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1.
Artigo em Inglês | MEDLINE | ID: mdl-33093765

RESUMO

Background: Patients with cardiac sarcoidosis (CS) are at increased risk of atrioventricular blocks, ventricular arrhythmias, and sudden cardiac death. Objectives We aimed to investigate the characteristics associated with appropriate therapy in implantable cardiac defibrillator (ICD) -implanted CS patients. Methods: We performed a PubMed and Web of Science search for studies reporting patients with CS who underwent an ICD implantation. The primary criterion was an appropriate therapy. Results: We screened 705 studies, of which 5 were included in the final analysis. We conducted a meta-analysis including 464 patients (mean age 55 years, 282 males (60%)). The mean follow-up was 3.5 years. Among the 464 patients, 180 received an appropriate therapy (39%). Patients who received an appropriate therapy were younger (-3.33, 95% confidence interval (CI) -6.42 to -0.23, p=0.004), were more likely to be male (OR 2.06, 95% CI 1.37-3.09, p=0.0005), had a lower left ventricular ejection fraction (LVEF) (-10.5, 95% CI -18.23 to -2.78, p=0.008), had a higher rate of complete heart block (OR 2.19, 95% CI 1.20 to 3.99, p=0.01), and more frequently had ventricular pacing (OR 6.44 95% CI 2.57 to 16.16, p<0.0001). Conclusions: Appropriate ICD therapy during CS is associated with young age, male sex, low LVEF, history of complete heart block, and ventricular pacing. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 17-23).


Assuntos
Cardiomiopatias/terapia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Bloqueio Cardíaco/terapia , Sarcoidose/terapia , Adulto , Fatores Etários , Idoso , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Bloqueio Cardíaco/diagnóstico por imagem , Bloqueio Cardíaco/mortalidade , Bloqueio Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Sarcoidose/diagnóstico por imagem , Sarcoidose/mortalidade , Sarcoidose/fisiopatologia , Fatores Sexuais , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
2.
Circ Arrhythm Electrophysiol ; 13(10): e008686, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907357

RESUMO

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.


Assuntos
Antivirais/administração & dosagem , Eletrocardiografia , Coração Fetal/efeitos dos fármacos , Bloqueio Cardíaco/congênito , Frequência Cardíaca/efeitos dos fármacos , Hidroxicloroquina/administração & dosagem , Antivirais/efeitos adversos , Antivirais/sangue , Cardiotoxicidade , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Sangue Fetal/metabolismo , Coração Fetal/fisiopatologia , Idade Gestacional , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Bloqueio Cardíaco/prevenção & controle , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/sangue , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
4.
Am J Physiol Heart Circ Physiol ; 319(2): H396-H409, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32678707

RESUMO

Myocardial ischemia leads to conduction slowing, cell-to-cell uncoupling, and arrhythmias. We previously demonstrated that varying perfusate sodium (Na+) and calcium (Ca2+) attenuates conduction slowing and arrhythmias during simulated ischemia with continuous perfusion. Cardioprotection was selectively associated with widening of the perinexus, a gap junction adjacent nanodomain important to ephaptic coupling. It is unknown whether perfusate composition affects the perinexus or ischemic conduction during nonsimulated ischemia, when coronary flow is reduced or halted. We hypothesized that altering preischemic perfusate composition could facilitate perinexal expansion and attenuate conduction slowing during global ischemia. To test this hypothesis, ex vivo guinea pig hearts (n = 49) were Langendorff perfused with 145 or 153 mM Na+ and 1.25 or 2.0 mM Ca2+ and optically mapped during 30 min of no-flow ischemia. Altering Na+ and Ca2+ did not substantially affect baseline conduction. Increasing Na+ and decreasing Ca2+ both lowered pacing thresholds, whereas increasing Ca2+ narrowed perinexal width (Wp). A least squares mean estimate revealed that reduced perfusate Na+ and Ca2+ resulted in the most severe conduction slowing during ischemia. Increasing Na+ alone modestly attenuated conduction slowing, yet significantly delayed the median time to conduction block (10 to 16 min). Increasing both Na+ and Ca2+ selectively widened Wp during ischemia (22.7 vs. 15.7 nm) and attenuated conduction slowing to the greatest extent. Neither repolarization nor levels of total or phosphorylated connexin43 correlated with conduction slowing or block. Thus, perfusate-dependent widening of the perinexus preserved ischemic conduction and may be an adaptive response to ischemic stress.NEW & NOTEWORTHY Conduction slowing during acute ischemia creates an arrhythmogenic substrate. We have shown that extracellular ionic concentrations can alter conduction by modulating ephaptic coupling. Here, we demonstrate increased extracellular sodium and calcium significantly attenuate conduction slowing during no-flow ischemia. This effect was associated with selective widening of the perinexus, an intercalated disc nanodomain and putative cardiac ephapse. These findings suggest that acute changes in ephaptic coupling may serve as an adaptive response to ischemic stress.


