Yumi Shiina

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.

Meeting the challenge: The evolving global landscape of adult congenital heart disease

BACKGROUND Only limited information is available on the worldwide distribution and volume of adult congenital heart disease (ACHD) centers. We aimed to assess the centers using a bibliometric approach. METHODS AND RESULTS We identified publications presenting original research in the field of ACHD between 1995 and 2011. A total of 94,119 articles were identified which underwent electronic filtering and manual review. Overall, a dramatic increase in ACHD publications was seen over the study period. This was accompanied by a matching increase in impact factors and an over-proportional rise in ACHD contributions relative to the general academic field. Research output correlated well with self-reported patient volume and the number of identified ACHD centers in Europe and North America was in agreement with published surveys, thus validating our methodology. We observed a steady increase in the number of publishing ACHD centers worldwide. The number of ACHD centers per 10-million population was highest for Europe (3.6), followed by North America (1.7), Oceania (1.5), South America (0.4), Asia (0.3) and Africa (0.1). In addition, we evaluated the relative research output between developed and emerging economies and provide an overview over the main areas of research in the ACHD field. CONCLUSIONS Global interest in ACHD is increasing and this is reflected, both, in the number of publishing centers and the volume of research. Our data provides insights into the geographical and temporal distribution of ACHD research over the last 1 1/2 decades. These results could serve as benchmarks for international comparisons and guide efforts for improving ACHD infrastructure.

Right atrium contractility and right ventricular diastolic function assessed by pulsed Tissue Doppler Imaging can predict brain natriuretic peptide in adults with acquired pulmonary hypertension

PURPOSE We evaluated right atrial (RA) contractility and right ventricular (RV) diastolic function in adult patients with acquired chronic pulmonary hypertension (PH) by pulsed Tissue Doppler Imaging (TDI) and assessed their relationship with serum brain natriuretic peptide (BNP). MATERIALS AND METHODS Systolic myocardial wave (Sa), early diastolic myocardial wave (Ea), and late diastolic myocardial wave (Aa) at the tricuspid annulus were recorded in 77 consecutive patients with acquired PH. Early (E) RV inflow waves were recorded from 4-chamber views. RV Aa was regarded as the parameter of RA contractility and RV E/Ea was taken as the parameter of RV diastolic function using TDI. RESULTS All subjects had elevated BNP (mean 188.9 +/- 244.0 pg/dl) and pulmonary arterial systolic pressure (PASP) estimated at 62.9 +/- 26.7 mm Hg. BNP levels were positively correlated with RV E/Ea, Aa and PASP (r = 0.47, p < 0.0001 and r = 0.35, p < 0.01, respectively) but negatively with Aa (r = -0.29, p < 0.05). Next, all predictor variables were used in a multiple regression model with serum BNP values as dependent variables, refined to include 3 predictors: RV E/Ea, Aa, and PASP, which were all found to influence serum BNP values (p < 0.0001) by the formula Y = 34.1X1**-19.11X2**+2.95X3* (**p < 0.001, *p < 0.01) where Y = BNP, X1 = E/Ea of RV, X2 = Aa, and X3 = PASP (standard regression coefficients were 0.37, -0.34 and 0.34, respectively). CONCLUSION Serum BNP correlates with RA contractility and RV diastolic dysfunction by RV TDI in adults with acquired PH. Increased BNP may be related to decreased RA systolic function and RV diastolic function in these patients.

Cardiac sarcoidosis evaluated by multimodality imaging

An asymptomatic 62-year-old female patient with sarcoidosis was referred to our hospital for new-onset right bundle-branch block by electrocardiogram (ECG). She had been diagnosed with sarcoidosis by lymph node biopsy 3 years previously, and followed up by chest X-ray and ECG from then onward. Chest X-ray on admission showed bilateral lymph node enlargement, which was unchanged. Transthoracic echocardiogram showed wall thinning and severe hypokinesis in the basal portion of the left ventricular (LV) posterior-inferior wall, and coronary heart disease was excluded by conventional coronary angiogram. ECG-gated enhanced 320 slice multislice computed tomography revealed contrast defects in the basal portion of the LV posterior-inferior wall with reduced wall thickness in the early phase, which were conversely abnormally enhanced in the late phase, suggesting fibrosis or edema with inflammation. Late gadolinium enhancement in contrast-enhanced magnetic resonance imaging (MRI) was observed in the same region. To evaluate for evidence of inflammation, we performed 67-gallium-citrate scintigraphy, T2-weighted MRI, and fasting 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET). Although the 67-Ga scintigram showed no significant uptake, T2-weighted MRI revealed high intensity images, and fasting 18F-FDG PET identified increased uptake of FDG in the basal portion of the LV posterior-inferior wall, suggesting inflammation. We started corticosteroid therapy, diagnosing her condition as active cardiac sarcoidosis.

