Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease.

OBJECTIVES: The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND: Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. METHODS: A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. RESULTS: At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (ß = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. CONCLUSIONS: A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036).

P-wave duration is a predictor for long-term mortality in post-CABG patients.

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05-1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients.

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study.

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.

Tratamento da sca no paciente diabético: o que mostram as evidências / Treatment of acs in the diabetic patient: what the evidence shows

O diabete mellitus (DM) é uma comorbidade muito frequente entre os pacientes com síndrome coronariana aguda (SCA), acometendo, aproximadamente, 20 a 37% desses. Além de ser um preditor de risco independente, também está relacionado a uma maior prevalência de quadros atípicos de SCA. Apesar disso, é importante ressaltar que no caso da SCA, a maioria dos pacientes com DM apresenta o mesmo quadro clínico que os pacientes sem a doença. Assim como para os pacientes não diabéticos, os scores de risco devem ser aplicados. Entretanto, essa comorbidade por si própria já prediz uma maior gravidade. Inclusive é mais aconselhável utilizar para esses pacientes uma estratégia invasiva precoce. Em relação ao tratamento medicamentoso da SCA, não há alterações significativas no tratamento dos pacientes com DM para os pacientes sem DM. Já no que diz respeito à terapia de reperfusão, muito se extrapola dos conhecimentos em angina estável, em que há uma superioridade do tratamento cirúrgico sobre o percutâneo para os pacientes com DM, ainda que haja falta de evidências no contexto agudo. Finalmente, o conjunto de evidências não é definitivo para indicar a melhor estratégia para o controle da hiperglicemia, entretanto, sabe-se que tanto a hiperglicemia quanto à hipoglicemia durante a internação está relacionada aos piores desfechos. Portanto, é importante evitar valores de glicemia superiores a 180 mg/dL e inferiores a 90 mg/dL, ficando a estratégia de controle rigoroso de glicemia com insulina intravenosa restrita aos pacientes selecionados.

Diabetes mellitus (DM) is a frequent comorbidity among patients with acute coronary syndrome (ACS), affecting about 20% to 37% of these patients. Besides being an independent risk predictor, it is also related to a higher prevalence of atypical presentations of ACS. Despite this, it is important to emphasize that in the case of ACS the majority of patients with DM have the same clinical presentation as patients without the disease. Just as for non-diabetic patients, risk scores should be applied. However, this comorbidity per se predicts a greater severity. Also, it is preferable to use an early invasive strategy for these patients. Regarding the medicinal treatment of ACS, there are no significant differences between the treatment of patients with DM and those without DM. In relation to reperfusion therapy, much of it is extrapolated from knowledge of stable angina, in which surgical treatment takes precedence over percutaneous treatment for patients with DM, despite the lack of evidence in the acute context. Finally, there is no definitive body of evidence to indicate the best strategy to control hyperglycemia, but it is known that both hyperglycemia and hypoglycemia during hospitalization are associated with worse outcomes. Thus, it is important to avoid glycemia values above 180 mg/dL and below 90 mg/dL, restricting the strategy of strict glycemic control with intravenous insulin to selected patients.

Terapia anticoagulante nas síndromes coronarianas agudas / Anticoagulant therapy in acute coronary syndromes

A necessidade de anticoagulação tem sido crescente em pacientes com síndromes coronarianas agudas, devido à fibrilação atrial com risco de tromboembolismo, presença de tromboembolismo venoso, doenças valvares ou próteses e à maior prevalência em idosos. Nesse cenário, a escolha da terapia antitrombótica mais adequada, notadamente para os pacientes que recebem tratamento percutâneo com inserção de stents, tem sido revista em diretrizes baseadas em estudos recentes, que incluíram novos anticoagulantes e antiplaquetários, em comparação com a estratégia padrão com anti-vitamina K e uso de terapia antiplaquetária dupla, com aspirina e tienopiridínico. Nesta revisão, incluímos estudos que fundamentam as estratégias atuais para o uso combinado de anticoagulantes orais e antiplaquetários em síndromes coronarianas agudas e as diferenças para o uso de anticoagulante em intervenções percutâneas eletivas

