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1.
Arch Biochem Biophys ; 662: 143-150, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30543786

RESUMO

ß-hydroxybutyrate is the primary ketone body produced by the body during ketosis and is used to meet its metabolic demands. The healthy adult heart derives most of its energy from fatty acid oxidation. However, in certain diseases, the heart alters its substrate preference and increases its ketone body metabolism. Little is known about the effects of ßOHB on ventricular myocyte excitation-contraction coupling. Therefore, we examined the effects of ketone body metabolism on single cell excitation-contraction coupling during normoxic and hypoxic conditions. Myocytes were isolated from adult rats, cultured for 18 h in RPMI 1640, RPMI 1640 no glucose, and M199, HEPES with/without various amount of ßOHB added. To simulate hypoxia, myocytes were incubated at 1%O2, 5% CO2 for 1 h followed by incubation at atmospheric oxygen (21%O2,5% CO2) for 30 min before recordings. Recordings were obtained using an IonOptix system at 36±1ᵒ C. Myocytes were paced at 0.5, 1, 2, 3, and 4 Hz. We found that exposure to ßOHB had no effect on excitation-contraction coupling. However, culturing cells with ßOHB results in a significant increase in both contraction and calcium in RPMI 1640 media. Dose response experiments demonstrated 0.5 mM ßOHB is enough to increase myocyte contraction in the absence of glucose. However, ßOHB has no measurable effects on myocytes cultured in a nutrient rich media, M199, HEPES. Therefore, ßOHB improves single cell excitation-contraction coupling, is protective against hypoxia, and may be a beneficial adaptation for the heart during periods of nutrient scarcity and or metabolic dysregulation.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Ventrículos do Coração/metabolismo , Corpos Cetônicos/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Cálcio/metabolismo , Glucose/metabolismo , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley
2.
J Mol Cell Cardiol ; 108: 86-94, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28526246

RESUMO

RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis. Understanding how loss of LAMP-2 expression leads to cardiomyocyte dysfunction and heart failure has important implications for the treatment of Danon disease as well as a variety of other cardiac disorders associated with impaired autophagy. OBJECTIVE: Elucidate the pathophysiology of cardiac dysfunction in Danon disease. METHODS AND RESULTS: We created hiPSCs from two patients with Danon disease and differentiated those cells into hiPSC-CMs using well-established protocols. Danon hiPSC-CMs demonstrated an accumulation of damaged mitochondria, disrupted mitophagic flux, depressed mitochondrial respiratory capacity, and abnormal gene expression of key mitochondrial pathways. Restoring the expression of LAMP-2B, the most abundant LAMP-2 isoform in the heart, rescued mitophagic flux as well as mitochondrial health and bioenergetics. To confirm our findings in vivo, we evaluated Lamp-2 knockout (KO) mice. Impaired autophagic flux was noted in the Lamp-2 KO mice compared to WT reporter mice, as well as an increased number of abnormal mitochondria, evidence of incomplete mitophagy, and impaired mitochondrial respiration. Physiologically, Lamp-2 KO mice demonstrated early features of contractile dysfunction without overt heart failure, indicating that the metabolic abnormalities associated with Danon disease precede the development of end-stage disease and are not merely part of the secondary changes associated with heart failure. CONCLUSIONS: Incomplete mitophagic flux and mitochondrial dysfunction are noted in both in vitro and in vivo models of Danon disease, and proceed overt cardiac contractile dysfunction. This suggests that impaired mitochondrial clearance may be central to the pathogenesis of disease and a potential target for therapeutic intervention.


