Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

AIMS: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). CONCLUSION: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

BACKGROUND: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. METHODS: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). RESULTS: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (ß: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). CONCLUSION: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Análise da Custo-Efetividade da Angiotomografia Coronariana no SUS, em Comparação com Outros Métodos Não Invasivos na Suspeita de DAC Estável / Cost-Effectiveness Analysis of CCTA in SUS, as Compared to Other Non-Invasive Imaging Modalities in Suspected Obstructive CAD

Resumo Fundamento Atualmente o sistema de saúde público brasileiro (SUS) não contempla a angiotomografia de coronárias. Objetivos Ranquear sob a perspectiva do SUS, a custo-efetividade de estratégias diagnósticas combinando teste ergométrico, cintilografia miocárdica, ecocardiograma por estresse e angiotomografia de coronárias para o diagnóstico de doença arterial coronariana em uma coorte hipotética de pacientes com probabilidade pré-teste intermediária. Métodos Análise de custo-efetividade por meio de árvore de decisão. Foram analisados a relação de custo-efetividade incremental e o benefício líquido em saúde das estratégias diagnósticas, com a adoção de múltiplos limiares de disposição a pagar entre 0,05 e 1 PIB per capita por diagnóstico correto. Nos casos de testes sequenciais, um segundo teste confirmatório era realizado quando o primeiro fosse positivo. Resultados Após exclusão das estratégias diagnósticas dominadas ou com dominância estendida, a fronteira de eficiência foi composta por três estratégias: teste ergométrico, teste ergométrico seguido de ecocardiograma de estresse, e ecocardiograma de estresse seguido de angiotomografia de coronárias, sendo esta última a estratégia mais custo-efetiva. Pelo critério do benefício líquido, o ranqueamento das estratégias mais custo-efetivas variou conforme a disposição a pagar. Conclusão Utilizando conceitos atuais de avaliação de tecnologias em saúde, este estudo fornece um ranqueamento para a tomada de decisão sobre qual estratégia diagnóstica utilizar, em uma população com risco pré-teste intermediário para DAC. Com estimativa factível de custos para a ATC, o impacto da inclusão desta ao rol do arsenal diagnóstico representaria uma estratégia custo-efetiva na maioria dos cenários avaliados nas variações de disposição a pagar.

Abstract Background The Brazilian public health system does not include computed tomography angiography (CTA). Objective Rank, according to the Brazilian public health system, the cost-effectiveness of different strategies for the diagnosis of coronary artery disease (CAD), combining exercise tests (ET), myocardial scintigraphy (MS), stress echocardiography (SE), and CTA in a hypothetical intermediate pre-test probability cohort of patients. Methods This study implemented a cost-effectiveness analysis through a decision tree. The incremental cost-effectiveness ratio (ICER) and net benefit were analyzed by adopting multiple thresholds of willingness to pay, from 0.05 to 1 GDP per capita per correct diagnosis. In sequential tests, a second confirmatory test was performed only when the first was positive. Results After excluding dominated or extended dominance diagnostic strategies, the efficiency frontier consisted of three strategies: ET, ET followed by SE, and SE followed by CTA, the last being the most cost-effective strategy. Through the net benefit, the ranking of the most cost-effective strategies varied according to willingness to pay. Conclusions Using current concepts of health technology assessment, this study provides a ranking for decision-making concerning which diagnostic strategy to use in a population with an intermediate pre-test risk for CAD. With a feasible cost estimate adopted for CTA, the impact of including this to the list of the diagnostic arsenal would represent a cost-effective strategy in most of the evaluated scenarios with broad variations in the willingness to pay.

Analysis of Three-Dimensional Scar Architecture and Conducting Channels by High-Resolution Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Chagas Heart Disease

ABSTRACT Background: We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events. Methods: Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range). Results: A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60). Conclusions: High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events.

