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1.
Nanomedicine ; 43: 102556, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35390527

RESUMO

There is an urgent need for contrast agents to detect the first inflammation stage of atherosclerosis by cardiovascular optical coherence tomography (CV-OCT), the imaging technique with the highest spatial resolution and sensitivity of those used during coronary interventions. Gold nanoshells (GNSs) provide the strongest signal by CV-OCT. GNSs are functionalized with the cLABL peptide that binds specifically to the ICAM-1 molecule upregulated in the first stage of atherosclerosis. Dark field microscopy and CV-OCT are used to evaluate the specific adhesion of these functionalized GNSs to activated endothelial cells. This adhesion is investigated under static and dynamic conditions, for shear stresses comparable to those of physiological conditions. An increase in the scattering signal given by the functionalized GNSs attached to activated cells is observed compared to non-activated cells. Thus, cLABL-functionalized GNSs behave as excellent contrast agents for CV-OCT and promise a novel strategy for clinical molecular imaging of atherosclerosis.


Assuntos
Aterosclerose , Tomografia de Coerência Óptica , Aterosclerose/diagnóstico por imagem , Meios de Contraste , Células Endoteliais , Ouro , Humanos , Tomografia de Coerência Óptica/métodos
2.
Fam Pract ; 36(6): 693-698, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31044230

RESUMO

BACKGROUND: Although both hospitalization and mortality due to heart failure (HF) have been widely studied, less is known about the impact of HF on disability and quality of life. AIM: To assess the degree of disability and quality of life in HF patients attended at family medicine centres. DESIGN AND SETTING: Cross-sectional study of a cohort of HF patients attended at family medicine centres. METHODS: Disability was assessed with the WHODAS 2 questionnaire, which provides a global and six domain scores that is understanding and communication, getting around, self-care, getting along with people, life activities and participation in society. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire, which furnishes a global and two domain scores, physical and emotional. RESULTS: A breakdown of the results showed that 28% of patients had moderate disability and 16.7% had severe disability, with the most important areas affected being: life activities, 8.9% extreme disability and 30.3% severe disability; getting around, 34.6% severe disability and 2% extreme disability; and participation in society, 53.3% moderate-severe disability. Quality of life was mildly affected. New York Heart Association (NYHA) Functional Classification and sex were the major determinants of disability and quality of life. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists were associated with better scores in the "getting around" and "life activity" domains. CONCLUSION: HF patients in primary care show an important degree of disability and an acceptable quality of life.


Assuntos
Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Qualidade de Vida , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Atenção Primária à Saúde , Autocuidado/estatística & dados numéricos , Espanha , Inquéritos e Questionários
4.
Heart Lung Circ ; 27(7): 885-892, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28918980

RESUMO

BACKGROUND: Previous trials have shown that, among high-risk patients with aortic stenosis, survival rates are similar for transcatheter aortic-valve implantation (TAVI) and surgical aortic valve replacement. The study aimed to compare the outcomes of aortic valve replacement according to the adopted surgical approach in intermediate and low risk patients. METHODS: This is a retrospective, observational, cohort study of prospectively collected data from 421 patients undergoing isolated aortic valve replacement between 2011 and 2015. A multinomial logit propensity score model based on preoperative risk factors was used to match patients 1:1:1 between conventional replacement (CAVR), minimally invasive (MIAVR) and TAVI groups, resulting in 50 matched three cohorts. RESULTS: After multinomial logit propensity score, the three groups were comparable in terms of preoperative characteristics. Mean age and Logistic EuroSCORE I of CAVR, MIAVR and TAVI groups were (84.2±5.1 vs. 82.3±4.8 vs. 85.6±4.9 years; p=0.002) and (11.4±3.6% vs. 8.3±3.4% vs. 15.8±5.4%; p<0.001) respectively. Overall mortality rates were similar for the three patient cohorts at one year. There were no significant differences related to stroke to 30 days. In the TAVI cohort, pacemaker implantation for new-onset total atrioventricular block became necessary in 30% of patients (p<0.001) and 16% of patients had some degree of paravalvular aortic regurgitation, which was more than mild (p<0.001). Total length of stay was shorter in the TAVI group when compared with surgical groups (11.5±5.3 vs. 10.1±6.9 vs 8.5±3.7 days; p=0.023). After discharge, the survival rate follow-up (average follow up: 46.7 months) was 70%, 84% and 72% for three cohorts (log Rank x2=2.40, p=0.3). CONCLUSIONS: In our experience, the three aortic valve replacement approaches offer very good results. Differences in the rate of complications were found between groups. Depending on patient's characteristics the Heart-Team group must offer the best surgical approach for each patient.