Assuntos
Doença de Depósito de Glicogênio Tipo IIb/genética , Doença de Depósito de Glicogênio Tipo IIb/metabolismo , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/metabolismo , Mitofagia/genética , Animais , Técnicas de Inativação de Genes , Doença de Depósito de Glicogênio Tipo IIb/diagnóstico , Hemodinâmica , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Imagem por Ressonância Magnética , Camundongos Knockout , Mitocôndrias Cardíacas/ultraestrutura , Modelos Biológicos , Miócitos Cardíacos/metabolismo
4.
Ann Thorac Surg ; 99(6): 2141-7; discussion 2147-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25886808

RESUMO

BACKGROUND: In 2007 we began a hybrid program for hypoplastic left heart syndrome (HLHS) variants to potentially improve outcome in high-risk patients. During implementation we offered both hybrid and Norwood approaches to all risk categories. The purpose of this study was to perform a comparative analysis of intermediate survival. METHODS: Newborns were evaluated jointly for high-risk characteristics, including birth weight less than 2.5 kg, prematurity (especially < 35 weeks), central nervous system abnormalities, multiorgan failure, intact or severely restrictive atrial septum, severe ventricular dysfunction, and severe atrioventricular valve regurgitation. We prefer Norwood for standard risk and hybrid for high risk, but all groups crossed over into all treatment pathways resulting in the following 5 treatment groups: standard risk Norwood; high-risk Norwood; standard risk hybrid ductal stent (HDS); high-risk hybrid DS; and high-risk hybrid prostaglandin E1 (HPGE). We reviewed all consecutive patients from 2007 to 2012, obtained follow-up, and analyzed the results. RESULTS: Sixty-eight newborns presented (median 2.96 kg, 8 days); 29 (43%) were high and 39 (57%) were standard risk. There were 14 stage I hospital deaths strongly associated with risk: 3 of 39 standard (7.7%) and 11 of 29 high (38%, p = 0.002). Stage I discharge mortality was highest for high-risk Norwood and high-risk HPGE groups (p < 0.001). Actuarial survival up to 5 years demonstrated superior survival for Norwood versus hybrid (78.1% vs 56.4%, p = 0.0182). With risk stratification there was suboptimal survival for all 3 high-risk groups (p = 0.003); HDS fared better than HPGE but had higher birth weight (p < 0.001). CONCLUSIONS: While a risk-stratified approach for HLHS variant patients with selective use of hybrid palliation resulted in acceptable stage I mortality, the longer term mortality for high-risk patients remains higher than for standard risk regardless of treatment modality. Intrinsic patient risk factors (rather than treatment modality) likely determine long-term outcome in experienced centers. Our current high-risk approach has evolved to HPGE application with Norwood conversion whenever deemed medically possible.


Assuntos
Prótese Vascular , Canal Arterial/cirurgia , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimentos de Norwood , Artéria Pulmonar/cirurgia , California/epidemiologia , Feminino , Seguimentos , Humanos , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Lactente , Recém-Nascido , Masculino , Cuidados Paliativos/métodos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento
5.
Stem Cell Res ; 11(3): 1335-47, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24095945

RESUMO

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers.


Assuntos
Miosinas Cardíacas/metabolismo , Separação Celular/métodos , Ventrículos do Coração/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Cadeias Leves de Miosina/metabolismo , Adenoviridae/genética , Miosinas Cardíacas/genética , Diferenciação Celular , Linhagem da Célula , Citometria de Fluxo , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Cadeias Leves de Miosina/genética , Fenótipo , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
6.
Ann Thorac Surg ; 96(3): 910-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23866807

RESUMO

BACKGROUND: Blood product transfusion during cardiopulmonary bypass has been demonstrated to be associated with increased morbidity and mortality in adult cardiac surgery populations. The aim of this study was to characterize the risk-adjusted occurrence of postoperative complications and mortality in relation to intraoperative blood product transfusion in our pediatric cardiac surgery population. METHODS: A retrospective review was performed on 1,631 consecutive cardiopulmonary bypass cases to determine the effects of intraoperative blood product transfusion on selected outcomes. After adjusting for patient and operative risk factors, multivariate analysis was performed to determine the association between blood product transfusion and postoperative complications. Cox proportional hazards model was used to examine the relationship of packed red blood cell transfusion to hospital length of stay. RESULTS: Red blood cell and fresh frozen plasma transfusion was associated with pulmonary complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.05 to 2.28; p=0.03). Red blood cell transfusion also correlated with prolonged hospital stay (p<0.01). Cryoprecipate transfusion was associated with postoperative pulmonary complications (adjusted odds ratio, 1.79; 95% confidence interval, 1.13 to 2.55; p=0.01), but decreased incidence of 30-day mortality (adjusted odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.02). Platelet transfusion was associated with decreased 30-day mortality (adjusted odds ratio, 0.51; 95% confidence interval, 0.28 to 0.93; p=0.04), but not overall mortality. CONCLUSIONS: Blood product transfusion was associated with an increased incidence of postoperative pulmonary complications and prolonged hospital length of stay, but not overall mortality. These findings suggest that minimizing blood product transfusion would be beneficial in the pediatric cardiopulmonary bypass surgery patient population.


