Circulating Aminoterminal Propeptide of Type III Procollagen as a Biomarker of Cardiovascular Events in Patients Undergoing Hemodialysis.

AIM: Type Ⅲ collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type Ⅲ procollagen (PⅢNP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis. METHODS: Serum PⅢNP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64±11 years; dialysis duration, 11.5±7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011. RESULTS: During the follow-up for 4.7±1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PⅢNP concentration (1 U/mL; hazard ratio, 1.616; P=0.0001). The median serum PⅢNP concentrations were higher in patients with cardiovascular events than in those without (2.30±0.19 U/mL vs 1.30±0.03 U/mL; P＜0.0001). When the patients were assigned to subgroups based on serum PⅢNP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P=0.0001) in the subgroup of serum PⅢNP ≥1.75 U/mL than in that of serum PⅢNP ＜1.75 U/mL (31.9% vs 88.2%). CONCLUSIONS: Serum PⅢNP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

Idiopathic pre-capillary pulmonary hypertension in patients with end-stage kidney disease: effect of endothelin receptor antagonists.

BACKGROUND: We examined the prevalence, prognosis, and effect of endothelin receptor antagonists on survival in end-stage kidney disease patients with idiopathic pre-capillary pulmonary hypertension. METHODS: We investigated 1988 end-stage kidney disease patients in Toujinkai Hospital from January 1, 2001 to December 31, 2014. Pulmonary hypertension was screened by symptoms (dyspnea, hypotension, or near syncope) and echocardiography, and diagnosed by computed tomography with enhancement, pulmonary flow scintigraphy, and right heart catheterization. RESULTS: Fifteen patients (67 ± 11 years; 12 women and 3 men) were diagnosed as idiopathic pre-capillary pulmonary hypertension; mean pulmonary arterial pressure, pulmonary vascular resistance, or pulmonary artery wedge pressure were 55 ± 11 mmHg, 7.5 ± 2.9 Woods units, or 12 ± 2 mmHg, respectively. Of the 15 patients, 14 received hemodialysis, and 1 was in a pre-dialysis stage. Patients were followed through December 31, 2015, and 11 died of heart failure; their mean survival time was 26.4 ± 21.0 months. Endothelin receptor antagonists were used for 11 patients, and mean survival times were 57.3 ± 12.1 months in patients with endothelin receptor antagonists and 7.5 ± 2.1 months in those without. In the Kaplan-Meier analysis, heart failure death-free survival rates were higher in patients with endothelin receptor antagonists than in those without (P < 0.001); 100 versus 25 % at one year and 71 versus 0 % at 3 years. CONCLUSION: The prognosis of idiopathic pre-capillary pulmonary hypertension seems to be poor in end-stage kidney disease patients. Administration of endothelin receptor antagonists might improve the survival by inhibiting heart failure death. Registration of clinical trials This study was registered to the ClinicalTrials.gov ( https://clinicaltrials.gov/ ): protocol identifier, NCT02743091.

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.

Effects of intravenous l-carnitine on myocardial fatty acid imaging in hemodialysis patients: responders or non-responders to l-carnitine.

We investigated whether chronic intravenous administration of l-carnitine could improve myocardial fatty acid imaging in patients on maintenance hemodialysis. We enrolled 72 hemodialysis patients who had impaired myocardial fatty acid imaging and left ventricular dysfunction not based on coronary lesion. l-Carnitine (1,000 mg) was intravenously administered after dialysis for 1 year to 36 participants (Carnitine group), while not in the other 36 participants (Control group). Single-photon emission computed tomography (SPECT) using an iodinated fatty acid analogue, BMIPP, was performed. Uptake on SPECT images was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. During follow-up, 19 participants were discontinued from the study, and 53 participants (65 ± 12 years: 27 carnitine, 26 control) were analyzed. The mean BMIPP summed scores 1 year after carnitine administration did not differ from that before in the carnitine group, nor from that in the control group. However, improved SPECT (Changes in BMIPP summed scores <-20%) was found in 7 (25.9%) participants in the carnitine, whereas in 2 (7.7%) in the control group. Multivariate logistic analysis showed the improved SPECT was inversely associated with baseline serum albumin levels (1 g/L: odds ratio, 0.669); the cut-off was 35 g/L. Chronic intravenous l-carnitine might improve myocardial fatty acid imaging in a selected group of hemodialysis patients with hypoalbuminemia.

