Arterial Stiffness in Adult Patients with Cyanotic Congenital Heart Disease

Background. Increased arterial stiffness is an important predictor of cardiovascular (CVS) morbidity and mortality. Adults suffering from cyanotic congenital heart disease (CCHD) represent a population of patients at particular risk of CVS events. Erythrocytosis is a cardinal feature of CCHD but little is known about any possible interaction between hematological derangements and arterial stiffness. Methods. Fourteen CCHD patients (6 men and 8 women, mean age 32 ± 3 years) and 13 age‐matched healthy subjects were recruited. Results. Mean arterial stiffness, as estimated by stiffness index of digital volume pulse (SI_DVP) values was similar in the 2 groups (7.9 ± 0.7m/s vs. 7.2 ± 0.4 m/s, P = .38). In the control subjects arterial stiffness showed a strong correlation with age and mean arterial pressure (r = 0.64, P = .02 and r = 0.58, P = .036, respectively). In patients with CCHD, arterial stiffness correlated with mean arterial pressure but not with age (r = 0.76, P = .002 and r =?0.13, P = .65, respectively). However, SI_DVP correlated with hematocrit in CCHD patients (r = 0.69, P = .006), but not in healthy controls. The mean arterial pressure in patients with CCHD but not in controls showed a highly significant, positive correlation with the hematocrit level (r = 0.68, P = .008). Conclusions. Arterial stiffness in CCHD patients is affected by arterial pressure and hematocrit concentration but did not differ significantly from that in age‐matched healthy controls. It is unlikely that increased arterial stiffness may contribute to cardio‐ and cerebrovascular complication in adults with CCHD.     

Cardiopulmonary Bypass and Serum Thyroid Hormone Profile in Pediatric Patients with Congenital Heart Disease

Objective: To study the effect of cardiopulmonary bypass (CPB) on serum thyroid hormone profile in children undergoing open‐heart surgery. Design: Prospective cross‐sectional study. Setting: Multispecialty tertiary level referral center. Patients: One hundred consecutive patients (age 15.9 ± 14.6 months, weight 6.7 ± 2.5 kg) undergoing open‐heart surgery under CPB. Interventions: None. Outcome Measures: Levels and trends of serum total thyroxine (TT4), free thyroxine (FT4), total tri‐iodothyronine (TT3), free tri‐iodothyronine (FT3) and thyroid stimulating hormone (TSH), survival, inotropic score, duration of mechanical ventilation, postoperative complications. Results: TT4 levels were 9.08 ± 3.6, 6.4 ± 2.5, 6.24 ± 2.1, 6.43 ± 2.4, 7.20 ± 3.0 µg/dL at baseline and at 1, 24, 48 and 72 hours; FT4 levels were 1.82 ± 0.5, 1.49 ± 0.3, 1.29 ± 0.3, 1.32 ± 0.4, and 1.43 ± 0.5 ng/dL; TT3 levels were 1.81 ± 0.4, 1.31 ± 0.3, 0.99 ± 0.2, 1.0 ± 0.37, and 1.17 ± 0.48 ng/ml; FT3 levels were 4.09 ± 1.0, 3.02 ± 0.8, 2.21 ± 0.6, 2.22 ± 0.7, and 2.66 ± 1.05 pg/ml; TSH levels were 5.40 ± 3.8, 2.0 ± 3.1, 1.24 ± 1.1, 2.90 ± 3.3, and 4.03 ± 3.4 mIU/L. There was significant fall (29.1% for FT4, 32.1% for TT4, 77% for TSH, 46% for FT3 and 45% for TT3, p < 0.0001). When area under curve (AUC) TT4 was compared between survivors (n = 87) and nonsurvivors (n = 12), significantly larger AUC was seen in survivors (492.81 ± 158.6) than nonsurvivors (360.75 ± 179.6 p = 0.0125). In survivors >72 hours, AUC TT4 was larger in patients with uneventful postoperative course versus those with postoperative complications (516.48 ± 18.6 vs. 394.78 ± 29.9, p = 0.001). AUC TT4 showed significant inverse correlation with inotropic score and borderline inverse correlation with duration of mechanical ventilation. Conclusion: Children undergoing surgery under CPB showed significant fall in thyroid hormones. Because TT4 level is modifiable, prophylactic administration of TT4 for improving outcomes needs to be studied further.     

