Hirotaka Ishido

Arterial haemodynamics in patients after repair of tetralogy of Fallot: influence on left ventricular after load and aortic dilatation

Background: Recent histological studies of the aortic wall of patients with tetralogy of Fallot (TOF) have shown massive degeneration of the tunica media of the aorta. Such changes in arterial wall structure may significantly alter arterial wall mechanical properties, and thus cause abnormal arterial haemodynamics. Objective: To test the hypothesis that after repair of TOF, there are abnormal arterial haemodynamics which are associated with aortic dilatation and which increased after load on the left ventricle. Methods and results: The subjects comprised 38 patients who had undergone complete repair of TOF, and 55 control subjects. Systemic arterial haemodynamics were investigated by measuring aortic input impedance during cardiac catheterisation. The patients with TOF had significantly higher characteristic impedance (158 (43) dyne.s.cm−5.m2 vs 105 (49) dyne.s.cm−5.m2) and pulse wave velocity (561 (139) cm/s vs 417 (91) cm/s) and significantly lower total peripheral arterial compliance (0.93 (0.39) ml/mm Hg/m2 vs 1.24 (0.58) ml/mm Hg/m2) than the controls (for all three variables, p<0.01 vs controls), suggesting that central and peripheral arterial wall stiffness are increased after TOF repair. Additionally, patients with TOF had significantly higher arterial wave reflection than the controls (reflection coefficient: 0.21 (0.12) vs 0.16 (0.06)). These abnormalities in patients with TOF increased the pulsatile load on the left ventricle and significantly contributed to decreased cardiac output, even when right ventricular function was taken into account by multivariate regression analysis. The increase in aortic wall stiffness was closely associated with the increase in aortic root diameter. Conclusion: These results indicating abnormal arterial haemodynamics after TOF repair highlight the importance of regular monitoring of the systemic arterial bed and potentially relevant cardiovascular events in long-term follow-up of TOF.

Ventricular-vascular stiffening in patients with repaired coarctation of aorta: integrated pathophysiology of hypertension.

Background— Despite successful repair, patients with coarctation of the aorta (COA) often show persistent hypertension at rest and/or during exercise. Previous studies indicated that the hypertension is mainly due to abnormalities in the arterial bed and its regulatory systems. We hypothesized that ventricular systolic stiffness also contributes to the hypertensive state in these patients in addition to increased vascular stiffness. Methods and Results— The study involved 43 patients with successfully repaired COA and 45 age-matched control subjects. Ventricular systolic stiffness (end systolic elastance) and arterial stiffness (effective arterial elastance) were measured invasively by ventricular pressure-area relationship during varying preload before and after &bgr;-adrenergic stimulation. The mean systolic blood pressure was significantly higher with concomitant increases in both end systolic elastance and effective arterial elastance in patients with COA compared with control subjects (113.2±16.8 versus 91.0±9.1 mm Hg, 44.5±17.0 versus 19.2±6.7 mm Hg/mL/m2, and 27.8±11.4 versus 20.2±4.8 mm Hg/mL/m2, respectively; P<0.01 for each). End systolic elastance and effective arterial elastance of patients with COA showed exaggerated responses to &bgr;-adrenergic stimulation, further amplifying blood pressure elevation. Quantification analyses assuming that ventricular systolic stiffness of patients with COA is equal to that of the control revealed that ventricular systolic stiffness accounts for approximately 50% to 70% of the elevated blood pressure in patients with COA. Furthermore, combined ventricular-arterial stiffening amplified systolic pressure sensitivity to increased preload during abdominal compression and limited stroke volume gain/relaxation improvement induced by &bgr;-adrenergic stimulation. Conclusions— Increased ventricular systolic stiffness, coupled with increased arterial stiffness, plays important roles in hypertension in patients with repaired COA. Thus, ventricular systolic stiffness is a potentially suitable target for reduction of blood pressure and improvement of prognosis of patients with COA.

Vasopressin in the treatment of vasodilatory shock in children

Abstract  Background : Many recent studies suggest that vasopressin deficiency is an important cause of catecholamine‐resistant hypotension with vasodilation in adults, but little is known about vasopressin deficiency in children.

Usefulness of early diastolic mitral annular velocity to predict plasma levels of brain natriuretic peptide and transient heart failure development after device closure of atrial septal defect.