Fluidodinâmica Computacional na Avaliação do Risco Futuro de Aneurismas de Aorta Ascendente / Computational Fluid Dynamics to Assess the Future Risk of Ascending Aortic Aneurysms

Resumo Fundamentos Uma metodologia para identificação de pacientes portadores de aneurisma de aorta ascendente (AAAs) sob alto risco de remodelamento aórtico não está completamente definida. Objetivo Esta pesquisa objetiva caracterizar numericamente o fluxo sanguíneo aórtico, relacionando a distribuição do estresse mecânico resultante com o crescimento de AAAs. Métodos Estudo analítico, observacional, unicêntrico, em que um protocolo de fluidodinâmica computacional (CFD - Computacional Fluid Dynamics) foi aplicado a imagens de angiotomografia computadorizada (ATC) de aorta de pacientes portadores de AAAs. Duas ATC de aorta com pelo menos um ano de intervalo foram obtidas. Dados clínicos dos pacientes foram registrados e, a partir das imagens de ATC, foram gerados modelos tridimensionais. Foram realizados estudos do campo de velocidade e estruturas coerentes (vórtices) com o objetivo de relacioná-los ao crescimento ou não do aneurisma e, posteriormente, compará-los com os dados clínicos dos pacientes. O teste de Kolmogorov-Smirnov foi utilizado para avaliar a normalidade da amostra e o teste não-paramétrico Wilcoxon signed-rank foi aplicado para comparações de dados pareados entre os ângulos aórticos. A significância estatística foi fixada em 5%. Resultados Para o grupo que apresentou crescimento do aneurisma, a incidência do jato na parede aórtica gerou áreas de recirculação posterior ao jato, induzindo à formação de vórtices complexos, ocasionando um incremento na pressão média no endotélio aórtico. O grupo sem crescimento do aneurisma apresentou diminuição na pressão média. Conclusão Este estudo piloto mostrou que a CFD baseada em ATC pode, em um futuro próximo, ser uma ferramenta auxiliar na identificação dos padrões de fluxo associados ao processo de remodelamento de AAAs.

Abstract Background A methodology to identify patients with ascending aortic aneurysm (AsAA) under high risk for aortic growth is not completely defined Objetive This research seeks to numerically characterize the aortic blood flow by relating the resulting mechanical stress distribution with AsAA growth. Methods Analytical, observational, single-center study in which a computational fluid dynamics (CFD) protocol was applied to aortic computed tomography angiogram (CTA) images of patients with AsAA. Two CTA exams taken at a minimum interval of one year were obtained. From the CTA-gathered images, three-dimensional models were built, and clinical data were registered. Study of velocity field and coherent structures (vortices) was performed aiming to relate them to the presence or absence of aneurysm growth, as well as comparing them to the patients' clinical data. The Kolmogorov-Smirnov test was used to evaluate the normality of the distribution, and the non-parametric Wilcoxon signed-rank test, for non-normal distribution, was used to compare the paired data of the aortic angles. Statistical significance was set at 5%. Results The incident jet in the aortic wall generated recirculation areas in the posterior region of the jet, inducing complex vortices formation in the group with aneurysm growth, leading to an average pressure increase in the ascending aortic wall between exams. In the group without aneurysm growth, the average pressure decreased. Conclusion This pilot study showed that CFD based on CTA may in the near future be a tool to help identify flow patterns associated with AsAA remodeling process.

Fibrose Cardíaca e Mudanças Evolutivas na Função Ventricular Esquerda em Pacientes com Cardiopatia Chagásica Crônica / Cardiac Fibrosis and Changes in Left Ventricle Function in Patients with Chronic Chagas Heart Disease

Resumo Fundamento A cardiopatia chagásica (CC) é uma condição de progressão lenta, cujo principal achado histopatológico é fibrose. Objetivos Avaliar se a fibrose cardíaca aumenta ao longo do tempo e se correlaciona com aumento no tamanho do ventrículo esquerdo (CE) e redução na fração de ejeção (FE) na CC crônica. Métodos Estudo retrospectivo que incluiu 20 indivíduos (50% homens; 60±10 anos) com CC crônica que se submeteram a dois exames de ressonância magnética cardíaca (RMC) com realce tardio com gadolínio em um intervalo mínimo de quatro anos entre os exames. Volume, FE e massa de fibrose do ventrículo esquerdo (VE) foram determinados por RMC. Associações da massa de fibrose na primeira RMC com alterações no volume do VE e FE ventricular esquerda na segunda RMC foram testadas por análise de regressão logística. Valores p<0,05 foram considerados significativos. Resultados Os pacientes foram classificados em: A (n=13; alterações típicas de CC no eletrocardiograma e função sistólica global e segmentar do VE normal) e B1 (n=7; alteração na motilidade da parede do VE e FE ≥45%). O tempo médio entre os dois estudos de RMC foi de 5,4±0,5 anos. Fibrose do VE (em % massa do VE) aumentou de 12,6±7.9% para 18,0±14,1% entre os exames de RMC (p=0,02). A massa de fibrose cardíaca no basal associou-se com uma diminuição > cinco unidades absolutas na FE ventricular esquerda da primeira para a segunda RMC (OR 1,48; IC95% 1,03-2,13; p=0,03). A massa de fibrose do VE foi maior e aumentou entre os dois estudos de RMC no grupo de pacientes que apresentaram diminuição na FE entre os testes. Conclusões Mesmo pacientes em estágios iniciais da CC apresentam um aumento na fibrose do miocárdio ao longo do tempo, e a presença de fibrose do VE no basal está associada a uma diminuição da função sistólica do VE.

