CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells.

Studies in murine models show that subthreshold TCR interactions with self-peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self-peptide, as read-out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear. Our study demonstrates that CD5 levels correlate with TCR signal strength in human naïve CD4+ T cells. Further, we describe a relationship between CD5 levels on naïve human CD4+ T cells and binding affinity to foreign peptide, in addition to a predominance of CD5hi T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5lo and CD5hi naïve human CD4+ T cells are consistent with observations in mice. Together, these data validate the use of CD5 surface levels as a marker of heterogeneity among human naïve CD4+ T cells with important implications for the identification of functionally biased T- cell populations that can be exploited to improve the efficacy of adoptive cell therapies.

Left Atrial Inexcitability in Children With Congenital Lupus-Induced Complete Atrioventricular Block.

BACKGROUND: Congenital atrioventricular block is a well-established immunologic complication of maternal systemic lupus erythematosus. We sought to further characterize the electrophysiological manifestations of maternal systemic lupus erythematosus on neonatal atria. METHODS AND RESULTS: Cases of isolated congenital atrioventricular block treated at our center over the past 41 years were identified. Data were extracted from clinical charts, pacemaker interrogations, ECGs, echocardiograms, and histopathological reports, when available. Of 31 patients with isolated congenital atrioventricular block, 18 were negative for maternal antibodies and had normal epicardial atrial sensing and pacing thresholds. In contrast, 12 of 13 patients with positive maternal antibodies had epicardial pacemakers, 5 (42%) of whom had left atrial (LA) inexcitability and/or atrial conduction delay. In 3 patients, the LA could not be captured despite high-output pacing. The fourth patient had acutely successful LA appendage and left ventricular lead placement. At early follow-up, an increased delay between the surface P-wave and intracardiac atrial depolarization was observed, indicative of atrial conduction delay. The fifth patient exhibited LA lead dysfunction, with atrial under-sensing and an increased capture threshold, 2 weeks after implantation. Biopsies of LA appendages performed in 2 patients showed no evidence of atrial fibrosis or loss of atrial myocytes. CONCLUSIONS: Herein, we report previously undescribed yet prevalent electrophysiological ramifications of maternal systemic lupus erythematosus, which extend beyond congenital atrioventricular block to encompass alterations in LA conduction, including LA inexcitability. These manifestations can complicate epicardial pacemaker implantation in newborns. In the absence of histological evidence of extensive atrial fibrosis, immune-mediated functional impairment of electrical activity is suspected.

Treatment of isolated ventricular septal defects in children: Amplatzer versus surgical closure.

BACKGROUND: Isolated hemodynamically significant ventricular septal defects (VSD) were previously treated surgically. Since the introduction of percutaneous (PC) devices, the management of isolated VSD has evolved. In our center, Amplatzer devices have been implanted for selected isolated perimembranous VSD since 2002. METHODS: The charts of all isolated PC perimembranous VSD closures and all surgical closures performed since 2002 were reviewed retrospectively. Clinical, electrocardiographic, and echocardiographic data were analyzed. The preclosure, immediate postclosure, and 1-month, 6-month, and 12-month postclosure results were assessed. RESULTS: Thirty-seven patients underwent PC closure, and 34 had surgical treatment. Mean follow-up was 42.1 ± 26.0 months. The PC group was significantly older (p < 0.01) and larger in size (p < 0.001). Surgical patients had more severe congestive heart failure and a significantly lower VSD gradient (p < 0.004). At follow-up, there were no differences in the incidence of residual shunting between the two groups (p = 0.92). All valvular regurgitations improved over time, except for 3 aortic regurgitations (5.4%) in the PC group that got worse. Two permanent pacemakers were implanted for early complete heart block in the PC group, and one was implanted in the surgical group (p = 0.94). CONCLUSIONS: The surgical results in our population were excellent. The selection of patients with perimembranous VSD remains a challenge to avoid post-PC intervention complications such as heart block and aortic insufficiency. For isolated VSD, PC closure, which avoids the morbidity of open heart surgery, should be considered as part of the therapeutic armamentarium.

Atrial resynchronization following heart transplantation in childhood.

Despite preserved left ventricular function, exercise capacity is often impaired after cardiac transplantation due to autonomic denervation of the donor's sinus node. We present our experience with atrio-atrial resynchronization in 2 pediatric heart transplant recipients. Both were highly active, suffered from chronotropic incompetence, and underwent successful atrial resynchronization with an objective improvement in exercise capacity, restoration of a physiologic chronotropic response, and resolution of dyspnea. Long-term stable recipient sinus node function may, therefore, be maintained in some cardiac transplant recipients with standard atrio-atrial anastomes. Atrio-atrial pacing may be feasible and effective years after transplantation.

Experience in a single centre with percutaneous aortic valvoplasty in children, including those with associated cardiovascular lesions.

