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BACKGROUND AND AIMS: Catheter-based therapies (CBTs) have been developed as a treatment option in patients with pulmonary embolism (PE). There remains a paucity of data to inform decision-making in patients with intermediate-risk or high-risk PE. The aim of this study was to characterize in-hospital and readmission outcomes in patients with intermediate-risk or high-risk PE treated with vs. without CBT in a large retrospective registry. METHODS: Patients hospitalized with intermediate-risk or high-risk PE were identified using the 2017-20 National Readmission Database. In-hospital outcomes included death and bleeding and 30- and 90-day readmission outcomes including all-cause, venous thromboembolism (VTE)-related and bleeding-related readmissions. Inverse probability of treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT. RESULTS: A total of 14 903 [2076 (13.9%) with CBT] and 42 829 [8824 (20.6%) with CBT] patients with high-risk and intermediate-risk PE were included, respectively. Prior to IPTW, patients with CBT were younger and less likely to have cancer and cardiac arrest, receive systemic thrombolysis, or be on mechanical ventilation. In the IPTW logistic regression model, CBT was associated with lower odds of in-hospital death in high-risk [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.80-0.87] and intermediate-risk PE (OR 0.76, 95% CI 0.70-0.83). Patients with high-risk PE treated with CBT were associated with lower risk of 90-day all-cause [hazard ratio (HR) 0.77, 95% CI 0.71-0.83] and VTE (HR 0.46, 95% CI 0.34-0.63) readmission. Patients with intermediate-risk PE treated with CBT were associated with lower risk of 90-day all-cause (HR 0.75, 95% CI 0.72-0.79) and VTE (HR 0.66, 95% CI 0.57-0.76) readmission. CONCLUSIONS: Among patients with high-risk or intermediate-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. Prospective, randomized trials are needed to confirm these findings.
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Readmissão do Paciente , Embolia Pulmonar , Humanos , Embolia Pulmonar/terapia , Embolia Pulmonar/mortalidade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Mortalidade Hospitalar , Sistema de Registros , Hemorragia/terapia , Hemorragia/mortalidade , Medição de Risco , Terapia Trombolítica/métodosRESUMO
Advances in cancer therapies have improved oncologic outcomes but can potentially expose patients to risk of cardiovascular toxicity. While left ventricular (LV) dysfunction is a well-known cardiotoxicity of cancer therapy. Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are seen with several cancer therapies, including alkylating agents, tyrosine kinase inhibitors (TKIs), and immunotherapy, and are associated with significant morbidity and mortality. Awareness and recognition of cancer therapy-associated PH and RV dysfunction is critical to identify underlying etiologies and institute the appropriate therapy. However, gaps exist in the current literature on the epidemiology of PH and RV dysfunction in cancer, underlying pathophysiology and optimal management strategies.
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BACKGROUND: Pulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter-based therapies (CBT), including catheter-directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high-risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients. AIMS: To characterize outcomes of patients with cancer admitted with intermediate or high-risk PE treated with CBT compared with no CBT. METHODS: Patients with an admission diagnosis of intermediate or high-risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in-hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression. RESULTS: A total of 2084 unweighted admissions (10,420 weighted) for intermediate or high-risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46-0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21-1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36-0.75) and high-risk PE (aOR 0.48, 95% CI 0.33-0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate-risk PE (aOR 2.12, 95% CI 1.67-2.69) but not in those with high-risk PE (aOR 0.84, 95% CI 0.66-1.07). CONCLUSIONS: Among patients with cancer hospitalized with intermediate or high-risk PE, treatment with CBT was associated with lower risk of in-hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.
