RESUMO
BACKGROUND: Many patients with repaired tetralogy of Fallot require pulmonary valve replacement (PVR) due to significant pulmonary regurgitation (PR). Transcatheter PVR (TPVR) is an equally effective and less invasive alternative to surgical PVR but many native right ventricular outflow tracts (RVOTs) are too large for TPVR at time of referral. Understanding the rate of growth of the RVOT may help optimize timing of referral. This study aims to examine the longitudinal growth of the native RVOT over time in repaired tetralogy of Fallot (TOF). METHODS: A retrospective review of serial cardiac MRI cardiovascular magnetic resonance (CMR) data from 121 patients with repaired TOF and a native RVOT (median age at first CMR 14.7 years, average interval between the first and last CMR of 8.1 years) was performed to measure serial changes in RVOT diameter, cross-sectional area, perimeter-derived diameter, and length. RESULTS: All parameters of RVOT size continued to grow with increasing age but growth was more rapid in the decade after TOF repair (for minimum systolic diameter, mean increase of 5.7 mm per 10 years up to year 12, subsequently 2.3 mm per 10 years). The RVOT was larger with a transannular patch and in patients without pulmonary stenosis (p < 0.001 for both), but this was not associated with rate of growth. More rapid RVOT enlargement was noted in patients with larger right ventricular end-diastolic volume (RVEDV), higher PR fraction, and greater rates of increases in RVEDV and PR (p < 0.001 for all) CONCLUSIONS: in patients with repaired TOF, using serial CMR data, we found that RVOT size increased progressively at all ages, but the rate was more rapid in the first decade after repair. More rapid RVOT enlargement was noted in patients with a larger RV, more PR, and greater rates of increases in RV size and PR severity. These results may be important in considering timing of referral for transcatheter pulmonary valves, in planning transcatheter and surgical valve replacement, and in designing future valves for the native RVOT.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Valor Preditivo dos Testes , Insuficiência da Valva Pulmonar , Tetralogia de Fallot , Função Ventricular Direita , Humanos , Tetralogia de Fallot/cirurgia , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/fisiopatologia , Estudos Retrospectivos , Adolescente , Fatores de Tempo , Criança , Adulto Jovem , Masculino , Feminino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Resultado do Tratamento , Adulto , Insuficiência da Valva Pulmonar/fisiopatologia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/etiologia , Estudos Longitudinais , Pré-Escolar , Imagem Cinética por Ressonância Magnética , Fatores Etários , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Valva Pulmonar/fisiopatologia , Lactente , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Coarctation of the aorta (COA) is associated with reduced aortic distensibility and systemic hypertension (HTN). 60-85% of COA patients have a bicuspid aortic valve (BAV). It is not known if the presence of a BAV accentuates the aortopathy and HTN in CoA patients. We examined whether patients with COA and a BAV had lower aortic distensibility by CMR, and a higher prevalence of systemic HTN compared with COA patients with a tricuspid aortic valve (TAV). METHODS: In successfully repaired COA patients excluding those with residual COA, ascending aorta (AAO) and descending aorta (DAO) distensibility was calculated by CMR. HTN was assessed using standard pediatric and adult criteria. RESULTS: Among 215 COA patients (median age 25.3 years), 67% had a BAV, and 33% had a TAV. Median AAO distensibility z-score was lower in the BAV group (- 1.2 versus - 0.7; p = 0.014) but DAO distensibility was similar in BAV and TAV patients. HTN prevalence was similar in BAV (32%) and TAV groups (36%, p = 0.56). On multivariable analysis controlling for confounders, HTN was not associated with BAV but was associated with male gender (p = 0.003) and older age at follow-up (p = 0.004). CONCLUSIONS: In young adults with treated COA, those with a BAV had stiffer AAO compared to those with a TAV, but DAO stiffness was similar. HTN was not related to BAV. These results suggest that although the presence of a BAV in COA exacerbates the AAO aortopathy, it does not exacerbate the more generalized vascular dysfunction and associated HTN.
