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.

Noncompaction cardiomyopathy: a substrate for a thromboembolic event.

BACKGROUND: Noncompaction cardiomyopathy (NCC) is a rare genetic cardiomyopathy characterized by a thin, compacted epicardial layer and an extensive noncompacted endocardial layer. The clinical manifestations of this disease include ventricular arrhythmia, heart failure, and systemic thromboembolism. CASE PRESENTATION: A 43-year-old male was anticoagulated by pulmonary thromboembolism for 1 year when he developed progressive dyspnea. Cardiovascular magnetic resonance imaging showed severe biventricular trabeculation with an ejection fraction of 15%, ratio of maximum noncompacted/compacted diastolic myocardial thickness of 3.2 and the presence of exuberant biventricular apical thrombus. CONCLUSION: Still under discussion is the issue of which patients and when they should be anticoagulated. It is generally recommended to those presenting ventricular systolic dysfunction, antecedent of systemic embolism, presence of cardiac thrombus and atrial fibrillation. In clinical practice the patients with NCC and ventricular dysfunction have been given oral anticoagulation, although there are no clinical trials showing the real safety and benefit of this treatment.

Differential effects of variation in athletes training on myocardial morphophysiological adaptation in men: focus on ¹²³I-MIBG assessed myocardial sympathetic activity.

PURPOSE: High intensity systematic physical training leads to myocardial morphophysiological adaptations. The goal of this study was to investigate if differences in training were correlated with differences in cardiac sympathetic activity. METHODS: 58 males (19-47 years), were divided into three groups: strength group (SG), (20 bodybuilders), endurance group (EG), (20 endurance athletes), and a control group (CG) comprising 18 healthy non-athletes. Cardiac sympathetic innervation was assessed by planar myocardial (123)I-metaiodobenzylguanidine scintigraphy using the early and late heart to mediastinal (H/M) ratio, and washout rate (WR). RESULTS: Left ventricular mass index was significantly higher both in SG (P < .001) and EG (P = .001) compared to CG without a statistical significant difference between SG and EG (P = .417). The relative wall thickness was significantly higher in SG compared to CG (P < .001). Both left ventricular ejection fraction and the peak filling rate showed no significant difference between the groups. Resting heart rate was significantly lower in EG compared to CG (P = .006) and SG (P = .002). The late H/M ratio in CG was significantly higher compared to the late H/M for SG (P = .003) and EG (P = .004). However, WR showed no difference between the groups. There was no significant correlation between the parameters of myocardial sympathetic innervation and parameters of left ventricular function. CONCLUSIONS: Strength training resulted in a significant increase in cardiac dimensions. Both strength and endurance training seem to cause a reduction in myocardial sympathetic drive. However, myocardial morphological and functional adaptations to training were not correlated with myocardial sympathetic activity.

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.

Morphological and functional cardiac alterations in children with congenital Zika syndrome and severe neurological deficits.