Assuntos
Ponte Cardiopulmonar/métodos , Transfusão de Eritrócitos/efeitos adversos , Mortalidade Hospitalar/tendências , Complicações Pós-Operatórias/mortalidade , Adolescente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Causas de Morte , Criança , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Transfusão de Eritrócitos/métodos , Feminino , Seguimentos , Humanos , Incidência , Lactente , Cuidados Intraoperatórios/métodos , Masculino , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
7.
Circulation ; 127(16): 1702-11, 2013 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-23538380

RESUMO

BACKGROUND: Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. METHODS AND RESULTS: This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. CONCLUSIONS: Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.


Assuntos
Transplante de Coração , Coração Auxiliar , Tamanho Corporal , Causas de Morte , Criança , Pré-Escolar , Comorbidade , Ensaios de Uso Compassivo , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/cirurgia , Cardiopatias/sangue , Cardiopatias/cirurgia , Transplante de Coração/estatística & dados numéricos , Hemorragia/epidemiologia , Humanos , Hiperbilirrubinemia/epidemiologia , Lactente , Nefropatias/epidemiologia , Hepatopatias/epidemiologia , Masculino , Mortalidade , Insuficiência de Múltiplos Órgãos/epidemiologia , Modelos de Riscos Proporcionais , Risco , Acidente Vascular Cerebral/epidemiologia , Taxa de Sobrevida , Resultado do Tratamento , Listas de Espera
8.
N Engl J Med ; 367(6): 532-41, 2012 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-22873533

RESUMO

BACKGROUND: Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS: We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS: For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS: Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).


Assuntos
Insuficiência Cardíaca Sistólica/terapia , Transplante de Coração , Coração Auxiliar , Adolescente , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca Sistólica/mortalidade , Coração Auxiliar/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Desenho de Prótese , Taxa de Sobrevida , Listas de Espera
9.
Ann Thorac Surg ; 93(4): 1274-8; discussion 1278-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22381450

RESUMO

BACKGROUND: The optimal surgical procedure for repair of supravalvar aortic stenosis (SVAS) remains uncertain. Proponents of multisinus repair techniques suggest improved outcomes compared with the single-patch technique. We evaluated the outcomes after an extended single-patch technique for relief of SVAS. METHODS: A cross-sectional retrospective analysis was performed of all SVAS patients who underwent repair from 1996 to 2009. Patient, procedural, and hospital course data were obtained through a review of the medical records. At follow-up, patients were evaluated for residual SVAS gradient, valvar aortic stenosis, aortic insufficiency, and need for reintervention. RESULTS: Twenty-two patients (mean age, 2.4 ± 2.4 years) underwent repair of SVAS (discrete form, 59%). Mean preoperative peak gradient was 77 ± 27 mm Hg (range, 20 to 139 mm Hg). There were no hospital deaths. Median postoperative length of stay was 5 days (range, 3 to 68 days). Mean follow-up was 4.1 ± 3.5 years (range, 0.7 to 13 years). Follow-up Doppler echocardiography revealed a peak left ventricular outflow tract gradient of 10 ± 12 mm Hg (range, 0 to 41 mm Hg). No patient had significant valvar aortic stenosis or insufficiency. Two patients (9%) required catheter-based reintervention that was unrelated to the SVAS repair. CONCLUSIONS: This study demonstrates that a simple, extended single-patch technique for repair of SVAS provides excellent medium-term results. A durable reduction in gradient with low complication and recurrence rates can be achieved without the need for more complicated multisinus patch repairs.


