RESUMO
KEY MESSAGE: A molecular analysis using informative SNP markers in 1570 clones of cassava from Vietnam reveals varietal composition from farmers' field and genebank collections Cassava is the most important smallholder cash crops in Southeast Asia and is especially used in industrial products. Yet, systematic genetic studies on molecular markers from Vietnamese germplasm have not been considered for breeding and conservation programs. We conducted a molecular analysis of 1570 clones of cassava germplasm from farms across six agro-ecological zones using informative SNP markers. We unraveled the genetic diversity and population structure and provided insights into the value of breeding and conservation programs. Duplicated genotypes comprised 98% of the total sample of the Central Highlands region. Ninety-six SNPs were amplified Central Highlands and South East provinces had the highest allelic richness, covering up to 83% of alleles. The average observed heterozygosity (Ho = 0.43) was slightly higher than expected (He = 0.40) across SNP markers, suggesting an excess of heterozygotes plants. Diversity indexes indicated that cassava populations from North West and Eastern Vietnam are genetically diverse (mean He = 0.40). Genetic parentage tests identified 85 unique genetic groups within the varieties KM94, KM419, BRA1305, KM101, KM140, PER262, KM60, KM57 and two unidentified varieties, which accounted for 82% of the frequency distribution. KM94 is the most dominant variety in Vietnamese farms surveyed (38%), reflecting its superior quality and productivity. Discriminant analysis of principal components (DAPC) revealed four main subgroups, which were partially corroborated by neighbor joining (NJ) analyses. After removing duplicates, 31 unique genotypes were distributed across five of the agro-ecological zones. These were well distributed in the subgroups revealed via DAPC and NJ analyses. The genetic groups identified herein could be used to select unique accessions that should ideally conform with ex situ germplasm collections and identify areas where on-farm conservation programs should be targeted. Newly identified genotypes may also contribute as genetic breeding resources that could be used to adapt cassava to future changes and farmers' needs.
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Impressões Digitais de DNA , Manihot , Melhoramento Vegetal , Manihot/genética , VietnãRESUMO
OBJECTIVES: Quantitative flow ratio (QFR) computes fractional flow reserve (FFR) based on invasive coronary angiography (ICA). Residual QFR estimates post-percutaneous coronary intervention (PCI) FFR. This study sought to assess the relationship of residual QFR with post-PCI FFR. METHODS: Residual QFR analysis, using pre-PCI ICA, was attempted in 159 vessels with post-PCI FFR. QFR lesion location was matched with the PCI location to simulate the performed intervention and allow computation of residual QFR. A post-PCI FFR < 0.90 was used to define a suboptimal PCI result. RESULTS: Residual QFR computation was successful in 128 (81%) vessels. Median residual QFR was higher than post-PCI FFR (0.96 Q1-Q3: 0.91-0.99 vs. 0.91 Q1-Q3: 0.86-0.96, p < 0.001). A significant correlation and agreement were observed between residual QFR and post-PCI FFR (R = 0.56 and intraclass correlation coefficient = 0.47, p < 0.001 for both). Following PCI, an FFR < 0.90 was observed in 54 (42%) vessels. Specificity, positive predictive value, sensitivity, and negative predictive value of residual QFR for assessment of the PCI result were 96% (95% confidence interval (CI): 87-99%), 89% (95% CI: 72-96%), 44% (95% CI: 31-59%), and 70% (95% CI: 65-75%), respectively. Residual QFR had an accuracy of 74% (95% CI: 66-82%) and an area under the receiver operating characteristic curve of 0.79 (95% CI: 0.71-0.86). CONCLUSIONS: A significant correlation and agreement between residual QFR and post-PCI FFR were observed. Residual QFR ≥ 0.90 did not necessarily commensurate with a satisfactory PCI (post-PCI FFR ≥ 0.90). In contrast, residual QFR exhibited a high specificity for prediction of a suboptimal PCI result.