INTRODUCTION: Zika virus infection during pregnancy causes fetal microcephaly and brain damage. Congenital Zika syndrome (CZS) is characterized by systemic involvement with diffuse muscle impairment, a high frequency of arthrogryposis, and microphthalmia. Cardiac impairment in CZS has rarely been evaluated. Our study assessed morphology and biventricular cardiac function in children with CZS and advanced neurological dysfunction. METHODS: This cross-sectional study was conducted on 52 children with CZS (Zika group; ZG) and 25 healthy children (control group; CG) in Paraiba, Brazil. Clinical evaluation, electrocardiogram (EKG), and transthoracic echocardiogram (TTE) were performed on all children. Additionally, troponin I and natriuretic peptide type B (BNP) levels, the degree of cerebral palsy, and neuroimaging findings were assessed in the ZG group. RESULTS: The median age of the study population was 5 years in both groups, and 40.4% (ZG) and 60% (CG) were female. The most prevalent electrocardiographic alteration was sinus arrhythmia in both the ZG (n = 9, 17.3%) and CG (n = 4, 16%). The morphological parameters adjusted for Z score were as follows: left ventricular (LV) end-diastolic diameter in ZG: -2.36 [-5.10, 2.63] vs. CG: -1.07 [-3.43, 0.61], p<0.001); ascending aorta (ZG: -0.09 [-2.08, 1.60] vs. CG: 0.43 [-1.47, 2.2], p = 0.021); basal diameter of the right ventricle (RV) (ZG: -2.34 [-4.90, 0.97] vs. CG: -0.96 [-2.21, 0.40], p<0.01); and pulmonary artery dimension (ZG: -2.13 [-5.99, 0.98] vs. CG: -0.24 [-2.53, 0.59], p<0.01). The ejection fractions (%) were 65.7 and 65.6 in the ZG and CG, respectively (p = 0.968). The left atrium volume indices (mL/m2) in the ZG and CG were 13.15 [6.80, 18.00] and 18.80 [5.90, 25.30] (p<0.01), respectively, and the right atrium volume indices (mL/m2) were 10.10 [4.90, 15.30] and 15.80 [4.10, 24.80] (p<0.01). The functional findings adjusted for Z score were as follows: lateral systolic excursion of the mitral annular plane (MAPSE) (ZG: 0.36 [-2.79, 4.71] vs. CG: 1.79 [-0.93, 4.5], p = 0.001); tricuspid annular plane systolic excursion (TAPSE) (ZG: -2.43 [-5.47, 5.09] vs. CG: 0.07 [-1.98, 3.64], p<0.001); and the S' of the RV (ZG: 1.20 [3.35, 2.90] vs. CG: -0.20 [-2.15, 1.50], p = 0.0121). No differences in biventricular strain measurements were observed between the groups. Troponin I and BNP levels were normal in in the ZG. Grade V cerebral palsy and subcortical calcification were found in 88.6% and 97.22% of children in the ZG group, respectively. CONCLUSION: A reduction in cardiac dimensions and functional changes were found in CZS patients, based on the TAPSE, S' of the RV, and MAPSE, suggesting the importance of cardiac evaluation and follow-up in this group of patients.

Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023. / Posicionamento do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia sobre o Uso do Strain Miocárdico na Rotina do Cardiologista ­ 2023.

Central Illustration : Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023 Proposal for including strain in the integrated diastolic function assessment algorithm, adapted from Nagueh et al.67 Am: mitral A-wave duration; Ap: reverse pulmonary A-wave duration; DD: diastolic dysfunction; LA: left atrium; LASr: LA strain reserve; LVGLS: left ventricular global longitudinal strain; TI: tricuspid insufficiency. Confirm concentric remodeling with LVGLS. In LVEF, mitral E wave deceleration time < 160 ms and pulmonary S-wave < D-wave are also parameters of increased filling pressure. This algorithm does not apply to patients with atrial fibrillation (AF), mitral annulus calcification, > mild mitral valve disease, left bundle branch block, paced rhythm, prosthetic valves, or severe primary pulmonary hypertension.

Figura Central : Posicionamento do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia sobre o Uso do Strain Miocárdico na Rotina do Cardiologista ­ 2023 Proposta de inclusão do strain no algoritmo integrado de avaliação da função diastólica, adaptado e traduzido de Nagueh et al. 67 AE: átrio esquerdo; Ap: duração da onda A reversa pulmonar; Am: duração da onda A mitral; DD: disfunção diastólica; FEVEr: fração de ejeção do ventrículo esquerdo reduzida; IT: insuficiência tricúspide; SAEr: strain do AE de reservatório; SLGVE: strain longitudinal global do ventrículo esquerdo. Se remodelamento concêntrico, confirmar com SLGVE. Na presença de FEVEr, tempo de desaceleração da onda E mitral (TDE) < 160 ms e onda S < D pulmonar também são parâmetros de pressão de enchimento aumentada. Esse algoritmo não se aplica a pacientes com fibrilação atrial (FA), calcificação do anel mitral ou valvopatia mitral maior que discreta, bloqueio de ramo esquerdo (BRE), ritmo de marca-passo, próteses valvares ou hipertensão pulmonar (HP) primária grave.

Effect of colchicine on myocardial injury induced by Trypanosoma cruzi in experimental Chagas disease.

