Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease.

Congenital heart disease (CHD) is the most common birth defect occurring in humans and some transcriptional factors have been identified as causative. However, additional mutation analysis of these genes is necessary to develop effective diagnostic and medical treatment methods. We conducted sequence analysis of the coding regions of NKX2.5, GATA4, TBX1, TBX5, TBX20, CFC1 and ZIC3 in 111 Japanese patients with non-syndromic CHD and 9 of their relatives. All patient samples were also analyzed by multiplex ligation-dependent probe amplification using probes involved in chromosome deletion related to CHD. Five novel variations of TBX5, GATA4 and TBX20 were detected in 6 of the patients, whereas none were found in 200 controls. The TBX5 variation p.Pro108Thr, located in the T-box domain, was identified in a patient with tricuspid atresia, an exon-intron boundary variation of GATA4 (IVS4+5G>A) was detected in a Tetralogy of Fallot patient and an 8p23 microdeletion was detected in one patient with atrioventricular septal defect and psychomotor delay. A total of seven non-synonymous polymorphisms were found in the patients and controls. Accumulation of novel variations of genes involving the cardiac development may be required for better understanding of CHD.

Risk factors for in-hospital mortality during infective endocarditis in patients with congenital heart disease.

Despite developments in preventative and medical therapy, infective endocarditis (IE) carries a high rate of mortality. Risk factors for mortality are unknown in pediatric and adult patients with congenital heart disease (CHD). We determined the risk factors for in-hospital mortality in pediatric and adult patients with CHD. A retrospective observational cohort study was conducted from January 1997 to December 2001 in Japan. Of the 239 patients for whom complete data were available, 216 patients with CHD were identified. Outcomes were alive or deceased. The proposed modified Duke's criteria identified 137 patients, aged 1 month to 62 years with a median of 12 years, with IE. In-hospital mortality was 10%. Four risk factors were independently associated with mortality by stepwise logistic regression analysis: (1) vegetation size > or =20 mm (odds ratio 40.6, 95% confidence interval 2.42 to 681); (2) age <1 year (odds ratio 19.5, 95% confidence interval 1.74 to 219); (3) presence of heart failure (odds ratio 7.16, 95% confidence ratio 1.34 to 38.4); and (4) Staphylococcus aureus as a causative organism (odds ratio 5.68, 95% confidence interval 1.16 to 27.9). Surgical intervention emerged as a predictive factor for lower in-hospital mortality (odds ratio 0.045, 95% confidence interval 0.003 to 0.70) by stepwise logistic regression analysis. In conclusion, surgical intervention, which decreases the risk of in-hospital mortality, should always be considered.

Myocardial scintigraphy after pacemaker implantation for congenital complete atrioventricular block.

Patients with isolated congenital complete atrioventricular block (CCAVB) occasionally develop dilated cardiomyopathy (DCM), despite early pacemaker implantation. However, the etiology of the DCM and its relationship to permanent ventricular pacing are not fully understood. Twenty-five patients with CCAVB underwent (99m) technetium (Tc) myocardial perfusion scintigraphy. Five patients were studied before and after pacing, providing a total of 30 image sets, which were divided into three groups; group 1: CCAVB before pacemaker implantation (PMI) (n = 11); group 2: CCAVB after PMI who did not subsequently develop DCM (n = 13); group 3: CCAVB after PMI who subsequently developed DCM (n = 6). Perfusion defects on single-photon-emission computed tomography (SPECT) were identified in group 1, 0 of 11 patients; group 2, 85% of patients; and group 3, 100% of patients. In groups 2 and 3, in patients with right ventricular pacing, the perfusion defects were mainly in the septum or between the apex and septum. On 20 segments' polar maps, the distribution of %uptake showed a similar pattern in groups 2 and 3, the degree of decreased %uptake and the number of segments with decreased %uptake being more severe in group 3. "Artificial" left bundle branch block (LBBB) pattern myocardial contraction induced by right ventricular pacing decreased myocardial perfusion around the apex and septum. Some patients with CCAVB will develop left ventricular dysfunction caused by artificial LBBB-induced interventricular asynchrony.

Heart rate dynamics during and after exercise in postoperative congenital heart disease patients. Their relation to cardiac autonomic nervous activity and intrinsic sinus node dysfunction.

