Tomohiko Toyoda

Prevalence of adult patients with congenital heart disease in Japan

BACKGROUND Today most patients with congenital heart disease (CHD) can be expected to survive into adulthood. Reports regarding the number of adults with CHD in Japan are scarce. Our study aims to define the number of these adults. MATERIAL AND METHODS The estimated number of infants born in Japan with major CHDs since 1947 was calculated together with mortality rates. We estimated the number of CHD survivors from data on survival rates of unoperated and postoperative patients. The number of deaths from 1968 to 1997 was analyzed using individual death certificates held by the Japanese Government. RESULTS In 1967, 163,058 patients with CHD including 53,846 adults were assumed to be alive. From 1968 to 1997, 548,360 patients with CHD were born and 82,919 died. A total of 622,800 patients, including 304,474 children (49%) and 318,326 adults (51%) were estimated to be alive in 1997. From 1997 to 2007, there has been an estimated increase of 9000 adults every year, and in 2007, 409,101 adults are estimated to be alive. CONCLUSIONS The prevalence in adults with CHD in Japan has explosively increased from 1967 to 2007. There were 409,101 adults with CHD in 2007 with an annual increase of 9000. These data are crucial for planning the establishment in Japan of special facilities and resources necessary for the care of these patients.

Measurement of acetylcholine-induced endothelium-derived nitric oxide in aorta using a newly developed catheter-type nitric oxide sensor.

Intra-aortic measurement of nitric oxide (NO) would provide valuable insights into NO bioavailability in systemic circulation and vascular endothelial function. In the present study, we thus developed a catheter-type NO sensor to measure intra-aortic NO concentration in vivo. An NO sensor was encased and fixed in a 4-Fr catheter. The sensor was then located in the thoracic aorta via the femoral artery through a 7-Fr catheter to measure intra-aortic plasma NO concentration in vivo in anesthetized dogs. Infusion of acetylcholine (10 microg/kg) increased base-to-peak plasma NO level in the aorta by 2.4+/-0.4 nM (n=7). After 20-min infusion of N(G)-methyl-L-arginine (NO synthase inhibitor), changes in plasma NO concentration in response to acetylcholine were attenuated significantly (1.8+/-0.4 nM, P<0.003, n=7). In conclusion, the newly developed catheter-type NO sensor successfully measured acetylcholine-induced changes in intra-aortic plasma concentration of endothelium-derived NO in vivo and demonstrated applicability to direct evaluation of intravascular NO bioavailability.

The prevalence and risk factors for cholelithiasis and asymptomatic gallstones in adults with congenital heart disease

PURPOSE Cyanosis is considered to be a risk factor for cholelithiasis which is an important complication of cyanotic congenital heart disease (CCHD) in adults. In this study, the prevalence of cholelithiasis and asymptomatic calcium bilirubinate gallstones was evaluated in adults with congenital heart disease (CHD). Furthermore, risk factors for this potentially high risk complication were assessed. MATERIALS AND METHODS Subjects were derived from 114 consecutive congenital patients who visited our center from May 2008 to January 2009. For analyses of risk factors, we divided them into 4 groups: group A, 15 CCHD patients without reparative surgery (7 men, 31.8 ± 7.0 years old); group B, 41 CCHD patients rendered acyanotic by reparative surgery (21 men, 32.5 ± 11.8 years old); group C, 23 unoperated acyanotic CHD patients (11 men, 42.4 ± 16.4 years old); and group D, 35 patients who were acyanotic before and after operation (18 men, 36.3 ± 14.8 years old). Gallstones were identified by abdominal ultrasound and risk factors were analyzed by a multivariate logistic regression model. RESULTS Cholecystectomy was performed in 5/114 (4.3%), asymptomatic gallstones were seen in 16/114 (14%), and symptomatic gallstones except for patients after cholecystectomy were seen in 7/114 (6.1%). In group A, 4 (27%) with gallstones underwent cholecystectomy (p<0.01). Non-cholesterol gallstones were observed in 5 patients (33%) in group A, 12 patients (29%) in group B, nobody in group C, and 3 patients (8.6%) in group D. By a multivariate logistic regression model, CCHD by nature regardless of repair, prolonged cyanosis periods, higher frequency of cardiopulmonary bypass (CPB), and lower platelet counts were significant factors predicting gallstones (odds ratio 4.48, 1.08, 3.96, and 0.87, 95% CI, 1.14-17.5, 1.00-1.18, 1.65-9.54, and 0.75-0.99, respectively). CONCLUSIONS The prevalence of cholelithiasis and asymptomatic gallstones is significantly high in CCHD patients regardless of cardiac repairs. CCHD by nature, prolonged cyanosis durations, high frequency of CPB and low platelet counts have influences on gallstone formation in adults with CHD.