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Neoplasias , Embolia Pulmonar , Humanos , Terapia Trombolítica/efeitos adversos , Mortalidade Hospitalar , Fibrinolíticos/efeitos adversos , Pacientes Internados , Estudos Prospectivos , Resultado do Tratamento , Embolia Pulmonar/terapia , Embolia Pulmonar/tratamento farmacológico , Catéteres , Hemorragia/induzido quimicamente , Neoplasias/complicações , Estudos RetrospectivosRESUMO
OPINION STATEMENT: Gastrointestinal cancers are a heterogenous group of cancers that share common risk factors with cardiovascular disease. Therapy for gastrointestinal cancers have improved cancer-specific outcomes at the cost of cardiotoxicity. The most common cardiotoxic therapies utilized in gastrointestinal cancers include conventional chemotherapy (including fluoropyrimidines and anthracyclines), targeted therapies including anti-vascular endothelial growth factor (VEGF) therapy and tyrosine kinase inhibitors (TKI), and immunotherapy. It is important for clinicians managing patients with gastrointestinal cancers to be aware of potential cardiotoxicity associated with these agents.
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INTRODUCTION: Patients with myeloproliferative neoplasms (MPNs) and atrial fibrillation (AF) are at increased risk of thrombosis and bleeding. However, the risk of thrombosis and bleeding in patients with AF and MPN compared with the general population with AF is unclear. Additionally, traditional risk scores (CHA2DS2-VASC and HAS-BLED) for risk/benefit estimation of thromboprophylaxis in AF do not account for MPN status. Therefore, we aimed to investigate bleeding and thrombosis risk in patients with MPN hospitalized for AF. METHODS: We utilized the National Readmission Database (NRD) to identify patients with AF with and without MPN. Primary bleeding and thrombosis outcomes were in-hospital or 30-day readmission for bleeding or thrombosis, respectively. We propensity score (PS) matched patients with and without MPN. Risk of primary outcomes in MPN was assessed in PS matched cohort using logistic regression. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of primary thrombosis and bleeding outcomes, respectively. RESULTS: 24,185 patients without MPN were matched with 1,617 patients with MPN and variables were balanced between groups. Patients with MPN were at increased risk of meeting the thrombosis (OR 1.98, 95% CI 1.23-3.21) but not bleeding (OR 0.87, 95% CI 0.63-1.19) primary outcomes. In MPN, CHA2DS2-VASC predicted thrombosis (C-statistic 0.66, 95% CI 0.54-0.78) but HAS-BLED was a poor predictor of bleeding (C-statistic 0.55, 95% CI 0.46-0.64). CONCLUSION: In patients with AF, MPN was associated with increased risk of bleeding and thrombosis. HAS-BLED scores did not accurately predict bleeding in MPN. Further investigation is needed to refine risk scores in MPN.
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Fibrilação Atrial , Neoplasias , Acidente Vascular Cerebral , Trombose , Tromboembolia Venosa , Humanos , Fibrilação Atrial/tratamento farmacológico , Readmissão do Paciente , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Neoplasias/complicações , Hemorragia/induzido quimicamente , Fatores de Risco , Medição de Risco , Trombose/induzido quimicamente , Hospitais , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Advances in cancer therapeutics have improved overall survival and prognosis in this patient population; however, this has come at the expense of cardiotoxicity including arrhythmia. SUMMARY: Cancer and its therapies are associated with cardiotoxicity via several mechanisms including inflammation, cardiomyopathy, and off-target effects. Among cancer therapies, anthracyclines and tyrosine kinase inhibitors (TKIs) are particularly known for their pro-arrhythmia effects. In addition to cardiomyopathy, anthracyclines may be pro-arrhythmogenic via reactive oxygen species (ROS) generation and altered calcium handling. TKIs may mediate their cardiotoxicity via inhibition of off-target tyrosine kinases. Ibrutinib-mediated inhibition of CSK may be responsible for the increased prevalence of atrial fibrillation. Further investigation is warranted to further elucidate the mechanisms behind arrhythmias in cancer therapies. KEY MESSAGES: Arrhythmias are a common cardiotoxicity of cancer therapies. Cancer therapies may induce arrhythmias via off-target effects. Understanding the mechanisms underlying arrhythmogenesis associated with cancer therapies may help design cancer therapies that can avoid these toxicities.