Assuntos
Estenose Aórtica Supravalvular/cirurgia , Aorta/cirurgia , Estenose Aórtica Supravalvular/diagnóstico , Aortografia , Prótese Vascular , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento
10.
Ann Thorac Surg ; 93(2): 614-8; discussion 619, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22197533

RESUMO

BACKGROUND: Single ventricle hearts can be surgically palliated by a series of operations culminating in the Fontan procedure, which establishes a total cavopulmonary connection. The second-stage procedure creates a physiologic connection between the superior vena cava and the pulmonary artery. METHODS: From 1998 to 2010, 557 patients with single ventricle heart disease underwent second-stage surgical palliation. This cohort was retrospectively analyzed to assess patient outcome by a number of anatomic, physiologic, and procedural factors. The analysis excluded patients undergoing hybrid first-stage procedures. RESULTS: The median age at operation was 165 days (range, 59 days to 49 years). The most common anatomic subtypes were hypoplastic left heart syndrome (52%), tricuspid atresia (12%), unbalanced atrioventricular septal defect (10%), double inlet left ventricle (9%), or other (17%). Left ventricular hypoplasia was present in 70%. A hemi-Fontan procedure was done in 89%, and 11% received a bidirectional Glenn. Concomitant atrioventricular valve repair was necessary in 9%. Early mortality was 4.7%, and 5.9% died after discharge but before Fontan. No early or late deaths occurred in patients with tricuspid atresia and double inlet left ventricle. Multivariate analysis demonstrated ventricular dysfunction, atrioventricular valve regurgitation, and unbalanced atrioventricular septal defect were significant adverse risk factors for survival to Fontan. CONCLUSIONS: Second-stage palliation can be performed at low risk for patients with left ventricular dominance, but significant risk remains for patients with left ventricular hypoplasia and unbalanced atrioventricular septal defect. Atrioventricular valve insufficiency is a persistent problem that has not been neutralized by repair strategies.


Assuntos
Técnica de Fontan , Ventrículos do Coração/anormalidades , Cuidados Paliativos , Artéria Pulmonar/cirurgia , Veia Cava Superior/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Técnica de Fontan/estatística & dados numéricos , Defeitos dos Septos Cardíacos/epidemiologia , Defeitos dos Septos Cardíacos/cirurgia , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Ventrículos do Coração/cirurgia , Síndrome de Heterotaxia/epidemiologia , Síndrome de Heterotaxia/cirurgia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/epidemiologia , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Hipóxia/etiologia , Hipóxia/cirurgia , Lactente , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Atresia Tricúspide/epidemiologia , Atresia Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/cirurgia , Adulto Jovem
11.
World J Pediatr Congenit Heart Surg ; 3(3): 382-4, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23804875

RESUMO

Right pulmonary artery to left atrial fistula is a rare congenital vascular anomaly which usually presents with cyanosis, clubbing, dyspnea, and signs and symptoms of a right to left shunt. Paradoxical embolism to the brain resulting in cerebral abscess formation and death is a rare and ominous complication that has been described. We describe an unusual presentation with abdominal pain resulting from splenic infarction.

12.
Pediatr Cardiol ; 32(5): 599-606, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21347834

RESUMO

Tricuspid valve regurgitation (TR) remains an obstacle for staged palliation of hypoplastic left heart syndrome (HLHS). Because previous results from our institution suggested that posterior leaflet obliteration (PLO) is effective in tricuspid valve repair (TVR), we preferentially used this method. This report analyzes the effect of this preference on repair success and patient survival. All HLHS patients with 3-4+ preoperative TR undergoing TVR between 2002 and 2007 were retrospectively analyzed. Clinical and echocardiographic data were used to determine outcomes. Seventy-one percent (17 of 24) of patients had success at early outcome; the remaining 29% experienced early failure. Sixty-three percent (15 of 24) of patients demonstrated success at late outcome. Early outcome status was found to be a predictor of late outcome status (OR 22.9, P = 0.0037). Overall survival was 71% (17 of 24). Survival could not be shown to be associated with early or late outcome status (odds ratio = 0.96). A preference for PLO was found to give improved, long-lasting results for HLHS patients. Success at immediate outcome was predictive of success with time. PLO has the advantage of being simple and reproducible and produces good outcomes in this challenging group. Continued follow-up will be necessary to confirm long-term outcomes.


