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Venetoclax is a standard treatment for patients with CLL following covalent BTK inhibitor (cBTKi) therapy, despite relatively limited prospective data in this setting. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that was designed to overcome the pharmacologic limitations of cBTKi and re-establish BTK inhibition. An unanchored matching-adjusted indirect comparison (MAIC) was conducted to estimate the treatment effect of pirtobrutinib versus venetoclax monotherapy in patients with cBTKi pre-treated CLL. Data from patients with CLL who were venetoclax-naïve and pre-treated with cBTKi received pirtobrutinib (n=146) in the phase 1/2 BRUIN study were compared with the only identified trial of patients with CLL receiving venetoclax after a cBTKi (n=91), as administered as monotherapy until progression. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). Both unweighted and weighted analyses were conducted. PFS and OS of pirtobrutinib and venetoclax were comparable in both unweighted and weighted analyses (weighted hazard ratios for PFS: 1.01, 95% CI: 0.58-1.73, p=0.98 and OS: 0.64, 95% CI: 0.25-1.67, p=0.34). ORR was significantly higher for pirtobrutinib (80.2% vs 64.8%, p=0.01). Grade ≥3 TEAEs were lower in weighted analyses for pirtobrutinib vs venetoclax (all p.
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BACKGROUND: Machine learning (ML) models of risk prediction with coronary artery calcium (CAC) and CAC characteristics exhibit high performance, but are not inherently interpretable. OBJECTIVES: To determine the direction and magnitude of impact of CAC characteristics on 10-year all-cause mortality (ACM) with explainable ML. METHODS: We analyzed asymptomatic subjects in the CAC consortium. We trained ML models on 80% and tested on 20% of the data with XGBoost, using clinical characteristics â+ âCAC (ML 1) and additional CAC characteristics of CAC density and number of calcified vessels (ML 2). We applied SHAP, an explainable ML tool, to explore the relationship of CAC and CAC characteristics with 10-year all-cause and CV mortality. RESULTS: 2376 deaths occurred among 63,215 patients [68% male, median age 54 (IQR 47-61), CAC 3 (IQR 0-94.3)]. ML2 was similar to ML1 to predict all-cause mortality (Area Under the Curve (AUC) 0.819 vs 0.821, p â= â0.23), but superior for CV mortality (0.847 vs 0.845, p â= â0.03). Low CAC density increased mortality impact, particularly ≤0.75. Very low CAC density ≤0.75 was present in only 4.3% of the patients with measurable density, and 75% occurred in CAC1-100. The number of diseased vessels did not increase mortality overall when simultaneously accounting for CAC and CAC density. CONCLUSION: CAC density contributes to mortality risk primarily when it is very low ≤0.75, which is primarily observed in CAC 1-100. CAC and CAC density are more important for mortality prediction than the number of diseased vessels, and improve prediction of CV but not all-cause mortality. Explainable ML techniques are useful to describe granular relationships in otherwise opaque prediction models.
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Aterosclerose , Doença da Artéria Coronariana , Calcificação Vascular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Angiografia Coronária/métodos , Cálcio , Fatores de Risco , Valor Preditivo dos Testes , Vasos Coronários , Aprendizado de Máquina , Medição de RiscoRESUMO
Resumo Fundamento A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. Objetivo Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. Métodos A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. Resultados Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). Conclusões A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.
Abstract Background The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. Objective To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. Methods The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. Results Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). Conclusions COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.
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AIMS: The relationship between AtheroSclerotic CardioVascular Disease (ASCVD) risk and vessel-specific plaque evaluation using coronary computed tomography angiography (CCTA), focusing on plaque extent and composition, has not been examined. To evaluate differences in quantified plaque characteristics (using CCTA) between the three major coronary arteries [left anterior descending (LAD), right coronary (RCA), and left circumflex (LCx)] among subgroups of patients with varying ASCVD risk. METHODS AND RESULTS: Patients were included from a prospective, international registry of consecutive patients who underwent CCTA for evaluation of coronary artery disease. ASCVD risk groups were <7.5% (low), 7.5-20% (intermediate), and ≥20% (high). Among the ASCVD risk groups, the three coronary arteries were compared regarding quantified plaque volume and composition. Whole-heart plaque quantification was performed in 1340 patients (age 60 ± 9 years, 58% men). Across low, intermediate, and high ASCVD risk patients, the volume of plaque increased proportionally but was least in the LCx (7.4, 9.0, and 25.3 mm3, respectively) as compared with the RCA (19.3, 32.6, and 67.0 mm3, respectively, all P ≤ 0.006) and LAD (39.9, 60.8, and 93.3 mm3, respectively, all P < 0.001). In each ASCVD risk group, the composition of plaque in the LCx exhibited the least necrotic core and fibrofatty plaque (P < 0.05 vs. LAD and RCA). CONCLUSION: Among patients with varying risk of ASCVD, plaque in the LCx is decidedly less and is comprised of less non-calcified plaque supporting prior evidence of the lower rates of acute coronary events in this vessel.
