Objectives: The aim of this study was to test the hypothesis that narrowing the landing zone using commercially available endografts would enable transcatheter pulmonary valve replacement (TPVR) using commercially available transcatheter heart valves. Background: TPVR is challenging in an outsized native or patch-repaired right ventricular outflow tract (RVOT). Downsizing the RVOT for TPVR is currently possible only using investigational devices. In patients ineligible because of excessive RVOT size, TPVR landing zones were created using commercially available endografts. Methods: Consecutive patients with native or patch-repaired RVOTs and high or prohibitive surgical risk were reviewed, and this report describes the authors’ experience with endograft-facilitated TPVR (EF-TPVR) offered to patients ineligible for investigational or commercial devices. All EF-TPVR patients were surgery ineligible, with symptomatic, severe pulmonary insufficiency, enlarged RVOTs, and severe right ventricular (RV) enlargement (>150 ml/m2). TPVR and surgical pulmonary valve replacement (SPVR) were compared in patients with less severe RV enlargement. Results: Fourteen patients had large RVOTs unsuitable for conventional TPVR; 6 patients (1 surgery ineligible) received investigational devices, and 8 otherwise ineligible patients underwent compassionate EF-TPVR (n = 5 with tetralogy of Fallot). Three strategies were applied on the basis of progressively larger RVOT size: single-barrel, in situ fenestrated, and double-barrel endografts as required to anchor 1 (single-barrel and fenestrated) or 2 (double-barrel) transcatheter heart valves. All were technically successful, without procedure-related, 30-day, or in-hospital deaths. Two late complications (stent obstruction and embolization) were treated percutaneously. One patient died of ventricular tachycardia 36 days after EF-TPVR. Compared with 48 SPVRs, RV enlargement was greater, but 30-day and 1-year mortality and readmission were no different. The mean transvalvular pressure gradient was lower after EF-TPVR (3.8 ± 0.8 mm Hg vs. 10.7 ± 4.1 mm Hg; p < 0.001; 30 days). More than mild pulmonary insufficiency was equivalent in both (EF-TPVR 0.0% [n = 0 of 8] vs. SPVR 4.3% [n = 1 of 43]; p = 1.00; 30 days). Conclusions: EF-TPVR may be an alternative for patients with pulmonic insufficiency and enlarged RVOTs ineligible for other therapies.
Objective: Risk factors for major adverse events late after Fontan palliation are unknown. Prior studies have suggested ventricular function and morphology as important risk factors. The aim of this study is to (1) characterize the late major adverse event profile in adult Fontan patients and (2) identify additional risk factors that may contribute to adverse outcomes. Design and Setting: A retrospective review of all adult patients >15 years post-Fontan seen at a tertiary academic center was conducted. Clinical, laboratory, cardiac data, and abdominal imaging were collected via chart review. Major adverse events (death, cardiac transplantation, or listing) were identified, and timing of events was plotted using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine independent predictors of late-term events. Results: A total of 123 adult Fontan patients were identified (mean time post-Fontan 22.4 years [±4.4]). Major adverse events occurred in 19/123 patients (15%). In this 15-year survivor cohort, transplant-free survival rates were 94.6%, 82.9%, and 59.8% at 20, 25, and 30 years postoperation, respectively. Modes of death were Fontan failure with preserved function (4), congestive heart failure with decreased function (2), sudden death (2), thromboembolic event (1), post-Fontan conversion (2), and posttransplant (2). No differences in adverse outcomes were found based on morphology of the systemic ventricle, Fontan type, or systolic ventricular function. On the other hand, features of portal hypertension (OR 19.0, CI 4.7-77.3, P < .0001), presence of a pacemaker (OR 13.4, CI 2.6-69.8, P=.002), and systemic oxygen desaturation (OR 0.86, CI 0.75-0.98, P=.02) were risk factors for major adverse events in the multivariate analysis. Conclusions: In adult Fontan patients surviving >15 years post-Fontan, portal hypertension, oxygen desaturation, and need for pacemaker were predictive of adverse events. Traditional measures may not predict late-term outcomes in adult survivors; further study of the liver's role in late outcomes is warranted.
Background. Mid-term survivors of the Fontan procedure are at risk for progressive heart failure, and endothelial dysfunction is thought to contribute to this process. Aldosterone antagonism has been shown to improve survival in adults with heart failure and the effects are mediated in part by changes in endothelial function. In the present study, we sought to determine if a short course of spironolactone improves endothelial function and alters serum cytokine profiles in adolescents and adults with single ventricle heart.
