Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation.

OBJECTIVES: To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR). METHODS: Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m2. These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the secondary endpoint was to obtain an improvement of functional capacity. RESULTS: Under treatment, New York Heart Association class improved for adolescents and adults. PVR decreased (P = .01) in all groups: in children from the median value 2.3 (interquartile range 2.0-3.1) to 1.9 (1.4-2.3) WU*m2, in adolescents from 2.3 (2.1-2.4) to 1.7 (1.4-1.8) WU*m2, and in adults from 2.8 (2.0-4.7) to 2.1 (1.8-2.8)WU*m2. In 71% of patients, PVR fell to less than 2 WU*m2. Cardiac index increased in adolescents from 2.6 (2.4-3.3) to 3.6 (3.4-4.3) L/min/m2, P = .04, and in adults from 2.1 (2.0-2.3) to 2.8 (2.3-4.7) L/min/m2, P = .03. CPET showed that only adolescents displayed a significant functional improvement. Anaerobic threshold improved from 17 (13-19) to 18 (13-20) mL/kg/min, P = .03; oxygen consumption and VO2 max increased from 1.3 (1.0-1.6) to 1.7 (1.1-1.9) L/min, P = .02 and from 25 (21-28) to 28 (26-31) L/min, P = .02, respectively. Oxygen pulse increased from 7.9 (5.7-10.4) to 11.2 (8.2-13.0) L/beat, P = .01. CONCLUSIONS: This is the first study that assesses by cardiac catheterization and CPET the effects of ERA in patients with Fontan circulation with increased PVR. These results suggest that ERAs might provide most pronounced hemodynamic and functional improvement in adults and adolescents.

Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy?

BACKGROUND: In patients with Fontan circulation, the liver is profoundly affected by chronic venous stasis. Little is known about early hepatic changes in this population. METHODS: We performed echocardiography, abdominal ultrasound, liver elastography, cardiac catheterization, esophago-gastro-duodenoscopy and calculated MELD-XI score in 64 Fontan patients (69% minors), at an interval of 1-15years since Fontan. RESULTS: Cardiac output remained stable in the first 5years after Fontan, then significantly decreased (r=-0.45, p(r=0)=0.003). NYHA class significantly increased after Fontan. Patients in NYHA class II/III (n=21, 14 minors) had significantly higher hepatic pressures, but normal ventricular function and pulmonary vascular resistances (PVR). Patients with pulmonary arterial pressure (PAP) ≥15mmHg (n=12, 6 minors) and those with PVR≥2WU*m(2) (n=27, 25 minors), had higher hepatic pressures (p<0.0001), a higher incidence of liver collaterals and/or esophageal varices (p<0.0001) and splenomegaly (p<0.02). Liver stiffness (LS) was elevated in most patients (median, 25th-75th percentile:17.3KPa, 14.1-21.4). It rapidly increased during the first 5-years after Fontan, compared to the following 5-years (from 12.2KPa, 9.8-14.1 to 17.5KPa, 14.3-24.5, p=0.007), then remained stable (19.1KPa, 16.9-22.6, p=0.60). MELD-XI score increased linearly with the time interval since Fontan (r=0.31, p(r=0)=0.01). For patients above 12years we found a linear correlation between LS and MELD-XI score in the 6-15years period after Fontan (r=0.40. p(r=0)=0.04). The overall incidence of established liver cirrhosis was 22%. CONCLUSIONS: This is the largest study showing that Fontan circulation prompts early, progressive and eventually irreversible liver damage. Precautions should be taken immediately after Fontan, to protect this fragile population.

Impact of obesity on left ventricular geometry and function in pediatric patients after successful aortic coarctation repair.

AIMS: To evaluate if obesity has an additional negative impact on left ventricular (LV) geometry and function in normotensive pediatric patients >12 months after successful treatment of aortic coarctation (CoA). METHODS AND RESULTS: We studied 40 CoA patients (mean age 14 ± 3 years, and male sex 70%), of them 10 were obese and 30 lean. Both groups were age and sex comparable. The entire studied sample underwent 24-ambulatory blood pressure (BP) monitoring, standard echocardiographic evaluation, and speckle tracking study. Both office and 24-hour diastolic BP were significantly increased in obese patients. Obese CoA patients showed increased LV mass (52 ± 13 g/m(2.7) vs. 43 ± 9 g/m(2.7) , P = 0.02), and significant reduction in E/A compared with lean CoA patients. Myocardial deformation properties were significantly reduced in obese CoA patients in all the three studied planes (longitudinal, radial, and circumferential) compared with CoA lean patients. LV twist values showed a significant reduction in the obese CoA group (9.9° ± 2.2° vs. 14.5° ± 2.3°, P < 0.0001). CONCLUSIONS: Our study shows that obesity in successfully treated CoA children, has an additional negative effect on BP, LV mass, and cardiac function. These findings are of particular concern, since life expectancy in CoA patients is limited mainly by atherosclerosis, and all the obesity-associated abnormalities found are harbingers of higher cardiovascular risk.