Assuntos
Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Pré-Escolar , Feminino , Seguimentos , Técnica de Fontan , Mortalidade Hospitalar , Humanos , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Lactente , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Técnicas de Sutura , Insuficiência da Valva Tricúspide/mortalidade , Função Ventricular Direita/fisiologia
13.
J Thorac Cardiovasc Surg ; 141(2): 419-24, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20709336

RESUMO

OBJECTIVE: As outcomes for the Fontan procedure have improved, it has become more difficult to select between a single-ventricle repair or biventricular repair for patients with complex anatomy and 2 ventricles. However, late complications after the Fontan procedure remain a concern. Our strategy, which has favored an aggressive preferential approach for biventricular repair in these patients, has also been applied to patients initially treated on a single-ventricle track elsewhere. METHODS: Nine patients (4 male patients) who had previously undergone the Fontan procedure (n=3) or bidirectional cavopulmonary shunting (n=6) with intent for a later Fontan procedure were referred to our center for complex 1½- or 2-ventricle repair over the last 10 years. Indications for conversion in these patients were protein-losing enteropathy (n=2), pulmonary arteriovenous malformation (n=1), and preference for biventricular anatomy (n=6). The conversion mainly consisted of takedown of the Fontan procedure or bidirectional cavopulmonary shunt connection, reconstruction of 1 or both of venae cavae, creation of an intraventricular pathway for left ventricular output, and placement of a right ventricle-pulmonary artery conduit (Rastelli-type operation). RESULTS: Five patients underwent 1½-ventricle repair, and 4 had complete biventricular repair. Median cardiopulmonary bypass and aortic crossclamp times were 202 minutes (range, 169-352 minutes) and 129 minutes (range, 100-168 minutes), respectively. There were 2 early deaths and 1 late death. At a median follow-up of 27 months (range, 3.3-99.8 months), all survivors are in New York Heart Association class I. CONCLUSIONS: Patients initially treated with intent to perform single-ventricle palliation can be converted to 1½- or 2-ventricle physiology with acceptable outcomes.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/cirurgia , Ponte Cardiopulmonar , Constrição , Feminino , Técnica de Fontan/efeitos adversos , Técnica de Fontan/mortalidade , Cardiopatias Congênitas/mortalidade , Ventrículos do Coração/anormalidades , Humanos , Masculino , Michigan , Cuidados Paliativos , Seleção de Pacientes , Fatores de Tempo , Resultado do Tratamento
14.
J Thorac Cardiovasc Surg ; 141(1): 200-6, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20621315

