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1.
Intern Med J ; 54(3): 382-387, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38323485

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted healthcare service provision worldwide. There is limited information on changes in invasive cardiovascular services during the pandemic, particularly in Australia. AIM: We sought to assess temporal trends on the use of interventional cardiology and cardiac surgery services before and following the COVID-19 pandemic in Australia. METHODS: Medicare Benefits Schedule items data from the Australian Government Services Australia on outpatient and private hospital interventional cardiology procedures (coronary angiogram, percutaneous coronary intervention and transcatheter aortic valve implantation) and cardiac surgery procedures (coronary artery bypass grafting [CABG] and surgical valve replacement, repair and annuloplasty) were analysed from March 2019 to 2021. This was superimposed on monthly COVID-19 case data obtained from the Australian Department of Health and Aged Care epidemiology reports. RESULTS: A sustained reduction in CABG (-10.1%) and surgical valve intervention (-11.1%) was appreciated from March 2019-2020 to March 2020-2021, in the first year of the COVID-19 pandemic. During this period, an overall increase (+25.9%) in the use of transcatheter aortic valve implantation was observed. Following the initial period of mandated isolation in March-April 2020, a reduction in coronary angiography (-29.1%) and percutaneous coronary intervention (-19.5%) was observed in comparison to March-April 2019; however, this was largely attenuated over time. CONCLUSIONS: The COVID-19 pandemic has resulted in reductions in the use of interventional cardiology and cardiac surgery services, with cardiac surgery most affected. However, an increase in uptake of transcatheter aortic valve implantation has been observed during the pandemic. This may have implications for future planning and resource allocation in the aftermath of the pandemic.


Assuntos
Estenose da Valva Aórtica , COVID-19 , Cardiologia , Intervenção Coronária Percutânea , Substituição da Valva Aórtica Transcateter , Idoso , Humanos , Pandemias , Austrália , Programas Nacionais de Saúde , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento
2.
Am Heart J ; 231: 157-159, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010246

RESUMO

During the COVID-19 pandemic there has been a reduction in hospital admissions for acute myocardial infarction. This manuscript presents the analysis of Google Trends meta-data and shows a marked spike in search volume for chest pain that is strongly correlated with COVID-19 case numbers in the United States. This raises a concern that fear of contracting COVID-19 may be leading patients to self-triage using internet searches.


Assuntos
COVID-19 , Dor no Peito , Controle de Doenças Transmissíveis/estatística & dados numéricos , Autoavaliação Diagnóstica , Uso da Internet/estatística & dados numéricos , Infarto do Miocárdio/epidemiologia , COVID-19/epidemiologia , COVID-19/psicologia , Dor no Peito/diagnóstico , Dor no Peito/epidemiologia , Dor no Peito/psicologia , Correlação de Dados , Medo , Humanos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , SARS-CoV-2 , Isolamento Social , Estados Unidos/epidemiologia
3.
Catheter Cardiovasc Interv ; 97(6): E771-E777, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33118694

RESUMO

OBJECTIVES: To assess the prognostic implications of the degree of coronary collaterals on outcomes in patients with a CTO. BACKGROUND: Coronary chronic total occlusions (CTO) are identified frequently in patients undergoing coronary angiography and have been associated with poorer prognosis. Whether the degree of coronary collaterals, the hallmark of CTOs impacts prognosis, is unknown. METHODS: A search of EMBASE, MEDLINE, and Cochrane Library was conducted to identify studies reporting on coronary collaterals and risk of all-cause mortality, acute myocardial infarction (AMI) and successful percutaneous coronary intervention (PCI). Patients with Rentrop grade 0 or 1 collaterals were defined as poor collaterals, while Rentrop grade 2 or 3 were defined as robust collaterals. RESULTS: Twelve studies with a total of 3,369 were included. Patients with robust collaterals did not have lower rates of AMI (OR: 0.89, 95%CI: 0.39-2.04) or lower rates of all-cause mortality (OR: 0.81, 95% CI: 0.42-1.58), however were more likely to have successful PCI (OR: 4.04, 95%CI: 1.10-14.85). CONCLUSION: The presence of robust collaterals is not associated with lower rates of AMI or mortality, but does increase the likelihood of successful CTO PCI. These results have importance implications with respect to the indications for CTO PCI as well as selecting appropriate patients to undergo the procedure.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Doença Crônica , Circulação Colateral , Angiografia Coronária , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Resultado do Tratamento
4.
J Nucl Cardiol ; 28(6): 2597-2608, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33025478

