Changes in left atrial function following two regimens of combined exercise training in patients with ischemic cardiomyopathy: a pilot study.

Purpose: Left atrial dysfunction has shown to play a prognostic role in patients with ischemic cardiomyopathy (ICM) and is becoming a therapeutic target for pharmacological and non-pharmacological interventions. The effects of exercise training on the atrial function in patients with ICM have been poorly investigated. In the present study, we assessed the effects of a 12-week combined training (CT) program on the left atrial function in patients with ICM. Methods: We enlisted a total of 45 clinically stable patients and randomly assigned them to one of the following three groups: 15 to a supervised CT with low-frequency sessions (twice per week) (CTLF); 15 to a supervised CT with high-frequency sessions (thrice per week) (CTHF); and 15 to a control group following contemporary preventive exercise guidelines at home. At baseline and 12 weeks, all patients underwent a symptom-limited exercise test and echocardiography. The training included aerobic continuous exercise and resistance exercise. The analysis of variance (ANOVA) was used to compare within- and inter-group changes. Results: At 12 weeks, the CTLF and CTHF groups showed a similar increase in the duration of the ergometric test compared with the control (ANOVA p < 0.001). The peak atrial longitudinal strain significantly increased in the CTHF group, while it was unchanged in the CTLF and control groups (ANOVA p = 0.003). The peak atrial contraction strain presented a significant improvement in the CTHF group compared with the CTLF and control groups. The left ventricular global longitudinal strain significantly increased in both the CTHF and the CTLF groups compared with the control group (ANOVA p = 0.017). The systolic blood pressure decreased in the CTHF and CTLF groups, while it was unchanged in the control group. There were no side effects causing the discontinuation of the training. Conclusions: We demonstrated that a CT program effectively improved atrial function in patients with ICM in a dose-effect manner. This result can help with programming exercise training in this population.

Hepatitis Delta Virus and Hepatocellular Carcinoma.

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 million people, carrying a significantly elevated risk of developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to an HBV mono-infection. Furthermore, HDV-associated HCC often manifests at a younger age and exhibits more aggressive characteristics. The intricate mechanisms driving the synergistic carcinogenicity of the HDV and HBV are not fully elucidated but are believed to involve chronic inflammation, immune dysregulation, and the direct oncogenic effects of the HDV. Indeed, recent data highlight that the molecular profile of HCC associated with HDV is unique and distinct from that of HBV-induced HCC. However, the question of whether the HDV is an oncogenic virus remains unanswered. In this review, we comprehensively examined several crucial aspects of the HDV, encompassing its epidemiology, molecular biology, immunology, and the associated risks of liver disease progression and HCC development.

Exploring the interplay between metabolic power and equivalent distance in training games and official matches in soccer: a machine learning approach.

Introduction: This study aimed to explore the interplay between metabolic power (MP) and equivalent distance (ED) and their respective roles in training games (TGs) and official soccer matches. Furthermore, the secondary objective was to investigate the connection between external training load (ETL), determined by the interplay of metabolic power and equivalent distance, and internal training load (ITL) assessed through HR-based methods, serving as a measure of criterion validity. Methods: Twenty-one elite professional male soccer players participated in the study. Players were monitored during 11 months of full training and overall official matches. The study used a dataset of 4269 training games and 380 official matches split into training and test sets. In terms of machine learning methods, the study applied several techniques, including K-Nearest Neighbors, Decision Tree, Random Forest, and Support-Vector Machine classifiers. The dataset was divided into two subsets: a training set used for model training and a test set used for evaluation. Results: Based on metabolic power and equivalent distance, the study successfully employed four machine learning methods to accurately distinguish between the two types of soccer activities: TGs and official matches. The area under the curve (AUC) values ranged from 0.90 to 0.96, demonstrating high discriminatory power, with accuracy levels ranging from 0.89 to 0.98. Furthermore, the significant correlations observed between Edwards' training load (TL) and TL calculated from metabolic power metrics confirm the validity of these variables in assessing external training load in soccer. The correlation coefficients (r values) ranged from 0.59 to 0.87, all reaching statistical significance at p < 0.001. Discussion: These results underscore the critical importance of investigating the interaction between metabolic power and equivalent distance in soccer. While the overall intensity may appear similar between TGs and official matches, it is evident that underlying factors contributing to this intensity differ significantly. This highlights the necessity for more comprehensive analyses of the specific elements influencing physical effort during these activities. By addressing this fundamental aspect, this study contributes valuable insights to the field of sports science, aiding in the development of tailored training programs and strategies that can optimize player performance and reduce the risk of injuries in elite soccer.

Acute Changes on Left Atrial Function during Incremental Exercise in Patients with Heart Failure with Mildly Reduced Ejection Fraction: A Case-Control Study.

