Satoshi Masutani

Ventricular Afterload and Ventricular Work in Fontan Circulation

Background—Recent studies have indicated that there are inherent limitations associated with Fontan physiology. However, there have been no quantitative analyses of the effects of right heart bypass on ventricular afterload, hydraulic power, and resultant overall hemodynamics. Methods and Results—During routine cardiac catheterization, aortic impedance and ventricular hydraulic power were determined, both at rest and under increased ventricular work induced by dobutamine, in 17 patients with Fontan circulation, 15 patients with a single ventricle whose pulmonary circulation was maintained only by Blalock-Taussig shunts, and 13 patients who had normal 2-ventricle circulation. Both vascular resistance (nonpulsatile load on the ventricle) and pulsatile components of ventricular afterload (represented by low-frequency impedance) were significantly higher in the Fontan group than in the other groups (P0.01), and this was associated with decreased cardiac output in the Fontan patients. In addition, hydraulic power cost per unit forward flow was 40% lower in the 2-ventricle circulation than in the single-ventricle circulation, suggesting lower ventricular efficiency in single-ventricle circulation attributable to the lack of a pulmonary ventricle. Furthermore, in the Fontan group, -adrenergic reserve was markedly decreased because of a limited preload reserve. Conclusions—Fontan physiology is associated with disadvantageous ventricular power and afterload profiles and has limited ventricular reserve capacity. Thus, to improve the long-term prognosis of patients after Fontan surgery, future research should be conducted into medical interventions that can overcome these limitations inherent in Fontan circulation. (Circulation. 2002;105:2885-2892.)

Age-associated changes in arterial elastic properties in children

Abstract. Age-associated changes in pulsatile components of the arterial system in normal children have not previously been studied. The purpose of the present study was to establish reference ranges for age-associated changes in arterial pulsatile properties in children. Arterial compliance (CA) and stiffness of the proximal aorta were estimated from data obtained by cardiac catheterisation in 112 paediatric patients (age range, 6 months to 20 years) who were considered to have normal systemic vascular beds. CA was calculated by the area method, using ascending aortic pressure tracings. Aortic wall stiffness was evaluated using the pressure-strain elastic modulus (Ep). CA significantly increased with age (CA =0.065× age +0.86, r=0.71, P<0.001). However, the value of CA/BSA, which represents normalisation of CA to body surface area (BSA) (to eliminate factors associated with development of arterial size), significantly decreased with age and declined fastest during the first several years of life, suggesting an increase in arterial wall stiffness with increasing age in children. Ep also significantly increased with age (Ep =9.8× age +177, r=0.50, P<0.001). Conclusion: these findings suggest that both peripheral and proximal arterial wall distensibility in children decline after birth, although total arterial buffering capacity increases. The present results provide the first quantification of in vivo age–associated changes in arterial elastic properties in children, and are potentially useful as a reference for future studies of patients with diseases that involve the vascular system.

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.

Ventricular energetics in Fontan circulation: Evaluation with a theoretical model

Abstract Background : Both pulmonary and systemic circulation must be maintained by a single pump in Fontan circulation. This unique property of Fontan circulation may be related to decreased exercise tolerance or increased instantaneous postoperative mortality rate, often observed in patients with this circulation. To better understand Fontan physiology, the present study theoretically investigated cardiac performance of Fontan circulation by using ventricular–vascular coupling framework analysis.

Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure.

Despite advances in device closure for atrial septal defect (ASD), post-closure heart failure observed in adult patients remains a clinical problem. Although right heart volume overload is the fundamental pathophysiology in ASD, the post-closure heart failure characterized by acute pulmonary congestion is likely because of age-related left ventricular diastolic dysfunction, which is manifested by acute volume loading with ASD closure. Aging also appears to play important roles in the pathophysiology of heart failure through several mechanisms other than diastolic dysfunction, including ventricular systolic and vascular stiffening and increased incidence of comorbidities that significantly affect cardiovascular function. Recent studies suggested that accurate assessment of preclosure diastolic function, such as test ASD occlusion, may help identify high-risk patients for post-closure heart failure. Anti-heart failure therapy before device closure or the use of fenestrated device appears to be effective in preventing post-closure heart failure in the high-risk patients. However, the long-term outcome of such patients remains to be elucidated. Future studies are warranted to construct an algorithm to identify and treat patients at high risk for heart failure after device closure of ASD.

Aortic stiffness and aortic dilation in infants and children with tetralogy of Fallot before corrective surgery: evidence for intrinsically abnormal aortic mechanical property

OBJECTIVE The present study tested the hypothesis that there is an intrinsic abnormality of aortic elasticity in infants/children with tetralogy of Fallot (TOF) before corrective surgery. The study also determined the independent and quantitative effects of aortic volume load on aortic dilation in this group of TOF patients. METHODS Aortic stiffness (pulse wave velocity; PWV) and aortic volume load (aortic volume flow) were measured during catheterization in 37 infants and children with TOF before corrective surgery and in 55 control subjects. RESULTS PWV was significantly higher in TOF patients than in controls, irrespective of age, sex, hemodynamic burden on the aortic wall, and existence of aorto-pulmonary shunt. Aortic diameter was also significantly greater in TOF patients than in controls. Multivariate regression analysis identified aortic volume load as an independent determinant of aortic dilation (aortic diameter = 0.72 aortic flow + 26.1 body surface area + 2.79, r(2) = 0.58, p < 0.001). Increased aortic-wall stiffness correlated with the increase in aortic diameter in patients with dominant left-to-right shunt (without aortic volume load); aortic diameter = 0.007 PWV + 13.5 body surface area (BSA) + 6.3 (r(2) = 0.73, p < 0.05). CONCLUSIONS The present study highlighted the intrinsic abnormality of the mechanical property of the aortic wall as a feature of aortopathy in TOF. The study also indicated that aortic volume overload and, to a lesser extent, intrinsically high aortic stiffness correlated significantly with aortic dilation in TOF.