Assuntos
Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Pontuação de Propensão , Medição de Risco , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Seguimentos , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
5.
Respir Res ; 18(1): 85, 2017 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-28477618

RESUMO

BACKGROUND: Pulmonary hypertension (PH) associated with lung disease has the worst prognosis of all types of PH. Pulmonary arterial vasculopathy is an early event in the natural history of chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). The present study characterized the alterations in the structure and function of the pulmonary arterial (PA) wall of COPD and ILD candidates for lung transplantation (LTx). METHODS: A cohort of 73 patients, 63 pre-LTx (30 COPD, 33 ILD), and ten controls underwent simultaneous right heart catheterisation and intravascular ultrasound (IVUS). Total pulmonary resistance (TPR), capacitance (Cp), and the TPR-Cp relationship were assessed. PA stiffness and the relative area of wall thickness were estimated as pulse PA pressure/IVUS pulsatility and as [(external sectional area-intimal area)/external sectional area] × 100, respectively. RESULTS: Twenty-seven percent of patients had pulmonary arterial wedge pressure > 15 mmHg and were not analyzed. PA stiffness and the area of wall thickness were increased in comparison with controls, even in patients without PH (p < 0.05). ILD patients showed a significant higher PA stiffness, and lower Cp beyond mean PA pressure (mPAP) and lower area of wall thickness than COPD patients (p < 0.05). TPR-Cp relationship was shifted downward left for ILD patients. CONCLUSIONS: Significant increase of PA stiffness and area of wall thickness were present even in patients without PH and can make the diagnosis of pulmonary vasculopathy at a preclinical stage in PH-lung disease candidates for LTx. ILD patients showed the worst PA stiffness and Cp with respect to COPD.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Artéria Pulmonar/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Pressão Propulsora Pulmonar , Rigidez Vascular , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
BMC Pulm Med ; 14: 69, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24762000

RESUMO

BACKGROUND: Exercise capacity is impaired in pulmonary arterial hypertension (PAH). We hypothesized that cardiovascular reserve abnormalities would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH. METHODS: Eighteen PAH patients (p) group 1 NYHA class II/III and ten controls underwent simultaneous right cardiac catheterization and intravascular ultrasound at rest and during low dose-dobutamine (10 mcg/kg/min) with trendelenburg (DST). We estimated cardiac output (CO), pulmonary vascular resistance (PVR) and capacitance (PC), and PA elastic modulus (EM). We concomitantly measured tricuspid annular plane systolic excursion (TAPSE), RV myocardial peak systolic velocity (Sm) and isovolumic myocardial acceleration (IVA) in PAH patients. Based on the rounded mean + 2 SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH p were divided into two groups according to mean PA pressure (mPAP) response during DST, 1: ΔmPAP > 5 mm Hg and 2: ΔmPAP ≤ 5 mm Hg. Cardiovascular reserve was estimated as the change (delta, Δ) during DST compared with rest, including ΔmPAP with respect to ΔCO (ΔmPAP/ΔCO). All patients were prospectively followed up for 2 years. RESULTS: PAH p showed significant lower heart rate and CO increase than controls during DST, with a significant mPAP and pulse PAP increase and higher ΔmPAP/ΔCO (p < 0.05). Neither hemodynamic, IVUS and echocardiographic data were different between both PAH groups at rest. In group 1, DST caused a higher ΔEM, ΔmPAP/ΔCO, ΔPVR, and ΔTAPSE than group 2, with a lower IVA increase and a negative ΔSV (p < 0.05). TAPSE correlated with mPAP and RVP (p < 0.05) and, IVA and Sm correlated with CO (p < 0.05). ΔEM correlated with ΔmPAP and ΔIVA with ΔCO (p < 0.05). There were two deaths/pulmonary transplantations in group 1 and one death in group 2 during the follow-up (p > 0.05). CONCLUSIONS: Pulmonary vascular reserve and RV systolic reserve are significantly impaired in patients with PAH. The lower recruitable cardiovascular reserve is significantly related to a worse hemodynamic response to DST and it could be associated with a poor clinical outcome.