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Fibrilação Atrial , Cardiomiopatias , Neoplasias , Humanos , Cardiotoxicidade/etiologia , Neoplasias/tratamento farmacológico , Cardiomiopatias/induzido quimicamente , Antraciclinas/efeitos adversosRESUMO
OPINION STATEMENT: Patients with cancer are at risk of developing cardiovascular disease (CVD) including atherosclerotic heart disease (AHD), valvular heart disease (VHD), and atrial fibrillation (AF). Advances in percutaneous catheter-based treatments, including percutaneous coronary intervention (PCI) for AHD, percutaneous valve replacement or repair for VHD, and ablation and left atrial appendage occlusion devices (LAAODs) for AF, have provided patients with CVD significant benefit in the recent decades. However, trials and registries investigating outcomes of these procedures often exclude patients with cancer. As a result, patients with cancer are less likely to undergo these therapies despite their benefits. Despite the inclusion of cancer patients in randomized clinical trial data, studies suggest that cancer patients derive similar benefits of percutaneous therapies for CVD compared with patients without cancer. Therefore, percutaneous interventions for CVD should not be withheld in patients with cancer, as they may still benefit from these procedures.
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Fibrilação Atrial , Doenças das Valvas Cardíacas , Neoplasias , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/cirurgia , Fatores de Risco , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Neoplasias/complicações , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The risk of thrombosis in myeloproliferative neoplasms, such as primary myelofibrosis varies depending on the type of key driving mutation (JAK2 [janus kinase 2], CALR [calreticulin], and MPL [myeloproliferative leukemia protein or thrombopoietin receptor]) and the accompanying mutations in other genes. In the current study, we sought to examine the propensity for thrombosis, as well as platelet activation properties in a mouse model of primary myelofibrosis induced by JAK2V617F (janus kinase 2 with valine to phenylalanine substitution on codon 617) mutation. Approach and Results: Vav1-hJAK2V617F transgenic mice show hallmarks of primary myelofibrosis, including significant megakaryocytosis and bone marrow fibrosis, with a moderate increase in red blood cells and platelet number. This mouse model was used to study responses to 2 models of vascular injury and to investigate platelet properties. Platelets derived from the mutated mice have reduced aggregation in response to collagen, reduced thrombus formation and thrombus size, as demonstrated using laser-induced or FeCl3-induced vascular injury models, and increased bleeding time. Strikingly, the mutated platelets had a significantly reduced number of dense granules, which could explain impaired ADP secretion upon platelet activation, and a diminished second wave of activation. CONCLUSIONS: Together, our study highlights for the first time the influence of a hyperactive JAK2 on platelet activation-induced ADP secretion and dense granule homeostasis, with consequent effects on platelet activation properties.
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Coagulação Sanguínea , Plaquetas/enzimologia , Lesões das Artérias Carótidas/enzimologia , Janus Quinase 2/sangue , Megacariócitos/enzimologia , Ativação Plaquetária , Mielofibrose Primária/enzimologia , Trombose/enzimologia , Animais , Lesões das Artérias Carótidas/sangue , Lesões das Artérias Carótidas/genética , Modelos Animais de Doenças , Janus Quinase 2/genética , Camundongos Transgênicos , Mutação , Agregação Plaquetária , Mielofibrose Primária/sangue , Mielofibrose Primária/genética , Trombopoese , Trombose/sangue , Trombose/genéticaRESUMO
Despite steady progress over the past 3 decades in advancing drug and device therapies to reduce morbidity and mortality in heart failure with reduced ejection fraction, large registries of usual care demonstrate incomplete use of these evidence-based therapies in clinical practice. Potential strategies to improve guideline-directed medical therapy include leveraging non-physician clinicians, solidifying transitions of care, incorporating telehealth solutions, and engaging in comprehensive comorbid disease management via multidisciplinary team structures. These approaches may be particularly relevant in an era of Coronavirus Disease 2019 and associated need for social distancing, further limiting contact with traditional ambulatory clinic settings.
