Dilated cardiomyopathy caused by a novel TNNT2 mutation-added value of genetic testing in the correct identification of affected subjects.

Diagnosing familial dilated cardiomyopathy requires careful family history taking and clinical evaluation in first degree relatives. Based on the results of these findings the diagnosis may be established in the proband. However, due to the age-dependent expression of the disease, doubt may persist regarding the exact status of other family members, especially in young individuals. Here we present a family with DCM in whom we identified an underlying cardiac troponin T (TNNT2) mutation. Genetic testing was essential for the detection of asymptomatic carriers as well as for exclusion of the disease in other family members.

Speech and language in Simpson-Golabi-Behmel syndrome: a case report.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked disorder caused by a mutation of the glypican-3 gene. The physical characteristics associated with SGBS have been documented in several papers, but information on the behavioral phenotype is scarce. We report on the speech and language characteristics in an 8 year-old-boy with SGBS. The boy performed very well on formal language tests but he also demonstrated poor pragmatic skills. Speech was characterized by a distorted articulation, distorted resonance, fluency failures, and a stereotype prosody. Many more case descriptions are necessary to delineate the full range of the behavioral phenotype of SGBS.

Is morbidity influenced by staging in the fontan palliation? A single center review.

In a retrospective study of 32 consecutive patients undergoing a total cavopulmonary connection (TCPC), we tried to determine if the trend for decreasing age at Fontan completion and reducing the intervals between the staged procedures during the past decade was associated with a change in morbidity and outcome. In 8 patients the Fontan circulation was completed in one stage and in 24 patients an intermediate step by hemi-Fontan or bidirectional cavopulmonary anastomosis was performed before Fontan completion. Mean age at TCPC and mean interval since the previous palliation have decreased significantly during the past decade. Although major complications were significantly reduced over time the occurrence and duration of postoperative pleural effusions were not. Decreasing age as well as intervals in staged Fontan palliation have beneficial influence on major complications and outcome, without significantly affecting the duration of pleural effusions at Fontan completion.

Percutaneous closure by a vascular plug of a fistula between the superior caval vein and the left atrium.

We report the case of a 7-year-old boy with a history of pulmonary atresia and intact septum who developed a fistula between the remnant of the ligated superior caval vein and the left atrium after bidirectional superior cavopulmonary (Glenn) anastomosis. The close proximity to the right pulmonary veins made closure by a standard occluder impossible. An Amplatzer vascular plug without rim enabled us to close the connection percutaneously without obstructing the pulmonary venous flow. The technique appeared to be easy, safe, and effective.

Long term outcome up to 30 years after the Mustard or Senning operation: a nationwide multicentre study in Belgium.

OBJECTIVE: To assess long term outcome of patients who underwent Mustard or Senning repair for transposition of the great arteries up to 30 years earlier. DESIGN: Retrospective review of medical records. SETTING: The six university hospitals in Belgium with paediatric cardiology departments. PATIENTS: 339 patients were reviewed, of whom 124 underwent the Mustard procedure and 215 the Senning procedure. This represents almost the entire population of patients in Belgium with either simple or complex transposition. MAIN OUTCOME MEASURES: Mortality, morbidity, functional abilities, social integration. RESULTS: Overall mortality was 24.2%. Early mortality (< or = 30 days after surgery) accounted for 16.5%, late mortality for 7.7%. Actuarial survival of early survivors at 10, 20, and 30 years after surgery was 91.7%, 88.6%, and 79.3%, respectively. Patients in the Senning cohort had a slightly better survival rate than those in the Mustard cohort (NS). Baffle obstruction occurred more often after Mustard repair (15.3%) than after the Senning procedure (1.4%). Arrhythmia-free survival did not differ between the two cohorts, but was determined by the complexity of the transposition. Survivors of the Senning cohort had better functional status, and tended to engage in more sports activities. CONCLUSIONS: The long term outcome for patients surviving the Mustard or Senning operation was favourable in terms of late mortality, morbidity, functional, and social status. Overall mortality in the Senning cohort did not differ from the Mustard group, but Senning patients had better functional status, greater participation in sports activities, and fewer baffle related problems.

The midwall stress-velocity relationship during manipulation of afterload.

