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1.
Eur Radiol ; 33(12): 8445-8453, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37369831

RESUMO

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.


Assuntos
Doença da Artéria Coronariana , Tomografia Computadorizada por Raios X , Humanos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Tecido Adiposo/diagnóstico por imagem , Obesidade , Software , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária/métodos
2.
Catheter Cardiovasc Interv ; 99(3): 554-562, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34390170

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a predictor of restenosis and late stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting-stents (DES). Real-world data on rates of early ST is lacking. We compared clinical outcomes of patients with and without DM from the Victorian cardiac outcomes registry. METHODS: Consecutive patients undergoing PCI with DES were analyzed with primary outcome being ST at 30-days. Secondary outcomes including major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Of 43,209 patients included, 9730 (22.5%) had DM. At 30 days, DM was independently associated with higher rates of early ST (0.7% vs. 0.5%) OR 1.41 (95% confidence interval; 1.05-1.87, p = 0.02), MACE (4.1% vs. 3.5%, p = 0.004) and mortality (1.9% vs. 1.5%, p = 0.01). Increased risk was not simply due to treatment. Patients with DM requiring insulin were equally affected in regard to MACE (4.7% vs. 3.9%, p = 0.069) and mortality (1.9%, vs. 1.8%, p = 0.746). On National Death Index linkage, patients with DM had increased all-cause mortality over five-year follow-up (OR 1.69 CI 1.55-1.83, p = < 0.001). CONCLUSION: In this large real-world-registry, DM was an independent predictor of early ST, MACE and mortality at 30 days. These data suggest additional therapeutic strategies are required to reduce the risk of early complications in patients with DM undergoing PCI with DES.


Assuntos
Diabetes Mellitus , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombose , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Sistema de Registros , Trombose/etiologia , Resultado do Tratamento
3.
Clin Transplant ; 36(2): e14523, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34724254

RESUMO

BACKGROUND: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) improve sensitivity of cardiac allograft vasculopathy (CAV) detection compared to invasive coronary angiography (ICA), but their ability to predict clinical events is unknown. We determined whether severe CAV detected with ICA, IVUS, or OCT correlates with graft function. METHODS: Comparison of specific vessel parameters between IVUS and OCT on 20 patients attending for angiography 12-24 months post-orthotopic heart transplant. Serial left ventricular ejection fraction (EF) was recorded prospectively. RESULTS: Analyzing 55 coronary arteries, OCT and IVUS correlated well for vessel CAV characteristics. A mean intimal thickness (MIT)OCT  > .25 mm had a sensitivity of 86.7% and specificity of 74.3% at detecting Stanford grade 4 CAV. Those with angiographically evident CAV had significant reduction in graft EF over 7.3 years follow-up (median ΔEF -2% vs +1.5%, P = .03). Patients with MITOCT  > .25 mm in at least one vessel had a lower median EF at time of surveillance (57% vs 62%, P = .014). Two MACEs were noted. CONCLUSION: Imaging with OCT correlates well with IVUS for CAV detection. Combined angiography and OCT to screen for CAV within 12-24 months of transplant predicts concurrent and future deterioration in graft function.


Assuntos
Doença da Artéria Coronariana , Cardiopatias , Transplante de Coração , Aloenxertos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Humanos , Volume Sistólico , Ultrassonografia de Intervenção , Função Ventricular Esquerda
4.
Biotechnol Bioeng ; 118(5): 2001-2015, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33580508

RESUMO

Age-related macular degeneration (AMD) associated with dysfunction of retinal pigment epithelial (RPE) cells is the most common cause of untreatable blindness. To advance gene therapy as a viable treatment for AMD there is a need for technologies that enable controlled, RPE-specific expression of therapeutic genes. Here we describe design, construction and testing of compact synthetic promoters with a pre-defined transcriptional activity and RPE cell specificity. Initial comparative informatic analyses of RPE and photoreceptor (PR) cell transcriptomic data identified conserved and overrepresented transcription factor regulatory elements (TFREs, 8-19 bp) specifically associated with transcriptionally active RPE genes. Both RPE-specific TFREs and those derived from the generically active cytomegalovirus-immediate early (CMV-IE) promoter were then screened in vitro to identify sequence elements able to control recombinant gene transcription in model induced pluripotent stem (iPS)-derived and primary human RPE cells. Two libraries of heterotypic synthetic promoters varying in predicted RPE specificity and transcriptional activity were designed de novo using combinations of up to 20 discrete TFREs in series (323-602 bp) and their transcriptional activity in model RPE cells was compared to that of the endogenous BEST1 promoter (661 bp, plus an engineered derivative) and the highly active generic CMV-IE promoter (650 bp). Synthetic promoters with a highpredicted specificity, comprised predominantly of endogenous TFREs exhibited a range of activities up to 8-fold that of the RPE-specific BEST1 gene promoter. Moreover, albeit at a lower predicted specificity, synthetic promoter transcriptional activity in model RPE cells was enhanced beyond that of the CMV-IE promoter when viral elements were utilized in combination with endogenous RPE-specific TFREs, with a reduction in promoter size of 15%. Taken together, while our data reveal an inverse relationship between synthetic promoter activity and cell-type specificity, cell context-specific control of recombinant gene transcriptional activity may be achievable.


