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1.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

2.
Can J Neurol Sci ; : 1-10, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34162448

RESUMO

BACKGROUND: Due to lack of data on the epidemiology, cardiac, and neurological complications among Ontario visible minorities (Chinese and South Asians) affected by coronavirus disease (COVID-19), this population-based retrospective study was undertaken to study them systematically. METHODS: From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population. RESULTS: Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) (p < 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) (p < 0.001). The 30-day crude rate for cardiac complications among Chinese was 169/10,000 (p = 0.069), while for South Asians, it was 64/10,000 (p = 0.008) and, for the general population, it was 112/10,000. For neurological complications, the 30-day crude rate for Chinese was 160/10,000 (p < 0.001); South Asians was 40/10,000 (p = 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population (p < 0.001), while it was lower in South Asians at 2.1% (p < 0.001). CONCLUSIONS: Chinese and South Asians in Ontario affected by COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.

3.
CJC Open ; 2(6): 563-576, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33305217

RESUMO

Background: We previously found large variation among family physicians in adherence to the Canadian Cardiovascular Harmonization of National Guidelines Endeavour (C-CHANGE). We assessed the role of patient- and physician-level factors in the variation in adherence to recommendations for managing cardiovascular disease risk factors. Methods: We conducted a retrospective study using multilevel logistic regression analyses with the Electronic Medical Record Administrative data Linked Database (EMRALD) housed at ICES in Ontario. Five quality indicators based on C-CHANGE guidelines were modelled. Effects of clustering and between-group variation, patient-level (sociodemographics, comorbidities) and physician-level characteristics (demographic and practice information) were assessed to determine odds ratios of receiving C-CHANGE recommended care. Results: In all, 324 Ontario physicians practicing in 41 clinics who provided care to 227,999 adult patients were studied. We found significant variation in quality indicators, with 15% to 39% of the total variation attributable to nonpatient factors. The largest variation was in performing 2-hour plasma glucose testing in prediabetic patients. Patient-level factors most frequently associated with recommendation adherence included sex, age, and multi-comorbidities. Women were more likely than men to have their body mass index measured, and their blood pressure controlled, but less likely to receive antiplatelet medications and liver-enzyme testing if overweight or obese. Conclusions: The majority of variations in adherence were attributable to patient attributes, but a substantial proportion of unexplained variation was due to differences among physicians and clinics. This finding may signal suboptimal processes or structures and warrant further investigation to improve the quality of primary care management of cardiovascular disease in Ontario.

4.
BMJ Open ; 10(11): e044126, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243819

RESUMO

OBJECTIVES: To examine the temporal trends in mortality and heart failure (HF) hospitalisation in ambulatory patients following a new diagnosis of HF. DESIGN: Retrospective cohort study SETTING: Outpatient PARTICIPANTS: Ontario residents who were diagnosed with HF in an outpatient setting between 1994 and 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause mortality within 1 year of diagnosis and the secondary outcome was HF hospitalisation within 1 year. Risks of mortality and hospitalisation were calculated using the Kaplan-Meier method and the relative hazard of death was assessed using multivariable Cox proportional hazard models. RESULTS: A total of 352 329 patients were studied (50% female). During the study period, there was a greater decline in age standardised 1-year mortality rates (AMR) in men (33%) than in women (19%). Specifically, female AMR at 1 year was 10.4% (95% CI 9.1% to 12.0%) in 1994 and 8.5% (95% CI 7.5% to 9.5%) in 2013, and male AMR at 1 year was 12.3% (95% CI 11.1% to 13.7%) in 1994 and 8.3% (95% CI 7.5% to 9.1%) in 2013. Conversely, age standardised HF hospitalisation rates declined in men (11.4% (95% CI 10.1% to 12.9%) in 1994 and 9.1% (95% CI 8.2% to 10.1%) in 2013) but remained unchanged in women (9.7% (95% CI 8.3% to 11.3%) in 1994 and 9.8% (95% CI 8.6% to 11.0%) in 2013). CONCLUSION: Among patients with HF over a 20-year period, there was a greater improvement in the prognosis of men compared with women. Further research should focus on the determinants of this disparity and ways to reduce this gap in outcomes.


