Satoru Yamazaki

Sympathetic overactivity and sudden cardiac death among hemodialysis patients with left ventricular hypertrophy

BACKGROUND We prospectively investigated whether cardiac autonomic imbalance is associated with sudden cardiac death (SCD) among a group of hemodialysis patients with left ventricular hypertrophy (LVH). METHODS In a prospective cohort study, we enrolled 196 asymptomatic patients on chronic hemodialysis who had LVH as determined by echocardiography and had undergone twenty-four-hour ambulatory Holter electrocardiography between dialysis sessions (males/females, 114/82; mean age, 65+/-12 years) to analyze heart rate variability. We calculated the percentage difference between adjacent NN intervals more than 50 ms (pNN50) and high-frequency component (HF, 0.15-0.40 Hz) as parameters of cardiac parasympathetic activity, and the low-frequency component (LF, 0.04-0.15 Hz)/HF component ratio as a parameter of sympathetic activity. RESULTS During 4.5+/-1.9-year follow-up, 21 patients who had undergone coronary revascularization within 60 days of enrollment were excluded from the analysis. Among the remaining 175 patients (male/female, 105/70; 66+/-12 years), SCD was recognized in 23 patients. On stepwise Cox hazard analysis, SCD was positively associated with age and LF/HF ratio, and tended to be inversely associated with pNN50. On Kaplan-Meier analysis, SCD-free survival rates at 5 years were 29.4% and 98.1% in patients with LF/HF ratios of 1.9 or more and below 1.9, respectively. CONCLUSIONS The presence of cardiac sympathetic overactivity may predict the occurrence of SCD in the asymptomatic hemodialysis patients with LVH.

Oral Nicorandil to Reduce Cardiac Death After Coronary Revascularization in Hemodialysis Patients: A Randomized Trial

BACKGROUND Survival after invasive coronary revascularization is worse in patients with chronic kidney disease than in patients without chronic kidney disease. We examined whether oral administration of nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve outcome after coronary revascularization in hemodialysis patients. STUDY DESIGN Open-labeled prospective randomized trial. SETTING & PARTICIPANTS Maintenance hemodialysis patients who underwent percutaneous coronary artery intervention and had complete coronary revascularization (absence of both restenosis and de novo coronary lesion) at coronary arteriography 6 months later. Enrollment occurred between January 1, 2002, and December 31, 2004. INTERVENTIONS Treatment with or without oral administration of nicorandil, 15 mg/d. OUTCOMES & MEASUREMENTS The primary end point was cardiac death (sudden cardiac death or death from acute myocardial infarction or congestive heart failure). The secondary end point was all-cause death. End-point adjudication was performed masked to the intervention. RESULTS 129 patients (91 men, 38 women) with a mean age of 66 +/- 9 (SD) years. During a 2.7 +/- 1.5-year follow-up, 26 died of cardiac events (acute myocardial infarction, 6; congestive heart failure, 5; sudden cardiac death, 15), and 12 died of noncardiac causes. Cardiac death-free survival rates were greater in the nicorandil group than in the control group (P = 0.009; at 3 years, 86.6% in the nicorandil group and 70.7% in the control group). All-cause death-free survival rates were also greater in the nicorandil group than in the control group (P = 0.01; at 3 years, 79.2% in the nicorandil group versus 60.5% in the control group). Additional percutaneous coronary artery intervention was performed in 6 participants in the nicorandil group and 2 participants in the control group. No serious side effects of nicorandil were reported during the course of the study. LIMITATIONS Small sample size and open-label design. CONCLUSIONS Oral administration of nicorandil may reduce cardiac death and improve the survival of hemodialysis patients after coronary revascularization.

Myocardial fatty acid imaging identifies a group of hemodialysis patients at high risk for cardiac death after coronary revascularization

We prospectively evaluated if impaired myocardial fatty acid metabolism is involved in cardiac death after revascularization by percutaneous coronary artery intervention in dialysis patients. A cohort of hemodialysis patients was assessed by dual single-photon emission computed tomography using the radioiodinated fatty acid analogue BMIPP and radiolabeled thallium chloride. Tomography was done within one month before the first coronary intervention and at the last follow-up angiography at which neither restenosis nor de novo lesions were detected. Radiolabel uptake on tomography images was graded in segments and calculated as summed BMIPP or thallium scores. Among the 90 hemodialysis patients in the study, 19 died of cardiac events. Multivariate Cox hazard analysis found a significant association of cardiac death with the BMIPP summed scores at the last follow-up angiography. Kaplan-Meier analysis showed the cardiac death-free survival rates at 3 years of follow-up were significantly higher in patients with lower BMIPP summed scores. These results suggest that myocardial fatty acid imaging may be a useful test to identify high risk groups of cardiac death in hemodialysis patients.