Assuntos
Cateterismo Cardíaco/métodos , Ecocardiografia sob Estresse/métodos , Hemodinâmica , Hipertensão Pulmonar/diagnóstico , Volume Sistólico , Disfunção Ventricular Direita/diagnóstico , Resistência das Vias Respiratórias/fisiologia , Estudos de Casos e Controles , Ecocardiografia/métodos , Tolerância ao Exercício/fisiologia , Feminino , Capacidade Residual Funcional , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Ultrassonografia de Intervenção/métodos , Resistência Vascular/fisiologia , Disfunção Ventricular Direita/fisiopatologia
8.
J Cardiovasc Dev Dis ; 11(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38786963

RESUMO

The constant and dynamic interaction between ventricular function and arterial afterload, known as ventricular-arterial coupling, is key to understanding cardiovascular pathophysiology. Ventricular-arterial coupling has traditionally been assessed invasively as the ratio of effective arterial elastance over end-systolic elastance (Ea/Ees), calculated from information derived from pressure-volume loops. Over the past few decades, numerous invasive and non-invasive simplified methods to estimate the elastance ratio have been developed and applied in clinical investigation and practice. The echocardiographic assessment of left ventricular Ea/Ees, as proposed by Chen and colleagues, is the most widely used method, but novel echocardiographic approaches for ventricular-arterial evaluation such as left ventricle outflow acceleration, pulse-wave velocity, and the global longitudinal strain or global work index have arisen since the former was first published. Moreover, multimodal imaging or artificial intelligence also seems to be useful in this matter. This review depicts the progressive development of these methods along with their academic and clinical application. The left ventricular-arterial coupling assessment may help both identify patients at risk and tailor specific pharmacological or interventional treatments.

9.
Coron Artery Dis ; 35(1): 50-58, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37990625

RESUMO

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions. METHODS: We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS. RESULTS: A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P <0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4-11.7, P <0.01) and long-term (median 36 vs. 31 months, P =0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5-8.2, P <0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P =0.01; and 12.6% vs. 0.7%, P <0.01) mainly driven by noncardiovascular deaths. CONCLUSION: Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients.


Assuntos
Síndrome Coronariana Aguda , Fibrilação Atrial , Anomalias dos Vasos Coronários , Cardiomiopatia de Takotsubo , Doenças Vasculares , Humanos , Feminino , Masculino , Volume Sistólico , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/epidemiologia , Estudos Prospectivos , Vasos Coronários , Função Ventricular Esquerda , Doenças Vasculares/epidemiologia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/complicações , Fibrilação Atrial/complicações , Anomalias dos Vasos Coronários/complicações , Angiografia Coronária/efeitos adversos
11.
Expert Rev Cardiovasc Ther ; 21(6): 373-378, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37144281

RESUMO

INTRODUCTION: Hyperlipidemia is the main underlying cause of atherosclerotic cardiovascular disease. Reducing low-density lipoprotein (LDL) cholesterol to recommended targets after an acute coronary syndrome (ACS) is of utmost importance as it is associated with a reduction of mortality and further cardiovascular events. Unfortunately, there are considerable gaps between guideline recommendations and clinical practice. In addition, the approach to treatment of this population is very heterogeneous, even in specialized cardiovascular units. Some easy-to-implement strategies may help to optimize the management of these patients. AREAS COVERED: The OPTA Project was developed to identify these gaps and to provide recommendations to improve and harmonize the management of patients with ACS, with a specific focus on lipids. EXPERT OPINION: Five areas of interest were defined: 1) evaluation of cardiovascular risk at admission, 2) development of a strategy to effectively and rapidly reduce LDL cholesterol levels, 3) determining LDL cholesterol goals (<55 mg/dL or stricter) and follow-up, 4) data collection during hospitalization, and 5) standardized discharge report. Specific recommendations are given to reduce inequalities, following the targets 'the lower, the better' and 'the earlier, the better.'