BACKGROUND: Abnormal exercise-related heart rate (HR) dynamics, that is, blunted exercise HR response, lower peak HR, and delayed HR recovery after exercise, are associated with high morbidity and mortality in adults with acquired and congenital heart disease (CHD). However, the precise mechanisms underlying the abnormal HR dynamics remain unclear. OBJECTIVES: The purpose of this study is to evaluate the precise contribution of cardiac autonomic nervous activity (CANA) and sinus node function on exercise-related HR dynamics in postoperative patients with CHD. METHODS: We analyzed our previous data in 53 postoperative patients with CHD who had undergone pharmacologic evaluation, including intrinsic HR, and compared the results with HR dynamics. RESULTS: Intrinsic HR (84% +/- 11%) was lower than the expected value and independently correlated with resting HR (P < .05). Univariate analysis demonstrated that all CANA indices significantly correlated with most HR dynamic parameters. On multivariate analysis, basal parasympathetic nervous activity significantly influenced all HR dynamics (P < .05-.0001), except for peak HR, whereas postsynaptic beta sensitivity of the sinus node significantly influenced all HR dynamics (P < .05-.001), except for early HR recovery. Resting plasma norepinephrine significantly correlated with all HR dynamics (P < .05-.001), except for resting HR. CONCLUSIONS: Lower resting and peak HRs are independently associated with intrinsic sinus node dysfunction and abnormal sympathetic CANA, respectively. A blunted HR increase and delayed early HR recovery are independently associated with impaired sympathetic and parasympathetic CANAs with the greater influence on a blunted exercise HR increase.

Long-term patency of internal thoracic artery grafts for coronary artery stenosis due to Kawasaki disease: comparison of early with recent results in small children.

BACKGROUND: The results of coronary artery bypass grafting using the internal thoracic artery (ITA) had been reported less satisfactory in patients < 12 years old with coronary artery lesions caused by Kawasaki disease. METHODS: Since 1983, 67 patients have undergone this operation in our hospital; their age at operation ranged from 1 to 59 years (median 11 years), and the total number of ITA grafts was 95. The interval from operation to latest graft patency as confirmed by angiogram or echocardiogram ranged from 4 months to 23 years (median 8 years). For analysis of graft patency rates, patients were divided into 4 groups based on year of coronary artery bypass grafting and age when grafted. The groups based on year were from 1983 to 1993 (early) and from 1994 to 2006 (later), whereas the age groups were age at operation < 12 years and age at operation > or = 12 years. From 1999, percutaneous transluminal balloon angioplasty was performed for postoperative anastomotic stenosis. RESULTS: Percutaneous transluminal balloon angioplasty for anastomotic stenosis in ITA graft was performed in 6 patients. When the age at operation was < 12 years, the 10-year patency rate in the later period was 94.4% (n = 18), significantly > the 70.0% (n = 30) seen in the earlier period (P < .05). CONCLUSION: Recent results of ITA grafts in patients < 12 years old have improved through the application of appropriate indications and percutaneous transluminal balloon angioplasty for anastomotic stenosis. Once good flow in the ITA 1 year after surgery is confirmed, graft patency will persist > 20 years.

Comparison of late post-operative cardiopulmonary responses in the Fontan versus ventricular septation for double-inlet left ventricular repair.

Ventricular septation (VS) and the Fontan procedure are alternatives for definitive repair in patients with double-inlet left ventricle; although VS is theoretically preferable, the current preference in practice is the Fontan procedure. However, the long-term outcomes of both procedures remain unclear. To address this issue, cardiopulmonary responses during exercise were measured in patients with double-inlet left ventricle, and the impact of the type of procedure performed, Fontan or VS, on long-term exercise capacity and late postoperative clinical profiles was assessed. Fourteen post-Fontan patients (mean age 17+/-6 years) and 13 VS patients (mean age 19+/-4 years) underwent exercise testing. Of the 13 VS patients, 5 required atrioventricular valve replacement (AVVR), and 7 required pacemaker implantation. Although no difference in peak oxygen uptake was found between the VS and Fontan patients, peak oxygen uptake was higher in VS patients without AVVR (30+/-8 ml/kg/min) than in VS patients with AVVR (19+/-1 ml/kg/min) and Fontan patients (22+/-6 ml/kg/min) (p<0.01). There was no significant difference in peak oxygen uptake between the VS patients with and without pacemaker implantation (p=0.09). The clinical profiles of the VS and Fontan patients were similar in terms of medication and freedom from tachyarrhythmias or reoperations during the follow-up period. In conclusion, the data suggest that VS without AVVR provides excellent future exercise capacity in selected patients with double-inlet left ventricle.