Abstract Background Chagas heart disease (CHD) is a slow progressing condition with fibrosis as the main histopathological finding. Objectives To study if cardiac fibrosis increases over time and correlates with increase in left ventricular (LV) size and reduction of ejection fraction (EF) in chronic CHD. Methods Retrospective study that included 20 individuals (50% men; 60±10 years) with chronic CHD who underwent two cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement with a minimum interval of four years between tests. LV volume, EF, and fibrosis mass were determined by cardiac MRI. Associations of fibrosis mass at the first cardiac MRI and changes in LV volume and EF at the second cardiac MRI were tested using logistic regression analysis. P values <0.05 were considered significant. Results Patients were classified as follows: A (n=13; changes typical of CHD in the electrocardiogram and normal global and segmental LV systolic function) and B1 (n=7; LV wall motion abnormality and EF≥45%). Mean time between cardiac MRI studies was 5.4±0.5 years. LV fibrosis (in %LV mass) increased from 12.6±7.9% to 18.0±14.1% between MRI studies (p=0.02). Cardiac fibrosis mass at baseline was associated with decrease in >5 absolute units in LV EF from the first to the second MRI (OR 1.48, 95% CI 1.03-2.13, p=0.03). LV fibrosis mass was larger and increased between MRI studies in the group that presented decrease in LV EF between the tests. Conclusions Even patients at an initial stage of CHD show an increase in myocardial fibrosis over time, and the presence of LV fibrosis at baseline is associated with a decrease in LV systolic function.

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm3 ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized ß = 0.24; 95% CI: 0.16, 0.32; P < .001) and both calcified (ß = 0.26; 95% CI: 0.18, 0.34; P < .001) and noncalcified (ß = 0.17; 95% CI: 0.08, 0.25; P < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (ß = 0.13; 95% CI: 0.03, 0.22; P = .01), driven solely by calcified plaque volume (ß = 0.24; 95% CI: 0.14, 0.34; P < .001) but not noncalcified plaque volumes (ß = -0.06; 95% CI: -0.14, 0.03; P = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.

Evaluation of Myocardial Perfusion by Computed Tomography - Principles, Technical Background and Recommendations.

Coronary computed tomography angiography (CCTA) has gained a prominent role in the evaluation of coronary artery disease. However, its anatomical nature does not allow the evaluation of the functional repercussion of coronary obstructions. It has been made possible to evaluate Myocardial computed tomography perfusion (Myocardial CTP) recently, based on myocardial contrast changes related to coronary stenoses. Several studies have validated this technique against the anatomical reference method (cardiac catheterization) and other functional methods, including myocardial perfusion scintigraphy and fractional flow reserve. The Myocardial CTP is performed in conjunction with the CCTA, a combined analysis of anatomy and function. The stress phase (with assessment of myocardial perfusion) can be performed before or after the resting phase (assessment of resting perfusion and coronary arteries), and different acquisition parameters are proposed according to the protocol and type of equipment used. Stressors used are based on coronary vasodilation (e.g. dipyridamole, adenosine). Image interpretation, similar to other perfusion assessment methods, is based on the identification and quantification of myocardial perfusion defects. The integration of both perfusion and anatomical findings is fundamental for the examination interpretation algorithm, allowing to define if the stenoses identified are hemodynamically significant and may be related to myocardial ischemia.

