Ken Watanabe

Abnormalities of Neurohormonal and Cardiac Autonomic Nervous Activities Relate Poorly to Functional Status in Fontan Patients

Background—Impaired cardiac autonomic nervous activities and increased neurohumoral activities (CANA, NHA) characterize Fontan patients. However, the clinical significance of these changes is not clearly understood. Our purpose was to clarify the clinical significance of the CANA and NHA in stable Fontan patients. Methods and Results—We divided 22 atriopulmonary connection (APC) and 75 total cavopulmonary connection (TCPC) patients into 4 subgroups according to New York Heart Association (NYHA) class (1.8±0.6) and measured various CANA and NHA indices. All NHA indices were elevated in the symptomatic patients (P<0.001). Natriuretic peptides were higher in the APC than in the TCPC patients, and the hemodynamics showed no correlation with brain natriuretic peptide in the APC patients. Low arterial oxygen saturation and impaired hemodynamics greatly influenced all elevated NHA indices (P<0.01), except for plasma renin activity, in the TCPC patients. Impaired CANA indices did not relate to NYHA class, although surgeries were associated with lower heart rate variability. In addition to poor correlation between NHA and CANA, age and ventricular morphology had no impact on all CANA and NHA indices, except for high norepinephrine in right ventricular Fontan patients. Conclusions—Although symptomatic Fontan patients exhibit higher NHA, CANA is not related to either NYHA class or NHA. APC itself is responsible for higher natriuretic peptides, and arterial oxygen desaturation has a great impact on elevated NHA in the TCPC patients. These characteristics of the NHA and CANA differ from those of heart failure patients with biventricular physiology.

Redirection of Hepatic Venous Drainage After Total Cavopulmonary Shunt in Left Isomerism

BACKGROUNDnConversion from total cavopulmonary shunt (TCPS) to the Fontan circulation can improve cyanosis in patients with potential risks of development of pulmonary arteriovenous fistula (PAVF).nnnMETHODSnInclusion of the hepatic veins in the pulmonary circulation was employed using an intra-atrial tube graft in 5 patients with left isomerism previously undergoing TCPS. Prior to the conversion, abnormal communication was identified between the azygos vein and either the hepatic or the portal vein in all. PAVF was seen in 3.nnnRESULTSnAll patients survived the procedure. Postoperative catheterization showed 13 +/- 2 mm Hg of superior caval venous pressure, and 2.3 +/- 0.4 L/min/m2 of cardiac index. Pulmonary arteriovenous fistula progressed markedly in the right lung even after the conversion in 2 patients, in whom the hepatic veins had been exclusively diverted to the left lung. Arterial oxygen saturation became below 65%, with exercise capacity reduced, in these 2 patients. The other patients remain asymptomatic.nnnCONCLUSIONSnTotal cavopulmonary shunt can be efficiently converted to the Fontan circulation by appropriately redirecting hepatic venous drainage to perfuse both lungs in a balanced fashion.

The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464xa0days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan–Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

Impact of Objective Malnutrition Status on the Clinical Outcomes in Patients With Peripheral Artery Disease Following Endovascular Therapy

BACKGROUNDnPeripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.Methodsu2004andu2004Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the CONUT score- and GNRI-based malnutrition status was an independent predictor of MACLEs. The Kaplan-Meier analysis demonstrated that the MACLE ratio increased with deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to the known risk factors significantly improved the net reclassification index and integrated discrimination index.nnnCONCLUSIONSnMalnutrition was common and closely associated with the clinical outcomes in patients with PAD, indicating that it is a novel therapeutic target in the management of these patients.

Ventricular wall stress and silent myocardial damage are associated with pulse pressure in the general population

Pulse pressure (PP) is a risk factor for cardiovascular diseases and is associated with increased afterload and myocardial oxygen demand. Brain natriuretic peptide (BNP) and heart‐type fatty acid–binding protein (H‐FABP) are known as biomarkers indicating ventricular wall stress and silent myocardial damage. However, the association between PP and ventricular wall stress and silent myocardial damage in the general population is unclear. The authors enrolled 3504 patients who participated in a community‐based annual health check. Serum levels of BNP and H‐FABP were measured as markers of ventricular wall stress and silent myocardial damage. Patients were divided into four groups according to the quartiles of PP. Patients in the highest PP group showed higher serum BNP and H‐FABP levels than that of the other groups. Multivariate logistic analysis showed that high PP was independently associated with ventricular wall stress and silent myocardial damage on the basis of BNP and H‐FABP levels. Compared with systolic blood pressure, diastolic blood pressure, and mean blood pressure, PP was superior in predicting ventricular wall stress and silent myocardial damage evaluated according to BNP and H‐FABP levels, which was reflected by the receiver operating characteristic analysis. Screening of healthy patients revealed that high PP was related to high BNP and H‐FABP levels, suggesting that an asymptomatic general population with high PP may be exposed to ventricular wall stress and myocardial damage and might be susceptible to silent heart failure.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, Pu2009=u20090.001) and the 2nd tertile group (OR 3.2, Pu2009=u20090.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.