Involvement of Interleukin-1 β/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects.@*METHODS@#Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively.@*RESULTS@#After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01).@*CONCLUSION@#EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway.

Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies / 中国结合医学杂志

OBJECTIVE@#To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).@*METHODS@#Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.@*RESULTS@#The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs.@*CONCLUSIONS@#STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats / 中国中药杂志

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

Acompanhamento a longo prazo de paciente do sexo masculino com fibroma cardíaco assintomático / Long-Term follow-up of an asymptomatic man with a cardiac fibroma

Descreve-se o caso de um homem de 19 anos assintomático com fibroma de ventrículo esquerdo em acompanhamento por 15 anos, sem tratamento.(AU)

Here we describe a case of a 19-year-old asymptomatic man with a left ventricular fibroma on follow-up for 15 years with no treatment required.(AU)

Fatores associados a anormalidades na cintilografia de perfusão miocárdica de pacientes diabéticos / Factors associated with abnormalities on myocardial perfusion scintigraphy in diabetic patients

O diabetes melito é o maior fator de risco para doença arterial coronariana. Além da longa duração de diabetes, outros fatores, como presença de doença arterial periférica e tabagismo são fortes preditores para anormalidades na cintilografia de perfusão do miocárdio. O objetivo deste estudo foi avaliar o impacto dos fatores de risco de pacientes diabéticos nos resultados da cintilografia de perfusão do miocárdio e comparar com os resultados de pacientes não diabéticos em uma clínica de medicina nuclear. Foi realizado um estudo transversal retrospectivo por meio da análise de prontuários de pacientes que realizaram cintilografia miocárdica no período de 2010 a 2019. Foram avaliados 34.736 prontuários. Analisando a fase de estresse da cintilografia de perfusão do miocárdio, os portadores de diabetes melito precisaram receber estímulo farmacológico duas vezes mais que os não diabéticos para sua realização. Também foram avaliados fatores que tivessem impacto negativo no resultado da cintilografia de perfusão do miocárdio, e foi visto que o diabetes melito (33,6%), a insulinoterapia (18,1%), a hipertensão arterial sistêmica (69,9%), a dislipidemia (53%), o sedentarismo (83,1%), o uso de estresse farmacológico (50,6%), a dor torácica típica (8,5%) e a angina limitante durante o teste (1,7%) estiveram associados significativamente (p<0,001) a anormalidades neste exame. (AU)

Diabetes mellitus (DM) is the greatest risk factor for coronary artery disease. In addition to a long duration of diabetes, the presence of peripheral arterial disease and smoking are strong predictors of abnormalities on myocardial perfusion scintigraphy (MPS). This study aimed to assess the impact of risk factors in diabetic patients on MPS results and compare them with those of non-diabetic patients in a nuclear medicine clinic. A retrospective cross-sectional study was performed through the analysis of the medical records of patients who underwent MPS in 2010­2019. A total of 34,736 medical records were evaluated. Analyzing the stress phase of MPS, DM patients required two-fold more pharmacological stimulation than non-diabetic patients for MPS. Factors that negatively impact the MPS results were also evaluated, and DM (33.6%), insulin therapy (18.1%), systemic arterial hypertension (69.9%), dyslipidemia (53%), sedentary lifestyle (83.1%), use of pharmacological stress (50.6%), typical chest pain (8.5%), and limiting angina during the test (1.7%) were significantly associated (p < 0.001) with test abnormalities. (AU)

Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Deformação miocárdica (strain) e fibrose miocárdica na forma cardíaca leve da Doença de Chagas / Myocardial deformation (strain) and myocardial fibrosis in mild cardiac Chagas Disease