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.

Major adverse events and atrial tachycardia in Ebstein’s anomaly predicted by cardiovascular magnetic resonance

Objectives Patients with Ebstein’s anomaly of the tricuspid valve (EA) are at risk of tachyarrhythmia, congestive heart failure and sudden cardiac death. We sought to determine the value of cardiovascular magnetic resonance (CMR) for predicting these outcomes. Methods Seventy-nine consecutive adult patients (aged 37±15 years) with unrepaired EA underwent CMR and were followed prospectively for a median 3.4 (range 0.4–10.9) years for clinical outcomes, namely major adverse cardiovascular events (MACEs: sustained ventricular tachycardia/heart failure hospital admission/cardiac transplantation/death) and first-onset atrial tachyarrhythmia (AT). Results CMR-derived variables associated with MACE (n=6) were right ventricular (RV) or left ventricular (LV) ejection fraction (EF) (HR 2.06, 95% CI 1.168 to 3.623, p=0.012 and HR 2.35, 95% CI 1.348 to 4.082, p=0.003, respectively), LV stroke volume index (HR 2.82, 95% CI 1.212 to 7.092, p=0.028) and cardiac index (HR 1.71, 95% CI 1.002 to 1.366, p=0.037); all remained significant when tested solely for mortality. History of AT (HR 11.16, 95% CI 1.30 to 95.81, p=0.028) and New York Heart Association class >2 (HR 7.66, 95% CI 1.54 to 38.20, p=0.013) were also associated with MACE; AT preceded all but one MACE, suggesting its potential role as an early marker of adverse outcome (p=0.011). CMR variables associated with first-onset AT (n=17; 21.5%) included RVEF (HR 1.55, 95% CI 1.103 to 2.160, p=0.011), total R/L volume index (HR 1.18, 95% CI 1.06 to 1.32, p=0.002), RV/LV end diastolic volume ratio (HR 1.55, 95% CI 1.14 to 2.10, p=0.005) and apical septal leaflet displacement/total LV septal length (HR 1.03, 95% CI 1.00 to 1.07, p=0.041); the latter two combined enhanced risk prediction (HR 6.12, 95% CI 1.67 to 22.56, p=0.007). Conclusion CMR-derived indices carry prognostic information regarding MACE and first-onset AT among adults with unrepaired EA. CMR may be included in the periodic surveillance of these patients.

Doppler imaging predicts cardiac events in chronic pulmonary thromboembolism

PURPOSE We evaluated whether right ventricular (RV) diastolic dysfunction assessed by pulsed tissue Doppler imaging (TDI) predicts cardiac events in patients with chronic pulmonary thromboembolism (CPTE). MATERIALS AND METHODS In 63 consecutive patients with CPTE, early diastolic myocardial velocity (Ea) at the tricuspid annulus by TDI and early diastolic tricuspid inflow (E) by conventional pulsed Doppler were obtained, and E/Ea was calculated as an indicator of RV diastolic dysfunction. Brain natriuretic peptide (BNP) and other echo parameters were also obtained. A cardiac event (rehospitalization caused by congestive heart failure or cardiac death) was the study endpoint. Incidence of cardiac events was determined over a 374+/-451 day follow-up period. RESULTS In the follow-up period twelve patients had cardiac events. We divided patients into group A with cardiac events and group B without events. E/Ea was significantly increased in group A as compared with group B (8.3+/-4.1 vs. 5.7+/-2.6, p<0.01). BNP was higher in group A than group B (221+/-191 vs. 121+/-140 mg/dl, p<0.05), and in addition E/Ea was significantly positively correlated with BNP (r=0.48, p<0.001). A logistic regression model for predicting cardiac events was constructed and E/Ea was associated with an increased incidence of cardiac events (relative risk=1.33, 95% CI 1.00-1.75). CONCLUSION Elevated values of E/Ea obtained by TDI may predict cardiac events in patients with CPTE. BNP may also be a significant predictor.