Assuntos
Doença da Válvula Aórtica Bicúspide , Hipertensão , Rigidez Vascular , Adulto , Criança , Humanos , Masculino , Adulto Jovem , Aorta , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Hipertensão/epidemiologia , Valor Preditivo dos TestesRESUMO
Double aortic arch associated with atresia of the left arch proximal to the left common carotid artery has been considered a theoretical possibility. To our knowledge, we report the first patient with this anatomy confirmed by surgical observation.
Assuntos
Aorta Torácica , Anel Vascular , Humanos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aorta Torácica/anormalidades , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/cirurgia , DocumentaçãoRESUMO
BACKGROUND: Cross-sectional studies have reported that ventricular dilation and dysfunction are associated with adverse clinical outcome in Fontan patients; however, longitudinal changes and their relationship with outcome are not known. METHODS: This was a single-center retrospective analysis of Fontan patients with at least 2 cardiovascular magnetic resonance (CMR) scans without intervening interventions. Serial measures of end-diastolic volume index (EDVI), end-systolic volume index (ESVI), ejection fraction (EF), indexed mass (massi), mass-to-volume ratio, and end-systolic wall stress (ESWS) were used to estimate within-patient change over time. Changes were compared for those with and without a composite outcome (death, heart transplant, or transplant listing) as well as between patients with left (LV) and right ventricular (RV) dominance. RESULTS: Data from 156 patients were analyzed with a mean age at 1st CMR of 17.8 ± 9.6 years. 490 CMRs were included with median of 3 CMRs/patient (range 2-9). On regression analysis with mixed effects models, volumes and ESWS increased, while mass, mass-to-volume ratio, and EF decreased over time. With a median follow-up of 10.2 years, 14% met the composite outcome. Those with the composite outcome had a greater increase in EDVI compared to those without (4.7 vs. 0.8 ml/BSA1.3/year). Compared with LV dominance, RV dominance was associated with a greater increase in ESVI (1.4 vs. 0.5 ml/BSA1.3/year), a greater decrease in EF (- 0.61%/year vs. - 0.24%/year), and a higher rate of the composite outcome (21% vs. 8%). CONCLUSIONS: Ventricles in the Fontan circulation exhibit a steady decline in performance with an increase in EDVI, ESVI, and ESWS, and decrease in EF, mass index, and mass-to-volume ratio. Those with death or need for heart transplantation have a faster increase in EDVI. Patients with rapid increase in EDVI (> 5 ml/BSA1.3/year) may be at a higher risk of adverse outcomes and may benefit from closer surveillance. RV dominance is associated with worse clinical outcomes and remodeling compared to LV dominance.
Assuntos
Técnica de Fontan , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Técnica de Fontan/efeitos adversos , Estudos Retrospectivos , Estudos Transversais , Valor Preditivo dos Testes , Ventrículos do Coração , Função Ventricular Esquerda , Volume SistólicoRESUMO
Myocarditis is a rare complication of the COVID-19 mRNA vaccine. We previously reported a case series of 15 adolescents with vaccine-associated myocarditis, 87% of whom had abnormalities on initial cardiac magnetic resonance (CMR), including late gadolinium enhancement (LGE) in 80%. We performed follow-up CMRs to determine the trajectory of myocardial recovery and better understand the natural history of vaccine-associated myocarditis. Case series of patients age < 19 years admitted to Boston Children's Hospital with acute vaccine-associated myocarditis following the BNT162b2 vaccine who had abnormal CMR at the time of initial presentation, and underwent follow-up testing. CMR assessment included left ventricular (LV) ejection fraction, T2-weighted myocardial imaging, LV global native T1, LV global T2, extracellular volume (ECV), and late gadolinium enhancement (LGE). Ten patients (9 male, median age 15 years) with vaccine-associated myocarditis underwent follow-up CMR at a median of 92 days (range 76-119) after hospital discharge. LGE was persistent in 80% of patients, though improved from prior in all cases. Two patients (20%) had abnormal LV global T1 at presentation, which normalized on follow-up. ECV decreased between acute presentation and follow-up in 6/10 patients; it remained elevated at follow-up in 1 patient and borderline in 3 patients. CONCLUSION: CMR performed ~3 months after admission for COVID-19 vaccine-associated myocarditis showed improvement of LGE in all patients, but persistent in the majority. Follow-up CMR 6-12 months after acute episode should be considered to better understand the long-term cardiac risks. WHAT IS KNOWN: ⢠Myocarditis is a rare side effect of COVID-19 mRNA vaccine. â¢Late gadolinium enhancement is present on most cardiac magnetic resonance at the time of acute presentation. WHAT IS NEW: â¢Late gadolinium enhancement improved on all repeat cardiac magnetic resonance at 3-month follow-up. â¢Most patients still had a small amount of late gadolinium enhancement, the clinical significance of which is yet to be determined.