Fundamento: A identificação precoce do dano miocárdico parece ser importante na abordagem do paciente com doença de Chagas. A ecocardiografia com strain obtida por speckle tracking e a avaliação da fibrose miocárdica por meio da ressonância magnética cardíaca podem ser métodos diagnósticos promissores nesse sentido. Objetivo: Avaliar o acometimento miocárdico especificamente na forma crônica cardíaca leve da doença de Chagas por meio do strain por speckle tracking e da fibrose miocárdica pela ressonância magnética cardíaca, além de suas correlações. Método: Estudo de corte transversal que analisou portadores da forma cardíaca crônica leve da doença de Chagas (fração de ejeção preservada) submetidos à ecocardiografia com strain por speckle tracking e à ressonância magnética cardíaca. Resultados: Foram incluídos 21 participantes (mulheres: 62%; idade: 54 ± 5 anos). A prevalência de fibrose miocárdica por meio do realce tardio miocárdico foi de 50%. O strain longitudinal global encontrava-se diminuído em 17 pacientes (81%), com mediana de 14,1% (intervalo interquartil de 12,1 a 16,3). Os valores do mapa T1 encontravam-se, em média, elevados nos portadores de doença de Chagas (993 ± 163 ms). O mapa T1 foi significativamente correlacionado com o strain longitudinal global (r= 0,634; p = 0,015). Além disso, o índice de dispersão mecânica, obtido por strain, estava aumentado (> 55 ms) em 84%, com a maior área sob a curva Característica de Operação do Receptor (área sob a curva de 0,696; intervalo de confiança de 95% de 0,412-0,981) para discriminação de fibrose pelo realce tardio miocárdico. Conclusão: O strain miocárdico e o mapa T1 se comportam como marcadores precoces do dano miocárdico na cardiopatia chagásica crônica leve. O índice de dispersão mecânica estava elevado e foi o parâmetro que melhor se correlacionou com o realce tardio miocárdico. (AU)

Background: The early identification of myocardial damage seems important in the management of patients with Chagas disease. However, it is unknown whether speckle tracking echocardiography strain and cardiac magnetic resonance imaging are promising methods for assessing myocardial involvement and fibrosis, respectively. Objective: To evaluate myocardial involvement in the mild chronic cardiac form of Chagas disease using speckle tracking strain and myocardial fibrosis by cardiac magnetic resonance and assess their correlations. Method: This cross-sectional study analyzed patients with the mild chronic cardiac form of Chagas disease (preserved ejection fraction) using speckle tracking echocardiography and cardiac magnetic resonance. Results: The study included 21 participants (women: 62%; age: 54 ± 5 years). The prevalence of myocardial fibrosis was 50% on delayed myocardial enhancement. The median global longitudinal strain was decreased (14.1%; interquartile range, 12.1­16.3%) in 17 patients (81%). The mean T1 mapping value was high in patients with Chagas disease (993 ± 163 ms). The T1 map was significantly correlated with the global longitudinal strain (r = 0.634; p = 0.015). In addition, the mechanical dispersion index obtained by strain was increased (>55 ms) by 84%, with the largest area under the receiver operating characteristic curve (area under the curve, 0.696; 95% confidence interval, 0.412­0.981) for fibrosis discrimination by delayed myocardial enhancement. Conclusion: Myocardial strain and T1 mapping are early markers of myocardial damage in mild chronic Chagas heart disease. The mechanical dispersion index was high and the most closely correlated with delayed myocardial enhancement. (AU)

Comportamento dos critérios de uso apropriado da cintilografia de perfusão miocárdica na avaliação de assintomáticos de alto risco cardiovascular ou com doença coronária conhecida / Appropriate use of myocardial perfusion scintigraphy criteria for assessing asymptomatic patients with high cardiovascular risk or known coronary disease