Device closure of atrial septal defect (ASD) is sometimes followed by elevation of plasma brain natriuretic peptide (BNP), a marker of heart failure, and progression to heart failure. This study tested the hypothesis that the underlying diastolic dysfunction, assessed on tissue Doppler images (TDI) before device closure, can predict BNP level after ASD closure. The study subjects were 39 consecutive patients (age 27.5 +/- 16.3 years, range 5 to 63) who underwent device closure for ASD. Echocardiographic evaluation using TDI and 2-dimensional and pulse wave Doppler were performed, together with plasma BNP measurement 1 day before and 2 days after ASD closure. Before ASD closure, an age-dependent decrease was noted in left ventricular relaxation, assessed by early diastolic mitral annular velocity. ASD closure resulted in a decrease in early diastolic mitral annular velocity (from 14.7 to 12.3 cm/s, p <0.05) despite an increase in the left ventricular dimension (84% to 92% vs normal, p <0.05). These changes were associated with a parallel increase in BNP (17.9 to 48.4 pg/ml, p <0.05). Stepwise multivariate linear regression identified early diastolic mitral annular velocity before ASD closure and age as independent predictors of BNP levels after ASD closure (p <0.05). Consistent with this result, 2 patients with the lowest early diastolic mitral annular velocity developed exertional dyspnea after the procedure. In conclusion, our results indicate that TDI measurements could be useful to detect underlying diastolic dysfunction that can potentially cause heart failure after ASD closure and emphasize the importance of ASD closure at a young age before impairment of left ventricular relaxation.

Migraine attacks after transcatheter closure of atrial septal defect

Objective The purpose of our study was to evaluate the effect of atrial septal defect (ASD) closure on migraine headache attacks (MHA). Methods A total of 247 patients who underwent percutaneous ASD closure at our facilities were sent a structured questionnaire. We diagnosed MHA according to the criteria of the International Headache Society. Results A total of 207 patients were included in the study. New-onset MHA occurred in 23 patients and persisted in 15 at a mean follow-up of 45 months. Of the 29 patients who had MHA prior to ASD closure, 11 reported exacerbation of MHA, 11 reported no change and seven reported improvement within three months after ASD closure. Compared with the patients who had no MHA, patients with de novo MHA were younger and patients with MHA improvement tended to be older. Switching from aspirin to ticlopidine or clopidogrel rapidly aborted frequent MHA in nine patients who had severe symptoms after ASD closure. Conclusions These results indicate that Amplatzer device implantation can act as a permanent trigger of MHA in not a few patients, and that age may be an important predictive factor of the influence of ASD closure on MHA.

Efficacy and safety of torasemide in children with heart failure

Objective: To examine the efficacy and safety of torasemide in children with chronic heart failure (HF). Methods: 102 children with chronic HF who had received oral torasemide were analysed. Of these, 62 (de novo group) were newly diagnosed as having HF and were given torasemide as a diuretic. The remaining 40 (replacement group) had been given furosemide for >3 months before the study, and furosemide was then replaced with torasemide. Clinical signs and symptoms of HF (assessed as the HF index), humoral factors and serum potassium concentrations before torasemide treatment were compared with those obtained 3–4 weeks after torasemide treatment. Patients were also monitored for adverse effects. Results: In the de novo group, torasemide significantly improved the HF index with concomitant improvement in plasma brain natriuretic peptide concentration (median (interquartile range) 52 (51) vs 43 (49) pg/ml). In a randomly selected group of 25 de novo patients with ventricular septal defect, echocardiography showed that torasemide significantly improved left ventricular geometry and function. In the replacement group, brain natriuretic peptide concentrations were also significantly decreased from 50 (104) to 45 (71) pg/ml after substitution of torasemide, but the HF index showed only a tendency for improvement (p = 0.07). Torasemide also had a potassium-sparing effect (de novo group, no change in potassium concentration; replacement group, significant increase from 4.2 (0.5) to 4.3 (0.5) mEq/l), and caused a significant rise in serum aldosterone concentration, consistent with the anti-aldosterone effect of this drug. Serum concentrations of sodium and uric acid had not changed after torasemide treatment, and there were no serious adverse events that necessitated drug withdrawal. Conclusion: Torasemide can be safely used, and appears to be effective for treatment of HF in children. Future clinical trials are warranted to verify the present results.

Arterial stiffness in patients after Kawasaki disease without coronary artery involvement: Assessment by performing brachial ankle pulse wave velocity and cardio-ankle vascular index

BACKGROUND It remains unclear whether systemic arterial beds other than the coronary arteries are truly healthy in patients without coronary artery lesions (CAL) after Kawasaki disease (KD). We tested the hypothesis that patients with KD without echocardiographic evidence of CAL during the acute phase of the disease have abnormal mechanical properties in systemic arteries later. METHODS AND RESULTS We studied 201 consecutive patients with KD (age 2-23 years, mean 10±4 years; 109 male, 92 female) without CAL during the acute phase. Data were compared with those in 129 control subjects (age 2-25 years, mean 10±4 years; 73 male, 56 female; control group). We examined arterial stiffness by using the brachial-ankle pulse wave velocity (baPWV) and the cardio-ankle vascular index (CAVI). The baPWV in the KD group was significantly higher than that in the control group (913±121cm/s vs. 886±135cm/s, p=0.04). In contrast, there was no significant difference in CAVI (4.0±1.0 vs. 4.2±1.0, p=0.9) between the two groups. Multivariate analysis indicated a highly significant difference in baPWV (higher baPWV in patients with KD than in controls, p=0.004), after controlling for age, gender, body height and weight, and systolic and diastolic blood pressure, but no difference in CAVI between the groups. CONCLUSION Years after KD occurs in patients without apparent CAL during the acute phase, there is a small but significant change in systemic arterial properties, characterized by increased wall stiffness. The clinical importance of these findings must be clarified by performing long-term follow-up studies.