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , LDL-Colesterol , Colesterol , Aterosclerose/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
12.
Eur J Echocardiogr ; 12(4): 272-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21266380

RESUMO

AIMS: To assess the usefulness of three-dimensional transoesophageal echocardiography (3D-TOE) vs. two-dimensional (2D)-TOE in the evaluation of morphological and dynamic findings of aortic dissection, and compare the results with those obtained by multi-slice computed tomography (CT). METHODS AND RESULTS: Twenty-six patients (21 men and 5 women, median age: 67 years, range: 28-74 years) diagnosed of chronic aortic dissection with patent false lumen were studied. A comprehensive 2D-TOE and a real-time 3D-TOE study targeted at assessing dissection variables were performed and compared with CT within 3 months. Both 3D-TOE and 2D-TOE visualized the intimal flap extension and presence of flow in aortic dissection lumina in the same aortic segments. Three-dimensional TOE correctly identified true lumen in all cases, being superior to 2D-TOE in three cases with a spiroidal course of the dissection in descending aorta. Maximum entry tear diameter measured by 3D-TOE showed a better correlation with CT than 2D-TOE (0.96 and 0.87, P< 0.001, respectively). Compared with CT, 2D-TOE underestimated maximum entry tear diameter (-1.75 ± 3.28 mm, P< 0.01) but 3D-TOE did not (-0.20 ± 1.92 mm, P: n.s.). However, entry tear area measured by 3D-TOE and CT showed the best correlation (r: 0.97) and agreement (0.05 ± 0.20 cm(2), P: n.s.). CONCLUSION: Three-dimensional TOE provides additional information to 2D-TOE in aortic dissection assessment, particularly in entry tear size quantification. Agreement between entry tear area defined by 3D-TOE and CT was excellent. Three-dimensional TOE permits better morphological and dynamic understanding of aortic dissection when the flap is spiroidal.


Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Adulto , Idoso , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
13.
Eur Heart J ; 31(4): 472-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20037148

RESUMO

AIMS: To determine the usefulness of contrast echocardiography in the diagnosis of aortic dissection (AD) and in the assessment of findings necessary for adequate patient management. METHODS AND RESULTS: Conventional and contrast-enhanced transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) were performed in 128 consecutive patients with clinically suspected acute AD. Results were validated independently against intraoperative findings in 45 patients and computed tomography information in 83. Sensitivity and specificity of conventional TTE increased after contrast enhancement from 73.7 to 86.8% (P< 0.005) and 71.2 to 90.4% (P < 0.05), respectively. Sensitivity and specificity of enhanced TTE were similar to conventional TOE in ascending aorta (93.3 vs. 95.6% and 97.6 vs. 96.4%, respectively) and in the arch (88.4 vs. 93.0% and 95.3 vs. 98.82%, respectively). Contrast-enhanced TOE permitted the location of non-visualized entry tear in seven cases (10.6%), helped to correctly identify the true lumen in six (9.1%), and diagnosed retrograde dissection in nine (13.6%). CONCLUSION: Contrast enhancement substantially improves TTE in the diagnosis of AD and should be considered as the initial imaging modality in the emergency setting. Contrast enhancement also has significant value for obtaining critical morphological and haemokinetic information by TOE useful for adequate patient management.


Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Meios de Contraste , Ecocardiografia/métodos , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
14.
Adv Healthc Mater ; 10(10): e2002186, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33594792

RESUMO

The unique combination of physical and optical properties of silica (core)/gold (shell) nanoparticles (gold nanoshells) makes them especially suitable for biomedicine. Gold nanoshells are used from high-resolution in vivo imaging to in vivo photothermal tumor treatment. Furthermore, their large scattering cross-section in the second biological window (1000-1700 nm) makes them also especially adequate for molecular optical coherence tomography (OCT). In this work, it is demonstrated that, after suitable functionalization, gold nanoshells in combination with clinical OCT systems are capable of imaging damage in the myocardium following an infarct. Since both inflammation and apoptosis are two of the main mechanisms underlying myocardial damage after ischemia, such damage imaging is achieved by endowing gold nanoshells with selective affinity for the inflammatory marker intercellular adhesion molecule 1 (ICAM-1), and the apoptotic marker phosphatidylserine. The results here presented constitute a first step toward a fast, safe, and accurate diagnosis of damaged tissue within infarcted hearts at the molecular level by means of the highly sensitive OCT interferometric technique.


