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1.
Phytochem Anal ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103248

RESUMO

OBJECTIVE: Cannabis sativa L. is renowned for its medicinal and recreational uses. With the increasing global legalization of C. sativa L.-based products for medicinal purposes, there is a growing need for well-characterized products. While the stability of cannabinoids such as tetrahydrocannabinol and cannabidiol is well understood, information on the chemical and enantiomeric stability of terpenes remains scarce. This is despite the fact that terpenes are also thought to have pharmacological activity and may contribute to the overall effect of C. sativa L. METHODS: To address these challenges, four analytical methods based on chiral, polar, and apolar gas chromatographic separation combined with either MS or FID detection were developed and validated. These methods successfully separated and quantified a total of 29 terpenes, including 13 enantiomers and 5 diastereomers specific to C. sativa L. Furthermore, terpenes and authentic C. sativa L. flowers and extracts were subjected to UV and heat treatments to observe potential degradation reactions over time. RESULTS: Each terpene generates a unique pattern of degradation products resulting in a diverse array of oxidation and cyclization products. P-cymene was identified as a major product of terpene aging. Notably, no enantiomeric conversion was detected, suggesting that the formation of (-)-α-pinene in cannabis extracts, for example, originates from other terpenes. CONCLUSION: Terpenes have different degradation rates, even though they are structurally similar. In addition, cultivar- and growth-condition-specific enantiomeric ratios were observed in C. sativa L., confirming that enantiomer production is species-specific and has to be considered for therapeutical applications.

2.
J Financ Stab ; 73: None, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39145044

RESUMO

This paper uses a stylized simulation model to assess the potential impact of climate transition risk on banks' balance sheets in a climate-stress-testing (i.e. short-run) framework. We show that a moderate to high transition risk increases overall bank losses only relatively modestly if the baseline is a stressed macroeconomic scenario. However, even in a benign macroeconomic scenario, if high-carbon assets are at least 13% riskier than comparable assets a fire sale mechanism could amplify an initially contained shock into a systemic crisis, resulting in significant losses for the EU banking sector. We show that transition risks are concentrated, and find that an additional capital buffer of 0.9% risk-weighted assets on average would be sufficient to protect the system.

3.
Insights Imaging ; 15(1): 208, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143443

RESUMO

AIM: To determine the effectiveness of functional stress testing and computed tomography angiography (CTA) for diagnosis of obstructive coronary artery disease (CAD). METHODS AND RESULTS: Two-thousand nine-hundred twenty symptomatic stable chest pain patients were included in the international Collaborative Meta-Analysis of Cardiac CT consortium to compare CTA with exercise electrocardiography (exercise-ECG) and single-photon emission computed tomography (SPECT) for diagnosis of CAD defined as ≥ 50% diameter stenosis by invasive coronary angiography (ICA) as reference standard. Generalised linear mixed models were used for calculating the diagnostic accuracy of each diagnostic test including non-diagnostic results as dependent variables in a logistic regression model with random intercepts and slopes. Covariates were the reference standard ICA, the type of diagnostic method, and their interactions. CTA showed significantly better diagnostic performance (p < 0.0001) with a sensitivity of 94.6% (95% CI 92.7-96) and a specificity of 76.3% (72.2-80) compared to exercise-ECG with 54.9% (47.9-61.7) and 60.9% (53.4-66.3), SPECT with 72.9% (65-79.6) and 44.9% (36.8-53.4), respectively. The positive predictive value of CTA was ≥ 50% in patients with a clinical pretest probability of 10% or more while this was the case for ECG and SPECT at pretest probabilities of ≥ 40 and 28%. CTA reliably excluded obstructive CAD with a post-test probability of below 15% in patients with a pretest probability of up to 74%. CONCLUSION: In patients with stable chest pain, CTA is more effective than functional testing for the diagnosis as well as for reliable exclusion of obstructive CAD. CTA should become widely adopted in patients with intermediate pretest probability. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Database for Systematic Reviews-CRD42012002780. CRITICAL RELEVANCE STATEMENT: In symptomatic stable chest pain patients, coronary CTA is more effective than functional testing for diagnosis and reliable exclusion of obstructive CAD in intermediate pretest probability of CAD. KEY POINTS: Coronary computed tomography angiography showed significantly better diagnostic performance (p < 0.0001) for diagnosis of coronary artery disease compared to exercise-ECG and SPECT. The positive predictive value of coronary computed tomography angiography was ≥ 50% in patients with a clinical pretest probability of at least 10%, for ECG ≥ 40%, and for SPECT 28%. Coronary computed tomography angiography reliably excluded obstructive coronary artery disease with a post-test probability of below 15% in patients with a pretest probability of up to 74%.