The need for anticoagulation is increasing in subjects with acute coronary syndromes, due to atrial fibrillation with risk of thromboembolism, the presence of venous thromboembolism, valve diseases or prostheses, and higher prevalence in the elderly. In this scenario, the choice of most appropriate antithrombotic therapy, particularly for patients who receive percutaneous treatment with the insertion of stents, has been reviewed in guidelines based on recent studies, which included new anticoagulants and antiplatelet agents in comparison with the standard strategy with anti-vitamin K and the use of dual antiplatelet therapy, with aspirin and thienopyridine. This review includes studies that form the basis of the current strategies for the combined use of oral anticoagulant and antiplatelets in acute coronary syndromes and the differences for the use of an anticoagulant in elective percutaneous interventions

Terapia antitrombótica na fase aguda das síndromes coronarianas aguda / Antithrombotic therapy in acute phase of acute coronary syndrome

A morbidade e a mortalidade nas síndromes coronarianas agudas – causadas principalmente pela instabilidade da placa aterosclerótica, levando à formação de trombos – foi bastante reduzida com o advento de antiplaquetários, antitrombóticos e revascularização precoce. Hoje, dispomos de quatro antitrombóticos para uso nestas condições: a heparina não fracionada, a de baixo peso molecular, o fondaparinux e a bivalirudina – sendo apenas as três primeiras disponíveis no Brasil. Como são agentes antiocoagulantes, o risco de sangramento não é desprezível e deve ser apropriadamente dosado com o fim de trazer o máximo benefício antitrombótico, sem grande risco hemorrágico. Nesta revisão sumarizamos o atual estado da arteno uso de antitrombóticos no Brasil...

Morbidity and mortality in the acute coronary syndromes – caused in the majorly by atherosclerotic plaque instability, with consequent thrombus formation – was drastically reduced by the advent of antiplatelet and antithrombotic agents, and by early revascularization. Nowadays, we have 4 antithrombotic agents: unfractionated heparin, low molecular weight heparin, fondaparinux and bivalirudin – with only the first 3 available in Brazil. As they comprise anticoagulant effects, the risk of bleedingis high and must be taken into account when prescribed, in order to bring the greater benefits without higher bleeding risk. In this review we summarized the current state of the art about the use of these agents in our country...

Desafio do diagnóstico da doença coronária aterosclerótica coronária subclínica / Challenge in diagnosis of subclinical coronary disease

A doenças aterosclerótica coronariana (DAC) continua sendo a principal causa de morte. Consequentemente, há interesse crescente no diagnóstico de DAC em assintomáticos. Entretanto, existem alguns questionamentos acerca da indicação e custo-benefício de tal rastreamento, bem como qual ferramenta diagnóstica seria a mais adequada. A DAC obstrutiva pode ocorrer em pacientes pouco sintomáticos ou mesmo assintomáticos, o pode ocorrer progredir rapidamente. A primeira manifestação clínica pode ser angina instável, infarto do miocárdio, ou mesmo morte súbita. A justificativa para a detecção precoce da DAC é que seu diagnóstico nos estágios subclínicos pode permitir a identificação dos indivíduos com risco aumentado de eventos cardíacos adversos e a instituição de tratamento adequado nos indivíduos de alto risco pode melhorar o prognóstico. De acordo com as diretrizes atuais, em pacientes assintomáticos, o teste ergométrico é recomendado apenas em pacientes de alto risco cardiovascular com ECG interpretável e paciente capas de se exercitar. Outros testes diagnósticos não invasivos como ecocardiografia de estresse, ressonância cardíaca de estresse, cintilografia miocárdica, escore de cálcio, angiotomografia coronária só são recomendados em casos selecionados após julgamento clínico. Esses exames são mais adequados em pacientes com ECG não passível de interpretação adequada no teste ergométrico convencional e em pacientes não capazes de se exercitar, com alto risco cardiovascular. Não é recomendado o rastreamento de rotina de DAC em assintomáticos com baixo risco cardiovascular. Naqueles com risco intermediário, os exames mais adequados, levando em consideração o julgamento clínico e o riso-benefício do exame, são o teste ergométrico convencional e o escore de risco.

