Heart transplantation for the failing Fontan Backer, Carl L; Russell, Hyde M; Pahl, Elfriede ...
The Annals of thoracic surgery,
10/2013, Letnik:
96, Številka:
4
Journal Article
Recenzirano
Patients with failing Fontan circulation are at high risk for complications after heart transplantation (HTx) because of multiple prior operations, elevated panel reactive antibody, hepatic ...dysfunction, coagulopathy, protein-losing enteropathy (PLE), and poor nutrition. The purpose of this review was to evaluate the outcome of HTx for these patients, including those who are status post-Fontan conversion.
Of 206 heart transplants at Ann & Robert H. Lurie Children's Hospital of Chicago from 1990 to 2012, 22 patients had a failing Fontan. Median age at HTx was 12.2 years, median interval from initial Fontan to HTx was 7.1 years. Potential preoperative risk factors included PLE (n = 15), mechanical ventilation (n = 8), prior Fontan conversion (n = 7), renal failure (n = 3), and plastic bronchitis (n = 2) Median number of prior operations was 3. Donor branch pulmonary arteries were used in 17 patients.
There were 5 early deaths (23%), due to graft failure (1), pulmonary hypertension (1), and infection (3). There were 3 late deaths (13%) at 1, 5, and 8 years. Two of 3 patients with preoperative renal failure died. Survivors who had preoperative PLE (n = 11) and preoperative plastic bronchitis (n = 2) experienced complete resolution of these pathological conditions after heart transplantation. Median length of stay was 30 days. Five of 7 Fontan conversion patients survived, and 6 of 8 preoperative ventilator-dependent patients survived. One-, 5-, and 10-year survival was 77%, 66%, and 45%, respectively.
The operative mortality of HTx for patients with a failing Fontan is high. Using the donor branch pulmonary arteries greatly facilitated the transplant. Because infection caused the majority of early deaths, lower intensity initial immunosuppression may be warranted. Transplantation was successful in treating PLE in all survivors. Prior Fontan conversion was not a risk factor. Preoperative mechanical ventilation was not a risk factor. Preoperative renal failure may be a relative contraindication. Earlier referral of failing Fontan patients may improve results.
The objective of this study was to describe a contemporary cohort of pediatric patients hospitalized for clinically suspected myocarditis. A retrospective chart review was performed at seven tertiary ...pediatric hospitals. Electronic medical records were searched between 2008 and 2012 for patients ≤18 years admitted with an ICD-9 code consistent with myocarditis. Patients were excluded if the admitting or consulting cardiologist did not suspect myocarditis during the admission or an alternative diagnosis was determined. One hundred seventy-one patients were discharged or died with a primary diagnosis of myocarditis. Median age was 13.1 years (IQR 2.1, 15.9), with a bimodal distribution; 24% <2 years and 46% between 13 and 18 years. Patients with moderate or severe systolic dysfunction were younger, had higher BNPs at admission, but had lower troponin. Mortality, heart transplantation, and readmission did not differ between patients who received only IVIG, only steroids, IVIG and steroids, and no immunotherapy. Ninety-four patients (55%) were discharged on heart failure medications, 16 were transplanted, and seven died. The presence at the time of admission of gastrointestinal (GI) symptoms (
p
= 0.01) and lower echo shortening fraction (SF) (
p
< 0.01) was associated with death/transplant. Within one year 16% had a readmission, one underwent heart transplant, and 39% received heart failure therapy. Pediatric myocarditis has a bimodal age distribution. The use of IVIG and steroids is not associated with mortality/heart transplantation. The presence of GI symptoms and lower echo SF may identify patients at risk for death and/or transplantation during the admission.
As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known ...about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9–24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger 14.9 (IQR: 11.0–19.1) years than those dying of cardiac 18 (IQR 15.5–24) years,
p
= 0.03 and non-cardiac 19 (IQR: 16.5–23) years,
p
= 0.002 causes. GC use was lower for those dying of cardiac causes compared to those living 2/8 (25%) vs. 304/378 (80.4%)
, p
= 0.001. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8,
p
= 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3,
p
= 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.
Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is ...unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1–6). Subjects with mutations starting at exon positions 40–54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18–∞),
p
= 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12–15) in subjects with mutations that started between exons 55–79,
p
= 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.
Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more ...intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials.
Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (
<0.0001). Rate of increase in indexed left ventricular end-diastolic (
=0.0132) and systolic (
<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (
=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups.
Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.
After pediatric heart transplant, commitment to lifelong immunosuppression is crucial to maintaining graft health. However, a review of the current literature surrounding adherence to ...immunosuppression in pediatric heart transplant patients is lacking. This systematic review aims to summarize the current landscape of adherence to immunosuppression in pediatric heart transplant patients. We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence to immunosuppression and the measurement of adherence was performed with an objective or otherwise validated measure of adherence (e.g., drug levels, adherence questionnaires). The titles/abstracts of 880 articles were reviewed. After initial screening, 106 articles underwent full text review. As such, 14 articles were included in the final review. Baseline adherence estimates varied greatly, with most values between 40% and 70%. Nonadherence to immunosuppression is associated with worse outcomes (rejection, hospitalization, mortality), impaired quality of life, and mental health concerns in pediatric heart transplant patients. As nonadherence to immunosuppression is common and associated with worse outcomes, there is a need for further development and evaluation of interventions in this space.
