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1.
Cardiovasc Eng Technol ; 13(6): 864-871, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35545751

RESUMO

OBJECTIVES: Previous studies have observed an increase in low frequency diastolic heart sounds in patients with coronary artery disease (CAD). The aim was to develop and validate a diagnostic, computerized acoustic CAD-score based on heart sounds for the non-invasive detection of CAD. METHODS: Prospective study enrolling 463 patients referred for elective coronary angiography. Pre-procedure non-invasive recordings of heart sounds were obtained using a novel acoustic sensor. A CAD-score was defined as the power ratio between the 10-90 Hz frequency spectrum and the 90-300 Hz frequency spectrum of the mid-diastolic heart sound. Quantitative coronary angiography analysis was performed by a blinded core laboratory and patients grouped according to the results: obstructive CAD defined by the presence of at least one ≥ 50% stenosis, non-obstructive CAD as patients with a maximal stenosis in the 25-50% interval and non-CAD as no coronary lesions exceeding 25%. We excluded patients with potential confounders or incomplete data (n = 245). To avoid over-fitting the final cohort of 218 patients was randomly divided into to a training group for development (n = 127) and a validation group (n = 91). RESULTS: In both the training and the validation group the CAD-score was significantly increased in CAD patients compared to non-CAD patients (p < 0.0001). In the validation group the area under the receiver-operating curve was 77% (95% CI 63-91%). Sensitivity was 71% (95% CI 59-82%) and specificity 64% (95% CI 45-83%). CONCLUSION: The acoustic CAD-score is a new, inexpensive, non-invasive method to detect CAD, which may supplement clinical risk stratification and reduce the need for subsequent non-invasive and invasive testing.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Ruídos Cardíacos , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Prospectivos , Constrição Patológica , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem
2.
Pharmacol Res ; 167: 105546, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33716167

RESUMO

CONTEXT: The comparative efficacy of gestational diabetes (GDM) treatments lack conclusive evidence for choice of first-line treatment. OBJECTIVES: The aim of this study was to compare the efficacy of metformin and glibenclamide to insulin using a core outcome set (COS) to unify outcomes across trials investigating the treatment of gestational diabetes mellitus. STUDY DESIGN: A network meta-analysis (NMA) was conducted. DATA-SOURCE: PubMed, Embase, and Cochrane Controlled Register of Trials were searched from inception to January 2020. STUDY SELECTION: RCTs that enrolled pregnant women who were diagnosed with GDM and that compared the efficacy of different pharmacological interventions for the treatment of GDM were included. META-ANALYSIS: A generalized pairwise modelling framework was employed. RESULTS: A total of 38 RCTs with 6046 participants were included in the network meta-analysis. Compared to insulin, the estimated effect of metformin indicated improvements for weight gain (WMD -2·39 kg; 95% CI -3·31 to -1·46), maternal hypoglycemia (OR 0.34; 95% CI 0.12 to 0·97) and LGA (OR 0.61; 95% CI 0.38 to 0·98). There were also improvements in estimated effects for neonatal hypoglycemia (OR 0.48; 95% CI 0.19 to 1·25), pregnancy induced hypertension (OR 0.63; 95% CI 0.37 to 1·06), and preeclampsia (OR 0.74; 95% CI 0.538 to 1·04), though with limited evidence against our model hypothesis of equivalence with insulin for these outcomes. CONCLUSION: Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , Feminino , Glibureto/uso terapêutico , Humanos , Gravidez , Resultado do Tratamento
3.
Diabetes Res Clin Pract ; 168: 108371, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32827593

