Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Diffuse Myocardial Fibrosis and Cardiomyocyte Diameter Are Associated With Heart Failure Symptoms in Chagas Cardiomyopathy.

Background: Chronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR). Methods: We performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death. Results: A total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = -0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6-2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death. Conclusion: In patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.

Increased Serum Mir-150-3p Expression Is Associated with Radiological Lung Injury Improvement in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19. Methods: We evaluated lung injury by computed tomography at hospital admission and discharge and the serum expression of 754 miRNAs using the TaqMan OpenArray after hospital discharge in 27 patients with COVID-19. In addition, miR-150-3p was validated by qRT-PCR on serum samples collected at admission and after hospital discharge. Results: OpenArray analysis revealed that seven miRNAs were differentially expressed between groups of patients without radiological lung improvement compared to those with lung improvement at hospital discharge, with three miRNAs being upregulated (miR-548c-3p, miR-212-3p, and miR-548a-3p) and four downregulated (miR-191-5p, miR-151a-3p, miR-92a-3p, and miR-150-3p). Bioinformatics analysis revealed that five of these miRNAs had binding sites in the SARS-CoV-2 genome. Validation of miR-150-3p by qRT-PCR confirmed the OpenArray results. Conclusions: The present study shows the potential association between the serum expression of seven miRNAs and lung injury in patients with COVID-19. Furthermore, increased expression of miR-150 was associated with pulmonary improvement at hospital discharge.

What Is the Clinical Impact of Stress CMR After the ISCHEMIA Trial?

After progressively receding for decades, cardiovascular mortality due to coronary artery disease has recently increased, and the associated healthcare costs are projected to double by 2030. While the 2019 European Society of Cardiology guidelines for chronic coronary syndromes recommend non-invasive cardiac imaging for patients with suspected coronary artery disease, the impact of non-invasive imaging strategies to guide initial coronary revascularization and improve long-term outcomes is still under debate. Recently, the ISCHEMIA trial has highlighted the fundamental role of optimized medical therapy and the lack of overall benefit of early invasive strategies at a median follow-up of 3.2 years. However, sub-group analyses excluding procedural infarctions with longer follow-ups of up to 5 years have suggested that patients undergoing revascularization had better outcomes than those receiving medical therapy alone. A recent sub-study of ISCHEMIA in patients with heart failure or reduced left ventricular ejection fraction (LVEF <45%) indicated that revascularization improved clinical outcomes compared to medical therapy alone. Furthermore, other large observational studies have suggested a favorable prognostic impact of coronary revascularization in patients with severe inducible ischemia assessed by stress cardiovascular magnetic resonance (CMR). Indeed, some data suggest that stress CMR-guided revascularization assessing the extent of the ischemia could be useful in identifying patients who would most benefit from invasive procedures such as myocardial revascularization. Interestingly, the MR-INFORM trial has recently shown that a first-line stress CMR-based non-invasive assessment was non-inferior in terms of outcomes, with a lower incidence of coronary revascularization compared to an initial invasive approach guided by fractional flow reserve in patients with stable angina. In the present review, we will discuss the current state-of-the-art data on the prognostic value of stress CMR assessment of myocardial ischemia in light of the ISCHEMIA trial results, highlighting meaningful sub-analyses, and still unanswered opportunities of this pivotal study. We will also review the available evidence for the potential clinical application of quantifying the extent of ischemia to stratify cardiovascular risk and to best guide invasive and non-invasive treatment strategies.

Noninvasive imaging assessment of rehabilitation therapy in heart failure with preserved and reduced left ventricular ejection fraction (IMAGING-REHAB-HF): design and rationale.

BACKGROUND: Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect. METHODS: IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) - will be necessary to achieve adequate power. CONCLUSION: This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients.

Effects of Warm-Up, Post-Warm-Up, and Re-Warm-Up Strategies on Explosive Efforts in Team Sports: A Systematic Review.

BACKGROUND: In team sports, it is imperative that the warm-up improves acute explosive performance. However, the exact strategies, methods, and consequences of different warm-up practices remain unclear. A time delay between the warm-up and match and during half-time could negate the positive metabolic effects of the warm-up. OBJECTIVES: We conducted a systematic review to synthesize and analyze the potential effects of strategies during a warm-up (before match), post-warm-up (time between the end of warm-up and the start of a match), and re-warm-up (half-time break within a match) on explosive performance in team sports. Furthermore, we examined optimal warm-up strategies based on the included studies. METHODS: We performed a search of four databases (Web of Science, Scopus, PubMed, and ScienceDirect) for original research articles published between January 1981 and August 2017. A total of 30 articles met the inclusion criteria, and the Cochrane risk of bias tool was used to assess the risk of bias. The results of the included studies were recalculated to determine effect sizes using Cohen's d. RESULTS: A warm-up comprising 8 sets of 60-m sprints (- 2.19%, d = 1.20) improved sprint performance. Additionally, 7 min of dynamic exercises after 5 min of jogging improved sprint (- 7.69%, d = 1.72), jumping (8.61%, d = 0.61), and agility performance (- 6.65%, d = 1.40). The use of small-sided games also seems to be a valid strategy, especially for jumping performance (6%, d = 0.8). These benefits resulted from the warm-up strategies combined with some passive rest (between 2 and 10 min) before the main performance. In this post-warm-up period, the use of heated garments could result in better outcomes than simple rest (- 0.89%, d = 0.39). However, if the transition was longer than 15 min, before entering the match, performing a re-warm-up with short-term explosive tasks to reactivate was the most effective approach (- 1.97%, d = - 0.86). At half-time, heated garments maintained better sprint (- 1.45%, d = 2.21) and jumping performance (3.13%, d = 1.62). CONCLUSION: Applying properly structured strategies in the warm-up and avoiding a long rest in the post-warm-up improves explosive performance. Studies tend to recommend a short active warm-up strategy (10-15 min), gradually increasing intensity (~ 50-90% of maximum heart rate), and the use of heated garments soon after the warm-up to maintain muscle temperature. However, 2 min of active re-warm-up with short-term sprints and jumps should be needed for transitions longer than 15 min (~ 90% of maximum heart rate). Last, at the half-time re-warm-up, combining heated garments to maintain muscle temperature and performing an active strategy, with explosive tasks or small-sided games for 5 min before re-entering the game, resulted in better explosive performance than 15 min of resting.