Assuntos
Bradicardia/prevenção & controle , Cálcio/metabolismo , Bloqueio Cardíaco/prevenção & controle , Sistema de Condução Cardíaco/metabolismo , Frequência Cardíaca , Isquemia Miocárdica/metabolismo , Sódio/metabolismo , Potenciais de Ação , Animais , Bradicardia/etiologia , Bradicardia/metabolismo , Bradicardia/fisiopatologia , Circulação Coronária , Modelos Animais de Doenças , Cobaias , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/metabolismo , Bloqueio Cardíaco/fisiopatologia , Preparação de Coração Isolado , Masculino , Isquemia Miocárdica/complicações , Isquemia Miocárdica/fisiopatologia , Transdução de Sinais , Fatores de Tempo
5.
Heart Vessels ; 35(12): 1735-1745, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32591894

RESUMO

Permanent pacemaker implantation (PPI) is a widely recognized complication associated with TAVI (incidence up to 20%). Smaller registries have identified several variables associated with PPI. The objective was to validate patient- and transcatheter aortic valve implantation (TAVI)-related procedural variables associated with PPI. We performed a retrospective analysis of patients from six European centers undergoing TAVI with the Edwards SAPIEN 3 prosthesis. Baseline variables and pre-procedural ECG characteristics and CT-scans were taken into account. Data for 1745 patients were collected; 191 (10.9%) required PPI after TAVI. The baseline variables pulmonary hypertension (OR 1.64; 95% CI 1.01-2.59), QRS duration > 117 ms (OR 2.58; 95% CI 1.73-3.84), right bundle branch block (RBBB; OR 5.14; 95% CI 3.39-7.72), left anterior hemi block (OR 1.92; 95% CI 1.19-3.02) and first-degree atrioventricular block (AVB, OR 1.63; 95%CI 1.05-2.46) were significantly associated with PPI. RBBB (OR 8.11; 95% CI 3.19-21.86) and first-degree AVB (OR 2.39; 95% CI 1.18-4.66) remained significantly associated in a multivariate analysis. Procedure-related variables included access site (TF; OR 1.97; 95% CI 1.07-4.05), implanted valve size (29 mm; OR 1.88; 95% CI 1.35-2.59), mean TAVI valve implantation depth below the annulus > 30% (OR 3.75; 95% CI 2.01-6.98). Patients receiving PPI had longer ICU stays and later discharges. Acute kidney injury stage 2/3 was more common in patients with PPI until discharge (15.2 vs. 3.1%; p = 0.007), but was not statistically significant thereafter. Further differences in outcomes at 30 days did not reach significance. The data will aid pre- and post-procedural patient management and prevent adverse long-term outcomes.Clinical Trial: NCT03497611.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Valvuloplastia com Balão/efeitos adversos , Estimulação Cardíaca Artificial , Bloqueio Cardíaco/terapia , Frequência Cardíaca , Próteses Valvulares Cardíacas , Marca-Passo Artificial , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Europa (Continente) , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/fisiopatologia , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
6.
Heart Vessels ; 35(11): 1563-1572, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32458055