Assuntos
COVID-19 , Miocardite , Adolescente , Adulto , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Criança , Meios de Contraste/efeitos adversos , Seguimentos , Gadolínio/efeitos adversos , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Miocardite/diagnóstico por imagem , Miocardite/etiologia , Miocárdio/patologia , Valor Preditivo dos Testes , Vacinas Sintéticas , Função Ventricular Esquerda , Adulto Jovem , Vacinas de mRNARESUMO
BACKGROUND: Right ventricular (RV) late gadolinium enhancement (LGE) occurs due to surgical scarring and RV remodeling, and has been shown to be associated with clinical outcomes in Tetralogy of Fallot (TOF). However, it is not known if cardiovascular magnetic resonance (CMR) LGE extent progresses over time, and therefore, it is not known if serial reassessment of LGE is necessary. We determined the rate of progression in the extent of RV LGE on serial CMR examinations in repaired TOF. METHODS: Retrospective review of 127 patients after TOF repair (49% male, median age at first CMR 18.9 years (Interquartile range (IQR) 13.3,27.0) who had at least two CMRs (median follow-up duration of 4.0 years (IQR 2.1,5.9)) was performed. 84/127 patients had no interventions between serial CMRs (Group 1) while 43/127 patients had transcatheter or surgical intervention between CMRs (Group 2). The extent of RV LGE was assessed using 2 methods: a semiquantitative RV LGE score and a quantitative RV LGE extent expressed as % of RV mass. Mixed effects linear regression modeling to estimate changes in LGE over time. RESULTS: RV LGE was present in all patients on the first CMR. % RV LGE extent and LGE score did not increase over time in either patient group. The mean 5 year rates of change were small and negative for both % RV LGE extent [- 2.3 (95% CI - 2.9, - 1.8, p < 0.001) in Group 1, and - 1.9 (95% CI - 3.2, - 0.7, p = 0.004) in Group 2], and RV LGE score [- 0.9 (95% CI - 1.1, - 0.6, p < 0.001) in Group 1, and - 0.5 (95% CI - 1.1, - 0.0, p = 0.047) in Group 2]. CONCLUSIONS: In this serial CMR evaluation of children and adults with repaired TOF, no significant progression in the extent of RV LGE was seen on intermediate term follow-up. Given recent concerns regarding the safety of gadolinium-based contrast agents, frequent assessment of LGE may not be necessary in follow-up.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Tetralogia de Fallot , Adolescente , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Meios de Contraste , Feminino , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgiaRESUMO
BACKGROUND: Aortic stiffness has been shown to be abnormal in patients with bicuspid aortic valve (BAV), and is considered a component of the aortopathy associated with this condition. Progressive aortic stiffening associated with aging has been previously described in normal adults. However, it is not known if aging related aortic stiffening occurs at the same rate in BAV patients. We determined the longitudinal rate of decline in segmental distensibility in BAV patients using serial cardiovascular magnetic resonance (CMR) studies, and compared to previously published results from a group of patients with connective tissue disorders (CTD). METHODS: A retrospective review of CMR and clinical data on children and adults with BAV (n = 49, 73% male; 23 ± 11 years) with at least two CMRs (total 98 examinations) over a median follow-up of 4.1 years (range 1-9 years) was performed to measure aortic distensibility at the ascending (AAo) and descending aorta (DAo). Longitudinal changes in aortic stiffness were assessed using linear mixed-effects modeling. The comparison group of CTD patients had a similar age and gender profile (n = 50, 64% male; 20.6 ± 12 years). RESULTS: Compared to CTD patients, BAV patients had a more distensible AAo early in life but showed a steeper decline in distensibility on serial examinations [mean 10-year decline in AAo distensibility (× 10-3 mmHg-1) 2.4 in BAV vs 1.3 in CTD, p = 0.005]. In contrast, the DAo was more distensible in BAV patients throughout the age spectrum, and DAo distensibility declined with aging at a rate similar to CTD patients [mean 10 year decline in DAo distensibility (× 10-3 mmHg-1) 0.3 in BAV vs 0.4 in CTD, p = 0.58]. CONCLUSIONS: On serial CMR measurements, AAo distensibility declined at significantly steeper rate in BAV patients compared to a comparison group with CTDs, while DAo distensibility declined at similar rates in both groups. These findings offer new mechanistic insights into the differing pathogenesis of the aortopathy seen in BAV and CTD patients.
