Mesenchymal Stromal Cell-Based Products: Challenges and Clinical Therapeutic Options.

Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells or embryonic stem cells. However, ATMP heterogeneity may impact product identity and potency, and, consequently, clinical trial outcomes. In this review, we discuss these topics and the need to establish minimal criteria regarding the manufacturing of MSCs so that these innovative therapeutics may be better positioned to contribute to the advancement of regenerative medicine.

Advanced cell and gene therapies in cardiology.

We review the evidence for the presence of stem/progenitor cells in the heart and the preclinical and clinical data using diverse cell types for the therapy of cardiac diseases. We highlight the failure of adult stem/progenitor cells to ameliorate heart function in most cardiac diseases, with the possible exception of refractory angina. The use of pluripotent stem cell-derived cardiomyocytes is analysed as a viable alternative therapeutic option but still needs further research at preclinical and clinical stages. We also discuss the use of direct reprogramming of cardiac fibroblasts into cardiomyocytes and the use of extracellular vesicles as therapeutic agents in ischemic and non-ischemic cardiac diseases. Finally, gene therapies and genome editing for the treatment of hereditary cardiac diseases, ablation of genes responsible for atherosclerotic disease, or modulation of gene expression in the heart are discussed.

Aging Triggers Mitochondrial Dysfunction in Mice.

Direct analysis of isolated mitochondria from old mice enables a better understanding of heart senescence dysfunction. Despite a well-defined senescent phenotype in cardiomyocytes, the mitochondrial state in aged cardiomyocytes is still unclear. Here, we report data about mitochondrial function in old mice. Isolated cardiomyocytes' mitochondria were obtained by differential centrifugation from old and young mice hearts to perform functional analyses of mitochondrial O2 consumption, transmembrane potential, ROS formation, ATP production, and swelling. Our results show that mitochondria from old mouse hearts have reduced oxygen consumption during the phosphorylative states of complexes I and II. Additionally, these mitochondria produced more ROS and less ATP than those of young hearts. Mitochondria from old hearts also showed a depolarized membrane potential than mitochondria from young hearts and, as expected, a greater electron leak. Our results indicate that mitochondria from senescent cardiomyocytes are less efficient in O2 consumption, generating more ROS and producing less ATP. Furthermore, the phosphorylative state of complexes I and II presents a functional defect, contributing to greater leakage of protons and ROS production that can be harmful to the cell.

First Evaluation of the Brazilian Advanced Life Support Training (TECA A)

Abstract Background Cardiac arrest (CA) is a common condition associated with high mortality. The Brazilian advanced life support training TECA A (Treinamento em Emergências Cardiovasculares Avançado — Advanced Cardiovascular Emergency Training) was created to train healthcare professionals in the management of CA. However, there are no studies evaluating the effectiveness of TECA A. Objective To assess the impact of TECA A on the management of CA using a simulated CA situation. Methods Fifty-six students underwent a simulated case of CA in a manikin. The students' performance in the management of CA was assessed for the time to first chest compression and defibrillation and for a global assessment score using a structured tool. These items were assessed and compared before and after the TECA A. Exclusion criteria were previous participation in CA trainings and absence from class. Categorical variables were compared using the McNemar test and quantitative variables using the Wilcoxon test. All tests were two-tailed, and statistical significance was set at p < 0.05. Results Compared with before TECA A, median global assessment scores were higher after TECA A (pre-training: 4.0 points [2.0-5.0] vs. 10 points [9.0-10.0]; p<0.001), the time to start chest compressions was shorter (pre-training: 25 seconds [15-34] vs. 19 seconds [16.2-23.0]; p=0.002) and so was the time to defibrillation (pre-training: 82.5 seconds [65.0-108.0] vs. 48 seconds [39.0-53.0]; p<0.001). Conclusions The TECA A promoted a higher adherence to cardiopulmonary resuscitation (CPR) guidelines and a reduction in the time elapsed from CA to first chest compression and defibrillation.

Additional improvement in regional myocardial ischemia after intracardiac injection of bone marrow cells during CABG surgery.