Two cases of parathyroid carcinoma in patients on long-term hemodialysis

Two cases of parathyroid carcinoma, in a 46-year-old male on maintenance hemodialysis for 135 months and a 55-year-old female on maintenance hemodialysis for 64 months were reported. In both cases, the parathyroid carcinoma showed local invasion and the other glands were hyperplasia and/or adenoma, which would support the concept of malignant transformation occurring in parathyroid hyperplasia. The concurrence of parathyroid carcinoma with hyperplasia and/or adenoma is a pertinent feature in patients on maintenance dialysis, although it is rare in primary parathyroid carcinoma.

Clinical Potential of Nicorandil to Inhibit Major Cardiac Events in Hemodialysis Patients with Suspected Myocardial Ischemia

Background/Aims: We examined whether nicorandil, which is a hybrid of an adenosine triphosphate-sensitive potassium channel opener and a nitrate, could inhibit major adverse cardiac events (MACE) in maintenance hemodialysis patients with suspected myocardial ischemia. Methods: We enrolled 148 asymptomatic patients on maintenance hemodialysis, who had exhibited potential myocardial ischemia as assessed by myocardial fatty acid imaging. The end-point was MACE including cardiac death and non-fatal acute myocardial infarction. A propensity-matched analysis was performed. Results: Over a mean duration of follow-up of 2.8 ± 1.6 years in the 82 propensity-matched patients (41 in the nicorandil group and 41 in the non-nicorandil group), we observed 17 cardiac deaths and 12 cases of nonfatal myocardial infarction. The incidence of MACE was lower (p = 0.0365) in the nicorandil group (10/41, 24.4%) than in the non-nicorandil group (19/41, 46.3%). On stepwise Cox hazard analysis, MACE was significantly inhibited by administration of nicorandil (hazard risk, 0.387; 95% CI 0.178–0.842; p = 0.0168). Kaplan-Meier survival estimates revealed that MACE-free survival rates at 3 years were 80.5 and 58.5% in patients with and without nicorandil, respectively. Conclusions: Oral administration of nicorandil may offer new potential for the inhibition of MACE in hemodialysis patients.

Association of Insulin Resistance with de novo Coronary Stenosis after Percutaneous Coronary Artery Intervention in Hemodialysis Patients

Background/Aims: De novo coronary atherosclerosis may be involved in the poor prognosis after percutaneous coronary artery intervention (PCI) in hemodialysis patients. We aimed to clarify the factors associated with de novocoronary lesion in this population. Methods: We enrolled 106 patients on hemodialysis (72 men, 34 women; mean age, 65.4 ± 8.9 years), who had firstly received PCI with bare-metal stents for single coronary lesions and undergone follow-up coronary angiography (CAG) 6 months thereafter. Coronary lesion with stenosis of >50% diameter that was newly recognized at follow-up CAG was defined as de novo coronary stenosis. The values of biochemical parameters were determined as the means of several measurements between PCI and follow-up CAG. Results: Follow-up CAG revealed de novo coronary stenosis in 40 (37.7%) of the 106 hemodialysis patients who had received PCI. Stepwise multiple logistic regression analysis showed that de novo coronary lesions were strongly associated with homeostasis model assessment insulin resistance index (HOMA-IR; 1 mM× [µU/ml]: odds ratio, 7.312; p =0.001). This significant association of HOMA-IR with de novo coronary stenosis was recognized in the diabetic and nondiabetic subgroups. Conclusions: Insulin resistance may be involved in the progression of nonculprit coronary atherosclerosis after PCI in hemodialysis patients.

Clinical Features of Aluminum-Associated Bone Disease in Long-Term Hemodialysis Patients

We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.

Clinical potential of oral nicorandil to improve myocardial fatty acid metabolism after percutaneous coronary intervention in hemodialysis patients.