RESUMO

Coronary chronic total occlusions (CTO) are common in patients undergoing coronary angiography, yet the optimal management strategy remains uncertain, with conflicting results from randomized trials. Appropriate patient selection and careful periprocedural planning are imperative for successful patient management. We review the role of adjunctive imaging modalities including myocardial perfusion imaging (MPI), cardiac magnetic resonance imaging (CMR), echocardiography and computed tomography coronary angiography (CTCA) in myocardial ischemic quantification, myocardial viability assessment, as well as procedural planning for CTO revascularization. An appreciation of the value, indications and limitations of these modalities prior to planned intervention are essential for optimal management.


Assuntos
Técnicas de Imagem Cardíaca , Oclusão Coronária/diagnóstico por imagem , Doença Crônica , Oclusão Coronária/cirurgia , Humanos
5.
J Thromb Thrombolysis ; 51(4): 1005-1016, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32930943

RESUMO

Acute coronary collateralisation of an infarct-related arterial (IRA) territory may be identified during angiography for ST elevation myocardial infarction (STEMI). Whether the presence or absence of these collaterals affects outcomes remains uncertain. A search of EMBASE, MEDLINE and Cochrane Library, using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines was conducted to identify studies which reported on the association between coronary collaterals and in-hospital and longer term mortality, left ventricular ejection fraction (LVEF), risk of repeat acute myocardial infarction (AMI) and repeat revascularisation. Patients with Rentrop grade 0 or 1 were defined as poor collaterals whilst those with Rentrop grade two or three were defined as those with robust collaterals. Studies were eligible if they included patients ≥ 18 years of age who had immediate coronary angiography for STEMI. Included studies were observational which recorded the degree of collateral blood flow to the IRA. Two investigators reviewed all citations using a predefined protocol with final consensus for all studies, the data from which was then independently entered to ensure fidelity of results. Inverse variance random effects model for the meta-analysis along with risk of bias assessment was performed. 20 studies with a total of 14,608 patients were identified and included in the analysis. Patients with robust collaterals had lower mortality (OR 0.55, 95% CI 0.48-0.64), both in-hospital (OR 0.47, 95% CI 0.35-0.63) and longer term (OR 0.58, 95% CI 0.46-0.75). Patients with robust collaterals also had a higher mean LVEF (SMD 0.23, 95% CI 0.10-0.37). There was no difference in the rates of AMI or repeat revascularisation between patients with robust or poor collaterals. The presence of robust collaterals during STEMI is associated with reduced in-hospital and longer term mortality and improved left ventricular function. These findings have implications for prognostication and identifying patients who require close monitoring following STEMI.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Angiografia Coronária , Circulação Coronária , Humanos , Prognóstico , Volume Sistólico , Função Ventricular Esquerda
6.
Heart Vessels ; 36(11): 1653-1660, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33914092

RESUMO

The impact of surgical or percutaneous coronary revascularization on prognosis in patients with a chronic total occlusion (CTO) remains uncertain. Particularly, whether revascularization of those with robust coronary collaterals improves prognosis is unknown. The objective of this study was to determine the predictors and prognostic impact of revascularization of a CTO, and to determine the clinical impact of robust coronary collaterals. Patients with a CTO diagnosed on coronary angiography between Jul 2010 and Dec 2019 were included in this study. Management strategy of the CTO was defined as percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical management. The degree of collateral robustness was determined by the Rentrop grading classification. Demographic, angiographic and clinical outcomes were recorded. A total of 954 patients were included in the study, of which 186 (19.5%) patients underwent CTO PCI, 296 (31.0%) patients underwent CABG and 472 (49.5%) patients underwent medical management of the CTO. 166 patients (17.4%) had Rentrop grade zero or one collaterals, 577 (60.5%) patients had Rentrop grade two and 211 (22.1%) had Rentrop grade three collaterals. The independent predictors of medical management of the CTO were older age, greater stenosis in the donor vessel, an emergent indication for angiography, a non-LAD CTO and female sex. The degree of collateral robustness was not associated with long-term mortality, while patients who were revascularized either through CABG or PCI had a significantly lower mortality compared to medical management alone (p < 0.0001). In patients with a CTO, the presence of robust collaterals is not associated with prognosis, while both surgical and percutaneous revascularization is associated with improved prognosis. Further research into the optimal revascularization strategy for a CTO is required.