Background: Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD). Objective: We evaluated whether autologous bone marrow-derived cells (BMC) contribute to additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG). Methods: In a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 ± 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC (n = 77) or placebo (n = 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG. Results: The reduction in global SIMI after CABG was comparable (p = 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group (p = 0.047). Baseline regional SIMI values were comparable [18.5 (16.2-21.0) vs. 18.5 (16.5-20.7)] and reached the lowest values at 1 month [9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85)] for BMC and placebo groups, respectively. The ischemia's improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) (p = 0.34) and all-cause mortality (p = 0.08) did not differ between groups 1 month post intervention. Conclusion: We provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT01727063.

Cell-Based Therapies for Heart Failure.

Heart failure has reached epidemic proportions with the advances in cardiovascular therapies for ischemic heart diseases and the progressive aging of the world population. Efficient pharmacological therapies are available for treating heart failure, but unfortunately, even with optimized therapy, prognosis is often poor. Their last therapeutic option is, therefore, a heart transplantation with limited organ supply and complications related to immunosuppression. In this setting, cell therapies have emerged as an alternative. Many clinical trials have now been performed using different cell types and injection routes. In this perspective, we will analyze the results of such trials and discuss future perspectives for cell therapies as an efficacious treatment of heart failure.

High-frequency (22-MHz) ultrasound for assessing the depth of basal cell carcinoma invasion.

BACKGROUND: High-frequency ultrasound (HFUS) has been studied in the diagnosis and therapeutic management of basal cell carcinoma (BCC). The accuracy of this method for location of deep margins remains unknown. This study evaluates HFUS for localization of deep surgical margins in BCC. MATERIALS AND METHODS: Ultrasound images of 83 lesions from 67 patients with clinical and dermoscopic diagnosis of BCC were compared with histopathological findings. Pearson's correlation coefficient was used to assess the relationship between thickness as measured by HFUS and histopathology. RESULTS: A strong correlation between HFUS and histopathological measurements was identified (r = 0.9744, P < .001). HFUS had sensitivity of 96%, specificity of 84%, and accuracy of 91% for measurement of deep tumor margins. Factors affecting tumor measurement on HFUS include marked basophilic degeneration of collagen, presence of peritumoral hypertrophic glands or hair follicles, fibrosis, and dense inflammatory changes related to the tumor itself or to prior procedures. CONCLUSION: High-frequency ultrasound was effective in localizing deep tumor margins in BCC. Therefore, we believe that this diagnostic imaging method is important when selecting a therapeutic approach, considering Mohs micrographic surgery, and evaluating the surgical site.

New Cardiomyokine Reduces Myocardial Ischemia/Reperfusion Injury by PI3K-AKT Pathway Via a Putative KDEL-Receptor Binding.

Background CDNF (cerebral dopamine neurotrophic factor) belongs to a new family of neurotrophic factors that exert systemic beneficial effects beyond the brain. Little is known about the role of CDNF in the cardiac context. Herein we investigated the effects of CDNF under endoplasmic reticulum-stress conditions using cardiomyocytes (humans and mice) and isolated rat hearts, as well as in rats subjected to ischemia/reperfusion (I/R). Methods and Results We showed that CDNF is secreted by cardiomyocytes stressed by thapsigargin and by isolated hearts subjected to I/R. Recombinant CDNF (exoCDNF) protected human and mouse cardiomyocytes against endoplasmic reticulum stress and restored the calcium transient. In isolated hearts subjected to I/R, exoCDNF avoided mitochondrial impairment and reduced the infarct area to 19% when administered before ischemia and to 25% when administered at the beginning of reperfusion, compared with an infarct area of 42% in the untreated I/R group. This protection was completely abrogated by AKT (protein kinase B) inhibitor. Heptapeptides containing the KDEL sequence, which binds to the KDEL-R (KDEL receptor), abolished exoCDNF beneficial effects, suggesting the participation of KDEL-R in this cardioprotection. CDNF administered intraperitoneally to rats decreased the infarct area in an in vivo model of I/R (from an infarct area of ≈44% in the I/R group to an infarct area of ≈27%). Moreover, a shorter version of CDNF, which lacks the last 4 residues (CDNF-ΔKTEL) and thus allows CDNF binding to KDEL-R, presented no cardioprotective activity in isolated hearts. Conclusions This is the first study to propose CDNF as a new cardiomyokine that induces cardioprotection via KDEL receptor binding and PI3K/AKT activation.