BACKGROUND: The hallmark of Chagas disease (CD) is multifocal myocarditis and extensive fibrosis. We investigated the potential effect of colchicine on myocardial remodeling in experimental CD. METHODS AND RESULTS: One hundred Syrian hamsters were randomly divided into noninfected untreated control (CG), noninfected control treated with colchicine (COLG 0.4 mg kg(-1) d(-1) by gavage), infected (IG), and infected treated with colchicine (ICOLG, 0.4 mg kg(-1) d(-1)) groups. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry with picrosirius red staining. The gelatinolytic activities of matrix metalloproteinase (MMP) 2 were examined with the use of zymography. Myocarditis was described according to the Dallas criteria. Statistical comparisons were performed with parametric analysis of variance and Tukey test. ICVF (%) accumulation was attenuated in infected colchicine-treated animals in the left (CG 0.81 ± 0.13, COLG 0.85 ± 0.13, IG: 1.35 ± 0.31,* ICOLG 1.06 ± 0.19; *P < .05 compared with ICOLG) and right ventricles (CG 1.4 ± 0.36, COLG 1.26 ± 0.14, IG 1.97 ± 0.058,* ICOLG: 1.52 ± 0.23; *P < .05 compared with ICOLG). A significant increase in MMP-2 enzymatic activity (UA) was observed in ICOLG (17,432.8*) compared with GC (3731.6), COLG (2,792.6), and IG (4,286.3; *P < .001). In IG, 66% of animals had myocarditis compared with only 49% in ICOLG. CONCLUSIONS: Colchicine had a protective effect on myocardium, indicated by decreased interstitial myocardial fibrosis, increased intensity of MMP-2, and attenuated myocardial inflammation.

Endomyocardial fibrosis of the right ventricle in a patient with schistosomiasis: a case report.

Background: Endomyocardial fibrosis (EMF) is a rare and underdiagnosed cause of restrictive cardiomyopathy. Its aetiology is not yet defined and could be caused by the influence of different clinical factors that seem to combine with genetic aspects of individuals susceptible to an inflammatory process that leads to formation of fibrosis. Case summary: We describe a case of a 50-year-old man from the northeastern region of Brazil, where there is high prevalence of schistosomiasis. He presented to our centre with symptoms of right heart failure. The echocardiogram showed normal left ventricular ejection fraction. Right ventricular had normal systolic function but in the apical region was filled with a homogeneous and hypoechoic image causing obliteration and restriction of the apex. The late gadolinium enhancement with cardiac magnetic resonance showed diffuse and heterogeneous subendocardial fibrosis in the right ventricle apex consistent with EMF, but declined endocardiectomy. Discussion: This report presents an interesting case of EMF and schistosomiasis simultaneously. The hypothesis of parasitosis as a probable cause of EMF was raised by helminth-induced hypereosinophilia. Complementary imaging tests such as magnetic resonance imaging and echocardiography, in addition to clinical and epidemiological suspicion, are essential for its diagnosis. Early surgical resolution becomes crucial for long-term survival.

Exercise training in heart failure with reduced ejection fraction and permanent atrial fibrillation: A randomized clinical trial.

BACKGROUND: Heart failure (HF) associated with atrial fibrillation increases patients' physical inactivity, worsening their clinical condition and mortality. Exercise training is safe and has clear benefits in HF. However, little is known about the effects of exercise training on patients with HF with reduced ejection fraction and permanent atrial fibrillation (HFAF). OBJECTIVE: The purpose of this study was to test the hypothesis that exercise training improves functional capacity, cardiac function, and quality of life in patients with HFAF. METHODS: This randomized clinical trial was conducted at the Heart Institute. Patients with HFAF, left ventricular ejection fraction ≤40%, and resting heart rate (HR) ≤80 beats/min were included in the study. Cardiopulmonary testing, echocardiography, nervous system, and quality of life assessment were performed before and after the 12-week protocol period. RESULTS: Twenty-six patients (mean age 58 ± 1 years) were randomized to exercise training (HFAF-trained group; n = 13) or no training (HFAF-untrained group; n = 13). At baseline, no differences between the groups were found. Exercise improved peak oxygen consumption, slope of ventilation per minute/carbon dioxide production, and quality of life. The HFAF-trained group had significantly decreased resting HR (from 73 ± 2 to 69 ± 2 beats/min; P = .02) and recovery HR (from 148 ± 11 to 128 ± 9 beats/min; P = .001). Concomitantly, left ventricular ejection fraction increased (from 31% ± 1% to 36% ± 0.9%; P = .01), left atrial dimension decreased (from 52 ± 1.2 to 47 ± 1 mm; P = .03), and left ventricular end-systolic volume and left ventricular end-diastolic volume deceased (from 69 ± 2 to 64 ± 1.8 mL/m2 and from 99 ± 2.1 to 91 ± 2 mL/m2, respectively; P < .05). No changes were observed in the HFAF-untrained group. CONCLUSION: Exercise training can improve exercise capacity, quality of life, and cardiac function in patients with HF with reduced ejection fraction and permanent atrial fibrillation.