RESUMO

Chronic RV pacing may lead to pacing induced cardiomyopathy in some patients and results in a higher risk of development of LV systolic dysfunction, heart failure, mitral regurgitation and atrial fibrillation. His bundle pacing emerged as the most physiologic form of ventricular pacing. However, wide adoption of this technique in routine clinical practice is limited by higher capture thresholds at implant sometimes, lower R wave amplitudes, atrial over sensing and increased risk for late rise in pacing thresholds (resulting in the need for lead revisions). Some recent studies have focused on left bundle branch area pacing as a solution to these problems. In our study, we have compared left bundle branch area pacing (in 22 patients) with conventional right ventricular apical pacing (in 28 patients) who presented to us with conventional indications for pacemaker implantations in term of procedure and fluoroscopy time and short-term lead performance and left ventricular function. The results of our study showed that left bundle branch area pacing is associated with shortened QRS duration (22.36 ± 9.36 ms) and better LV function (higher left ventricular ejection fraction 64.00 ± 3.03 vs. 59.73 ± 6.73 with a p value of 0.013 and lower left ventricular diastolic internal diameter 4.58 ± 0.32 vs. 5.23 ± 0.40 cm with a p value of < 0.001) in comparison to right ventricular apical pacing. The total procedure time and fluoroscopy time was similar (63.15 ± 7.02 vs. 55.15 ± 6.16 min, p value 0.142 and 6.08 ± 1.42 vs. 5.06 ± 1.30 min, p value 0.332 respectively) in left bundle branch area pacing group. The results of this study indicate that left bundle branch area pacing may be an option for physiological pacing in patients requiring a high percentage of ventricular pacing.


Assuntos
Potenciais de Ação , Fascículo Atrioventricular/fisiopatologia , Estimulação Cardíaca Artificial/métodos , Bloqueio Cardíaco/terapia , Frequência Cardíaca , Idoso , Estimulação Cardíaca Artificial/efeitos adversos , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda , Função Ventricular Direita
7.
Circ Arrhythm Electrophysiol ; 13(5): e008161, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32301327

RESUMO

BACKGROUND: Obese patients are more vulnerable to development of atrial fibrillation but pathophysiology underlying this relation is only partly understood. The aim of this study is to compare the severity and extensiveness of conduction disorders between obese patients and nonobese patients measured at a high-resolution scale. METHODS: Patients (N=212) undergoing cardiac surgery (male:161, 63±11 years) underwent epicardial mapping of the right atrium, Bachmann bundle, and left atrium during sinus rhythm. Conduction delay (CD) was defined as interelectrode conduction time of 7 to 11 ms and conduction block (CB) as conduction time ≥12 ms. Prevalence of CD/CB, continuous CDCB (cCDCB), length of CD/CB/cCDCB lines, and severity of CB were analyzed. RESULTS: In obese patients, the overall incidence of CD (3.1% versus 2.6%; P=0.002), CB (1.8% versus 1.2%; P<0.001), and cCDCB (2.6% versus 1.9%; P<0.001) was higher and CD (P=0.012) and cCDCB (P<0.001) lines are longer. There were more conduction disorders at Bachmann bundle and this area has a higher incidence of CD (4.4% versus 3.3%, P=0.002), CB (3.1% versus 1.6%, P<0.001), cCDCB (4.6% versus 2.7%, P<0.001) and longer CD (P<0.001) or cCDCB (P=0.017) lines. The severity of CB is also higher, particularly in the Bachmann bundle (P=0.008) and pulmonary vein (P=0.020) areas. In addition, obese patients have a higher incidence of early de-novo postoperative atrial fibrillation (P=0.003). Body mass index (P=0.037) and the overall amount of CB (P=0.012) were independent predictors for incidence of early postoperative atrial fibrillation. CONCLUSIONS: Compared with nonobese patients, obese patients have higher incidences of conduction disorders, which are also more extensive and more severe. These differences in heterogeneity in conduction are already present during sinus rhythm and may explain the higher vulnerability to atrial fibrillation of obese patients.