Assuntos
Genes Sintéticos/genética , Terapia Genética/métodos , Regiões Promotoras Genéticas/genética , Epitélio Pigmentado da Retina/citologia , Biologia Sintética/métodos , Células Cultivadas , Células Epiteliais/citologia , Humanos , Especificidade de Órgãos/genética , Transcriptoma/genética
5.
Biotechnol Bioeng ; 118(2): 1013-1021, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33128388

RESUMO

We describe scalable and cost-efficient production of full length, His-tagged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein trimer by Chinese hamster ovary (CHO) cells that can be used to detect SARS-CoV-2 antibodies in patient sera at high specificity and sensitivity. Transient production of spike in both human embryonic kidney (HEK) and CHO cells mediated by polyethyleneimine was increased significantly (up to 10.9-fold) by a reduction in culture temperature to 32°C to permit extended duration cultures. Based on these data GS-CHO pools stably producing spike trimer under the control of a strong synthetic promoter were cultured in hypothermic conditions with combinations of bioactive small molecules to increase yield of purified spike product 4.9-fold to 53 mg/L. Purification of recombinant spike by Ni-chelate affinity chromatography initially yielded a variety of co-eluting protein impurities identified as host cell derived by mass spectrometry, which were separated from spike trimer using a modified imidazole gradient elution. Purified CHO spike trimer antigen was used in enzyme-linked immunosorbent assay format to detect immunoglobulin G antibodies against SARS-CoV-2 in sera from patient cohorts previously tested for viral infection by polymerase chain reaction, including those who had displayed coronavirus disease 2019 (COVID-19) symptoms. The antibody assay, validated to ISO 15189 Medical Laboratories standards, exhibited a specificity of 100% and sensitivity of 92.3%. Our data show that CHO cells are a suitable host for the production of larger quantities of recombinant SARS-CoV-2 trimer which can be used as antigen for mass serological testing.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/biossíntese , Animais , Células CHO , COVID-19/virologia , Cricetinae , Cricetulus , Humanos , Proteínas Recombinantes/biossíntese , Testes Sorológicos/métodos
6.
J Interv Cardiol ; 2020: 7467943, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565755

RESUMO

Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Angiografia Coronária , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Hemodinâmica , Humanos , Complicações Pós-Operatórias/fisiopatologia , Stents , Resultado do Tratamento
7.
Eur Heart J ; 40(18): 1411-1422, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30907406

RESUMO

AIMS: The focal distribution of atherosclerotic plaques suggests that local biomechanical factors may influence plaque development. METHODS AND RESULTS: We studied 40 patients at baseline and over 12 months by virtual-histology intravascular ultrasound and bi-plane coronary angiography. We calculated plaque structural stress (PSS), defined as the mean of the maximum principal stress at the peri-luminal region, and wall shear stress (WSS), defined as the parallel frictional force exerted by blood flow on the endothelial surface, in areas undergoing progression or regression. Changes in plaque area, plaque burden (PB), necrotic core (NC), fibrous tissue (FT), fibrofatty tissue, and dense calcium were calculated for each co-registered frame. A total of 4029 co-registered frames were generated. In areas with progression, high PSS was associated with larger increases in NC and small increases in FT vs. low PSS (difference in ΔNC: 0.24 ± 0.06 mm2; P < 0.0001, difference in ΔFT: -0.15 ± 0.08 mm2; P = 0.049). In areas with regression, high PSS was associated with increased NC and decreased FT (difference in ΔNC: 0.15 ± 0.04; P = 0.0005, difference in ΔFT: -0.31 ± 0.06 mm2; P < 0.0001). Low WSS was associated with increased PB vs. high WSS in areas with progression (difference in ΔPB: 3.3 ± 0.4%; P < 0.001) with a similar pattern observed in areas with regression (difference in ΔPB: 1.2 ± 0.4%; P = 0.004). Plaque structural stress and WSS were largely independent of each other (R2 = 0.002; P = 0.001). CONCLUSION: Areas with high PSS are associated with compositional changes consistent with increased plaque vulnerability. Areas with low WSS are associated with more plaque growth in areas that progress and less plaque loss in areas that regress. The interplay of PSS and WSS may govern important changes in plaque size and composition.