Diagnostic Accuracy of Dobutamine Stress Echocardiography for Detection of Cardiac Allograft Vasculopathy in Orthotopic Heart Transplant Patients.

OBJECTIVE: Cardiac allograft vasculopathy is one of the leading causes of late graft failure and subsequent death in orthotopic heart transplant. Although invasive coronary angiography is the gold standard modality for detection of cardiac allograft vasculopathy, dobutamine stress echocardiography has been recently frequently used as an alternative. Our aim was to evaluate the diagnostic performance of dobutamine stress echocardiography for detection of cardiac allograft vasculopathy in transplant patients. METHODS: A retrospective analysis was conducted using a total of 150 dobutamine stress echocardiographic exams that were performed on 99 patients in our institution, with paired coronary angiogram and no acute rejection, within a median of 538 [interquartile range 371-816] days. Sensitivity and specificity of dobutamine echocardiography to detect allograft vasculopathy was evaluated. Allograft vasculopathy was defined as Grade 1 or higher based on ISHLT criteria. A positive dobutamine stress echo result was defined by new or worsening wall motion abnormality. RESULTS: Median age of the population at transplant was 34 [interquartile range 22-46] years; 76 (77%) patients were male. Allograft vasculopathy was present in 31 (20.6%) out of 150 coronary angiograms. Only 7 (4.6%) of that number were positive on dobutamine stress echocardiography. Sensitivity and specificity for allograft vasculopathy detection was 3% and 94%, respectively. Out of 7 false positive dobutamine stress echocardiograms, two were in patients with myocardial bridging. Two patients with mild acute rejection had both negative dobutamine stress echo. CONCLUSIONS: Overall, positivity of dobutamine stress echocardiography in patients after heart transplant is low. It has high specificity, but very low sensitivity for detection of cardiac allograft vasculopathy. Dobutamine stress echocardiography should only be cautiously used as an alternative to coronary angiography.

Worsening of heart failure by coronavirus disease 2019 is associated with high mortality.

AIMS: Patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and concurrent coronavirus disease 2019 (COVID-19) might have a higher risk of severe events. METHODS AND RESULTS: We retrospectively studied 16 patients with advanced HFrEF who developed COVID-19 between 1 March and 29 May 2020. Follow-up lasted until 30 September. Ten patients previously hospitalized with decompensated HFrEF were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during hospitalization. Six patients undergoing ambulatory care at initiation of COVID-19 symptoms were hospitalized because of advanced HFrEF. All patients who experienced worsening of HFrEF due to COVID-19 required higher doses or introduction of additional inotropic drugs or intra-aortic balloon pump in the intensive care unit. The mean intravenous dobutamine dose before SARS-CoV-2 infection in previously hospitalized patients (n = 10) and the median (inter-quartile range) peak intravenous dobutamine dose during SARS-CoV-2 infection in all patients (n = 16) were 2 (0-7) µg/kg/min and 20 (14-20) (P < 0.001), respectively. During follow-up, 56% underwent heart transplantation (n = 2) or died (n = 7). Four patients died during hospitalization from mixed shock consequent to severe acute respiratory syndrome with inflammatory storm syndrome associated with septic and cardiogenic shock during COVID-19. After COVID-19 recovery, two patients died from mixed septic and cardiogenic shock and one from sustained ventricular tachycardia and cardiogenic shock. Five patients were discharged from hospital to ambulatory care. Four were awaiting heart transplantation. CONCLUSION: Worsening of advanced HF by COVID-19 is associated with high mortality. This report highlights the importance of preventing COVID-19 in patients with advanced HF.

A machine learning framework for the evaluation of myocardial rotation in patients with noncompaction cardiomyopathy.