4.
Int J Occup Saf Ergon ; : 1-8, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39185579

RESUMO

Objectives. This study aimed to evaluate the influence of individual characteristics (sex, age, body mass index [BMI] and smoking habits) on the tolerance time, pain ratings and rewarming time of hand cold stress testing (CST). Methods. We included 153 subjects (63% men) working in a Swedish open-pit mine (participation rate 41%). The right hand was immersed in 3 °C circulating water for up to 45 s. Pain ratings were registered every fifth second using a visual analog scale. Results. The tolerance time (mean ± standard deviation) was 35 ± 12 s for men and 29 ± 14 s for women (p = 0.007). The youngest age group (18-29 years) had the longest tolerance time, while the oldest group (54-65 years) had the shortest (p = 0.005). Women had significantly higher pain ratings than men after 5, 10 and 25 s. The group with the highest BMI had the shortest rewarming time (p < 0.001). Conclusions. Age and sex influenced the tolerance time of hand CST, while only sex affected the pain ratings and BMI the rewarming time. When performing CST in future studies, these parameters should be considered.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39174434

RESUMO

BACKGROUND: Guidelines and international appropriate use criteria increasingly endorse non-invasive stress testing to evaluate patients with suspected chronic coronary disease (CCD). We sought to review the real-world utilisation of non-invasive stress testing and investigate whether their use prior to PCI associates with outcomes in patients with CCD. METHODS: Consecutive patients from a multicentre registry who underwent PCI for CCD between 2006 and 2018 were included. Clinical characteristics and outcomes were stratified according to whether stress testing was performed prior to PCI (stress vs no-stress groups). The primary outcome was 3-year all-cause mortality. RESULTS: Among the 8251 patients included, 4970 (60.2 %) underwent pre-PCI stress testing and this proportion increased over time (p-for-trend<0.001). The stress group had a lower prevalence of prior revascularization, myocardial infarction, or heart failure, and a lower incidence of triple vessel disease, in stent re-stenosis, and ACC/AHA class B2/C lesions (all p < 0.001). When comparing post-procedural outcomes, the stress group had lower rates of arrhythmia (1.5 % vs 2.6 %, p = 0.001), new heart failure (0.2 % vs 0.8 %, p = 0.001), renal impairment, and a shorter length of stay (1.6 vs 2.1 days, p < 0.001). Mortality at 3-years was lower in those undergoing PCI following stress testing (5.8 % vs 8.8 %, p < 0.001). After adjusting for key clinical variables, stress guided revascularization was associated with a significantly lower risk of 3-year mortality (adjusted Hazard Ratio 0.77, 95 % CI 0.64-0.92). CONCLUSIONS: In patients with CCD, PCI guided by non-invasive stress testing is increasingly utilized and associated with improved survival. Further studies are necessary to investigate whether this results from differences in patient characteristics, optimized patient selection, or refined choice of target vessel.