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Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , HumanosRESUMO
BACKGROUND: Mismatch between myocardial innervation and perfusion assessed with positron emission tomography (PET) is a potential risk marker for ventricular arrhythmias in patients with ischemic cardiomyopathy. This mismatch zone originates from residual viable myocardium that has sustained ischemic nerve injury. Heterogenic scar size assessed with late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR) is also a risk marker of ventricular arrhythmias. These two imaging parameters may represent identical morphological tissue features. The current study explored the relation between innervation-perfusion mismatch and heterogenic scar size. METHODS: Twenty-eight patients (26 males, age 67 ± 8 years) with ischemic cardiomyopathy and a left ventricular ejection fraction below 35%, eligible for ICD implantation were included. All patients underwent both [11C]-hydroxyephedrine and [15O]-water PET studies to assess myocardial sympathetic innervation and perfusion. LGE CMR was conducted to assess total myocardial scar size, scar core size, and heterogenic scar size. RESULTS: Perfusion defect size was 16.6 ± 9.9% and innervation defect size was 33.7 ± 10.8%, which resulted in an innervation-perfusion mismatch of 17.6 ± 8.9%. Total scar size, scar core size, and heterogenic scar size were 21.2 ± 8.6%, 14.7 ± 6.6%, and 6.5 ± 2.9%, respectively. No relation between scar core size and perfusion deficit size was observed (r = 0.18, P = .36). Total scar size was correlated with the innervation defect size (r = 0.52, P = .004) and the heterogenic scar zone displayed a significant correlation with the innervation-perfusion mismatch area (r = 0.67, P < .001). CONCLUSIONS: Denerved residual viable myocardium in ischemic cardiomyopathy as observed with innervation-perfusion PET is related to the heterogenic scar zone as assessed with LGE CMR.
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Cardiomiopatias/diagnóstico por imagem , Cicatriz/diagnóstico por imagem , Coração/diagnóstico por imagem , Coração/inervação , Imagem Cinética por Ressonância Magnética/métodos , Isquemia Miocárdica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Idoso , Cardiomiopatias/complicações , Cicatriz/etiologia , Denervação , Feminino , Humanos , Masculino , Isquemia Miocárdica/complicações , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The perfusable tissue index (PTI) is a marker of myocardial viability. Recent technological advances have made it possible to generate parametric PTI images from a single [(15)O]H(2)O PET/CT scan. The purpose of this study was to validate these parametric PTI images. METHODS: The study population comprised 46 patients with documented or suspected coronary artery disease who were studied with [(15)O]H(2)O PET and late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR). RESULTS: Of the 736 myocardial segments included, 364 showed some degree of LGE. PTI and perfusable tissue fraction (PTF) diminished with increasing LGE. The areas under the curve of the PTI and PTF, used to predict (near) transmural LGE on CMR, were 0.86 and 0.87, respectively. Optimal sensitivity and specificity were 91 % and 73 % for PTI and 69 % and 87 % for PTF, respectively. CONCLUSION: PTI and PTF assessed with a single [(15)O]H(2)O scan can be utilized as markers of myocardial viability in patients with coronary artery disease.
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Gadolínio , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Miocárdio/patologia , Tomografia por Emissão de Pósitrons , Sobrevivência de Tecidos , Tomografia Computadorizada por Raios X , Água , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Marcação por Isótopo , Masculino , Radioisótopos de Oxigênio , Estudos RetrospectivosRESUMO
BACKGROUND: There has been increasing interest in quantitative myocardial blood flow (MBF) imaging over the last years and it is expected to become a routinely used technique in clinical practice. Positron emission tomography (PET) using [(15)O]H(2)O is the established gold standard for quantification of MBF in vivo. A fundamental issue when performing quantitative MBF imaging is to define the limits of MBF in a clinically suitable population. The aims of the present study were to determine the limits of MBF and to determine the relationship among coronary artery disease (CAD) risk factors, gender and MBF in a predominantly symptomatic patient cohort without significant CAD. METHODS: A total of 128 patients (mean age 54 ± 10 years, 50 men) with a low to intermediate pretest likelihood of CAD were referred for noninvasive evaluation of CAD using a hybrid PET/computed tomography (PET/CT) scanner. MBF was quantified with [(15)O]H(2)O at rest and during adenosine-induced hyperaemia. Obstructive CAD was excluded in these patients by means of invasive or CT-based coronary angiography. RESULTS: Global average baseline MBF values were 0.91 ± 0.34 and 1.09 ± 0.30 ml·min(-1)·g(-1) (range 0.54-2.35 and 0.59-2.75 ml·min(-1)·g(-1)) in men and women, respectively (p < 0.01). However, no gender-dependent difference in baseline MBF was seen following correction for rate-pressure product (0.98 ± 0.45 and 1.09 ± 0.30 ml·min(-1)·g(-1) in men and women, respectively; p = 0.08). Global average hyperaemic MBF values were 3.44 ± 1.20 ml·min(-1)·g(-1) in the whole study population, and 2.90 ± 0.85 and 3.78 ± 1.27 ml·min(-1)·g(-1) (range 1.52-5.22 and 1.72-8.15 ml·min(-1)·g(-1)) in men and women, respectively (p < 0.001). Multivariate analysis identified male gender, age and body mass index as having an independently negative impact on hyperaemic MBF. CONCLUSION: Gender, age and body mass index substantially influence reference values and should be corrected for when interpreting hyperaemic MBF values.