Assuntos
Vasos Coronários/patologia , Hemodinâmica/fisiologia , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia de Intervenção/instrumentação , Fenômenos Biomecânicos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/fisiopatologia , Progressão da Doença , Humanos , Necrose/patologia , Estresse Mecânico
8.
Heart Lung Circ ; 29(1): 149-155, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30686645

RESUMO

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) negates the requirement for extracorporeal circulation used with the traditional on-pump approach. However, off-pump CABG is technically more challenging and may theoretically lead to less complete revascularisation. Recent data suggests a prognostic benefit for traditional on-pump CABG, but the mechanism for this remains unclear. We hypothesised that the inferior outcomes with off-pump CABG could be driven by the need for repeat revascularisation, with this benefit only becoming clear at long-term follow-up. We therefore evaluated short, medium and long-term outcomes of patients undergoing revascularisation with on vs. off-pump CABG. METHODS: Electronic databases were searched to identify suitable randomised controlled trials enrolling ≥100 patients in each arm. Clinical outcomes were extracted at 30-days, 12-months or >4years. The primary outcome was long-term all-cause death, while secondary outcomes included 30-day, 12-month and >4-year cardiac death, stroke, myocardial infarction or revascularisation. RESULTS: Thirteen (13) studies comprising 13,234 patients were included. Off-pump CABG was associated with an increased risk of all-cause death (Odds Ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.32, p=0.01) and repeat bypass surgery (OR 2.57, 95%CI 1.23-5.39, p=0.01) at long-term follow-up. A significant, increased requirement for revascularisation in off-pump was seen at 12-month follow-up (OR 1.59, 95%CI 1.09-2.33, p=0.02). No differences were noted between groups at 30-days, 12-months and >4years for myocardial infarction or stroke. CONCLUSIONS: Off-pump CABG is associated with significantly higher rates of all-cause mortality rate at long-term follow-up. These outcomes demonstrate a temporal relationship that may be driven by a greater requirement for repeat revascularisation at 1- and 5-year follow-up. STUDY REGISTRATION: CRD42018102019 (PROSPERO).


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Circulação Extracorpórea/efeitos adversos , Infarto do Miocárdio , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
9.
Biotechnol Bioeng ; 116(2): 375-387, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30345502

RESUMO

The output from protein biomanufacturing systems is a function of total host cell biomass synthetic capacity and recombinant protein production per unit cell biomass. In this study, we describe how these two properties can be simultaneously optimized via design of a product-specific combination of synthetic DNA parts to maximize flux through the protein synthetic pathway and the use of a host cell chassis with an increased capability to synthesize both cell and product biomass. Using secreted alkaline phosphatase (SEAP) production in Chinese hamster ovary cells as our example, we demonstrate how an optimal composition of input components can be assembled from a minimal toolbox containing rationally designed promoters, untranslated regions, signal peptides, product coding sequences, cell chassis, and genetic effectors. Product titer was increased 10-fold, compared with a standard reference system by (a) identifying genetic components that acted in concert to maximize the rates of SEAP transcription, translation, and translocation, (b) selection of a cell chassis with increased biomass synthetic capacity, and (c) engineering the host cell factory's capacity for protein folding and secretion. This whole synthetic pathway engineering process to design optimal expression cassette-chassis combinations should be applicable to diverse recombinant protein and host cell-type contexts.


