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1.
Sci Transl Med ; 12(541)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350133

RESUMO

Recent clinical trials have revealed that aggressive insulin treatment has a neutral effect on cardiovascular risk in patients with diabetes despite improved glycemic control, which may suggest confounding direct effects of insulin on the human vasculature. We studied 580 patients with coronary atherosclerosis undergoing coronary artery bypass surgery (CABG), finding that high endogenous insulin was associated with reduced nitric oxide (NO) bioavailability ex vivo in vessels obtained during surgery. Ex vivo experiments with human internal mammary arteries and saphenous veins obtained from 94 patients undergoing CABG revealed that both long-acting insulin analogs and human insulin triggered abnormal responses of post-insulin receptor substrate 1 downstream signaling ex vivo, independently of systemic insulin resistance status. These abnormal responses led to reduced NO bioavailability, activation of NADPH oxidases, and uncoupling of endothelial NO synthase. Treatment with an oral dipeptidyl peptidase 4 inhibitor (DPP4i) in vivo or DPP4i administered to vessels ex vivo restored physiological insulin signaling, reversed vascular insulin responses, reduced vascular oxidative stress, and improved endothelial function in humans. The detrimental effects of insulin on vascular redox state and endothelial function as well as the insulin-sensitizing effect of DPP4i were also validated in high-fat diet-fed ApoE-/- mice treated with DPP4i. High plasma DPP4 activity and high insulin were additively related with higher cardiac mortality in patients with coronary atherosclerosis undergoing CABG. These findings may explain the inability of aggressive insulin treatment to improve cardiovascular outcomes, raising the question whether vascular insulin sensitization with DPP4i should precede initiation of insulin treatment and continue as part of a long-term combination therapy.

2.
Cardiovasc Res ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32090243

RESUMO

Rapid technological advances in non-invasive imaging, coupled with the availability of large data sets and the expansion of computational models and power, have revolutionized the role of imaging in medicine. Non-invasive imaging is the pillar of modern cardiovascular diagnostics, with modalities such as cardiac computed tomography (CT) now recognized as first-line options for cardiovascular risk stratification and the assessment of stable or even unstable patients. To date, cardiovascular imaging has lagged behind other fields, such as oncology, in the clinical translational of artificial intelligence (AI)-based approaches. We hereby review the current status of AI in non-invasive cardiovascular imaging, using cardiac CT as a running example of how novel machine learning (ML)-based radiomic approaches can improve clinical care. The integration of ML, deep learning, and radiomic methods has revealed direct links between tissue imaging phenotyping and tissue biology, with important clinical implications. More specifically, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging and CT, as well as lessons that can be learned from other areas. Finally, we propose a scientific framework in order to ensure the clinical and scientific validity of future studies in this novel, yet highly promising field. Still in its infancy, AI-based cardiovascular imaging has a lot to offer to both the patients and their doctors as it catalyzes the transition towards a more precise phenotyping of cardiovascular disease.

4.
JACC Cardiovasc Imaging ; 13(2 Pt 1): 385-392, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31326491

RESUMO

OBJECTIVES: The aim of this systematic review was to explore the prognostic value of late gadolinium enhancement (LGE) in patients with aortic stenosis (AS). BACKGROUND: Myocardial fibrosis is a common feature of many cardiac diseases. Cardiac magnetic resonance (CMR) has the ability to noninvasively detect regional fibrosis by using the LGE technique. Several studies have explored whether LGE is associated with adverse outcome in patients with AS. METHODS: Electronic databases were searched to identify studies investigating the ability of LGE to predict all-cause mortality in patients with AS. A random effects model meta-analysis was conducted. Heterogeneity was assessed with the I2 statistic. RESULTS: Six studies comprising 1,151 patients met our inclusion criteria. LGE was present in 49.1% of patients with AS. In the pooled analysis, LGE was found to be a strong univariate predictor of all-cause mortality (pooled unadjusted odds ratio: 2.56; 95% confidence interval: 1.83 to 3.57; I2 = 0%). Four of the included studies reported adjusted hazard ratios for mortality. LGE was independently associated with mortality, even after adjusting for baseline characteristics (pooled adjusted hazard ratio: 2.50; 95% confidence interval: 1.64 to 3.83; I2 = 0%). CONCLUSIONS: Fibrosis on LGE-CMR is a powerful predictor of all-cause mortality in patients with AS and may serve as a novel marker for risk stratification. Future studies should explore whether LGE-CMR can also be used to optimize timing of AS-related interventions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31606176