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Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Água , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Reserva Fracionada de Fluxo Miocárdico , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid (15)O-water PET/CT imaging. METHODS: We evaluated 173 (mean age 56 ± 10, 78 men) patients with a low to intermediate likelihood for coronary artery disease (CAD), without a documented history of CAD, undergoing vasodilator stress (15)O-water PET/CT and CAC scoring. Obstructive coronary artery disease was excluded by means of invasive (n = 44) or CT-based coronary angiography (n = 129). RESULTS: 91 of 173 patients (52%) had a CAC score of zero. Of those with CAC, the CAC score was 0.1-99.9, 100-399.9, and ≥400 in 31%, 12%, and 5% of patients, respectively. Global CAC score showed significant inverse correlation with hyperemic MBF (r = -0.32, P < .001). With increasing CAC score, there was a decline in hyperemic MBF on a per-patient basis [3.70, 3.30, 2.68, and 2.53 mL · min(-1) · g(-1), with total CAC score of 0, 0.1-99.9, 100-399.9, and ≥400, respectively (P < .001)]. CFR showed a stepwise decline with increasing levels of CAC (3.70, 3.32, 2.94, and 2.93, P < .05). Multivariate analysis, including age, BMI, and CAD risk factors, revealed that only age, male gender, BMI, and hypercholesterolemia were associated with reduced stress perfusion. Furthermore, only diabetes and age were independently associated with CFR. CONCLUSION: In patients without significant obstructive CAD, a greater CAC burden is associated with a decreased hyperemic MBF and CFR. However, this association disappeared after adjustment for traditional CAD risk factors. These results suggest that CAC does not add incremental value regarding hyperemic MBF and CFR over established CAD risk factors in patients without obstructive CAD.
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Calcinose/diagnóstico , Calcinose/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Hiperemia/diagnóstico , Imagem de Perfusão do Miocárdio/estatística & dados numéricos , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Feminino , Humanos , Hiperemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Radioisótopos de Oxigênio , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Técnica de Subtração , ÁguaRESUMO
PURPOSE: Parametric imaging of absolute myocardial blood flow (MBF) using [(15)O]H(2)O enables determination of MBF with high spatial resolution. The aim of this study was to develop a method for generating reproducible, high-quality and quantitative parametric MBF images with minimal user intervention. METHODS: Nineteen patients referred for evaluation of MBF underwent rest and adenosine stress [(15)O]H(2)O positron emission tomography (PET) scans. Ascending aorta and right ventricular (RV) cavity volumes of interest (VOIs) were used as input functions. Implementation of a basis function method (BFM) of the single-tissue model with an additional correction for RV spillover was used to generate parametric images. The average segmental MBF derived from parametric images was compared with MBF obtained using nonlinear least-squares regression (NLR) of VOI data. Four segmentation algorithms were evaluated for automatic extraction of input functions. Segmental MBF obtained using these input functions was compared with MBF obtained using manually defined input functions. RESULTS: The average parametric MBF showed a high agreement with NLR-derived MBF [intraclass correlation coefficient (ICC) = 0.984]. For each segmentation algorithm there was at least one implementation that yielded high agreement (ICC > 0.9) with manually obtained input functions, although MBF calculated using each algorithm was at least 10% higher. Cluster analysis with six clusters yielded the highest agreement (ICC = 0.977), together with good segmentation reproducibility (coefficient of variation of MBF <5%). CONCLUSION: Parametric MBF images of diagnostic quality can be generated automatically using cluster analysis and a implementation of a BFM of the single-tissue model with additional RV spillover correction.
