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1.
Am J Cardiol ; 206: 191-199, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37708750

RESUMO

Antiplatelet therapy (APT) with aspirin and a P2Y12 inhibitor is commonly given to patients who underwent coronary artery bypass grafting (CABG) to reduce thrombotic events. APT resistance, the inadequate antiplatelet effect of these drugs, is a growing concern. This review aimed to assess APT resistance prevalence in patients who underwent CABG and its impact on clinical outcomes. We conducted a comprehensive search for relevant studies published to date. The included studies measured platelet function through laboratory assays and reported on clinical outcomes in patients who underwent CABG. The primary outcomes were major adverse cardiovascular events (MACEs) and mortality, whereas the secondary outcomes included acute coronary syndrome (ACS), stroke, and thromboembolic events. The meta-analysis used random-effects models, with heterogeneity assessed using the I2 statistic. The initial search identified 45 studies, with 11 meeting the inclusion criteria, involving 3,122 patients. The overall prevalence of APT resistance in patients who underwent CABG was 39%. Patients with APT resistance had significantly higher risks of MACEs and death (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06 to 2.83, p = 0.03) and postoperative myocardial infarction (OR 2.25, 95% CI 1.13 to 4.48, p = 0.02) than those without resistance. However, no significant association was found between APT resistance and stroke (OR 2.25, 95% CI 0.80 to 6.35, p = 0.12) or other thromboembolic events (OR 1.72, 95% CI 0.72 to 4.08, p = 0.22). In conclusion, APT resistance is prevalent in a significant proportion of patients who underwent CABG, increasing the risk of MACEs and postoperative myocardial infarction. These findings emphasize the need for further research to develop tailored antiplatelet strategies in this patient population.

3.
Nat Cardiovasc Res ; 2(8): 733-745, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38666037

RESUMO

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

4.
J Card Surg ; 37(12): 5521-5523, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36285534

RESUMO

BACKGROUND: Chest compressions during cardiopulmonary resuscitation (CPR) may cause sternal or rib fractures and chest wall instability. This can complicate medical management and significantly impair respiratory function. Surgical management of flail chest is technically demanding, and it becomes even more challenging if the patient requires a concomitant cardiac procedure. CASE PRESENTATION: A 78-year-old male suffered a cardiac arrest and sustained sternal and bilateral rib fractures during a successful CPR. He underwent a concomitant coronary artery bypass grafting and aortic valve replacement combined with stabilization of the chest wall. We discuss the possibility of fixation of bilateral rib fractures and its role in postoperative recovery after cardiac surgery. CONCLUSIONS: Chest wall stabilization for an already fragile patient, with impaired respiratory system performance, could help improve overall outcomes, pulmonary function, weaning from mechanical ventilation, and rehabilitation. It may be used together with a cardiac procedure for a life-threatening cardiac pathology.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Reanimação Cardiopulmonar , Tórax Fundido , Fraturas das Costelas , Masculino , Humanos , Idoso , Fraturas das Costelas/etiologia , Fraturas das Costelas/cirurgia , Tórax Fundido/etiologia , Tórax Fundido/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Respiração Artificial/efeitos adversos , Reanimação Cardiopulmonar/efeitos adversos
5.
BMC Cardiovasc Disord ; 21(1): 434, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521355

RESUMO

BACKGROUND: The coronavirus-disease 2019 (COVID-19) pandemic imposed an unprecedented burden on the provision of cardiac surgical services. The reallocation of workforce and resources necessitated the postponement of elective operations in this cohort of high-risk patients. We investigated the impact of this outbreak on the aortic valve surgery activity at a single two-site centre in the United Kingdom. METHODS: Data were extracted from the local surgical database, including the demographics, clinical characteristics, and outcomes of patients operated on from March 2020 to May 2020 with only one of the two sites resuming operative activity and compared with the respective 2019 period. A similar comparison was conducted with the period between June 2020 and August 2020, when operative activity was restored at both institutional sites. The experience of centres world-wide was invoked to assess the efficiency of our services. RESULTS: There was an initial 38.2% reduction in the total number of operations with a 70% reduction in elective cases, compared with a 159% increase in urgent and emergency operations. The attendant surgical risk was significantly higher [median Euroscore II was 2.7 [1.9-5.2] in 2020 versus 2.1 [0.9-3.7] in 2019 (p = 0.005)] but neither 30-day survival nor freedom from major post-operative complications (re-sternotomy for bleeding/tamponade, transient ischemic attack/stroke, renal replacement therapy) was compromised (p > 0.05 for all comparisons). Recommencement of activity at both institutional sites conferred a surgical volume within 17% of the pre-COVID-19 era. CONCLUSIONS: Our institution managed to offer a considerable volume of aortic valve surgical activity over the first COVID-19 outbreak to a cohort of higher-risk patients, without compromising post-operative outcomes. A backlog of elective cases is expected to develop, the accommodation of which after surgical activity normalisation will be crucial to monitor.