Despite providing a physiological correction, measurements of contractility using the midwall stress-velocity relationship still show evidence of an unexplained hypercontractile state in some children. We investigated if by using midwall shortening indexes, the known overestimation of contractility at low afterload could be prevented. In 12 piglets (5 or 6 weeks old), afterload was manipulated by balloon occlusion of the descending aorta and infusion of sodium nitroprusside up to 5 mg/kg/min, and left ventricular function was measured using multiple variables. The regression line between the echocardiographically derived midwall velocity of circumferential fiber shortening and end systolic wall stress differed from the regression line of the endocardial stress-velocity relationship. Although the midwall regression line was almost horizontal (or afterload independent) for end systolic wall stress values of more than 30 g/cm2, the slope was still steeper below a certain point of afterload. The increased midwall velocity of fiber shortening at low afterload is comparable to the endocardial stress-velocity relationship and could account for the pseudo-hypercontractile state found in some children.

Limitations of Doppler echocardiography for the post-operative evaluation of aortic coarctation.

Doppler blood flow measurements and derived pressure differences, through the Bernoulli equation, are used in the diagnosis of aortic coarctation, a congenital stenosis distal to the left subclavian artery. Doppler velocities remain elevated at the coarctation site after successful repair of coarctation, leading to high Doppler derived pressure differences without significant arm-leg pressure differences. We studied this apparent contradiction of two diagnostic methods, in vivo using patient and control data, and in vitro using a hydraulic model. Clinical and echocardiographic data from 31 patients, aged 13.0 +/- 4.0, 10.5 +/- 4.7 yr after coarctectomy by end-to-end anastomosis, and 18 age-matched healthy subjects were reviewed. Doppler peak velocities at the aortic isthmus were elevated in patients (2.2 +/- 0.4 vs. 1.2 +/- 0.2m/s, P < 0.001), corresponding to significant Doppler differences (20 +/- 7 mmHg), however, without significant arm-leg pressure differences. In all patients, a mild anatomic stenosis could still be observed. Local stiffness was increased. The hypothesis that the less distensible surgical scar in post-coarctectomy patients leads to a significant dynamic obstruction in systole was validated in a latex model of the aorta. Rigid rings (0.5-1.5 cm), matching the unloaded aortic diameter, were mounted around the aorta. Under loading conditions, Doppler peak velocities increased by 40 +/-7%, yielding Doppler differences of 21 +/- 3 mmHg, without a significant pressure drop. An alternative expression to calculate pressure differences, using both velocity and geometric information, was validated in the model. In conclusion, post-operatively, Doppler velocities remain elevated due to a mild anatomical and significant dynamic narrowing, but the specific geometry, resembling a tubular hypoplasia rather than an abrupt stenosis, permits an almost complete pressure recovery explaining the occurrence of Doppler differences in disagreement with the negligible arm-leg pressure difference.

Fixed region of nondistensibility after coarctation repair: in vitro validation of its influence on Doppler peak velocities.

After coarctectomy, local loss of distensibility is noted in addition to mild anatomic narrowing. We hypothesize that the increased Doppler peak velocities measured at the aortic isthmus in these patients partly reflect obstruction secondary to the stiff surgical scar. The hypothesis was studied in a pulsatile hydraulic model. Thirty-one patients (13.0 +/- 4.0 years of age), 10.5 +/- 4.7 years after coarctectomy by end-to-end anastomosis, were studied clinically and echocardiographically. Indexes of distensibility were calculated. The effect of isolated increased stiffness was studied in vitro with a stiff and a compliant 1:1 scale latex model of the aorta mounted in a pulsatile full-scale circulation loop. Local stiffening was obtained by a rigid ring mounted around the aorta, fitted to the dimension of the unloaded aorta. For different pressure and flow regimens, pressures and Doppler velocities were measured across the ring. Mean peak velocities at the surgical scar were 2.2 +/- 0.4 m/s. Mild anatomic stenosis was present. All distensibility indexes indicated locally increased stiffness (P <.001). In the stiff latex model, Doppler peak velocities increased from 1.89 +/- 0.04 m/s to 2.32 +/- 0.06 m/s (P <.03); in the compliant model, from 1.15 +/- 0.03 m/s to 1.79 +/- 0.05 m/s (P <.001). The increase of Doppler peak velocities depends on model compliance only and is independent of flow rate, length of the noncompliant segment, and viscosity of the perfusion fluid. Velocities do not change when semicircular stiffening is applied. We have demonstrated in vitro that isolated local nondistensibility leads to vessel narrowing during vascular distension. The relative contribution of local scar stiffness in the increase of Doppler peak velocities after coarctectomy was hereby assessed.

The influence of low afterload on the nature of the stress-velocity relationship.