Extracardiac Complications in Adults with Congenital Heart Disease

With the increasing number of adults living with repaired, or unrepaired, congenital heart disease, there is a growing incidence of extracardiac comorbidities. These comorbidities can affect various organ systems in complex ways, and may have a significant impact on a patient's quality of life and survival. Many of these potential complications may go undiagnosed until there is already a significant bearing on the patient's life. Therefore, it is important for physicians who care for the adult congenital patient to be mindful of these potential extracardiac complications, and actively assess for these complications in their adult congenital practice. Continued research to identify modifiable risk factors is needed so that both preventative and therapeutic management options for these extracardiac complications may be developed.     

Sepsis in Premature Newborns with Congenital Heart Disease

Objective. To determine the incidence and distribution of neonatal sepsis in premature newborns with congenital heart disease (CHD) according to gestational and postnatal age, time of onset, and type and frequency of causing agents, and compare it with premature newborns without CHD. Design, Setting, Patients. A clinical investigation on 80 premature newborns admitted to neonatal intensive care unit (NICU) of Pediatric Clinic University Medical Center Sarajevo, Bosnia and Herzegovina, between October 23, 2007 and March 18, 2009. We analyzed the incidence and distribution of neonatal sepsis in premature newborns with CHD according to gestational and postnatal age, time of onset, and type and frequency of causing agents, and compared it with premature NICU patients without CHD. Results. Of the 80 premature newborns included in our study, 14 had CHD with patent ductus arteriosus as the most common type of anomaly. Culture-proven sepsis was diagnosed in 28.57% premature newborns with CHD and 12.12% premature newborns without CHD. The three most common causing agents were Staphylococcus aureus, Klebsiella species, and Serratia species. Conclusion. Premature newborns with CHD have a higher risk of acquiring sepsis during hospitalization in NICU, probably because of longer duration of hospitalization and need for invasive procedures such as mechanical ventilation, central venous catheters, and parenteral nutrition.     

Lymphatic Obstruction and Protein‐losing Enteropathy in Patients with Congenital Heart Disease

Objective. Protein‐losing enteropathy (PLE) is a known complication of surgical procedures for congenital heart disease. The pathogenesis and pathophysiology of PLE remain poorly understood. However, lymphatic insufficiency appears central to the disease process. We sought to investigate the role of lymphatic obstruction and central venous catheter‐related central venous thrombosis in patients with congenital heart disease and PLE. Design. A case‐control study design was constructed consisting of patients with congenital heart disease and PLE and 2:1 matched controls having undergone the same definitive surgical procedure. Obstruction to lymphatic return was considered present if the thoracic duct was ligated, or if there was complete central venous obstruction at the usual site of thoracic duct drainage. Results. Obstruction to lymphatic return was identified in 4 of 16 cases (25%) and 1 of 32 controls (4%), P = .06. There was no association between PLE and central venous catheter use or duration, and no discriminating characteristics between cases and controls with respect to anatomy, pre‐Fontan hemodynamic variables, operative or perioperative factors, or hemodynamic variables at the time of PLE diagnosis. Mortality for patients with PLE was 25% compared with 9% in controls (P = not significant). Long‐term resolution of PLE was obtained in six patients (38%). Conclusion. There is a high prevalence of apparent lymphatic obstruction in patients with congenital heart disease and PLE, suggesting that physical lymphatic obstruction may play an important, and previously unrecognized role in the development of PLE in patients with complex congenital heart disease.     

Electrophysiology Procedures in Adults with Congenital Heart Disease

Background. In adult congenital heart disease (CHD), arrhythmias contribute significantly to morbidity and mortality. Often, these adult patients are treated at a freestanding pediatric facility. Limited data exist looking at this cohort. Methods. A retrospective review was performed of all electrophysiology (EP) procedures performed in adults at our institution during a 5‐year period from January 1, 2006 through December 31, 2010. Results. There were 99 cases performed in a total of 87 adults with CHD during this time period. The mean patient age was 27.1 years (18–51 years). The most common congenital cardiac diagnoses were: 27% with D‐transposition of the great arteries (n = 27)—of which 85% (n = 23) have had a previous atrial switch procedure, 20% with tetralogy of Fallot (n = 20), and 16% with previous Rastelli repair (n = 16). Overall, 37 EP studies were performed, with the majority done in patients with complex CHD. There were 74 additional cases. These procedures consisted of: 38 pacemakers (51%), 26 implantable cardiac defibrillators (36%), six laser lead extractions (8%), two loop recorders (3%), and two pocket revisions (3%). During this 5‐year period, there was one major complication (1%) and seven minor complications (7%). Conclusions. The complex care of adults with CHD requiring EP procedures can be safely and effectively accomplished in a freestanding pediatric hospital with low complications, provided institutional support of an adult CHD program.     