The impact of sleep deprivation on the coronary circulation

Epidemiologic studies have reported that sleep deprivation is associated with cardiovascular events. However, it remains unknown how sleep deprivation affects the coronary circulation. We assessed the impact of sleep deprivation on the coronary circulation using coronary flow velocity reserve (CFVR) measurements with transthoracic Doppler echocardiography. We studied 26 healthy male volunteers. Each subjects CFVR was measured in the morning after sleep deprivation (less than 4 h) or normal sleep (more than 7 h) on different days. Sleep durations were 3.7 ± 0.9 h (sleep deprivation) and 7.1 ± 0.2 h (normal sleep). CFVR after sleep deprivation was significantly lower than that after normal sleep (3.3 ± 0.6 versus 4.2 ± 0.9, p<0.001). Short sleep duration attenuated CFVR compared with normal sleep duration. This finding suggests that sleep deprivation might serve as a trigger for cardiovascular events.

Serum asymmetric dimethylarginine as a marker of coronary microcirculation in patients with non-insulin dependent diabetes mellitus: correlation with coronary flow reserve

Abnormalities of coronary microcirculation without large vessel atherosclerosis have been known in patients with non-insulin dependent diabetes mellitus (NIDDM). Coronary flow reserve (CFR) has been considered an important physiological parameter in the coronary circulation reflecting the function of large epicardial arteries and the microcirculation, including endothelial function. Reduced CFR and impaired endothelium mediated, nitric oxide dependent coronary vasodilatation1,2 have been observed in NIDDM without overt coronary artery disease. Asymmetric dimethylarginine (ADMA) is a major endogenous nitric oxide synthase inhibitor and has been considered a novel risk factor of cardiovascular disease.3 Serum or plasma concentration of ADMA is increased in patients with NIDDM3 and may attenuate vascular function. However, to our knowledge, the relation between ADMA and CFR has not been examined in patients with NIDDM. Our goal was to examine the relation between serum ADMA concentration and CFR in patients with NIDDM by means of non-invasive transthoracic Doppler echocardiography. We studied 47 patients with NIDDM without a history of cardiovascular disease. We limited our study population to non-smokers and patients treated with diet or oral hypoglycaemic agents alone. All patients underwent two dimensional echocardiography and a treadmill exercise test …

P-226 The Frequency and Risk Factors for Cholelithiasis and Gallstone in Adult Patients with Cyanotic Congenital Heart Disease

Purpose: Cyanotic congenital heart disease (CCHD) induces secondary erythrocytosis and CCHD is thought to be one of the risk factors for cholelithiasis, but the frequency of cholelithiasis and/or gallstones in patients with CCHD is unknown. Materials and Methods: A hundred and two patients with CHD were divided into 4 groups: group A 22 CCHD without reparative surgery or with palliative surgery; group B 35 CCHD after repair who were eliminated cyanosis; group C 17 acyanotic CHD without repair; and group D 28 acyanotic CHD after repair. Gallstones were studied by abdominal ultrasonography or CT in each patient. For analysis of risk factors, patient records regarding cyanotic period, family history and past abdominal surgery were reviewed and blood pressures, lipid profiles, blood sugar and liver enzyme were evaluated. Results: Cholecystectomy due to cholelithiasis was underwent in 7 of 279 CCHD patients (2.5%). In group A, 7 patients (31%) underwent cholecystectomy, and 3 patients (18%) have gallstones. In group B, 11 patients (37%) had gallstones. In group C, nobody had gallstones, and in group D 2 patients (7%) had gallstones. SPO2 was significantly lower and red blood cell, hemoglobin, hematocrit, HbA1C and total bilirubin levels were significantly higher in group A (p 19.8, 95%CI 1.30 300.1). Conclusions: The incidence of cholelithiasis and gallstones is significantly high in CCHD regardless of repair. The most important factor related to gallstones was having CCHD even after desaturation was improved by surgical repair.