Redução na Hospitalização e Aumento na Mortalidade por Doenças Cardiovasculares durante a Pandemia da COVID-19 no Brasil / Reduction in Hospitalization and Increase in Mortality Due to Cardiovascular Diseases during the COVID-19 Pandemic in Brazil

Resumo Fundamento Na pandemia pela COVID-19, o aumento da ocorrência e da mortalidade por doenças cardiovasculares (DCV) vem sendo reconhecido no mundo. No Brasil, é essencial que o impacto da COVID-19 na DCV seja analisado. Objetivos Avaliar o impacto desta pandemia nos números de internações hospitalares (IH), óbitos hospitalares (OH) e letalidade intra-hospitalar (LH) por DCV a partir de dados epidemiológicos do Sistema Único de Saúde (SUS). Métodos Estudo observacional de séries temporais por meio da análise comparativa das taxas de IH, OH e LH por DCV registrados entre janeiro e maio de 2020, usando como referência os valores obtidos no mesmo período entre 2016 e 2019 e os valores projetados por métodos de regressão linear para o ano de 2020. O nível significância estatística utilizado foi de 0,05. Resultados Em comparação com o mesmo período de 2019, houve um decréscimo de 15% na taxa de IH e de 9% no total de OH por DCV entre março e maio de 2020, acompanhado de um aumento de 9% na taxa de LH por esse grupo de doenças, sobretudo entre pacientes com idade de 20-59 anos. As taxas de IH e LH registradas em 2020 diferiram significativamente da tendência projetada para o corrente ano (p=0,0005 e 0,0318, respectivamente). Conclusões Durante os primeiros meses da pandemia, observou-se um declínio na IH associado a um aumento da LH por DCV no Brasil. Esses dados possivelmente são consequência do planejamento inadequado no manejo das DCV durante a pandemia, sendo necessária a implementação de ações imediatas para modificar esse cenário. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background In the COVID-19 pandemic, the increase in the incidence of cardiovascular diseases (CVD) and mortality from them has been recognized worldwide. In Brazil, the impact of COVID-19 on CVD must be evaluated. Objectives To assess the impact of the current pandemic on the numbers of hospital admissions (HA), in-hospital deaths (ID), and in-hospital fatality (IF) from CVD by use of national epidemiological data from the Brazilian Unified Public Health System. Methods Time-series observational study using comparative analysis of the HA, ID, and IF due to CVD recorded from January to May 2020, having as reference the values registered in the same period from 2016 to 2019 and the values projected by linear regression methods for 2020. The statistical significance level applied was 0.05. Results Compared to the same period in 2019, there was a 15% decrease in the HA rate and a 9% decrease in the total ID due to CVD between March and May 2020, followed by a 9% increase in the IF rate due to CVD, especially among patients aged 20-59 years. The HA and IF rates registered in 2020 differed significantly from the projected trend for 2020 (p = 0.0005 and 0.0318, respectively). Conclusions During the first months of the pandemic, there were a decline in HA and an increase in IF due to CVD in Brazil. These data might have resulted from the inadequate planning of the CVD management during the pandemic. Thus, immediate actions are required to change this scenario. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Left ventricular assessment in patients with systemic light chain amyloidosis: a 3-dimensional speckle tracking transthoracic echocardiographic study.