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Processamento de Imagem Assistida por Computador/métodos , Imagem de Perfusão do Miocárdio/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Água , Adulto , Idoso , Algoritmos , Automação , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de TempoRESUMO
The introduction of the implantable cardioverter defibrillator (ICD) has had a major impact on survival and treatment of patients with ischaemic cardiomyopathy. However, only a third of patients receive appropriate ICD discharges during the first 3 years of follow-up, hence creating opportunities for improvement in patient care as well as for health care costs containment. Therefore, refinement of ICD implantation criteria is needed. Evaluation of pathophysiological substrates related to electrical instability with imaging modalities such as nuclear imaging, cardiac magnetic resonance imaging, and echocardiography might yield important prognostic information. This review discusses the currently available literature regarding the value of these imaging modalities for prediction of ventricular arrhythmias in patients with ischaemic cardiomyopathy.
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Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiologia , Desfibriladores Implantáveis , Humanos , Fatores de Risco , Taquicardia Ventricular/terapiaRESUMO
BACKGROUND: Percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) are high risk procedures with low success rates compared to standard PCI. Recently the 'hybrid approach' method has been developed to increase success rate. In 2015 we set up a dedicated program to systematically treat CTOs by this hybrid approach. This retrospective, observational registry aims to report achieved results in a single PCI centre. METHODS AND RESULTS: We reviewed all CTO procedures between January 2012 and December 2017. Procedures performed by dedicated operators after December 2014 were assigned to the hybrid cohort, procedures done before this time or performed by a non-CTO operator were assigned to the non-hybrid cohort. Procedural techniques, difficulty of lesions, J-CTO scores, outcomes and complications were analysed. In total 505 procedures were included. Average J-CTO score was 1.9 ± 1.1, which was significantly higher in the hybrid cohort (2.1 ± 1.2 vs. 1.6 ± 1.1; p < 0.001). Overall procedural success rate was 75.4% with significantly higher success rates in the hybrid cohort (81.2% vs. 68.2%; p < 0.001). Combining both cohorts, overall success rate increased over the years (2012-2017 respectively 65.2%, 60.0%, 71.7%, 83.2%, 77.9% and 81.4%). Complication rate was higher in the hybrid cohort compared to the non-hybrid cohort (4.6% vs 0.4%, respectively; p = 0.026). CONCLUSION: By introducing a systematic CTO program, including use of the hybrid approach, we observed higher success rates of PCI CTO, despite increased complexity of the lesions (higher J-CTO score). The occurrence of MACE was in accordance with current literature. CONDENSED ABSTRACT: Our registry demonstrates that introduction of a dedicated CTO program increases success rates of CTO treatments despites increased lesions difficulty and with acceptable MACEs rates.
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Oclusão Coronária , Intervenção Coronária Percutânea , Doença Crônica , Angiografia Coronária , Humanos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: This study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs). BACKGROUND: Improved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking. METHODS: Seventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [15O]H2O and [11C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated. RESULTS: In total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA. CONCLUSIONS: In patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.
Assuntos
Arritmias Cardíacas , Cardiomiopatias , Desfibriladores Implantáveis , Arritmias Cardíacas/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Humanos , Espectroscopia de Ressonância Magnética , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Fatores de Risco , Volume Sistólico , Função Ventricular EsquerdaRESUMO
OBJECTIVE: Individuals with familial hypobetalipoproteinemia (FHBL) have been reported to be prone to fatty liver disease (FLD). Conversely, the profound reduction of low-density lipoprotein (LDL) cholesterol in this disorder might decrease cardiovascular risk. In the present study, we assessed hepatic steatosis as well as noninvasive surrogate markers for cardiovascular disease (CVD) in subjects with FHBL and in matched controls. METHODS AND RESULTS: Hepatic steatosis was assessed by abdominal ultrasonography. Carotid intima-media thickness (IMT) and distal common carotid arterial wall stiffness as surrogate markers for CVD risk were measured using high-resolution B-mode ultrasonography. Whereas transaminase levels were only modestly elevated, both prevalence (54% versus 29%; P=0.01) and severity of steatosis were significantly higher in FHBL individuals compared with controls. Despite similar IMT measurements, arterial stiffness was significantly lower in FHBL (P=0.04) compared with controls. Additionally, the increase in arterial stiffness as seen in the presence of traditional risk factors was attenuated, suggesting that very low levels of apoB-containing lipoproteins can negate the adverse effects of other risk factors on the vasculature. CONCLUSIONS: FHBL is characterized by an increased prevalence and severity of fatty liver disease. The observed decreased level of arterial wall stiffness, most pronounced in the presence of nonlipid risk factors, is indicative of cardiovascular protection in these subjects.