Methods. Subjects had baseline assessment of flow-mediated dilation and cytokine profiles (C-reactive protein, interleukin-6, interleukin-1b, interleukin-10, tumor necrosis factor-alpha). They were started on spironolactone 25 mg once a day and uptitrated to 50mg once daily. After 4 weeks, flow-mediated dilation and cytokine profiles were re-evaluated.
Results. Ten subjects (median age 28 years) were enrolled and completedthe protocol. The median flow-mediated dilation at baseline was 9.1% and did not change significantly after 4 weeks of spironolactone 7.6%, P =.46. There was mild elevation in serum cytokine profiles and only interleukin-1b decreased significantly with therapy, 0.39 to 0.23 pg/mL, P =.04.
Conclusions. In this small study, a short course of spironolactone did not improve endothelial function or alter the majority of serum cytokine levels. Whether single ventricle patients might realize other potential benefits of aldosterone antagonism such as reduced cardiac fibrosis remains to be determined.
Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann–Whitney U and Fisher’s exact tests. Eighteen ACHD patients aged 21–40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.
Improved treatment of congenital heart defects (CHDs) has resulted in women with CHDs living to childbearing age. However, no US population-based systems exist to estimate pregnancy frequency or complications among women with CHDs. Cases were identified in multiple data sources from 3 surveillance sites: Emory University (EU) whose catchment area included 5 metropolitan Atlanta counties; Massachusetts Department of Public Health (MA) whose catchment area was statewide; and New York State Department of Health (NY) whose catchment area included 11 counties. Cases were categorized into one of 5 mutually exclusive CHD severity groups collapsed to severe versus not severe; specific ICD-9-CM codes were used to capture pregnancy, gestational complications, and nongestational co-morbidities in women, age 11 to 50 years, with a CHD-related ICD-9-CM code. Pregnancy, CHD severity, demographics, gestational complications, co-morbidities, and insurance status were evaluated. ICD-9-CM codes identified 26,655 women with CHDs, of whom 5,672 (21.3%, range: 12.8% in NY to 22.5% in MA) had codes indicating a pregnancy. Over 3 years, age-adjusted proportion pregnancy rates among women with severe CHDs ranged from 10.0% to 24.6%, and 14.2% to 21.7% for women with nonsevere CHDs. Pregnant women with CHDs of any severity, compared with nonpregnant women with CHDs, reported more noncardiovascular co-morbidities. Insurance type varied by site and pregnancy status. These US population-based, multisite estimates of pregnancy among women with CHD indicate a substantial number of women with CHDs may be experiencing pregnancy and complications. In conclusion, given the growing adult population with CHDs, reproductive health of women with CHD is an important public health issue.
Background: Adults with congenital heart defects (ACHD) face long-term complications related to prior surgery, abnormal anatomy, and acquired cardiovascular conditions. Although self-care is an important part of chronic illness management, few studies have explored self-care in the ACHD population. The purpose of this study is to describe self-care and its antecedents in the ACHD population.
Methods: Persons with moderate or severe ACHD (N=132) were recruited from a single ACHD center. Self-care (health maintenance behaviors, monitoring and management of symptoms), and potential antecedents including sociodemographic and clinical characteristics, ACHD knowledge, behavioral characteristics (depressive symptoms and self-efficacy), and family-related factors (parental overprotection and perceived family support) were collected via self-report and chart review. Multiple regression was used to identify antecedents of self-care maintenance, monitoring, and management.
Results: Only 44.7%, 27.3%, and 23.3% of participants performed adequate levels of self-care maintenance, monitoring and management, respectively. In multiple regression analysis, self-efficacy, education, gender, perceived family support, and comorbidities explained 25% of the variance in self-care maintenance (R2=.248, F(5, 123)=9.44, p<.001). Age, depressive symptoms, self-efficacy, and NYHA Class explained 23% of the variance in self-care monitoring (R2=.232, F(2, 124)=10.66, p<.001). Self-efficacy and NYHA Class explained 9% of the variance in self-care management (R2=.094, F(2, 80)=5.27, p=.007).
Conclusions: Low levels of self-care are common among persons with ACHD. Multiple factors, including modifiable factors of self-efficacy, depressive symptoms, and perceived family support, are associated with self-care and should be considered in designing future interventions to improve outcomes in the ACHD population.