Acute Myocardial Infarction Reduces Respiration in Rat Cardiac Fibers, despite Adipose Tissue Mesenchymal Stromal Cell Transplant.

Adipose-derived mesenchymal stromal cell (AD-MSC) administration improves cardiac function after acute myocardial infarction (AMI). Although the mechanisms underlying this effect remain to be elucidated, the reversal of the mitochondrial dysfunction may be associated with AMI recovery. Here, we analyzed the alterations in the respiratory capacity of cardiomyocytes in the infarcted zone (IZ) and the border zone (BZ) and evaluated if mitochondrial function improved in cardiomyocytes after AD-MSC transplantation. Female rats were subjected to AMI by permanent left anterior descending coronary (LAD) ligation and were then treated with AD-MSCs or PBS in the border zone (BZ). Cardiac fibers were analyzed 24 hours (necrotic phase) and 8 days (fibrotic phase) after AMI for mitochondrial respiration, citrate synthase (CS) activity, F0F1-ATPase activity, and transmission electron microscopy (TEM). High-resolution respirometry of permeabilized cardiac fibers showed that AMI reduced numerous mitochondrial respiration parameters in cardiac tissue, including phosphorylating and nonphosphorylating conditions, respiration coupled to ATP synthesis, and maximal respiratory capacity. CS decreased in IZ and BZ at the necrotic phase, whereas it recovered in BZ and continued to drop in IZ over time when compared to Sham. Exogenous cytochrome c doubled respiration at the necrotic phase in IZ. F0F1-ATPase activity decreased in the BZ and, to more extent, in IZ in both phases. Transmission electron microscopy showed disorganized mitochondrial cristae structure, which was more accentuated in IZ but also important in BZ. All these alterations in mitochondrial respiration were still present in the group treated with AD-MSC. In conclusion, AMI led to mitochondrial dysfunction with oxidative phosphorylation disorders, and AD-MSC improved CS temporarily but was not able to avoid alterations in mitochondria function over time.

Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy.

Chagas disease discovered more than a century ago remains an incurable disease. The objective of this work was to investigate the therapeutic potential of cardiomyocytes derived from mouse embryonic stem cells (CM-mESC) in a model of chronic Chagasic cardiomyopathy (CCC). Mouse embryonic stem cells (mESC) were characterized, transduced with luciferase, and submitted to cardiac differentiation. CM-mESC were labeled with superparamagnetic iron oxide particles. To induce CCC, mice were infected with Brazil strain trypomastigotes. At 150 days post-infection (dpi), infected animals were treated with CM-mESC or PBS. Cells were detected by magnetic resonance imaging (MRI) and bioluminescence. Cardiac function was evaluated by MRI and electrocardiogram at 150 and 196 dpi. CCC mice showed significant differences in MRI and ECG parameters compared to non-infected mice. However, no differences were observed in contractile and electrical parameters between cell and PBS injected groups, 45 days after cell transplantation. Cells were detected 24 h after transplantation by MRI. CM-mESC bioluminescence tracking demonstrated over 90% decrease in signal 8 days after treatment. Nevertheless, the Infected + CM-mESC group showed a significant reduction in the percentage of collagen fibers when compared to the Infected + PBS group. In conclusion, CM-mESC therapy was not effective in reversing cardiac functional changes induced by Chagas disease despite some improvement in myocardial fibrosis.

Periapical and Endodontic Status Scale for Endodontically Treated Teeth and Their Association with Maxillary Sinus Abnormalities: A Cone-beam Computed Tomographic Study.