AIMS: Noncompaction cardiomyopathy (NCC) is considered a genetic cardiomyopathy with unknown pathophysiological mechanisms. We propose to evaluate echocardiographic predictors for rigid body rotation (RBR) in NCC using a machine learning (ML) based model. METHODS AND RESULTS: Forty-nine outpatients with NCC diagnosis by echocardiography and magnetic resonance imaging (21 men, 42.8±14.8 years) were included. A comprehensive echocardiogram was performed. The layer-specific strain was analyzed from the apical two-, three, four-chamber views, short axis, and focused right ventricle views using 2D echocardiography (2DE) software. RBR was present in 44.9% of patients, and this group presented increased LV mass indexed (118±43.4 vs. 94.1±27.1g/m2, P = 0.034), LV end-diastolic and end-systolic volumes (P< 0.001), E/e' (12.2±8.68 vs. 7.69±3.13, P = 0.034), and decreased LV ejection fraction (40.7±8.71 vs. 58.9±8.76%, P < 0.001) when compared to patients without RBR. Also, patients with RBR presented a significant decrease of global longitudinal, radial, and circumferential strain. When ML model based on a random forest algorithm and a neural network model was applied, it found that twist, NC/C, torsion, LV ejection fraction, and diastolic dysfunction are the strongest predictors to RBR with accuracy, sensitivity, specificity, area under the curve of 0.93, 0.99, 0.80, and 0.88, respectively. CONCLUSION: In this study, a random forest algorithm was capable of selecting the best echocardiographic predictors to RBR pattern in NCC patients, which was consistent with worse systolic, diastolic, and myocardium deformation indices. Prospective studies are warranted to evaluate the role of this tool for NCC risk stratification.

Pulmonary Hypertension in Obese Mice Is Accompanied by a Reduction in PPAR-γ Expression in Pulmonary Artery.

Obesity and insulin resistance (IR) are well-studied risk factors for systemic cardiovascular disease, but their impact on pulmonary hypertension (PH) is not well clarified. This study aims to investigate if diet-induced obesity induces PH and if peroxisome-proliferator-activated receptor (PPAR-γ) and/or endoplasmic reticulum (ER) stress are involved in this process. Mice were maintained on a high-fat diet (HFD) for 4 months, and IR and PH were confirmed. In a separate group, after 4 months of HFD, mice were treated with pioglitazone (PIO) or 4-phenylbutyric acid for the last month. The results demonstrated that HFD for at least 4 months is able to increase pulmonary artery pressure, which is maintained, and this animal model can be used to investigate the link between IR and PH, without changes in ER stress in the pulmonary artery. There was also a reduction in circulating adiponectin and in perivascular adiponectin expression in the pulmonary artery, associated with a reduction in PPAR-γ expression. Treatment with PIO improved IR and PH and reversed the lower expression of adiponectin and PPAR-γ in the pulmonary artery, highlighting this drug as potential benefit for this poorly recognized complication of obesity.

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

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).

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).

Use of sacubitril/valsartan in non-compaction cardiomyopathy: a case report.

The use of sacubitril/valsartan significantly reduces death or hospitalization in patients with ejection fraction < 40%. There is no study evaluating this drug effects in non-compaction cardiomyopathy (NCCM) individuals. The aim of this article is to report a case of a patient with NCCM initially refractory to gold standard treatment and afterwards treated with sacubitril/valsartan and its improvements. This is a case report of a 48-year-old woman, presenting with NCCM heart failure, who had received standard guideline-directed medical therapy for 18 months without any improvement in clinical and echocardiographic parameters. After that period, sacubitril/valsartan was initiated. After 18 months of refractory usage of guideline-directed medical therapy, sacubitril/valsartan was started, and significant change in functional class (III to I) and important ventricular remodelling were achieved with an improvement of 29% in the ejection fraction, reduction of 7 mm in ventricular diastolic diameter, and mild to none mitral valve functional regurgitation. In this case report, sacubitril/valsartan use was associated with improvement of echocardiographic and clinical parameters in a patient with NCCM.

Biventricular imaging markers to predict outcomes in non-compaction cardiomyopathy: a machine learning study.