RESUMO

OBJECTIVES: Early saphenous vein graft (SVG) occlusion is typically attributed to technical factors. We aimed at exploring clinical, anatomical, and operative factors associated with the risk of early SVG occlusion (within 12 months postsurgery). METHODS: Published literature in MEDLINE was searched for studies reporting the incidence of early SVG occlusion. Individual patient data (IPD) on early SVG occlusion were used from the SAFINOUS-CABG Consortium. A derivation (n = 1492 patients) and validation (n = 372 patients) cohort were used for model training (with 10-fold cross-validation) and external validation respectively. RESULTS: In aggregate data meta-analysis (48 studies, 41,530 SVGs) the pooled estimate for early SVG occlusion was 11%. The developed IPD model for early SVG occlusion, which included clinical, anatomical, and operative characteristics (age, sex, dyslipidemia, diabetes mellitus, smoking, serum creatinine, endoscopic vein harvesting, use of complex grafts, grafted target vessel, and number of SVGs), had good performance in the derivation (c-index = 0.744; 95% confidence interval [CI], 0.701-0.774) and validation cohort (c-index = 0.734; 95% CI, 0.659-0.809). Based on this model. we constructed a simplified 12-variable risk score system (SAFINOUS score) with good performance for early SVG occlusion (c-index = 0.700, 95% CI, 0.684-0.716). CONCLUSIONS: From a large international IPD collaboration, we developed a novel risk score to assess the individualized risk for early SVG occlusion. The SAFINOUS risk score could be used to identify patients that are more likely to benefit from aggressive treatment strategies.

6.
Arterioscler Thromb Vasc Biol ; 39(11): 2207-2219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31510795

RESUMO

Unstable coronary plaques that are prone to erosion and rupture are the major cause of acute coronary syndromes. Our expanding understanding of the biological mechanisms of coronary atherosclerosis and rapid technological advances in the field of medical imaging has established cardiac computed tomography as a first-line diagnostic test in the assessment of suspected coronary artery disease, and as a powerful method of detecting the vulnerable plaque and patient. Cardiac computed tomography can provide a noninvasive, yet comprehensive, qualitative and quantitative assessment of coronary plaque burden, detect distinct high-risk morphological plaque features, assess the hemodynamic significance of coronary lesions and quantify the coronary inflammatory burden by tracking the effects of arterial inflammation on the composition of the adjacent perivascular fat. Furthermore, advances in machine learning, computational fluid dynamic modeling, and the development of targeted contrast agents continue to expand the capabilities of cardiac computed tomography imaging. In our Review, we discuss the current role of cardiac computed tomography in the assessment of coronary atherosclerosis, highlighting its dual function as a clinical and research tool that provides a wealth of structural and functional information, with far-reaching diagnostic and prognostic implications.

7.
Eur Heart J ; 40(43): 3529-3543, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31504423

RESUMO

BACKGROUND: Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction. METHODS AND RESULTS: We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62-0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOT-HEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (Δ[C-statistic] = 0.126, P < 0.001). In Study 3, FRP was significantly higher in 44 patients presenting with acute myocardial infarction compared with 44 matched controls, but unlike FAI, remained unchanged 6 months after the index event, confirming that FRP detects persistent PVAT changes not captured by FAI. CONCLUSION: The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art.

8.
Sci Transl Med ; 11(510)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534019

RESUMO

Obesity is associated with changes in the secretome of adipose tissue (AT), which affects the vasculature through endocrine and paracrine mechanisms. Wingless-related integration site 5A (WNT5A) and secreted frizzled-related protein 5 (SFRP5), adipokines that regulate noncanonical Wnt signaling, are dysregulated in obesity. We hypothesized that WNT5A released from AT exerts endocrine and paracrine effects on the arterial wall through noncanonical RAC1-mediated Wnt signaling. In a cohort of 1004 humans with atherosclerosis, obesity was associated with increased WNT5A bioavailability in the circulation and the AT, higher expression of WNT5A receptors Frizzled 2 and Frizzled 5 in the human arterial wall, and increased vascular oxidative stress due to activation of NADPH oxidases. Plasma concentration of WNT5A was elevated in patients with coronary artery disease compared to matched controls and was independently associated with calcified coronary plaque progression. We further demonstrated that WNT5A induces arterial oxidative stress and redox-sensitive migration of vascular smooth muscle cells via Frizzled 2-mediated activation of a previously uncharacterized pathway involving the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) and the GTPase RAC1. Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans.