RESUMO

AIMS: The effectiveness of physical activity (PA) programs for prevention of gestational diabetes (GDM) lacks conclusive evidence. The aim of this study was to generate clear evidence regarding the effectiveness of physical activity programs in GDM prevention to guide clinical practice. METHODS: PubMed/Medline, ISI Web of Science, Scopus, and EMBASE were searched to identify the randomized trials (RCTs) published until June 2019. Randomised controlled trials enrolling women at high risk before the 20th week of gestation comparing the effect of PA interventions with usual care for prevention of GDM were retrieved. Data obtained were synthesised using a bias-adjusted model of meta-analysis. RESULTS: A total of 1467 adult women in 11 eligible trials were included. The risk of GDM was significantly lower with PA, but only when it was delivered in the healthcare facility (RR 0.53; 95% CI 0.38-0.74). The number needed to treat with PA in pregnancy (compared to usual care) to prevent one GDM event was 18 (95% CI 14 - 29). The overall effect of PA interventions regardless of location of the intervention was RR 0.69 (95% CI 0.51 - 0.94). CONCLUSIONS: This study provides evidence that in-facility physical activity programs started before the 20th week of gestation can significantly decrease the incidence of GDM among women at high risk.


Assuntos
Diabetes Gestacional/prevenção & controle , Exercício Físico/fisiologia , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
4.
Biomed Tech (Berl) ; 65(2): 219-227, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31527289

RESUMO

Coronary stents made of zinc (Zn)-0.8 copper (Cu) (in wt%) alloy were developed as biodegradable metal stents (Zn-Cu stents) in this study. The mechanical properties of the Zn-Cu stents and the possible gain effects were characterized by in vitro and in vivo experiments compared with 316L stainless steel stents (316L stents). Young's modulus of the as-extruded Zn-0.8Cu alloy and properties of the stents, including their intrinsic elastic recoil, stent trackability were evaluated compared with 316L stents. In vivo study was also conducted to evaluate restoration of pulsatility of vessel segment implanted stents. Both Zn-Cu stents and 316L stents have good acute lumen gain. By comparison, the advantages of Zn-Cu stents are as follows: (I) Zn-Cu stents have less intrinsic elastic recoil than 316L stents; (II) stent trackability indicates that Zn-Cu stents have a smaller push force when passing through curved blood vessels, which may cause less mechanical stimulation to blood vessels; (III) in vivo study suggests that Zn-Cu stents implantation better facilitates the recovery of vascular pulsatility.


Assuntos
Ligas/química , Materiais Biocompatíveis/química , Stents , Zinco/química , Módulo de Elasticidade , Aço Inoxidável
5.
Catheter Cardiovasc Interv ; 96(2): E119-E128, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31659805

RESUMO

OBJECTIVES: The aim of this study is to improve local-drug delivery efficiency and tissue absorption using the ultrasound (US)-responsible drug coating based on a newly developed US-controlled paclitaxel release balloon. BACKGROUND: Low availability of the drug coating remains a major concern of the current drug coated balloon (DCB). The goal of this study is to develop a method to use an US-responsible paclitaxel-loaded microcapsules (PM) as the main content of balloon drug coating to enhance bioavailability of DCB. METHODS: An US-controlled paclitaxel release balloon is designed and fabricated based on the US-responsible paclitaxel-loaded poly (lactic-co-glycolic acid) (PLGA) microcapsules. Rapid exchange percutaneous transluminal coronary angioplasty (PTCA) balloon catheters were coated with the PM. The deployment processes of the paclitaxel-loaded microcapsules coated balloons (PMCB) under US, PMCB without US and a homogenous matrix of paclitaxel and iopromide coated balloon (PICB) were then placed in healthy and stent implanted porcine coronary arteries. RESULTS: In vitro release assay demonstrated an ability of US (1 MHz, 1.22 W/cm2 , 1 minute) to affect the release kinetics of paclitaxel from PM by inducing a 76 ± 5.4% increase in the rate of release. The paclitaxel content in target vessels are 203 ± 37 µg/g for PMCB under US, 85 ± 23 µg/g for PMCB without US, and 107 ± 31 µg/g for PICB 1-hr post-surgery. The availability of the drug for the PMCB reaches 27% under US. CONCLUSIONS: The US-controlled paclitaxel release balloon significantly improved the drug content of the target vessels in the porcine model.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Vasos Coronários/metabolismo , Paclitaxel/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ondas Ultrassônicas , Animais , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacocinética , Preparações de Ação Retardada , Portadores de Fármacos , Liberação Controlada de Fármacos , Masculino , Paclitaxel/química , Paclitaxel/farmacocinética , Solubilidade , Sus scrofa
6.
Obes Rev ; 21(1): e12964, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31667980

