Progressive aortic root and pulmonary artery aneurysms in a neonate with Loeys-Dietz syndrome type 1B.

Loeys-Dietz Syndrome (LDS) is an autosomal dominant aortic aneurysm syndrome with multisystem involvement, caused by heterozygous mutations of transforming growth factor beta receptor type 1 (TGFBR1) or type 2 (TGFBR2) genes. We report on a neonate with the disorder caused by a known TGFBR2 mutation, who developed neonatal-onset progressive dilation of the aortic valve and aneurysms of the aortic root and main pulmonary artery (PA) associated with a large left-to-right shunt via a ventricular septal defect (VSD) and an atrial septal defect. He also had skeletal features (flexion contractures of the fingers, talipes equinovarus, a cleft palate, and joint laxity), mild facial dysmorphisms, and developmental delay. The dilation and aneurysms progressed after PA banding at age 12 days; and the patient received an intracardiac repair of the defects and PA plasty at age 42 days, followed by no further progression of the dilation and the aneurysms. Neonates with generalized hypotonia, a cleft palate, inguinal herniae, musculoskeletal features such as camptodactyly and talipes equinovarus, and a cardiac murmur should be suspected to have LDS, and extensive cardiovascular evaluation and testing of TGFBR1 and TGFBR2 are recommended. LDS patients with cardiac defects that lead to a large left-to-right shunt and congestive heart failure such as VSD should be considered for intracardiac repair even in early infancy.

Effect of exercise testing protocol on the relationship between minute ventilation and carbon dioxide production.

BACKGROUND: The effect of exercise protocol on the slope of the relationship between minute ventilation and carbon dioxide production (deltaVE/deltaVCO2) has not fully been studied. METHODS: Twenty-five healthy volunteers performed two sessions of incremental bicycle exercise, one with a rapidly increasing staged (RIS: 25W every minute) protocol and another with a slowly increasing staged (SIS: 25W every 3 minutes) protocol to calculate the deltaVE/deltaVCO2. Six of the subjects also participated in sessions of steady state exercise (SSE) test various work rates. RESULTS: The deltaVE/deltaVCO2 was significantly lower when the RIS protocol was used than when the SIS protocol was used (23.3 +/- 2.3 vs. 24.9 +/- 1.8, p < 0.001). Data from the subjects who also underwent SSE sessions revealed that the deltaVE/deltaVCO2 from the SSE protocols was greater than that from the RIS protocol and identical with that from the SIS protocol (125.1 +/- 3.7. 20.6 +/- 1.7, and 24.0 +/- 2.7, respectively, p < 0.05), while arterial partial pressure of carbon dioxide during exercise was not different between the protocols (43.0 +/- 3.3. 39.9 +/- 2.1, and 40.8 +/- 2.6, respectively, n.s.). C ONCLUSIONS: Care must be taken in the interpretation of the values of deltaVE/deltaVCC2, as they are influenced by the difference in exercise protocol.

Successful treatment of pulmonary hypertension with beraprost and sildenafil after cord blood transplantation for infantile leukemia.

Pulmonary hypertension (PH) is an infrequently reported complication after hematopoietic stem cell transplantation, and its etiology and therapeutic strategies, especially in infants, remain unclear. We report a case of severe PH that developed in an infant with acute leukemia following administration of busulfan as a preconditioner for cord blood transplantation; the case was successfully treated with sildenafil and beraprost, which to our knowledge is the first reported successful use of this regimen in PH following transplantation for infantile leukemia. From a review of all previous reports, use of busulfan in infants may raise the risk of developing PH, and unlike definitive pulmonary veno-occlusive disease, PH in this subgroup may be reversible by early detection and treatment.

Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan.

BACKGROUND: Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. METHODS AND RESULTS: Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of beta-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. CONCLUSIONS: Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.