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Assistência Ambulatorial , Infecções por Coronavirus , Insuficiência Cardíaca/terapia , Pandemias , Pneumonia Viral , Assistência Ambulatorial/métodos , Assistência Ambulatorial/organização & administração , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Insuficiência Cardíaca/epidemiologia , Humanos , Inovação Organizacional , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , SARS-CoV-2RESUMO
The extracellular matrix (ECM) is a key acellular structure in constant remodeling to provide tissue cohesion and rigidity. Deregulation of the balance between matrix deposition, degradation, and crosslinking results in fibrosis. Bone marrow fibrosis (BMF) is associated with several malignant and nonmalignant pathologies severely affecting blood cell production. BMF results from abnormal deposition of collagen fibers and enhanced lysyl oxidase-mediated ECM crosslinking within the marrow, thereby increasing marrow stiffness. Bone marrow stiffness has been recently recognized as an important regulator of blood cell development, notably by modifying the fate and differentiation process of hematopoietic or mesenchymal stem cells. This review surveys the different components of the ECM and their influence on stem cell development, with a focus on the impact of the ECM composition and stiffness on the megakaryocytic lineage in health and disease. Megakaryocyte maturation and the biogenesis of their progeny, the platelets, are thought to respond to environmental mechanical forces through a number of mechanosensors, including integrins and mechanosensitive ion channels, reviewed here.
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Plaquetas/citologia , Medula Óssea/fisiologia , Matriz Extracelular/fisiologia , Hematopoese/fisiologia , Megacariócitos/citologia , Animais , Proteínas da Matriz Extracelular/química , Proteínas da Matriz Extracelular/fisiologia , Glicosaminoglicanos/fisiologia , Células-Tronco Hematopoéticas/citologia , Humanos , Integrinas/fisiologia , Canais Iônicos/fisiologia , Mecanotransdução Celular , Células-Tronco Mesenquimais/citologia , Camundongos , Proteínas de Neoplasias/fisiologia , Neoplasias/patologia , Mielofibrose Primária/patologia , Proteína-Lisina 6-Oxidase/fisiologia , Trombopoese/fisiologiaAssuntos
Plaquetas/enzimologia , Megacariócitos/enzimologia , Adesividade Plaquetária/fisiologia , Mielofibrose Primária/enzimologia , Proteína-Lisina 6-Oxidase/fisiologia , Aminopropionitrilo/farmacologia , Células Cultivadas , Colágeno Tipo I/química , Colágeno Tipo I/farmacologia , Indução Enzimática , Colágenos Associados a Fibrilas/farmacologia , Humanos , Adesividade Plaquetária/efeitos dos fármacos , Mielofibrose Primária/sangue , Mielofibrose Primária/patologia , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Proteína-Lisina 6-Oxidase/biossíntese , Regulação para CimaAssuntos
Anemia Falciforme , Linfo-Histiocitose Hemofagocítica , Doenças Vasculares , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Pessoa de Meia-Idade , Doenças Vasculares/diagnóstico , Doenças Vasculares/etiologia , Doenças Vasculares/patologia , Doenças Vasculares/terapiaRESUMO
BACKGROUND: Cancer patients are at risk of pulmonary embolism (PE). Catheter-based therapies (CBT) are novel reperfusion options for PE though data in patients with cancer is lacking. STUDY DESIGN AND METHODS: Patients with intermediate- or high-risk PE were identified using the National Readmission Database (NRD) from 2017 to 2020. Primary outcome were in-hospital death and 90-day readmission. Secondary outcomes were in-hospital bleeding, 90-day readmission for venous thromboembolism (VTE)-related or right heart failure-related reasons and bleeding. Propensity scores were estimated using logistic regression and inverse-probability treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT as well as CBT versus systemic thrombolysis. RESULTS: A total of 7785 patients were included (2511 with high-risk PE) of whom 1045 (13.4%) were managed with CBT. After IPTW, CBT was associated with lower rates of index hospitalization death (OR 0.89, 95% CI 0.83-0.96) and 90-day readmission (HR 0.75, 95% CI 0.69-0.81) but higher rates of in-hospital bleeding (OR 1.11, 95% CI 1.03-1.20) which was predominantly post-procedural bleeding. CBT was associated with lower risk of major bleeding (20.8% vs 24.8%; OR 0.80, 95% CI 0.68-0.94) compared with systemic thrombolysis. INTERPRETATION: Among patients with cancer with intermediate or high-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. CBT was also associated with decreased risk of index hospitalization major bleeding compared with systemic thrombolysis. Prospective, randomized trials with inclusion of patients with cancer are needed to confirm these findings.
