article [2]. Firstly, we are sorry for insufficient description or information about the patient in our article. On admission, the patient's right grip strength was 11 kg and left grip strength was 9 kg, his muscular strength deteriorated remarkably for his age. The cataract was confirmed on the ophthalmological examination. Cerebral computerized tomographic scan revealed bilateral basal ganglia calcifications and diffuse atrophy. In our case, the lactate level of cerebrospinal fluid was 46 mg/dl. We don't have precise reference levels of lactate in cerebrospinal fluid. In the other article, Koga et al. mentioned ⁎ Corresponding author. Tel.: +81 853 20 2249; fax: +81 853 20 2204. E-mail address: [email protected] (T. Shimada).
that the reference level is less than 1.2 mmol/L [3]. Our measured value recalculated to mmol/L was equal to 5.1 mmol/L with high value in your reference level [4]. As Prof. Finsterer pointed, it is very difficult to exclude hypertrophic cardiomyopathy completely without myocardial biopsy. As a cause of left ventricular hypertrophy, we also doubted Fabry disease, but his α-galactosidase activity of peripheral blood was within the normal range. Cardiac echocardiogram didn't demonstrate the findings of left ventricular hypertrabeculation/noncompaction. In this case, we identified the mitochondrial A3243G mutation in the patient's both skeletal muscle and leukocyte. However, we measured the heteroplasmy rate only in the patient's skeletal muscle. Additionally, repeated measurement of heteroplasmy rate has not been performed and we couldn't measure the activities of respiratory chain complexes.