RESUMO
BACKGROUND: This study evaluated right ventricular (RV) volume, strain, and morphology using cardiac 4-dimensional computed tomography (4D-CT) to detect pulmonary hypertension (PH) in adults with repaired tetralogy of Fallot (TOF) scheduled for transcatheter pulmonary valve implantation (TPVI). METHODS AND RESULTS: Using cardiac 4D-CT data, we calculated RV strain in 3 different geometries and RV outflow tract (RVOT) mass in 42 patients with repaired TOF. We compared RV strain and RVOT mass between patients with and without PH. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance of these measurements for identifying PH. Four-chamber (4ch) strain was significantly smaller for patients with (n=10) than without (n=32) PH (8.8±1.7% vs. 11.1±2.4%, respectively; P<0.01), whereas RVOT mass was significantly larger in the PH group (12.5±3.5 vs. 9.2±3.2 cm2; P<0.01). ROC analysis of the diagnostic performance revealed that the respective sensitivity and specificity was 70% and 84% (area under the curve [AUC]=0.784) for 4ch strain of 8.8%; 80% and 69% (AUC=0.766) for RVOT mass of 10.7 cm2; and 80% and 81% (AUC=0.844) for a 4ch strain/RVOT mass ratio of 0.97. CONCLUSIONS: RVOT mass and 4ch strain obtained from cardiac 4D-CT may be helpful for identifying PH in patients with repaired TOF.
RESUMO
PURPOSE: To assess right heart diastolic energy loss (EL) as a cardiac workload and evaluate its association with major cardiac events (MACE) in adult patients with pulmonary atresia with an intact ventricular septum (PAIVS). METHODS: We retrospectively enrolled and compared 30 consecutive adult patients (18 with PAIVS and 12 with pulmonary stenosis [PS] as controls) who underwent right ventricular (RV) outflow tract reconstruction and 4D flow MRI. EL, conventional parameters on MRI, and the severity of tricuspid regurgitation (TR) on echocardiography were assessed. We also evaluated the association between MACE including arrhythmias, heart failure, surgical intervention, and imaging parameters in adults with PAIVS. RESULTS: Patients with PAIVS were younger, had a higher diastolic EL/cardiac output (CO) ratio, and had a more significant TR than those with PS (controls). However, RV volume, ejection fraction (EF), and pulmonary regurgitation (PR) severity did not differ between the two groups. Higher RV end-diastolic pressure (EDP) and lower cardiac index (CI) correlated with the diastolic EL/CO in patients with PAIVS. Univariate logistic analysis demonstrated that older age and a higher diastolic EL/CO ratio were important factors for MACE in adults with PAIVS (P = 0.048, 0.049). CONCLUSION: A higher diastolic EL/CO ratio was associated with a higher RV EDP and lower CI. A high diastolic EL/CO ratio is also associated with MACE in adults with PAIVS. Even in adults with normal RV volume and EF, the right heart EL was elevated, suggesting an excessive right-sided cardiac workload that integrated both afterload and preload beyond the RV size in adult patients with PAIVS.
RESUMO
AIM: In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels. METHODS: We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50 U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50 U/L were defined as improved (n = 33). RESULTS: Patients with GGT levels ≥50 U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6 mg/dL), AST (22 vs. 28 U/L), and ALT (18 vs. 27 U/L) levels than nonimproved cases (n = 29, p < 0.05), and the change in platelet count (-0.5 vs. -3.0 × 10-4/µL) was significantly lower in the latter (p = 0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50 U/L compared to cases not treated with UDCA (18.2%, p = 0.04). CONCLUSION: In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.