6.
AAPS J ; 26(5): 96, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174806

RESUMO

Stress testing (also known as forced degradation) of pharmaceutical drug substances and products is a critical part of the drug development process, providing insight into the degradation pathways of drug substances and drug products. This information is used to support the development of stability-indicating methods (SIMs) capable of detecting pharmaceutically relevant degradation products that might potentially be observed during manufacturing, long-term storage, distribution, and use. Assessing mass balance of stressed samples is a key aspect of developing SIMs and is a regulatory expectation. However, the approaches to measure, calculate, and interpret mass balance can vary among different pharmaceutical companies. Such disparities also pose difficulties for health authorities when reviewing mass balance assessments, which may result in the potential delay of drug application approvals. The authors have gathered input from 10 pharma companies to map out a practical review of science-based approaches and technical details to assess and interpret mass balance results. Key concepts of mass balance are introduced, various mass balance calculations are demonstrated, and recommendations on how to investigate poor mass balance results are presented using real-world case studies. Herein we provide a single source reference on the topic of mass balance in pharmaceutical forced degradation for small molecule drug substances and drug products in support of regulatory submissions with the goal of facilitating a shared understanding among pharmaceutical scientists and health authorities.


Assuntos
Estabilidade de Medicamentos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Indústria Farmacêutica/métodos , Humanos , Desenvolvimento de Medicamentos/métodos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38985691

RESUMO

AIM: To determine in patients undergoing stress CMR whether fully automated stress artificial intelligence (AI)-based left ventricular ejection fraction (LVEFAI) can provide incremental prognostic value to predict death above traditional prognosticators. MATERIEL AND RESULTS: Between 2016 and 2018, we conducted a longitudinal study that included all consecutive patients referred for vasodilator stress CMR. LVEFAI was assessed using AI-algorithm combines multiple deep learning networks for LV segmentation. The primary outcome was all-cause death assessed using the French National Registry of Death. Cox regression was used to evaluate the association of stress LVEFAI with death after adjustment for traditional risk factors and CMR findings.In 9,712 patients (66±15 years, 67% men), there was an excellent correlation between stress LVEFAI and LVEF measured by expert (LVEFexpert) (r=0.94, p<0.001). Stress LVEFAI was associated with death (median [IQR] follow-up 4.5 [3.7-5.2] years) before and after adjustment for risk factors (adjusted hazard ratio [HR], 0.84 [95% CI, 0.82-0.87] per 5% increment, p<0.001). Stress LVEFAI had similar significant association with death occurrence compared with LVEFexpert. After adjustment, stress LVEFAI value showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.11; NRI=0.250; IDI=0.049, all p<0.001; LR-test p<0.001), with an incremental prognostic value over LVEFAI determined at rest. CONCLUSION: AI-based fully automated LVEF measured at stress is independently associated with the occurrence of death in patients undergoing stress CMR, with an additional prognostic value above traditional risk factors, inducible ischemia and LGE.

8.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892037

RESUMO

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.


Assuntos
Adenosina , Doença da Artéria Coronariana , Humanos , Adenosina/metabolismo , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/tratamento farmacológico , Animais , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia
9.
Circulation ; 149(23): e1239-e1311, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38718139

RESUMO

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.


Assuntos
American Heart Association , Cardiologia , Cardiomiopatia Hipertrófica , Humanos , Cardiologia/normas , Cardiomiopatia Hipertrófica/terapia , Cardiomiopatia Hipertrófica/diagnóstico , Gerenciamento Clínico , Estados Unidos
10.
J Am Soc Echocardiogr ; 37(8): 740-748, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38754746