Focal impairment in myocardial fatty acid imaging in the left anterior descending artery area, a strong predictor for cardiac death in hemodialysis patients without obstructive coronary artery disease.

PURPOSE: We investigated whether impaired patterns of myocardial fatty acid imaging were associated with cardiac death in dialysis patients without coronary lesions. METHODS: We prospectively enrolled 155 hemodialysis patients without obstructive coronary artery disease, who had been examined by single-photon emission computed tomography (SPECT) using the iodinated fatty acid analogue BMIPP. Uptake of BMIPP on SPECT was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. Of the enrolled 155 participants, we analyzed 95 who had BMIPP summed scores ≥ 6 (52 men and 43 women, 65 ± 11 years). BMIPP scores ≥ 2 in ≥ 2 consecutive segments in SPECT were defined as focal, and the others as non-focal pattern. RESULTS: Of 95 participants analyzed, 42 (44.2 %) showed focal and 53 (55.8 %) non-focal type. During follow-up for 5.1 ± 2.0 years, 42 died of cardiac events. The occurrence of cardiac death was higher in the focal than in the non-focal group (30/42 [71.4 %] versus 12/53 [22.6 %], p = 0.001). In stepwise Cox hazard analysis, focal pattern was associated with cardiac death (hazard ratio 2.266), independent of impairment of BMIPP SPECT (BMIPP summed scores ≥ 12). The predictive potential of BMIPP SPECT for cardiac death was higher (p < 0.001) in the left anterior descending artery area compared with other coronary territories. CONCLUSIONS: Focal impairment in myocardial fatty acid imaging in the left anterior descending area may strongly predict cardiac death in this population.

Improvement of myocardial fatty acid metabolism by oral nicorandil in hemodialysis patients without coronary artery disease.

BACKGROUND: We investigated the potential of oral nicorandil to improve myocardial fatty acid metabolism assessed by single-photon emission computed tomography (SPECT) using (123)I-ß-methyliodophenyl pentadecanoic acid (BMIPP) in hemodialysis patients without obstructive coronary artery disease (CAD). METHODS: This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive CAD, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years); 50 with oral administration of nicorandil (15 mg/d, nicorandil group) and 50 without (control). BMIPP SPECT was performed every year after angiography. Uptake on SPECT was graded in 17 segments on a five-point scale (0 normal, 4 absent) and assessed as BMIPP summed scores (SS). RESULTS: Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients. Myocardial uptake of BMIPP in SPECT improved in the nicorandil group compared with the control group from 2 years of administration. In Kaplan-Meier survival analyses, free survival rate from cardiac death was higher in patients with a BMIPP SS improvement rate of ≥20% compared to those with ≥0% <20% or with <0% BMIPP SS improvement rate. At multiple logistic analysis, a ≥20% BMIPP SS improvement rate was positively associated with serum albumin concentration and oral nicorandil. CONCLUSIONS: Long-term oral nicorandil may inhibit cardiac death by improving myocardial fatty acid metabolism in hemodialysis patients without obstructive CAD.

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 (123)I-ß-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.

Tarsal tunnel syndrome in hemodialysis patients: a case series.

BACKGROUND: The purpose of our study was to investigate tarsal tunnel syndrome (TTS) arising in patients who have undergone maintenance dialysis at our facility and to evaluate the frequency, pathological characteristics, and diagnosis of TTS. METHODS: We evaluated 1011 patients (mean age 65.1 years) undergoing maintenance dialysis from 2000 to 2006 at our hospital. In patients diagnosed with TTS, we examined clinical symptoms and imaging findings. In addition, we evaluated intraoperative findings in patients who had undergone surgery. A follow-up study was conducted for at least 1 year. RESULTS: Five patients (7 ankles) (mean age 57.8 years) were diagnosed as have TTS, with a mean dialysis duration of 23.4 years (range, 7-30 years). With conservative treatment consisting of rest and a steroid injection, 4 ankles showed improvement. Surgery was performed on 3 ankles. Amyloidoma, nodular tumor fragile deposits in the soft tissue or thecal surface, proliferation of the synovial tendon sheath, and thickened joint capsule were recognized in 3 ankles, and a concomitant ganglion was recognized in 1 ankle. Histologically, the deposition of hyaline material was recognized in all tissues, including the walls of the ganglion or joint capsule, by staining to a pale red color using Congo red stain. An immunohistochemical study indicated positive staining by ß-2 microglobulin staining. The flexor retinaculum was thin in all cases, with retinaculum-like thickness not found in carpal tunnel syndrome. CONCLUSIONS: We believe that the occurrence of TTS in dialysis patients was 0.5%, with a tendency to be more prevalent among patients undergoing maintenance dialysis for 5 or more years. The pathological process of TTS may be different from that of carpal tunnel syndrome. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Survey of the effects of a column for adsorption of ß2-microglobulin in patients with dialysis-related amyloidosis in Japan.

Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of ß2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of ß2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis-related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self-evaluation by patients, worsening of symptoms was inhibited in 84.9-96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis-related amyloidosis in most patients.

Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND AND AIMS: To compare the prognosis of chronic hemodialysis patients with or without parathyroidectomy. METHODS: Among 158 chronic hemodialysis patients who underwent total parathyroidectomy between July 1998 and April 2009, 88 patients were matched with 88 controls for sex, age, underlying disease and prior dialysis history. Then a retrospective evaluation of their prognosis was performed over a median observation period of 4.41 years. RESULTS: The overall survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control group. The cardiovascular death-free survival rate was 94.6% in the parathyroidectomy group and 76.3% in the control group. During observation, intact parathyroid hormone was measured every 6 months, and its average serum level was 37 ± 92 ng/L in the total parathyroidectomy group versus 274 ± 233 ng/L in the control group (p=0.0001). The total parathyroidectomy group had a significantly lower corrected calcium level and higher serum albumin level. Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and serum albumin were significant factors for both total and cardiovascular mortality. CONCLUSION: Total parathyroidectomy was associated with better survival, probably due to decreased cardiovascular mortality.

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.

Plasma S100A12 level is associated with cardiovascular disease in hemodialysis patients.

BACKGROUND AND OBJECTIVES: S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants. RESULTS: Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n=197; 33.8 ± 28.1 ng/ml) than in those without it (n=353; 20.2 ± 16.1 ng/ml; P<0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P<0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P=0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P=0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n=348). CONCLUSIONS: These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients.

Plasma S100A12 levels and peripheral arterial disease in end-stage renal disease.

BACKGROUND: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. METHODS: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. RESULTS: HD patients with PAD (n = 26; 21.9 [13.6-33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5-17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29-25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40-0.74; p < 0.001). CONCLUSION: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.

Risk stratification for cardiac death in hemodialysis patients without obstructive coronary artery disease.

The incidence of cardiac death is higher among patients receiving dialysis compared with the general population. Although obstructive coronary artery disease is involved in cardiac deaths in the general population, deaths in hemodialysis patients occur in the apparent absence of obstructive coronary artery disease. To study this further, we prospectively enrolled 155 patients receiving hemodialysis after angiography had confirmed the absence of obstructive coronary lesions. All patients were examined by single-photon emission computed tomography using the iodinated fatty acid analog, BMIPP, the uptake of which was graded in 17 standard myocardial segments and assessed as summed scores. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). During a mean follow-up of 5.1 years, 42 patients died of cardiac events. Stepwise Cox hazard analysis associated cardiac death with reduced BMIPP uptake and increased insulin resistance. Patients were assigned to subgroups based on BMIPP summed scores and HOMA-IR cutoff values for cardiac death of 12 and 5.1, respectively, determined by receiver operating characteristic analysis. Cardiac death-free survival rates at 5 years were the lowest (32.2%) in the subgroup with both a summed score and assessment equal to or above the cutoff values compared with any other combination (52.9-98.7%) above, equal to, or below the thresholds. Thus, impaired myocardial fatty acid metabolism and insulin resistance may be associated with cardiac death among hemodialysis patients without obstructive coronary artery disease.

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.

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.

Clinical utility of myocardial fatty acid imaging in patients with end-stage renal disease.

The prevalence of coronary artery disease (CAD) appears to be much higher in patients with end-stage renal disease (ESRD) undergoing dialysis than in a non-ESRD population. Cardiac death due to myocardial ischemia significantly contributes to the high mortality rate of ESRD patients. However, the method for screening for CAD in ESRD patients has not been established, because the frequency of silent myocardial ischemia is high and examinations requiring stress are often difficult to perform among this population. Myocardial fatty acid imaging may be a new modality to detect myocardial ischemia and identify the group at high risk for cardiac death among ESRD patients without adding any stress.

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.

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 x [microU/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.