9.
JAMA Cardiol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365032

RESUMO

Importance: Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries. Objective: To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA). Design, Setting, and Participants: This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline. Exposures: Biologic therapy for psoriasis. Main Outcomes and Measures: Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status. Results: Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti-tumor necrosis factor α, anti-interleukin [IL] 12/23, or anti-IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI -71.22 HU [interquartile range (IQR), -75.85 to -68.11 HU] at baseline vs -76.09 HU [IQR, -80.08 to -70.37 HU] at 1 year; P < .001) concurrent with skin disease improvement (median PASI, 7.7 [IQR, 3.2-12.5] at baseline vs 3.2 [IQR, 1.8-5.7] at 1 year; P < .001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, -71.98 [IQR, -77.36 to -65.64] at baseline vs -72.66 [IQR, -78.21 to -67.44] at 1 year; P = .39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents, including anti-tumor necrosis factor α (median FAI, -71.25 [IQR, -75.86 to -66.89] at baseline vs -75.49 [IQR, -79.12 to -68.58] at 1 year; P < .001) and anti-IL-12/23 or anti-IL-17 therapy (median FAI, -71.18 [IQR, -75.85 to -68.80] at baseline vs -76.92 [IQR, -81.16 to -71.67] at 1 year; P < .001). Conclusions and Relevance: In this study, biologic therapy for moderate to severe psoriasis was associated with reduced coronary inflammation assessed by perivascular FAI. This finding suggests that perivascular FAI measured by CCTA may be used to track response to interventions for coronary artery disease.

10.
JAMA Cardiol ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433450

RESUMO

Importance: Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy-related cardiac dysfunction (CTRCD) has not been performed, to our knowledge. Objective: To explore the prognostic value of GLS for the prediction of CTRCD. Data Sources: Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018. Study Selection: Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD. Data Extraction and Synthesis: Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Main Outcomes and Measures: The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms. Results: Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from -21.0% to -13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27; 95% CI, 7.73-19.47; area under the HSROC, 0.86; 95% CI, 0.83-0.89). For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82; 95% CI, 5.84-42.85; area under the HSROC, 0.86; 95% CI, 0.83-0.89). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity. Conclusions and Relevance: In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.

11.
Am J Cardiol ; 124(8): 1246-1251, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31466694

RESUMO

Residual aortic regurgitation (AR) is a major complication after transcatheter aortic valve implantation (TAVI). Although the echocardiographic assessment of post-TAVI AR remains challenging, cardiac magnetic resonance (CMR) allows direct quantification of AR. The aim of this study was to review the level of agreement between 2-dimensional transthoracic echocardiography (2D TTE) and CMR on grading the severity of AR after TAVI, and determine the accuracy of TTE in detecting moderate or severe AR. Electronic databases were searched in order to identify studies comparing 2D TTE to CMR for post-TAVI AR assessment. Kappa coefficient was used to determine the level of agreement between the 2 imaging modalities. CMR was used as the reference standard in order to assess the diagnostic accuracy of 2D TTE. Seven studies were included in this systematic review. Six studies reported a low correlation between 2D TTE and CMR (kappa coefficient ranging from -0.02 to 0.41), whereas one study showed good agreement with a kappa coefficient of 0.72. Given the heterogeneity in the included studies the diagnostic accuracy of TTE was evaluated by estimating the hierarchical summary receiver operator characteristic curve. The area under the curve for detection of moderate or severe AR with TTE was 0.83 (95% confidence interval 0.79 to 0.86). In conclusion, despite the reported significant disconcordance between TTE and CMR grading of AR, TTE has sufficient ability to discriminate moderate or severe AR from mild or none AR after TAVI in the clinical setting. CMR should be considered when TTE results are equivocal.

13.
Oncologist ; 24(5): e196-e197, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30910868

RESUMO

This letter to the editor describes myocarditis screening among patients undergoing combination immune checkpoint inhibitor therapy, in light of the consensus document from the Checkpoint Inhibitor Safety Working Group.

14.
Nat Rev Cardiol ; 16(2): 83-99, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30287946

RESUMO

Accumulating knowledge on the biology and function of the adipose tissue has led to a major shift in our understanding of its role in health and disease. The adipose tissue is now recognized as a crucial regulator of cardiovascular health, mediated by the secretion of several bioactive products, including adipocytokines, microvesicles and gaseous messengers, with a wide range of endocrine and paracrine effects on the cardiovascular system. The adipose tissue function and secretome are tightly controlled by complex homeostatic mechanisms and local cell-cell interactions, which can become dysregulated in obesity. Systemic or local inflammation and insulin resistance lead to a shift in the adipose tissue secretome from anti-inflammatory and anti-atherogenic towards a pro-inflammatory and pro-atherogenic profile. Moreover, the interplay between the adipose tissue and the cardiovascular system is bidirectional, with vascular-derived and heart-derived signals directly affecting adipose tissue biology. In this Review, we summarize the current knowledge of the biology and regional variability of adipose tissue in humans, deciphering the complex molecular mechanisms controlling the crosstalk between the adipose tissue and the cardiovascular system, and their possible clinical translation. In addition, we highlight the latest developments in adipose tissue imaging for cardiovascular risk stratification and discuss how therapeutic targeting of the adipose tissue can improve prevention and treatment of cardiovascular disease.