Evaluation of Myocardial Perfusion by Computed Tomography - Principles, Technical Background and Recommendations / Avaliação da Perfusão Miocárdica por Tomografia Computadorizada - Princípios, Fundamentação Técnica e Recomendações

Abstract Coronary computed tomography angiography (CCTA) has gained a prominent role in the evaluation of coronary artery disease. However, its anatomical nature does not allow the evaluation of the functional repercussion of coronary obstructions. It has been made possible to evaluate Myocardial computed tomography perfusion (Myocardial CTP) recently, based on myocardial contrast changes related to coronary stenoses. Several studies have validated this technique against the anatomical reference method (cardiac catheterization) and other functional methods, including myocardial perfusion scintigraphy and fractional flow reserve. The Myocardial CTP is performed in conjunction with the CCTA, a combined analysis of anatomy and function. The stress phase (with assessment of myocardial perfusion) can be performed before or after the resting phase (assessment of resting perfusion and coronary arteries), and different acquisition parameters are proposed according to the protocol and type of equipment used. Stressors used are based on coronary vasodilation (e.g. dipyridamole, adenosine). Image interpretation, similar to other perfusion assessment methods, is based on the identification and quantification of myocardial perfusion defects. The integration of both perfusion and anatomical findings is fundamental for the examination interpretation algorithm, allowing to define if the stenoses identified are hemodynamically significant and may be related to myocardial ischemia.

Resumo A angiografia coronariana por tomografia computadorizada (ACTC) assumiu um papel de destaque na avaliação da doença arterial coronariana. Entretanto, sua natureza anatômica não permitia a avaliação da repercussão funcional das obstruções coronarianas. Recentemente, tornou-se possível a avaliação da perfusão miocárdica por tomografia computadorizada (PMTC), baseando-se nas alterações de contrastação miocárdicas relacionadas às estenoses coronarianas. Diversos estudos permitiram validar esta técnica perante o método anatômico de referência (cateterismo cardíaco) e outros métodos funcionais, incluindo cintilografia de perfusão miocárdica e a reserva de fluxo fracionada. A PMTC é realizada conjuntamente com a ACTC, em uma análise combinada de anatomia e função. A fase de estresse (com avaliação da perfusão miocárdica) pode ser realizada antes ou depois da fase de repouso (avaliação da perfusão de repouso e artérias coronárias), e diferentes parâmetros de aquisição são propostos conforme o protocolo e o tipo de equipamento utilizados. Os agentes estressores utilizados baseiam-se na vasodilatação coronariana (ex: dipiridamol, adenosina). A interpretação das imagens, semelhante a outros métodos de avaliação perfusional, baseia-se na identificação e quantificação de defeitos de perfusão miocárdicos. A integração dos achados perfusionais e anatômicos é parte fundamental do algoritmo de interpretação do exame, permitindo definir se as estenoses identificadas são hemodinamicamente significativas, podendo se relacionar com isquemia miocárdica.

Prevalence and Prediction of Obstructive Coronary Artery Disease in Patients Undergoing Primary Heart Valve Surgery.

BACKGROUND: The prevalence of coronary artery disease (CAD) in valvular patients is similar to that of the general population, with the usual association with traditional risk factors. Nevertheless, the search for obstructive CAD is more aggressive in the preoperative period of patients with valvular heart disease, resulting in the indication of invasive coronary angiography (ICA) to almost all adult patients, because it is believed that coronary artery bypass surgery should be associated with valve replacement. OBJECTIVES: To evaluate the prevalence of obstructive CAD and factors associated with it in adult candidates for primary heart valve surgery between 2001 and 2014 at the National Institute of Cardiology (INC) and, thus, derive and validate a predictive obstructive CAD score. METHODS: Cross-sectional study evaluating 2898 patients with indication for heart surgery of any etiology. Of those, 712 patients, who had valvular heart disease and underwent ICA in the 12 months prior to surgery, were included. The P value < 0.05 was adopted as statistical significance. RESULTS: The prevalence of obstructive CAD was 20%. A predictive model of obstructive CAD was created from multivariate logistic regression, using the variables age, chest pain, family history of CAD, systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and male gender. The model showed excellent correlation and calibration (R² = 0.98), as well as excellent accuracy (ROC of 0.848; 95%CI: 0.817-0.879) and validation (ROC of 0.877; 95%CI: 0.830 - 0.923) in different valve populations. CONCLUSIONS: Obstructive CAD can be estimated from clinical data of adult candidates for valve repair surgery, using a simple, accurate and validated score, easy to apply in clinical practice, which may contribute to changes in the preoperative strategy of acquired heart valve surgery in patients with a lower probability of obstructive disease.