RESUMO

Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively. This work assesses the efficacy of metformin in pregnancy to avert one outcome-incident GDM in women at high risk. We included RCTs comparing metformin with usual care or placebo controls in terms of incident GDM and recruiting women at high risk during early pregnancy. Eleven eligible trials enrolled 2370 adult women whose intervention arm consisted of metformin started at conception or before 20 weeks of gestation. Risk of GDM was similar in intervention compared with controls (risk ratio [RR] 1.03; 95% confidence interval [CI], 0.85-1.24). The data were of sufficient quality meeting the criteria for consistency and directness. We conclude that metformin does not contribute to averting the GDM outcome in women at high risk when initiated in pregnancy. The evidence provided by this synthesis affirms that further broad clinical trials investigating this question are no longer needed.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Acta Biomater ; 97: 657-670, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401346

RESUMO

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ±â€¯13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. STATEMENT OF SIGNIFICANCE: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.


Assuntos
Implantes Absorvíveis , Vasos Coronários , Teste de Materiais , Stents , Tomografia de Coerência Óptica , Animais , Cobre/química , Cobre/metabolismo , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Suínos , Fatores de Tempo , Zinco/química , Zinco/metabolismo
8.
J Cardiovasc Electrophysiol ; 30(9): 1671-1678, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31310416

RESUMO

BACKGROUND AND OBJECTIVES: The success rate of leadless cardiac pacemaker (LP) retrieval remains a major concern for this disruptive technology. The present paper performed a systematic review of the safety and feasibility of the retrieval of LPs. METHODS: Primary publications that performed LP retrieval were collected and included five animal experiments and two worldwide retrieval experiences in human. The procedural details, such as indication, days post implantation, extraction success rate, and complications, were described. The present paper analyzed factors affecting the retrieval and management of the nonfunctional devices. RESULTS: Retrieval animal models was possible at least up to 2.5 years post implantation, and data from humans suggest that removal of a device that was implanted longer (eg, 4 years and 9 months for Nanostim; 4 years for Micra) could be performed within a reasonable safety profile. The fixed mechanism, implant site, and encapsulation of the LP systems may affect the retrieval process. CONCLUSIONS: A high success rate in the relatively chronic retrieval of LPs was demonstrated, which promotes the extensive use of these devices in the treatment arrhythmia in the future.


Assuntos
Estimulação Cardíaca Artificial , Remoção de Dispositivo/métodos , Marca-Passo Artificial , Idoso , Idoso de 80 Anos ou mais , Animais , Remoção de Dispositivo/efeitos adversos , Desenho de Equipamento , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
BMC Med Educ ; 19(1): 155, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113457

RESUMO

BACKGROUND: Identification and assessment of professional competencies for medical students is challenging. We have recently developed an instrument for assessing the essential professional competencies for medical students in Problem-Based Learning (PBL) programs by PBL tutors. This study aims to evaluate the reliability and validity of professional competency scores of medical students using this instrument in PBL tutorials. METHODS: Each group of seven to eight students in PBL tutorials (Year 2, n = 46) were assessed independently by two faculty members. Each tutor assessed students in his/her group every five weeks on four occasions. The instrument consists of ten items, which measure three main competency domains: interpersonal, cognitive and professional behavior. Each item is scored using a five-point Likert scale (1 = poor, 5 = exceptional). Reliability of professional competencies scores was calculated using G-theory with raters nested in occasions. Furthermore, criterion-related validity was measured by testing the correlations with students' scores in written examination. RESULTS: The overall generalizability coefficient (G) of the professional competency scores was 0.80. Students' professional competencies scores (universe scores) accounted for 27% of the total variance across all score comparisons. The variance due to occasions accounted for 10%, while the student-occasion interaction was zero. The variance due to raters to occasions represented 8% of the total variance, and the remaining 55% of the variance was due to unexplained sources of error. The highest reliability measured was the interpersonal domain (G = 0.84) and the lowest reliability was the professional behavior domain (G = 0.76). Results from the decision (D) study suggested that an adequate dependability (G = 0.71) can be achieved by using one rater for five occasions. Furthermore, there was a positive correlation between the written examination scores and cognitive competencies scores (r = 0.46, P < 0.01), but not with the other two competency domains (interpersonal and professionalism). CONCLUSIONS: This study demonstrates that professional competency assessment scores of medical students in PBL tutorials have an acceptable reliability. Further studies for validating the instrument are required before using it for summative evaluation of students by PBL tutors.