Left Atrial Systolic Force in Children: Reference Values for Normal Children and Changes in Cardiovascular Disease With Left Ventricular Volume Overload or Pressure Overload

BACKGROUND Recent studies in adults have indicated that left atrial (LA) systolic force (LASF) provides useful information about LA pump function and can be used to predict cardiovascular events. However, normal values of LASF in children are not available, and little is known about atrial function in pediatric patients with heart disease. The objectives of the present study were to provide reference values for LASF in children and to determine LA pump performance in pediatric patients with heart disease using LASF. METHODS LASF was measured using combined two-dimensional imaging and Doppler echocardiography in 185 healthy children and 71 pediatric patients with ventricular septal defects (VSDs; as a representative heart disease with chronic left ventricular [LV] volume overload; n=48) or coarctation of the aorta (COA; as a representative heart disease with chronic LV pressure overload; n=23). RESULTS LASF in children significantly increased with advancing age (P<.005). The major determinants of this change were body surface area, stroke volume, and heart rate, with a linear model fit (r2) of 0.72. In patients with VSD and those with COA, LASF was significantly elevated in proportion to the degree of LV volume or pressure load, suggesting adaptive mechanisms of LA pump function to facilitate LV filling in chronically overloaded hearts. LASF was normalized after anatomic correction of VSDs but remained elevated even after the relief of COA, indicating persistent overwork of the left atrium. CONCLUSIONS The present study provides reference data for the evaluation of atrial function in pediatric patients with cardiac disease. In addition, altered LASF in patients with VSDs with even small left-to-right shunts and in those with COA even after anatomic correction may have pathologic implications that could lead to a novel therapeutic target.

Novel mechanisms for cerebral blood flow regulation in patients with congenital heart disease.

BACKGROUND The mechanisms that regulate cerebral flow in patients after surgery for congenital heart diseases (CHDs) remain poorly understood. We tested our hypothesis that postoperative patients with CHD have disease- or hemodynamic-specific compensatory mechanisms for maintaining cerebral perfusion. METHODS A total of 89 children with specific hemodynamics including Glenn (n = 14), Fontan (n = 19), repaired tetralogy of Fallot (n = 24), and control patients (n = 32) were enrolled. The resistance and blood flow distribution between the brain (Rc and CIc) and lower body (Rs and CIs) were calculated by measuring the hemodynamic changes resulting from inferior vena cava occlusion during cardiac catheterization. RESULTS Despite considerable differences in cardiac index and superior vena cava pressure (SVCp), cerebral blood flow was preserved in all noncontrol groups, with a ratio between the vascular resistances in the cerebral and lower body circulation (Rc/Rs) that was significantly lower than that in controls. Interestingly, the reduced Rc/Rs of Glenn patients was mediated by the reduced Rc, whereas augmented Rs was conducive to the reduced Rc/Rs in the Fontan and tetralogy of Fallot groups. Multivariate analysis revealed that high SVCp was significantly associated with low Rc. Although low cardiac index was significantly associated with increased Rc and Rs, its impact was much greater on Rs than on Rc. CONCLUSIONS Compensatory mechanisms for cerebral flow regulation occur according to hemodynamic abnormality type in postoperative patients with CHD. Because such a regulation mechanism implies cerebral circulation fragility, further investigations are needed to address the impacts of cerebral circulation properties on neurodevelopmental outcomes.

Landiolol hydrochloride infusion for treatment of junctional ectopic tachycardia in post-operative paediatric patients with congenital heart defect

AIMS Junctional ectopic tachycardia (JET) after cardiopulmonary bypass surgery for congenital heart defects is often therapy-resistant and associated with high morbidity and mortality. Improvement of pharmacological therapy is needed. METHODS AND RESULTS We retrospectively analysed the clinical data of four patients with congenital heart defects, who developed post-operative JET and were treated with landiolol hydrochloride, representing all such patients treated at our university. In two patients, landiolol was used after failure of response to anti-arrhythmic therapies, including thermal control, sedation, discontinuation of catecholamines, and pharmacological therapy with nifekalant and amiodarone. Landiolol was used as a first-line therapy in the other two patients. In all patients, landiolol, at a dose ranging from 1.0 to 10.0 µg/kg/min, achieved successful sinus conversion within 15 min. No adverse events, such as bradycardia, hypotension, or hypoglycaemia, were encountered in all four patients. CONCLUSION Although limited to a small and heterogeneous group of patients, the results suggest that landiolol is a potentially useful therapeutic option for the well-known difficult condition of post-operative JET, and warrant further investigation in large-scale controlled studies.