Coronary heart disease (CHD) remains the leading cause of mortality. There is na increasing interest in the diagnosis of CHD when patients are still asymptomatic. However, questions remaing regarding the appropriateness and cost effectiveness of screening and the best test. Obstructive CHD can exist with few or no symptoms, and can progress rapidly. The The first clinical manifestations can be: acute myocardial infarction (MI), unstable angina, or sudden cardiac death. The explanation for early detection of CHD is that detection during the subclinical stages of disease might permit the identification of patients at increased risk of na acute cardiac event and that appropriate therapy might improve the prognosis of those at high risk. Based on last guidelines, exercise testing in recommended in asymptomatic adults with high cardiovascular risk, able to exercise, and with interpretable ECG. Other non-invasive tests such as stress echocardiography, cardiac resonance, nuclear imaging, coronary tomography, calcium quantification, are only recommended in selected cases after clinical assessment. These tests are more adequate in patients with no interpretable ECG or not able recommended routine screening of CHD in asymptomatic adults with low cardiovascular risk. In those with moderate risk, exercise testing and calcium coronary quatification may be recommended, after clinical assessment.

Peri-infarct zone characterized by cardiac magnetic resonance imaging is directly associated with the inflammatory activity during acute phase myocardial infarction.

Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55 ± 10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p = 0.02), IL-2 (3.6 vs. 3.4 times; p = 0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p = 0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r = 0.69), delta-CRP (r = 0.7), IL-2-D5 (r = 0.5), delta-IL-2 (r = 0.6), TNF-α (r = 0.5), delta-TNF-α (r = 0.4; p = 0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.

Amlodipine reduces cardiac iron overload in patients with thalassemia major: a pilot trial.

BACKGROUND: Iron chelation therapy in patients with thalassemia major may not prevent iron overload in all organs, especially those in which iron enters cells through specific calcium channels. We designed a controlled pilot study to assess the potential of the calcium channel blocker amlodipine in strengthening the efficacy of iron chelation. METHODS: Fifteen patients with thalassemia major undergoing chelation therapy were randomized to receive amlodipine added to standard treatment in a 1:2 allocation for 12 months. T2* values for assessment of iron overload in the liver and heart using magnetic resonance imaging were obtained at baseline and at 6 and 12 months. RESULTS: In the amlodipine-treated group, heart T2* increased significantly in comparison to baseline at 6 and 12 months (21.7 ± 7.2 ms to 28.2 ± 7.9 ms and 28.3 ± 8.0 ms, with P = .007 and .03, respectively), while no differences were observed in the control group (25.1 ± 8.8 ms to 24.7 ± 7.8 ms and 26.2 ± 11.4 ms; P = .99 and 0.95, respectively); significant differences between groups were observed at 6 months (28.2 ± 7.9 ms vs 24.7 ± 7.8 ms in the control group, P = .03). A significant reduction in ferritin levels also was observed in the treated group at 12 months. CONCLUSIONS: The use of amlodipine in conjunction with standard chelation therapy may suggest a new strategy in preventing and treating iron overload in patients with thalassemia major, especially in organs where iron absorption depends on active uptake by calcium channels like the heart.