In children with fulminant myocarditis (FM), we sought to describe presenting characteristics and clinical outcomes, and identify risk factors for cardiac arrest and mechanical circulatory support ...(MCS). A retrospective review of patients with FM admitted at our institution between January 1, 2004, and June 31, 2015, was performed. We compared characteristics and outcomes of FM patients who received cardiopulmonary resuscitation (CPR) and/or were placed on MCS (CPR/MCS group) to those who did not develop these outcomes (Control group). There were 28 patients who met criteria for FM. Median age was 1.2 years (1 day–17 years). Recovery of myocardial function occurred in 13 patients (46%); 6 (21%) had chronic ventricular dysfunction, 6 (21%) underwent heart transplantation, and 3 (11%) died prior to hospital discharge (including one death following heart transplant). Of the 28 FM patients, 13 (46%) developed cardiac arrest (
n
= 11) and/or received MCS (
n
= 8). When compared to controls, patients in the CPR/MCS group had a higher peak b-type natriuretic peptide (BNP) levels (
p
= 0.03) and peak inotropic scores (
p
= 0.02). No significant differences were found between groups in demographics; chest radiograph, electrocardiogram, or echocardiogram findings; or initial laboratory values including BNP, troponin, C-reactive protein, lactate, and creatinine (
p
> 0.05 for all). Children with FM are at high risk of cardiovascular collapse leading to the use of CPR or MCS. Aside from peak BNP levels and inotropic scores, the most presenting characteristics were not helpful for predicting these outcomes. FM patients should ideally receive care in centers that provide emergent MCS.
Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this ...population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF) < 35% and/ or shortening fraction (SF) < 16% on final echocardiogram. SLVD was present in 57/436 (13.1%) patients, of which 12 (21.1%) died during the study period. Of these 12, (mean EF 20.9 ± 6.2% and SF 13.7 ± 7.2%), 8 received GDMT, 5 received steroids, and none received an ICD. ICDs were placed in 9/57 (15.8%) patients with SLVD (mean EF 31.2 ± 8.5% and SF 10.3 ± 4.9%) at a mean age of 20.4 ± 6.3 years; 8/9 received GDMT, 7 received steroids, and all were alive at study end; mean ICD duration was 36.1 ± 26.2 months. Nine ICDs were implanted at six different institutions, associated with two appropriate shocks for ventricular tachycardia in two patients, no inappropriate shocks, and one lead fracture. ICD use may be associated with improved survival and minimal complications in DMD cardiomyopathy with SLVD. However, inconsistent GDMT utilization may be a significant confounder. Future studies should define optimal indications for ICD implantation in patients with DMD cardiomyopathy.
Early recognition of anthracycline-induced cardiomyopathy may reduce morbidity and mortality in children, but risk stratification tools are lacking. This study evaluates whether electrocardiogram ...(ECG) changes precede echocardiographic abnormalities in children with anthracycline-induced cardiomyopathy.
We performed a retrospective analysis of 589 pediatric cancer patients who received anthracyclines at a tertiary referral center. ECG endpoints were sum of absolute QRS amplitudes in the 6 limb leads (ΣQRS(6 L)) and corrected QT interval (QTc). Cardiomyopathy was defined by echocardiogram as ejection fraction < 50%, shortening fraction < 26%, or left ventricular end-diastolic diameter z-score > 2.5.
Median age at start of therapy was 7.8 years (IQR 3.7-13.6); median follow-up time was 3.6 years (IQR 1.1-5.8). 19.5% of patients met criteria for cardiomyopathy. Male sex, race, older age at first dose, and larger body surface area were associated with development of cardiomyopathy. A 0.6 mV decrease in ΣQRS(6 L) and 10 ms increase in QTc were associated with an increased risk of developing cardiomyopathy with hazard ratios of 1.174 (95% CI = 1.057-1.304,
= 0.003) and 1.098 (95%CI = 1.027-1.173,
= 0.006) respectively. Kaplan-Meier estimates showed a lower chance of cardiomyopathy-free survival for QTc ≥ 440 ms and ΣQRS(6 L) ≤ 3.2 mV over time. After controlling for confounders, total anthracycline dose predicted a decrease in ΣQRS(6 L) and an increase in QTc independent of cardiomyopathy status (
= 0.01 and
< 0.001 respectively). Cardiotoxic radiation did not predict changes in ECG parameters. Cardiomyopathy was associated with increased mortality (34% versus 12%,
< 0.001).
In children receiving anthracyclines, decrease in ΣQRS(6 L) and QTc prolongation are associated with increased risk of developing cardiomyopathy. ECG is a potential non-invasive risk stratification tool for prediction of anthracycline-induced cardiomyopathy and requires prospective validation.
To enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors.
A 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American ...College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC.
Sixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (
= 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%,
< 0.01). The most common indications for referral to cardiology at pediatric centers were abnormal test results (
= 31,48%) and history of chemotherapy exposure (
= 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%).
The survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.
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