Missed Congenital Heart Disease in Neonates

Objectives. The purpose of this study was to determine the incidence of missed congenital heart disease in neonates in the state of Wisconsin leading to death or readmission during the first 2 weeks of life. Design. Wisconsin hospitalization and death records were reviewed from 2002 to 2006. Only those neonates discharged home after birth without a cardiac or major non-cardiac diagnosis were considered. Wisconsin hospital records identified those neonates readmitted during the first 2 weeks of life with a diagnosis of heart disease using International Classification of Diseases, 9th Revision (ICD-9) codes. Wisconsin death records also identified patients who died within the first 14 days of life who had a diagnosis of heart disease using International Classification of Diseases, 10th Revision (ICD-10) codes. Adverse events were attributed to congenital heart disease if the diagnosis was a left-sided obstructive lesion or a cyanotic heart defect. Other adverse events were attributed to heart disease if no other major diagnosis was present and the data suggested an intention to treat. The 114 Wisconsin hospitals, which delivered 340 203 babies during 2002–2006, were stratified into quartiles based on the total number of deliveries to determine if there was a difference in incidence of missed congenital heart disease based on hospital birth size. Results. Congenital heart disease led to death or rehospitalization during the first 2 weeks of life in 14 out of 345 573 births (1 : 24 684) in Wisconsin between 2002 and 2006. Coarctation of the aorta and hypoplastic left heart syndrome were the most common diagnoses. There did not appear to be a difference in the incidence of missed diagnosis of congenital heart disease based on the number of deliveries performed at the birth hospital. Conclusions. Death or readmission events in neonates under 2 weeks of age because of a missed diagnosis of congenital heart disease occurred in 1 : 24 684 neonates in the state of Wisconsin between 2002 and 2006. Critical left sided obstructive lesions were the most common cause of these events.     

Menstrual Cycle and its Disorders in Women with Congenital Heart Disease

Objectives. To investigate the age at menarche, the prevalence of menstrual cycle (interval) disorders, and determinants in women with congenital heart disease (CHD). Design. Using two CHD registries, 1802 (82%) of the 2196 women with CHD contacted (aged 18–58 years) provided written informed consent. After exclusion of patients with genetic disorders known to be associated with menstrual cycle disorders, 1593 eligible patients remained. Interviews by telephone and reviews of medical records were conducted. Results. Overall, the age at menarche was slightly increased in women with CHD (13.3 vs. 13.1 years in the general population), mainly attributable to an increased prevalence of primary amenorrhea (n = 147; 9.2%). Other menstrual cycle disorders were documented: secondary amenorrhea (n = 181, 11.4%), polymenorrhea (n = 103, 6.5%), oligomenorrhea (n = 90, 5.6%), and menorrhagia (n = 117, 6.5%). The occurrence of these disorders also depended on the presence of cyanotic heart disease, surgical status, the number of surgical interventions, and the severity of CHD. Discussion. Menstrual cycle disturbances, in particular primary amenorrhea, were frequently observed in this population. Patients with complex (cyanotic) heart disease needing repeated surgical interventions prior to menarche are especially at risk.     

Intracardiac Echocardiography in Congenital Heart Disease

The use of intracardiac echocardiography (ICE) in congenital heart disease has become well established over the past 7 years since its introduction into clinical imaging. The greatest experience has been to guide percutaneous device closures of secundum atrial septal defects and patent foramen ovale, with excellent safety and clinical results. However, ICE has also been used for the evaluation and management of many other congenital heart defects given its unique blood/transducer interface and close proximity to relevant cardiac anatomy. Clinical application of ICE is expanding, with the current ICE catheters being used as micro-transesophageal echo probes, and three-dimensional prototypes already developed and tested in animal models. It is expected that ICE will further increase in use with refinements in technology and greater operator experience, aiding the management of complex congenital heart disease.     