Medidas morfofuncionais do coração obtidas por ressonância magnética em brasileiros / Morphological and functional measurements of the heart obtained by magnetic resonance imaging in Brazilians

FUNDAMENTO: Medidas ainda hoje utilizadas como referência na ressonância magnética cardíaca foram obtidas principalmente de estudos realizados em populações norte-americanas e europeias. OBJETIVO: Obter medidas do diâmetro diastólico, diâmetro sistólico, volume diastólico final, volume sistólico final, fração de ejeção e massa miocárdica dos ventrículos esquerdo e direito em brasileiros. MÉTODOS: Foram submetidos à ressonância magnética cardíaca, utilizando técnica de precessão livre em estado de equilíbrio, 54 homens e 53 mulheres, com idade média de 43,4 ± 13,1 anos, assintomáticos, sem cardiopatias. RESULTADOS: As médias e os desvios padrão dos parâmetros do ventrículo esquerdo foram: diâmetro diastólico = 4,8 ± 0,5 cm; diâmetro sistólico = 3,0 ± 0,6 cm; volume diastólico final = 128,4 ± 29,6 mL; volume sistólico final = 45,2 ± 16,6 mL; fração de ejeção = 65,5 ± 6,3%; massa = 95,2 ± 30,8 g. Para o ventrículo direito, foram: diâmetro diastólico = 3,9 ± 1,3 cm; diâmetro sistólico = 2,5 ± 0,5 cm; volume diastólico final = 126,5 ± 30,7 mL; volume sistólico final = 53,6 ± 18,4 mL; fração de ejeção = 58,3 ± 8,0% e massa = 26,1 ± 6,1 g. As massas e os volumes foram significativamente maiores nos homens, exceto para o volume sistólico final do ventrículo esquerdo. A fração de ejeção do ventrículo direito foi significativamente maior nas mulheres. Houve correlação significativa e inversa do volume sistólico do volume direito com o aumento da idade. CONCLUSÃO: Este estudo descreveu, pela primeira vez, medidas cardíacas obtidas pela ressonância magnética cardíaca em brasileiros assintomáticos, sem cardiopatias, mostrando diferenças de acordo com o gênero e a idade.

BACKGROUND: Still today, measurements used as a reference in the cardiac magnetic resonance imaging have been obtained mainly from studies carried out in North-American and European populations. OBJECTIVE: To obtain measurements of the diastolic diameter, systolic diameter, end diastolic volume, end systolic volume, ejection fraction, and myocardial mass of the left and right ventricles in Brazilians. METHODS: 54 men and 53 women, with mean age of 43.4 ± 13.1 years, asymptomatic, with no cardiomyopathies, have been subjected to the cardiac magnetic resonance imaging, using a balanced steady state free precession technique. RESULTS: The averages and the standard deviations of the parameters for the left ventricle have been: diastolic diameter = 4.8 ± 0.5 cm; systolic diameter = 3.0 ± 0.6 cm; end diastolic volume = 128.4 ± 29.6 mL; end systolic volume = 45.2 ± 16.6 mL; ejection fraction = 65.5 ± 6.3%; mass = 95.2 ± 30.8 g. For the right ventricle, they have been: diastolic diameter = 3.9 ± 1.3 cm; systolic diameter = 2.5 ± 0.5 cm; end diastolic volume = 126.5 ± 30.7 mL; end systolic volume = 53.6 ± 18.4 mL; ejection fraction = 58.3 ± 8.0%, and mass = 26.1 ± 6.1 g. The masses and the volumes were significantly greater in the men, except for the end systolic volume of the left ventricle. The ejection fraction of the right ventricle has been significantly greater in the women. There has been a significant and inverted correlation of the systolic volume of the right volume with the progression of the age. CONCLUSION: This study has described, for the first time, cardiac measurements obtained through the cardiac magnetic resonance imaging in Brazilians, asymptomatic, with no cardiomyopathies, showing differences in accordance with gender and age.

Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis.