RESUMO
BACKGROUND: Peripheral pulmonary stenosis (PPS) is a condition characterized by the narrowing of the pulmonary arteries, which impairs blood flow to the lung. The mechanisms underlying PPS pathogenesis remain unclear. Thus, the aim of this study was to investigate the genetic background of patients with severe PPS to elucidate the pathogenesis of this condition. METHODS AND RESULTS: We performed genetic testing and functional analyses on a pediatric patient with PPS and Williams syndrome (WS), followed by genetic testing on 12 patients with WS and mild-to-severe PPS, 50 patients with WS but not PPS, and 21 patients with severe PPS but not WS. Whole-exome sequencing identified a rare PTGIS nonsense variant (p.E314X) in a patient with WS and severe PPS. Prostaglandin I2 synthase (PTGIS) expression was significantly downregulated and cell proliferation and migration rates were significantly increased in cells transfected with the PTGIS p.E314X variant-encoding construct when compared with that in cells transfected with the wild-type PTGIS-encoding construct. p.E314X reduced the tube formation ability in human pulmonary artery endothelial cells and caspase 3/7 activity in both human pulmonary artery endothelial cells and human pulmonary artery smooth muscle cells. Compared with healthy controls, patients with PPS exhibited downregulated pulmonary artery endothelial prostaglandin I2 synthase levels and urinary prostaglandin I metabolite levels. We identified another PTGIS rare splice-site variant (c.1358+2T>C) in another pediatric patient with WS and severe PPS. CONCLUSIONS: In total, 2 rare nonsense/splice-site PTGIS variants were identified in 2 pediatric patients with WS and severe PPS. PTGIS variants may be involved in PPS pathogenesis, and PTGIS represents an effective therapeutic target.
Assuntos
Sistema Enzimático do Citocromo P-450 , Oxirredutases Intramoleculares , Estenose da Valva Pulmonar , Síndrome de Williams , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Movimento Celular , Proliferação de Células , Células Cultivadas , Códon sem Sentido , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Sequenciamento do Exoma , Predisposição Genética para Doença , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Fenótipo , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/enzimologia , Estenose da Valva Pulmonar/genética , Estenose da Valva Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Síndrome de Williams/genética , Síndrome de Williams/fisiopatologia , Síndrome de Williams/enzimologiaRESUMO
Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect. Using whole-exome sequencing, the c.1617del variant was identified in two siblings with PTA in a Japanese family and in three of the 26 DNAs obtained from Japanese individuals with PTA. The c.1617del of TMEM260 has been found only in East Asians, especially Japanese and Korean populations, and the frequency of this variant in PTA is estimated to be next to that of the 22q11.2 deletion, the most well-known genetic cause of PTA. Phenotype of patients with c.1617del appears to be predominantly in the heart, although TMEM260 is responsible for structural heart defects and renal anomalies syndrome (SHDRA). The mouse TMEM260 variant (p.W535Cfs*56), synonymous with the human variant (p.W539Cfs*9), exhibited truncation and downregulation by western blotting, and aggregation by immunocytochemistry. In situ hybridization demonstrated that Tmem260 is expressed ubiquitously during embryogenesis, including in the development of cardiac OFT implicated in PTA. This expression may be regulated by a ~ 0.8 kb genomic region in intron 3 of Tmem260 that includes multiple highly conserved binding sites for essential cardiac transcription factors, thus revealing that the c.1617del variant of TMEM260 is the major single-gene variant responsible for PTA in the Japanese population.