Possible role of adrenomedullin in the regulation of Fontan circulation: mature form of plasma adrenomedullin is extracted in the lung in patients with Fontan procedure.

OBJECTIVE: We investigated the pathophysiological significance of molecular forms of adrenomedullin (AM) in patients after the Fontan procedure. METHODS: Plasma concentrations of mature AM (AM-m), an active form, glycine-extended AM (AM-Gly), an inactive form, and total AM (AM-T: AM-m+AM-Gly) were measured by specific immunoradiometric assay in the femoral vein, pulmonary artery and femoral artery of 29 consecutive patients after the Fontan procedure. The eleven patients who had history of Kawasaki disease and have normal coronary and hemodynamics served as control. RESULTS: Patients who underwent Fontan procedure had significantly higher venous concentrations of AM-T, AM-Gly, and AM-m than age-matched normal controls (AM-T, 12.0+/-3.3 vs. 9.6+/-2.0; AM-Gly, 10.4+/-3.0 vs. 8.5+/-1.6; AM-m, 1.6+/-0.7 vs. 1.0+/-0.6 pmol/l, each p<0.05). In patients with Fontan procedure, there were no differences in plasma AM-T, AM-Gly or AM-m levels between the femoral vein and pulmonary artery, however, there was a significant step-down in the AM-m levels, but not in plasma AM-T or AM-Gly levels, between the pulmonary artery and femoral artery (1.3+/-0.6 to 1.0+/-0.6, p<0.05). The venous concentrations of AM-m correlated negatively with systemic blood flow (cardiac output) (r=-0.46, p<0.05). CONCLUSIONS: Results suggest that in Fontan circulation plasma AM-m is increased in parallel with those of AM-T and AM-Gly and that AM-m is extracted in the lung. Extracted AM-m may be involved in the regulation of pulmonary arterial tonus, although further studies are necessary to elucidate the exact role of AM in Fontan circulation.

Change in plasma volume during peak exercise in patients with cyanotic congenital heart disease after definitive operation.

OBJECTIVES: To evaluate changes in plasma volume (deltaPV) during exercise in patients with single ventricular physiology with cyanosis; post-Fontan patients; and in patients after right ventricular outflow tract reconstruction (RVOTR). BACKGROUND: Compensatory mechanisms which regulate body fluid volumes operate in heart failure patients to maintain blood pressure. A better understanding of this pathophysiological process, especially during exercise, should help manage and follow such patients. METHODS: Twenty-six CHD patients (14+/-4 years), including 5 cyanotic patients, 12 after the Fontan operation, 9 after RVOTR, and 13 controls (14+/-5 years), performed a treadmill exercise test. DeltaPV from rest to peak was calculated and compared with changes in cardiovascular responses, plasma total protein (TP), norepinephrine (NE), osmolality (Osm), and blood lactate concentration (La). RESULTS: DeltaPV was smaller in CHD patients than in controls (Cyanotic: -5.9%, Fontan: -10.0%, RVOTR: -11.4%, CONTROLS: -14.5%, p<0.001). In all subjects, peak heart rate, systolic blood pressure and oxygen uptake correlated inversely with deltaPV (p<0.05 to 0.005). DeltaPV correlated inversely with changes in TP, NE, and La (p<0.005 for all), but not with the change in Osm. In CHD patients, the deltaPV correlated only with the NE increase (p<0.01). CONCLUSIONS: DeltaPV is smaller in CHD patients than in controls, especially in cyanotic patients. The smaller increases in cardiovascular responses during exercise and La are associated with the small deltaPV. These mechanisms may help to maintain cardiac output and increased sympathetic nervous activity may be beneficial to ensure sufficient perfusion pressure against deltaPV during exercise.

Effects of postural change on oxygen saturation and respiration in patients after the Fontan operation: platypnea and orthodeoxia.