INTRODUCTION: This retrospective cross-sectional study investigated the applicability of the periapical and endodontic status scale (PESS) to determine the association of endodontically treated teeth with maxillary sinus (MS) abnormalities through cone-beam computed tomographic imaging. METHODS: A total of 631 endodontically treated teeth were analyzed. MS abnormalities were classified as mucosal thickening, sinus polyp, antral pseudocyst, nonspecific opacification, periostitis, and antral calcification. The PESS was used to evaluate the quality of endodontic treatment as well as periapical tissue conditions. The data were analyzed by chi-square tests (P < .05). RESULTS: MS abnormalities were detected in 70.52% of the sample, with a greater prevalence of mucosal thickening (38.19%), whereas periapical lesions were observed in 55.94% of the cases. Treated root canals with unsatisfactory filling, homogeneity, and coronal sealing had an odds Ratio (OR) of 2.21, 2.88, and 2.99, respectively (P < .001). Periapical lesions larger than 5 mm (OR = 314.95), in more than 1 root (OR = 3.72), involving the furcation region (OR = 5.21), in contact with important structures (OR = 7.37), and with cortical bone destruction (OR = 4.09) were significantly related to the presence of MS abnormalities (P < .001). An OR of 99,668 was observed in periostitis lesions greater than 5 mm (P < .001). CONCLUSIONS: The PESS proved to be an important tool for the analysis of endodontic and periapical conditions and was applicable to determine potential associations with MS abnormalities.

Combined high-frequency and Doppler ultrasound in early diagnosis of atrophoderma of Pasini and Pierini.

Atrophoderma of Pasini and Pierini is a skin disorder affecting dermal collagen and is clinically characterized by well-defined plaques of depressed skin. Histopathological changes are subtle, and in most cases, the diagnosis requires a comparative study with healthy skin from the same anatomical site. High frequency ultrasound is a useful imaging method for diagnosis of atrophic skin changes. A case is presented in which ultrasound can support the clinical and the histopathological diagnosis of atrophoderma of Pasini and Pierini.

Combined high-frequency and Doppler ultrasound in early diagnosis of atrophoderma of Pasini and Pierini

Abstract: Atrophoderma of Pasini and Pierini is a skin disorder affecting dermal collagen and is clinically characterized by well-defined plaques of depressed skin. Histopathological changes are subtle, and in most cases, the diagnosis requires a comparative study with healthy skin from the same anatomical site. High frequency ultrasound is a useful imaging method for diagnosis of atrophic skin changes. A case is presented in which ultrasound can support the clinical and the histopathological diagnosis of atrophoderma of Pasini and Pierini.

Prevalence of atrial fibrillation and stroke risk assessment based on telemedicine screening tools in a primary healthcare setting.

BACKGROUND: Worldwide atrial fibrillation (AF) prevalence varies between 0.1% and 4.0%, and has been increasing. Little is known about the prevalence of AF in Brazil. Our objective was to estimate the prevalence of AF in several regions of Brazil using recordings of long-distance electrocardiogram (ECG) transmission. METHODS: Patients from 125 outpatient general practitioner units covered by the telemedicine service of the Federal University of São Paulo were included. Only one ECG was considered per patient. A scripted telephone interview was also performed. We analyzed the data to project the prevalence of AF in the Brazilian population and estimate it for the year 2025. The overall AF prevalence was calculated based on ECGs from primary care units where patients went for routine visits. RESULTS: Based on 676,621 ECG exams from January 2009 through April 2016, the mean age (±SD) of patients was 51.38 (±19.05) years, with 57.5% being female. The 7-year period prevalence of AF was 2.2% (n = 14,968). The prevalence of AF countrywide was projected to be 1.5% in 2016 and 1.7% in 2025. In the subset of patients with AF who were interviewed (n = 301), 91 (30.2%) were not receiving any type of treatment for rate or rhythm control. Among patients interviewed, 189 (62.8%) were at high risk for stroke; only 28 (14.8%) were regular oral anticoagulant users. CONCLUSIONS: Our study highlights the importance of screening for AF in the primary care setting in Brazil and identifies important gaps in the treatment of AF in this population.