Prevalence and Prediction of Obstructive Coronary Artery Disease in Patients Undergoing Primary Heart Valve Surgery / Prevalência e Predição de Doença Arterial Coronariana Obstrutiva em Pacientes Submetidos a Cirurgia Valvar Primária

Abstract Background: The prevalence of coronary artery disease (CAD) in valvular patients is similar to that of the general population, with the usual association with traditional risk factors. Nevertheless, the search for obstructive CAD is more aggressive in the preoperative period of patients with valvular heart disease, resulting in the indication of invasive coronary angiography (ICA) to almost all adult patients, because it is believed that coronary artery bypass surgery should be associated with valve replacement. Objectives: To evaluate the prevalence of obstructive CAD and factors associated with it in adult candidates for primary heart valve surgery between 2001 and 2014 at the National Institute of Cardiology (INC) and, thus, derive and validate a predictive obstructive CAD score. Methods: Cross-sectional study evaluating 2898 patients with indication for heart surgery of any etiology. Of those, 712 patients, who had valvular heart disease and underwent ICA in the 12 months prior to surgery, were included. The P value < 0.05 was adopted as statistical significance. Results: The prevalence of obstructive CAD was 20%. A predictive model of obstructive CAD was created from multivariate logistic regression, using the variables age, chest pain, family history of CAD, systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and male gender. The model showed excellent correlation and calibration (R² = 0.98), as well as excellent accuracy (ROC of 0.848; 95%CI: 0.817-0.879) and validation (ROC of 0.877; 95%CI: 0.830 - 0.923) in different valve populations. Conclusions: Obstructive CAD can be estimated from clinical data of adult candidates for valve repair surgery, using a simple, accurate and validated score, easy to apply in clinical practice, which may contribute to changes in the preoperative strategy of acquired heart valve surgery in patients with a lower probability of obstructive disease.

Resumo Fundamento: A prevalência de doença arterial coronariana (DAC) nos pacientes valvares é semelhante à da população geral, com associação usual aos fatores de risco tradicionais. Ainda assim, a busca por DAC obstrutiva é mais agressiva nos valvulopatas em pré-operatório, determinando a angiografia coronariana invasiva (ACI) a praticamente todos os pacientes adultos, uma vez que se acredita que a cirurgia de revascularização miocárdica deva ser associada à troca valvar. Objetivos: Avaliar a prevalência de DAC obstrutiva e identificar fatores a ela associados em adultos candidatos à cirurgia cardíaca primariamente valvar entre os anos de 2001 a 2014 no Instituto Nacional de Cardiologia (INC) e elaborar um modelo preditivo de DAC obstrutiva através de escore derivado de análise multivariada. A partir da estimativa da probabilidade pré-teste de DAC obstrutiva, espera-se melhor estratégia pré-operatória para cada paciente. Métodos: Estudo transversal avaliando 2.898 pacientes com indicação de cirurgia cardíaca por qualquer etiologia. Desses, foram estudados 712 pacientes valvopatas submetidos à ACI nos 12 meses anteriores à cirurgia. Diferenças com valor de p < 0,05 foram consideradas estatisticamente significativas. Resultados: A prevalência de DAC obstrutiva foi de 20%. Um modelo preditivo de DAC obstrutiva foi criado a partir de regressão logística multivariada, utilizando as variáveis idade, dor torácica, história familiar de DAC, hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e sexo masculino. O modelo demonstrou excelente correlação e calibração (R2 = 0,98), além de ótima acurácia (ROC de 0,848; IC95% 0,817 - 0,879) e validação em diferente população valvar (ROC de 0,877; IC 95%: 0,830 - 0,923). Conclusões: É possível estimar DAC obstrutiva a partir de dados clínicos com elevada acurácia, o que pode vir a permitir estabelecer estratégias pré-operatórias de acordo com a probabilidade pré-teste individual, evitando a indicação indiscriminada de procedimentos desnecessários e invasivos, principalmente nos grupos de menor probabilidade de DAC obstrutiva. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0)