Assuntos
Células CHO/metabolismo , Engenharia Metabólica/métodos , Proteínas Recombinantes/biossíntese , Fosfatase Alcalina/biossíntese , Fosfatase Alcalina/genética , Animais , Cricetulus , Proteínas Recombinantes/genética
10.
Catheter Cardiovasc Interv ; 94(3): E96-E103, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30604558

RESUMO

OBJECTIVES: We sought to assess the validity of the DILEMMA score against instantaneous wave-free ratio (iFR) and evaluate its utility in rationalizing the number of patients referred for invasive physiological assessment. BACKGROUND: The DILEMMA score is a validated angiographic scoring tool incorporating minimal lumen diameter, lesion length and subtended myocardial area that has been shown to predict the functional significance of lesions as assessed by fractional flow reserve (FFR). METHODS: Patients in the DEFINE-FLAIR study who had coronary stenosis of intermediate severity were randomized to either FFR or iFR. DILEMMA score was calculated retrospectively on a subset of this cohort by operators blinded to FFR or iFR values. RESULTS: Three hundred and forty-six lesions (181 assessed by FFR; 165 by iFR) from 259 patients (mean age 66.0 years, 79% male) were included. A DILEMMA score ≤ 2 had a negative predictive value of 96.3% and 95.7% for identifying lesions with FFR >0.80 and iFR >0.89, respectively. A DILEMMA score ≥ 9 had a positive predictive value of 88.9% and 100% for identifying lesions with FFR ≤0.80 and iFR ≤0.89, respectively. The receiver operating characteristic area under the curve values for DILEMMA score to predict FFR ≤0.80 and iFR ≤0.89 were 0.83 (95% CI 0.77-0.90) and 0.82 (0.75-0.89) respectively. A DILEMMA score ≤ 2 or ≥9 occurred in 172 of the 346 lesions (49.7%). CONCLUSIONS: Using DILEMMA score in patients with coronary stenosis of intermediate severity may reduce the need for pressure wire use, offering potential cost-savings and minimizing the risks associated with invasive physiological lesion assessment.


Assuntos
Cateterismo Cardíaco , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Idoso , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença
11.
Nucleic Acids Res ; 45(18): 10906-10919, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-28977454

RESUMO

Comprehensive de novo-design of complex mammalian promoters is restricted by unpredictable combinatorial interactions between constituent transcription factor regulatory elements (TFREs). In this study, we show that modular binding sites that do not function cooperatively can be identified by analyzing host cell transcription factor expression profiles, and subsequently testing cognate TFRE activities in varying homotypic and heterotypic promoter architectures. TFREs that displayed position-insensitive, additive function within a specific expression context could be rationally combined together in silico to create promoters with highly predictable activities. As TFRE order and spacing did not affect the performance of these TFRE-combinations, compositions could be specifically arranged to preclude the formation of undesirable sequence features. This facilitated simple in silico-design of promoters with context-required, user-defined functionalities. To demonstrate this, we de novo-created promoters for biopharmaceutical production in CHO cells that exhibited precisely designed activity dynamics and long-term expression-stability, without causing observable retroactive effects on cellular performance. The design process described can be utilized for applications requiring context-responsive, customizable promoter function, particularly where co-expression of synthetic TFs is not suitable. Although the synthetic promoter structure utilized does not closely resemble native mammalian architectures, our findings also provide additional support for a flexible billboard model of promoter regulation.


Assuntos
Simulação por Computador , Regiões Promotoras Genéticas , Animais , Sítios de Ligação , Células CHO , Cricetulus , Biologia Sintética , Fatores de Transcrição/metabolismo , Transcrição Gênica
12.
Catheter Cardiovasc Interv ; 92(7): 1414-1416, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30218474

RESUMO

INTRODUCTION: Leaflet thrombosis (LT) defined by computed tomography (CT) following transcatheter aortic valve replacement (TAVR) has been shown to increase cerebrovascular events. The neo-sinus plays an important role in the development of LT. Intra-annular valves (IAV) have a larger neo-sinus when compared to supra-annular valves (SAV), and has been associated with larger thrombus burden. The prevalence of LT with IAV and SAV in a larger, diverse cohort is unknown. METHODS: We performed a systematic review to assess the prevalence of LT in IAV versus SAV TAVR prostheses. Inclusion criteria were (1) reported CT-defined LT following TAVR, (2) comparison between LT and non-LT cohort, (3) separate registry/database, and (4) fully published status. A total of 2,013 citations were reviewed and 7 studies were included. RESULTS: Overall, 1,644 patients were included from 7 observational studies and the prevalence of LT following TAVR was 12.8%. The Portico valve system (IAV) had the highest prevalence of LT with 35.2%, followed by Symetis Acurate Neo (SAV) at 15.4% and the Lotus valve system (IAV) at 14.5%. LT occurred more frequently in IAV than SAV (13.5% vs. 7%, P = 0.02). Subanalysis of IAV versus SAV with the exclusion of the Portico valve was performed to ensure results were not influenced by this valve system and revealed IAV still had higher rates of LT (12.1% vs. 7%, P = 0.05). CONCLUSION: In summary, IAV prostheses appear to be associated with higher rates of LT when compared with SAV.