Comparison of Biological and Mechanical Prostheses for Heart Valve Surgery: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The choice of a mechanical (MP) or biological prosthesis (BP) for patients with valvular heart disease undergoing replacement is still not a consensus. OBJECTIVE: We aimed to determine the clinical outcomes of MP or BP placement in those patients. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared biological prostheses and mechanical prostheses in patients with valvular heart diseases and assessed the outcomes. RCTs were searched in the MEDLINE, EMBASE, LILACS, CENTRAL, SCOPUS and Web of Science (from inception to November 2014) databases. Meta-analyses were performed using inverse variance with random effects models. The GRADE system was used to rate the quality of the evidence. A P-value lower than 0.05 was considered significant. RESULTS: A total of four RCTs were included in the meta-analyses (1,528 patients) with follow up ranging from 2 to 20 years. Three used old generation mechanical and biological prostheses, and one used contemporary prostheses. No significant difference in mortality was found between BP and MP patients (risk ratio (RR = 1.07; 95% CI 0.99-1.15). The risk of bleeding was significantly lower in BP patients than MP patients (RR = 0.64; 95% CI 0.52-0.78); however, reoperations were significantly more frequent in BP patients (RR = 3.60; 95% CI 2.44-5.32). There were no statistically significant differences between BP and MP patients with respect to systemic arterial embolisms and infective endocarditis (RR = 0.93; 95% CI 0.66-1.31, RR = 1.21; CI95% 0.78-1.88, respectively). Results in the trials with modern and old prostheses were similar. CONCLUSIONS: The mortality rate and the risk of thromboembolic events and endocarditis were similar between BP and MP patients. The risk of bleeding was approximately one third lower for BP patients than for MP patients, while the risk of reoperations was more than three times higher for BP patients.

Back pain and sagittal spine alignment in obese patients eligible for bariatric surgery.

OBJECTIVE: The objective of this research was to evaluate the prevalence of cervical and lumbar pain in obese patients eligible for bariatric surgery and to investigate possible changes in sagittal spine alignment in these patients. METHODS: The following parameters were compared in 30 obese patients and a control group of 25 non-obese volunteers: body mass index, prevalence of cervical and lumbar pain assessed by visual analog scale (VAS), Neck Disability Index [NDI] and Oswestry Disability Index [ODI], as well as radiographic parameters of the spine and pelvis measured with Surgimap software. RESULTS: The cervical and lumbar VAS and the NDI and ODI were significantly worse in obese patients. Compared with the control group, the cervical sagittal vertical axis (cSVA) of the obese group had higher variance (p value = 0.0025) and the cervical lordosis was diminished (p value = 0.0023). Thoracic kyphosis, lumbar lordosis, and the pelvic parameters were not significantly different between the groups. CONCLUSIONS: Obese patients demonstrated lower functional performance compared with their non-obese counterparts, while cervical lordosis was diminished and the cSVA was increased in obese patients. These slides can be retrieved under Electronic Supplementary Material.

Comparison of Biological and Mechanical Prostheses for Heart Valve Surgery: A Systematic Review of Randomized Controlled Trials / Comparação de Próteses Biológicas e Mecânicas para Cirurgia de Válvula Cardíaca: Revisão Sistemática de Estudos Controlados Randomizados

Abstract Background: The choice of a mechanical (MP) or biological prosthesis (BP) for patients with valvular heart disease undergoing replacement is still not a consensus. Objective: We aimed to determine the clinical outcomes of MP or BP placement in those patients. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared biological prostheses and mechanical prostheses in patients with valvular heart diseases and assessed the outcomes. RCTs were searched in the MEDLINE, EMBASE, LILACS, CENTRAL, SCOPUS and Web of Science (from inception to November 2014) databases. Meta-analyses were performed using inverse variance with random effects models. The GRADE system was used to rate the quality of the evidence. A P-value lower than 0.05 was considered significant. Results: A total of four RCTs were included in the meta-analyses (1,528 patients) with follow up ranging from 2 to 20 years. Three used old generation mechanical and biological prostheses, and one used contemporary prostheses. No significant difference in mortality was found between BP and MP patients (risk ratio (RR = 1.07; 95% CI 0.99-1.15). The risk of bleeding was significantly lower in BP patients than MP patients (RR = 0.64; 95% CI 0.52-0.78); however, reoperations were significantly more frequent in BP patients (RR = 3.60; 95% CI 2.44-5.32). There were no statistically significant differences between BP and MP patients with respect to systemic arterial embolisms and infective endocarditis (RR = 0.93; 95% CI 0.66-1.31, RR = 1.21; CI95% 0.78-1.88, respectively). Results in the trials with modern and old prostheses were similar. Conclusions: The mortality rate and the risk of thromboembolic events and endocarditis were similar between BP and MP patients. The risk of bleeding was approximately one third lower for BP patients than for MP patients, while the risk of reoperations was more than three times higher for BP patients.