Assuntos
Angiografia Coronária/métodos , Oclusão Coronária , Intervenção Coronária Percutânea , Idoso , Doença Crônica , Circulação Colateral/fisiologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Feminino , Humanos , Prognóstico , Resultado do Tratamento
7.
Lung ; 199(4): 409-416, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34374863

RESUMO

PURPOSE: Obstructive sleep apnoea (OSA) which results in hypoxia may affect the ability to recruit coronary collaterals. The aim of this study was to determine whether the severity of OSA affects collateral recruitment in patients with total coronary occlusions. METHODS: Patients with total coronary artery occlusion were reviewed. Records from the sleep investigation laboratory were reviewed to identify those patients who had undergone diagnostic polysomnography. Robust coronary collaterals were those with Rentrop grade 2 or 3 collaterals. RESULTS: Sixty-four patients with a total coronary occlusion had polysomnography performed, of whom 60 patients had OSA. Thirty-two patients (53.3%) had poor collaterals, whilst 28 (46.7%) had robust collaterals. Twenty-four (40%) patients had mild OSA, 10 (16.7%) had moderate OSA and 26 (43.3%) had severe OSA. Patients with robust collaterals were more likely to be males (96.4% vs 74.3%, p < 0.05) and have a history of hypercholesterolaemia (88.9% vs 51.6%, p < 0.01). Patients with robust collaterals had a lower apnoea-hypopnoea index (13.6 vs 45.5, p < 0.05), a higher MinSaO2 (85.4% vs 79.8%, p < 0.05), less time SaO2 < 90% (0 min vs 30.4 min, p < 0.05) and lower oxygen desaturation index (6.9 vs 26.8, p < 0.05). Those with moderate OSA had a higher mean Rentrop grade (1.6 ± 0.3) than those with mild OSA (1.5 ± 1.1) and severe OSA (0.6 ± 0.2). CONCLUSION: The presence of more severe OSA is associated with poorer coronary collateral recruitment in patients with total coronary artery occlusion. The effect of treatment of OSA on subsequent ability to recruit collaterals and other cardioprotective mechanisms requires further research.


Assuntos
Oclusão Coronária , Apneia Obstrutiva do Sono , Oclusão Coronária/complicações , Oclusão Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Oxigênio , Polissonografia , Sono , Apneia Obstrutiva do Sono/complicações
8.
Heart Lung Circ ; 30(12): 1883-1890, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34366217

RESUMO

BACKGROUND: Obstructive sleep apnoea (OSA) occurs frequently in patients with coronary artery disease, with associated intermittent hypoxia a possible stimulus for coronary collateral recruitment through ischaemic preconditioning. We sought to determine whether OSA affects recruitment of coronary collaterals and prognosis of patients presenting with ST elevation myocardial infarction (STEMI). METHODS: Patients with a STEMI undergoing percutaneous coronary intervention (PCI) from July 2010 to December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA. Patients with robust collaterals were defined as Rentrop Grade 2 or 3. RESULTS: 1,863 patients were included, of which 143 (7.7%) patients had documented evidence of OSA in their health record. Patients with OSA had a higher body mass index (BMI) (30.2 kg/m2 vs 27 kg/m2, p<0.0001), greater rate of hypertension (61.1% vs 45.1%, p<0.0001), hypercholesterolaemia (47.4% vs 38.4%, p<0.05) and diabetes mellitus (22.6% vs 15.9%, p<0.05). Patients with OSA were more likely to have robust coronary collaterals (OR: 2.2 [95% CI: 1.5-3.2]) and a lower rate of left ventricular (LV) impairment (50.7% vs 63.1%, p<0.01), a higher LV ejection fraction (50.3% vs 46.7%, p<0.0001) and a lower peak troponin-I level (26,452 ng/L vs 39,469 ng/L, p<0.01). There were no differences in rates of in-hospital or longer term mortality, in patients with OSA compared to those without. CONCLUSIONS: Patients with documented OSA presenting with STEMI appear to have more robust coronary collaterals observed on angiography which likely mediates lower myocardial necrosis. Broader implications of this finding on treatment require further investigation.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Apneia Obstrutiva do Sono , Circulação Colateral , Angiografia Coronária , Circulação Coronária , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
9.
Microvasc Res ; 132: 104058, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32798552