Assuntos
Cardiopatias Congênitas , Proteínas de Membrana , Animais , Feminino , Humanos , Masculino , Camundongos , Povo Asiático/genética , População do Leste Asiático , Sequenciamento do Exoma , Predisposição Genética para Doença , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Japão , Proteínas de Membrana/genética , Linhagem , FenótipoRESUMO
BACKGROUND: Chronic liver disease leads to liver fibrosis, and an accurate diagnosis of the fibrosis stage is crucial for medical management. Connective tissue growth factor (CTGF) is produced by endothelial cells and platelets and plays a central role in inducing fibrosis in various organs. In the present study, we tested the validity of measuring the serum levels of two types of CTGF to estimate the biopsy-confirmed liver fibrosis stage. METHODS: We used two detection antibodies targeting the N- and C-terminal of CTGF to measure the serum levels of two forms of CTGF consisting of its full length and its N-terminal fragment. We analyzed the level of CTGF (via enzyme-linked immunosorbent assay) and the liver fibrosis stage in 38 patients with Fontan-associated liver disease (FALD) (26 cases of which were diagnosed pathologically). Correlations were determined by multivariate analysis and the area under the receiver operating characteristic curve. The 65 patients with nonalcoholic fatty liver disease (NAFLD) were included as a disease control group for examination. RESULTS: Full-length CTGF was significantly inversely correlated with liver fibrosis in patients with FALD. Although the platelet count was also associated with the liver fibrosis stage, full-length CTGF was more closely correlated with the fibrosis stage. Furthermore, the level of full-length CTGF was inversely associated with high central venous pressure. Conversely, the serum level of CTGF was not correlated with the fibrosis stage in NAFLD. CONCLUSION: The serum level of full-length CTGF may be useful for estimating the liver fibrosis stage in patients with FALD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Crescimento do Tecido Conjuntivo , Células Endoteliais , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologiaRESUMO
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.
Assuntos
Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/genética , Endoglina/genética , Japão/epidemiologia , Mutação , Testes Genéticos , Receptores de Activinas Tipo II/genéticaRESUMO
PURPOSE: To assess flow energy loss (EL) pattern inside the pulmonary circulation in adult patients with repaired tetralogy of Fallot (TOF), particularly in TOF with pulmonary stenosis (PS) and pulmonary regurgitation (PR), as a cardiac workload parameter and its relationship to symptoms and major adverse cardiovascular events (MACE). METHODS: Prospectively, 51 consecutive TOF adults after intracardiac repair, who underwent four-dimensional flow magnetic resonance imaging, were enrolled. All of them had significant PR (PR regurgitant fraction >25â¯%). TOF patients who had already reached the conventional criteria were excluded. We defined MACE as the following: 1) fatal arrhythmias, 2) sudden cardiac death, 3) surgical pulmonary valvular repair (PVR), 4) right heart failure (HF) needing diuretics and/or hospitalization within 2â¯years. RESULTS: A total of 15 patients had MACE; 1) 10 patients underwent PVR within 2â¯years, 2) 2 patients had ventricular tachycardia, and 3) 6 patients developed right HF (overlapped). Right ventricular (RV) end diastolic volume index (EDVI), RV end systolic volume index (ESVI), average EL/cardiac output (CO), and diastolic EL/CO in patients with MACE were greater than ones without MACE. On a multivariate logistic analysis, the diastolic EL/CO ratio and RVEDVI had the highest odds with MACE in all TOF (odds ratio, 40.7 and 1.15. 95%CI, 1.83-905 and 1.02-13.0; p-value, 0.02 and 0.03). In sub-analysis within 29 patients with moderate PS with PR, and 10 patients with MACE showed higher diastolic EL/CO. Average and diastolic EL/CO negatively correlated with RV ejection fraction (EF) in this sub-analysis. CONCLUSIONS: High EL, particularly, high diastolic EL/CO, were the important factors for MACE in adult TOF. Higher diastolic EL/CO was also related to lower RV EF and deteriorated RV function in adult TOF with PS and PR. Right-sided EL can be a sensitive marker of excessive cardiac workload which integrates both afterload and preload in adult patients with TOF, beyond the RV size.
