Yuji Kasamaki

Influence of Continuous Infusion of Low-Dose Human Atrial Natriuretic Peptide on Renal Function During Cardiac Surgery A Randomized Controlled Study

OBJECTIVES The purpose of this study was to determine the effect of human atrial natriuretic peptide (hANP) in patients who underwent coronary artery bypass grafting (CABG) on renal function. BACKGROUND Acute renal failure after cardiac surgery is associated with high morbidity and mortality. METHODS A total of 504 patients who underwent CABG were divided into 2 groups: 1 group received hANP at 0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1 group did not receive hANP (placebo group). Various parameters were measured before and after surgery. RESULTS There was no difference in mortality between the 2 groups, but post-operative complications were less frequent in the hANP group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly lower and urinary Cr and Cr clearance were significantly higher from post-operative day 1 to week 1. The maximum post-operative Cr level and percent increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo group, showing a significant difference (p = 0.0374). Four patients in the placebo group and none in the hANP group required hemodialysis, but the difference was not statistically significant. CONCLUSIONS Continuous infusion of low-dose hANP from the start of cardiopulmonary bypass effectively maintained post-operative renal function. Infusion of hANP prevents early post-operative acute renal failure and helps to achieve safer cardiac surgery. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000001440).

Impact of Biomarkers of Inflammation and Extracellular Matrix Turnover on the Outcome of Atrial Fibrillation Ablation: Importance of Matrix Metalloproteinase‐2 as a Predictor of Atrial Fibrillation Recurrence

MMP‐2 Predicts the Outcome of AF Ablation. Introduction: Although catheter ablation can effectively eliminate atrial fibrillation (AF), the progression of atrial remodeling increases the risk of recurrence. AF is associated with inflammation and subsequent myocardial fibrosis. We therefore examined the possibility of determining the postablation prognosis of patients with AF using biomarkers of inflammation and collagen turnover.

Continuous Low-Dose Infusion of Human Atrial Natriuretic Peptide in Patients With Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting: The NU-HIT (Nihon University working group study of low-dose Human ANP Infusion Therapy during cardiac surgery) for Left Ventricular Dysfunction

OBJECTIVES Continuous low-dose infusion of human atrial natriuretic peptide (hANP) in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) inhibits the renin-angiotensin-aldosterone system and compensates for the adverse effects of CPB. BACKGROUND We examined the influence of hANP infusion on cardiac and renal function in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). METHODS The subjects were 133 patients who underwent CABG and had a pre-operative ejection fraction < or =35%. They were randomized to receive 0.02 microg/kg/min of hANP from the initiation of CPB (hANP group) or placebo (saline) infusion. RESULTS Early post-operative mortality did not show a significant difference between the 2 groups, but perioperative complications were significantly less frequent in the hANP group (p = 0.015). Long-term all-cause mortality showed no difference, but the cardiac death-free rate at 5 or 8 years post-operatively was 98.5% in the hANP group and 85.5% in the placebo group (p = 0.0285). Post-operative ejection fraction was significantly larger and the post-operative brain natriuretic peptide level was significantly lower in the hANP group. Serum creatinine was significantly lower in the hANP group than the placebo group at 1 month, 6 months, and 1 year post-operatively, whereas the estimated glomerular filtration rate was significantly higher in the hANP group at these times. CONCLUSIONS In patients with left ventricular dysfunction undergoing CABG, hANP showed renal- and cardio-protective effects and reduced post-operative complications. It also improved the long-term prognosis. We suggest that hANP should be considered as part of perioperative management of patients with cardiac dysfunction undergoing cardiac surgery. (NU-HIT trial for LVD; UMIN000001652).

Study of the factors related to atrial fibrillation after coronary artery bypass grafting: a search for a marker to predict the occurrence of atrial fibrillation before surgical intervention.