Assuntos
Valva Aórtica/cirurgia , COVID-19 , Procedimentos Cirúrgicos Cardíacos/tendências , Doenças das Valvas Cardíacas/cirurgia , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências , Padrões de Prática Médica/tendências , Cirurgiões/tendências , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Bases de Dados Factuais , Procedimentos Cirúrgicos Eletivos/tendências , Feminino , Doenças das Valvas Cardíacas/mortalidade , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Cardiovasc Revasc Med ; 28S: 176-179, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33627297

RESUMO

Surgical pericardiectomy is the accepted treatment for patients with constrictive pericarditis. Right ventricular failure in patients that undergo pericardiectomy is a frequent complication due to sudden volume overload. Impella RP is used to bypass the right ventricle and tackle the transient right ventricular failure. It is implanted percutaneously and provides enough support to achieve haemodynamical stability and recover end-organ function. We report the case of a patient that developed acute right ventricular failure in the early postoperative period of a pericardiectomy. He underwent the implantation of an Impella RP in the setting of acute right ventricular failure and was successfully explanted after 6 days of support.


Assuntos
Insuficiência Cardíaca , Pericardite Constritiva , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pericardiectomia , Pericardite Constritiva/diagnóstico por imagem , Pericardite Constritiva/etiologia
7.
JMIR Med Inform ; 9(2): e22164, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565992

RESUMO

BACKGROUND: Myocardial infarction (MI; location and extent of infarction) can be determined by late enhancement cardiac magnetic resonance (CMR) imaging, which requires the injection of a potentially harmful gadolinium-based contrast agent (GBCA). Alternatively, emerging research in the area of myocardial strain has shown potential to identify MI using strain values. OBJECTIVE: This study aims to identify the location of MI by developing an applied algorithmic method of circumferential strain (CS) values, which are derived through a novel hierarchical template matching (HTM) method. METHODS: HTM-based CS H-spread from end-diastole to end-systole was used to develop an applied method. Grid-tagging magnetic resonance imaging was used to calculate strain values in the left ventricular (LV) myocardium, followed by the 16-segment American Heart Association model. The data set was used with k-fold cross-validation to estimate the percentage reduction of H-spread among infarcted and noninfarcted LV segments. A total of 43 participants (38 MI and 5 healthy) who underwent CMR imaging were retrospectively selected. Infarcted segments detected by using this method were validated by comparison with late enhancement CMR, and the diagnostic performance of the applied algorithmic method was evaluated with a receiver operating characteristic curve test. RESULTS: The H-spread of the CS was reduced in infarcted segments compared with noninfarcted segments of the LV. The reductions were 30% in basal segments, 30% in midventricular segments, and 20% in apical LV segments. The diagnostic accuracy of detection, using the reported method, was represented by area under the curve values, which were 0.85, 0.82, and 0.87 for basal, midventricular, and apical slices, respectively, demonstrating good agreement with the late-gadolinium enhancement-based detections. CONCLUSIONS: The proposed applied algorithmic method has the potential to accurately identify the location of infarcted LV segments without the administration of late-gadolinium enhancement. Such an approach adds the potential to safely identify MI, potentially reduce patient scanning time, and extend the utility of CMR in patients who are contraindicated for the use of GBCA.