AIMS: Left ventricular non-compaction cardiomyopathy (LVNC) is a genetic heart disease, with heart failure, arrhythmias, and embolic events as main clinical manifestations. The goal of this study was to analyse a large set of echocardiographic (echo) and cardiac magnetic resonance imaging (CMRI) parameters using machine learning (ML) techniques to find imaging predictors of clinical outcomes in a long-term follow-up of LVNC patients. METHODS AND RESULTS: Patients with echo and/or CMRI criteria of LVNC, followed from January 2011 to December 2017 in the heart failure section of a tertiary referral cardiologic hospital, were enrolled in a retrospective study. Two-dimensional colour Doppler echocardiography and subsequent CMRI were carried out. Twenty-four hour Holter monitoring was also performed in all patients. Death, cardiac transplantation, heart failure hospitalization, aborted sudden cardiac death, complex ventricular arrhythmias (sustained and non-sustained ventricular tachycardia), and embolisms (i.e. stroke, pulmonary thromboembolism and/or peripheral arterial embolism) were registered and were referred to as major adverse cardiovascular events (MACEs) in this study. Recruited for the study were 108 LVNC patients, aged 38.3 ± 15.5 years, 48.1% men, diagnosed by echo and CMRI criteria. They were followed for 5.8 ± 3.9 years, and MACEs were registered. CMRI and echo parameters were analysed via a supervised ML methodology. Forty-seven (43.5%) patients had at least one MACE. The best performance of imaging variables was achieved by combining four parameters: left ventricular (LV) ejection fraction (by CMRI), right ventricular (RV) end-systolic volume (by CMRI), RV systolic dysfunction (by echo), and RV lower diameter (by CMRI) with accuracy, sensitivity, and specificity rates of 75.5%, 77%, 75%, respectively. CONCLUSIONS: Our findings show the importance of biventricular assessment to detect the severity of this cardiomyopathy and to plan for early clinical intervention. In addition, this study shows that even patients with normal LV function and negative late gadolinium enhancement had MACE. ML is a promising tool for analysing a large set of parameters to stratify and predict prognosis in LVNC patients.

Ivabradine for treatment of heart failure.

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) is associated with a worse outcome. Heart rate (HR) is related to outcome in HFrEF. Ivabradine selectively inhibits If (funny) channels in a concentration-dependent manner reducing HR. AREAS COVERED: The effects of ivabradine in HF were reviewed. The SHIFT trial results indicated that ivabradine improves chronic HFrEF outcomes, whereas published data suggest that amiodarone, digoxin, or verapamil may not be safe or the safety is controversial in HFrEF patients. In the CONSTATHE-DHF study, ivabradine reduced HR and improved left ventricular (LV) ejection fraction, LV diastolic functions, and right ventricle function in acute decompensated HF (ADHF). In chagasic patients, ivabradine reduced HR and a trend toward reduction in all-cause death was observed with ivabradine (p = 0.07). In children with HFrEF, ivabradine increased NYHA functional class. The most common side effects with ivabradine are bradycardia, atrial fibrillation, and phosphenes. Ivabradine was approved for HFrEF treatment by the EMA and FDA and seems to be cost-effective in HFrEF treatment. Ivabradine is indicated for HFrEF by the ESC HF Guidelines (IIa) and by the 2016 ACC/AHA/HFSA Guidelines (IIa-B-R). EXPERT OPINION: Published evidences demonstrate that ivabradine improves the outcome of chronic HFrEF and it seems to have a promising role in ADHF.

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.

Endomyocardial fibrosis: pathological and molecular findings of surgically resected ventricular endomyocardium.

Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown etiology prevalent in tropical regions affecting the inflow tract and apex of one or both ventricles, which show fibrous thickening of the endocardium and adjacent myocardium. Surgical treatment is recommended for patients in functional classes III or IV (New York Heart Association). The gross and histological features of the heart have been comprehensively studied in autopsies, but studies in surgical samples are still lacking. Histological and immunohistochemical features of EMF in surgical samples collected from 32 patients were described and correlated with clinical data. Polymerase chain reaction (PCR) and reverse transcription-PCR, performed on formalin fixed endomyocardial samples, were used retrospectively to detect genomes of certain cardiotropic viruses and Toxoplasma gondii. Ventricular endocardium was thickened by superficial acellular hyaline collagen fibers type I and III, with predominance of the former type. Besides fibrosis, a chronic inflammatory process and an anomalous lymphatic rich vascular pattern were observed in the deep endocardium, connected to the terminal coronary circulation of the myocardium, which might be an important pathological finding concerning EMF pathogenesis. Molecular analysis of the endomyocardium revealed high incidence of cardiotropic infective agents (6/12, 50%); however, their role in the disease pathogenesis is still controversial.