Two-dimensional strain and atrial function: a study on patients after percutaneous closure of atrial septal defect.

AIMS: To assess the value of two-dimensional (2D) strain in assessing regional myocardial function along the atrial wall. METHODS AND RESULTS: We studied 20 patients late after successful percutaneous atrial septal defect (ASD) closure. The analysis was performed for atrial longitudinal peak systolic strain on the interatrial septum, in correspondence of the device, and on the lateral wall of the left atrium. The speckle tracking indexes demonstrated almost the absence of any deformation on the Amplatzer ASD occluder, a bulky non-contractile element, passively moved by global heart motion. This study in a simple clinical model demonstrates that 2D strain is not influenced by global heart motion and tethering from adjacent segments and can also be used to study the regional atrial function. Moreover, both acquisition and post-processing times of 2D strain were very short, and the reproducibility was very good. CONCLUSION: All these above-mentioned characteristics make the 2D strain a tool fully compatible with the clinical scanning, able to provide additional clinical information.

[Obesity in children and hypertension]. / Obesità in età pediatrica ed ipertensione arteriosa.

According to the World Health Organization, obesity is one of the most common nutritional problem among children. The major determinant of this enormous increase in obesity prevalence is modern lifestyle and the consumption of very caloric foods such as fast-food products. Actually, there is a strong relationship between obesity and hypertension, type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea, and orthopedic problems. The aim of this review is to discuss the main mechanisms that link obesity to cardiovascular disease.

Atrial myocardial deformation properties in obese nonhypertensive children.

BACKGROUND: Obesity in adulthood is associated with a higher occurrence of atrial arrhythmias. Obese children, without arterial hypertension, may be a unique clinical opportunity to evaluate the effect of obesity, per se, on atrial myocardial function, excluding the influence of possible comorbidities. We sought to define the preclinical effects of obesity on the atrial function of healthy children with excess weight who have no other clinically appreciable cause of heart disease, by using the more sensitive ultrasonic-derived strain (S) and S rate imaging. METHODS: We studied 320 children divided into two groups: obese children (group O; n = 160; age 12 +/- 3 years); and healthy lean children, comparable for age, sex, and pubertal stage (referents; n = 160; mean age 12 +/- 3 years). RESULTS: Systolic blood pressure (BP) and diastolic BP, as well as 24-hour systolic BP and 24-hour diastolic BP were comparable between groups. Left ventricular mass/height(2.7) and left atrial dimensions were increased (P < .0001) in group O (46 +/- 12 g/m(2.7)) compared with referents (31 +/- 14 g/m(2.7)). Standard echocardiographic indices of global left ventricular systolic function were similar in the two groups. Obese children showed atrial peak systolic S rate (2.5 +/- 1.2 (s-1)) values lower (P < .0001) than that of referents (4.9 +/- 1.6(s-1)) in both left and right atria. In multivariable analysis, average peak systolic atrial S was significantly correlated with glycemia (P < .05, coefficient -0.23), body mass index (P < .01, coefficient -0.19), and left ventricular mass (P < .05, coefficient -0.17). CONCLUSIONS: Our study demonstrated that obesity, in absence of hypertension, is associated with reduced atrial myocardial deformation properties already in childhood involving both right and left atria.

Abnormal regional myocardial deformation properties and increased aortic stiffness in normotensive patients with aortic coarctation despite successful correction: an ABPM, standard echocardiography and strain rate imaging study.