Assuntos
Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas , Trombose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Substituição da Valva Aórtica Transcateter/instrumentação , Valva Aórtica/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Prevalência , Desenho de Prótese , Medição de Risco , Fatores de Risco , Trombose/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
13.
Circ Res ; 118(4): 750-69, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26892971

RESUMO

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Vasos Coronários , Diagnóstico por Imagem/métodos , Placa Aterosclerótica , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Humanos , Angiografia por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia de Coerência Óptica , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção
14.
J Interv Cardiol ; 31(5): 608-616, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29797804

RESUMO

BACKGROUND: Polymer-free drug eluting stents (PF-DES) were developed, in part, to overcome risk of late ischemic events observed with permanent polymer-coated DES (PP-DES). However, trial results are inconsistent with longer-term safety and efficacy of PF-DES remaining unknown. We performed a meta-analysis of randomized trials assessing outcomes of patients receiving PF-DES versus PP-DES for treatment of coronary artery disease (CAD). METHODS: Electronic searches were performed for randomized trials comparing outcomes between PF-DES and PP-DES. Trials reporting major adverse cardiovascular events (MACE), myocardial infarction (MI), stent thrombosis (ST), all-cause death, target lesion/vessel revascularization (TLR/TVR), and late lumen loss (LLL) were included. Analyses were performed at longest follow-up and landmarked beyond 1-year. RESULTS: Twelve trials (6,943 patients) were included. There was no significant difference in MACE between PF-DES and PP-DES at longest follow-up (Odds Ratio [OR] 0.96, 95%CI 0.85-1.10, P = 0.59) or landmark analysis beyond 1-year (OR 0.96, 95%CI 0.76-1.20, P = 0.70). Although PF-DES were associated with a significant reduction in all-cause death (OR 0.85, 95%CI 0.72-1.00, P < 0.05), this effect was not present on landmark analysis beyond 1-year (OR 0.89, 95%CI 0.73-1.10, P = 0.30). There were no differences observed for MI (OR 1.00, 95%CI 0.77-1.28, P = 0.99) or ST (OR 0.95, 95%CI 0.54-1.68, P = 0.86), with similar efficacy outcomes including TVR (OR 1.07, 95%CI 0.91-1.26, P = 0.42), TLR (OR 1.03, 95%CI 0.88-1.21, P = 0.68) and angiographic LLL (pooled mean difference 0.01 mm, 95%CI -0.08 to 0.11, P = 0.76). CONCLUSIONS: PF-DES are as safe and efficacious as PP-DES for the treatment of patients with CAD, but do not significantly reduce late ischemic complications.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Polímeros/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Stents Farmacológicos/classificação , Humanos , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Clin Transplant ; 32(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29194769

RESUMO

OBJECTIVE: Cardiac allograft vasculopathy (CAV) can be detected early with intravascular ultrasound (IVUS), but there is limited information on the most efficient imaging protocol. METHODS: Coronary angiography and IVUS of the three coronary arteries were performed. Volumetric IVUS analysis was performed, and a Stanford grade determined for each vessel. RESULTS: Eighteen patients were included 18 (range 12-24) months after transplantation. Angiographic CAV severity ranged from none (CAV0) to mild (CAV1), whereas IVUS CAV severity ranged from none (Stanford grade I) to severe (grade IV). Maximal intimal thickness measured with IVUS was significantly greater in the LAD (0.84 ± 0.48 mm) than in the LCX (0.46 ± 0.32 mm) or the RCA (0.53 ± 0.41 mm, P = .005). Diagnostic accuracy of IVUS in the left anterior descending artery was 100% (18 of 18 Stanford grades matched the patient's highest overall Stanford grade), 66% in the right coronary artery (12 of 18), and 56% in the left circumflex artery (11 of 18). The minimal required length of left anterior descending artery pullbacks to attain 100% accuracy was 36 mm (range 3-36 mm) distal from the guide catheter ostium. CONCLUSIONS: These data suggest that focal IVUS imaging of the proximal LAD followed by volumetric analysis may suffice when screening for transplant vasculopathy.