Assuntos
Aorta/diagnóstico por imagem , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Angiografia por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Valva Mitral/diagnóstico por imagem , Rigidez Vascular , Adolescente , Adulto , Aorta/fisiopatologia , Criança , Doenças do Tecido Conjuntivo/fisiopatologia , Feminino , Humanos , Masculino , Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies. METHODS: Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations. Memoranda, Core Lab reports, and adjudication logs were reviewed. A centre-level questionnaire provided information regarding local processes for data collection. Descriptive statistics were used, and chi-square tests determined differences in imaging quality. RESULTS: For the 19 participating centres, challenges with enrolment included variations in Institutional Review Board definitions of "retrospective" eligibility, overestimation of non-White participants, centre categorisation of Hispanic participants that differed from National Institutes of Health definitions, and exclusion of potential participants due to missing demographic data. Institutional Review Board amendments resolved many of these challenges. There was an unanticipated burden imposed on centres due to high numbers of echocardiograms that were reviewed but failed to meet submission criteria. Additionally, image transfer software malfunctions delayed Core Lab image review and feedback. Between the early and late study periods, the proportion of unacceptable echocardiograms submitted to the Core Lab decreased (14 versus 7%, p < 0.01). Most protocol violations were from eligibility violations and inadvertent protected health information disclosure (overall 2.5%). Adjudication committee reviews led to protocol changes. CONCLUSIONS: Numerous challenges encountered during the Normal Echocardiogram Database Study prolonged study enrolment. The retrospective design and flaws in image transfer software were key impediments to study completion and should be considered when designing future studies collecting echocardiographic images as a primary outcome.
Assuntos
Ecocardiografia/estatística & dados numéricos , Cardiopatias Congênitas/diagnóstico , Criança , Feminino , Seguimentos , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Inquéritos e QuestionáriosAssuntos
Cardiopatias Congênitas , Progéria , Humanos , Progéria/genética , Estudos Longitudinais , Estudos ProspectivosRESUMO
Syzygium cumini (Myrtaceae) is commonly called as Jamun or Jambolan. It has antidiabetic, anti-inflammatory, antipyretic, and antioxidant activities. Hepatocellular carcinoma is the most frequent and deadliest cancers worldwide. We investigated the cytotoxic potentials of S. cumini methanolic seed kernel extract against human hepatoma HepG2 cells. HepG2 cells were treated with 10, 20, and 40 µg/mL of seed kernel extract for 24 hours and cytotoxic analysis was performed by MTT assay. S. cumini induced apoptosis related morphological changes in HepG2 cells were analyzed by annexin V and propidium iodide double staining. Nuclear fragmentation and chromatin condensation were analyzed by Hoechst nuclear staining. Mitochondrial membrane potential (MMP) was investigated by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) staining. Protein expressions of hepatocyte nuclear factor-1α (HFN-1α) was performed using western blotting. S. cumini treatments caused a significant and a concentration-dependent increase in the cytotoxicity of HepG2 cells. S. cumini treatments increased the percentage of cells in an early and late apoptosis stage. This treatment also caused chromatin condensation and nuclear fragmentation. Further, S. cumini treatments decreased MMP and also caused a significant downregulation of HFN-1α protein expression. The present study demonstrated that S. cumini seed extract induced apoptosis in HepG2 cells through decrease in MMP and downregulation of HFN-1α.