Resumo Fundamento: A escolha de próteses mecânicas ou biológicas para pacientes com doença de válvula cardíaca ainda não é um consenso. Objetivo: Determinar os desfechos clínicos de próteses mecânicas e biológicas nesses pacientes. Métodos: Conduzimos uma revisão sistemática e metanálise e estudos controlados randomizados (RCTs) que compararam próteses mecânicas e biológicas em pacientes com doenças de válvulas cardíaca, e avaliamos seus resultados. A busca por RCTs foi feita nas bases de dados MEDLINE, EMBASE, LILACS, CENTRAL, SCOPUS e Web of Science (do início a novembro de 2014). As metanálises foram realizadas usando variação inversa com modelos de efeitos aleatórios. Usamos o sistema GRADE para avaliar a qualidade da evidência. Um valor menor que 0,05 foi considerado significativo. Resultados: Um total de quatro RCTs foi incluído na metanálise (1528 pacientes) com acompanhamento de 2 a 20 anos. Em três estudos, foram utilizadas próteses mecânicas e biológicas mais antigas, e em um estudo próteses contemporâneas. Não foi observada diferença de mortalidade entre os pacientes que receberam próteses mecânicas e biológicas (risco relativo, RR = 1,07; IC95% 0,99-1,15). O risco de sangramento foi significativamente mais baixo nos pacientes que receberam próteses biológicas que naqueles com próteses mecânicas (RR = 0,64; IC95% 0,52-0,78). Contudo, as reoparações foram mais frequentes em pacientes com próteses biológicas (RR = 3,60; IC95% 2,44-5,32). Não houve diferenças estatisticamente significativas entre pacientes com próteses biológicas e mecânicas em relação à embolia arterial sistêmica e endocardite infecciosa (RR = 0,93; IC95% 0,66-1,31; RR = 1,21; IC95% 0,78-1,88, respectivamente). Resultados entre os estudos com próteses modernas e antigas foram similares. Conclusões: A taxa de mortalidade e o risco de eventos tromboembólicos e endocardite foram similares entre os pacientes que receberam próteses biológicas e mecânicas. O risco de sangramentos foi aproximadamente um terço menor nos pacientes com próteses biológicas que mecânicas, ao passo que o risco de reoperação foi mais que três vezes maior nos pacientes com próteses biológicas.

Regional QT Interval Dispersion as an Early Predictor of Reperfusion in Patients with Acute Myocardial Infarction after Fibrinolytic Therapy / A Dispersão do Intervalo QT Regional como Preditor Precoce de Reperfusão em Pacientes com Infarto Agudo do Miocárdio Pós-terapia Fibrinolítica

Abstract Background: Patients with ST-elevation acute myocardial infarction attending primary care centers, treated with pharmaco-invasive strategy, are submitted to coronary angiography within 2-24 hours of fibrinolytic treatment. In this context, the knowledge about biomarkers of reperfusion, such as 50% ST-segment resolution is crucial. Objective: To evaluate the performance of QT interval dispersion in addition to other classical criteria, as an early marker of reperfusion after thrombolytic therapy. Methods: Observational study including 104 patients treated with tenecteplase (TNK), referred for a tertiary hospital. Electrocardiographic analysis consisted of measurements of the QT interval and QT dispersion in the 12 leads or in the ST-segment elevation area prior to and 60 minutes after TNK administration. All patients underwent angiography, with determination of TIMI flow and Blush grade in the culprit artery. P-values < 0.05 were considered statistically significant. Results: We found an increase in regional dispersion of the QT interval, corrected for heart rate (regional QTcD) 60 minutes after thrombolysis (p = 0.06) in anterior wall infarction in patients with TIMI flow 3 and Blush grade 3 [T3B3(+)]. When regional QTcD was added to the electrocardiographic criteria for reperfusion (i.e., > 50% ST-segment resolution), the area under the curve increased to 0.87 [(0.78-0.96). 95% IC. p < 0.001] in patients with coronary flow of T3B3(+). In patients with ST-segment resolution >50% and regional QTcD > 13 ms, we found a 93% sensitivity and 71% specificity for reperfusion in T3B3(+), and 6% of patients with successful reperfusion were reclassified. Conclusion: Our data suggest that regional QTcD is a promising non-invasive instrument for detection of reperfusion in the culprit artery 60 minutes after thrombolysis.