The aim of this study was to assess whether platypnea and orthodeoxia occur in Fontan patients. We divided 14 Fontan patients into 2 groups: 8 patients who had pulmonary arteriovenous fistulas and/or intra-atrial shunts (group A) and 6 patients who had neither pulmonary arteriovenous fistulas nor intra-atrial shunts (group B). They were compared with 9 controls (group C). Arterial oxygen saturation, minute ventilation per body weight and ventilatory equivalent for carbon dioxide were measured in the supine and then sitting positions. In group A, 1 patient had platypnea and 3 patients had orthodeoxia (changes in the saturation from the supine position to the sitting position were -4% to -7%) accompanied with slight hyperpnea, and all 4 patients had both pulmonary arteriovenous fistulas and intra-atrial shunts. Contrary, patients in group B had neither platypnea nor orthodeoxia. The saturation was significantly lower and the minute ventilation was significantly higher in the sitting position than in the supine position in group A (p < 0.05). The other groups showed no significant difference in the saturation or the minute ventilation between the 2 positions. All groups showed the ventilatory equivalent was significantly higher in the sitting position than in the supine position (p < 0.05 to 0.01). We demonstrated platypnea and orthodeoxia in Fontan patients with pulmonary arteriovenous fistulas and intra-atrial shunts. We believe platypnea and orthodeoxia should be regard as a complication in Fontan patients with pulmonary arteriovenous fistulas and/or intra-atrial shunts.

Risk factors for arrhythmia and late death in patients with right ventricle to pulmonary artery conduit repair--Japanese multicenter study.

BACKGROUND: Arrhythmia and late cardiac deaths are thought to be major complications in patients after right ventricle (RV) to pulmonary artery (PA) conduit repair, although the incidence and predictors of these complications remain unknown. The aim of this study was to clarify the incidence and risk factors for arrhythmia and late deaths in patients with the RV to PA conduit repair through a Japanese multicenter study. METHODS: Three hundred fifty-one hospital survivors who underwent the RV to PA conduit repair before 1995 were studied. RESULTS: Survival rate after repair was 92% at 10 years, 88% at 20 and 25 years, respectively. Late death was observed in 30 (8.5%) including 4 patients with sudden death (SD). Higher right ventricular pressure (p = 0.02), larger cardio-thoracic ratio after repair (p = 0.02) and higher incidence of brady- or tachy-arrhythmia and SD (9/30) were associated with late death. Six (1.7%) patients developed ventricular tachycardia or ventricular fibrillation (VT/Vf). There were 22 patients who had 23 new-onset supraventricular tachy-arrhythmia (SVT). Right ventricular hypertension (p = 0.04) was associated with VT/Vf or SD. Male sex (p < 0.01), absence of previously aorto-pulmonary shunt (p < 0.05), older age at repair (p < 0.01) or longer length of follow-up (p < 0.01) were associated with SVT. CONCLUSION: Arrhythmia and late sudden death are relatively common late after the RV to PA conduit repair. Our data support recent surgical strategies of earlier primary operation and timely reoperation for progressive right ventricular outflow stenosis that may reduce the incidence of late arrhythmias and SD.

Abnormal postexercise cardiovascular recovery and its determinants in patients after right ventricular outflow tract reconstruction.

BACKGROUND: Abnormal responses of heart rate (HR) and oxygen uptake (VO2) during exercise characterize patients after right ventricular outflow tract reconstruction (RVOTR) for congenital heart defects. However, little is known about the postexercise dynamics. METHODS AND RESULTS: We evaluated postexercise cardiovascular dynamics in 52 patients after closure of an atrioventricular septal defect (group A), 79 patients after RVOTR (group B), and 44 control subjects. HR variability, arterial baroreflex sensitivity (BRS), plasma norepinephrine, and hemodynamics were measured. Although there was no difference between group A and control subjects, declines in HR and VO2 after light and peak exercise and in systolic blood pressure (SBP) after peak exercise were delayed in group B. Age, low-frequency component of HR variability, and plasma norepinephrine were independent determinants of early HR decline. Peak SBP and VO2 had a great impact on the corresponding recoveries. When the peak values were excluded, body weight, BRS, and right ventricular ejection fraction were independent determinants of early SBP decline. BRS and the pulmonary artery resistance were independent determinants of VO2 decline throughout recovery, and age and right systolic ventricular pressure also determined the early VO2 decline. BRS and low-frequency component of HR variability were determined independently by the number of surgical procedures. CONCLUSIONS: In RVOTR patients, in addition to metabolic and autonomic maturation, surgery-related abnormal cardiac autonomic nervous activity and impaired hemodynamics have a great impact on delayed postexercise cardiovascular recovery.