Assuntos
Apoptose/efeitos dos fármacos , Myrtaceae/química , Extratos Vegetais/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metanol/química , Myrtaceae/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/química , Sementes/química , Sementes/metabolismoRESUMO
The ventriculoarterial coupling (VAC) ratio, the ratio of arterial elastance (Ea) to ventricular end-systolic elastance (Ees), reflects cardiovascular efficiency. Little is known about this ratio in patients who have undergone the Fontan procedure. Our aim was to assess the VAC ratio in a cohort of Fontan patients using a cardiac magnetic resonance (CMR) method, and to examine its relation to outcomes. We retrospectively assessed VAC from CMR data on 195 Fontan patients (age 19.6 ± 10.7 years) and 42 controls (age 15.2 ± 2.2 years). The VAC ratio was calculated as Ea/Ees (Ea = mean arterial blood pressure (MBP)/ventricular stroke volume; Ees = MBP/end-systolic volume). Compared with controls, Fontan patients had lower body surface area-adjusted median Ees (1.54 vs. 2.4, p < 0.001) and Ea (1.35 vs. 1.48, p = 0.01), and a higher median VAC ratio (0.88 vs. 0.62, p < 0.001). After a median follow-up of 4 years (range 1-10), 20 patients reached a composite endpoint of death or heart transplant listing. On multivariable modeling, being in the lowest tertile of the VAC ratio was independently associated with the composite endpoint (odds ratio 11.39, p = 0.02), and inclusion of the VAC ratio in the model improved prediction compared to traditional risk factors. In patients without ventricular dilation, the VAC ratio was the only factor predictive of the composite endpoint (p = 0.02). In conclusion, we found evidence for inefficient ventriculoarterial coupling in Fontan patients. The VAC ratio improved prediction of outcomes and was especially useful in patients without ventricular dilation. Further investigation into the clinical significance of ventriculoarterial coupling in this patient population is warranted.
Assuntos
Artérias/fisiopatologia , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Imagem Cinética por Ressonância Magnética/métodos , Adolescente , Adulto , Artérias/diagnóstico por imagem , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Seguimentos , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Transplante de Coração , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico/fisiologia , Taxa de Sobrevida , Função Ventricular Esquerda/fisiologia , Adulto JovemRESUMO
Extracellular vesicles (EVs) have been proposed as a means to promote intercellular communication. We show that when human primary cells are exposed to cancer cell EVs, rapid cell death of the primary cells is observed, while cancer cells treated with primary or cancer cell EVs do not display this response. The active agents that trigger cell death are 29- to 31-nucleotide (nt) or 22- to 23-nt processed fragments of an 83-nt primary transcript of the human RNY5 gene that are highly likely to be formed within the EVs. Primary cells treated with either cancer cell EVs, deproteinized total RNA from either primary or cancer cell EVs, or synthetic versions of 31- and 23-nt fragments trigger rapid cell death in a dose-dependent manner. The transfer of processed RNY5 fragments through EVs may reflect a novel strategy used by cancer cells toward the establishment of a favorable microenvironment for their proliferation and invasion.
Assuntos
Vesículas Extracelulares/metabolismo , Neoplasias/metabolismo , RNA/metabolismo , Comunicação Celular/fisiologia , Morte Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Células K562RESUMO
BACKGROUND: Aortic diameter is an imperfect predictor of aortic complications in connective tissue disorders (CTDs). Novel indicators of vascular phenotype severity such as aortic stiffness and vertebral tortuosity index have been proposed. We assessed the relation between aortic stiffness by cardiac MRI, surgical root replacement, and rates of aortic root dilation in children and young adults with CTDs. METHODS AND RESULTS: Retrospective analysis of cardiac MRI data on children and young adults with a CTD was performed to derive aortic stiffness measures (strain, distensibility, and ß-stiffness index) at the aortic root, ascending aorta, and descending aorta. Vertebral tortuosity index was calculated as previously described. Rate of aortic root dilation before cardiac MRI was calculated as change in echocardiographic aortic root diameter z score per year. In 83 CTD patients (median age, 24 years; range, 1-55; 17% <18 years of age; 60% male), ascending aorta distensibility was reduced in comparison with published normative values: median z score, -1.93 (range, -8.7 to 1.3; P<0.0001 versus normals). Over a median follow-up period of 2.7 years, there were no aortic dissections or deaths, but 16 of 83 (19%) patients underwent surgical aortic root replacement. In multivariable analysis, lower aortic root strain (P=0.05) and higher vertebral tortuosity index (P=0.01) were independently associated with aortic root replacement. Lower ascending aorta strain (P=0.02) was associated with a higher rate of aortic root dilation. CONCLUSIONS: Higher aortic stiffness is associated with higher rates of surgical aortic replacement and aortic root dilation in children and young adults with CTDs.