Background/Aims: The assessment of myocardial fatty acid metabolism impairment by single-photon emission computed tomography (SPECT) using 123I-β-methyliodophenyl-pentadecanoic acid (BMIPP) might predict the risk of cardiac death in hemodialysis patients. We investigated the potential of oral nicorandil to improve myocardial fatty acid metabolism after percutaneous coronary intervention (PCI) in this population. Methods: We evaluated 128 hemodialysis patients who had obtained coronary revascularization by PCI (90 men and 38 women, 66 ± 9 years). Participants for the analysis were randomly assigned to either the nicorandil (n = 63) or control group (n = 65). BMIPP SPECT was performed every year after coronary revascularization by PCI. Uptake on SPECT was graded in 17 segments on a 5-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores (SS). Results: The incidence of cardiac death was lower (p = 0.004) in the nicorandil group (7/63, 11.1%) than in the control group (21/65, 32.3%) during a mean follow-up of 2.7 ± 1.4 years. BMIPP SS reduction rates improved in the nicorandil group compared with the control group from 3 years of administration. In Kaplan-Meier analyses, free survival rate of cardiac death was higher in patients with a ≥20% BMIPP SS reduction rate as compared with those with a <20% BMIPP SS reduction rate (p = 0.0001). In multiple logistic analysis, oral administration of nicorandil was associated with ≥20% reduction rates of BMIPP SS (odds ratio 2.823, p = 0.011). Conclusion: Long-term oral administration of nicorandil may improve impaired myocardial fatty acid metabolism after coronary revascularization by PCI in hemodialysis patients.

Oral nicorandil for prevention of cardiac death in hemodialysis patients without obstructive coronary artery disease: a propensity-matched patient analysis.

Background/Aims: We examined the potential of oral administration of nicorandil for protecting against cardiac death in hemodialysis patients without obstructive coronary artery disease. Methods: This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive coronary lesions, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years), including 50 who received oral administration of nicorandil (15 mg/day, nicorandil group) and 50 who did not (control). The efficacy of nicorandil in preventing cardiac death was investigated. Results: Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients, including 6 due to acute myocardial infarction, 11 due to heart failure, and 8 due to sudden cardiac death. The incidence of cardiac death was lower (p < 0.001) in the nicorandil group (4/50, 8%) than in the control (21/50, 42%). On multivariate Cox hazard analysis, cardiac death was inversely associated with oral nicorandil (hazard ratio, 0.123; p = 0.0002). On Kaplan-Meier analysis, cardiac death-free survival rates at 5 years were higher in the nicorandil group than in the control group (91.4 vs. 66.4%). Conclusion: Oral nicorandil may inhibit cardiac death of hemodialysis patients without obstructive coronary artery disease.

Possible Inhibitory Effect of Erythropoiesis-Stimulating Agents at the Predialysis Stage on Early-Phase Coronary Events after Hemodialysis Initiation

Background: We examined whether the use of erythropoiesis-stimulating agents (ESAs) to correct anemia at the predialysis stage could inhibit early-phase coronary events after hemodialysis initiation. Methods: We enrolled 242 patients with chronic kidney disease who had received continued medical treatments and initiated maintenance hemodialysis from 1 September 2000 to 31 December 2014 at Toujinkai Hospital. Patients with a previous history of blood transfusion or any cardiovascular events or interventions were excluded. The coronary events were followed for 1 year after initiation of hemodialysis. Results: Coronary events occurred in 51 of 242 patients: 10 patients had acute coronary syndrome [9 with percutaneous coronary intervention (PCI), 1 without intervention], and 41 had elective coronary revascularization (38 PCI and 3 coronary artery bypass graft). ESA was administered in 118 of 242 patients (48.8%). In stepwise logistic analysis, coronary events were positively associated with nonuse of ESA at the predialysis stage (odds ratio 2.66, p = 0.005) and diabetes mellitus (odds ratio 5.33, p < 0.001). When dividing the patients into 4 subgroups by blood hemoglobin (Hb) level (8.5 g/dl) and the use/nonuse of ESA, coronary event-free survival rates were higher (p = 0.005) in those with Hb ≥8.5 g/dl, ESA+ (86.6%, n = 82) and tended to be higher (p = 0.055) in those with Hb <8.5 g/dl, ESA+ (86.1%, n = 36) than in patients with Hb <8.5 g/dl, ESA- (68.6%, n = 86) in a Kaplan-Meier analysis. Conclusions: The use of ESA to correct anemia at the predialysis stage may inhibit early-phase coronary events after hemodialysis initiation.