Long-Term Levocarnitine Ameliorates Left Ventricular Diastolic as Well as Systolic Dysfunction in Hemodialysis Patients　- Multi-Center Study.

Background: Levocarnitine has been reported to improve the left ventricular (LV) systolic function and decrease LV hypertrophy in hemodialysis (HD) patients. Its effect on LV diastolic dysfunction, however, has not yet been clarified. Methods and Results: HD patients (n=88) were given levocarnitine i.v. 1,000 mg for 12 months at the end of every dialysis session through the dialysis circuit of the venous site. LV ejection fraction (EF), E/A, E/e', left atrial volume index (LAVI) and LV mass index (LVMI) were measured before and 3, 6, 9, and 12 months after the start of levocarnitine on echocardiography. We regarded E/A≤0.8, E/e'>14 and LAVI>34 mL/m2 as LV diastolic dysfunction, and LVEF<55% as LV systolic dysfunction. We also investigated the effect of levocarnitine on HFpEF. Plasma brain natriuretic peptide, total carnitine, free carnitine, and acyl-carnitine and biochemistry parameters were measured. Levocarnitine significantly improved LV diastolic function in HD patients with LV diastolic dysfunction, but did not affect LV diastolic function in those with normal LV diastolic function. Levocarnitine significantly improved HFpEF. Levocarnitine significantly improved the LV systolic function in HD patients with LV systolic dysfunction but did not affect the LV systolic function in those with normal LV systolic function. Levocarnitine significantly decreased LVMI and increased plasma total, free, and acyl-carnitine. Conclusions: Levocarnitine ameliorates LV diastolic as well as LV systolic dysfunction in HD patients.

Renoprotective effect of the addition of losartan to ongoing treatment with an angiotensin converting enzyme inhibitor in type-2 diabetic patients with nephropathy.

Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects. To many patients who are nonresponsive to monotherapy with these agents, combination therapy appears to be a good treatment option. In the present study, we examined the effects of the addition of an ARB (losartan) followed by titration upon addition and at 3 and 6 months (n=14) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months (n=20) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure (BP) of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and provided renal protection in patients with type-2 diabetic nephropathy.

In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings.

BACKGROUND: The purpose of the present study was to define whether integrated backscatter (IB) combined with conventional intravascular ultrasound (IVUS) makes tissue characterization of coronary arterial plaques possible. METHODS AND RESULTS: IB-IVUS was performed in coronary arteries (total 18 segments) of 9 patients at autopsy, and the findings were compared with the histology. RF signals, which were digitized at 2 GHz in 8-bit resolution, were obtained with an IVUS system with a 40-MHz catheter. IB values of the RF signal from the region of interest (ROI) (100-microm depth, 1.4 degrees per line) were calculated by use of a personal computer. IB values on the ROIs were divided into 5 categories, compared with each of the plaque histologies: category 1 (thrombus), -88 < IB < or = -80; category 2 (intimal hyperplasia or lipid core), -73 < IB < or = -63; category 3 (fibrous tissue), -63 < IB < or = -55; category 4 (mixed lesions), -55 < IB < or = -30; and category 5 (calcification), -30 < IB < or = -23. On the basis of these categories, we analyzed 5120 ROIs per segment in each ring-like arterial specimen. Color-coded maps of plaques were constructed by use of these IB data and conventional IVUS data, which reflected the plaque histology of autopsied coronary arteries well. Then, the same method was undertaken in 24 segments with plaque from 12 patients in vivo with angina pectoris. Comparisons between coronary angioscopy and IB-IVUS revealed that the surface color of plaques in angioscopy reflected the thickness of the fibrous cap rather than the size of the lipid core. CONCLUSIONS: IB-IVUS represents a new and useful tool for evaluating the tissue structure of human coronary arterial plaques.

Assessment of arterial medial characteristics in human carotid arteries using integrated backscatter ultrasound and its histological implications.

Recently, ultrasound tissue characterization of the carotid arteries with an integrated backscatter (IB) analysis was shown to identify a high-risk group of atherosclerosis. To clarify whether IB ultrasound is useful in assessing arterial sclerosis as well as stiffness beta and whether IB values reflect the histological structure, we measured IB values of common carotid media in 52 subjects without coronary risk factors and in 10 patients with systemic sclerosis (SSc) in the clinical studies and 12 patients in the histological studies with a Philips Medical Systems Sonos 5500. IB values were correlated with age (r=0.69, P<0.0001), intima-media thickness (r=0.72, P<0.0001) and stiffness beta (r=0.80, P<0.0001) in the control subjects. IB values and stiffness beta in the SSc group were greater than in an age- and sex-matched control group (IB values: 9.6+/-2.7dB versus 16.1+/-1.8dB; stiffness beta: 11.5+/-4.5 versus 20.6+/-5.6, P<0.01). IB values of the media were correlated with the elastic fragmentation index (r=0.63, P=0.029) and the collagen fiber index (r=0.59, P=0.046). Measurements of IB values of carotid media are useful for non-invasively evaluating arterial sclerosis.

Decrease of beta-cells and increase of alpha-cells in a diabetic patient with mitochondrial DNA 3243 (A-->G) mutation.

We report here a case of a 53-year-old woman with mitochondrial 3243 (A-->G) mutation diabetes. Diabetes mellitus was diagnosed at 39 years of age. At 50 years of age, cardiomyopathy and hypothyroidism were noted. At 53 years of age, the patient was admitted to our hospital for treatment of necrotic ulceration of toes. However, she died of massive heart failure. Pathological examination at autopsy showed a decrease in size, number, and acidophilicity of islets in the pancreas. Immunohistochemical stain revealed a decrease in the beta-cell population to 20.5+/-9.2% and a relative increase in alpha-cell population to 48.6+/-11.5%.