9.
Eur J Cardiothorac Surg ; 57(3): 512-519, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31549144

RESUMO

OBJECTIVES: Despite evidence from several randomized controlled trials and observational studies validating short-term safety and efficacy of off-pump coronary artery bypass grafting (CABG), concerns persist regarding the impact of off-pump CABG on long-term survival and freedom from reintervention. This persistent scepticism regarding off-pump CABG prompted us to review our practice of CABG over the last 20 years with a view to comparing the impact of off-pump and on-pump CABG on short-term and long-term outcomes in a high-volume off-pump coronary surgery centre. METHODS: We retrospectively analysed prospectively collected data from the Patients Analysis and Tracking System database (Dendrite Clinical Systems, Oxford, UK) for all isolated first-time CABG procedures with at least 2 grafts performed at our institution from January 1996 to September 2017. Over the study period, 5995 off-pump CABG and 4875 on-pump CABG were performed by surgeons with exclusive off-pump and on-pump practices, respectively. Multivariable logistic regression and the Cox model were used to investigate the effect of off-pump versus on-pump procedures on short-term outcomes and long-term survival. Propensity score matching was used to compare the 2 matched groups. RESULTS: Off-pump CABG was associated with a lower risk for 30-day mortality [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.32-0.55; P < 0.001], reintubation/tracheostomy (OR 0.58, 95% CI 0.47-0.72; P < 0.001) and re-exploration for bleeding (OR 0.48, 95% CI 0.37-0.62; P < 0.001). The benefit in terms of operative deaths from off-pump was significant in those with Society of Cardio-Thoracic Surgery logistic EuroSCORE >2 (interaction P = 0.04). When compared with on-pump CABG, off-pump CABG did not significantly reduce the risk of stroke (OR 0.96, 95% CI 0.88-1.12; P = 0.20) and postoperative haemofiltration (OR 0.98, 95% CI 0.86-1.20; P = 0.35). At the median follow-up of 12 years (interquartile range 6-17, max 21), off-pump CABG did not affect late survival [log rank P = 0.24; hazard ratio (HR) 0.95, 95% CI 0.89-1.02] or the need for reintervention (log rank P = 0.12; HR 1.19, 95% CI 0.95-1.48). CONCLUSIONS: This large volume, single-centre study with the longest reported follow-up confirms that off-pump CABG performed by experienced surgeons, who perform only off-pump procedures in a high-volume off-pump coronary surgery centre, is associated with lower risk of operative deaths, fewer postoperative complications and similar 20-year survival and freedom from reintervention rates compared with on-pump CABG.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana , Ponte de Artéria Coronária , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Seguimentos , Humanos , Complicações Pós-Operatórias/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
10.
Sci Rep ; 9(1): 12450, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462651

RESUMO

Myocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers.


Assuntos
Algoritmos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Modelos Cardiovasculares , Miocárdio , Humanos
11.
Sci Rep ; 8(1): 4475, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540762

RESUMO

Cardiovascular disease diagnosis and prognosis can be improved by measuring patient-specific in-vivo local myocardial strain using Magnetic Resonance Imaging. Local myocardial strain can be determined by tracking the movement of sample muscles points during cardiac cycle using cardiac motion estimation model. The tracking accuracy of the benchmark Free Form Deformation (FFD) model is greatly affected due to its dependency on tunable parameters and regularisation function. Therefore, Hierarchical Template Matching (HTM) model, which is independent of tunable parameters, regularisation function, and image-specific features, is proposed in this article. HTM has dense and uniform points correspondence that provides HTM with the ability to estimate local muscular deformation with a promising accuracy of less than half a millimetre of cardiac wall muscle. As a result, the muscles tracking accuracy has been significantly (p < 0.001) improved (30%) compared to the benchmark model. Such merits of HTM provide reliably calculated clinical measures which can be incorporated into the decision-making process of cardiac disease diagnosis and prognosis.


Assuntos
Coração/fisiologia , Modelos Teóricos , Movimento (Física) , Algoritmos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Coração/fisiopatologia , Humanos
12.
Med Biol Eng Comput ; 56(9): 1615-1631, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29479659

RESUMO

Identification of in vivo passive biomechanical properties of healthy human myocardium from regular clinical data is essential for subject-specific modelling of left ventricle (LV). In this work, myocardium was defined by Holzapfel-Ogden constitutive law. Therefore, the objectives of the study were (a) to estimate the ranges of the constitutive parameters for healthy human myocardium using non-invasive routine clinical data, and (b) to investigate the effect of geometry, LV end-diastolic pressure (EDP) and fibre orientations on estimated values. In order to avoid invasive measurements and additional scans, LV cavity volume, measured from routine MRI, and empirical pressure-normalised-volume relation (Klotz-curve) were used as clinical data. Finite element modelling, response surface method and genetic algorithm were used to inversely estimate the constitutive parameters. Due to the ill-posed nature of the inverse optimisation problem, the myocardial properties was extracted by identifying the ranges of the parameters, instead of finding unique values. Additional sensitivity studies were carried out to identify the effect of LV EDP, fibre orientation and geometry on estimated parameters. Although uniqueness of the solution cannot be achieved, the normal ranges of the parameters produced similar mechanical responses within the physiological ranges. These information could be used in future computational studies for designing heart failure treatments. Graphical abstract.