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Mortalidade Hospitalar , Neoplasias , Readmissão do Paciente , Embolia Pulmonar , Humanos , Embolia Pulmonar/terapia , Embolia Pulmonar/mortalidade , Embolia Pulmonar/epidemiologia , Masculino , Feminino , Neoplasias/complicações , Neoplasias/terapia , Neoplasias/epidemiologia , Idoso , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Readmissão do Paciente/tendências , Mortalidade Hospitalar/tendências , Resultado do Tratamento , Estudos Retrospectivos , Terapia Trombolítica/métodos , Idoso de 80 Anos ou maisRESUMO
Background: Cardiogenic shock (CS) is the leading cause of death among patients with acute myocardial infarction (AMI) and is managed with temporary mechanical circulatory support (tMCS) in advanced cases. Patients with cancer are at high risk of AMI and CS. However, outcomes of patients with cancer and AMI-CS managed with tMCS have not been rigorously studied. Methods: Adult patients with AMI-CS managed with tMCS from 2006 to 2018 with and without cancer were identified using the National Inpatient Sample. Propensity score matching (PSM) was performed for variables associated with cancer. Primary outcome was in-hospital death, and secondary outcomes were major bleeding and thrombotic complications. Results: After PSM, 1287 patients with cancer were matched with 12,870 patients without cancer. There was an increasing temporal trend for prevalence of cancer among patients admitted with AMI-CS managed with tMCS (P trend < .001). After PSM, there was no difference in in-hospital death (odds ratio [OR], 1.00; 95% CI, 0.88-1.13) or thrombotic complications (OR, 1.10; 95% CI, 0.91-1.34) between patients with and without cancer. Patients with cancer had a higher risk of major bleeding (OR, 1.29; 95% CI, 1.15-1.46). Conclusions: Among patients with AMI-CS managed with tMCS, cancer is becoming increasingly frequent and associated with increased risk of major bleeding, although there was no difference in in-hospital death. Further studies are needed to further characterize outcomes, and inclusion of patients with cancer in trials of tMCS is needed.
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BACKGROUND: Many patients with mildly to moderately reduced left ventricular ejection fraction (LVEF) who require permanent pacemaker (PPM) implantation do not have a concurrent indication for implantable cardioverter-defibrillator (ICD) therapy. However, the risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in this population is unknown. OBJECTIVE: The aim of this study was to describe the risk of VT/VF after PPM implantation in patients with mildly to moderately reduced LVEF. METHODS: Retrospective analysis was performed of 243 patients with LVEF between 35% and 49% who underwent PPM placement and did not meet indications for an ICD. The primary end point was occurrence of sustained VT/VF. Competing risks regression was performed to calculate subhazard ratios for the primary end point. RESULTS: Median follow-up was 27 months; 73% of patients were male, average age was 79 ± 10 years, average LVEF was 42% ± 4%, and 70% were New York Heart Association class II or above. Most PPMs were implanted for sick sinus syndrome (34%) or atrioventricular block (50%). Of 243 total patients, 11 (4.5%) met the primary end point of VT/VF. Multivessel coronary artery disease (CAD) was associated with significantly higher rates of VT/VF, with a subhazard ratio of 5.4 (95% CI, 1.5-20.1; P = .01). Of patients with multivessel CAD, 8 of 82 (9.8%) patients met the primary end point for an annualized risk of 4.3% per year. CONCLUSION: Patients with mildly to moderately reduced LVEF and multivessel CAD undergoing PPM implantation are at increased risk for the development of malignant ventricular arrhythmias. Patients in this population may benefit from additional risk stratification for VT/VF and consideration for upfront ICD implantation.