High Serum Levels of Procollagen Type III-N-terminal Amino Peptide in Patients with Congenital Heart Disease

Objective: The serum concentration of aminoterminal procollagen type III (PIIIP) is considered a useful marker of tissue fibrogenesis. The present study tested the hypothesis that: serum PIIIP levels are elevated in patients with congenital heart disease (CHD) and abnormal haemodynamic loading and/or hypoxaemia; PIIIP levels are associated with the severity of haemodynamic load or hypoxaemia, both of which enhance myocardial fibrosis. Methods and Results: Serum PIIIP levels were measured in five groups of CHD patients (42 patients with ventricular septal defect (VSD), 26 with coarctation of the aorta (COA, n  =  19) or aortic stenosis (AS, n  =  7), 36 with atrial septal defect (ASD), 39 with pulmonary stenosis (PS) and 20 with tetralogy of Fallot (TOF)). PIIIP levels of CHD patients were significantly higher than those of 42 control subjects (p<0.05, each). Serum PIIIP levels increased in parallel with increased ventricular volume load in VSD and ASD, and with the severity of PS. In TOF patients, PIIIP levels correlated negatively with arterial oxygen saturation. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) was associated with low levels of PIIIP in COA/AS patients despite the existing haemodynamic load. Conclusion: The increased serum PIIIP levels in proportion to the severity of ventricular load or cyanosis suggest enhanced myocardial synthesis of collagen type III in patients with CHD. Suppression of the PIIIP level by ACEI suggests the involvement of the renin–angiotensin–aldosterone system in myocardial fibrosis. These data provide the basis for the development of new diagnostic and therapeutic strategies in patients with CHD.

Cerebral Circulation in Patients With Fontan Circulation: Assessment by Carotid Arterial Wave Intensity and Stiffness

BACKGROUND Information about the cerebral circulation in the Fontan physiology is scarce. We tested our hypothesis that cerebral perfusion is impaired in the Fontan circulation by analyzing wavefront behavior (wave intensity) and assessing arterial stiffness at the carotid artery. METHODS The carotid arterial wave intensity and stiffness were computed in 34 consecutive Fontan patients (11.5±8.6 years) and 20 control subjects (13.4±6.0 years) using an echocardiographic vascular tracking system, which enabled simultaneous measurements of instantaneous carotid arterial pressure and flow velocity. RESULTS The carotid arterial blood flow was significantly lower in the Fontan patients than in the controls (p<0.05). Wave intensity analysis demonstrated a significant decrease in the compression and acceleration wave, an important forward traveling wave for cerebral circulation, in the Fontan patients compared with the control subjects (31.0±2.6 versus 48.1±4.4 mm Hg⋅m⋅s3⋅10(3); p=0.001). In addition, the negative wave intensity normalized to the first positive wave, representing a wave reflection from peripheral cerebral vessels, was significantly increased in the Fontan patients compared with that in control subjects. Carotid arterial stiffness and central venous pressure were also significantly increased in the Fontan patients and were independent determinants of the decreased first positive wave, suggesting the pathophysiologic importance of carotid arterial stiffness and central venous pressure as inflow and outflow resistance to the cerebral circulation, respectively, in the Fontan physiology. CONCLUSIONS These results suggest impaired cerebral perfusion caused by vascular stiffening and high central venous pressure in patients with Fontan circulation. Longitudinal studies examining the association between cerebral circulation and neurodevelopmental outcome after Fontan operation are warranted.

Marked disparity in mechanical wall properties between ascending and descending aorta in patients with tetralogy of Fallot

OBJECTIVES Recent studies have linked abnormal aortic medial pathology to progressive aortic root dilatation in patients with tetralogy of Fallot (TOF). To explore whether the aortic medial pathology in TOF is linked to aortic mechanical property, the present study tested the hypothesis that the distribution of impaired aortic elasticity corresponds to the known distribution of abnormal medial pathology (confined to the ascending aorta) in TOF. METHODS Pulse wave velocity (PWV) of the proximal and distal aortas was measured with a high-fidelity micromanometer in 98 TOF patients (64 with repaired TOF and 34 with unrepaired TOF) and 63 control subjects. RESULTS PWV of the proximal aorta was significantly higher in TOF than in the control, but similar in repaired and unrepaired TOF (repaired: 588 ± 205 cm/s, unrepaired: 680 ± 288 cm/s, control: 439 ± 101 cm/s, P < 0.001 for each TOF group vs. control, P = 0.07 for repaired vs. unrepaired TOF). In contrast, PWV of the distal aorta was almost identical among the three groups (repaired: 441 ± 189 cm/s, unrepaired: 430 ± 114 cm/s, control: 461 ± 164 cm/s, P = 0.73, analysis of variance), indicating that abnormal aortic mechanical property is confined to the proximal aorta regardless of the operative status of TOF. This was also confirmed by comparison within the group; PWV of the proximal aorta was significantly higher than that of the distal aorta in both TOF groups (P < 0.001, each), whereas there was no difference in PWV between the proximal and distal aortas in the control subjects (P = 0.61). CONCLUSIONS Consistent with the known histopathological disparity between the media of the ascending and descending aortas, aortic stiffness is markedly increased in the proximal but not in the distal aorta of TOF. These results suggest that aortic wall stiffness is a potentially useful clinical marker of aortic dilation in patients with TOF.