Assuntos
Fibrilação Atrial/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Bloqueio Cardíaco/epidemiologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Obesidade/epidemiologia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
8.
J Thorac Cardiovasc Surg ; 160(2): 490-496, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32192723

RESUMO

OBJECTIVE: To visualize and quantify the atrioventricular conduction axis in the setting of ventricular septal defect using phase contrast computed tomography. METHODS: We used the SPring-8 synchrotron radiation facility in Hyogo prefecture in Japan, processing and reconstructing the data with 3-dimensional software. RESULTS: We studied 8 hearts obtained from patients known to have had ventricular septal defects, aged from 6 to 150 days, with a median of 24.5 days. None of the individuals, however, had undergone corrective surgery. The penetrating bundle was found at a median of 1.43 mm from the septal crest, with a range of 0.99 to 1.54 mm. The distance to the nonbranching bundle to the right ventricular endocardium was 1.10 mm, with a range from 0.49 to 2.49 mm, to the origin of the left bundle branch was 2.46 mm, with a range from 1.7 to 3.18 mm, and to the origin of the right bundle branch was 2.34 mm, with a range from 0.50 to 2.59 mm. The median distance from the edge of the caudal limb of the septomarginal trabeculation to the right bundle branch was 1.04 mm, with a range from 0.81 to 1.16 mm. CONCLUSIONS: We were able to show the precise location of the axis, with our findings suggesting that longitudinal sutures placed along the posteroinferior rim should be effective in avoiding iatrogenic injury, but sutures should not be placed in the valley between the limbs of the septomarginal trabeculation.


Assuntos
Sistema de Condução Cardíaco/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Tomada de Decisão Clínica , Feminino , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/fisiopatologia , Bloqueio Cardíaco/prevenção & controle , Sistema de Condução Cardíaco/fisiopatologia , Comunicação Interventricular/fisiopatologia , Comunicação Interventricular/cirurgia , Humanos , Doença Iatrogênica , Imageamento Tridimensional , Lactente , Recém-Nascido , Japão , Masculino , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Técnicas de Sutura/efeitos adversos
9.
Am J Cardiol ; 125(8): 1263-1269, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32081367

RESUMO

Implantation of a permanent pacemaker is a negative prognostic marker in patients with Fontan palliation; however, data delineating outcomes in adult patients with pacemaker requirements are lacking. We hypothesize that high ventricular pacing burden is associated with adverse outcomes in adult Fontan patients. We performed a retrospective review comprising adult patients with history of Fontan repair. A high burden of ventricular pacing was defined as ≥40% pacing. Major adverse clinical events (MACE) were defined as all-cause mortality or need for advanced cardiac therapies (ventricular assist device or heart transplant). A total of 145 adult patients with Fontan were studied for a median of 3.1 years. Twenty (14%) patients had implanted pacemakers with ≥40% ventricular pacing. Twelve events occurred in those with ≥40% ventricular pacing (incidence 60.0%) versus 11 in those without (incidence 8.8%). In multivariable analysis, ≥40% ventricular-pacing (odds ratio 12.51, confidence interval [CI] 3.56 to 43.83, p <0.001) was associated with MACE independent of initial Fontan type, New York Heart Association functional class at baseline, or history of atrial tachyarrythmia. In survival analysis, patients with ≥40% ventricular pacing had nearly 8 times the risk of MACE compared with those with a lower ventricular pacing burden (hazard ratio 7.79, 95% CI 2.56 to 23.66, p <0.001), whereas patients with atrial-only or <40% ventricular pacing burden had a trend toward higher hazard of MACE compared with those without permanent pacemaker (hazard ratio 3.38, 95% CI 0.92 to 12.47, p = 0.07) that did not meet statistical significance. These findings suggest that high ventricular pacing burden contributes to poor outcomes in the adult Fontan patients and bear consideration when determining optimal treatment of tachyarrhythmias in this population.