Resumo Fundamento: Pacientes com infarto do miocárdico com elevação do segmento-ST atendidos em centros de atendimento primário e tratados de acordo com a estratégia fármaco-invasiva são submetidos à fibrinólise seguida de coronariografia em período de 2-24h. Neste cenário, o conhecimento de marcadores de reperfusão como a redução em 50% do segmento-ST é fundamental. Objetivo: Analisar o desempenho da dispersão do intervalo QT em adição aos critérios clássicos, como marcador precoce de reperfusão pós-terapia trombolítica. Métodos: Estudo observacional com a inclusão de 104 pacientes tratados com tenecteplase (TNKase) e referenciados a hospital de atendimento terciário. A análise dos eletrocardiogramas (ECG) consistiu em mensuração do intervalo QT e sua dispersão nas 12 derivações, e também apenas na região com supradesnivelamento-ST antes e 60min pós-TNKase. A angiografia foi realizada em todos os pacientes com obtenção do fluxo TIMI e Blush da artéria culpada. Foram considerados significantes valores de p < 0,05. Resultados: Observamos aumento da dispersão do intervalo QT, corrigido pela frequência cardíaca, regional (dQTcR) 60min pós-lise (p = 0,006) em infartos de parede anterior nos casos com fluxo TIMI 3 e Blush 3 [T3B3(+)]. Adicionando a dQTcR ao critério ECG (redução do ST > 50%) de reperfusão, a área sob a curva aumentou para 0,87 [(0,78-0,96), IC95%, p < 0,001] em pacientes com fluxo coronário T3B3(+). Nos pacientes com critério de ECG para reperfusão e dQTcR > 13 ms a sensibilidade e especificidade foram 93% e 71%, respectivamente, para reperfusão em T3B3(+), possibilitando reclassificar 6% dos pacientes com sucesso de reperfusão. Conclusão: Os dados sugerem a dQTcR como instrumento promissor na identificação não invasiva de reperfusão na artéria coronária culpada, 60min pós-trombólise.

Alteração letrocardiográfica incomum por oclusão de coronária descendente anterior: padrão "De Winter" / Uncommon ECG abnormality due to proximal occlusion of lad coronary artery: De Winter pattern

O eletrocardiograma (ECG) é fundamental na avaliação dos pacientes com síndrome coronariana aguda (SCA), pois possibilita a identificação precoce dos pacientes com sinais de oclusão coronariana (infarto agudo do miocárdio com supradesnivelamento do segmento ST - IAMCSSST), que se beneficiam com estratégias de reperfusão miocárdica de emergência. Os casos de SCA sem supradesnivelamento de segmento ST pressupõem ausência de oclusão coronariana, e o ECG pode mostrar sinais de isquemia como inversão simétrica de ondas T, infradesnivelamento de segmento ST, ou mesmo ser normal em até 15% dos casos. No entanto, recentemente foi descrito um padrão eletrocardiográfico raro, conhecido como padrão "De Winter", relacionado à oclusão coronariana aguda da artéria descendente anterior (ADA) em seu terço proximal, na ausência de supradesnivelamento de segmento ST. Este é o relato de um paciente jovem, do sexo masculino, com quadro clínico anginoso típico, menos de uma hora depois de angioplastia eletiva da ADA, que apresentou padrão "De Winter" no ECG e teve confirmada trombose aguda de stent. O reconhecimento desse padrão eletrocardiográfico incomum é fundamental para garantir terapia de reperfusão coronariana emergencial em casos de síndrome coronariana aguda