Assuntos
Miocárdio/metabolismo , Animais , Fenômenos Biomecânicos , Pressão Sanguínea/fisiologia , Diástole/fisiologia , Análise de Elementos Finitos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imagem Cinética por Ressonância Magnética , Estresse Mecânico , Sus scrofa
13.
J Biomech ; 52: 95-105, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28065473

RESUMO

Left-ventricular (LV) remodelling, associated with diastolic heart failure, is driven by an increase in myocardial stress. Therefore, normalisation of LV wall stress is the cornerstone of many therapeutic treatments. However, information regarding such regional stress-strain for human LV is still limited. Thus, the objectives of our study were to determine local diastolic stress-strain field in healthy LVs, and consequently, to identify the regional variations amongst them due to geometric heterogeneity. Effects of LV base movement on diastolic model predictions, which were ignored in the literature, were further explored. Personalised finite-element modelling of five normal human bi-ventricles was carried out using subject-specific myocardium properties. Model prediction was validated individually through comparison with end-diastolic volume and a new shape-volume based measurement of LV cavity, extracted from magnetic resonance imaging. Results indicated that incorporation of LV base movement improved the model predictions (shape-volume relevancy of LV cavity), and therefore, it should be considered in future studies. The LV endocardium always experienced higher fibre stress compared to the epicardium for all five subjects. The LV wall near base experienced higher stress compared to equatorial and apical locations. The lateral LV wall underwent greater stress distribution (fibre and sheet stress) compared to other three regions. In addition, normal ranges of different stress-strain components in different regions of LV wall were reported for five healthy ventricles. This information could be used as targets for future computational studies to optimise diastolic heart failure treatments or design new therapeutic interventions/devices.


Assuntos
Diástole , Ventrículos do Coração/anatomia & histologia , Modelos Cardiovasculares , Movimento , Função Ventricular Esquerda , Ventrículos do Coração/patologia , Humanos , Estresse Mecânico , Remodelação Ventricular
14.
Pacing Clin Electrophysiol ; 39(10): 1052-1060, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27501471

RESUMO

BACKGROUND: Transvenous left ventricular (LV) lead placement for cardiac resynchronization therapy is unsuccessful in 5-10% of reported cases. These patients may benefit from isolated surgical placement of an epicardial LV lead via minithoracotomy approach. AIM: To evaluate the success of this approach at long-term follow-up. METHODS: Retrospective evaluation of all consecutive patients undergoing isolated epicardial LV lead placement after failed transvenous attempt over a 6-year period. Data collected on baseline parameters, procedural details, and outcome at follow-up (hospital stay, complications, mortality, and clinical response). RESULTS: Forty-two patients underwent epicardial lead implant. Five died within 1 year (11.9%): two (4.8%) died within 30-days post op (one from intraoperative hemorrhage, the other from multiple organ failure); 39 (95.1%) were admitted to the high dependency unit and transferred to the ward <24 hours. Median hospital stay was 3.4 ± 1.9 days. The overall complication rate was 17.5% (n = 7): 15.0% (n = 6) short term and 2.5% (n = 1) long term; these included three (7.5%) LV noncapture events all treated with reprogramming. There were two (5.0%) wound infections requiring oral antibiotics and two (5.0%) device infections requiring intravenous antibiotics (one had device resiting, the other developed septic shock requiring intensive care admission). Assessment of clinical response was possible in 34 (81.0%) at follow-up: 21 (61.8%) were responders and 13 (28.2%) nonresponders with no significant differences between these groups; no clinical predictors of response were identified. CONCLUSION: Isolated epicardial LV lead implant using minithoracotomy is relatively safe and effective at successful LV pacing. Response rate and postoperative recovery at long-term follow-up are reasonable in these high-risk patients.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Ventrículos do Coração , Idoso , Terapia de Ressincronização Cardíaca/mortalidade , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pericárdio , Complicações Pós-Operatórias , Estudos Retrospectivos , Toracotomia/métodos
15.
J Biomech ; 48(4): 604-612, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25596634