Assuntos
Estimulação Cardíaca Artificial/estatística & dados numéricos , Técnica de Fontan , Bloqueio Cardíaco/terapia , Cardiopatias Congênitas/cirurgia , Transplante de Coração/estatística & dados numéricos , Coração Auxiliar/estatística & dados numéricos , Mortalidade , Complicações Pós-Operatórias/terapia , Adulto , Feminino , Bloqueio Cardíaco/fisiopatologia , Defeitos dos Septos Cardíacos/cirurgia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Masculino , Razão de Chances , Marca-Passo Artificial , Complicações Pós-Operatórias/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Síndrome do Nó Sinusal/fisiopatologia , Síndrome do Nó Sinusal/terapia , Atresia Tricúspide/cirurgia , Adulto Jovem
12.
Card Electrophysiol Clin ; 11(2): 261-281, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31084850

RESUMO

Sinus node dysfunction or atrioventricular blocks are the causes of bradycardias. Diagnosis and management begin with evaluation of patient's hemodynamic status and diagnosis of bradycardia's cause. This is followed by an in depth evaluation of pathophysiology of the arrhythmia, its severity, and likelihood of progression. Implementing emergent measures depends on the presence of subsidiary pace makers maintaining cardiac output. Many of these decisions are greatly helped by 12 lead electrocardiogram, because its tracings are often diagnostic of the cause of the bradycardia and help to assess its persistence and progression and to evaluate the presence and reliability of subsidiary pacemakers.


Assuntos
Bradicardia , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Eletrocardiografia , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Humanos
17.
Pharmacol Res ; 141: 443-450, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30677516

RESUMO

Despite recent advances in the treatment of cardiac arrhythmia, the available options are still limited and associated with some complications. Induction of biological pacemakers via Tbx18 gene insertion in the heart tissue has been suggested as a promising therapeutic strategy for cardiac arrhythmia. Following a previous in vitro study reporting the production of Tbx18-expressing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), we aimed to investigate the efficacy of these engineered cells to generate pacemaker rhythms in a murine model of complete heart block. We also attempted to generate a functional pacemaker by Tbx18 overexpression in native cardiac cells of rat heart. The hiPSC-derived pacemaker cells were produced by lentiviral delivery of Tbx18 gene to stem cells during a small molecule-based differentiation process. In the present study, 16 male albino Wistar rats were randomly assigned to Tbx18-lentivirus (n = 4) and Tbx18-pacemaker cells (n = 4) administered via injection into the left ventricular anterolateral wall. The control rats received GFP-lentiviruses (n = 4) and GFP-pacemaker cells (n = 4). Fourteen days after the injection, the rats were sacrificed and analyzed by electrocardiography (ECG) recording using a Langendorff-perfused heart model following complete heart block induced by hypokalemia and crashing. Immunofluorescence staining was used to investigate the expression of Tbx18, HCN4 and connexin 43 (Cx43) proteins in Tbx18-delivered cells of heart tissues. The heart rate was significantly reduced after complete heart block in all of the experimental rats (P < 0.05). Heart beating in the Tbx18-transduced hearts was slower compared with rats receiving Tbx18-pacemaker cells (P = 0.04). The duration of ventricular fibrillation (VF) was higher in the lentiviral Tbx18 group compared with the GFP-injected controls (P = 0.02) and the Tbx18-pacemaker cell group (P = 0.02). The ECG recording data showed spontaneous pacemaker rhythms in both intervention groups with signal propagation in Tbx18-transduced ventricles. Immunostaining results confirmed the overexpression of HCN4 and downregulation of Cx43 as a result of the expression of the Tbx18 gene and spontaneously contracting myocyte formation. We confirmed the formation of a functional pacemaker after introduction of Tbx18 via cell and gene therapy strategies. Although the pacemaker activity was better in gene-received hearts since there were longer VF duration and signal propagation from the injection site, more data should be gathered from the long-term activity of such pacemakers in different hosts.