Risk factors for atherosclerosis may contribute to chronic low-grade inflammation. A highly cytotoxic and inflammatory CD4(+) cell subset (CD4(+)CD28(null) cells) has been associated with inflammatory diseases, including acute coronary syndromes (ACS). The aim of this study was to quantify and characterize CD4(+)CD28(null) cells in individuals with risk factors for atherosclerosis and patients with coronary artery disease (CAD). In order to achieve this goal, peripheral blood mononuclear cells (PBMCs) from individuals with risk factors for atherosclerosis and patients with CAD were analyzed using flow cytometry to detect cytotoxic molecules and evaluate the expression of homing receptors and inflammatory cytokines in CD4(+) cell subsets. The cells were evaluated ex vivo and after stimulation in culture. We found no differences in the proportions of CD4(+)CD28(null) cells among the groups. Compared with the CD4(+)CD28(+) population, the ex vivo CD4(+)CD28(null) subset from all groups expressed higher levels of granzymes A and B, perforin, granulysin and interferon-γ (IFN-γ). Individuals with risk factors and patients with ACS showed the highest levels of cytotoxic molecules. After stimulation, tumor necrosis factor-α (TNF-α) expression in the CD4(+)CD28(null) subset from these groups increased more than in the other groups. Stimulation with LPS decreased the expression of cytotoxic molecules by CD4(+)CD28(null) cells in all groups. In conclusion, our results show that risk factors for atherosclerosis may alter the CD4(+)CD28(null) cells phenotype, increasing their cytotoxic potential. Our findings also suggest that CD4(+)CD28(null) cells may participate in the early phases of atherosclerosis.

Cintilografia de perfusão miocárdica na detecção da isquemia silenciosa em pacientes diabéticos assintomáticos / Myocardial perfusion scintigraphy in the detection of silent ischemia in asymptomatic diabetic patients

OBJECTIVE: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1) and type 2 diabetes mellitus (DM2) without previous diagnoses of coronary artery disease (CAD) or cerebral infarction. MATERIALS AND METHODS: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2) underwent myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS). They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. RESULTS: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). CONCLUSION: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia.

OBJETIVO: Este estudo teve por finalidade avaliar a perfusão miocárdica de pacientes com diabetes mellitus tipo 1 (DM1) e tipo 2 (DM2) assintomáticos, sem diagnóstico prévio de doença arterial coronariana (DAC) ou acidente vascular cerebral. MATERIAIS E MÉTODOS: Cinquenta e nove pacientes consecutivos (16 DM1, 43 DM2) foram submetidos a cintilografia de perfusão miocárdica com sestamibi-99mTc (CPM). Foram avaliados quanto ao índice de massa corpórea, controle metabólico do diabetes, dislipidemia, terapia para o diabetes, hipertensão arterial sistêmica, nefropatia, retinopatia, neuropatia periférica, tabagismo e história familiar de DAC. RESULTADOS: CPM foi anormal em 25,4%: 12 (20,3%) com alterações de perfusão e 3 com disfunção ventricular esquerda isolada. Os mais fortes preditores de perfusão miocárdica anormal foram: idade igual ou maior a 60 anos (p = 0,017, odds ratio [OR] = 6,0), neuropatia periférica (p = 0,028, OR = 6,1), nefropatia (p = 0,031, OR = 5,6) e ECG de esforço positivo para isquemia (p = 0,049, OR = 4,08). CONCLUSÃO: A isquemia miocárdica silenciosa ocorre em mais de um em cada cinco diabéticos assintomáticos. Os mais fortes preditores de isquemia foram: idade avançada, neuropatia periférica, nefropatia, retinopatia e ECG de esforço positivo para isquemia.

Trombectomia adjunta em intervenção percutânea primária para infarto agudo do miocárdio / Adjunctive thrombectomy in primary percutaneous intervention for acute myocardial infarction / Trombectomía adyuvante en intervención percutánea primaria para infarto agudo del miocardio