Fundamentos: O papel da cintilografia de perfusão miocárdica em pacientes assintomáticos permanece restrito a situações clínicas muito específicas, muitas delas abordadas nos Critérios de Uso Apropriado (AUC) de Cintilografia de Perfusão Miocárdica. Objetivo: Realizar uma análise crítica da aplicação desses critérios nas indicações de exames realizados em pacientes assintomáticos do Instituto Dante Pazzanese de Cardiologia, cuja população é notadamente de alto risco cardiovascular. Métodos: Foram selecionados pacientes assintomáticos que realizaram cintilografia de perfusão miocárdica para pesquisa de isquemia. As indicações dos exames foram classificadas em apropriadas, inapropriadas ou incertas. Hipocaptação fixa, hipocaptação transitória ou dilatação isquêmica transitória foram consideradas exames alterados. Na análise estatística, buscou-se avaliar a correlação entre o grau de recomendação das indicações e a presença de exames alterados. Resultados: A partir de uma seleção inicial de 2.999 prontuários, 490 foram considerados assintomáticos e incluídos conforme critérios de inclusão estabelecidos previamente. Apenas 9,8% das indicações foram inapropriadas, enquanto que 61,4% foram apropriadas, e 28,8% foram incertas. A hipocaptação fixa do radiofármaco ocorreu em 43,5% dos casos e a hipocaptação transitória, em 16,1%. Solicitar o exame de maneira apropriada ou incerta foi fator preditor de exame com resultado alterado nesta população. Conclusão: O uso dos critérios de uso apropriado da cintilografia de perfusão miocárdica mostrou-se eficaz em predizer exames alterados em uma população assintomática de alto risco cardiovascular, especialmente no grupo de pacientes com indicação incerta, o que pode significar que algumas das indicações consideradas incertas talvez sejam apropriadas para uma população de alto risco cardiovascular. (AU)

The potential role of long non-coding RNA Dnm3os in the activation of cardiac fibroblasts / 生物医学工程学杂志

Long non-coding RNA (lncRNA) Dnm3os plays a critical role in peritendinous fibrosis and pulmonary fibrosis, but its role in the process of cardiac fibrosis is still unclear. Therefore, we carried out study by using the myocardial fibrotic tissues obtained by thoracic aortic constriction (TAC) in an early study of our group, and the

Alterações cardiorrespiratórias em indivíduos hemiparéticos crônicos pós-acidente vascular cerebral / Cardiorespiratory changes in chronic post-stroke hemiparetic patients

Objetivo: Analisar a função cardiorrespiratória em pacientes he- miparéticos crônicos pós-acidente vascular cerebral. Métodos: Estudo retrospectivo, por meio da análise de dados de prontuários de pacientes submetidos ao teste de caminhada de 6 minutos e manovacuometria em uma clínica de fisioterapia de um centro universitário. Foram analisados os dados de sete prontuários. Re- sultados: A média de metros percorridos pelos participantes no teste de caminhada de 6 minutos foi de 199,5. Os valores percentuais da manovacuometria foram de -41,34 na pressão inspiratória máxima e de 57,85 na pressão expiratória máxima. Conclusão: Os dados desta pesquisa sugerem que indivíduos hemiparéticos crônicos apresentam fadiga respiratória e muscular, diminuição da capacidade funcional durante a marcha e fraqueza dos músculos respiratórios.

Objective: To analyze the cardiorespiratory function in chronic post-stroke hemiparetic patients. Methods: This is a retrospective study, through data analysis of medical records from patients who underwent the 6-minute walk test and manovacuometry, in a physical therapy clinic of a university center. Results: The mean number of meters walked by participants in the 6-minut walk test was 199.5 meters. The percentage values of manovacuometry were -41,34 in the maximun inspiratory pressure and 57.85 in the maximun expiratory pressure. Conclusion: The data from this survey suggest that chronic hemiparetic individuals have respiratory and muscle fatigue, decreased functional capacity during gait, and respiratory muscle weakness.