Assuntos
Insuficiência Cardíaca , Insuficiência da Valva Pulmonar , Estenose da Valva Pulmonar , Valva Pulmonar , Tetralogia de Fallot , Adulto , Humanos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Carga de Trabalho , Estenose da Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/cirurgia , Insuficiência Cardíaca/etiologia , Imageamento por Ressonância Magnética , Função Ventricular DireitaRESUMO
BACKGROUND: α/ß- and ß-blockers are essential in pregnant women's perinatal congenital heart disease management. Nevertheless, data on the effects of α/ß- and ß-blockers on pregnant women and fetuses are limited. We examined the risks of neonatal hypoglycemia and small for gestational age (SGA) associated with maternal exposure to α/ß- and ß-blockers.MethodsâandâResults: All consecutive pregnant women with heart disease admitted to our hospital between January 2014 and October 2020 were included. Of 306 pregnancies (267 women), 32 were in the α/ß-blocker group, 11 were in the ß-blocker group, and 263 were in the control group. All 32 pregnancies in the α/ß-blocker group were treated with carvedilol. In the ß-blocker group, 4 women were treated with bisoprolol, 3 were treated with propranolol, 2 were treated with atenolol, 1 was treated with metoprolol, and 1 was treated nadolol. The incidence of neonatal hypoglycemia was higher in pregnant women taking carvedilol than in the control group (P=0.025). SGA was observed significantly more frequently in pregnant women taking ß-blockers than in the carvedilol and control groups (P<0.001). CONCLUSIONS: Carvedilol administration during pregnancy was associated with neonatal hypoglycemia; however, it did not occur in a time- or dose-dependent manner. Routine monitoring of blood glucose levels in newborns exposed to α/ß- and ß-blockers is essential.
Assuntos
Antagonistas Adrenérgicos beta , Hipoglicemia , Feminino , Recém-Nascido , Humanos , Gravidez , Carvedilol/efeitos adversos , Idade Gestacional , Antagonistas Adrenérgicos beta/efeitos adversos , Metoprolol , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologiaRESUMO
OBJECTIVE: Fontan-associated liver disease (FALD) is widely recognised as a common complication in patients long after the Fontan operation. However, data on the predictors of FALD that can guide its screening and management are lacking. The present study aimed to identify the predictors of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in post-Fontan patients. METHODS: This was a multi-institutional retrospective cohort study. Clinical data of all perioperative survivors of Fontan operation before 2011 who underwent postoperative catheterisation were collected through a retrospective chart review. RESULTS: A total of 1117 patients (538 women, 48.2%) underwent their first Fontan operation at a median age of 3.4 years. Postoperative cardiac catheterisation was conducted at a median of 1.0 year. During a median follow-up period of 10.3 years, 67 patients (6.0%) died; 181 (16.2%) were diagnosed with liver fibrosis, 67 (6.0%) with LC, 54 (4.8%) with focal nodular hyperplasia and 7 (0.6%) with HCC. On multivariable analysis, high central venous pressure (CVP) (HR, 1.28 (95% CI 1.01 to 1.63) per 3 mm Hg; p=0.042) and severe atrioventricular valve regurgitation (HR, 6.02 (95% CI 1.53 to 23.77); p=0.010) at the postoperative catheterisation were identified as independent predictors of LC/HCC. CONCLUSIONS: Patients with high CVP and/or severe atrioventricular valve regurgitation approximately 1 year after the Fontan operation are at increased risk of developing advanced liver disease in the long term. Whether therapeutic interventions to reduce CVP and atrioventricular valve regurgitation decrease the incidence of advanced liver disease requires further elucidation.