Assuntos
Tecido Adiposo/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Tecido Adiposo/fisiologia , Humanos
15.
Lancet ; 392(10151): 929-939, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30170852

RESUMO

BACKGROUND: Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown. METHODS: In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features. FINDINGS: Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]). Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as -70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality. INTERPRETATION: The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients. FUNDING: British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Adipócitos , Tecido Adiposo/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Vasos Coronários/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Adulto Jovem
16.
Heart ; 104(20): 1654-1662, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29853488

RESUMO

Adipose tissue (AT) is no longer viewed as a passive, energy-storing depot, and a growing body of evidence supports the concept that both quantitative and qualitative aspects of AT are critical in determining an individual's cardiometabolic risk profile. Among all AT sites, perivascular AT (PVAT) has emerged as a depot with a distinctive biological significance in cardiovascular disease given its close anatomical proximity to the vasculature. Recent studies have suggested the presence of complex, bidirectional paracrine and vasocrine signalling pathways between the vascular wall and its PVAT, with far-reaching implications in cardiovascular diagnostics and therapeutics. In this review, we first discuss the biological role of PVAT in both cardiovascular health and disease, highlighting its dual pro-atherogenic and anti-atherogenic roles, as well as potential therapeutic targets in cardiovascular disease. We then review current evidence and promising new modalities on the non-invasive imaging of epicardial AT and PVAT. Specifically, we present how our expanding knowledge on the bidirectional interplay between the vascular wall and its PVAT can be translated into novel clinical diagnostics tools to assess coronary inflammation. To this end, we present the example of a new CT-based method that tracks spatial changes in PVAT phenotype to extract information about the inflammatory status of the adjacent vasculature, highlighting the numerous diagnostic and therapeutic opportunities that arise from our increased understanding of PVAT biology.


Assuntos
Tecido Adiposo/metabolismo , Aterosclerose/etiologia , Vasos Sanguíneos/metabolismo , Doença da Artéria Coronariana/etiologia , Metabolismo Energético , Tecido Adiposo/patologia , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Vasos Sanguíneos/patologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Humanos , Fatores de Risco
17.
Cardiovasc Revasc Med ; 19(7 Pt B): 859-867, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29724516

RESUMO

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical aortic valve replacement (SAVR) for the treatment of severe aortic valve stenosis (AS). The impact of concomitant baseline elevated pulmonary artery pressures on outcomes after TAVI has not been established, since different studies used different definitions of pulmonary hypertension (PH). OBJECTIVE: To determine the association of PH with early and late cardiac and all-cause mortality after TAVI. METHODS: We performed a meta-analysis of studies comparing patients with elevated pulmonary artery pressures (defined as pulmonary hypertension or not) versus patients without elevated pulmonary artery pressures undergoing TAVI. We first performed stratified analyses based on the different PH cut-off values utilized by the included studies and subsequently pooled the studies irrespective of their cut-off values. We used a random effects model for the meta-analysis and assessed heterogeneity with I-square. Separate meta-analyses were performed for studies reporting outcomes as hazards ratios (HRs) and relative risks (RRs). Subgroup analyses were performed for studies published before and after 2013. Meta-regression analysis in order to assess the effect of chronic obstructive pulmonary disease and mitral regurgitation were performed. RESULTS: In total 22 studies were included in this systematic review. Among studies presenting results as HR, PH was associated with increased late cardiac mortality (HR: 1.8. 95% CI: 1.3-2.3) and late all-cause mortality (HR: 1.56; 95% CI: 1.1-2). The PH cut-off value that was most likely to be associated with worst outcomes among the different endpoints was pulmonary artery systolic pressure of 60 mm Hg (HR: 1.8; 95% CI: 1.3-2.3; I2 = 0, for late cardiac mortality and HR: 1.52; 95% CI: 1-2.1; I2 = 85% for late all-cause mortality). CONCLUSION: This systematic review and meta-analysis emphasizes the importance of baseline PH in predicting mortality outcomes after TAVI. Additional studies are needed to clarify the association between elevated baseline pulmonary artery pressures and outcomes after TAVI.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Pressão Arterial , Hipertensão Pulmonar/mortalidade , Artéria Pulmonar/fisiopatologia , Substituição da Valva Aórtica Transcateter/mortalidade , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Causas de Morte , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Masculino , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
18.
Ann Cardiothorac Surg ; 7(1): 3-11, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29492379