OBJECTIVES: Correct assessment of contractility by conventional methods during manipulation of afterload is often disappointing. To this purpose, the stress-velocity relationship offers assessment of contractility at different levels of afterload. We decided to study the influence of afterload on the nature of the stress-velocity relation. BACKGROUND: Although linear at baseline conditions in a population older than two years, data in newborns or after administration of low-dose dobutamine suggest a different nature of this relationship at low afterload. METHODS: Ten healthy piglets (five to six weeks; 11 to 13 kg) were studied. End-systolic meridional wall stress (ESWS) and rate-corrected velocity of circumferential fiber shortening (VcFc) were measured in these piglets at baseline, after balloon occlusion of the descending aorta, and at nitroprusside infusion rates of 1, 2 and 5 microg/kg/min. To eliminate inotropic influences mediated by reflex tachycardia, we subsequently studied five piglets and six adult pigs after bilateral cervical vagotomy. RESULTS: The ESWS changed from a baseline mean of 50 g/cm2 to 137 g/cm2 after balloon occlusion and to 19 g/cm2 at 5 microg/kg/min of nitroprusside. The VcFc changed from 1.19 c/s (circumference/second) to values of 0.9 c/s and 1.73 c/s, respectively. The ensuing stress-velocity regression line proved to be curvilinear instead of linear. The steeper slope at low afterload could suggest enhanced contractility compared to expected values had the relationship been linear. CONCLUSIONS: Data from young piglets and adult pigs suggest a curvilinear relationship of the stress-velocity relationship. This could probably explain some of the "hypercontractile states" encountered in conditions with low afterload.

Influence of age and low afterload on the stress-velocity relation of the left ventricle.

The relation between systolic meridional wall stress (WS) and velocity of circumferential fiber shortening (VcFc) is widely accepted as a preload-independent index of contractility, with a linear relation in most subjects older than 2 y. However, this relation seems to become different in infants and after administration of inotropic agents. We decided to study the nature of the stress-velocity relation by a cross-sectional assessment of the influence of age, low afterload, and increased contractility. Study subjects were 30 healthy infants, 32 healthy older children, and 35 asymptomatic older children after completion of anthracycline chemotherapy. WS and VcFc at rest were studied in these infants and children. WS and VcFc were also studied after dobutamine infusion in both groups of older children. Linear regression analysis of the stress-velocity relation showed parallel slopes between the older children at rest and the post anthracycline children after dobutamine. The regression lines between the infants at rest and the healthy older children after dobutamine were also parallel, but with a different and steeper slope compared with the former groups. When comparing the stress-velocity relation of the overall population at rest with the overall population after dobutamine, the resulting regression lines are curvilinear and parallel, with a steeper slope at low afterload. The stress-velocity relation in infants and after dobutamine, resulting in low afterload is different compared with the stress- velocity relation in older children at rest and at higher afterload. Data of the overall population at rest and after dobutamine suggest a curvilinear relation.

Low-dose dobutamine stress echocardiography in children and young adults.

Dobutamine stress echocardiography has become widely accepted in the evaluation of adult patients with coronary heart disease. We wanted to assess the feasibility and the physiologic responses of stress echocardiography at low doses of dobutamine in a population of normal children and adults. Once achieved, we submitted a group of post-anthracycline patients to the test to assess the sensitivity of low-dose dobutamine stress echocardiography in the detection of cardiac dysfunction. Thirty-two healthy children and young adults (19 male and 13 female subjects, median age 15 years [range 6 to 26]) were studied. After the initial study of normal subjects, we submitted a cohort of 39 patients (18 female and 21 male, aged 6 to 25 years), who completed anthracycline chemotherapy, to the same protocol. Dobutamine was infused at rates of 0.5 to 2.5 and 5 microg/kg/min and echocardiographic measurements were obtained at rest and at the end of each stage. The test could be completed in 100% of the subjects without major complications. Statistically significant differences between resting echocardiographic values of systolic and diastolic function and values at 2.5 and 5 microg/kg/min of dobutamine were found. Moreover, dobutamine revealed or enhanced differences between normal subjects and the post-anthracycline patients. Thus, low-dose dobutamine stress echocardiography is feasible and safe in older children. The test is very sensitive for the detection of subclinical cardiac dysfunction in post-anthracycline patients and could possibly assess functional myocardial reserve.

Entrapment of a guide wire during percutaneous occlusion of a coronary artery fistula.

Coronary artery fistulas are extremely rare and coil occlusion by intervention techniques seems to be the therapy of choice. We describe the case of a 3-month-old infant with a coronary artery fistula. During occlusion of the fistula a coronary guide wire got entrapped in a small coronary branch, but could be successfully retrieved with a microsnare without damage to the heart. The microsnare technique prevented rupture of the guide wire.