Introduction: The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities. Materials and methods: The mechanism of cardiac allograft rejection in the context of PD-1 antibody therapy was explored in a patient with cutaneous squamous cell cancer complicating long-standing cardiac allograft. Immune cell infiltrate in the myocardium and peripheral blood lymphocyte repertoire were assessed using myocardial biopsy and temporal analysis of peripheral blood samples. The efficacy of high-intensity immunosuppression to reverse graft rejection was explored. Results: Endomyocardial biopsy showed acute moderate diffuse cellular rejection with a predominant population of CD3+, CD8+ and CD4+ infiltrating lymphocytes; peripheral blood circulating lymphocytes showed a high frequency of proliferating and activated CD8+ T cells expressing PD-1 compared to a normal control. There was no difference in the activation and proliferation of CD4+ T cells compared to a normal control. Cardiac function improved following high-intensity immunosuppression and patient survived for up to 7 months after discontinuation of nivolumab. Conclusions: Immune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents.
Objective:
Transfer of congenital heart disease care from the pediatric to adult setting has been identified as a priority and is associated with better outcomes. Our objective is to determine what percentage of patients with congenital heart disease transferred to adult congenital cardiac care.
Design:
A retrospective cohort study.
Setting:
Referrals to a tertiary referral center for adult congenital heart disease patients from its pediatric referral base.
Patients:
This resulted in 1,514 patients age 16–30, seen at least once in three pediatric Georgia healthcare systems during 2008–2010.
Interventions:
We analyzed for protective factors associated with age-appropriate care, including distance from referral center, age, timing of transfer, gender, severity of adult congenital heart disease and comorbidities.
Outcome Measures:
We analyzed initial care by age among patients under pediatric care from 2008–2010 and if patients under pediatric care subsequently transferred to an adult congenital cardiologist in this separate pediatric and adult health system during 2008–2015.
Results:
Among 1,514 initial patients (39% severe complexity), 24% were beyond the recommended transfer age of 21 years. Overall, only 12.1% transferred care to the referral affiliated adult hospital. 90% of these adults that successfully transferred were seen by an adult congenital cardiologist, with an average of 33.9 months between last pediatric visit and first adult visit. Distance to referral center contributed to delayed transfer to adult care. Those with severe congenital heart disease were more likely to transfer (18.7% vs. 6.2% for not severe).
Conclusion:
Patients with severe disease are more likely to transfer to adult congenital heart disease care than non-severe disease. Most congenital heart disease patients do not transfer to adult congenital cardiology care with distance to referral center being a contributing factor. Both pediatric and adult care providers need to understand and address barriers in order to improve successful transfer.
Background: Right ventricular dysfunction occurs in many patients with significant pulmonary valve regurgitation late after initial total repair of tetralogy of Fallot. Methods to predict which of these patients are at increased risk of late morbidity and mortality are not yet known.
Hypothesis: This study evaluated electrocardiographic (ECG) predictors of severe right ventricular dilatation determined by magnetic resonance imaging (MRI) volumes in patients with tetralogy of Fallot late after initial corrective repair.
Methods: We retrospectively reviewed the ECGs and MRI right ventricular volume measurements of 20 patients (age 4.4 to 19.3 years, mean 10.0 years) with significant pulmonary valve regurgitation late after repair of tetralogy of Fallot. All patients had enlarged, hypokinetic right ventricles by echocardiography. The patients were grouped based on an indexed fight ventricular end-diastolic volume (RVEDV/BSA) of < 102 ml/m2 (Group 1) or ≥102 ml/m2 (Group 2). We determined the sensitivity, specificity, positive and negative predictive values of QRS duration, and mean frontal plane QRS axis for predicting right ventricular volumes.
Results: A maximal QRS duration of ≥ 150 ms or a northwest quadrant frontal plane ORS axis had 85% sensitivity, 86% specificity, 92% positive predictive value, and 75% negative predictive value for predicting an RVEDV/BSA of ≥102 ml/m2. The mean QRS duration was significantly longer in Group 2 than in Group 1 patients (156 ms vs. 123 ms, p = 0.005).
Conclusions: In patients late after repair of tetralogy of Fallot with significant pulmonary valve regurgitation, a maximal manually measured QRS duration of ≥ 150 ms and/or a frontal plane QRS northwest quadrant axis can predict patients with marked fight ventricular enlargement. The presence of either of these findings on the ECG signifies patients who require further evaluation and consideration for pulmonary valve replacement.