Stratification of pediatric heart failure on the basis of neurohormonal and cardiac autonomic nervous activities in patients with congenital heart disease.

BACKGROUND: Stratification of pediatric patients with congenital heart disease (CHD) has been based on their hemodynamics and/or functional capacity. Our purpose was to compare cardiac autonomic nervous activity (CANA) and neurohormonal activities (NHA) with postoperative status in stable CHD patients with biventricular physiology. METHODS AND RESULTS: We divided 379 subjects (297 CHD patients, 28 dilated cardiomyopathy patient, and 54 control subjects) into 4 subgroups according to New York Heart Association (NYHA) class (1.3+/-0.7) and measured various CANA and NHA indices. Stepwise decreases in baroreflex sensitivity (BRS), heart rate variability (HRV), adrenergic imaging, and vital capacity (VC) were observed in proportion to functional capacity in normal to NYHA II patients (P<0.001). However, there were no differences in these indices between NYHA II and III+IV groups, whereas a stepwise proportional increase in NHA indices was observed in these groups (P<0.001). Natriuretic peptides differentiated all NYHA classes. BRS, HRV, and VC were greater in the adult patients than in the child patients (P<0.05 to 0.01), although the functional class in adult patients was lower. Cardiac surgeries resulted in low BRS and VC, and the VC reduction independently determined a small HRV. Even if functional class and ejection fraction were comparable, CANA and brain natriuretic peptide were lower in CHD patients than in dilated cardiomyopathy patients (P<0.05 to 0.001). CONCLUSIONS: CANA and NHA indices are useful to stratify mild and severe heart failure in stable postoperative CHD patients, respectively. However, careful attention should be paid to age- and surgery-related influences on these indices.

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.

Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome.

OBJECTIVES: This study was designed to test the hypothesis that epinephrine infusion may be a provocative test able to unmask nonpenetrant KCNQ1 mutation carriers. BACKGROUND: The LQT1 form of congenital long QT syndrome is associated with high vulnerability to sympathetic stimulation and appears with incomplete penetrance. METHODS: The 12-lead electrocardiographic parameters before and after epinephrine infusion were compared among 19 mutation carriers with a baseline corrected QT interval (QTc) of > or =460 ms (Group I), 15 mutation carriers with a QTc of <460 ms (Group II), 12 nonmutation carriers (Group III), and 15 controls (Group IV). RESULTS: The mean corrected Q-Tend (QTce), Q-Tpeak (QTcp), and Tpeak-end (Tcp-e) intervals among 12-leads before epinephrine were significantly larger in Group I than in the other three groups. Epinephrine (0.1 microg/kg/min) increased significantly the mean QTce, QTcp, Tcp-e, and the dispersion of QTcp in Groups I and II, but not in Groups III and IV. The sensitivity and specificity of QTce measurements to identify mutation carriers were 59% (20/34) and 100% (27/27), respectively, before epinephrine, and the sensitivity was substantially improved to 91% (31/34) without the expense of specificity (100%, 27/27) after epinephrine. The mean QTce, QTcp, and Tcp-e before and after epinephrine were significantly larger in 15 symptomatic than in 19 asymptomatic mutation carriers in Groups I and II, and the prolongation of the mean QTce with epinephrine was significantly larger in symptomatic patients. CONCLUSIONS: Epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.

Estimation of PaCO2 during exercise in children and postoperative pediatric patients with congenital heart disease.