OBJECTIVE Atrial fibrillation after cardiac surgery is a frequent complication. In this study we studied various factors in addition to trying to identify a marker that would predict the potential for atrial fibrillation before surgical intervention to prevent its occurrence. METHODS We targeted 234 cases in which isolated coronary artery bypass grafting had been performed. The items for study included age, EuroSCORE, and maximum values of creatine phosphokinase-MB, troponin I, and angiotensin II after surgical intervention and preoperative values of atrial natriuretic peptide, brain natriuretic peptide, and C-reactive protein. As fibrotic markers, we measured levels of the sialylated carbohydrate antigen KL-6 in the blood, hyaluronic acid, and pyridinoline cross-linked carboxyterminal telepeptide of type I collagen C. At the time of surgical intervention, a section of the right atrium was extracted, and atrial natriuretic peptide, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen levels were measured. RESULTS Atrial fibrillation was observed in 73 (31.2%) cases, and preoperative factors that showed statistically significant differences in the occurrence of atrial fibrillation included age, EuroSCORE, and preoperative values of atrial natriuretic peptide, angiotensin II, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen in the blood. As for intraoperative and postoperative factors, statistically significant differences were observed in the postoperative maximum of angiotensin II, atrial natriuretic peptide of the right atrium, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen levels. CONCLUSION The fibrosis of tissue associated with age is believed to be closely related to the occurrence of atrial fibrillation after coronary artery bypass grafting. This study suggests that the preoperative values of atrial natriuretic peptide, angiotensin II, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen in the blood are useful as a new index for the occurrence of atrial fibrillation after coronary artery bypass grafting.

A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men

Objective CYP4A11, a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite involved in blood pressure regulation in humans. Disruption of the murine cyp4a14 and cyp4a10 genes, homologues of human CYP4A11, was reported recently to cause hypertension. The gene-disrupted male mice had higher blood pressure than the gene-disrupted female mice. The present study aimed to assess the association between the human CYP4A11 gene and essential hypertension, using a haplotype-based case–control study including separate analysis of the gender groups. Methods The 304 essential hypertension patients and 207 age-matched control individuals were genotyped for three single-nucleotide polymorphisms of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). Data were assessed for three separate groups: total participants, men and women. Results For total participants, the genotypic distribution of rs1126742 differed significantly between the two groups (P = 0.005). For total participants, men and women, the recessive model (CC versus TC + TT) of rs1126742 differed significantly between the two groups (P = 0.007, P = 0.043, and P = 0.045, respectively). Logistic regression analysis showed the TC + TT genotype was significantly higher in essential hypertension patients than in control individuals for total participants and men (P = 0.022 and P = 0.043, respectively). The A-T-G haplotype frequency (established by rs2269231, rs1126742, rs9333025) was significantly higher in essential hypertension men than in control men (P = 0.043). Conclusions Essential hypertension is associated with the TC + TT genotype of rs1126742 in the human CYP4A11 gene. The A-T-G haplotype appears a useful genetic marker of essential hypertension in Japanese men.

A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

BACKGROUND CYP4F2, a member of the cytochrome P450 family, acts mainly as an enzyme and is involved not only in the metabolism of leukotriene B4, but also in that of arachidonic acid. It converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the regulation of the vascular tone in the brain. The aim of this study was to assess the association between the human CYP4F2 gene and cerebral infarction (CI), using a haplotype-based case-control study with separate analyses of data from the gender groups. METHODS A total of 175 CI patients and 246 control subjects were genotyped for five single-nucleotide polymorphisms (SNPs) of the human CYP4F2 gene (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For data analysis, three separate groups were assessed: all subjects, men, and women. RESULTS In the male subjects, the G allele frequency for rs2108622 was significantly higher in CI patients as compared to control subjects (P = 0.025). The overall distribution of the haplotypes in the men was significantly different between the CI patients and the control subjects (P = 0.027). Additionally, the frequency of the T-C-G haplotype for men was significantly higher in the CI patients than in the control subjects (P = 0.008). Multiple logistic regression analysis also revealed the significance of the T-C-G haplotype in men, even after adjustment for confounding factors. CONCLUSIONS The results of this study indicate that, in Japanese men, CI is associated with the G allele of rs2108622 and, in addition, that the T-C-G haplotype appears to be a useful genetic marker for CI.

Prediction of the efficacy of pulmonary vein isolation for the treatment of atrial fibrillation by the signal-averaged P-wave duration

Background: The noninvasive methods for predicting a successful pulmonary vein isolation (PVI) have not been well described. The aim of this study was to assess the usefulness of the P‐wave signal‐averaged electrocardiogram (P‐SAECG) in predicting the chance of a successful PVI in patients with atrial fibrillation (AF).