RESUMO

BACKGROUND: Stress echocardiographic (SE) testing is an important modality in cardiovascular risk stratification and obstructive coronary artery disease assessment. Binary sex-based parameters are classically used for the interpretation of these studies, even among transgender women (TGW). Coronary artery disease is a leading cause of morbidity and mortality in this population. Yet, it remains unclear whether TGW exhibit a distinct stress testing profile from their cisgender counterparts. METHODS: Using a matched case-control study design, the authors compared the echocardiographic stress testing profiles of TGW (n = 43) with those of matched cisgender men (CGM; n = 84) and cisgender women (CGW; n = 86) at a single center. Relevant data, including demographics, comorbidities, and cardiac testing data, were manually extracted from the patients' charts. RESULTS: The prevalence of hypertension and dyslipidemia was similar between TGW and CGW and lower than that of CGM (P = .003 and P = .009, respectively). The majority of comorbidities and laboratory values were similar. On average, TGW had higher heart rates than CGM (P = .002) and had lower blood pressures than CGM and CGW (P < .05). TGW's double product and metabolic equivalents were similar to those among CGW and lower than those of CGM (P = .016 and P = .018, respectively). On echocardiography, left ventricular end-diastolic and end-systolic diameters among TGW were similar to those of CGW but lower than those of CGM (P = .023 and P = .018, respectively). Measures of systolic and diastolic function, except for exercise mitral valve E/e' ratio, which was lower in TGW than CGW (P = .029), were largely similar among the three groups. There was no difference in the wall motion score index, and therefore, no difference in the percentage of positive SE test results. CONCLUSIONS: This study shows, for the first time, that TGW have a SE profile that is distinct from that of their cisgender counterparts. Larger, multicenter, prospective studies are warranted to further characterize the SE profile of TGW.


Assuntos
Ecocardiografia sob Estresse , Pessoas Transgênero , Humanos , Feminino , Ecocardiografia sob Estresse/métodos , Pessoa de Meia-Idade , Masculino , Pessoas Transgênero/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Minnesota/epidemiologia , Prevalência , Estudos Retrospectivos
11.
J Am Coll Cardiol ; 83(23): 2324-2405, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38727647

RESUMO

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.


Assuntos
American Heart Association , Cardiomiopatia Hipertrófica , Cardiomiopatia Hipertrófica/terapia , Cardiomiopatia Hipertrófica/diagnóstico , Humanos , Estados Unidos , Cardiologia/normas , Gerenciamento Clínico
12.
Vasc Med ; : 1358863X241247537, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708691

RESUMO

BACKGROUND: There is wide variation in stress test utilization before major vascular surgery and adherence to practice guidelines is unclear. We defined rates of stress test compliance at our institution and led a quality improvement initiative to improve compliance with American Heart Association (ACC/AHA) guidelines. METHODS: We implemented a stress testing order set in the electronic medical record at one tertiary hospital. We reviewed all patients who underwent elective, major vascular surgery in the 6 months before (Jan 1, 2022 - Jul 1, 2022) and 6 months after (Aug 1, 2022 - Jan 31, 2023) implementation. We studied stress test guideline compliance, changes in medical or surgical management, and major adverse cardiac events (MACE). RESULTS: Before order set implementation, 37/122 patients (30%) underwent stress testing within the past year (29 specifically ordered preoperatively) with 66% (19/29) guideline compliance. After order set implementation, 50/173 patients (29%) underwent stress testing within the past year (41 specifically ordered preoperatively) with 80% (33/41) guideline compliance. In the pre- and postimplementation cohorts, stress testing led to a cardiovascular medication change or preoperative coronary revascularization in 24% (7/29) and 27% (11/41) of patients, and a staged surgery or less invasive anesthetic strategy in 14% (4/29) and 4.9% (2/41) of patients, respectively. All unindicated stress tests were surgeon-ordered and none led to a change in management. There was no change in MACE after order set implementation. CONCLUSIONS: Electronic medical record-based guidance of perioperative stress testing led to a slight decrease in overall stress testing and an increase in guideline-compliant testing. Our study highlights a need for improved preoperative cardiovascular risk assessment prior to major vascular surgery, which may eliminate unnecessary testing and more effectively guide perioperative decision-making.

13.
Curr Cardiol Rep ; 26(6): 497-503, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38722493

RESUMO

PURPOSE OF REVIEW: This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). RECENT FINDINGS: The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.