Assuntos
Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Fatores Sexuais
5.
Circulation ; 142(23): 2240-2258, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33070627

RESUMO

BACKGROUND: Cardiac hypertrophy is a key biological response to injurious stresses such as pressure overload and, when excessive, can lead to heart failure. Innate immune activation by danger signals, through intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain 1 (Nod1) and its adaptor receptor-interacting protein 2 (RIP2), might play a major role in cardiac remodeling and progression to heart failure. We hypothesize that Nod1/RIP2 are major contributors to cardiac hypertrophy, but may not be sufficient to fully express the phenotype alone. METHODS: To elucidate the contribution of Nod1/RIP2 signaling to cardiac hypertrophy, we randomized Nod1-/-, RIP2-/-, or wild-type mice to transverse aortic constriction or sham operations. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. RESULTS: Nod1 and RIP2 proteins were upregulated in the heart after transverse aortic constriction, and this was paralleled by increased expression of mitochondrial proteins, including mitochondrial antiviral signaling protein (MAVS). Nod1-/- and RIP2-/- mice subjected to transverse aortic constriction exhibited better survival, improved cardiac function, and decreased cardiac hypertrophy. Downstream signal transduction pathways that regulate inflammation and fibrosis, including NF (nuclear factor) κB and MAPK (mitogen-activated protein kinase)-GATA4/p300, were reduced in both Nod1-/- and RIP2-/- mice after transverse aortic constriction compared with wild-type mice. Coimmunoprecipitation of extracted cardiac proteins and confocal immunofluorescence microscopy showed that Nod1/RIP2 interaction was robust and that this complex also included MAVS as an essential component. Suppression of MAVS expression attenuated the complex formation, NF κB signaling, and myocyte hypertrophy. Interrogation of mitochondrial function compared in the presence or ablation of MAVS revealed that MAVS serves to suppress mitochondrial energy output and mediate fission/fusion related dynamic changes. The latter is possibly linked to mitophagy during cardiomyocytes stress, which may provide an intriguing link between innate immune activation and mitochondrial energy balance under stress or injury conditions. CONCLUSIONS: We have identified that innate immune Nod1/RIP2 signaling is a major contributor to cardiac remodeling after stress. This process is critically joined by and regulated through the mitochondrial danger signal adapter MAVS. This novel complex coordinates remodeling, inflammatory response, and mitochondrial energy metabolism in stressed cardiomyocytes. Thus, Nod1/RIP2/MAVS signaling complex may represent an attractive new therapeutic approach toward heart failure.

8.
Hypertension ; 76(4): 1104-1112, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32673499

RESUMO

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.


Assuntos
Infecções por Coronavirus , Creatina Quinase Forma MB/sangue , Cardiopatias , Peptídeo Natriurético Encefálico/sangue , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral , Troponina I/sangue , Betacoronavirus/isolamento & purificação , Biomarcadores/sangue , COVID-19 , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Cardiopatias/sangue , Cardiopatias/mortalidade , Cardiopatias/virologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , SARS-CoV-2
10.
Cell Metab ; 32(2): 176-187.e4, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592657

RESUMO

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/efeitos dos fármacos , COVID-19 , Comorbidade , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2
12.
Circ Res ; 126(12): 1671-1681, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32302265

RESUMO

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Infecções por Coronavirus/epidemiologia , Mortalidade Hospitalar , Hipertensão/epidemiologia , Pneumonia Viral/epidemiologia , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações
13.
Eur Heart J ; 41(36): 3477-3484, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32337540

RESUMO

This state-of-the-art review aims to provide an up-to-date look at breakthrough omic technologies that are helping to unravel heart failure (HF) disease mechanisms and heterogeneity. Genomics, transcriptomics, proteomics, and metabolomics in HF are reviewed in depth. In addition, there is a thorough, expert discussion regarding the value of omics in identifying novel disease pathways, advancing understanding of disease mechanisms, differentiating HF phenotypes, yielding biomarkers for diagnosis or prognosis, or identifying new therapeutic targets in HF. The combination of multiple omics technologies may create a more comprehensive picture of the factors and physiology involved in HF than achieved by either one alone and provides a rich resource for predictive phenotype modelling. However, the successful translation of omics tools as solutions to clinical HF requires that the observations are robust and reproducible and can be validated across multiple independent populations to ensure confidence in clinical decision-making.