RESUMO

Majority of heart failure patients who suffer from diastolic dysfunction retain normal systolic pump action. The dysfunction remodels the myocardial fibre structure of left-ventricle (LV), changing its regular diastolic behaviour. Existing LV diastolic models ignored the effects of right-ventricular (RV) deformation, resulting in inaccurate strain analysis of LV wall during diastole. This paper, for the first time, proposes a numerical approach to investigate the effect of fibre-angle distribution and RV deformation on LV diastolic mechanics. A finite element modelling of LV passive inflation was carried out, using structure-based orthotropic constitutive law. Rule-based fibre architecture was assigned on a bi-ventricular (BV) geometry constructed from non-invasive imaging of human heart. The effect of RV deformation on LV diastolic mechanics was investigated by comparing the results predicted by BV and single LV model constructed from the same image data. Results indicated an important influence of RV deformation which led to additional LV passive inflation and increase of average fibre and sheet stress-strain in LV wall during diastole. Sensitivity of LV passive mechanics to the changes in the fibre distribution was also examined. The study revealed that LV diastolic volume increased when fibres were aligned more towards LV longitudinal axis. Changes in fibre angle distribution significantly altered fibre stress-strain distribution of LV wall. The simulation results strongly suggest that patient-specific fibre structure and RV deformation play very important roles in LV diastolic mechanics and should be accounted for in computational modelling for improved understanding of the LV mechanics under normal and pathological conditions.


Assuntos
Simulação por Computador , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Modelos Cardiovasculares , Miocárdio/patologia , Fenômenos Biomecânicos/fisiologia , Diástole/fisiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Modelos Teóricos , Sístole/fisiologia , Remodelação Ventricular/fisiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-26737787

RESUMO

Fibre orientation of myocardial wall plays a significant role in ventricular wall stress, which is assumed to be responsible for many cardiac mechanics, including ventricular remodelling, associated with heart failure. Previous studies, conducted to identify the effects of fibre orientation on left -ventricle (LV) diastolic mechanics, used only animal's myocardium properties (no human data) and therefore, may not apply for predicting human cardiac mechanics. In the present study, computational modelling of LV diastole was carried out to investigate the effects of fibre orientation on LV end diastolic pressure volume relation (EDPVR) and wall stress distribution using subject-specific in vivo passive properties of human myocardium for two human hearts. Results indicated that LV inflation increased when fibres were aligned more towards LV longitudinal axis and the effect was more notable when the fibre angle was higher in endocardium than epicardium wall. Changes in fibre angle distribution considerably altered fibre stress distribution of LV wall and the changes were significant in anterior and lateral regions of equatorial and apical locations. Furthermore, the regions of high fibre stress from midwall to endocardium were gradually confined towards endocardium with the decrease in fibre angle. Such information will be useful for future studies/diagnoses of LV mechanics in normal and pathological conditions.


Assuntos
Diástole/fisiologia , Ventrículos do Coração/anatomia & histologia , Coração , Modelos Cardiovasculares , Função Ventricular/fisiologia , Simulação por Computador , Coração/anatomia & histologia , Coração/parasitologia , Humanos
17.
PLoS One ; 9(2): e87102, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24498293

RESUMO

AIMS: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. METHODS AND RESULTS: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (ßKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-ßKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast ßKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. CONCLUSION: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Obesidade/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/farmacologia , Expressão Gênica , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Técnicas In Vitro , Masculino , Microscopia Confocal , Isquemia Miocárdica/genética , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Obesidade/genética , Fosfatidilinositol 3-Quinase/metabolismo , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos
18.
JAMA ; 305(4): 381-90, 2011 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-21266685