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Marca-Passo Artificial , Volume Sistólico , Taquicardia Ventricular , Humanos , Masculino , Feminino , Volume Sistólico/fisiologia , Idoso , Estudos Retrospectivos , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/terapia , Seguimentos , Medição de Risco/métodos , Fatores de Risco , Desfibriladores Implantáveis , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapia , Função Ventricular Esquerda/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/terapiaRESUMO
INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events. MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and for men ≤45 years, as points of reference. RESULTS: Among 6585 outpatients, 169 were pregnant at diagnosis. By 90-day follow-up, two pregnant women during the third trimester had lower extremity venous thrombosis, one deep and one superficial vein thrombosis. The cumulative incidence of thrombotic events was 1.20 % (95 % confidence interval [CI]: 0.0 to 2.84 %). Respective rates were 0.47 % (95 % CI: 0.14 % to 0.79 %) among non-pregnant women, and 0.49 % (95 % CI: 0.06 % to 0.91 %) among men ≤45 years. No non-thrombotic cardiovascular events occurred in pregnant women. The rates of cardiovascular events were 0.53 % (95 % CI: 0.18 to 0.87) among non-pregnant women, and 0.68 % (95 % CI: 0.18 to 1.18) in men aged ≤45 years. CONCLUSIONS: Thrombotic and cardiovascular events are rare among outpatients with COVID-19. Although a higher event rate among outpatient pregnant women cannot be excluded, the absolute event rates are low and do not warrant population-wide cardiovascular interventions to optimize outcomes.
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COVID-19 , Pacientes Ambulatoriais , Trombose , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Gravidez , Feminino , Adulto , Pacientes Ambulatoriais/estatística & dados numéricos , Trombose/etiologia , Trombose/epidemiologia , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Pessoa de Meia-Idade , Sistema de Registros , SARS-CoV-2 , Complicações Infecciosas na Gravidez/epidemiologia , Incidência , Trombose Venosa/epidemiologia , Trombose Venosa/etiologiaRESUMO
Angiotensin-converting enzyme 2 (ACE2) catalyzes conversion of ANG II to ANG-(1-7). The present study uses newly established proteomic approaches and genetic mouse models to examine the contribution of alternative renal peptidases to ACE2-independent formation of ANG-(1-7). In situ and in vitro mass spectrometric characterization showed that substrate concentration and pH control renal ANG II processing. At pH ≥6, ANG-(1-7) formation was significantly reduced in ACE2 knockout (KO) mice. However, at pH <6, formation of ANG-(1-7) in ACE2 KO mice was similar to that in wild-type (WT) mice, suggesting alternative peptidases for renal ANG II processing. Furthermore, the dual prolyl carboxypeptidase (PCP)-prolyl endopeptidase (PEP) inhibitor Z-prolyl-prolinal reduced ANG-(1-7) formation in ACE2 KO mice, while the ACE2 inhibitor MLN-4760 had no effect. Unlike the ACE2 KO mice, ANG-(1-7) formation from ANG II in PEP KO mice was not different from that in WT mice at any tested pH. However, at pH 5, this reaction was significantly reduced in kidneys and urine of PCP-depleted mice. In conclusion, results suggest that ACE2 metabolizes ANG II in the kidney at neutral and basic pH, while PCP catalyzes the same reaction at acidic pH. This is the first report demonstrating that renal ANG-(1-7) formation from ANG II is independent of ACE2. Elucidation of ACE2-independent ANG-(1-7) production pathways may have clinically important implications in patients with metabolic and renal disease.