Cardiac involvement in systemic light chain (AL) amyloidosis carries a poor prognosis mainly through involvement of the left ventricular (LV) myocardium. Despite its limitations, two-dimensional transthoracic echocardiography (2D-TTE) remains the main tool used for the assessment of LV systolic function in AL patients. We hypothesize that 3D-TTE coupled with speckle tracking imaging allows earlier detection of LV systolic dysfunction than 2D-TTE in AL amyloidosis. We prospectively studied 71 subjects including 58 patients with confirmed AL amyloidosis (mean age 66 ± 10 years, 60% male) and 21 healthy control (mean age 64 ± 7 years, 48% male) from 2011 to 2014 at the University Hospital of Limoges. The AL patients were divided into three groups according to Mayo Clinic (MC) staging and all subjects underwent 2D-TTE and 3D-TTE at the same setting. Using 2D-TTE, there was no significant difference in LV ejection fraction (EF) between the groups [LVEF = 63 ± 7% (control), 59 ± 6% (MC stage I), 60 ± 8% (MC stage II) and 57 ± 14% (MC stage III) (p = 0.24)]. In contrast, 3D-TTE demonstrated significantly worse LV systolic function in stage II and III patients using 3D-LVEF [MC II and III 45 ± 8% and 39 ± 12% vs. control 53 ± 8% (p < 0.0001)], global longitudinal strain (GLS) [MC II and III - 11 ± 4% and - 8 ± 3% vs. control - 15 ± 3% (p < 0.0001)] and global radial strain (GRS) [MC II and III 14 ± 9% and 10 ± 8% vs. control 25 ± 10% (p < 0.0001)]. Furthermore, MC III patients had significantly worse global circumferential strain and area tracking [- 17 ± 6% and - 25 ± 8% vs. - 24 ± 7% and - 36 ± 7% for control (p < 0.0001)]. Additionally, MC I had significantly better 3D GLS, GRS and global strain (- 15 ± 3%, 25 ± 10% and 28 ± 12%) than MC II (- 11 ± 4%, 14 ± 9% and 16 ± 10%) and MC III patients (- 8 ± 3%, 10 ± 8% and 12 ± 8%), respectively. Despite an apparently preserved LVEF by 2D-TTE, AL patients in MC stage II and III demonstrate evidence of LV systolic dysfunction by 3D imaging using LVEF and strain analysis. Worse LV involvement by AL amyloidosis was associated with more impaired 3D-TTE LV systolic parameters.

Erythropoietin reduces collagen deposition after myocardial infarction but does not improve cardiac function.

Myocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into the following groups: control (CT), control + EPO (CT + EPO), myocardial infarction + EPO (MI + EPO), and myocardial infarction (MI). The interstitial collagen volume fraction (ICVF) was quantified and echocardiography was performed. We quantified asymmetric dimethylarginine and glutathione by ELISA, and used real-time PCR to assess apoptosis and inflammation. Western blotting was used to evaluate inflammatory proteins and tissue inhibitors of metalloproteinases (TIMPs), and TUNEL staining was used to detect apoptosis. For matrix metalloproteinases (MMPs), we performed zymography. Parametric and nonparametric analyses were performed according to normality testing. ICVF was greater in MI groups (p < 0.001) and was attenuated by EPO (p = 0.05). The MMP-2 did not show any difference between groups. The TIMP-1 and TIMP-2 did not have difference between groups. The MI groups had worse fraction shortening (p < 0.001), without EPO protection (p = 0.666). The MI groups had increased left ventricle diastolic dimension (p < 0.001) without EPO attenuation (p = 0.79). EPO did not act on oxidative stress. Apoptosis and inflammation were not modulated by EPO. We concluded that EPO attenuated interstitial collagen accumulation, but did not protect from heart dilation or dysfunction.

Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1ß, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins.NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy by reducing oxidative/nitrosative stress, apoptosis, and inflammation along with upregulation of cardiac vitamin C transporter proteins. The latter may have a crucial role in improving antioxidant status in this cardiomyopathy.

Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.

Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6 ). On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51%) in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB6 group. Ejection fraction (EF) was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters (AU)

Dysregulation of Autonomic Nervous System in Chagas' Heart Disease Is Associated with Altered Adipocytokines Levels.

BACKGROUND: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. METHODS AND RESULTS: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. CONCLUSIONS: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease.

Exercise-induced decrease in myocardial high-energy phosphate metabolites in patients with Chagas heart disease.

BACKGROUND: The influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood. METHODS AND RESULTS: Changes in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with (31)P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac (31)P-MRS. The myocardial phosphocreatine to [ß-phosphate]adenosine triphosphate ratio (PCr/ß-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc-sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/ß-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P < .001) and was lower in group I (0.89 ± 0.24) versus groups II (1.44 ± 0.23) and III (1.40 ± 0.37; P < .001). There was no stress-induced change in cardiac PCr/ß-ATP (1.88 ± 0.08 at rest vs 1.89 ± 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/ß-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/ß-ATP was 1.44 ± 0.23 at rest and 0.97 ± 0.37 during exercise (33% decrease; P < .001). In group III, PCr/ß-ATP was 1.40 ± 0.37 at rest and 0.60 ± 0.19 during exercise (57% decrease; P < .001). CONCLUSIONS: Myocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.

The effect of beta-blockade on myocardial remodelling in Chagas' cardiomyopathy

OBJECTIVE: Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model. METHODS: We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red. RESULTS: The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality. CONCLUSION: Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.