Assuntos
Infarto do Miocárdio , Nanoconchas , Ouro , Humanos , Infarto , Imagem Molecular , Infarto do Miocárdio/diagnóstico por imagem
15.
Coron Artery Dis ; 32(6): 509-516, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186146

RESUMO

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two relatively common nonatherosclerotic causes of acute coronary syndrome particularly frequent in women. METHODS: This study sought to compare the baseline clinical and angiographic characteristics and in-hospital outcomes of patients from two large prospective registries on SCAD and TTS (the prospective nation-wide Spanish SCAD Registry and a prospective single-center TTS registry). RESULTS: A total of 318 SCAD and 106 TTS consecutive patients were included. Most patients in both groups (88%) were women. Patients in the TTS group were older [74 (interquartile range, IQR 67-81) vs. 53 years-old (IQR 47-60), P < 0.001] and presented a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS (56% vs. 42%, P = 0.009) but emotional stress was more common in the SCAD group (25% vs. 15%, P = 0.037). TTS patients showed a reduced release of cardiac biomarkers but had more severe left ventricular dysfunction (ejection fraction <50%: 73% vs. 12%, P < 0.001). In-hospital major adverse cardiovascular events occurred more frequently in TTS patients (12% vs. 4.7%, P < 0.001). Notably, TTS patients showed more frequently congestive heart failure (10% vs. 0.6%, P < 0.001), atrial fibrillation (11% vs. 1%, P < 0.001) and had a higher all-cause in-hospital mortality (5.7% vs. 1.3%, P = 0.032). CONCLUSION: TTS patients are older and present a higher prevalence of some cardiovascular risk factors than patients with SCAD. TTS is linked to a worse in-hospital prognosis with higher mortality.


Assuntos
Angiografia Coronária , Anomalias dos Vasos Coronários/diagnóstico por imagem , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Doenças Vasculares/congênito , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Anomalias dos Vasos Coronários/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Cardiomiopatia de Takotsubo/mortalidade , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/mortalidade
16.
J Physiol ; 588(Pt 7): 1139-51, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20156849

RESUMO

Connexin 43 (Cx43) plays an important role in cardioprotective signalling by mechanisms at least in part independent of gap junctional communication. To investigate whether this role is related to specific properties of this connexin isoform, we used a knock-in mouse model in which the coding region of Cx43 is replaced by that of Cx32. Homozygous Cx43KI32 mice showed reduced cell-to-cell Lucifer Yellow transfer (P < 0.01), but QRS duration and left ventricular fractional shortening (echocardiography) were similar to those in wild-type animals. NMR spectroscopy detected reduced ATP and increased lactate content in myocardium from homozygous Cx43KI32 animals (P < 0.05). Despite this, isolated homozygous Cx43KI32 hearts showed smaller infarcts after ischaemia-reperfusion (40 min/60 min) as compared to hearts from heterozygous and wild-type animals (13 and 31% reduction, respectively, P < 0.05). Cardiac myocytes isolated from Cx43KI32 mouse hearts also showed a reduced rate of cell death after simulated ischaemia-reperfusion. In a separate series of experiments, both ischaemic (4 cycles of 3.5 min of ischaemia and 5 min of reperfusion) and pharmacological (50 micromol l(-1) diazoxide, 10 min) preconditioning reduced infarct size in hearts from wild-type mice (by 24.84 and 26.63%, respectively, P < 0.05), but only ischaemic preconditioning was effective in hearts from heterozygous animals and both preconditioning strategies failed to protect Cx43KI32 homozygous hearts. These results demonstrate that Cx43 has an important and previously unknown modulatory effect in myocardial energy metabolism and tolerance to ischaemia, and plays a critical role in preconditioning protection, by mechanisms that are specific for this connexin isoform.