RESUMO

The coronary collateral circulation is a rich anastomotic network of primitive vessels which have the ability to augment in size and function through the process of arteriogenesis. In this review, we evaluate the current understandings of the molecular and cellular mechanisms by which this process occurs, specifically focussing on elevated fluid shear stress (FSS), inflammation, the redox state and gene expression along with the integrative, parallel and simultaneous process by which this occurs. The initiating step of arteriogenesis occurs following occlusion of an epicardial coronary artery, with an increase in FSS detected by mechanoreceptors within the endothelium. This must occur within a 'redox window' where an equilibrium of oxidative and reductive factors are present. These factors initially result in an inflammatory milieu, mediated by neutrophils as well as lymphocytes, with resultant activation of a number of downstream molecular pathways resulting in increased expression of proteins involved in monocyte attraction and adherence; namely vascular cell adhesion molecule 1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor beta (TGF-ß). Once monocytes and other inflammatory cells adhere to the endothelium they enter the extracellular matrix and differentiate into macrophages in an effort to create a favourable environment for vessel growth and development. Activated macrophages secrete inflammatory cytokines such as tumour necrosis factor-α (TNF-α), growth factors such as fibroblast growth factor-2 (FGF-2) and matrix metalloproteinases. Finally, vascular smooth muscle cells proliferate and switch to a contractile phenotype, resulting in an increased diameter and functionality of the collateral vessel, thereby allowing improved perfusion of the distal myocardium subtended by the occluded vessel. This simultaneously reduces FSS within the collateral vessel, inhibiting further vessel growth.


Assuntos
Circulação Colateral , Circulação Coronária , Oclusão Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Neovascularização Fisiológica , Remodelação Vascular , Proteínas Angiogênicas/metabolismo , Animais , Doença Crônica , Oclusão Coronária/metabolismo , Vasos Coronários/metabolismo , Citocinas , Humanos , Mediadores da Inflamação/metabolismo , Mecanorreceptores/metabolismo , Mecanotransdução Celular , Estresse Oxidativo
10.
Heart Vessels ; 35(3): 291-296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31482216

RESUMO

The spontaneous recruitment of acute coronary collaterals in the setting of an ST elevation myocardial infarction (STEMI) is seen frequently in those patients undergoing primary percutaneous coronary intervention (pPCI) and is associated with improved clinical outcomes. However, it is unknown whether in patients who present with a recurrent STEMI, the degree of collateral recruitment remains the same as in the index procedure. We reviewed all patients presenting to our tertiary centre with a STEMI undergoing primary or rescue percutaneous coronary intervention (PCI) from July 2010 until December 2018. We identified patients who presented with a recurrent STEMI following their index procedure. We defined patients with poor collateral recruitment as Rentrop grade 0 or 1, whilst patients with robust collateral recruitment as Rentrop grade 2 or 3. Of the 1795 patients who were identified, there were 27 cases in 25 patients who presented with a repeat STEMI following their index procedure. The median time between cases was 12.8 days (IQR 2.3-589.5 days). Compared to the index case, there was no statistically significant difference in the degree of collateral recruitment in recurrent presentations (Z = - 0.378, p = 0.70). In those patients presenting more than 6 months following the index procedure, the median time between cases was 654.5 days (IQR 479.5-1151.9). There was no difference in the degree of collateral recruitment in recurrent presentations (Z = 0.000, p = 1.0). Cases which had poorer collateral recruitment in recurrent presentations were less likely to be current smokers (0% vs 50%, p < 0.001) and less likely to have diabetes (0% vs 27.3%, p < 0.05) The recruitment of spontaneous coronary collaterals remains constant in recurrent STEMI presentations suggesting an innate biological process rather than merely a manifestation of alteration of haemodynamic blood flow. Further investigations to identify these processes is required.


Assuntos
Síndrome Coronariana Aguda/terapia , Circulação Colateral , Circulação Coronária , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Recidiva , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
11.
Int J Mol Sci ; 21(5)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32121587

RESUMO

: Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3ß) pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.