Myosin-binding Protein C Compound Heterozygous Variant Effect on the Phenotypic Expression of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes encoding sarcomere proteins. It is the major cause of sudden cardiac death in young high-level athletes. Studies have demonstrated a poorer prognosis when associated with specific mutations. The association between HCM genotype and phenotype has been the subject of several studies since the discovery of the genetic nature of the disease. This study shows the effect of a MYBPC3 compound variant on the phenotypic HCM expression. A family in which a young man had a clinical diagnosis of HCM underwent clinical and genetic investigations. The coding regions of the MYH7, MYBPC3 and TNNT2 genes were sequenced and analyzed. The proband present a malignant manifestation of the disease, and is the only one to express HCM in his family. The genetic analysis through direct sequencing of the three main genes related to this disease identified a compound heterozygous variant (p.E542Q and p.D610H) in MYBPC3. A family analysis indicated that the p.E542Q and p.D610H alleles have paternal and maternal origin, respectively. No family member carrier of one of the variant alleles manifested clinical signs of HCM. We suggest that the MYBPC3-biallelic heterozygous expression of p.E542Q and p.D610H may cause the severe disease phenotype seen in the proband. Resumo A cardiomiopatia hipertrófica (CMH) é uma doença autossômica dominante causada por mutações em genes que codificam as proteínas dos sarcômeros. É a principal causa de morte súbita cardíaca em atletas jovens de alto nível. Estudos têm demonstrado um pior prognóstico associado a mutações específicas. A associação entre genótipo e fenótipo em CMH tem sido objeto de diversos estudos desde a descoberta da origem genética dessa doença. Este trabalho apresenta o efeito de uma mutação composta em MYBPC3 na expressão fenotípica da CMH. Uma família na qual um jovem tem o diagnóstico clínico de CMH foi submetida à investigação clínica e genética. As regiões codificadoras dos genes MYH7, MYBPC3 e TNNT2 foram sequenciadas e analisadas. O probando apresenta uma manifestação maligna da doença e é o único em sua família a desenvolver CMH. A análise genética pelo sequenciamento direto dos três principais genes relacionados à essa doença identificou uma variante em heterozigose composta (p.E542Q e p.D610H) em MYBPC3. A análise da família mostrou que os alelos p.E542Q e p.D610H tem origem paterna e materna, respectivamente. Nenhum familiar portador de um dos alelos variantes manifestou sinais clínicos de CMH. Sugerimos que a expressão heterozigótica bialélica de p.E542Q e p.D610H pode ser responsável pelo fenótipo severo da doença encontrada no probando.

Factors Associated With Coronary Artery Disease Progression Assessed By Serial Coronary Computed Tomography Angiography / Fatores Associados com Progressão da Doença Arterial Coronariana Avaliada por Angiografia Coronariana por Tomografia Computadorizada Seriada

Abstract Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR 1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression.

Resumo Fundamento: Angiografia coronariana por tomografia computadorizada (ACTC) permite fenotipagem não invasiva da doença arterial coronariana (DAC). Fatores relacionados à progressão da DAC têm valor epidemiológico. Objetivo: Identificar os fatores associados com a progressão da DAC em pacientes submetidos à avaliação sequencial por ACTC. Métodos: Nós analisamos retrospectivamente 384 pacientes consecutivos que apresentavam pelo menos duas avaliações por ACTC entre dezembro de 2005 e março de 2013. Devido às limitações na quantificação da progressão da DAC, os pacientes que haviam sido submetidos previamente à revascularização cirúrgica ou intervenção coronariana percutânea (ICP) entre as avaliações foram excluídos. A progressão da DAC foi definida como qualquer aumento no escore adaptado de estenose segmentar (calculado com utilização do número de segmentos afetados e gravidade da estenose) em todos os segmentos coronarianos sem stent (restenose intra-stent foi excluída da análise). Regressão logística stepwise foi utilizada para avaliar as variáveis associadas com a progressão da DAC. Resultados: De uma população final de 234 pacientes, um total de 117 (50%) pacientes apresentaram progressão da DAC. Em um modelo considerando os principais fatores de risco para DAC e outras características basais, apenas a idade (odds ratio [OR] 1,04, intervalo de confiança de 95% [IC95%] 1,01-1,07), intervalo entre avaliações (OR 1,03, IC95% 1,01-1,04) e ICP prévia (OR 3,66, IC95% 1,77-7,55) mostraram uma relação independente com a progressão da DAC. Conclusões: Uma história de ICP com implante de stent esteve independentemente associada a um aumento de 3,7 vezes na chance de progressão da DAC, excluindo a restenose intra-stent. Idade e intervalo entre avaliações também foram preditores independentes de progressão.