RESUMO

OBJECTIVE: Primary biventricular repair for left ventricular outflow tract obstruction and ventricular septal defect remains challenging. The intermediate-term outcomes and risk factors for mortality remain undefined. METHODS: All patients undergoing primary biventricular repair of left ventricular outflow tract obstruction and ventricular septal defect from 1995 to 2008 at the C. S. Mott Children's Hospital, University of Michigan Health Systems were analyzed. RESULTS: Thirty-one patients (mean age, 18 days; 20 male) with a median follow-up of 6.7 years (range, 0.3-13.5 years) were identified. The ventricular septal defect was enlarged in 15 patients, and a limited atrial septal defect was constructed in 16 patients. There were 6 hospital and 2 late deaths. Ten-year patient survival was 72.3%. Lower body weight (P = .040), complete atrial septal defect closure (P = .026), and longer cardiopulmonary bypass time (P = .026) were risk factors of hospital mortality. An atrial septal defect was patent in 16 patients at discharge, 2 of whom required later surgical closure. Relief of recurrent left ventricular outflow tract obstruction was performed in 1 patient. No patient required pacemaker implantation. Five-year freedom from right ventricle-to-pulmonary artery conduit replacement was 39.3%. Smaller-sized conduit (P = .020) and use of aortic allograft (P = .048) were risk factors for early failure. CONCLUSION: Primary biventricular repair for patients with left ventricular outflow tract obstruction and ventricular septal defect provides good early and intermediate-term outcomes. Maintaining a small atrial septal defect may improve hospital mortality. Selective ventricular septal defect enlargement and careful construction of the intraventricular pathway result in a low incidence of recurrent left ventricular outflow tract obstruction, as well as avoidance of heart block. Maximizing valve diameter and avoiding aortic allografts may lengthen conduit longevity.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Comunicação Interventricular/cirurgia , Obstrução do Fluxo Ventricular Externo/cirurgia , Aorta/transplante , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Feminino , Comunicação Interatrial/complicações , Comunicação Interatrial/cirurgia , Comunicação Interventricular/complicações , Comunicação Interventricular/mortalidade , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Michigan , Procedimentos de Norwood , Modelos de Riscos Proporcionais , Artéria Pulmonar/cirurgia , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/mortalidade
15.
J Heart Lung Transplant ; 30(1): 1-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21145473

RESUMO

BACKGROUND: Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation. METHODS: Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available. RESULTS: Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR. CONCLUSIONS: This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.


Assuntos
Cardiomiopatia Dilatada/cirurgia , Cardiopatias Congênitas/cirurgia , Transplante de Coração/instrumentação , Coração Auxiliar , Miocardite/cirurgia , Adolescente , Fatores Etários , Superfície Corporal , Cardiomiopatias/cirurgia , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Transplante de Coração/mortalidade , Coração Auxiliar/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , América do Norte , Estudos Retrospectivos , Fatores de Risco , Choque Cardiogênico/cirurgia , Resultado do Tratamento
16.
Ann Thorac Surg ; 90(1): 36-41, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20609744

RESUMO

BACKGROUND: Mitral valve repair is the preferred approach for congenital mitral valve stenosis in children. However, repairs in this population remain challenging. METHODS: From 2001 to 2009, mitral valve repair was attempted in 20 consecutive congenital mitral valve stenosis patients. The median age and body weight at operation were 1.4 +/- 1.9 years and 7.4 +/- 4.1 kg, respectively. Multiple level left-side heart obstruction was present in 14 patients (70%). Moderate or more mitral insufficiency was present in 5 patients. RESULTS: The main etiology of the stenosis was valvular in 5 patients, supravalvular mitral ring in 4, single or predominant papillary muscle in 9, and hammock mitral valve in 2. Freedom from hospital death or transplantation was 85% (17 of 20). Two patients required replacement before discharge. In the 15 successfully repaired patients, mean mitral valve inflow pressure gradient improved from 13.9 +/- 2.7 mm Hg to 5.5 +/- 1.6 mm Hg (p < 0.0001). There were no late deaths at a mean follow-up of 46 +/- 31 months (range, 6.3 to 98.5). One patient required a second repair, and no patient has required replacement. At the last follow-up, mean mitral valve inflow pressure gradient was 7.5 +/- 4.1 mm Hg, and moderate or more mitral insufficiency was detected in 2 patients. CONCLUSIONS: Mitral valve repair for congenital mitral valve stenosis can be performed in this challenging population of patients with good early survival and freedom from transplantation. Conditional follow-up for successfully repaired patients demonstrates preserved mitral valve function without need for replacement.