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Doenças das Artérias Carótidas/epidemiologia , Fígado Gorduroso/epidemiologia , Hipobetalipoproteinemias/epidemiologia , Adulto , Apolipoproteínas B/sangue , Apolipoproteínas B/genética , Doenças das Artérias Carótidas/diagnóstico por imagem , LDL-Colesterol/sangue , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Hipobetalipoproteinemias/sangue , Hipobetalipoproteinemias/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , UltrassonografiaRESUMO
UNLABELLED: (11)C-meta-hydroxyephedrine ((11)C-HED) kinetics in the myocardium can be quantified using a single-tissue-compartment model together with a metabolite-corrected arterial blood sampler input function (BSIF). The need for arterial blood sampling, however, limits clinical applicability. The purpose of this study was to investigate the feasibility of replacing arterial sampling with imaging-derived input function (IDIF) and venous blood samples. METHODS: Twenty patients underwent 60-min dynamic (11)C-HED PET/CT scans with online arterial blood sampling. Thirteen of these patients also underwent venous blood sampling. Data were reconstructed using both 3-dimensional row-action maximum-likelihood algorithm (3DR) and a time-of-flight (TF) list-mode reconstruction algorithm. For each reconstruction, IDIF results were compared with BSIF results. In addition, IDIF results obtained with venous blood samples and with a transformed venous-to-arterial metabolite correction were compared with results obtained with arterial metabolite corrections. RESULTS: Correlations between IDIF- and BSIF-derived K1 and VT were high (r(2) > =0.89 for 3DR and TF). Slopes of the linear fits were significantly different from 1 for K1, for both 3DR (slope = 0.94) and TF (slope = 1.06). For VT, the slope of the linear fit was different from 1 for TF (slope = 0.93) but not for 3DR (slope = 0.98). Use of venous blood data introduced a large bias in VT (r(2) = 0.96, slope = 0.84) and a small bias in K1 (r(2) = 0.99, slope = 0.98). Use of a second-order polynomial venous-to-arterial transformation was robust and greatly reduced bias in VT (r(2) = 0.97, slope = 0.99) with no effect on K1 CONCLUSION: IDIF yielded precise results for both 3DR and TF. Venous blood samples can be used for absolute quantification of (11)C-HED studies, provided a venous-to-arterial transformation is applied. A venous-to-arterial transformation enables noninvasive, absolute quantification of (11)C-HED studies.
Assuntos
Cardiomiopatias/metabolismo , Efedrina/análogos & derivados , Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Modelos Cardiovasculares , Miocárdio/metabolismo , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Cardiomiopatias/diagnóstico , Simulação por Computador , Efedrina/farmacocinética , Humanos , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Especificidade de Órgãos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição TecidualRESUMO
OBJECTIVE: Non-invasive imaging of myocardial perfusion, sympathetic denervation and scar size contribute to enhanced risk prediction of ventricular arrhythmias (VA). Some of these imaging parameters, however, may be intertwined as they are based on similar pathophysiology. The aim of this study was to assess the predictive role of myocardial perfusion, sympathetic denervation and scar size on the inducibility of VA in patients with ischaemic cardiomyopathy in a head-to-head fashion. METHODS: 52 patients with ischaemic heart disease and left ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation, were included. Late gadolinium-enhanced cardiovascular MRI was performed to assess LV volumes, function and scar size. Using [(15)O]H2O and [(11)C]hydroxyephedrine positron emission tomography, both resting and hyperaemic myocardial blood flow (MBF), and sympathetic innervation were assessed. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA. RESULTS: Patients with a positive EPS (n=25) showed more severely impaired global hyperaemic MBF (p=0.003), larger sympathetic denervation size (p=0.048) and tended to have larger scar size (p=0.07) and perfusion defect size (p=0.06) compared with EPS-negative patients (n=27). No differences were observed in LV volumes, LVEF and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperaemic MBF was the single best independent predictor for VA inducibility (OR 0.78, 95% CI 0.65 to 0.94, p=0.007). A combination of risk markers did not yield incremental predictive value over hyperaemic MBF alone. CONCLUSIONS: Of all previously validated approaches to evaluate the arrhythmic substrate, global impaired hyperaemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value.