Assuntos
Currículo , Educação de Graduação em Medicina/métodos , Aprendizagem Baseada em Problemas , Competência Profissional , Estudantes de Medicina/psicologia , Avaliação Educacional/métodos , Processos Grupais , Humanos , Reprodutibilidade dos Testes
10.
Ann N Y Acad Sci ; 1448(1): 19-29, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30937913

RESUMO

Calmodulin (CaM) is a universal calcium (Ca2+ )-binding messenger that regulates many vital cellular events. In cardiac muscle, CaM associates with ryanodine receptor 2 (RyR2) and regulates excitation-contraction coupling. Mutations in human genes CALM1, CALM2, and CALM3 have been associated with life-threatening heart disorders, such as long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia. A novel de novo LQTS-associated missense CaM mutation (E105A) was recently identified in a 6-year-old boy, who experienced an aborted first episode of cardiac arrest. Herein, we report the first molecular characterization of the CaM E105A mutation. Expression of the CaM E105A mutant in zebrafish embryos resulted in cardiac arrhythmia and increased heart rate, suggestive of ventricular tachycardia. In vitro biophysical and biochemical analysis revealed that E105A confers a deleterious effect on protein stability and a reduced Ca2+ -binding affinity due to loss of cooperativity. Finally, the CaM E105A mutation resulted in reduced CaM-RyR2 interaction and defective modulation of ryanodine binding. Our findings suggest that the CaM E105A mutation dysregulates normal cardiac function by a complex mechanism involving alterations in both CaM-Ca2+ and CaM-RyR2 interactions.


Assuntos
Arritmias Cardíacas/genética , Calmodulina/genética , Calmodulina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Taquicardia Ventricular/genética , Animais , Arritmias Cardíacas/patologia , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Criança , Acoplamento Excitação-Contração/fisiologia , Frequência Cardíaca/genética , Frequência Cardíaca/fisiologia , Humanos , Masculino , Miócitos Cardíacos/metabolismo , Taquicardia Ventricular/fisiopatologia , Peixe-Zebra
11.
J Vasc Access ; 20(6): 577-582, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30838913

RESUMO

BACKGROUND: Recently, intracavitary electrocardiogram technology has been applied to peripherally inserted central catheter placement and demonstrates many potential advantages. However, the tip positioning accuracy of intracavitary electrocardiogram technology compared to conventional X-ray method is unknown. OBJECTIVE: We did a meta-analysis to compare the tip positioning accuracy between intracavitary electrocardiogram technology and conventional X-ray method. DATA SOURCES: We searched several databases, including Cochrane Library, PubMed, Web of science, and Embase. Additional studies were identified through hand searches of bibliographies and Internet searches. All human studies published in full text, abstract, or poster form were eligible for inclusion. Search terms included peripherally inserted central catheter, PICC, intracavitary electrocardiogram, IC-ECG, EKG, ECG, and catheter tip location. STUDY ELIGIBILITY CRITERIA: Only randomized controlled trials of using intracavitary electrocardiogram technology versus X-ray method for peripherally inserted central catheter placement were included. All studies included adult patients aged at least 18 years. STUDY APPRAISAL AND SYNTHESIS METHODS: Independent extraction of articles by two authors using predefined data fields, including study quality indicators. Of the 178 citations identified, 5 studies that included 1672 patients met the eligibility criteria. It was found that statistical heterogeneity existed among the various studies (I2 = 16%, p < 0.00001); therefore, the fixed effect model was used in the meta-analysis (p < 0.05). The meta-analysis compared the tip positioning accuracy between intracavitary electrocardiogram technology and X-ray method and showed that intracavitary electrocardiogram technology had a better positioning accuracy (odds ratio: 2.88, 95% confidence interval: 2.15-3.87, p < 0.0001). LIMITATIONS: Only five randomized trial met inclusion criteria, and the lack of an incomplete search led to the publication bias seen in these results. CONCLUSION: The intracavitary electrocardiogram method had a more favorable positioning accuracy versus traditional X-ray method for peripherally inserted central catheter placement in adult patients. The intracavitary electrocardiogram can be a promising technique to guide tip positioning of peripherally inserted central catheter.