Fixação pedicular percutânea de fraturas vertebrais toracolombares sem compromisso neurológico / Percutaneous pedicle fixation of thoracolumbar vertebral fractures without neurological deficits / Fijación pedicular percutánea de las fracturas vertebrales toracolumbares sin comprometimiento neurológico

OBJETIVO: Avaliar a eficácia e a segurança da fixação pedicular percutânea em fraturas toraco-lombares, sem compromisso neurológico. MÉTODOS: Foram incluídos no estudo os pacientes com idade compreendida entre os 18 e 70 anos com fratura toracolombar AO tipo (A.3), cifose> 30º ou redução da altura do corpo vertebral> 50% ou compressão do canal vertebral >50% que foram submetidos a tratamento cirúrgico com fixação pedicular percutânea. Foram avaliados os parâmetros radiológicos: ângulo de Cobb, colapso vertebral, acunhamento anterior e compressão do canal vertebral no pré-operatório, pós-operatório e no fim do seguimento. O resultado funcional e clínico foi avaliado pelo Oswestry Disability Index (ODI). RESULTADOS: O tempo operatório médio foi de 81 minutos (Mín. 69, Máx. 95 min). O volume médio de perda sanguínea intraoperatória foi de 85 ml (Mín. 75 e Máx. 155 ml). O seguimento médio foi de sete meses (Min. três meses, Máx. 14 meses). Apresentaram um ODI médio final de 18% (excelente). CONCLUSÕES: Os resultados clínicos sugerem que a fixação pedicular percutânea pode ser uma técnica cirúrgica alternativa para o tratamento das fraturas toracolombares AO tipo (A.3), sem défices neurológicos. Esta técnica demonstrou ser eficaz e segura, apresentando as vantagens de uma abordagem minimamente invasiva.

OBJECTIVE: To evaluate the efficacy and safety of percutaneous pedicle fixation in thoracolumbar fractures without neurologic compromise. METHODS: The study included patients aged between 18 and 70 with AO thoracolumbar fracture type (A.3) and kyphosis >30° or reduction of vertebral body height >50% or >50% of spinal canal compromise, who underwent surgery with percutaneous pedicle fixation in the first ten days after fracture. Radiological parameters were evaluated: Cobb angle, vertebral collapse, anterior wedging and spinal canal compromise preoperatively, postoperatively and at the end of follow-up. The clinical and functional outcome was assessed by the Oswestry Disability Index (ODI). RESULTS: Mean operative time was 81 minutes (Min 69, Max 95 min). The mean volume of intraoperative blood loss was 85ml (75 Min and Max 155 ml). The mean follow-up was seven months (3 months Min, Max, 14 months) with an average ODI of 18% (excellent). CONCLUSIONS: The clinical results suggest that the pedicle fixation percutaneous technique may be an alternative to surgical treatment of thoracolumbar fractures type (A.3), without neurological deficits. This technique has proved to be safe and effective, with the advantages of a minimally invasive approach.

OBJETIVO: Evaluar la eficacia y la seguridad de la fijación percutánea pedicular de fracturas toracolumbares sin comprometimiento neurológico. MÉTODOS: Se incluyeron en el estudio los pacientes de edades comprendidas entre 18 y 70 años, con fractura toracolumbar tipo AO (A.3), cifosis >30° o reducción de la altura del cuerpo vertebral >50% o compresión del canal vertebral >50%, quienes fueron sometidos a tratamiento quirúrgico mediante fijación percutánea pedicular. Se evaluaron los parámetros radiológicos: el ángulo de Cobb, el colapso vertebral, el acuñamiento anterior y la compresión del canal vertebral antes de la operación, después de la operación y al final del seguimiento. La evolución clínica y funcional fue evaluada por el Oswestry Disability Index (ODI). RESULTADOS: El tiempo quirúrgico promedio fue 81 minutos (mínimo 69, máximo 95 min.) El volumen promedio de la pérdida de sangre intraoperatoria fue 85 ml (mínimo 75 y máximo 155 ml). El promedio de seguimiento fue siete meses (mínimo 3 meses, máximo 14 meses). Se presentó un ODI promedio final de 18% (excelente). CONCLUSIONES: Los resultados clínicos sugieren que la fijación percutánea pedicular puede ser una técnica quirúrgica alternativa para el tratamiento de las fracturas toracolumbares tipo AO (A.3), sin déficits neurológicos. Esta técnica ha demostrado ser eficaz y segura, y presenta las ventajas de un enfoque mínimamente invasivo.