Assuntos
Arritmias Cardíacas/etiologia , Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Isquemia Miocárdica/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , Área Sob a Curva , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/prevenção & controle , Cicatriz/diagnóstico por imagem , Cicatriz/patologia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Técnicas Eletrofisiológicas Cardíacas , Feminino , Coração/inervação , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Isquemia Miocárdica/complicações , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Miocárdio/patologia , Razão de Chances , Valor Preditivo dos Testes , Prevenção Primária/instrumentação , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sistema Nervoso Simpático/diagnóstico por imagem , Sistema Nervoso Simpático/fisiopatologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapiaRESUMO
UNLABELLED: Mismatch between areas of reduced myocardial blood flow (MBF) and reduced myocardial innervation (defect areas) may be used to estimate the risk for ventricular arrhythmias. The presence of a mismatch zone can be derived using a combined protocol consisting of both an MBF scan and an (11)C-meta-hydroxyephedrine ((11)C-HED) scan. The rate of influx from blood to myocardium (K1) of (11)C-HED is proportional to MBF and can potentially be used as an index for defining MBF defects. The aim of this study was to assess whether K1 derived from an (11)C-HED scan can be used as an index of MBF, potentially allowing for an assessment of MBF-innervation mismatch areas from a single (11)C-HED scan. METHODS: Seventeen patients with known ischemic cardiomyopathy underwent dynamic (15)O-water and (11)C-HED scans. Discrete arterial blood samples were taken during (11)C-HED scans for metabolite correction of the image-derived input function. (11)C-HED influx rate was obtained using a single-tissue-compartment model and compared with transmural MBF (MBFT), defined as MBF as measured with (15)O-water multiplied by perfusable tissue fraction. Defect sizes were obtained from parametric K1 and MBFT images, using 50% of a remote control segment as the cutoff value. RESULTS: There was a significant correlation between MBFT and K1 (y = 0.40x + 0.05 mL·g(-1)·min(-1), r = 0.80, P < 0.001), although K1 was significantly lower than MBFT (slope of the regression line significantly different from 1, P < 0.001). Correlation between MBFT and K1 defect sizes was high (y = 0.89x + 1.38%, r = 0.95, P < 0.001), with no significant difference in mean defect size based on K1 or MBFT (20.9% ± 11.3% and 20.1% ± 10.7% for MBFT and K1, respectively, P = 0.41). CONCLUSION: (11)C-HED influx rate K1 can be used as an alternative to a separate MBF scan for assessing mismatch areas between MBF and myocardial innervation.
Assuntos
Efedrina/análogos & derivados , Isquemia Miocárdica/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Coração/inervação , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Cintilografia , Reprodutibilidade dos Testes , Sistema Nervoso Simpático/diagnóstico por imagemRESUMO
The main eligibility criterion for primary prevention implantable cardioverter defibrillator (ICD) therapy, that is, left ventricular ejection fraction (LVEF), is based on large clinical trials using primarily 2-dimensional echocardiography (2DE). Presently, cardiac magnetic resonance imaging (MRI) is considered the gold standard for LVEF assessment. It has been demonstrated that cardiac MRI assessment results in lower LVEFs compared with 2DE. Consequently, cardiac MRI-LVEF assessment may lead to more patients eligible for ICD implantation with potential clinical consequences. The aim of this study was to evaluate the clinical impact of cardiac MRI-LVEF versus 2DE-LVEF assessment for ICD eligibility. A total of 149 patients with cardiac MRI-LVEF ≤35% referred for primary prevention ICD implantation who underwent both 2DE and cardiac MRI-LVEF assessment were retrospectively included. 2DE-LVEF was computed by Simpson's biplane method. Cardiac MRI-LVEF was computed after outlining the endocardial contours in short-axis cine images. Appropriate device therapy (ADT) and all-cause mortality were evaluated during 2.9 ± 1.7 years of follow-up. The present study found that cardiac MRI-LVEF was significantly lower compared with 2DE-LVEF (23 ± 8% vs 30 ± 8%, respectively, p <0.001), resulting in 29 (19%) more patients eligible for ICD implantation according to the current guidelines (LVEF ≤35%). Patients with 2DE-LVEF >35% but cardiac MRI-LVEF ≤35% experienced a lower ADT rate compared with patients having 2DE-LVEF ≤35% (2.1% vs 10.4% per year, respectively, p = 0.02). Application of cardiac MRI-LVEF cutoff of 30% resulted in 119 eligible patients experiencing 9.9% per year ADT, comparable with 2DE-LVEF cut-off value of 35%. In conclusion, cardiac MRI-LVEF assessment resulted in more patients eligible for ICD implantation compared with 2DE who showed a relatively low event rate during follow-up. The event rate in patients with cardiac MRI-LVEF ≤30% was comparable with patients having a 2DE-LVEF ≤35%. This study suggests the need for re-evaluation of cardiac MRI-based LVEF cut-off values for ICD eligibility.