Assuntos
Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Eletrocardiografia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Cateteres Venosos Centrais , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Radiografia Intervencionista , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Cardiovasc Pharmacol ; 73(4): 241-247, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30688797

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) and antiarrhythmic drugs (AADs) are the main treatments used for atrial fibrillation (AF). In recent years, a number of articles comparing the 2 treatments have begun to emerge. Though, the influence of follow-up time in the meta-analysis was not considered in these articles. However, more recently, large-scale clinical trial articles have included follow-up with the patients up to 5 years after treatment. Therefore, the aim of this study was to assess the impact of variable follow-up times on the recurrence of AF by observing both the short-term and long-term efficacy and safety of catheter ablation and AADs for the treatment of AF. METHODS AND RESULTS: The primary investigators of eligible randomized controlled trials were invited to contribute standardized outcome data. Random effect summary estimates were calculated as standardized mean differences and odds ratios with 95% confidence intervals for continuous and binary outcomes. In this study, 9 randomized controlled trials (n = 1542 patients) were included. The rate of recurrence of AF with no limit on follow-up time, >12 months, >18 months, >24 months, >30 months, and approximately 36 months was compared. Furthermore, the gap between the RFA and AAD groups in the recurrence rate of AF was found to decrease inversely to follow-up time. When the follow-up time reached 24 months, the difference between RFA and AAD was relatively stable with an odds ratio of 0.45 (95% confidence interval: 0.32-0.62). Overall, RFA decreased adverse events in the remaining trials; however, AAD performed better in terms of safety and had fewer adverse events with RFA usually causing more serious complications. CONCLUSION: RFA is more advantageous in terms of recurrence rate of AF than drug therapy. In addition, the analysis suggests that this effect persists during long-term follow-up; however, these benefits appear to decrease with longer follow-up time. Finally, AAD performed better in terms of safety and had fewer adverse events.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Frequência Cardíaca/efeitos dos fármacos , Potenciais de Ação , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Biochem J ; 475(24): 3933-3948, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30446606

RESUMO

The most common inherited cardiac disorder, hypertrophic cardiomyopathy (HCM), is characterized by thickening of heart muscle, for which genetic mutations in cardiac myosin-binding protein C3 (c-MYBPC3) gene, is the leading cause. Notably, patients with HCM display a heterogeneous clinical presentation, onset and prognosis. Thus, delineating the molecular mechanisms that explain how disparate c-MYBPC3 variants lead to HCM is essential for correlating the impact of specific genotypes on clinical severity. Herein, five c-MYBPC3 missense variants clinically associated with HCM were investigated; namely V1 (R177H), V2 (A216T), V3 (E258K), V4 (E441K) and double mutation V5 (V3 + V4), all located within the C1 and C2 domains of MyBP-C, a region known to interact with sarcomeric protein, actin. Injection of the variant complementary RNAs in zebrafish embryos was observed to recapitulate phenotypic aspects of HCM in patients. Interestingly, V3- and V5-cRNA injection produced the most severe zebrafish cardiac phenotype, exhibiting increased diastolic/systolic myocardial thickness and significantly reduced heart rate compared with control zebrafish. Molecular analysis of recombinant C0-C2 protein fragments revealed that c-MYBPC3 variants alter the C0-C2 domain secondary structure, thermodynamic stability and importantly, result in a reduced binding affinity to cardiac actin. V5 (double mutant), displayed the greatest protein instability with concomitant loss of actin-binding function. Our study provides specific mechanistic insight into how c-MYBPC3 pathogenic variants alter both functional and structural characteristics of C0-C2 domains leading to impaired actin interaction and reduced contractility, which may provide a basis for elucidating the disease mechanism in HCM patients with c-MYBPC3 mutations.