We evaluated how Paco(2) and respiratory variables relate during and after exercise and derived a new noninvasive estimation of Paco(2) in children and postoperative patients with congenital heart disease. We randomly selected 8 subjects from each of three categorized groups from our previous studies: 15 control subjects (8 to 21 years old), 16 Fontan procedure patients (9 to 22 years old), and 13 patients after right ventricular outflow tract reconstruction (RVOTR) [7 to 21 years old], and used their respiratory variables during exercise testing to estimate Paco(2) (study 1). In a stepwise multiple regression analysis, end-tidal carbon dioxide tension (Petco(2)), age, ventilatory equivalent for carbon dioxide (minute ventilation [Ve]/carbon dioxide production [Vco(2)]), and gas exchange ratio (R) were major determinants of Paco(2) in control subjects: Paco(2) = 12.0 + 0.54 Petco(2) + 0.15 Ve/Vco(2) - 3.6 R + 0.22 age (r = 0.86). In addition to Petco(2) and Ve/Vco(2), arterial oxygen saturation and tidal volume were additional major determinants for Fontan procedure and RVOTR patients, respectively. We derived equations to predict the Paco(2) (r = 0.92 for Fontan procedure and r = 0.74 for RVOTR). These equations were applied to the remaining study subjects to estimate Paco(2) (study 2). Estimated values correlated with the measured Paco(2) (r = 0.71 to 0.86), and the mean differences for the control subjects, Fontan procedure, and RVOTR patients were - 0.1, - 0.1, and - 1.0, with limits of agreement of +/- 3.3, +/- 4.4, and +/- 3.1, respectively. Although estimated Paco(2) based on the Jones equation correlated with the measured Paco(2) in all groups, their slopes were significantly flatter than ours. Paco(2) throughout exercise testing may be estimated in control children and postoperative pediatric patients. The Jones equation should be applied with great care in pediatric subjects.

Impact of noncoronary cusp prolapse in addition to right coronary cusp prolapse in patients with a perimembranous ventricular septal defect.

BACKGROUND: Few data are available with regard to the impact of aortic cusp herniation on the evolution of aortic regurgitation (AR) in patients with a perimembranous ventricular septal defect (VSD). METHODS: One hundred and two patients with a perimembranous ventricular septal defect with right coronary cusp prolapse were divided to two groups depending on the development of aortic regurgitation. The original defect diameter, the right coronary cusp deformity index (RCCD), and the right coronary cusp imbalance index were obtained as we reported previously. RESULTS: Mild aortic regurgitation was detected in 35 patients, and moderate in three. No aortic regurgitation was observed in 64 patients. A significantly larger number of patients had noncoronary cusp prolapse and the right coronary cusp imbalance index >/=1.30 in the aortic regurgitation group than in the no regurgitation group. Relative risk and odds ratio of noncoronary cusp prolapse and the right coronary cusp imbalance index >/=1.30 for development of aortic regurgitation were 3.69 (95% CI, 0.91-15.03) and 27.90 (95.94-130.85), and 2.23 (0.83-5.98) and 4.70 (1.44-15.27), respectively. Surgical closure was performed in 29 patients. All patients with no noncoronary cusp prolapse underwent simple patch closure of the ventricular septal defect, while five patients with noncoronary cusp prolapse and aortic regurgitation underwent aortic valvuloplasty. Among these, one patient needed aortic valve replacement. CONCLUSIONS: The additional complication of noncoronary cusp prolapse is a strong risk factor for the development of aortic regurgitation in patients with a perimembranous ventricular septal defect with right coronary cusp prolapse.

Post-exercise heart rate, blood pressure and oxygen uptake dynamics in pediatric patients with Fontan circulation Comparison with patients after right ventricular outflow tract reconstruction.

BACKGROUND: Post-exercise heart rate (HR) and oxygen uptake (V O(2)) recover more slowly in patients with the Fontan circulation, but little is known about the determinants of the delayed recovery. PURPOSE: To evaluate the post-exercise cardiovascular dynamics and clinical profiles in these patients. METHODS AND RESULTS: We studied 51 Fontan patients (14+/-4 years) (atriopulmonary connection, APC = 18 and total cavopulmonary connection, TCPC = 33) and compared the results with 34 patients after right ventricular outflow tract reconstruction (RVOTR) with identical exercise capacity and arterial baroreflex sensitivity (BRS) (15+/-4 years) and with 26 controls (14+/-4 years). There were no differences in post-exercise HR or VO2 declines between the Fontan and RVOTR groups. Although the systolic blood pressure (SBP) decline was delayed in the RVOTR group (p < 0.01), its early decline in the Fontan group was rapid and equivalent to that in controls. In Fontan patients, BRS had a great impact on early HR decline (p < 0.05) and early VO2 decline was determined by peak VO2, age and cardiac index (p < 0.05-0.001). TCPC and lower BRS were the main determinants of the slower SBP decline (p < 0.05). In another study of repeated paired exercise tests before and after Fontan operation, post-exercise SBP decline became greater after the operation (p < 0.07). CONCLUSIONS: In the Fontan group, post-exercise HR and VO2 declines are markedly delayed and are determined by cardiac vagal nervous activity, exercise capacity and age, respectively. Despite identical impaired hemodynamics and exercise capacity, post-exercise SBP decline is greater in the Fontan group, especially after APC, than in the RVOTR patients.