Assuntos
Estenose da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valva Mitral/anatomia & histologia , Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/diagnóstico , Resultado do Tratamento
17.
Ann Thorac Surg ; 90(2): 610-3, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20667359

RESUMO

BACKGROUND: Pulmonary allografts are commonly used in the reconstruction of the right ventricular outflow tract. However, in pediatric patients, allografts that are small enough are often unavailable. To downsize larger, more readily available conduits, one leaflet can be excised, forming a bicuspid valve. The aim of this study was to assess the intermediate-term durability of bicuspidized allografts compared with standard allografts. METHODS: Forty-seven patients who received a bicuspidized allograft from 1998 to 2008 were compared with 51 patients who received a standard allograft during the same time period. Outcome measures included need for and timing of reintervention, degree of pulmonary stenosis, insufficiency at most recent follow-up, and survival. RESULTS: On average, the bicuspidized allograft patients were younger, weighed less, and received smaller valves more frequently placed in a heterotopic position than the standard allograft patients. The mean peak gradient across the conduit and the degree of pulmonary insufficiency at discharge were similar between the comparison groups. No statistical differences in need for or timing of reintervention were observed between the surgical groups. CONCLUSIONS: Bicuspidized allografts performed similarly to that of standard allografts with regard to the need for reintervention, the development of stenosis or regurgitation, and patient survival. Based on this patient sample, the bicuspidized allograft technique appears to provide an excellent option to expand the availability of small-sized allografts for the reconstruction of the right ventricular outflow tract.


Assuntos
Cardiopatias Congênitas/cirurgia , Valva Pulmonar/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Pré-Escolar , Feminino , Valvas Cardíacas/transplante , Humanos , Masculino , Valva Pulmonar/transplante , Estudos Retrospectivos , Fatores de Tempo
18.
Ann Thorac Surg ; 89(6): 1827-32; discussion 1832, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20494035

RESUMO

BACKGROUND: Although good intermediate-term results for the Ross procedure in adults and older children have been reported, only short-term outcomes of this procedure in neonates and infants have been published. The objective of this study was to review our intermediate-term results of the Ross procedure for neonates and infants. METHODS: The records of all 31 neonates and infants undergoing a Ross procedure between March 1993 and June 2008 were reviewed. Major study outcomes included patient survival, autograft function, and need for reoperation. RESULTS: The median age at the time of operation was 18 days, and median weight was 3.95 kg. Fifteen patients had aortic stenosis with or without insufficiency, 2 patients had isolated severe aortic insufficiency, and 14 patients had aortic stenosis with other left-side heart lesions, such as arch obstruction or mitral valve disease. Twenty-five patients required aortic annular enlargement (Ross-Konno procedure), and 14 required concomitant arch or mitral valve surgery. There were 5 early and 2 late deaths at a median follow-up of 6.0 years (range, 1.1 to 15.4 years). All early deaths were in patients requiring concomitant arch or mitral valve repair. Actuarial survival rate was 76.7% at 5, 10, and 15 years. There were 19 reinterventions, including 2 procedures on the autograft. Overall freedom from reoperation was 59.1% at 5 years and 50.6% at 10 years. Freedom from autograft reoperation was 95.2% at 5 and 10 years and 63.5% at 15 years. CONCLUSIONS: The Ross procedure for neonates and infants has good intermediate-term results with low mortality and acceptable rates of reintervention. The patients requiring concomitant arch or mitral valve surgery have higher initial operative risks although conditional survival remains good.


Assuntos
Valva Aórtica , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
J Thorac Cardiovasc Surg ; 140(1): 161-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20434179

RESUMO

OBJECTIVES: Heart transplantation in patients with adult congenital heart disease is increasing, yet no large studies have defined how this subgroup differs from other adult recipients. We investigated outcomes and risk factors for mortality and retransplantation among patients with adult congenital heart disease compared with adult recipients. METHODS: A review was performed of 18- to 45-year-old patients undergoing heart transplantation from 1990-2008 reported to the United Network for Organ Sharing database. Trends were compared between 2 eras: era 1 (1990-1998) and era 2 (1999-2008). Multivariable semiparametric hazard models identified factors associated with time-related death and retransplantation. RESULTS: Of 8496 patients identified, 575 had adult congenital heart disease. The prevalence of heart transplantation among adult recipients decreased by 28% over time (P < .001) and increased among patients with adult congenital heart disease by 41% (P < .001). Induction therapy use was less in patients with adult congenital heart disease (66%) compared with that seen in adult recipients (71%, P = .02). Steroid maintenance was less in patients with adult congenital heart disease (92%) compared with that seen in adult recipients (97%, P < .001). Post-heart transplantation survival among adult recipients improved over time (P = .02) but not among patients with adult congenital heart disease (P = .81). Overall post-heart transplantation mortality (P = .006) and retransplantation (P = .03) were significantly higher for patients with adult congenital heart disease than for adult recipients, mainly because of an early hazard phase. Adult congenital heart disease was a risk factor for both death (P < .001) and retransplantation (P = .04). Any induction therapy and steroid maintenance was associated with improved survival for all recipients (P = .001). CONCLUSIONS: Adult congenital heart disease represent an increasing proportion of heart transplant recipients. Compared with adult recipients, patients with adult congenital heart disease experience higher post-heart transplantation mortality and retransplantation. Immunosuppression differs among patients with adult congenital heart disease and adult recipients. Further studies should investigate whether post-heart transplantation outcomes would be improved by more aggressive induction therapy or judicious steroid tapers.