Assuntos
Carcinoma Hepatocelular , Técnica de Fontan , Cardiopatias Congênitas , Neoplasias Hepáticas , Humanos , Feminino , Pré-Escolar , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Estudos Retrospectivos , Técnica de Fontan/efeitos adversos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/complicações , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Fatores de Risco , Resultado do TratamentoRESUMO
Progression to acute kidney injury (AKI) under treatment in adult congenital heart disease (ACHD) patients with heart failure is associated with poor prognosis, early detection and interventions are necessary. We aimed to explore the utility of urinary liver-type fatty acid binding protein (L-FABP) in ACHD patients hospitalized for acute decompensated heart failure (ADHF). We prospectively evaluated hemodynamic, biochemical data, and urinary biomarkers including urinary L-FABP in ACHD patients hospitalized in our institution from June 2019 to March 2022. The primary outcomes were the development of AKI and death. AKI was defined as serum creatinine level increased by 0.3 mg/dl or more within 5 days after hospitalization. A total of 104 ADHF patients aged 31 (36-51) years were enrolled. 26 cases (25% of ADHF patients) developed AKI during hospitalization and 4 died after hospital discharge. Serum creatinine (sCr), serum total bilirubin, brain natriuretic peptide (BNP), and urinary L-FABP in AKI patients were significantly higher than in non-AKI patients, whereas systemic oxygen saturation of the peripheral artery (SpO2) and estimated glomerular filtration ratio in AKI patients were lower than non-AKI patients. There was no difference in the intravenous diuretic dose on admission and during hospitalization between the two groups. In the receiver operating characteristic (ROC) analysis, the maximum area under the curve (AUC) of urinary biomarkers in AKI patients was urinary L-FABP (AUC = 0.769, p < 0.001) with a cutoff value of 4.86 µg/gCr. Urinary L-FABP level on admission was associated with a predictor for AKI development during hospitalization after adjusting for sCr, BNP and SpO2. Urinary L-FABP was a useful predictor for the development of AKI in ACHD patients hospitalized for ADHF. Monitoring of urinary L-FABP allows us to detect a high-risk patient earlier than the conventional biomarkers.
Assuntos
Injúria Renal Aguda , Cardiopatias Congênitas , Insuficiência Cardíaca , Humanos , Adulto , Prognóstico , Creatinina , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/complicações , Biomarcadores , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Proteínas de Ligação a Ácido Graxo , Peptídeo Natriurético Encefálico , FígadoRESUMO
Lymphatic congestion is known to play an important role in the development of late Fontan complications. This study aimed to (1) develop a gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) contrast three-dimensional heavily T2-weighed MR technique that can detect abnormal lymphatic pathway in the abdomen while simultaneously evaluating hepatocellular carcinoma (HCC) and to (2) propose a new classification of abnormal abdominal lymphatic pathway using a non-invasive method in adults with Fontan circulation. Twenty-seven adults with Fontan circulation who underwent Gd-EOB-DTPA abdominal MR imaging were prospectively enrolled in this study. We proposed MR lymphangiography that suppresses the vascular signal on heavily T2-weighted imaging after EOB contrast. The patients were classified as follows: grade 1 with almost no lymphatic pathway, grade 2 with a lymphatic pathway mainly around the bile duct and liver surface, and grade 3 with a lymphatic pathway mainly around the vertebral body and inferior vena cava. The grade 3 group showed the lowest oxygen saturation level, highest central venous pressure, highest incidence of massive ascites, HCC, and focal nodular hyperplasia. This group also tended to have patients with the oldest age and highest cardiac index; however, the difference was not statistically significant. As for the blood test, the grade 3 group showed the lowest platelet count and serum albumin level and the highest fibrosis-4 index. A novel technique, Gd-EOB-DTPA MR lymphangiography, can detect abnormal abdominal lymphatic pathways in Fontan circulation, which can reflect the severity of failing Fontan.
Assuntos
Carcinoma Hepatocelular , Técnica de Fontan , Neoplasias Hepáticas , Adulto , Humanos , Carcinoma Hepatocelular/patologia , Meios de Contraste , Linfografia , Neoplasias Hepáticas/patologia , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Abdome , Espectroscopia de Ressonância MagnéticaRESUMO
As long-term surgical outcome of congenital heart disease has continued to improve, most pediatric patients with congenital heart disease are able to reach adulthood. However, adult congenital heart disease (ACHD) patients have increased risk of arrhythmia, valvular diseases, infectious endocarditis, and heart failure. The end-stage ACHD patients with advanced heart failure may require mechanical circulatory support to improve the heart failure symptoms or to recover from circulatory collapse, and may eventually aim to heart transplant or destination therapy. In general, long-term mechanical support for dilated cardiomyopathy or ischemic cardiomyopathy has been achieved with left ventricular assist device with excellent survival outcomes and improved quality of life. However, the ventricular assist device for end-stage ACHD patients can be challenging due to patient-specific anatomical feature, multiple histories of surgical and catheter-based interventions and possible multiple end-organ dysfunctions, and offered less frequently compared to non-ACHD patients. The Interagency Registry for Mechanically Assisted Circulatory Support data published recently showed that ACHD patients receiving long-term mechanical circulatory support consisted <1â¯% of all registrants and had higher mortality after mechanical support than non-ACHD patients. However, the ACHD patients supported with left ventricular assist device had similar survival with non-ACHD patients and a large proportion of the mortality difference between ACHD and non-ACHD patients seemed to result from operative and perioperative factors. Therefore, the ventricular assist device therapy can be an excellent treatment for selected ACHD patients. In this paper, we describe the current status of ventricular assist device support for end-stage ACHD patients and consideration to the future.
Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Doenças Vasculares , Humanos , Adulto , Criança , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Qualidade de Vida , Resultado do Tratamento , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnósticoRESUMO
AIMS: The incidence of hepatocellular carcinoma (HCC) in patients with Fontan-associated liver disease (i.e., FALD-HCC) has increased over time. However, the risk factors for HCC development remain unclear. Here, we compared the levels of non-invasive markers to the survival rate of FALD-HCC patients. METHODS: From 2003 to 2021, 154 patients (66 men, 42.9%) developed liver disease after undergoing Fontan procedures. HCC was diagnosed in 15 (9.7%) (8 men, 53.3%) at a median age of 34 years (range, 21-45 years). We compared FALD-HCC and non-HCC cases; we generated marker level cutoffs using receiver operating characteristic curves. We sought to identify risk factors for HCC and mortality. RESULTS: The incidence of HCC was 4.9% in FALD patients within 20 years after the Fontan procedure. Compared with non-HCC patients, FALD-HCC patients exhibited higher incidences of polysplenia and esophageal varices. At the time of HCC development, the hyaluronic acid (HA) level (p = 0.04) and the fibrosis-4 index (p = 0.02) were significantly higher in FALD-HCC patients than in non-HCC patients; the total bilirubin (T-BIL) level (p = 0.07) and the model for end-stage liver disease score [excluding the international normalized ratio (MELD-XI)] (p = 0.06) tended to be higher in FALD-HCC patients. Within approximately 20 years of the Fontan procedure, 10 patients died (survival rate, 96.9%). Kaplan-Meier curve analysis indicated that patients with T-BIL levels ≥ 2.2 mg/dL, HA levels ≥ 55.5 ng/mL, and MELD-XI scores ≥ 18.7 were at high risk of HCC, a generally poor prognosis, and both polysplenia and esophageal varices. Multivariate Cox regression analyses indicated that the complication of polysplenia [Hazard ratio (HR): 10.915] and a higher MELD-XI score (HR: 1.148, both p < 0.01) were independent risk factors for FALD-HCC. CONCLUSIONS: The complication of polysplenia and a MELD-XI score may predict HCC development and mortality in FALD patients.
Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Neoplasias Hepáticas , Adulto , Biomarcadores , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Doença Hepática Terminal/complicações , Varizes Esofágicas e Gástricas/complicações , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Patients with heart failure (HF) reportedly have activated platelets with increased platelet distribution width (PDW) and mean platelet volume (MPV), which lead to thrombotic events. These platelet indices are easily measured by routine blood tests and have been proposed as potential markers of cardiac events. We performed the present study to clarify whether platelet indices correlate to the severity of HF and to the prognosis of patients with congenital heart disease (CHD). We performed a retrospective single-center study including 400 patients with CHD [median age, 34 years (range 12-76); 49% males] hospitalized between 2014 and 2017. We assessed their clinical data, correlation between platelet indices and severity of HF, and prognosis of HF-related hospitalization and thrombus formation. In multivariate analysis, a significant correlation was found between PDW and logBNP (log-transformed brain natriuretic peptide; r = 0.30, p < 0.001), as well as between MPV and logBNP (r = 0.24, p < 0.001). After treatment for heart failure, a significant reduction was found in PDW (average value before treatment: 14.2; after: 13.2, p = 0.017). In multivariate logistic regression analysis, PDW [hazard ratio (HR) 1.365; 95% confidence interval (CI) 1.005-1.768] and MPV (HR 1.472; 95% CI 1.055-2.052) were predictors of HF-related hospitalization. Similarly, PDW (HR 1.998; 95% CI 1.461-2.630) and MPV (HR 1.792; 95% CI 1.155-2.781) were predictors of thrombus formation. Platelet volume indices correlate to severity of heart failure and have prognostic value for both cardiac and thrombotic events in patients with CHD.
Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Trombose , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Peptídeo Natriurético Encefálico , Volume Plaquetário Médio , Plaquetas , Trombose/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Insuficiência Cardíaca/diagnósticoRESUMO
AIMS: The criteria for 'good' Fontan haemodynamics have been poorly defined in relation to long-term outcomes. The aim of this study was to identify the risk factors for mortality among haemodynamic parameters obtained early after the Fontan operation. METHODS AND RESULTS: Clinical data of all perioperative survivors of the Fontan operation performed before 2011, from nine institutions, were collected through a retrospective chart review. In total, 1260 patients were included. The median age at the time of Fontan operation was 3.6 years. Post-operative cardiac catheterization was conducted in 1117 patients at a median period of 1.0 years after the operation. During the median follow-up period of 10.2 years, 107 patients died. The mortality rates at 10, 20, and 25 years after the operation were 5%, 12%, and 22%, respectively. On multivariable analysis, older age at the time of the operation {≥15 years, hazard ratio (HR) [95% confidence interval (CI)]: 3.2 (1.7-5.9)} and haemodynamic parameters obtained at post-operative catheterization, such as low ejection fraction [<30%, HR (95% CI): 7.5 (3.2-18)], low systemic oxygen saturation [<80%, HR (95% CI): 3.8 (1.6-9.1)], high central venous pressure [≥16 mmHg, HR (95% CI): 2.3 (1.3-3.9)], and low mean systemic arterial pressure [<60 mmHg, HR (95% CI): 3.0 (1.4-6.2)] were identified as independent predictors of mortality. The predictive model based on these parameters had a c-index of 0.75 at 10 years. CONCLUSIONS: Haemodynamic parameters obtained at a median period of 1.0 years, post-operatively, can accurately identify patients with a high mortality risk, who may need intensive management to improve long-term outcomes.
Assuntos
Técnica de Fontan , Técnica de Fontan/efeitos adversos , Hemodinâmica , Humanos , Estudos Retrospectivos , Fatores de Risco , SobreviventesRESUMO
AIM: This study aimed to summarize cases of successful pregnancy and delivery in patients with transposition of the great arteries (TGA) after atrial switch operation (ASO), to provide management, clinical experience, and maternal and fetal outcomes. METHODS: During a 16-year period (2004-2019), we experienced 30 pregnancies in 15 patients after ASO at our institution. We retrospectively reviewed the medical records of the patients. RESULTS: In 30 pregnancies, there were 21 (70%) live births, five (17%) miscarriages, and four (13%) artificial abortions. There were no maternal or neonatal deaths. Cardiac complications occurred in nine (43%) patients: deterioration of right ventricular (RV) function in one, symptomatic heart failure (HF) in three, supraventricular tachyarrhythmia requiring electrical cardioversion in two, sick sinus syndrome that required pacemaker implantation in two, and hemoptysis in one. Obstetric complications occurred in five (24%). Neonatal complications were premature births (delivery at <37 weeks of gestation) in 15 (71%), and birthweight <2500 g in 18 (86%). The mode of delivery consisted of vaginal delivery (VD) in five (24%), and cesarean section (CS) in 16 (76%). CONCLUSION: A high incidence of preterm CS and cardiac complications including deterioration of RV function was observed in patients who had undergone ASO for TGA.