Negative chronotropic response to low-dose atropine is associated with parasympathetic nerve-mediated cardiovascular response in postoperative patients with congenital heart disease.

OBJECTIVES: To investigate the negative chronotropic response (NCR) to low-dose atropine in postoperative patients with congenital heart disease (CHD). BACKGROUND: Low-dose atropine causes a NCR through the central nervous system muscarinic receptor and is attenuated in adult heart failure patients. It has never been evaluated in CHD patients. METHODS: NCR corrected for basal heart rate (HR) (minimal HR/basal HR=cNCR) was determined after low-dose atropine (3 microg/kg) administration in 124 postoperative CHD patients (97 biventricular repair and 27 Fontan patients) and 11 controls and was compared with the cardiac autonomic nervous and functional status. RESULTS: The cNCR in simple CHD (post atrial or ventricular septal defect closure), complex biventricular CHD, and Fontan patients were 0.92+/-0.04, 0.94+/-0.04 and 0.96+/-0.04, respectively, and higher than in controls (0.87+/-0.03, p<0.001). In the complex CHD patients, higher cNCR was mainly associated with the lower pharmacologically determined cardiac parasympathetic nervous tone (PST), HR variability, high atrial natriuretic peptide, and lower right ventricular ejection fraction (p<0.0001). In Fontan patients, the lower beta sensitivity of the sinus node and the PST mainly determined the higher cNCR (p<0.01) and the cNCR did not correlate with either hemodynamics or exercise capacity. CONCLUSIONS: NCR is attenuated in proportion to the impaired cardiac parasympathetic nervous system and hemodynamics in postoperative complex biventricular CHD patients. In addition to PST, beta sensitivity of the sinus node significantly influences the NCR in Fontan patients.

Blood pressure dynamics during simulated ventricular tachycardia in patients after right ventricular outflow tract reconstruction mainly for tetralogy of Fallot compared with patients after ventricular septal defect closure.

We studied hemodynamic changes during simulated ventricular tachycardia using ventricular pacing. Hemodynamic deterioration during pacing is more significant in patients after right ventricular outflow tract reconstruction, especially in adults, than after closure of a ventricular septal defect. The cardiac autonomic nervous system has a significant impact on hemodynamics during simulated ventricular tachycardia.

Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome.

OBJECTIVES: The aim of this study was to test the hypothesis that epinephrine test may have diagnostic value for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome (LQTS). BACKGROUND: A differential response of dynamic QT interval to epinephrine infusion between LQT1, LQT2, and LQT3 syndromes has been reported, indicating the potential diagnostic value of the epinephrine test for genotyping the three forms. METHODS: The responses of 12-lead ECG parameters to epinephrine were retrospectively examined in 15 LQT1, 10 LQT2, 8 LQT3, and 10 healthy volunteers to select the best ECG criteria for separating the four groups. The epinephrine test then was prospectively conducted in 42 probands clinically affected with LQTS, their 67 family members, and 10 new volunteers. The best criteria were applied in a blinded fashion to prospectively separate a different group of 31 LQT1, 23 LQT2, 6 LQT3, and 30 Control patients (10 genotype-negative LQT1, 10 genotype-negative LQT2 family members, and 10 volunteers). RESULTS: The sensitivity (penetrance) by ECG diagnostic criteria was lower in LQT1 (68%) than in LQT2 (83%) or LQT3 (83%) before epinephrine and was improved with steady-state epinephrine in LQT1 (87%) and LQT2 (91%) but not in LQT3 (83%), without the expense of specificity (100%). The sensitivity and specificity to differentiate LQT1 from LQT2 were 97% and 96%, those from LQT3 were 97% and 100%, and those from Control were 97% and 100%, respectively, when Delta mean corrected Q-Tend >/=35 ms at steady state was used. The sensitivity and specificity to differentiate LQT2 from LQT3 or Control were 100% and 100%, respectively, when Delta mean corrected Q-Tend >/=80 ms at peak was used. CONCLUSIONS: Epinephrine infusion is a powerful test to predict the genotype of LQT1, LQT2, and LQT3 syndromes as well as to improve the clinical diagnosis of genotype-positive patients, especially those with LQT1 syndrome.