Assuntos
Vasos Coronários/patologia , Rejeição de Enxerto/diagnóstico , Transplante de Coração/efeitos adversos , Complicações Pós-Operatórias , Ultrassonografia/métodos , Doenças Vasculares/diagnóstico , Adolescente , Adulto , Idoso , Aloenxertos , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Diagnóstico Precoce , Procedimentos Endovasculares , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico por imagem , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia , Adulto Jovem
16.
Circ J ; 82(7): 1735-1742, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29618696

RESUMO

Subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement (TAVR) has been increasingly recognized. SLT has the hallmark features of hypo-attenuated leaflet thickening (HALT) on multidetector computed tomography (MDCT), which may result in hypoattenuation affecting motion (HAM). The actual prevalence of this condition is uncertain, with limited observational registries. SLT has caught the attention of the cardiovascular community because of concerns regarding its clinical sequelae, specifically the potential increased incidence of cerebrovascular events. There are available, albeit sparse, data to suggest that when left untreated, SLT may lead to valve deterioration with potential hemodynamic compromise and potentially clinically overt prostheses thrombosis. Some clinicians have opted to treat patients with SLT with anticoagulation. Although anticoagulation may be a rational treatment option, little data exist on the safety and efficacy of this treatment. This is particularly important considering TAVR patients also have higher bleeding risk than the standard population. In this review, we aim to summarize the current evidence on SLT, explore its pathophysiological mechanism, discuss the current treatment options and future trials that may clarify the optimal antithrombotic strategies of SLT.


Assuntos
Tomografia Computadorizada Multidetectores/métodos , Trombose/diagnóstico , Substituição da Valva Aórtica Transcateter/métodos , Anticoagulantes/uso terapêutico , Hemorragia/etiologia , Humanos , Trombose/tratamento farmacológico , Trombose/fisiopatologia , Substituição da Valva Aórtica Transcateter/efeitos adversos
17.
Intern Med J ; 48(5): 587-591, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29722189

RESUMO

The accuracy of photoplethysmography (PPG) for heart rate (HR) estimation in cardiac arrhythmia is unknown. PPG-HR was evaluated in 112 hospitalised inpatients (cardiac arrhythmias (n = 60), sinus rhythm (n = 52)) using a continuous electrocardiogram monitoring as a reference standard. Strong agreement was observed in sinus rhythm HR < 100 and atrial flutter (bias 1 beat), modest agreement in sinus tachycardia (bias 24 beats) and complete heart block (bias -6 beats) and weak agreement with significant HR underestimation was seen in atrial fibrillation (bias 23 beats). Routine utilisation of PPG for HR estimation may delay early recognition of clinical deterioration in certain arrhythmias and sinus tachycardia.


Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Frequência Cardíaca/fisiologia , Hospitalização , Fotopletismografia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia/métodos , Eletrocardiografia/tendências , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Fotopletismografia/métodos , Fotopletismografia/tendências
19.
Heart Lung Circ ; 27(6): e73-e77, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29475592

RESUMO

Catheter induced coronary dissection is an uncommon but potentially catastrophic complication of coronary angiography. We report a case of a 48-year-old female with normal coronary arteries on angiography complicated by extensive catheter induced spiral dissection. Wiring into the true lumen was a formidable challenge as a consequence of the large false lumen obliterating the true lumen. We present management strategies and in particular, highlight the important role of intravascular ultrasound (IVUS) imaging.


Assuntos
Catéteres/efeitos adversos , Angiografia Coronária/efeitos adversos , Vasos Coronários/lesões , Lesões do Sistema Vascular/diagnóstico por imagem , Ponte de Artéria Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Stents Farmacológicos , Feminino , Humanos , Doença Iatrogênica , Pessoa de Meia-Idade , Ultrassonografia de Intervenção , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia
20.
Heart Lung Circ ; 27(4): 406-419, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29191506

RESUMO

The presence and extent of myocardial ischaemia is a major determinant of prognosis and benefit from revascularisation in patients with stable coronary artery disease. Fractional Flow Reserve (FFR) is accepted as the reference standard for invasive assessment of ischaemia. Its ability to detect lesion specific ischaemia makes it a useful test in a wide range of patient and lesion subsets, with FFR guided intervention improving clinical outcomes and reducing health care costs compared to assessment with coronary angiography alone. This article will review the basic principles in FFR, practical tips in FFR guided revascularisation and the role of emerging non-hyperaemic indices of ischaemia.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Revascularização Miocárdica/normas , Guias de Prática Clínica como Assunto , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Humanos , Prognóstico
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