Assuntos
Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Ecocardiografia/métodos , Imagem Cinética por Ressonância Magnética/métodos , Seleção de Pacientes , Prevenção Primária/métodos , Taquicardia Ventricular/diagnóstico , Idoso , Morte Súbita Cardíaca/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Taquicardia Ventricular/complicações , Taquicardia Ventricular/terapiaRESUMO
AIMS: Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium. METHODS AND RESULTS: Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [(15)O]H2O- and [(11)C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [(11)C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [(11)C]HED RI was correlated with resting MBF (r = 0.41, P < 0.001) and hyperaemic MBF (r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes (r = -0.40, P = 0.001), LV mass (r = -0.31, P = 0.008), and wall thickening (r = 0.45, P < 0.001) correlated with remote [(11)C]HED RI. Multivariable analysis revealed that hyperaemic MBF (B = 0.79, P < 0.001), wall thickening (B = 0.01, P = 0.03), and LVEDV (B = -0.03, P = 0.02) were independent predictors for remote [(11)C]HED RI. CONCLUSION: Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.
Assuntos
Cardiomiopatia Dilatada/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Microvasos/fisiopatologia , Isquemia Miocárdica/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Simpatectomia/métodos , Idoso , Velocidade do Fluxo Sanguíneo , Cardiomiopatia Dilatada/mortalidade , Estudos de Coortes , Circulação Coronária/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Contração Miocárdica/fisiologia , Infarto do Miocárdio , Isquemia Miocárdica/mortalidade , Imagem de Perfusão do Miocárdio/métodos , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
BACKGROUND: The aims of this study were to determine the optimal tracer kinetic model for [(11)C]-meta-hydroxyephedrine ([(11)C]HED) and to evaluate the performance of several simplified methods. METHODS: Thirty patients underwent dynamic 60-min [(11)C]HED scans with online arterial blood sampling. Single-tissue and both reversible and irreversible two-tissue models were fitted to the data using the metabolite-corrected arterial input function. For each model, reliable fits were defined as those yielding outcome parameters with a coefficient of variation (CoV) <25%. The optimal model was determined using Akaike and Schwarz criteria and the F-test, together with the number of reliable fits. Simulations were performed to study accuracy and precision of each model. Finally, quantitative results obtained using a population-averaged metabolite correction were evaluated, and simplified retention index (RI) and standardized uptake value (SUV) results were compared with quantitative volume of distribution (V T) data. RESULTS: The reversible two-tissue model was preferred in 75.8% of all segments, based on the Akaike information criterion. However, V T derived using the single-tissue model correlated highly with that of the two-tissue model (r (2) = 0.94, intraclass correlation coefficient (ICC) = 0.96) and showed higher precision (CoV of 24.6% and 89.2% for single- and two-tissue models, respectively, at 20% noise). In addition, the single-tissue model yielded reliable fits in 94.6% of all segments as compared with 77.1% for the reversible two-tissue model. A population-averaged metabolite correction could not be used in approximately 20% of the patients because of large biases in V T. RI and SUV can provide misleading results because of non-linear relationships with V T. CONCLUSIONS: Although the reversible two-tissue model provided the best fits, the single-tissue model was more robust and results obtained were similar. Therefore, the single-tissue model was preferred. RI showed a non-linear correlation with V T, and therefore, care has to be taken when using RI as a quantitative measure.