Assuntos
Técnicas de Transferência de Genes , Engenharia Genética , Bloqueio Cardíaco/terapia , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/transplante , Proteínas com Domínio T/genética , Animais , Diferenciação Celular , Modelos Animais de Doenças , Vetores Genéticos/genética , Bloqueio Cardíaco/fisiopatologia , Frequência Cardíaca , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lentivirus/genética , Masculino , Miócitos Cardíacos/metabolismo , Ratos , Ratos Wistar
18.
Circ Cardiovasc Imaging ; 12(1): e007508, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30636515

RESUMO

BACKGROUND: The risk of conduction system abnormalities (CSA) after transcatheter aortic valve implantation remains high. We aimed to evaluate the impact of mitral annular calcium (MAC) score on the development of CSA after transcatheter aortic valve implantation. METHODS: Consecutive patients (n=168), with severe AoV stenosis, without prior CSA, underwent computed tomography transcatheter AoV implantation followed by device implantation; CoreValve (n=72) and SAPIEN (n=96). MAC, AoV, and left ventricular outflow tract calcium (Ca++) scores were quantitated from noncontrast ECG-gated computed tomography using Agatston method. The primary end point was a combination of complete left bundle branch block or high-degree atrioventricular block. Logistic regression was used to analyze the predictive value of Ca++ scores of different locations. RESULTS: The primary end point was documented in 62% of the fourth quartile MAC score (>2700) patients as compared with 31% of the first quartile (<140); P=0.03. Logistic regression analysis documented MAC score as an independent predictor either of primary end point as a continuous variable (odds ratio: 1.02, 95% [CI]: 1.00 - 1.03, p = 0.021) or as quartile cutoffs, whereas Q4 was a strong and independent predictor (odds ratio: 3.69, 95% [CI]: 1.37 - 9.95, p = 0.010). CONCLUSIONS: MAC score was found to be an independent predictor of CSA in patients undergoing transcatheter aortic valve implantation without preexisting CSA. Therefore, the current study suggests that patients with high MAC score category (fourth MAC score quartile) should be considered at high risk for CSA, warranting closer monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02023060.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Calcinose/diagnóstico por imagem , Bloqueio Cardíaco/etiologia , Valva Mitral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Calcinose/complicações , Calcinose/fisiopatologia , Bases de Dados Factuais , Eletrocardiografia , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Humanos , Masculino , Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Ultrasound Obstet Gynecol ; 54(1): 87-95, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30620419