Assuntos
Doença da Artéria Coronariana , Teste de Esforço , Intervenção Coronária Percutânea , Padrão de Cuidado , Humanos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Análise Custo-Benefício , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco
14.
Int J Cardiovasc Imaging ; 40(7): 1543-1553, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38780711

RESUMO

PURPOSE: Exercise imaging using current modalities can be challenging. This was patient focused study to establish the feasibility and reproducibility of exercise-cardiovascular magnetic resonance imaging (EX-CMR) acquired during continuous in-scanner exercise in asymptomatic patients with primary mitral regurgitation (MR). METHODS: This was a prospective, feasibility study. Biventricular volumes/function, aortic flow volume, MR volume (MR-Rvol) and regurgitant fraction (MR-RF) were assessed at rest and during low- (Low-EX) and moderate-intensity exercise (Mod-EX) in asymptomatic patients with primary MR. RESULTS: Twenty-five patients completed EX-CMR without complications. Whilst there were no significant changes in the left ventricular (LV) volumes, there was a significant increase in the LVEF (rest 63 ± 5% vs. Mod-EX 68 ± 6%;p = 0.01). There was a significant reduction in the right ventricular (RV) end-systolic volume (rest 68 ml(60-75) vs. Mod-EX 46 ml(39-59);p < 0.001) and a significant increase in the RV ejection fraction (rest 55 ± 5% vs. Mod-EX 65 ± 8%;p < 0.001). Whilst overall, there were no significant group changes in the MR-Rvol and MR-RF, individual responses were variable, with MR-Rvol increasing by ≥ 15 ml in 4(16%) patients and decreasing by ≥ 15 ml in 9(36%) of patients. The intra- and inter-observer reproducibility of LV volumes and aortic flow measurements were excellent, including at Mod-EX. CONCLUSION: EX-CMR is feasible and reproducible in patients with primary MR. During exercise, there is an increase in the LV and RV ejection fraction, reduction in the RV end-systolic volume and a variable response of MR-Rvol and MR-RF. Understanding the individual variability in MR-Rvol and MR-RF during physiological exercise may be clinically important.


Assuntos
Teste de Esforço , Estudos de Viabilidade , Imagem Cinética por Ressonância Magnética , Insuficiência da Valva Mitral , Valva Mitral , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda , Função Ventricular Direita , Humanos , Masculino , Feminino , Estudos Prospectivos , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Idoso , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Doenças Assintomáticas , Variações Dependentes do Observador , Adulto
15.
Prog Cardiovasc Dis ; 83: 84-91, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452909

RESUMO

Endurance and resistance physical activity have been shown to stimulate the production of immunoglobulins and boost the levels of anti-inflammatory cytokines, natural killer cells, and neutrophils in the bloodstream, thereby strengthening the ability of the innate immune system to protect against diseases and infections. Coronavirus disease 19 (COVID-19) greatly impacted people's cardiorespiratory fitness (CRF) and health worldwide. Cardiopulmonary exercise testing (CPET) remains valuable in assessing physical condition, predicting illness severity, and guiding interventions and treatments. In this narrative review, we summarize the connections and impact of COVID-19 on CRF levels and its implications on the disease's progression, prognosis, and mortality. We also emphasize the significant contribution of CPET in both clinical evaluations of recovering COVID-19 patients and scientific investigations focused on comprehending the enduring health consequences of SARS-CoV-2 infection.


Assuntos
COVID-19 , Aptidão Cardiorrespiratória , Teste de Esforço , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/diagnóstico , SARS-CoV-2
16.
JACC Cardiovasc Imaging ; 17(8): 894-906, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38483420