The long-term follow-up data subsequent to a successful repair of AoC (aortic coarctation) show that life expectancy remains reduced. Previous standard echocardiographic studies have demonstrated normal or increased systolic cardiac function in patients following successful repair of AoC. SR (strain rate) imaging is a new technique able to detect subclinical myocardial abnormalities. In the present study we investigated whether young patients (without hypertension, as assessed using ambulatory blood pressure monitoring and an exercise test) following successful AoC repair already have abnormal myocardial deformation properties, and the relationship of the deformation properties with aortic stiffness. We studied 166 subjects, 83 AoC non-hypertensive patients (mean age 12+/-4 years) a number of years after successful repair of AoC and 83 age- and sex-matched subjects as controls. Peak systolic SR (1/s) for both regional longitudinal and radial function was assessed. The aortic stiffness index was calculated from the echocardiographically derived thoracic aortic diameters, and the measurement of blood pressure was obtained by cuff sphygmomanometry. The LV (left ventricular) ejection fraction was significantly increased in AoC patients, whereas regional longitudinal SRs were significantly reduced (-1.1+/-0.9 compared with -2+/-0.5, P<0.0001) in patients. The aortic stiffness index was significantly increased in AoC patients (12+/-9, P<0.0001). At multilinear regression analysis, age at repair (P=0.005; coefficient, -0.201; S.E.M., 0.027) and the aortic stiffness index (P=0.0029; coefficient, 0.334; S.E.M., 0.423) predicted longitudinal SR. Despite the presence of a successful repair for AoC, in the absence of hypertension, longitudinal deformation properties were significantly impaired. Moreover, the degree of longitudinal SR impairment was correlated with age at repair and aortic stiffness. Early repair can delay the onset of hypertension in postcoarctectomy patients, but cannot prevent the innate structural and functional abnormalities of the aorta and their deleterious effect on myocardial deformation properties.

[Quantitative evaluation of regional myocardial function using strain and strain rate imaging: normal values in pediatric age]. / Valutazione quantitativa della funzione ventricolare regionale destra e sinistra con strain e strain rate imaging, valori di normalità in età pediatrica.

BACKGROUND: Based on color Doppler methodology, regional myocardial strain rate (SR) and strain (epsilon) can now be calculated by comparing local myocardial velocity profiles. These deformation data sets may be an important new approach to quantify regional function of the left or right ventricle in congenital heart disease. The aim of the present study was to provide normal value for epsilon and SR in pediatric age. METHODS: We studied 45 healthy subjects (25 males, 20 females, mean age 11 +/- 6 years, range 4-16 years). For each subject we measured regional peak systolic, early and late diastolic E and SR. RESULTS: Left ventricular (LV) longitudinal deformations were homogeneous for LV basal, mid and apical segments (peak systolic SR -1.9 +/- 0.7 s(-1), systolic epsilon -24 +/- 8%). Longitudinal SR and epsilon values were significantly higher in the right ventricle, compared with LV walls, and were maximal in the mid part of the right ventricle free wall (peak systolic SR -3.4 +/- 0.9 s(-1), systolic epsilon -35 +/- 5%). The LV systolic and diastolic SR and epsilon values were higher for deformations in the radial direction compared with the longitudinal direction [radial peak systolic epsilon 55 +/- 6% vs longitudinal peak systolic epsilon (-)24 +/- 8%, p < 0.0001; radial peak early diastolic epsilon (-)40 +/- 15% vs longitudinal peak early diastolic epsilon 17.22 +/- 7%, p < 0.0001; radial peak systolic SR 2.7 +/- 0.5 s(-1) vs longitudinal peak systolic SR (-)1.9 +/- 0.7 s(-1); radial peak early diastolic SR (-)6.2 +/- 1.5 s(-1) vs longitudinal peak early diastolic SR 2.24 +/- 1.2 s(-1), p < 0.0001]. CONCLUSIONS: This study provides normal values for epsilon/SR in the largest published series of normal healthy children using a high frame rate (> or = 200 frames/s) and a commercially available software.

[New echocardiographic techniques in the study of coronary artery disease: strain and strain rate]. / Nuove tecniche ecocardiografiche nello studio della cardiopatia ischemica: lo strain e lo strain rate.

Strain/strain rate are a new echocardiographic technique able to quantify regional myocardial deformation. Since myocardial velocity, obtained by standard tissue Doppler, is affected by global heart motion, cardiac rotation and influence from velocities in other segments, strain/strain rate have been introduced to measure regional shortening fraction and shortening rate, respectively. The present review discusses the most recent developments in the application of strain/strain rate in coronary artery disease.