Assuntos
Autofagia , Cardiotônicos/metabolismo , Interleucina-6/metabolismo , Precondicionamento Isquêmico Miocárdico , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Sobrevivência Celular , Ratos , Regulação para Cima
12.
Int Heart J ; 61(2): 223-230, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32173707

RESUMO

The predictors and prognostic implications of well-matured collaterals in those with a chronic total occlusion (CTO) are unknown. We sought to identify the determinants of collateral maturation and to determine its effects on procedural outcomes and prognosis.Patients presenting for CTO percutaneous coronary intervention (PCI) between April 2010 and July 2019 were included. Patients with a previous coronary artery bypass (CABG) to the CTO and those with only bridging collaterals were excluded. The degree of collateral maturation was determined by the Rentrop grading classification. Demographic, biochemical, and anatomical factors and procedural and longer-term outcomes were identified.A total of 212 patients were included in the study. Patients with well-matured collaterals were more likely to be females (29.7% versus 15.2% versus 0%, P < 0.005 for Rentrop grade 3, 2, and 0 or 1, respectively), less likely to have chronic kidney disease (CKD) (8.8% versus 4.5% versus 19.2%, P < 0.05) and less likely to have had a prior CABG (15.6% versus 18.7% versus 19.2%). Patients with well-matured collaterals had lower neutrophil-to-leukocyte ratio (NLR) (2.8 versus 4.0 versus 5.7, P < 0.0001). Patients with well-matured collaterals were more likely to have procedural success (90.5% versus 62.5% versus 34.6%, P < 0.0001). The degree of collateral maturation was not associated with longer-term mortality.Improved collateral maturation was associated with female sex and lower rates of CKD and CABG and a lower NLR. Those with well-matured collaterals had a significantly higher rate of procedural success but not improved prognosis.


Assuntos
Circulação Colateral , Oclusão Coronária/terapia , Intervenção Coronária Percutânea/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Oclusão Coronária/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
14.
Heart Lung Circ ; 28(10): 1484-1489, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31078427

RESUMO

A coronary chronic total occlusion (CTO) is a common finding during coronary angiography and is associated with increased mortality and poorer cardiovascular prognosis. Technological developments in percutaneous strategies for revascularisation have resulted in increased interest in this area. However, until recently, there has been a paucity of robust scientific randomised data comparing the efficacy of medical management with percutaneous strategies. Both observational data, and to a lesser extent, randomised data, suggest that CTO percutaneous coronary intervention (PCI) should be considered in symptomatic patients. However, in the absence of any randomised data, CTO PCI should not be performed for prognostic benefit. Ongoing trials are needed to confirm these findings as well as to identify the optimal timing and strategy of such interventions.


Assuntos
Oclusão Coronária/cirurgia , Vasos Coronários/cirurgia , Intervenção Coronária Percutânea/métodos , Doença Crônica , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico , Vasos Coronários/diagnóstico por imagem , Humanos , Fatores de Tempo
16.
J Am Heart Assoc ; 13(9): e034102, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38639330

RESUMO

BACKGROUND: Large observational studies have demonstrated a clear inverse association between renal function and risk of aortic stenosis (AS). Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional 2-sample Mendelian randomization approach. METHODS AND RESULTS: We collected summary statistics for the primary analysis of chronic kidney disease (CKD) and AS from genome-wide association study meta-analyses including 480 698 and 653 867 participants, respectively. We collected further genome-wide association study summary statistics from up to 1 004 040 participants for sensitivity analyses involving estimated glomerular filtration rate (eGFR) derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. Inverse-variance weighted was the primary analysis method, with weighted-median, weighted-mode, Mendelian randomization-Egger, and Mendelian randomization-Pleiotropy Residual Sum and Outlier as sensitivity analyses. We did not find evidence of a causal relationship between genetically predicted CKD liability as the exposure and AS as the outcome (odds ratio [OR], 0.94 per unit increase in log odds of genetic liability to CKD [95% CI, 0.85-1.04], P=0.26) nor robust evidence of AS liability as the exposure and CKD as the outcome (OR, 1.04 per unit increase in log odds of genetic liability to AS [95% CI, 0.97-1.12], P=0.30). The sensitivity analyses were neutral overall, as were the analyses using eGFR derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. All positive controls demonstrated strong significant associations. CONCLUSIONS: The present study did not find evidence of a substantial effect of genetically predicted renal impairment on risk of AS. This has important implications for research efforts that attempt to identify prevention and treatment targets for both CKD and AS.