RESUMO

BACKGROUND: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs. OBJECTIVES: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCTISCHEMIA) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE). METHODS: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed. In both studies, symptomatic patients with suspected stable coronary artery disease had prospectively undergone coronary computed tomography angiography (CTA), myocardial perfusion imaging (MPI), SPECT, or PET, fractional flow reserve by CT (FFRCT), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCTISCHEMIA model was developed in the derivation cohort of the CREDENCE study, and its diagnostic performance for coronary ischemia (FFR ≤0.80) was evaluated in the CREDENCE validation cohort and PACIFIC-1. Its prognostic value was investigated in PACIFIC-1. RESULTS: In CREDENCE validation (n = 305, age 64.4 ± 9.8 years, 210 [69%] male), the diagnostic performance by area under the receiver-operating characteristics curve (AUC) on per-patient level was 0.80 (95% CI: 0.75-0.85) for AI-QCTISCHEMIA, 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFRCT, and 0.65 (95% CI: 0.59-0.71; P < 0.001) for MPI. In PACIFIC-1 (n = 208, age 58.1 ± 8.7 years, 132 [63%] male), the AUCs were 0.85 (95% CI: 0.79-0.91) for AI-QCTISCHEMIA, 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFRCT, 0.89 (95% CI: 0.84-0.93; P = 0.262) for PET, and 0.72 (95% CI: 0.67-0.78; P < 0.001) for SPECT. Adjusted for clinical risk factors and coronary CTA-determined obstructive stenosis, a positive AI-QCTISCHEMIA test was associated with aHR: 7.6 (95% CI: 1.2-47.0; P = 0.030) for MACE. CONCLUSIONS: This newly developed coronary CTA-based ischemia model using coronary atherosclerosis and vascular morphology characteristics accurately diagnoses coronary ischemia by invasive FFR and provides robust prognostic utility for MACE beyond presence of stenosis.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Reserva Fracionada de Fluxo Miocárdico , Imagem de Perfusão do Miocárdio , Valor Preditivo dos Testes , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Reprodutibilidade dos Testes , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Prognóstico , Inteligência Artificial , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia
17.
Med Clin North Am ; 108(3): 427-439, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548455

RESUMO

There are unique advantages and disadvantages to functional versus anatomic testing in the work-up of patients who present with symptoms suggestive of obstructive coronary artery disease. Evaluation of these individuals starts with an assessment of pre-test probability, which guides subsequent testing decisions. The choice between anatomic and functional testing depends on this pre-test probability. In general, anatomic testing has particular utility among younger individuals and women; while functional testing can be helpful to rule-in ischemia and guide revascularization decisions. Ultimately, selection of the most appropriate test should be individualized to the patient and clinical scenario.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Feminino , Doença da Artéria Coronariana/diagnóstico , Angiografia Coronária , Isquemia Miocárdica/diagnóstico , Teste de Esforço
18.
J Pharm Biomed Anal ; 242: 116039, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387128

RESUMO

Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist used to treat the indications and symptoms associated with dry eye disease (DED), one of the most common ocular surface diseases. Lifitegrast has a chiral center, and the S-enantiomer (S-Lif) is responsible for the therapeutic effects, while the R-enantiomer (R-Lif) lacks efficacy in the treatment of DED. Lifitegrast ophthalmic solution containing 5% lifitegrast was approved by the United States Food and Drug Administration (FDA) in July 2016 for the treatment of DED in patients 17 years of age and older. The objective of this study was to develop a chiral HPLC method for the determination of the enantiomeric impurity of lifitegrast in the drug substance and in the ophthalmic product. In addition, we aimed to investigate the effect of stress and stability conditions on the enantiomeric purity of lifitegrast in both drug substance and ophthalmic solution. During the method development studies, four known lifitegrast impurities (Lif. Imp. A-D) and stressed lifitegrast samples were injected to ensure the specificity of the developed method. The enantiomers of lifitegrast are well separated with a resolution of higher than 4.0. They are also well separated from the peaks of the diluent, impurities, and the placebo used to prepare the ophthalmic solution without interference in 20 min. Chiral separation was achieved using a Chiralpak AD-H column (250 × 4.6 mm, 5.0 µm) at 40 °C with a mobile phase consisting of a mixture of n-hexane, 2-propanol, and formic acid (500:500:2, v/v/v) at a flow rate of 1.0 mL/min and a detection wavelength of 260 nm. Methanol was used as the diluent, and the drug substance solution was found to be stable for 48 h at 15 °C. The optimized chiral HPLC method for lifitegrast was validated according to ICH Q2, and the calibration curves showed excellent linearity for R-Lif (0.0369 - 1.816 µg/mL). This is the first stability-indicating, specific / selective, sensitive, linear, precise, accurate, and robust chiral HPLC method for the determination of R-Lif in S-Lif. The amount of enantiomeric impurity R-Lif in S-Lif increased under all stress and photostability test conditions without exceeding the acceptable impurity limit, with the most significant increase observed at elevated temperatures (105 °C) for both the drug substance in powder form and the ophthalmic drug solution.