A intervenção coronariana percutânea (ICP) primária tem se tornado a estratégia favorita para reperfusão em infarto agudo do miocárdio com elevação do segmento ST (STEMI). Um grau mais baixo de perfusão miocárdica pós-ICP, no-reflow e até trombose de stent farmacológico tem sido relacionados à presença de trombo intracoronário. A trombectomia adjunta refere-se a procedimentos e dispositivos que removem o material trombótico da artéria associada ao infarto, em teoria, antes que a embolização distal possa ocorrer. Há significante variabilidade entre estudos controlados randomizados de trombectomia em ICP primária em relação aos dispositivos testados, características dos procedimentos, terapia médica adjuvante e desfechos analisados. Em geral, melhoras nos endpoints de perfusão miocárdica não são traduzidas em reduções nos desfechos clínicos. Ainda assim, um número crescente de estudos com maior tempo de seguimento relatou benefícios tardios após o infarto do miocárdio inicial. Cateteres de aspiração simples também podem produzir melhores desfechos do que dispositivos que fragmentam o trombo antes de aspirar os resíduos. As variáveis clínicas ou angiográficas que melhor predizem os benefícios do uso da trombectomia ainda precisam ser definidas. O objetivo dessa revisão é dar uma perspectiva sobre as conclusões de estudos disponíveis e meta-análises de trombectomia adjunta em infarto agudo do miocárdio. Também são discutidos os objetivos para futuros estudos.

Primary percutaneous coronary intervention (PCI) has become the favored reperfusion strategy in acute ST-segment elevation myocardial infarction. Lower post-PCI myocardial perfusion grade, no-reflow and even drug-eluting stent thrombosis have been related to the presence of intracoronary thrombus. Adjunctive thrombectomy refers to procedures and devices that remove thrombotic material from the infarctionrelated artery, in theory, before distal embolization can occur. There is substantial variability between randomized controlled trials of thrombectomy in primary PCI with regards to tested devices, procedural characteristics, adjuvant medical regimen and examined outcomes. As a general statement, improvements in myocardial perfusion endpoints do not translate into reductions in clinical outcomes. Yet, an increasing number of trials with a longer follow-up reported benefits arising late after the index myocardial infarction. Simple aspiration catheters may also produce better outcomes than devices that fragment the thrombus before aspirating debris. Clinical or angiographic variables which best predict benefits from the use of thrombectomy remain to be defined. The aim of this review is to provide perspective on the conclusions of available trials and meta-analysis of adjunctive thrombectomy in acute myocardial infarction. Targets for future studies are discussed.

La intervención coronaria percutánea (ICP) primaria se ha convertido en la estrategia favorita para la reperfusión en el infarto agudo del miocardio con la elevación del segmento ST (STEMI). Un grado más bajo de perfusión miocárdica post- ICP, no-reflow e incluso trombosis de stent farmacológico ha sido relacionado con la presencia de trombo intracoronario. La trombectomía adyuvante se refiere a procedimientos y dispositivos que retiran el material trombótico de la arteria asociada al infarto y en teoría, antes que la embolización distal pueda ocurrir. Existe una significativa variación entre los estudios controlados randomizados de trombectomía en ICP primaria, con relación a los dispositivos testados, características de los procedimientos, terapia médica adyuvante y desenlaces analizados. En general, las mejorías en los endpoints de perfusión miocárdica no se traducen en reducciones en los desenlaces clínicos. Pero incluso así, un gran número de estudios con mayor tiempo de seguimiento indicó que se notan beneficios tardíos después del infarto del miocardio inicial. Los catéteres de aspiración simple también pueden producir mejores desenlaces que los dispositivos que fragmentan el trombo antes de aspirar los residuos. Las variables clínicas o angiográficas que mejor pueden predecir los beneficios del uso de la trombectomía, todavía tienen que ser definidas. El objetivo de esta revisión es ofrecer una perspectiva sobre las conclusiones de estudios existentes y de metanálisis de trombectomía adyuvante en infarto agudo del miocardio. También se discuten aquí los objetivos para futuros estudios.

Timing and dose of statin therapy define its impact on inflammatory and endothelial responses during myocardial infarction.

OBJECTIVE: Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. METHODS AND RESULTS: ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001). CONCLUSIONS: This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.