Assuntos
Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Transplante de Coração/mortalidade , Doadores de Tecidos/provisão & distribução , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Distribuição de Qui-Quadrado , Bases de Dados como Assunto , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
20.
Ann Thorac Surg ; 89(2): 537-42; discussion 542-3, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20103338

RESUMO

BACKGROUND: The combination of an atrioventricular septal defect with a common atrioventricular junction guarded by a common valve, and double-outlet right ventricle, is a rare lesion that presents a challenge for surgical repair. This report describes our surgical approach and results in 16 patients undergoing biventricular repair for such a combination of lesions. METHODS: A retrospective analysis was performed for all patients undergoing biventricular repair of atrioventricular septal defect with common atrioventricular valve and double-outlet right ventricle between 1991 and 2008. Patients with tetralogy of Fallot and common atrioventricular valve were excluded from analysis. Early and actuarial outcomes were evaluated using the chi(2) test for categorical variables and Wilcoxon rank sum for ordinal variables. RESULTS: The median age at operation was 16 months. Heterotaxy syndrome was present in 12 of the 16 patients (9 right isomerism and 3 left isomerism), and 6 had concurrent totally anomalous pulmonary venous connections. Primary repair was achieved in 6 patients, and 10 underwent one or more prior operations (most frequently a shunt, banding of the pulmonary trunk, or repair of the anomalous pulmonary venous connections). Enlargement of the ventricular septal defect by resection of the muscular outlet septum was required in 11 patients, in whom the ventricular septal defect emptied entirely or primarily to the inlet of the right ventricle. A conduit was placed from the right ventricle to the pulmonary arteries in 13. There was 1 death before discharge from hospital, 1 late death, and 2 episodes of heart block. Among survivors, follow-up was complete with a median follow-up of 66 months. No patient had late obstruction of the left ventricular outflow tract. The presence of heterotaxy with totally anomalous pulmonary venous connections was associated with combined mortality and significant morbidity (p = 0.008). CONCLUSIONS: Although technically challenging, the surgical repair can be accomplished with acceptable early results. Heterotaxy syndrome, with concurrent anomalous connections of the pulmonary veins, represented the strongest identified risk factor for death or significant complication.


Assuntos
Dupla Via de Saída do Ventrículo Direito/cirurgia , Comunicação Interatrial/cirurgia , Comunicação Interventricular/cirurgia , Valva Mitral/anormalidades , Valva Tricúspide/anormalidades , Implante de Prótese Vascular , Ponte Cardiopulmonar , Pré-Escolar , Comorbidade , Dupla Via de Saída do Ventrículo Direito/mortalidade , Feminino , Átrios do Coração/cirurgia , Comunicação Interatrial/mortalidade , Comunicação Interventricular/mortalidade , Septos Cardíacos/cirurgia , Ventrículos do Coração/cirurgia , Mortalidade Hospitalar , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Veias Pulmonares/anormalidades , Estudos Retrospectivos , Fatores de Risco , Situs Inversus/mortalidade , Situs Inversus/cirurgia , Análise de Sobrevida , Técnicas de Sutura
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