Cardiovascular involvement in COVID-19: not to be missed

Abstract In December 2019, a striking appearance of new cases of viral pneumonia in Wuhan led to the detection of a novel coronavirus (SARS-CoV2). By analyzing patients with severe manifestations, it became apparent that 20 to 35% of patients who died had preexisting cardiovascular disease. This finding warrants the important need to discuss the influence of SARS-CoV2 infection on the cardiovascular system and hemodynamics in the context of clinical management, particularly during mechanical ventilation. The SARS-CoV2 enters human cells through the spike protein binding to angiotensin-converting enzyme 2 (ACE2), which is important to cardiovascular modulation and endothelial signaling. As ACE2 is highly expressed in lung tissue, patients have been progressing to acute respiratory injury at an alarming frequency during the Coronavirus Disease (COVID-19) pandemic. Moreover, COVID-19 leads to high D-dimer levels and prothrombin time, which indicates a substantial coagulation disorder. It seems that an overwhelming inflammatory and thrombogenic condition is responsible for a mismatching of ventilation and perfusion, with a somewhat near-normal static lung compliance, which describes two types of pulmonary conditions. As such, positive pressure during invasive mechanical ventilation (IMV) must be applied with caution. The authors of this review appeal to the necessity of paying closer attention to assess microhemodynamic repercussion, by monitoring central venous oxygen saturation during strategies of IMV. It is well known that a severe respiratory infection and a scattered inflammatory process can cause non-ischemic myocardial injury, including progression to myocarditis. Early strategies that guide clinical decisions can be lifesaving and prevent extended myocardial damage. Moreover, cardiopulmonary failure refractory to standard treatment may necessitate the use of extreme therapeutic strategies, such as extracorporeal membrane oxygenation.

Biomarcadores de Lesão Miocárdica e Complicações Cardíacas Associadas à Mortalidade em Pacientes com COVID-19 / Myocardial Injury Biomarkers and Cardiac Complications Associated with Mortality in Patients with COVID-19

Resumo Fundamento O SARS-CoV-2 é um vírus de RNA emergente associado à doença respiratória aguda grave conhecida como COVID-19. Embora a COVID-19 seja predominantemente uma doença pulmonar, alguns pacientes apresentam graves danos cardiovasculares. Realizamos uma síntese de evidências quantitativas de dados clínicos, biomarcadores de lesão miocárdica e complicações cardíacas associadas ao óbito hospitalar em pacientes com COVID-19. Métodos Buscamos nas bases de dados PubMed, Embase e Google Scholar para identificar estudos que comparassem dados clínicos, biomarcadores de lesão miocárdica e complicações cardíacas entre pacientes sobreviventes e não sobreviventes da COVID-19. Os tamanhos dos efeitos foram apresentados como diferença média ou diferença média padronizada para variáveis contínuas e razão de risco para variáveis dicotômicas, com intervalos de confiança de 95%. Foi utilizado um modelo de efeitos aleatórios para agrupar os resultados. Resultados Foram incluídos seis estudos retrospectivos que relataram dados de 1.141 pacientes (832 sobreviventes e 309 não sobreviventes). Verificamos que condições cardiovasculares subjacentes; elevação de troponina cardíaca I de alta sensibilidade; N-terminal do pró-hormônio do peptídeo natriurético do tipo B e creatina quinase-MB; e complicações cardíacas foram associadas ao aumento do risco de óbito em pacientes com infecção por SARS-CoV-2. Conclusões A confirmação de que condições cardiovasculares subjacentes, elevação de biomarcadores de lesão miocárdica durante a infecção por COVID-19 e descompensação cardiovascular aguda são preditores de mortalidade na infecção por SARS-CoV-2 deve incentivar novas pesquisas para esclarecer possíveis mecanismos e testar tratamentos adequados. (Arq Bras Cardiol. 2020; 115(2):273-277)