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Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Placa Aterosclerótica , Idoso , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos ProspectivosRESUMO
BACKGROUND: The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. OBJECTIVE: To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. RESULTS: Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). CONCLUSIONS: COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.
FUNDAMENTO: A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. OBJETIVO: Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. MÉTODOS: A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. RESULTADOS: Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). CONCLUSÕES: A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.
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COVID-19 , Cardiopatias , COVID-19/diagnóstico , COVID-19/epidemiologia , Cardiopatias/epidemiologia , Humanos , América Latina/epidemiologia , Pandemias , Inquéritos e QuestionáriosRESUMO
Although acute coronary syndrome culprit lesions occur more frequently in the proximal coronary artery, whether the proximal clustering of high-risk plaque is reflected in earlier-stage atherosclerosis remains unclarified. We evaluated the longitudinal distribution of stable atherosclerotic lesions on coronary computed tomography angiography (CCTA) in 1,478 patients (mean age, 61 years; men, 58%) enrolled from a prospective multinational registry of consecutive patients undergoing serial CCTA. Of 3,202 coronary artery lesions identified, 2,140 left lesions were classified (based on the minimal lumen diameter location) into left main (LM, n = 128), proximal (n = 739), and other (n = 1,273), and 1,062 right lesions were classified into proximal (n = 355) and other (n = 707). Plaque volume (PV) was the highest in proximal lesions (median, 26.1 mm3), followed by LM (20.6 mm3) and other lesions (15.0 mm3, p <0.001), for left lesions, and was lager in proximal (25.8 mm3) than in other lesions (15.2 mm3, p <0.001) for right lesions. On both sides, proximally located lesions tended to have greater necrotic core and fibrofatty components than other lesions (left: LM, 10.6%; proximal, 5.8%; other, 3.4% of the total PV, p <0.001; right: proximal, 8.4%; other 3.1%, p <0.001), with less calcified plaque component (left: LM, 18.3%; proximal, 30.3%; other, 37.7%, p <0.001; right: proximal, 23.3%, other, 36.6%, p <0.001), and tended to progress rapidly (adjusted odds ratios: left: LM, reference; proximal, 0.95, p = 0.803; other, 0.64, p = 0.017; right: proximal, reference; other, 0.52, p <0.001). Proximally located plaques were larger, with more risky composition, and progressed more rapidly.
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Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Placa Aterosclerótica/complicações , Placa Aterosclerótica/patologia , Idoso , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Sistema de RegistrosRESUMO
Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm3), with necrotic core and fibro-fatty PV regression (- 5.7 mm3 and - 5.6 mm3, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (- 2.4 mm3). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm3). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm3), predominantly increasing in calcified PV (+ 35.9 mm3). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.
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Doença da Artéria Coronariana/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem , Idoso , Análise por Conglomerados , Angiografia Coronária , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/classificação , Placa Aterosclerótica/patologia , Calcificação Vascular/patologiaRESUMO
OBJECTIVES: We aimed to explore the impact of the COVID-19 pandemic on cardiac diagnostic testing and practice and to assess its impact in different regions in Europe. METHODS: The online survey organised by the International Atomic Energy Agency Division of Human Health collected information on changes in cardiac imaging procedural volumes between March 2019 and March/April 2020. Data were collected from 909 centres in 108 countries. RESULTS: Centres in Northern and Southern Europe were more likely to cancel all outpatient activities compared with Western and Eastern Europe. There was a greater reduction in total procedure volumes in Europe compared with the rest of the world in March 2020 (45% vs 41%, p=0.003), with a more marked reduction in Southern Europe (58%), but by April 2020 this was similar in Europe and the rest of the world (69% vs 63%, p=0.261). Regional variations were apparent between imaging modalities, but the largest reductions were in Southern Europe for nearly all modalities. In March 2020, location in Southern Europe was the only independent predictor of the reduction in procedure volume. However, in April 2020, lower gross domestic product and higher COVID-19 deaths were the only independent predictors. CONCLUSION: The first wave of the COVID-19 pandemic had a significant impact on care of patients with cardiac disease, with substantial regional variations in Europe. This has potential long-term implications for patients and plans are required to enable the diagnosis of non-COVID-19 conditions during the ongoing pandemic.