Assuntos
Actinas/metabolismo , Cardiomiopatia Hipertrófica/metabolismo , Proteínas de Transporte/metabolismo , Variação Genética/fisiologia , Mutação de Sentido Incorreto/fisiologia , Actinas/genética , Adulto , Animais , Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/química , Proteínas de Transporte/genética , Humanos , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína , Peixe-Zebra
14.
Pacing Clin Electrophysiol ; 41(10): 1365-1371, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30066363

RESUMO

INTRODUCTION: Leadless cardiac pacemaker (LCP) implantation using a transcatheter was recently developed to avoid pocket- and lead-related complications. Although a LCP has an active fixation mechanism using tines or a helix, LCP and lead dislodgement issues remain a major safety concern for patients. This article reviews the literature to determine the incidence of lead and LCP dislodgement. METHODS AND RESULTS: A total of 18 studies which included 17,321 patients undergoing conventional single- or dual-chamber pacemaker implantation and three studies which included 2,116 patients undergoing LCP device implantation were reviewed. The incidence of lead dislodgement ranged from 1% to 2.69% in individual studies with a mean of 1.63%, weighted mean of 1.71%, and median of 1.60 %. There was a relatively higher lead dislodgement rate between atrial and ventricular electrodes (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.9-6.70; P  =  0.6; I2   =  0%), and between magnetic resonance imaging conditional and conventional leads (OR, 2.79; 95% CI, 1.30-5.99; P  =  0.16; I2   =  46%). The use of active fixation leads (OR, 1.06; 95% CI, 0.66-1.70; P  =  0.29; I2   =  20%) showed no significant difference in dislodgement risk compared to passive fixation leads. The incidence of LCP device dislodgement was 0%, 0.13%, and 1% in three leadless pacemaker studies. CONCLUSIONS: The incidence rates of conventional pacemaker lead dislodgement vary in individual studies with an overall high incidence. Use of the currently available LCP systems appears to result in a lower rate of device dislodgement. This may reflect the effectiveness of this novel technology and the fixation design of LCP devices.


Assuntos
Falha de Equipamento , Marca-Passo Artificial/efeitos adversos , Desenho de Equipamento , Humanos , Incidência , Fatores de Risco
15.
Clin Pharmacol Ther ; 103(6): 1100-1106, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28940299

RESUMO

The hypothesis of the study is that Torsades de pointes (TdP) history can be better identified using T-wave morphology compared to Fridericia-corrected QT interval (QTcF) at baseline. ECGs were recorded at baseline and during sotalol challenge in 20 patients with a history of TdP (+TdP) and 16 patients without previous TdP (-TdP). The QTcF and T-wave morphology combination score (MCS) were calculated. At baseline, there was no significant difference in QTcF between the groups (+TdP: QTcF = 446 ± 9 ms; -TdP: QTcF = 431 ± 9 ms, P = 0.27). In contrast, MCS was significantly different between the groups at baseline (+TdP: MCS = 1.07 ± 0.095; -TdP: MCS = 0.74 ± 0.07, P = 0.012). Both QTcF and MCS could be used to discriminate between +TdP and -TdP after sotalol but only MCS reached statistical significance at baseline. Combining QTcF with MCS provided a significantly larger difference between groups than QTcF alone.


Assuntos
Antiarrítmicos/farmacologia , Eletrocardiografia/efeitos dos fármacos , Sotalol/farmacologia , Torsades de Pointes/induzido quimicamente , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Front Biosci (Landmark Ed) ; 22(3): 407-415, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27814621

RESUMO

The aim of this study was to investigate the drug release profiles of biodegradable polymer sirolimus- or paclitaxel-eluting stents with asymmetrical coating (BPSES-A or BPPES-A) both in vitro and in vivo. In vitro, the drug release profile was characterized by measuring the drug concentration by HPLC over a time-course. In vivo, a porcine aorta stenting model was employed. The results showed that the drug release rates of BPSES-A and BPPES-A were slower, more stable and less burst releasing than those of conventionally coated stents (BPSES-C and BPPES-C respectively), both in vitro and in vivo. Based on the in vivo results, the sirolimus and paclitaxel content of the local coronary wall was maintained at a higher and more effective level with BPSES-A and BPPES-A than with BPSES-C and BPPES-C, respectively. The drug levels in peripheral tissue samples were below detection levels. These data demonstrated the effectiveness of both sirolimus and paclitaxel as stent coating agents, and revealed the favorable drug release kinetics and pharmacokinetics of asymmetrical coated stents compared with conventional coated stents.