Abstract Background SARS-CoV-2 is an emerging RNA virus associated with a severe acute respiratory disease known as COVID-19. Although COVID-19 is predominantly a pulmonary disease, some patients have severe cardiovascular damage. We performed a quantitative evidence synthesis of clinical data, myocardial injury biomarkers, and cardiac complications associated with in-hospital death in patients with COVID-19. Methods We searched the databases PubMed, Embase, and Google Scholar to identify studies comparing clinical data, myocardial injury biomarkers, and cardiac complications between non-survivors and survivors of COVID-19. Effect sizes were reported as mean difference or standardized mean difference for continuous variables and risk ratio for dichotomous variables with 95% confidence intervals. A random effects model was used to pool the results. Results Six retrospective studies reporting data from 1,141 patients (832 survivors and 309 non-survivors) were included. We found that underlying cardiovascular conditions; elevation of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and creatine kinase-MB; and cardiac complications were associated with increased risk of death for patients with SARS-CoV-2 infection. Conclusions The confirmation that underlying cardiovascular conditions, elevation of myocardial injury biomarkers during COVID-19 infection, and acute cardiovascular decompensation are predictors for mortality in SARS-CoV-2 infection must encourage new research to clarify potential mechanisms and test appropriate treatments. (Arq Bras Cardiol. 2020; 115(2):273-277)

Disfunção miocárdica secundária a sepse em cão: relato de caso / Myocardial dysfunction secondary to sepsis in dog: case report

A redução do empenho do miocárdio é um achado frequente em casos de sepse ou choque séptico, sendo a piometra uma das principais causas de sepse em cães. No presente trabalho relata-se um caso de sepse secundária à piometra levando à disfunção miocárdica em um canino, fêmea, da raça White West Highland Terrier, de dez anos de idade com histórico de prostração e hiporexia. Ao exame físico foi observada presença de secreção vulvar purulenta, abdômen abaulado e tenso à palpação. Foram realizados exames complementares, incluindo hemograma com resultado compatível com quadro infeccioso, bioquímica revelando hipocalemia e hipocalcemia, e exames de imagem. Observou-se por meio do exame ultrassonográfico presença de grande quantidade de líquido com celularidade em cornos e corpo uterino, compatível com piometra. Alterações compatíveis com sepse foram observadas durante o atendimento e estabilização do animal. No exame ecocardiográfico foi observado aumento dos diâmetros sistólico e diastólico do ventrículo esquerdo com diminuição da fração de encurtamento e ejeção, compatível com disfunção sistólica do ventrículo esquerdo. A referida paciente recebeu alta médica após correção cirúrgica e estabilização dos parâmetros clínicos, incluindo a disfunção sistólica, sendo relatado óbito sete dias após. Sugere-se que a causa mortis tenha sido a disfunção sistólica causada pela sepse. Conclui-se que a disfunção miocárdica é um fator determinante de prognóstico em casos de sepse, o que ressalta a importância de seu diagnóstico e tratamento precoce.

The reduction of myocardial commitment is a frequent finding in cases of sepsis or septic shock, and piometra is one of the main causes of sepsis in dogs. In the present study, the case of sepsis secondary to piometra is reported leading to myocardial dysfunction in a canine, female, of the 10-year-old White West Highland Terrier with a history of prostration and hyporexia. On physical examination, the presence of purulent vulvar secretion, bulging abdomen and taut palpation was observed. Complementary tests were performed, including blood count, biochemistry and imaging tests. It was observed through ultrasound examination the presence of a large amount of fluid with cellularity in horns and uterine body, compatible with piometra. Alterations compatible with sepsis were observed during the care and stabilization of the animal. On echocardiographic examination, an increase in systolic and diastolic diameters of the left ventricle was observed with decreased shortening and ejection fraction, compatible with systolic dysfunction of the left ventricle. The patient received medical discharge after surgical correction and stabilization of clinical parameters, and died seven days later. It is suggested that the cause of death was systolic dysfunction caused by sepsis. It is concluded that myocardial dysfunction is a prognostic determinant factor in cases of sepsis, emphasizing the importance of its diagnosis and early treatment.

Predictive value of neutrophil/lymphocyte ratio on myocardial injury in severe COVID-19 patients / 中华心血管病杂志

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.

Clinical feature changes of a COVID-19 patient from mild to critical condition and cardiopulmonary pathological results / 中华心血管病杂志

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.