Intravenous Administration of Class I Antiarrhythmic Drug Induced T Wave Alternans in an Asymptomatic Brugada Syndrome Patient

A 53‐year‐old man with an abnormal ECG was referred to the Nihon University School of Medicine. The 12‐lead ECG showed right bundle branch block and saddleback‐type ST elevation in leads V1–V3 (Brugada‐type ECG). Signal‐averaged ECG showed positive late potentials. Double ventricular extrastimuli (S1: 500 ms, S2: 250 ms, S3: 210 ms) induced VF. Amiodarone (200 mg/day) was administered for 6 months and programmed ventricular stimulation was repeated. VF was induced again by double ventricular stimuli (S1: 600 ms, S2: 240 ms, S3: 170 ms). Intravenous administration of class Ic antiarrhythmic drug, pilsicainide (1 mg/kg), augmented ST‐T elevation in leads V1–V3, and visible ST‐T alternans that was enhanced by atrial pacing was observed in leads V2 and V3. Visible ST‐T wave alternans disappeared in 15 minutes. However, microvolt T wave alternans was present during atrial pacing at a rate of 70/min without visible ST‐T alternans. (PACE 2003; 26:1900–1903)

Risk stratification of cardiovascular events in patients at all stages of chronic kidney disease using myocardial perfusion SPECT

BACKGROUND Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Therefore, stratification of the prognostic risk of cardiovascular events is useful for their clinical management. We evaluated the ability of electrocardiogram (ECG)-gated myocardial perfusion single photon emission computed tomography (SPECT) to predict cardiac events among Japanese patients at all stages of CKD including those on hemodialysis. METHODS Patients with CKD undergoing ECG-gated myocardial perfusion SPECT to investigate suspected ischemic heart disease were followed up to monitor retrospectively major cardiac events including cardiac death, non-fatal myocardial infarction, and unstable angina pectoris. Summed stress score, summed rest score, and summed difference score were estimated with a 20 segment 5-point scoring model. The severity of CKD was divided into five levels based on estimated glomerular filtration rate (eGFR) revised for the Japanese population. RESULTS The follow-up period was 25.8 ± 11.0 months. Sixty-two major cardiac events (cardiac death, n=30; non-fatal myocardial infarction, n=13; unstable angina pectoris, n=19) developed in 2243 patients during the first year of follow-up. The findings of multivariate Cox proportional hazards regression analysis indicated that diabetes, eGFR, the summed difference score, and summed stress score were significant independent predictors of cardiac events. The major cardiac event rate at one year increased in proportion to the progression of CKD stage. The major cardiac event-free survival rate decreased steeply over time in patients with CKD stage 5 compared with those who had CKD stages 4 or less. CONCLUSION Myocardial perfusion SPECT can contribute to the prediction of cardiac events and survival in patients at all stages of CKD including those on hemodialysis.

Fifteen years of experience with ATS mechanical heart valve prostheses

BACKGROUND ATS Medical, Inc, developed a mechanical heart valve that has been in use since 1992. In this article, we present the results of 15 years of follow-up of patients who have undergone ATS heart valve replacement at our hospital. METHODS AND RESULTS We performed ATS heart valve replacements on 231 patients between September 1993 and March 2008. Our operative mortality rate for the study period was 2.2%. The survival for postoperative thromboembolic events was 0.29%/pt-y for aortic valve replacement, 0.48%/pt-y for mitral, 0.80%/pt-y for double valve replacement, and overall 0.44%/pt-y. The survival after bleeding events was 0.29%/pt-y for aortic valve replacement, 0.16%/pt-y for mitral, 0%/pt-y for double valve replacement, and overall 0.19%/pt-y. Patient-prosthesis mismatch, as determined by echocardiography, was found in 83.3% of patients at 19 mm, but other sizes showed good valve function. Prosthetic valve noise was undetectable in 92.8% of patients, and quality of life was excellent. CONCLUSIONS Few prosthetic valve-related complications were seen with ATS heart valve replacements in this study, and the follow-up results were favorable. The international normalized ratio was maintained in the range 1.6 to 2.0 in patients with aortic valve replacement in sinus rhythm. Not only bleeding events, seen at a rate of 0.19%/pt-y, but also thromboembolic events, at 0.44%/pt-y, were low when compared with conventional mechanical valves. Prosthetic valve noise is low, and this appears to be an excellent mechanical valve from the quality of life standpoint. The ATS valve has an excellent safety profile when compared with other mechanical valves.