Caregiver Anxiety upon Discharge for Neonates with Congenital Heart Disease

Introduction. Parents of children with congenital heart disease (CHD) have been shown to be at an increased risk of having psychosocial morbidities including anxiety, depression, and somatization. Little is known about the anxiety level of these parents during the initial hospital course. The goal of this study was to evaluate the anxiety level of the parents at the time of hospital discharge and to determine if certain characteristics predict higher anxiety levels. Methods. Caregivers of neonates admitted with CHD within the first 30 days of life were recruited. Anxiety levels were measured by using the Spielberger State‐Trait Anxiety Scale just prior to discharge. Spearman correlations were performed between state and trait scales vs. clinical variables. Results. Fifty‐nine questionnaires were completed for 38 neonates. Based on state score measure of anxiety, 81% of parents denied anxiety, 14% reported borderline anxiety, and 5% reported significant anxiety. Trait scores of anxiety reflected 93% of parents who denied anxiety, 2% who reported borderline anxiety, and 5% who reported significant anxiety. There was a significant positive correlation between state score and level of education (ρ= 0.30, P < .05) and the trait score and level of education (ρ= 0.23, P < .10). Number of medications was also significantly negatively associated with standard trait score (ρ=–0.37, P < .05). Conclusion. In general, anxiety trait scores were low for caregivers of neonates with CHD; however, there was a higher proportion of caregivers that reported anxiety in the state anxiety score. Higher education was associated with a higher level of anxiety. Future studies are needed to determine how to minimize anxiety levels during this stressful time period.     

Shifts in Exercise Capacity Are Not Reported Adequately in Patients with Congenital Heart Disease

Objective. In cross‐sectional studies, self‐reported health status and quality of life have only poorly correlated with objective exercise capacity in patients with congenital heart disease (CHD). We tested the hypothesis whether longitudinal changes in exercise ability are related to changes in self‐reported quality of life. Patients and Methods. One hundred eighty‐two patients (79 female, 103 male, age 14–70 years) with various congenital heart defects were investigated twice. Every time, they completed the SF‐36 quality of life survey and performed a symptom‐limited cardiopulmonary exercise test. Between the two tests, 32 patients had open heart surgery, 10 had a catheter intervention, 48 patients had a medication change, and 92 had no changes in their management for at least 6 months. Results. Patients were classified into three groups. Peak oxygen uptake increased by more than 10% in 43 patients; in 84, patients it did not change substantially (±10%); and in 55 patients, it declined by more than 10%. Comparing the three groups, the changes in any of the life quality scales did not differ significantly. Even in self‐reported physical functioning, we could not find any differences (Kruskal–Wallis test, P= .563). Conclusions. In patients with CHD, there was no detectable relation of changes in exercise capacity and changes in self‐reported health status or quality of life.     

Rehabilitation Program in Adult Congenital Heart Disease Patients with Pulmonary Hypertension

Introduction. It is commonly believed that physical activity may have a negative impact on pulmonary hypertension patients. The object of this study is to determine the tolerability of a directed exercise program in congenital heart disease patients with pulmonary hypertension. Methods. Eight congenital heart disease patients with pulmonary hypertension were studied and followed up during a 1-year period. Four of them were enrolled in a 3-month rehabilitation program. Results. No significant changes in analytical data, hand and leg strength, or quality of life were seen at the end of the training program in rehabilitation and nonrehabilitation patients. However, patients in the rehabilitation group improved 6 minutes' walk test minimum hemoglobin oxygen saturation and functional class after ending the training program without having adverse events such as progression of symptoms or heart failure. Conclusions. Cardiopulmonary rehabilitation appears to be a safe intervention in patients with congenital heart disease and pulmonary hypertension.     

先天性心脏病遗传学研究现状及挑战

先天性心脏病（先心病）是一类重要的有临床意义的出生缺陷,保守估计其发生率为50/1000活产儿。该病的遗传学机制相当复杂：染色体畸变,单基因突变和多基因突变都有可能导致先天性心脏畸形。本综述回顾了近年来该领域研究的现状及面临的挑战,并提出未来可能的研究方向。     

Coronary Artery Anatomy in Congenital Heart Disease

Expanded surgical options and improved outcomes for children born with structural heart defects have ushered a greater clinical interest in the normal and abnormal development of the coronary circulation. Anatomic variations of the coronary system may impact surgical candidacy or operative technique during neonatal life, while others may impact long‐term clinical management and planning for subsequent interventions. This review aims to characterize coronary artery anatomy in symptomatic congenital heart disease, emphasizing the clinical consequence of these variations and anomalies.