Simultaneous delivery of two patent arterial duct coils via one venous sheath.

A female child, 10 months of age, weighing 7.2 kg, was catheterised for closure of a patent arterial duct. Aortography was performed in the lateral projection and the minimum diameter of the arterial duct was assessed by comparing it to the size of the catheter. The duct size was estimated between 3 and 3.5 mm at the narrowest point, therefore, it was decided to deliver two 5 mm patent arterial duct coils to avoid placement of an 8 mm coil in this small child. Similar operations were subsequently performed in two further children. Simultaneous delivery of two coils via a single long venous sheath is easy, fast, and safe. This simple and inexpensive procedure can reduce irradiation and anaesthesia time.

Reduced decrease of peripheral vascular resistance during exercise in young type I diabetic patients.

OBJECTIVE: In normal subjects, peripheral vascular resistance decreases during dynamic exercise. We studied blood pressure and peripheral vascular resistance responses to dynamic exercise in young normotensive type I diabetic patients. RESEARCH DESIGN AND METHODS: Thirty adolescent diabetic patients (9-19 years of age) underwent a maximal exercise test on a cycle ergometer. In a subset of 14 patients, cardiac output was measured by a CO2 rebreathing method and peripheral vascular resistance was calculated. Twenty-four normal individuals, age and sex matched, served as control subjects. RESULTS: Diastolic blood pressure was significantly higher in diabetic patients at intermediate workload (77 +/- 2 vs. 71 +/- 1 mmHg) and peak exercise (86 +/- 2 vs. 73 +/- 2 mmHg). Peripheral vascular resistance was significantly higher in diabetic patients at intermediate workload (17.0 +/- 1.1 vs. 12.6 +/- 0.5 mmHg.l-1.min-1.m-2) and peak exercise (16.3 +/- 1.3 vs. 11.4 +/- 0.5 mmHg.l-1.min-1.m-2). There were no significant correlations with the patient's age, diabetes duration, or diabetes control. CONCLUSIONS: We observed the decrease of vasodilator response during dynamic exercise in normotensive young type I diabetic patients.

Lack of increase in stroke volume during exercise in asymptomatic adolescents in sinus rhythm after intraatrial repair for simple transposition of the great arteries.

We studied stroke volume during exercise in 12 male asymptomatic patients in sinus rhythm after intraatrial repair for d-transposition of the great arteries. Data indicate that during exercise, stroke volume did not increase in the patient group, while in control subjects stroke volume increased.

Dobutamine stress echocardiography in the evaluation of late anthracycline cardiotoxicity in childhood cancer survivors.

Late anthracycline cardiotoxicity has been of increasing concern to pediatric oncologists. An increasing number of patients with cardiac dysfunction has been reported without a good correlation between cardiac function or symptoms and routine echocardiographic follow-up. We studied dobutamine stress echocardiography in patients who had received moderate doses of anthracyclines years before. Twenty-three patients (14 male, 9 female; 7-25 y) who completed chemotherapy with moderate doses of anthracyclines (180-380 mg/m2) more than 2 y previously underwent dobutamine stress echocardiography and were compared with a control group of 26 healthy young people (15 male, 11 female; 6-26 y) matched for age and weight. Dobutamine was administered in three periods up to a rate of 5 micro g/kg/min. Eighty-five percent of the patients showed an abnormal response to dobutamine. Both systolic and diastolic functions were affected. The systolic dysfunction was not related to diminished contractility but to an elevated systolic wall stress due to inadequate cardiac muscle thickening. The diminished wall thickening was related to the length of follow-up. Dobutamine proved to be a very sensitive method to detect clinical and subclinical cardiac dysfunction in patients post anthracycline chemotherapy and questions the concept of a safe dose.

Cardiorespiratory variables during a continuous ramp exercise protocol in normal young adults.

The purpose of the present study was to determine whether the cardiorespiratory variables measured during an exercise test with a continuously increasing workload (ramp) protocol are reproducible and to compare them to the values obtained with a step-wise incremental (James) protocol. Twenty normal adolescents and young adults performed two exercise tests on a cycle-ergometer, one with each protocol, and twelve of these subjects additionally performed a second identical ramp test. The results show that the cardiorespiratory variables measured during exercise with ramp protocol are reproducible and that peak values are not different from those obtained with step-wise incremental exercise protocol, except for a higher peak power. At intermediate equivalent workloads, there were significant correlations between cardiorespiratory variables measured in steady-state conditions with the incremental protocol and those obtained in non-steady-state conditions with the ramp protocol.