Left atrial compensatory function in subjects with early stage primary hypertension assessed by using left atrial volumetric emptying fraction acquired by transthoracic echocardiography

PURPOSE To evaluate left atrial (LA) function in subjects with early stage primary hypertension (HT) and without enlargement of LA, we used transthoracic echocardiogram and measured LA volumetric emptying fraction and compared the results with those in healthy volunteers. MATERIALS AND METHODS 42 subjects with early stage primary HT (21 males, aged 61+/-12 years), within 1 year of HT diagnosis and starting initial treatment, were enrolled in the study. An additional inclusion criterion was normal sinus rhythm electrocardiogram without enlargement of LA. As the control group, 31 healthy volunteers with normal sinus rhythm electrocardiogram (13 male, aged 57+/-11 years) were enrolled. Maximum and minimum volume of LA (LAV max and min, respectively) were selected manually and visually in B mode images acquired from a four-chamber view from apex of left ventricle (LV) using a modified Simpson method, and the LA emptying fraction (LAEF) was calculated by the following formula: LAV min/LAV max x 100 (%). RESULTS There were no significant differences in age, male:female ratio, end-diastolic and end-systolic LV diameter, LA maximum volume, LV ejection fraction and E/A in mitral annulus between the two groups. However, we found that end-diastolic inter-ventricular septum thickness and end-diastolic LV posterior wall thickness were significantly larger in the HT group in comparison with the control group (P<0.01), but the HT group did not fit the classical criteria of LV myocardial hypertrophy. The systolic and diastolic blood pressure, the end-diastolic and end-systolic volume of LV, the total weight of LV myocardium and the LAEF were significantly higher in the HT group than in the control group (P<0.05). CONCLUSIONS In subjects with early stage primary HT with normal sinus rhythm, in spite of a normal LAV, the LAEF may increase. This increase of LAEF may be regarded as one of the compensatory reactions against preload to the left side of the heart and precedes the occurrence of LA enlargement.

Aortic Dilatation in Repaired Tetralogy of Fallot

Although the high prevalence of aortic root dilatation in adults with repaired tetralogy of Fallot (rTOF) is well established [(1,2)][1], evidence to guide clinical follow-up and decision making remains sparse. We sought to define the features, determinants, and rate of progression of aortic

Global strain and dyssynchrony of the single ventricle predict adverse cardiac events after the Fontan procedure: Analysis using feature-tracking cine magnetic resonance imaging

BACKGROUND The aim of this study was to determine whether major adverse cardiac events (MACE) during the late phase of the Fontan procedure could be predicted by strain measurements of single ventricles using cardiac magnetic resonance imaging with feature tracking (CMR-FT). METHODS One hundred adolescent patients who underwent the Fontan procedure (mean age, 21 years) were examined retrospectively with CMR-FT to assess the systemic single-ventricle function. Vertical long-axis cine imaging was divided into six myocardial segments. Global longitudinal strain (GLS) was determined by averaging the peak strain values of each of the six segments. The dyssynchrony index was defined as the standard deviation of the time to peak strain for six segments. The primary outcome was MACE, defined as cardiac death and unscheduled hospitalization. RESULTS MACE occurred in 18 patients during a mean follow-up of 62 months. According to the multivariate logistic regression analysis results for potential predictor variables, GLS and the dyssynchrony index are independent predictors of MACE. Patients with GLS ≥11.8% had significantly higher MACE-free rates than did those with GLS <11.8% [log-rank value, 14.15; p = 0.0002; hazard ratio, 6.82; 95% confidence interval (CI), 2.51-18.56]. Patients with a dyssynchrony index <63.5 ms had significantly higher MACE-free rates than did those with dyssynchrony index ≥63.5 ms (log-rank value, 28.17; p < 0.0001; hazard ratio, 21.69; 95% CI, 6.96-67.56). CONCLUSION GLS and the dyssynchrony index found using CMR-FT are independent predictors of MACE for adolescent patients after the Fontan procedure and provide information regarding risk stratification beyond clinical parameters and biomarkers.