BACKGROUND: We report the experience in a single institution with balloon aortic valvoplasty for congenital aortic stenosis. Unlike most other reported series, we included patients with associated lesions involving the left side of the heart. METHODS: Between November, 1986, and November, 2006, we performed 161 interventions on 143 patients, of whom 33 were neonates, 33 infants, and 77 children, just over one-quarter (28.6%) having associated lesions. RESULTS: The overall reduction in peak-to-peak gradient of 60 ± 24% (p < 0.01), was more effective in primary versus secondary intervention (63 ± 24% versus 47 ± 23%; p < 0.03), and in those with fused bifoliate as opposed to truly bifoliate valves (66 ± 17% versus 53 ± 30%; p = 0.01). Patients with associated lesions were younger (40.89 ± 60.92 months versus 81.9 ± 72.9 months; p = 0.001), and were less likely to achieve a final pressure gradient of less than 20 mmHg (35.0% versus 61.2%; p < 0.01). Overall mortality was higher in cases with associated lesions (27.5% versus 1.9%; p < 0.0001) but not catheter-related death (2.5% versus 1.9%; p = 1.0). Reintervention was more frequently required in infants (p = 0.02) but not in cases with associated lesions (p = 0.35). CONCLUSIONS: Balloon valvoplasty is a safe and effective method for the treatment of congenital aortic stenosis. Prior surgery to the aortic valve, reintervention, associated cardiovascular lesions, and the anatomy of the valve predict a less effective reduction in the gradient. Major complications and catheterization-related death are mainly secondary to very young age, but not to associated cardiac lesions.

Transcatheter ablation via a sternotomy approach as a hybrid procedure in a univentricular heart.

Hybrid procedures that combine surgical and interventional techniques are increasingly utilized in patients with congenital heart disease. We performed a novel hybrid intervention involving transcatheter ablation via a sternotomy approach and atriotomy incision. A recalcitrant accessory pathway was successfully ablated in a patient with hemodynamically unstable supraventricular tachycardia and an extracadiac Fontan for hypoplastic left heart syndrome.

Cardiac resynchronization therapy in congenital heart disease.

While cardiac resynchronization therapy (CRT) is of proven benefit in selected patients with severe ischemic or dilated cardiomyopathy, refractory symptoms, and conduction delay, extrapolation to congenital heart disease is not straightforward. This rapidly expanding patient population commonly suffers from heart failure, particularly in the presence of a single or systemic right ventricle. Surgical repair may also contribute to ventricular asynchrony. In this systematic review, the current state of knowledge regarding CRT in congenital heart disease is presented. Issues specific to congenital heart disease including right bundle branch block, right (pulmonary) ventricular dysfunction, systemic right ventricular dysfunction, and single ventricle dysfunction are explored. Evidence-based CRT applications for each of these particular conditions are reviewed. Initial experience with CRT in the acute postoperative setting and longer-term, including our own, is elaborated. Unlike standard indications based on multiple randomized clinical trials, supporting evidence for CRT in congenital heart disease is limited to case reports, case series, and small experimental crossover studies in the acute postoperative setting. The heterogeneous patient population, technical limitations from patient size, vascular access issues, and unique forms of ventricular asynchrony further obscure the selection of potential beneficiaries. Despite these limitations, experience thus far has been favorable. Quality of current data precludes definitive evidence-based recommendations, but optimistic initial results suggest that research endeavors in this field should be pursued. Multicenter prospective collaborative efforts are to be encouraged.

Thirty years of experience with epicardial pacing in children.

Due to underlying cardiovascular anatomy and size, epicardial pacing may be the preferred method of pacing in small children. To assess long-term safety, we reviewed all epicardial pacemakers implanted in children between 1971 and 2001. We found that 122 patients, with a median age of 5.4 years, had a total of 181 pacemakers and 260 electrodes implanted over a total follow-up of 789 patient-years. Of the total, 12 patients died after the first implantation, with one death attributable to dysfunction of the pacemaker. Reintervention was required in 75 patients after 5.0 +/- 3.2 years, due to depletion of the battery in 45 patients (60%), fracture or dysfunction of electrodes in 27 patients (36%), and infection in 3 patients (4%). In univariate analyses, risk factors for reintervention were an approach via a median sternotomy, with a relative risk of 2.3 (p = 0.0087), and an indication for pacing other than atrioventricular block, with a relative risk of 1.7 (p = 0.0314). In multivariate analyses, the approach via the median sternotomy independently predicted the need for reintervention, with a relative risk of 2.1, and 95% confidence intervals from 1.1 to 4.1 (p = 0.0256). The longevity of the second pacemaker and/or its electrode, assessed in 26 patients, was 3.7 +/- 2.6 years, not shorter than the first implantation (p = 0.4037). We conclude that epicardial pacing is a reliable means of achieving permanent pacing in children, with low morbidity and mortality. A substantial proportion, nonetheless, requires reintervention within five years, warranting meticulous follow-up.