Assuntos
Aorta/patologia , Doenças do Tecido Conjuntivo/patologia , Rigidez Vascular/fisiologia , Adolescente , Adulto , Fatores Etários , Aorta/cirurgia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Angiografia por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Accurate and reproducible aortic measurements are essential in aortopathy patients. Transthoracic echocardiography (TTE) is commonly used but has several limitations. Cardiac magnetic resonance (CMR) can offset these limitations but has not been directly compared with TTE. We compared the reproducibility of CMR and TTE measurements at multiple aortic levels. Patients with a connective tissue disorder (CTD) or bicommissural aortic valve (BAV) (n = 41; 22 CTD, 19 BAV; mean age 18.8 ± 8.9 years) with TTE and CMR imaging performed within 3 months of each other were randomly selected. Two blinded observers measured the aorta at multiple anatomic levels. Intra- and interobserver variability and agreement between techniques were assessed. Aortic root diameter measurements by TTE and CMR were equally reproducible (% error 4-10 %), but TTE measurements were systematically smaller by 5-7 % (p < 0.0001). Systematic differences were larger in BAV (11-12 %, p < 0.0001) due to root asymmetry. CMR measurements of aortic root cross-sectional area were feasible and highly reproducible (% error 5-8 %). Compared with CMR, ascending aorta measurements by TTE were less reproducible, especially in BAV (% error 21-24 vs. 6-7 %, p = 0.01). Distal aortic measurements by TTE were 14-29 % smaller and had poor reproducibility compared with CMR (% error 24-42 vs. 9-10 %; p < 0.0001). CMR measurement of the largest aortic root dimension is more reliable than TTE, especially when the root is asymmetric. Measurements of the thoracic aorta distal to the root by CMR are more accurate and reproducible than by TTE. These data support a role for CMR in aortopathy patients.
Assuntos
Aorta/fisiopatologia , Aortografia , Ecocardiografia , Imagem Cinética por Ressonância Magnética , Adolescente , Adulto , Aorta/diagnóstico por imagem , Valva Aórtica/anormalidades , Valva Aórtica/diagnóstico por imagem , Doença da Válvula Aórtica Bicúspide , Criança , Pré-Escolar , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultrarare disorder of segmental premature aging that is associated with the development of advanced atherosclerosis and significant cardiovascular and cerebrovascular disease. Treatment with lonafarnib has improved survival in patients with HGPS; however, in extended longitudinal follow-up, there has been an increase in the prevalence of rapidly progressive calcific aortic stenosis. The evolving course of HGPS has prompted reconsideration of conservative management and led to the development of strategies for anatomic treatment. In this case report, we describe the anesthetic management of patients with HGPS undergoing surgical management of aortic stenosis with cardiopulmonary bypass.
Assuntos
Ponte Cardiopulmonar , Progéria , Humanos , Anestesia/métodos , Estenose da Valva Aórtica/cirurgia , Progéria/cirurgiaRESUMO
BACKGROUND: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling. METHODS: SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. RESULTS: SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased. CONCLUSIONS: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes.
Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Humanos , Pré-Escolar , Criança , Adolescente , Veia Cava Superior/diagnóstico por imagem , Veia Cava Superior/cirurgia , Veia Cava Superior/fisiologia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Fígado/diagnóstico por imagem , Hemodinâmica/fisiologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgiaRESUMO
Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.