RESUMO

Background: The optimal treatment for advanced heart failure (HF) patients with regards to mortality remains unknown. Heart transplantation (HTx) and left ventricular assist devices (LVAD) used either as a bridge to transplant (BTT) or destination therapy (DT) have been compared in a number of studies, without definite conclusions with regards to mortality benefit. We sought to systematically review the pertinent literature and perform a meta-analysis of all the available studies presenting head-to-head comparisons between HTx and LVAD BTT or LVAD DT for late (>6 months) all-cause mortality. Methods: We performed a systematic search of Medline and Cochrane Central databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a meta-analysis of late mortality comparing HTx vs. BTT LVAD and HTx vs. DT LVAD using a random effects model. Results: Eight studies were included in our meta-analysis, reporting data on 7,957 patients in total. Although the available studies are of high quality [8 stars in Newcastle-Ottawa Scale (NOS) on average], there is paucity of mortality data. Specifically, seven studies compared HTx with BTT and five studies compared HTx with DT for 1-year mortality. Our pooled estimates showed that there was no difference in late mortality among these strategies. Conclusions: Our meta-analysis highlights the small number and the heterogeneity of available studies referring to the optimal invasive management of advanced HF, and shows that there are no differences between HTx and LVAD for these patients with regards to late mortality.

19.
Oncologist ; 23(8): 965-973, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29593100

RESUMO

BACKGROUND: Long-term childhood cancer survivors (CCS) are at increased risk of adverse cardiovascular events; however, there is a paucity of risk-stratification tools to identify those at higher-than-normal risk. SUBJECTS, MATERIALS, AND METHODS: This was a population-based study using data from the Surveillance, Epidemiology, and End Results Program (1973-2013). Long-term CCS (age at diagnosis ≤19 years, survival ≥5 years) were followed up over a median time period of 12.3 (5-40.9) years. Independent predictors of cardiovascular mortality (CVM) were combined into a risk score, which was developed in a derivation set (n = 22,374), and validated in separate patient registries (n = 6,437). RESULTS: In the derivation registries, older age at diagnosis (≥10 years vs. reference group of 1-5 years), male sex, non-white race, a history of lymphoma, and a history of radiation were independently associated with an increased risk of CVM among long-term CCS (p < .05). A risk score derived from this model (Childhood and Adolescence Cancer Survivor CardioVascular score [CHACS-CV], range: 0-8) showed good discrimination for CVM (Harrell's C-index [95% confidence interval (CI)]: 0.73 [0.68-0.78], p < .001) and identified a high-risk group (CHACS-CV ≥6), with cumulative CVM incidence over 30 years of 6.0% (95% CI: 4.3%-8.1%) versus 2.6% (95% CI: 1.8%-3.7%), and 0.7% (95% CI: 0.5%-1.0%) in the mid- (CHACS-CV = 4-5) and low-risk groups (CHACS-CV ≤3), respectively (plog-rank < .001). In the validation set, the respective cumulative incidence rates were 4.7%, 3.1%, and 0.8% (plog-rank < .001). CONCLUSION: We propose a simple risk score that can be applied in everyday clinical practice to identify long-term CCS at increased cardiovascular risk, who may benefit from early cardiovascular screening, and risk-reduction strategies. IMPLICATIONS FOR PRACTICE: Childhood cancer survivors (CCS) are known to be at increased cardiovascular risk. Currently available prognostic tools focus on treatment-related adverse events and late development of congestive heart failure, but there is no prognostic model to date to estimate the risk of cardiovascular mortality among long-term CCS. A simple clinical tool is proposed for cardiovascular risk stratification of long-term CCS based on easily obtainable information from their medical history. This scoring system may be used as a first-line screening tool to assist health care providers in identifying those who may benefit from closer follow-up and enable timely deployment of preventive strategies.


Assuntos
Doenças Cardiovasculares/etiologia , Neoplasias/complicações , Adulto , Sobreviventes de Câncer , Feminino , Humanos , Masculino , Neoplasias/mortalidade , Fatores de Risco , Adulto Jovem
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