Assuntos
Liberação Controlada de Fármacos , Stents Farmacológicos , Animais , Materiais Revestidos Biocompatíveis , Vasos Coronários/metabolismo , Vasos Coronários/cirurgia , Sistemas de Liberação de Medicamentos , Técnicas In Vitro , Cinética , Masculino , Teste de Materiais , Paclitaxel/sangue , Paclitaxel/farmacocinética , Sirolimo/sangue , Sirolimo/farmacocinética , Suínos , Porco Miniatura
17.
Medicine (Baltimore) ; 95(38): e4820, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27661023

RESUMO

BACKGROUND: The biodegradable polymer drug-eluting stents (DES) were developed to improve vascular healing. However, further data and longer-term follow-up are needed to confirm safety and efficacy of these stents. This randomized clinical trial aimed to compare safety and efficacy of 2 sirolimus-eluting stents (SES): Cordimax-a novel abluminal biodegradable polymer SES and Cypher Select-a durable polymer SES, at 9 months angiographic and 5-year clinical follow-up. METHODS: We randomized 402 patients with coronary artery disease to percutaneous coronary intervention with Cordimax (n = 202) or Cypher select (n = 200). Angiographic follow-up was performed at 9 months after the index procedure and clinical follow-up annually up to 5 years. The primary endpoint was angiographic in-stent late luminal loss (LLL). Secondary endpoints included angiographic restenosis rate, target vessel revascularization (TVR), and major adverse cardiac events (MACEs; defined as cardiac death, myocardial infarction, or TVR) at 5-year follow-up. RESULTS: Cordimax was noninferior to Cypher select for in-stent LLL (0.25 ±â€Š0.47 vs 0.18 ±â€Š0.49 mm; P = 0.587) and in-stent mean diameter stenosis (22.19 ±â€Š12.21% vs 19.89 ±â€Š10.79%; P = 0.064) at 9 months angiographic follow-up. The MACE rates were not different at 1 year (5.9% vs 4.0%, P = 0.376); however, MACE rates from 2 to 5 years were lower in the Cordimax group (6.8% vs 13.1%; P = 0.039). CONCLUSION: Abluminal biodegradable polymer SES is noninferior to durable polymer SES at 9-month angiographic and 1-year clinical follow-up. However, MACE rates from 2 to 5 years were less in the abluminal biodegradable polymer group.


Assuntos
Angiografia Coronária/estatística & dados numéricos , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Complicações Pós-Operatórias/etiologia , Implantes Absorvíveis , Idoso , Reestenose Coronária/epidemiologia , Reestenose Coronária/etiologia , Equipamentos Médicos Duráveis , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Polímeros , Complicações Pós-Operatórias/epidemiologia , Desenho de Prótese , Sirolimo/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
18.
Physiol Meas ; 37(7): 1163-71, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27328380

RESUMO

This observational study investigated digital auscultation for the purpose of assessing the clinical feasibility of monitoring vascular sounds in pregnancy. The study was performed at the Regional Hospital Viborg, Denmark, and included 29 pregnant women, 10 non-pregnant women and 10 male participants. Digital auscultation was performed with an electronic stethoscope bilaterally near the uterine arteries and correlated to the clinical diagnosis of preeclampsia (PE), intrauterine growth restriction (IUGR) or normal pregnancy in the group of pregnant participants. In the group of non-pregnant participants, digital auscultation was performed as control measurements in the same anatomical positions. The auscultations displayed pulse waveforms comprising systolic and diastolic periods in 20 of the 29 pregnant participants. However, in the non-pregnant and male participants, the pulse waveforms were absent. The pulsatile patterns are thus likely to originate from the arteries in relation to the pregnant uterus. In the participants displaying pulse waveforms, the presence of a dicrotic notch appeared with a sensitivity of 89% and a specificity of 100% in the discrimination of normal pregnancies (n = 11) from pregnancies with PE or IUGR (n = 9), (p < 0.001). This preliminary study shows the potential of identifying vascular complications during pregnancy such as preeclampsia and intrauterine growth restriction. The morphology of the derived pulse contour should be investigated and could be further developed to identify pathophysiology.