RESUMO
PURPOSE: To assess the interstudy variability of cardiac magnetic resonance imaging (CMR) parameters of ventricular size and function in repaired tetralogy of Fallot (TOF). MATERIALS AND METHODS: Patients with TOF (n = 30, median age 23.5 years, 43% male) were enrolled prospectively. Each patient underwent two consecutive CMR examinations on the same day. Each examination was analyzed for ventricular size and function by two observers and multiple comparisons were made with assessment of agreement using Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: Agreement for most measures of ventricular size and function was high when a single observer analyzed both studies. Agreement was worse when different observers analyzed sequential studies. This effect was most prominent on measurements of right ventricular (RV) mass and there was slight improvement when mass was measured during systole. Aside from ventricular mass, agreement was similar for RV and left ventricular (LV) parameters. CONCLUSION: CMR measures of ventricular size and function have acceptable repeatability across serial examinations in patients with repaired TOF. Measurements of RV mass are subject to higher variability. For most parameters, agreement limits are wider when measurements are performed by multiple operators. These results will aid in the interpretation of study-to-study variations in the follow-up of individual patients and in designing future clinical trials.
Assuntos
Ventrículos do Coração/fisiopatologia , Imageamento por Ressonância Magnética , Miocárdio/patologia , Tetralogia de Fallot/diagnóstico , Tetralogia de Fallot/patologia , Adolescente , Adulto , Criança , Feminino , Ventrículos do Coração/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Sístole , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Adulto JovemRESUMO
OBJECTIVE: To review the short and medium term outcome of transcatheter pulmonary valve perforation (PVP) in patients with pulmonary atresia-intact ventricular septum and non-right ventricular dependant coronary circulation (PA/IVS non-RVDCC). BACKGROUND: PVP in patients with PA/IVS non-RVDCC has become more common in the past two decades. However, data on outcomes with this strategy are mixed. METHODS: Data were reviewed retrospectively for all patients with PA/IVS non-RVDCC treated from 1996- 2010 at our institution. Patients who had severe neonatal Ebstein malformation, or initial interventional management at another institution were excluded. RESULTS: PVP was attempted in 30 of 50 patients (60%); 26 (87%) of these had a successful procedure. Twenty-four patients (48%) had surgery without PVP. There were no deaths in the cohort. Complications of PVP included 5 (17%) myocardial perforations. Of those with successful PVP, 10 (38%) did not have surgery (PVP-NS) and 16 (62%) had surgery (PVP-S) prior to discharge. Tricuspid valve (TV) Z-score was larger in the PVP-NS than in PVP-S patients, with median TV diameter Z-scores of +0.7 (-0.9, 1.7) and -1.1 (-2.8, 2), respectively (P = 0.01). Time from PVP to either hospital discharge (PVP-NS group) or surgery (PVP-S group) was significantly different between groups: 15 (7, 22) and 8 days (0, 46), respectively (P = 0.01). There were no differences in the number of trials or lowest arterial PaO2 off prostaglandins between groups. All patients in the PVP-NS group had a biventricular circulation at a median follow-up of 4.3 years. CONCLUSIONS: The results of a collaborative approach to treating neonates with PA/IVS non-RVDCC are excellent. Smaller TV size is associated with greater likelihood of surgery prior to discharge, and may serve as a surrogate for early RV inadequacy.
Assuntos
Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Atresia Pulmonar/cirurgia , Boston , Cateterismo Cardíaco/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Estudos de Coortes , Ecocardiografia Doppler/métodos , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico por imagem , Hospitais Pediátricos , Humanos , Recém-Nascido , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Atresia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
It has been widely acknowledged that non-coding RNAs are master-regulators of genomic functions. However, the significance of the presence of ncRNA within introns has not received proper attention. ncRNA within introns are commonly produced through the post-splicing process and are specific signals of gene transcription events, impacting many other genes and modulating their expression. This study, along with the following discussion, details the association of thousands of ncRNAs--snoRNA, miRNA, siRNA, piRNA and long ncRNA--within human introns. We propose that such an association between human introns and ncRNAs has a pronounced synergistic effect with important implications for fine-tuning gene expression patterns across the entire genome.