RESUMO

CONTEXT: Stroke is a devastating and potentially preventable complication of coronary artery bypass graft (CABG) surgery. Better understanding of the timing and risk factors for stroke associated with CABG are needed. OBJECTIVES: To investigate temporal trends in stroke after CABG and to identify stroke risk factors and association with longitudinal outcomes. DESIGN, SETTING, AND PATIENTS: Prospective study conducted from 1982 through 2009 at a single US academic medical center among 45,432 consecutive patients (mean age, 63 [SD, 10] years) undergoing isolated primary or reoperative CABG surgery. Strokes occurring following CABG were recorded prospectively and classified as having occurred intraoperatively or postoperatively. Complications and survival after stroke were assessed in propensity-matched groups. INTERVENTION: CABG performed using 4 different operative strategies (off-pump, on-pump with beating heart, on-pump with arrested heart, on-pump with hypothermic circulatory arrest). MAIN OUTCOME MEASURES: Hospital complications; late survival. RESULTS: Among 45,432 patients undergoing CABG surgery, 705 (1.6% [95% confidence interval {CI}, 1.4%-1.7%]) experienced a stroke. The prevalence of stroke peaked in 1988 at 2.6% (95% CI, 1.9%-3.4%), then declined at 4.69% (95% CI, 4.68%-4.70%) per year (P = .04), despite increasing patient comorbidity. Overall, 279 strokes (40%) occurred intraoperatively and 409 (58%) occurred postoperatively (timing indeterminate in 17 patients). Postoperative stroke peaked at 40 hours, decreasing to 0.055%/d (95% CI, 0.047%-0.065%) by day 6. Risk factors for both intraoperative and postoperative stroke included older age (odds ratio, 8.5 [95% CI, 3.2-22]) and variables representing arteriosclerotic burden. Intraoperative stroke rates were lowest in off-pump CABG (0.14% [95% CI, 0.029%-0.40%]) and on-pump beating-heart CABG (0% [95% CI, 0%-1.6%]), intermediate with on-pump arrested-heart CABG (0.50% [95% CI, 0.41%-0.61%]), and highest with on-pump CABG with hypothermic circulatory arrest (5.3% [95% CI, 2.0%-11%]). Patients with stroke had worse adjusted hospital outcomes, longer intensive care and postoperative stays, and worse downstream survival (mean, 11 [SD, 8.6] years). CONCLUSION: Among patients undergoing CABG surgery at a single center over the past 30 years, the occurrence of stroke declined despite an increasing patient risk profile, and more than half of strokes occurred postoperatively rather than intraoperatively.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Centros Médicos Acadêmicos/estatística & dados numéricos , Idoso , Comorbidade , Feminino , Humanos , Complicações Intraoperatórias/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Análise de Sobrevida , Fatores de Tempo
19.
J Cardiothorac Surg ; 2: 31, 2007 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-17615074

RESUMO

There are certain situations in redo cardiac surgery in adults where it may not be possible to use alternate arterial cannulation sites like the common femoral artery and axillary artery. We report a case where we established safe cardiopulmonary bypass with common carotid artery cannulation in an adult patient. The patient underwent aortic valve replacement for severe aortic regurgitation 8 months after repair of type A aortic dissection plus aortic valve resuspension.


Assuntos
Ponte Cardiopulmonar/métodos , Artéria Carótida Primitiva/cirurgia , Cateterismo , Toracotomia , Procedimentos Cirúrgicos Cardiovasculares , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação
20.
J Am Coll Cardiol ; 49(13): 1465-71, 2007 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-17397676

RESUMO

OBJECTIVES: Among patients undergoing aortic valve surgery for chronic aortic regurgitation (AR), we sought to: 1) compare survival among those with and without severe left ventricular dysfunction (LVD); 2) identify risk factors for death, including LVD and date of operation; and 3) estimate contemporary risk for cardiomyopathic patients. BACKGROUND: Patients with chronic AR and severe LVD have been considered high risk for aortic valve surgery, with limited prognosis. Transplantation is considered for some. METHODS: From 1972 to 1999, 724 patients underwent surgery for chronic AR; 88 (12%) had severe LVD. They were propensity matched to patients with nonsevere LVD to compare hospital mortality, interaction of operative date with severity of LVD, and late survival. Propensity score-adjusted multivariable analysis was performed for all 724 patients to identify risk factors for death. RESULTS: Survival was lower (p = 0.04) among patients with severe LVD than among matched patients with nonsevere LVD (30-day, 1-, 5-, and 25-year survival estimates were 91% vs. 96%, 81% vs. 92%, 68% vs. 81%, and 5% vs. 12%, respectively). However, survival of patients with severe LVD improved dramatically across the study time frame (p = 0.0004): hospital mortality decreased from 50% in 1975 to 0% after 1985, and time-related survival in patients with severe LVD operated on since 1985 became equivalent to that of matched patients with nonsevere LVD (p = 0.96). CONCLUSIONS: Neutralizing risk of severe LVD has improved early and late survival such that aortic valve surgery for chronic AR and cardiomyopathy is no longer a high-risk procedure for which transplantation is the best option.


Assuntos
Insuficiência da Valva Aórtica/mortalidade , Insuficiência da Valva Aórtica/cirurgia , Disfunção Ventricular Esquerda/mortalidade , Adulto , Idoso , Insuficiência da Valva Aórtica/complicações , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Disfunção Ventricular Esquerda/complicações
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