Assuntos
Insuficiência Cardíaca , Metabolômica , Biomarcadores , Genômica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Humanos , Proteômica
14.
Circulation ; 142(1): 68-78, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32293910

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.


Assuntos
Sistema Cardiovascular/metabolismo , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Coagulação Sanguínea , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , COVID-19 , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Imunidade Inata , Interleucina-6/metabolismo , Linfopenia/etiologia , Masculino , Pandemias , Peptidil Dipeptidase A/metabolismo , Fenótipo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Prognóstico , SARS-CoV-2 , Serina Endopeptidases/metabolismo , Taxa de Sobrevida
15.
Nat Rev Drug Discov ; 19(1): 57-75, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31548636

RESUMO

Fibrosis is the abnormal deposition of extracellular matrix, which can lead to organ dysfunction, morbidity, and death. The disease burden caused by fibrosis is substantial, and there are currently no therapies that can prevent or reverse fibrosis. Metabolic alterations are increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types. As a result, metabolically targeted therapies could become important strategies for fibrosis reduction. Indeed, some of the pathways targeted by antifibrotic drugs in development - such as the activation of transforming growth factor-ß and the deposition of extracellular matrix - have metabolic implications. This Review summarizes the evidence to date and describes novel opportunities for the discovery and development of drugs for metabolic reprogramming, their associated challenges, and their utility in reducing fibrosis. Fibrotic therapies are potentially relevant to numerous common diseases such as cirrhosis, non-alcoholic steatohepatitis, chronic renal disease, heart failure, diabetes, idiopathic pulmonary fibrosis, and scleroderma.


Assuntos
Reprogramação Celular , Proteínas da Matriz Extracelular/metabolismo , Fibrose/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Fibrose/metabolismo , Fibrose/patologia , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Fator de Crescimento Transformador beta
16.
Clin Transplant ; 34(1): e13765, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31815308

RESUMO

Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV1-2 (mild-moderate CAV), CAV3 (severe CAV), and CAV0 (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies.


Assuntos
Doença da Artéria Coronariana , Transplante de Coração , Aloenxertos , Biomarcadores , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Feminino , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteômica
17.
Circulation ; 140(2): 80-91, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31390169

RESUMO

Recent developments in cancer therapeutics have improved outcomes but have also been associated with cardiovascular complications. Therapies harnessing the immune system have been associated with an immune-mediated myocardial injury described as myocarditis. Immune checkpoint inhibitors are one such therapy with an increasing number of case and cohort reports describing a clinical syndrome of immune checkpoint inhibitor­associated myocarditis. Although the full spectrum of immune checkpoint inhibitor­associated cardiovascular disease still needs to be fully defined, described cases of myocarditis range from syndromes with mild signs and symptoms to fatal events. These observations in the clinical setting stand in contrast to outcomes from randomized clinical trials in which myocarditis is a rare event that is investigator reported and lacking in a specific case definition. The complexities associated with diagnosis, as well as the heterogeneous clinical presentation of immune checkpoint inhibitor­associated myocarditis, have made ascertainment and identification of myocarditis with high specificity challenging in clinical trials and other data sets, limiting the ability to better understand the incidence, outcomes, and predictors of these rare events. Therefore, establishing a uniform definition of myocarditis for application in clinical trials of cancer immunotherapies will enable greater understanding of these events. We propose an operational definition of cancer therapy-associated myocarditis that may facilitate case ascertainment and report and therefore may enhance the understanding of the incidence, outcomes, and risk factors of this novel clinical syndrome.