Assuntos
Conexina 43/fisiologia , Metabolismo Energético , Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Animais , Conexina 43/genética , Conexinas/genética , Conexinas/fisiologia , Diazóxido/farmacologia , Feminino , Técnicas de Introdução de Genes , Masculino , Camundongos , Camundongos Transgênicos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/complicações , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Proteína beta-1 de Junções Comunicantes
17.
J Mol Cell Cardiol ; 46(2): 160-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19084534

RESUMO

Different lines of evidence suggest that inhibition of COX-2 activity exacerbates reperfusion injury, but direct data showing beneficial effects of increased COX-2 activity are lacking. The aim of this study was to determine the effect of constitutive expression of COX-2 on cardiomyocyte tolerance to ischemia-reperfusion injury. We generated a transgenic mouse (B6D2-Tg (MHC-PTGS2)17Upme) that constitutively expresses functional human COX-2 in cardiomyocytes under the control of alpha-myosin heavy chain promoter. COX-2 expression was confirmed by immunoblotting and by increased levels of PGE(2) and PGI(2) in myocardium. Histological and echocardiographic analysis revealed no differences in the phenotype of transgenic mice (TgCOX-2) with respect to wild type (Wt) mice. Tolerance to ischemia-reperfusion injury was analysed in a Langendorff system. Reperfused TgCOX-2 hearts after 40 min of ischemia improved functional recovery (32.9+/-6.2% vs. 9.45+/-4.4%, P=0.004) and reduced cell death assessed by LDH release (43% of reduction, P<0.001) and triphenyltetrazolium staining (41% of reduction, P=0.002). Cardioprotection was not further increased by ischemic preconditioning. Pretreatment of mice with the COX-2 inhibitor DFU attenuated cardioprotection with a correlation between myocardial PGE(2) levels and the extent of cell death. NMR spectroscopy showed a marked reduction in arachidonic acid (AA) content in TgCOX-2 hearts. Both, DFU pretreatment and perfusion of TgCOX-2 hearts with AA increased myocardial AA to values similar to those measured in Wt hearts and reversed cardioprotection. We conclude that constitutive expression of COX-2 in cardiomyocytes confers a permanent cardioprotective state against reperfusion injury. Increased PGE(2) synthesis and reduced AA content could explain this effect.


Assuntos
Ciclo-Oxigenase 2/fisiologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Animais , Ácido Araquidônico/metabolismo , Ciclo-Oxigenase 2/genética , Ecocardiografia , Feminino , Imunofluorescência , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Transgênicos
18.
Pulm Circ ; 9(1): 2045894018816972, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30430894

RESUMO

Regression of pulmonary hypertension (PH) is often incomplete after successful left-sided valve replacement (LSVR). Proximal pulmonary arterial (PPA) wall disease can be involved in patients with persistent-PH after LSVR, affecting the right ventricular to pulmonary arterial (RV-PA) coupling. Fifteen patients underwent successful LSVR at least one year ago presenting PH by echo (> 50 mmHg). Prosthesis-patient mismatch and left ventricular dysfunction were discarded. All patients underwent hemodynamic and intravascular ultrasound (IVUS) study. We estimated PPA stiffness (elastic modulus [EM]) and the relative area wall thickness (AWT). Acute vasoreactivity was assessed by inhaled nitric oxide (iNO) testing. RV-PA coupling was estimated by the tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure ratio. Patients were classified as isolated post-capillary PH (Ipc-PH; pulmonary vascular resistance [PVR] ≤ 3 WU and/or diastolic pulmonary gradient [DPG] < 7 mmHg) and combined post- and pre-capillary PH (Cpc-PH; PVR > 3 WU and DPG ≥ 7 mmHg). Both Ipc-PH and Cpc-PH showed a significant increase of EM and AWT. Despite normal PVR and DPG, Ipc-PH had a significant decrease in pulmonary arterial capacitance and RV-PA coupling impairment. Cpc-PH had worse PA stiffness and RV-PA coupling to Ipc-PH ( P < 0.05). iNO decreased RV afterload, improving the cardiac index and stroke volume only in Cpc-PH ( P < 0.05). Patients with persistent PH after successful LSVR have PPA wall disease and RV-PA coupling impairment beyond the hemodynamic phenotype. Cpc-PH is responsive to iNO, having the worse PA stiffness and RV-PA coupling. The PPA remodeling could be an early event in the natural history of PH associated with left heart disease.