Assuntos
Fenilalanina/análogos & derivados , Sulfonas , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Estereoisomerismo , Soluções Oftálmicas
19.
Int J Cardiol ; 401: 131863, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38365012

RESUMO

BACKGROUND: Despite its potential benefits, the utilization of stress-only protocol in clinical practice has been limited. We report utilizing stress-first single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: We assessed 12,472 patients who were referred for SPECT-MPI between 2013 and 2020. The temporal changes in frequency of stress-only imaging were assessed according to risk factors, mode of stress, prior coronary artery disease (CAD) history, left ventricular function, and symptom status. The clinical endpoint was all-cause mortality. RESULTS: In our lab, stress/rest SPECT-MPI in place of rest/stress SPECT-MPI was first introduced in November 2011 and was performed more commonly than rest/stress imaging after 2013. Stress-only SPECT-MPI scanning has been performed in 30-34% of our SPECT-MPI studies since 2013 (i.e.. 31.7% in 2013 and 33.6% in 2020). During the study period, we routinely used two-position imaging (additional prone or upright imaging) to reduce attenuation and motion artifact and introduced SPECT/CT scanner in 2018. The rate of stress-only study remained consistent before and after implementing the SPECT/CT scanner. The frequency of stress-only imaging was 43% among patients without a history of prior CAD and 19% among those with a prior CAD history. Among patients undergoing treadmill exercise, the frequency of stress-only imaging was 48%, while 32% among patients undergoing pharmacologic stress test. In multivariate Cox analysis, there was no significant difference in mortality risk between stress-only and stress/rest protocols in patients with normal SPECT-MPI results (p = 0.271). CONCLUSION: Implementation of a stress-first imaging protocol has consistently resulted in safe cancellation of 30% of rest SPECT-MPI studies.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Imagem de Perfusão do Miocárdio/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Doença da Artéria Coronariana/diagnóstico , Fatores de Risco , Teste de Esforço
20.
J Am Coll Cardiol ; 83(9): 890-900, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38418002

RESUMO

BACKGROUND: The optimal surveillance strategy after percutaneous coronary intervention (PCI) for high-risk patients with multivessel or left main coronary artery disease (CAD) remains uncertain. OBJECTIVES: This study aims to determine the prognostic role of routine functional testing in patients with multivessel or left main CAD who underwent PCI. METHODS: The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial randomized high-risk PCI patients to routine functional testing at 1 year or standard care alone during follow-up. This analysis focused on participants with multivessel or left main CAD. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. RESULTS: Among 1,706 initially randomized patients, 1,192 patients with multivessel (n = 833) or left main (n = 359) were identified, with 589 in the functional testing group and 603 in the standard care group. Two-year incidences of primary outcome were similar between the functional testing group and the standard care group (6.2% vs 5.7%, respectively; HR: 1.09; 95% CI: 0.68-1.74; P = 0.73). This trend persisted in both groups of multivessel (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.62-1.89; P = 0.78) and left main disease (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.46-2.56; P = 0.85) (P for interaction = 0.90). Routine surveillance functional testing was associated with increased rates of invasive angiography and repeat revascularization beyond 1 year. CONCLUSIONS: In high-risk patients with multivessel or left main CAD who underwent PCI, there was no incremental clinical benefit from routine surveillance functional-testing compared with standard care alone during follow-up. (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention [POST-PCI]; NCT03217877).


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio/etiologia , Prognóstico , Teste de Esforço/efeitos adversos , Resultado do Tratamento
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