RESUMO
BACKGROUND: Risk stratification for ventricular arrhythmias (VAs) is important to refine selection criteria for primary prevention implantable cardioverter defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and nonischemic cardiomyopathy, which may be attributed to electric instability inducing VAs. The aim of this pilot study was to assess whether hyperemic MBF impairment may be related with VA inducibility in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Thirty patients with ischemic cardiomyopathy referred for primary prevention implantable cardioverter defibrillator implantation were prospectively included (26 men; 65±8 years old; left ventricular ejection fraction, 29±6%). [15O]H2O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL·min(-1)·g(-1); P<0.01) and coronary flow reserve (1.59±0.49 versus 2.12±0.48; P<0.01) compared with electrophysiological study negative patients (n=18). In electrophysiological study positive patients, the number of scar segments>75% transmurality was higher (P<0.05), although scar size and border zone did not differ. Receiver-operating characteristic curve analysis indicated that impaired hyperemic MBF (area under the curve, 0.84; 95% confidence intervals [0.69-0.99]) and coronary flow reserve (area under the curve, 0.77; 95% confidence intervals [0.57-0.96]) were associated with VA inducibility. CONCLUSIONS: In this pilot study, impaired hyperemic MBF and coronary flow reserve were associated with VA inducibility in patients with ischemic cardiomyopathy. These results are hypothesis generating for a potential role of quantitative positron-emission tomography perfusion imaging in risk stratification for VAs.
Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatias/etiologia , Circulação Coronária , Hiperemia/fisiopatologia , Isquemia Miocárdica/complicações , Idoso , Área Sob a Curva , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Razão de Chances , Projetos Piloto , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Medição de Risco , Fatores de Risco , Volume Sistólico , Função Ventricular EsquerdaRESUMO
UNLABELLED: Hybrid imaging using PET in conjunction with CT-based coronary angiography (PET/CTCA) enables near-simultaneous quantification of myocardial blood flow (MBF) and anatomical evaluation of coronary arteries. CTCA is an excellent imaging modality to rule out obstructive coronary artery disease (CAD), but functional assessment is warranted in the presence of a CTCA-observed stenosis because the specificity of CTCA is relatively low. Quantitative H(2)(15)O PET/CTCA may yield complementary information and enhance diagnostic accuracy. The purpose of this study was to evaluate the diagnostic accuracy of quantitative H(2)(15)O PET/CTCA in a clinical cohort of patients with suspected CAD who underwent both cardiac H(2)(15)O PET/CTCA and invasive coronary angiography (ICA). In addition, this study aimed to evaluate and compare the accuracy of hyperemic MBF versus coronary flow reserve (CFR). METHODS: Patients (n = 120; mean age ± SD, 61 ± 10 y; 77 men and 43 women) with a predominantly intermediate pretest likelihood for CAD underwent both quantitative H(2)(15)O PET/CTCA and ICA. A ≥50% stenosis at ICA or a fractional flow reserve ≤ 0.80 was considered significant. RESULTS: Obstructive CAD was diagnosed in 49 of 120 patients (41%). The diagnostic accuracy of hyperemic MBF was significantly higher than CFR (80% vs. 68%, respectively, P = 0.02), with optimal cutoff values of 1.86 mL/min/g and 2.30, respectively. On a per-patient basis, the sensitivity, specificity, negative predictive value, and positive predictive value of CTCA were 100%, 34%, 100%, and 51%, respectively, as compared with 76%, 83%, 83%, and 76%, respectively, for quantitative hyperemic MBF PET. Quantitative H(2)(15)O PET/CTCA reduced the number of false-positive CTCA studies from 47 to 6, although 12 of 49 true-positive CTCAs were incorrectly reclassified as false-negative hybrid scans on the basis of (presumably) sufficient hyperemic MBF. Compared with CTCA (61%) or H(2)(15)O PET (80%) alone (both P < 0.05), the hybrid approach significantly improved diagnostic accuracy (85%). CONCLUSION: The diagnostic accuracy of quantitative H(2)(15)O PET/CTCA is superior to either H(2)(15)O PET or CTCA alone for the detection of clinically significant CAD. Hyperemic MBF was more accurate than CFR, implying that a single measurement of MBF in diagnostic protocols may suffice.
Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Água , Estudos de Coortes , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
AIMS: There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). METHODS AND RESULTS: We evaluated 120 patients (mean age 56 ± 9 years, 58 men) without a documented history of CAD in whom obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress (15)O-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 ± 6, 27 ± 11, and 28 ± 9 mmHg mL(-1)min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 ± 9, 27 ± 8, 32 ± 10, and 32 ± 7 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. CONCLUSION: C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.