19.
PLoS One ; 14(8): e0221434, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31419267

RESUMO

BACKGROUND: Heart failure (HF) is the leading cause of hospitalization in people over age 65. Predictive hospital admission models have been developed to help reduce the number of these patients. AIM: To develop and internally validate a model to predict hospital admission in one-year for any non-programmed cause in heart failure patients receiving primary care treatment. DESIGN AND SETTING: Cohort study, prospective. Patients treated in family medicine clinics. METHODS: Logistic regression analysis was used to estimate the association between the predictors and the outcome, i.e. unplanned hospitalization over a 12-month period. The predictive model was built in several steps. The initial examination included a set of 31 predictors. Bootstrapping was used for internal validation. RESULTS: The study included 251 patients, 64 (25.5%) of whom were admitted to hospital for some unplanned cause over the 12 months following their date of inclusion in the study. Four predictive variables of hospitalization were identified: NYHA class III-IV, OR (95% CI) 2.46 (1.23-4.91); diabetes OR (95% CI) 1.94 (1.05-3.58); COPD OR (95% CI) 3.17 (1.45-6.94); MLHFQ Emotional OR (95% CI) 1.07 (1.02-1.12). AUC 0.723; R2N 0.17; Hosmer-Lemeshow 0.815. Internal validation AUC 0.706.; R2N 0.134. CONCLUSION: This is a simple model to predict hospitalization over a 12-month period based on four variables: NYHA functional class, diabetes, COPD and the emotional dimension of the MLHFQ scale. It has an acceptable discriminative capacity enabling the identification of patients at risk of hospitalization.


Assuntos
Insuficiência Cardíaca/terapia , Hospitalização , Modelos Cardiovasculares , Atenção Primária à Saúde , Idoso , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
20.
Rev Esp Cardiol (Engl Ed) ; 72(9): 732-739, 2019 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30042008

RESUMO

INTRODUCTION AND OBJECTIVES: Late functional tricuspid regurgitation after rheumatic left-sided valve surgery is an important predictor of poor prognosis. This study investigated the usefulness and accuracy of 3-dimensional transthoracic echocardiography tricuspid area compared with conventional 2-dimensional diameter (2DD) for assessing significant tricuspid annulus dilatation, providing cutoff values that could be used in clinical practice to improve patient selection for surgery. METHODS: We prospectively included 109 patients with rheumatic heart disease in the absence of previous valve replacement. Tricuspid regurgitation was divided into 3 groups: mild, moderate, and severe. Optimal 3-dimensional area (3DA) and 2DD cutoff points for identification of significant tricuspid annulus dilatation were obtained and compared with current guideline thresholds. Predictive factors for 3DA dilatation were also assessed. RESULTS: Optimal cutoff points for both absolute and adjusted to body surface area (BSA) tricuspid annulus dilatation were identified (3DA: 10.4 cm2, 6.5 cm2/m2; 2DD: 35 mm, 21 mm/m2); 3DA/BSA had the best diagnostic performance (AUC=0.83). Three-dimensional transthoracic echocardiography tricuspid area helped to reclassify surgical indication in 14% of patients with mild tricuspid regurgitation (95%CI, 1%-15%; P=.03) and 37% with moderate tricuspid regurgitation (95%CI, 22%-37%; P<.0001), whereas 3DA/BSA changed surgery criteria in cases of mild tricuspid regurgitation (17%; 95%CI, 3%-17%; P=.01) compared with 2DD/BSA. On multivariable analysis, right and left atrial volumes and basal right ventricle diameter were independently correlated with 3DA. CONCLUSIONS: The current 40 mm threshold underestimates tricuspid annulus dilatation. Although 21 mm/m2 seems to be a reasonable criterion, the combination with 3DA assessment improves patient selection for surgery.


Assuntos
Anuloplastia da Valva Cardíaca/métodos , Ecocardiografia Tridimensional/métodos , Seleção de Pacientes , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico
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