Assuntos
Auscultação/métodos , Diagnóstico Pré-Natal/métodos , Pulso Arterial/métodos , Artéria Uterina , Auscultação/instrumentação , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Índice de Massa Corporal , Equipamentos e Provisões Elétricas , Estudos de Viabilidade , Feminino , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Masculino , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Segundo Trimestre da Gravidez/fisiologia , Terceiro Trimestre da Gravidez/fisiologia , Diagnóstico Pré-Natal/instrumentação , Pulso Arterial/instrumentação , Sensibilidade e Especificidade , Estetoscópios , Ultrassonografia Doppler , Artéria Uterina/fisiologia , Artéria Uterina/fisiopatologia
19.
J Med Internet Res ; 18(3): e53, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26932229

RESUMO

As telehealth plays an even greater role in global health care delivery, it will be increasingly important to develop a strong evidence base of successful, innovative telehealth solutions that can lead to scalable and sustainable telehealth programs. This paper has two aims: (1) to describe the challenges of promoting telehealth implementation to advance adoption and (2) to present a global research agenda for personalized telehealth within chronic disease management. Using evidence from the United States and the European Union, this paper provides a global overview of the current state of telehealth services and benefits, presents fundamental principles that must be addressed to advance the status quo, and provides a framework for current and future research initiatives within telehealth for personalized care, treatment, and prevention. A broad, multinational research agenda can provide a uniform framework for identifying and rapidly replicating best practices, while concurrently fostering global collaboration in the development and rigorous testing of new and emerging telehealth technologies. In this paper, the members of the Transatlantic Telehealth Research Network offer a 12-point research agenda for future telehealth applications within chronic disease management.


Assuntos
Pesquisa Biomédica , Medicina de Precisão/tendências , Telemedicina/organização & administração , Doença Crônica/terapia , Gerenciamento Clínico , Previsões , Saúde Global , Humanos , Telemedicina/tendências
20.
Int J Cardiovasc Imaging ; 32(2): 235-245, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26335368

RESUMO

Optimizing risk assessment may reduce use of advanced diagnostic testing in patients with symptoms suggestive of stable coronary artery disease (CAD). Detection of diastolic murmurs from post-stenotic coronary turbulence with an acoustic sensor placed on the chest wall can serve as an easy, safe, and low-cost supplement to assist in the diagnosis of CAD. The aim of this study was to evaluate the diagnostic accuracy of an acoustic test (CAD-score) to detect CAD and compare it to clinical risk stratification and coronary artery calcium score (CACS). We prospectively enrolled patients with symptoms of CAD referred to either coronary computed tomography or invasive coronary angiography (ICA). All patients were tested with the CAD-score system. Obstructive CAD was defined as more than 50 % diameter stenosis diagnosed by quantitative analysis of the ICA. In total, 255 patients were included and obstructive CAD was diagnosed in 63 patients (28 %). Diagnostic accuracy evaluated by receiver operating characteristic curves was 72 % for the CAD-score, which was similar to the Diamond-Forrester clinical risk stratification score, 79 % (p = 0.12), but lower than CACS, 86 % (p < 0.01). Combining the CAD-score and Diamond-Forrester score, AUC increased to 82 %, which was significantly higher than the standalone CAD-score (p < 0.01) and Diamond-Forrester score (p < 0.05). Addition of the CAD-score to the Diamond-Forrester score increased correct reclassification, categorical net-reclassification index = 0.31 (p < 0.01). This study demonstrates the potential use of an acoustic system to identify CAD. The combination of clinical risk scores and an acoustic test seems to optimize patient selection for diagnostic investigation.


Assuntos
Angina Estável/complicações , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Som , Acústica , Idoso , Angina Estável/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/complicações , Estenose Coronária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade
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