Myosin-binding Protein C Compound Heterozygous Variant Effect on the Phenotypic Expression of Hypertrophic Cardiomyopathy / Mutação em Hetrozigose Composta no Gene da Proteína C Ligante de Miosina e sua Expressão Fenotípica na Cardiomiopatia Hipertrófica

Abstract Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes encoding sarcomere proteins. It is the major cause of sudden cardiac death in young high-level athletes. Studies have demonstrated a poorer prognosis when associated with specific mutations. The association between HCM genotype and phenotype has been the subject of several studies since the discovery of the genetic nature of the disease. This study shows the effect of a MYBPC3 compound variant on the phenotypic HCM expression. A family in which a young man had a clinical diagnosis of HCM underwent clinical and genetic investigations. The coding regions of the MYH7, MYBPC3 and TNNT2 genes were sequenced and analyzed. The proband present a malignant manifestation of the disease, and is the only one to express HCM in his family. The genetic analysis through direct sequencing of the three main genes related to this disease identified a compound heterozygous variant (p.E542Q and p.D610H) in MYBPC3. A family analysis indicated that the p.E542Q and p.D610H alleles have paternal and maternal origin, respectively. No family member carrier of one of the variant alleles manifested clinical signs of HCM. We suggest that the MYBPC3-biallelic heterozygous expression of p.E542Q and p.D610H may cause the severe disease phenotype seen in the proband.

Resumo A cardiomiopatia hipertrófica (CMH) é uma doença autossômica dominante causada por mutações em genes que codificam as proteínas dos sarcômeros. É a principal causa de morte súbita cardíaca em atletas jovens de alto nível. Estudos têm demonstrado um pior prognóstico associado a mutações específicas. A associação entre genótipo e fenótipo em CMH tem sido objeto de diversos estudos desde a descoberta da origem genética dessa doença. Este trabalho apresenta o efeito de uma mutação composta em MYBPC3 na expressão fenotípica da CMH. Uma família na qual um jovem tem o diagnóstico clínico de CMH foi submetida à investigação clínica e genética. As regiões codificadoras dos genes MYH7, MYBPC3 e TNNT2 foram sequenciadas e analisadas. O probando apresenta uma manifestação maligna da doença e é o único em sua família a desenvolver CMH. A análise genética pelo sequenciamento direto dos três principais genes relacionados à essa doença identificou uma variante em heterozigose composta (p.E542Q e p.D610H) em MYBPC3. A análise da família mostrou que os alelos p.E542Q e p.D610H tem origem paterna e materna, respectivamente. Nenhum familiar portador de um dos alelos variantes manifestou sinais clínicos de CMH. Sugerimos que a expressão heterozigótica bialélica de p.E542Q e p.D610H pode ser responsável pelo fenótipo severo da doença encontrada no probando.

Prognostic performance of coronary computed tomography angiography in asymptomatic individuals as compared to symptomatic patients with an appropriate indication.

INTRODUCTION: Current Appropriatene Usa Criteria exclude coronary computed tomography angiography (CTA) in asymptomatic individuals. We compared the prognostic value of coronary CTA in asymptomatic individuals to symptomatic patients with "definitely appropriate" indications for coronary CTA. METHODS: Consecutive patients without previously known CAD referred for a CTA exam were divided into 2 groups. One group consisted ofasymptomatic individuals, the other of symptomatic patients with a "definitely appropriate" indication for coronary CT (unable to exercise and/or with an uninterpretable electrocardiogram and at an intermediate pre-test probability of obstructive coronary artery disease). Patients that did not fit into either groups were excluded. The segment stenosis score (SSS) was calculated based on coronary CTA and patients were followed for a composite endpoint of all-cause death, acute myocardial infarction and late revascularization. RESULTS: A total of 1080 patients (60 ± 12 years, 65% male) were included in the study (674 "asymptomatic" and 406 "appropriate"). SSS >4 was more frequent in "asymptomatic" than in "appropriate" CT data sets (27% vs 20%, p = 0.02). After a mean follow-up of 4.4 ± 1.8 yrs, 49 patients reached the composite endpoint. On multivariable analysis adjusting for CAD risk factors and symptoms, only a high-risk CTA study and past smoking were independently predictive of events. CONCLUSIONS: Although currently not regarded as "definitely appropriate", the use of coronary CTA in a selected asymptomatic population had higher yield for identifying high-risk individuals than appropriately indicated studies in symptomatic patients and provided thequal prognostic information.