Assuntos
Cardiologia/tendências , Oncologia/tendências , Miocardite/terapia , Neoplasias/terapia , Antineoplásicos Imunológicos/uso terapêutico , Cardiologia/métodos , Ensaios Clínicos como Assunto/métodos , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Oncologia/métodos , Miocardite/epidemiologia , Miocardite/imunologia , Neoplasias/epidemiologia , Neoplasias/imunologia
18.
Int J Cardiol ; 291: 177-182, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31153653

RESUMO

BACKGROUND: Previous studies have identified ethnic differences in outcomes after episodes of acute heart failure in natives of Asia as compared to those of Europe. Whether these ethnic differences in outcomes would still exist, years after migration to a different geographical and cultural setting remain unclear. We investigated the one-year mortality after an episode of acute heart failure admission in Ontario residents of South Asian and Chinese descent as compared to the General Population. METHODS: We conducted a population-based, retrospective cohort study of adult Ontarions who were hospitalized for AHF between April 1, 2010 and March 31, 2016. Ethnicity was categorized using validated surname-based algorithms. The primary outcome was all-cause one-year mortality. Mortality rates were calculated using the Kaplan-Meier method. The relative hazard of death was assessed using a multivariable Cox proportional hazard model. RESULTS: Of 82,125 patients, 1287 (1.6%) were Chinese, 1662 (2.0%) were South Asians, and the remaining 79,176 (96.4%) were of the General Population. The risk of mortality was markedly lower amongst South Asians (adjusted HR 0.81, 95% CI [0.73-0.89]) relative to the General Population. There was no statistically significant difference in the risk of mortality between Chinese and the General Population (adjusted HR 1.00 [0.91-1.10]). In addition, guideline-directed medical therapies were associated with similar survival benefit in patients of all three ethnic origins. CONCLUSIONS: We found a lower risk of one-year mortality after acute heart failure hospitalization amongst South Asians compared to Chinese and the General Population, and similar benefit of medical therapy in all three groups. Further studies are needed to explore the etiologies of these ethnic disparities to truly improve outcomes at the population level.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Grupos Étnicos , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Mortalidade/tendências , Ontário/etnologia , Estudos Retrospectivos , Resultado do Tratamento
19.
Nat Rev Dis Primers ; 5(1): 32, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073128

RESUMO

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different aetiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases. The heterogeneous aetiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodelling, and immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter-defibrillators may be required to prevent life-threatening arrhythmias. In addition, identifying the probable cause of DCM helps tailor specific therapies to improve prognosis. An improved aetiology-driven personalized approach to clinical care will benefit patients with DCM, as will new diagnostic tools, such as serum biomarkers, that enable early diagnosis and treatment.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/terapia , Autoimunidade/genética , Autoimunidade/fisiologia , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia/métodos , Eletrocardiografia/métodos , Insuficiência Cardíaca/etiologia , Humanos , Inflamação/complicações , Inflamação/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Prognóstico , Qualidade de Vida/psicologia , Fatores Sexuais
20.
J Clin Med ; 8(4)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027170

RESUMO

Right ventricular failure (RVF) is a major risk factor for end organ morbidity and mortality following cardiac surgery. Perioperative RVF is difficult to predict and detect, and to date, no convenient, accurate, or reproducible measure of right ventricular (RV) function is available. Few studies have examined the use of biomarkers in RVF, and even fewer have examined their utility in the perioperative setting of patients undergoing cardiac surgery. Of the available classes of biomarkers, this review focuses on biomarkers of (1) inflammation and (2) myocyte injury/stress, due to their superior potential in perioperative RV assessment, including Galectin 3, ST2/sST2, CRP, cTN/hs-cTn, and BNP/NT-proBNP. This review was performed to help highlight the importance of perioperative RV function in patients undergoing cardiac surgery, to review the current modalities of RV assessment, and to provide a review of RV specific biomarkers and their potential utilization in the clinical and perioperative setting in cardiac surgery. Based on current evidence, we suggest the potential utility of ST2, sST2, Gal-3, CRP, hs-cTn, and NT-proBNP in predicting and detecting RVF in cardiac surgery patients, as they encompass the multifaceted nature of perioperative RVF and warrant further investigation to establish their clinical utility.

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