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Angiotensina II/urina , Angiotensina I/urina , Carboxipeptidases/metabolismo , Fragmentos de Peptídeos/urina , Peptidil Dipeptidase A/metabolismo , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Carboxipeptidases/antagonistas & inibidores , Carboxipeptidases/farmacocinética , Dipeptídeos/farmacologia , Imidazóis/farmacologia , Rim/metabolismo , Leucina/análogos & derivados , Leucina/farmacologia , Masculino , Camundongos , Camundongos Knockout , Peptidil Dipeptidase A/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. As treatments have improved prognosis of VWD, age-related diseases, including acute myocardial infarction (AMI), have become more prevalent. The treatment of AMI includes antithrombotic therapies, which increase the risk of bleeding. Current guidelines suggest weighing risks/benefits of antithrombotic therapy in patients with VWD. However, data to inform these discussions are lacking. Objective: To characterize outcomes of patients with VWD after AMI. Methods: We conducted a retrospective cohort study utilizing the National Readmissions Database of patients with and without VWD admitted with AMI in 2017 and 2018. Primary outcomes were 90-day any-cause, bleeding-related, and arterial thrombosis-related readmissions. Case-control matching was performed for age, sex (male or female), ST-elevation myocardial infarction, percutaneous coronary intervention, diabetes, and chronic kidney disease. Time-to-event analysis was performed after matching using Cox proportional hazards regression. Results: A total of 136 patients with VWD were matched with 3400 controls without VWD. At 90 days, there were no differences in all-cause (10.7% vs 11.5%; P = 1.00), arterial thrombosis (1.9% vs 3.1%; P = .77), and bleeding (1.9% vs 0.4%; P = .083) readmission in patients with VWD. VWD was associated with increased risk of 90-day bleeding (hazard ratio [HR], 4.75; 95% CI, 1.05-21.66) but not all-cause (HR, 0.91; 95% CI, 0.50-1.67) or arterial thrombosis (HR, 0.54; 95% CI, 0.39-2.19) readmission. Conclusion: Among patients admitted with AMI, VWD was associated with higher risk of 90-day readmission for bleeding but not any-cause and arterial thrombosis-related readmissions. Further studies are needed to balance bleeding and thrombotic risks post-AMI in patients with VWD.
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Background: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell neoplasms with a high risk of thrombosis, including acute myocardial infarction (AMI). However, outcomes after AMI have not been thoroughly characterized. Objectives: The purpose of this study was to characterize outcomes after AMI in patients with MPNs compared with patients without MPNs. Methods: Patients with a primary admission of AMI from January 2006 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest included in-hospital death or cardiac arrest (CA) and major bleeding. Propensity score weighting was used to compare outcomes between MPN and non-MPN groups. Results: A total of 1,644,304 unweighted admissions for AMI were included; of these admissions, 5,374 (0.3%) were patients with MPNs. After propensity score weighting, patients with MPNs had a lower risk of in-hospital death or CA (OR: 0.83; 95% CI: 0.82-0.84) but a higher risk of major bleeding (OR: 1.29; 95% CI: 1.28-1.30) compared with non-MPN patients. There was a decreasing temporal rate of in-hospital death or CA and bleeding in patients without MPNs (Ptrend < 0.001 for both). However, there was an increasing temporal rate of in-hospital death or CA (Ptrend < 0.001) and a stable rate of major bleeding (Ptrend = 0.48) in patients with MPNs. Conclusions: Among patients hospitalized with AMI, patients with MPNs have a lower risk of in-hospital death or CA compared with patients without MPNs, although they have a higher risk of bleeding. More investigation is needed in order to improve post-AMI bleeding outcomes in patients with MPN.