he electrocardiogram (ECG) is a crucial tool in the evaluation of patients with acute coronary syndrome (ACS), since it allows the early identification of patients with signs of coronary occlusion (ST-elevation myocardial infarction ­ STEMI), who benefit from emergency myocardial reperfusion strategies. On the other hand, cases of non-ST-elevation ACS presumably have no coronary occlusion, and the ECG may show signs of ischemia such as symmetrical T-wave inversion, ST-segment depression, or even be normal in up to 15% of cases. However, a rare ECG pattern, known as the "De Winter" pattern, related to an acute occlusion of the Left Anterior Descending (LAD) coronary artery in its proximal third segment, has been recently described without ST-segment elevation. This is a case report of a young male patient with typical chest pain symptoms less than one hour after an elective LAD angioplasty, who presented with "De Winter" pattern on the ECG and had confirmed acute stent thrombosis. The recognition of this unusual electrocardiographic pattern is essential to guarantee emergency coronary reperfusion therapy in cases of acute coronary syndrome

Dissecção aguda de aorta manifestando-se com infarto agudo do miocárdio: relato de caso / Acute aortic dissection manifesting with acute myocardial infarction: case report

A dissecção aguda da aorta (DAA) é uma emergência cardiovascular que acarreta mortalidade alta, 50% a 68% em 48 horas e até 85% em um mês. Este caso refere-se a um homem com 65 anos, ex-tabagista, que teve precordialgia com queimação irradiada para membros superiores, associada a náuseas. O eletrocardiograma mostrou upradesnivelamento ST em parede inferolateral. Recebeu tratamento para infarto agudo do miocárdio com AAS, clopidogrel, enoxaparina e tenecteplase. O cateterismo cardíaco evidenciou DAA tipo A de Stanford e coronárias sem obstruções. O ecocardiograma transtorácico mostrou insuficiência aórtica moderada e dissecção estendendo-se da raiz da aorta até a porção descendente proximal. O paciente foi submetido à cirurgia de Bentall de Bono e enxerto safeno-coronário direito devido à obstrução durante a cirurgia, com boa evolução pós-operatória. A DAA continua a ser um desafio diagnóstico na sala de emergência. De acordo com International Registry of Acute Aortic Dissection, os achados clínicos nas dissecções tipo A incluem dor torácica súbita e intensa (86%), irradiação dorsal (47%), sopro de insuficiência aórtica (44%), assimetria de pressão arterial (50%) e pulsos (30%), alargamento de mediastino à radiografia de tórax (63%) e supradesnivelamento de ST (4%), majoritariamente por oclusão de óstio da coronária direita. O caso destaca-se pela evolução favorável a despeito do tratamento com potencial catastrófico inicialmente direcionado para doença coronariana aguda aterotrombótica

Acute Aortic Dissection (AAD) is a cardiovascular emergency that entails high mortality - 50-68% in 48 hours and up to 85% in one month. This case involves a 65-year-old male ex-smoker who had onset of precordial pain with a burning sensation, radiating into the upper limbs, in combination with nausea. Electrocardiogram showed inferolateral wall ST elevation. He received treatment for acute myocardial infarction with acetylsalicylic acid, clopidogrel, enoxaparin and tenecteplase. Cardiac catheterization revealed Stanford type A AAD and unobstructed coronary arteries. Transthoracic echocardiogram showed moderate aortic regurgitation and aortic dissection extending from the aortic root to its proximal descending portion. The patient underwent a Bentall-De Bono procedure and right coronary artery bypass grafting using the saphenous vein due to obstruction during surgery, with good postoperative progress. AAD remains a diagnostic challenge in the emergency room. According to the International Registry of Acute Aortic Dissection, clinical findings in type A dissections include: sudden severe chest pain (86%), dorsal irradiation (47%), aortic regurgitation murmur (44%), asymmetric blood pressure (50%) or pulse (30%), mediastinal widening on chest radiograph (63%) and ST-segment elevation (4%), mainly due to right coronary ostium occlusion. The case is distinctive because of favorable progress in spite of the potentially catastrophic treatment initially targeting acute coronary atherothrombotic disease