RESUMO

OBJECTIVES: Assuming that autoimmune congenital heart block (CHB) is a progressive disease amenable to therapeutic modulation, we introduced a surveillance program for at-risk pregnancies with the dual aim of investigating if fetal atrioventricular block (AVB) could be detected and treated before becoming complete and irreversible, and to establish the incidence of AVB I, II and III in a large prospective cohort. METHODS: This was a prospective study of 212 anti-Ro52 antibody-exposed pregnancies at risk of fetal AVB that were followed weekly between 18 and 24 weeks' gestation at our tertiary fetal cardiology center from 2000 to 2015. A 12-lead electrocardiogram (ECG) was recorded within 1 week after birth. Fetal Doppler atrioventricular (AV) intervals were converted to Z-scores using reference standard values derived from normal pregnancies. Each fetus was represented by the average value of the two recordings, obtained at two consecutive visits, which resulted in the longest AV interval. AV interval values were classified into normal AV conduction (Z-score ≤ 2.0) and three levels of delayed AV conduction: Z-score > 2.0 and ≤ 3.0, Z-score > 3.0 and ≤ 4.0, and Z-score > 4.0. RESULTS: AVB II or III developed in 6/204 (2.9%) pregnancies without a CHB history and 1/8 (12.5%) of those with a CHB history. AV intervals > 2 and ≤ 3, > 3 and ≤ 4, and > 4 were detected in 16.0%, 7.5% and 2.8% of cases, respectively, and were related to the PR interval on 185 available ECGs. Three of the five cases with AVB III and one of two cases with 2:1 AVB II developed within 1 week of AV interval Z-score of 1.0, 1.9, 2.8 and 1.9, respectively. Transplacental treatment with betamethasone was associated with restoration of 1:1 AV conduction in the two fetuses with AVB II, with a better long-term result (normal ECG vs AVB I or II) observed in the case in which treatment was started within 1 week after AVB developed. Betamethasone treatment did not reverse AVB III, although a temporary effect on AV conduction was observed in 1/5 cases. Notably, the three cases in which treatment was started within 1 week after AVB III development responded with a higher ventricular rate than the other two cases and did not require pacemaker implantation until a later age (2-5 years vs 1.5-2 months). CONCLUSION: Fetal AV interval is a poor predictor of CHB progression, but CHB surveillance still allows detection of fetuses with AVB II or III shortly after its development, allowing for timely treatment initiation and potentially better outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Bloqueio Atrioventricular/prevenção & controle , Ecocardiografia/métodos , Coração Fetal/diagnóstico por imagem , Feto/diagnóstico por imagem , Bloqueio Cardíaco/congênito , Bloqueio Atrioventricular/classificação , Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/fisiopatologia , Autoanticorpos , Doenças Autoimunes/sangue , Doenças Autoimunes/tratamento farmacológico , Betametasona/administração & dosagem , Betametasona/uso terapêutico , Ecocardiografia Doppler/métodos , Feminino , Coração Fetal/fisiopatologia , Feto/patologia , Idade Gestacional , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/imunologia , Bloqueio Cardíaco/fisiopatologia , Humanos , Incidência , Lactente , Recém-Nascido , Gravidez/sangue , Gravidez/imunologia , Estudos Prospectivos , Resultado do Tratamento
20.
Int Heart J ; 60(1): 12-18, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30518714

RESUMO

Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients having EDMD show the triad of muscle dystrophy, joint contracture, and cardiac disease. In almost all patients, cardiac involvement is prevalent and is the most severe aspect of EDMD. Cardiac disease is predominantly shown by conduction defects, atrial fibrillation/flutter, and atrial standstill. Sudden death and heart failure because of left ventricular dysfunction are important causes of mortality, particularly in those patients that have the LMNA mutation. Medical treatment of EDMD is limited to addressing symptoms and ambulation support; moreover, pacemaker implantation is necessary when there are severe conduction defects and bradycardia occurs. Note that automated defibrillation devices may be considered for those patients who have a high risk of sudden death, rate, or rhythm control. Also, anticoagulation should be initiated in those patients who have atrial fibrillation/flutter. Thus, for optimal management, a multidisciplinary approach is required.


Assuntos
Fibrilação Atrial/terapia , Distrofia Muscular de Emery-Dreifuss/genética , Disfunção Ventricular Esquerda/mortalidade , Anormalidades Múltiplas/epidemiologia , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Cardiomiopatias/fisiopatologia , Fissura Palatina/complicações , Fissura Palatina/epidemiologia , Contratura/complicações , Contratura/epidemiologia , Morte Súbita/epidemiologia , Feminino , Doenças Genéticas Inatas/fisiopatologia , Átrios do Coração/anormalidades , Átrios do Coração/fisiopatologia , Bloqueio Cardíaco/fisiopatologia , Cardiopatias/complicações , Cardiopatias/epidemiologia , Humanos , Hidrocefalia/complicações , Hidrocefalia/epidemiologia , Comunicação Interdisciplinar , Deformidades Congênitas dos Membros/complicações , Deformidades Congênitas dos Membros/epidemiologia , Masculino , Distrofias Musculares/complicações , Distrofias Musculares/epidemiologia , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Distrofia Muscular de Emery-Dreifuss/terapia , Marca-Passo Artificial/normas , Disfunção Ventricular Esquerda/epidemiologia
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