Assuntos
Estenose da Valva Aórtica , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular , Análise da Randomização Mendeliana , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/epidemiologia , Taxa de Filtração Glomerular/genética , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/fisiopatologia , Cistatina C/sangue , Cistatina C/genética , Fatores de Risco , Rim/fisiopatologia , Predisposição Genética para Doença , Creatinina/sangue , Medição de Risco , Polimorfismo de Nucleotídeo Único , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea
17.
Am J Cardiol ; 205: 329-337, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37633070

RESUMO

Elevated blood pressure, dyslipidemia, and impaired glycemic control are well-established cardiovascular risk factors in Europeans, but there are comparatively few studies focused on East Asian populations. This study evaluated the potential causal relations between traditional cardiovascular risk factors and disease risk in East Asians through a 2-sample Mendelian randomization approach. We collected summary statistics for blood pressure parameters, lipid subsets, and type 2 diabetes mellitus liability from large genome-wide association study meta-analyses conducted in East Asians and Europeans. These were paired with summary statistics for ischemic heart disease (IHD), ischemic stroke (IS), peripheral vascular disease, heart failure (HF) and atrial fibrillation (AF). We performed univariable Mendelian randomization analyses for each exposure-outcome pair, followed by multivariable analyses for the available lipid subsets. The genetically predicted risk factors associated with IHD and AF were similar between East Asians and Europeans. However, in East Asians only genetically predicted elevated blood pressure was significantly associated with IS (odds ratio 1.05, 95% confidence interval 1.04 to 1.06, p <0.0001) and HF (odds ratio 1.05, 95% confidence interval 1.04 to 1.06, p <0.0001), whereas nearly all genetically predicted risk factors were significantly associated with IS and HF in Europeans. In conclusion, this study provides supportive evidence for similar causal relations between traditional cardiovascular risk factors and IHD and AF in both East Asian and European ancestry populations. However, the identified risk factors for IS and HF differed between East Asians and Europeans, potentially highlighting distinct disease etiologies between these populations.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , População do Leste Asiático , Hipertensão , Humanos , Fibrilação Atrial , Pressão Sanguínea/genética , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca , Hipertensão/epidemiologia , Hipertensão/genética , AVC Isquêmico , Lipídeos , Análise da Randomização Mendeliana , Isquemia Miocárdica , População Europeia
18.
Sci Rep ; 13(1): 18810, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914784

RESUMO

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1ß inhibitor) and colchicine (ß-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1ß or ß-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45-0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51-1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99-592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management.


Assuntos
Estenose da Valva Aórtica , Agentes de Imunomodulação , Humanos , Estudo de Associação Genômica Ampla , Proteína C-Reativa/genética , Colchicina/farmacologia , Colchicina/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
19.
BMJ Open ; 13(3): e070219, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36889832

RESUMO

INTRODUCTION: Aortic stenosis is the most common cardiac valve pathology worldwide and has a mortality rate of over 50% at 5 years if left untreated. Transcatheter aortic valve implantation (TAVI) is a minimally invasive and highly effective alternative treatment option to open-heart surgery. High-grade atrioventricular conduction block (HGAVB) is one of the most common complications after TAVI and requires a permanent pacemaker. Due to this, patients are typically monitored for 48 hours post TAVI, however up to 40% of HGAVB may delayed, and occur after discharge. Delayed HGAVB can cause syncope or sudden unexplained cardiac death in a vulnerable population, and no accurate methods currently exist to identify patients at risk. METHODS AND ANALYSIS: The prospective observational study on the accuracy of predictors of high-grade atrioventricular conduction block after transcatheter aortic valve implantation (CONDUCT-TAVI) trial is an Australian-led, multicentre, prospective observational study, aiming to improve the prediction of HGAVB, after TAVI. The primary objective of the trial is to assess whether published and novel invasive electrophysiology predictors performed immediately before and after TAVI can help predict HGAVB after TAVI. The secondary objective aims to further evaluate the accuracy of previously published predictors of HGAVB after TAVI, including CT measurements, 12-lead ECG, valve characteristics, percentage oversizing and implantation depth. Follow-up will be for 2 years, and detailed continuous heart rhythm monitoring will be obtained by inserting an implantable loop recorder in all participants. ETHICS AND DISSEMINATION: Ethics approval has been obtained for the two participating centres. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12621001700820.


Assuntos
Estenose da Valva Aórtica , Bloqueio Atrioventricular , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/terapia , Austrália , Coração , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento , Estudos Observacionais como Assunto
20.
Lancet ; 388(10060): 2569-2570, 2016 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-27806899
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