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COVID-19 , Técnicas de Imagem Cardíaca/tendências , Cardiologistas/tendências , Disparidades em Assistência à Saúde/tendências , Cardiopatias/diagnóstico por imagem , Padrões de Prática Médica/tendências , Europa (Continente) , Pesquisas sobre Atenção à Saúde , Humanos , Valor Preditivo dos TestesRESUMO
OBJECTIVES: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. BACKGROUND: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. METHODS: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. RESULTS: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. CONCLUSIONS: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection.
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COVID-19 , Pandemias , Teste para COVID-19 , Humanos , Valor Preditivo dos Testes , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: The INCAPS COVID Oceania study aimed to assess the impact caused by the COVID-19 pandemic on cardiac procedure volume provided in the Oceania region. METHODS: A retrospective survey was performed comparing procedure volumes within March 2019 (pre-COVID-19) with April 2020 (during first wave of COVID-19 pandemic). Sixty-three (63) health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, and 846 facilities outside of Oceania. The percentage change in procedure volume was measured between March 2019 and April 2020, compared by test type and by facility. RESULTS: In Oceania, the total cardiac diagnostic procedure volume was reduced by 52.2% from March 2019 to April 2020, compared to a reduction of 75.9% seen in the rest of the world (p<0.001). Within Oceania sites, this reduction varied significantly between procedure types, but not between types of health care facility. All procedure types (other than stress cardiac magnetic resonance [CMR] and positron emission tomography [PET]) saw significant reductions in volume over this time period (p<0.001). In Oceania, transthoracic echocardiography (TTE) decreased by 51.6%, transoesophageal echocardiography (TOE) by 74.0%, and stress tests by 65% overall, which was more pronounced for stress electrocardiograph (ECG) (81.8%) and stress echocardiography (76.7%) compared to stress single-photon emission computerised tomography (SPECT) (44.3%). Invasive coronary angiography decreased by 36.7% in Oceania. CONCLUSION: A significant reduction in cardiac diagnostic procedure volume was seen across all facility types in Oceania and was likely a function of recommendations from cardiac societies and directives from government to minimise spread of COVID-19 amongst patients and staff. Longer term evaluation is important to assess for negative patient outcomes which may relate to deferral of usual models of care within cardiology.
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COVID-19 , Cardiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. OBJECTIVES: The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices. METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. RESULTS: Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth. CONCLUSIONS: COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted.
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COVID-19 , Cardiopatias/diagnóstico , Técnicas de Diagnóstico Cardiovascular/estatística & dados numéricos , Saúde Global , Pesquisas sobre Atenção à Saúde , Humanos , Agências InternacionaisRESUMO
Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.
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Gene therapy for hematological disorders relies on the genetic modification of CD34(+) cells, a heterogeneous cell population containing about 0.01% long-term repopulating cells. Here, we show that the lentiviral vector CD133-LV, which uses a surface marker on human primitive hematopoietic stem cells (HSCs) as entry receptor, transfers genes preferentially into cells with high engraftment capability. Transduction of unstimulated CD34(+) cells with CD133-LV resulted in gene marking of cells with competitive proliferative advantage in vitro and in immunodeficient mice. The CD133-LV-transduced population contained significantly more cells with repopulating capacity than cells transduced with vesicular stomatitis virus (VSV)-LV, a lentiviral vector pseudotyped with the vesicular stomatitis virus G protein. Upon transfer of a barcode library, CD133-LV-transduced cells sustained gene marking in vivo for a prolonged period of time with a 6.7-fold higher recovery of barcodes compared to transduced control cells. Moreover, CD133-LV-transduced cells were capable of repopulating secondary recipients. Lastly, we show that this targeting strategy can be used for transfer of a therapeutic gene into CD34(+) cells obtained from patients suffering of X-linked chronic granulomatous disease. In conclusion, direct gene transfer into CD133(+) cells allows for sustained long-term engraftment of gene corrected cells.