Daniel Medeiros Moreira

Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

AbstractCoronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1β, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the “foam cells.” Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

Rationale and Design of the TETHYS Trial: The Effects of Methotrexate Therapy on Myocardial Infarction with ST-Segment Elevation

Introduction: Methotrexate is a drug that has shown anti-ischemic effects in animal studies and positive results in heart failure clinical trials. Methods: We will randomly assign 80 patients with acute myocardial infarction to receive methotrexate (0.05 mg/kg bolus followed by 0.05 mg/kg/h for 6 h) or matching placebo. The primary outcome will be the area under the curve (AUC) for creatine kinase (CK) release for 72 h. Secondary outcomes will be the peak levels of CK, CK-MB fraction and troponin I, AUC for CK-MB and troponin I, levels of B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) at admission and at 30 days, left ventricular ejection fraction (LVEF) at baseline and at 30 days, death, TIMI (thrombolysis in myocardial infarction) frame count in the culprit artery, Killip score after 72 h and rate of reinfarction at 30 days. Results: We expect a reduction in the AUC for CK, CK-MB and troponin release in the methotrexate group compared to the placebo group. We also expect a reduction in the levels of BNP, hsCRP and ESR and an improvement of LVEF and TIMI frame count in the methotrexate group. Conclusion: This trial may be the first to demonstrate the anti-inflammatory and anti-ischemic effects of methotrexate in patients with acute myocardial infarction.

MethotrexaTE THerapy in ST-Segment Elevation MYocardial InfarctionS: A Randomized Double-Blind, Placebo-Controlled Trial (TETHYS Trial)

Purpose: Methotrexate is an anti-inflammatory drug that has been shown to have anti-ischemic effects. Our aim was to evaluate if methotrexate could reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI). Methods: We randomly assigned patients with STEMI to receive either methotrexate or placebo. Primary outcome was infarct size determined by calculating the area under the curve (AUC) for creatine kinase (CK) release. Secondary outcomes were AUC of CK MB (CK-MB) and AUC of troponin I; peak CK, peak CK-MB, and troponin I; B-type natriuretic peptide (BNP) level, high-sensitivity C-reactive protein (hsCRP) result, and erythrocyte sedimentation rate (ESR); left ventricular ejection fraction (LVEF); thrombolysis in myocardial infarction (TIMI) frame count; Killip score; mortality and reinfarction incidence; and incidence of adverse reactions. Results: We included 84 patients. Median AUC of CK was 78 861.0 in the methotrexate group and 68 088.0 in the placebo group (P = .10). Patients given methotrexate and placebo exhibited, respectively, median AUC for CK-MB of 9803.4 and 8037.0 (P = .42); median AUC for troponin of 3691.1 and 2132.6 (P = .09); peak CK of 2806.0 and 2147.0 (P = .05); peak CK-MB of 516.0 and 462.3 (P = .25); and peak troponin of 121.0 and 85.1 (P = .06). At 3 months, LVEF was lower in patients who received methotrexate (49.0% ± 14.1%) than in patients given placebo (56.4% ± 10.0%; P = .01). There were no differences in hsCRP, ESR, BNP, Killip scores, TIMI frame count, reinfarction, and mortality rates. There was a higher median serum glutamic–pyruvic transaminase levels in the methotrexate group. Conclusion: Methotrexate did not reduce infarction size and worsened LVEF at 3 months (Clinicaltrials.gov identifier NCT01741558).

Correlation between Clinical and Educational Factors and Delayed Hospital Arrival in Myocardial Infarction

Myocardial ischemia and, consequently, acute myocardial infarction (AMI) are mentioned as one of the main causes of worldwide morbimortality. Estimated at around 30% in the 1950s, hospital mortality due to AMI showed a significant decline in the last decades, both in Europe and the United States, as well as in Brazil.1-3 Currently, with the use of thrombolytics or primary angioplasty, its occurrence is estimated at between 8 and 10%, mainly due to the benefits of early recanalization of the coronary artery related to the event. The Delta Time (∆-T) between the onset of the first symptoms and the arrival at the emergency service is directly related to the disease morbimortality, and rapid specialized care is essential. However, it is estimated that only 20% of individuals with chest pain reports reach the emergency unit within 2 hours of symptom onset.4

Correlation Between Physical Activity and Clinical Variables in Patients with Acute Myocardial Infarction

Mailing Address: Ana Teresa Glaser Carvalho Rod. Haroldo Soares Glavan, 929 casa 24. Postal Code: 88050-005, Cacupé, Florianópolis, SC Brazil. E-mail: dra.anacarvalho@hotmail.com Correlation Between Physical Activity and Clinical Variables in Patients with Acute Myocardial Infarction Ana Teresa Glaser Carvalho,1 Thays Fraga Duarte,1 Andressa Sarda Maiochi,1 Roberto Leo da Silva,1,2 Tammuz Fattah,1 Daniel Medeiros Moreira1,3 Instituto de Cardiologia de Santa Catarina – ICSC,1 São José, SC; Hospital Universitário Professor Polydoro Ernani de São Thiago HU/UFSC,2 Florianópolis, SC; Universidade do Sul de Santa Cataria – Unisul,3 Palhoça, SC – Brazil

Asystole during exercise stress test: analysis of cardioinhibitory response

Episodes of vasovagal reaction are described as part of the main complications during exercise test and may range from a brief episode of hypotension to extreme cases, translated by asystole. Cardiac asystole related to exercise in patients without structural heart disease is uncommon in clinical practice.1 In the literature, cases of asystole most often occur outside the period of stress, most commonly in the recovery stage of the exercise test. We report the case of a young patient without a structural cardiac disease who presented cardiac asystole in the stress stage of the exercise test.

Correlation between leukocyte count and infarct size in ST segment elevation myocardial infarction

Introduction Regarding the inflammatory mechanisms involved in ischemic heart disease, currently the leukocyte count is the subject of studies related to its association with the prognosis and mortality of ST segment elevation myocardial infarction (STEMI). Our aim is correlate the leukocyte count rise with the size of STEMI, evaluated with the area under the curve (AUC) and the peak of necrosis markers release. Material and methods This study is a sub-analysis of the TETHYS trial, a clinical trial that evaluated the effects of methotrexate in STEMI. We evaluated the correlation between quantitative variables with Pearson’s correlation, and the variables that did not follow a normal distribution were subjected to logarithmic transformation to base 10. The value of p < 0.05 indicated statistical significance. Results Males accounted for 73% of the participants, who had an average age of 59 years. A total of 58% were hypertensive and 53% smokers. The leukocyte count at hospital admission was significantly correlated with the AUC creatine kinase (CK) (r = 0.256, p = 0.021), troponin AUC (r = 0.247, p = 0.026), peak CK (r = 0.270, p = 0.015) and troponin peak (r = 0.233, p = 0.037). The leukocyte count at 72 h was significantly correlated with CK AUC (r = 0.238, p = 0.032), AUC of MB portion of CK (r = 0.240, p = 0.031) and peak CK (r = 0.224, p = 0.045). Conclusions White blood cell count correlates with STEMI size assessed by serial cardiac biomarker levels.

Correlation between RDW, Infarct Size and Coronary Flow after Primary Angioplasty

Background: RDW is a laboratory parameter that measures the anisocytosis index. Its elevation may be related to inflammation, which is also considered primarily responsible for the reduction of post-angioplasty coronary flow. Objectives: To correlate the RDW of patients with ST segment elevation acute myocardial infarction (AMI) and coronary flow, infarction size and post-angioplasty ventricular function. Methods: The IAM size was measured by the areas under the curve (AUC) and biomarker peaks. The correlation between RDW on admission and in 72 hours and other numerical variables was performed using Pearson’s correlation coefficient for normal data or Kendall’s correlation for non-normal data. In this study, p values <0.05 were considered statistically significant. Results: There was a negative correlation between the RDW on admission and the AMI size assessed by peak of CK-MB mass, r=-0.15 (p=0.04). The other parameters used to measure the area of infarction showed no significant relationship with RDW. There were no significant correlations between the RDW and post-angioplasty coronary flow, or with left ventricular ejection fraction (LVEF) or with negative cardiovascular outcomes. Conclusions: There is a weak negative correlation between RDW and the AMI size assessed by CK-MB mass peak, but there is no correlation between RDW and CK or troponin I peak, or RDW and CK AUC, CK-MB mass or troponin I. There is no correlation between RDW and TIMI frame count or between RDW and LVEF.