BACKGROUND: the aim of this study was to assess acute changes in left atrial (LA) function during incremental aerobic exercise in patients with heart failure with mildly reduced ejection fraction (HFmrEF) in comparison to healthy subjects (HS). METHODS: twenty patients with established HFmrEF were compared with 10 HS, age-matched controls. All subjects performed a stepwise exercise test on a cycle ergometer. Echocardiography was performed at baseline, during submaximal effort, at peak of exercise, and after 5 min of recovery. RESULTS: HS obtained a higher value of METs at peak exercise than HFmrEF (7.4 vs. 5.6; between group p = 0.002). Heart rate and systolic blood pressure presented a greater increase in the HS group than in HFmrEF (between groups p = 0.006 and 0.003, respectively). In the HFmrEF group, peak atrial longitudinal strain (PALS) and conduit strain were both increased at submaximal exercise (p < 0.05 for both versus baseline) and remained constant at peak exercise. Peak atrial contraction strain (PACS) did not show significant changes during the exercise. In the HS group, PALS and PACS increased significantly at submaximal level (p < 0.05 for both versus baseline), but PALS returned near baseline values at peak exercise; conduit strain decreased progressively during the exercise in HS. Stroke volume (SV) increased in both groups at submaximal exercise; at peak exercise, SV remained constant in the HFmrEF, while it decreased in controls (between groups p = 0.002). CONCLUSIONS: patients with HFmrEF show a proper increase in LA reservoir function during incremental aerobic exercise that contributes to maintain SV throughout the physical effort.

The Improvement of Left Atrial Function after Twelve Weeks of Supervised Concurrent Training in Patients with Heart Failure with Mid-Range Ejection Fraction: A Pilot Study.

Left atrial dysfunction is associated with exercise intolerance and poor prognosis in heart failure (HF). The effects of exercise training on atrial function in patients with HF with mid-range ejection fraction (HFmrEF) are unknown. The purpose of the present study was to assess the effects of a supervised concurrent training (SCT) program, lasting 12 weeks, on left atrial function of patients with HFmrEF. The study included 70 stable patients, who were randomly assigned into two groups: SCT with (three sessions/week) or a control (CON) group directed to follow contemporary exercise preventive guidelines at home. Before starting the training program and at 12 weeks, all patients performed an ergometric test, a 6 min walk test, and echocardiography. Between-group comparisons were made by analysis of variance (ANOVA). At 12 weeks, the duration of the ergometric test and distance walked at 6 min walk test presented a significant greater increase in SCT compared to the control (between-group p 0.0001 and p 0.004 respectively). Peak atrial longitudinal strain and conduit strain presented an increase of 29% and 34%, respectively, in the SCT, and were unchanged in CON (between-group p 0.008 and p 0.001, respectively). Peak atrial contraction strain increased by 21% in SCT, with no changes in CON (between-group p 0.002). Left ventricular global longitudinal strain increased significantly in SCT compared to control (between-groups p 0.03). In conclusions, SCT improved left atrial and left ventricular function in HFmrEF. Further studies are needed in order to verify whether these favourable effects of SCT on LA function are sustained and whether they will translate into clinical benefits for patients with HFmrEF.

Mitochondrial DNA is a target of HBV integration.

Hepatitis B virus (HBV) may integrate into the genome of infected cells and contribute to hepatocarcinogenesis. However, the role of HBV integration in hepatocellular carcinoma (HCC) development remains unclear. In this study, we apply a high-throughput HBV integration sequencing approach that allows sensitive identification of HBV integration sites and enumeration of integration clones. We identify 3339 HBV integration sites in paired tumour and non-tumour tissue samples from 7 patients with HCC. We detect 2107 clonally expanded integrations (1817 in tumour and 290 in non-tumour tissues), and a significant enrichment of clonal HBV integrations in mitochondrial DNA (mtDNA) preferentially occurring in the oxidative phosphorylation genes (OXPHOS) and D-loop region. We also find that HBV RNA sequences are imported into the mitochondria of hepatoma cells with the involvement of polynucleotide phosphorylase (PNPASE), and that HBV RNA might have a role in the process of HBV integration into mtDNA. Our results suggest a potential mechanism by which HBV integration may contribute to HCC development.

Chronic heart failure: the role of di vericiguat.

The introduction of multiple new pharmacological agents over the past three decades in the field of heart failure with reduced ejection fraction (HFrEF) has led to reduced rates of mortality and hospitalizations, and consequently, the prevalence of HFrEF has increased, and up to 10% of patients progress to more advanced stages, characterized by high rates of mortality and hospitalizations and poor quality of life. Vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. In these patients, vericiguat reduced the primary outcome of death from cardiovascular causes or first hospitalization for heart failure in comparison with placebo. By reducing hospital admissions in a population at a very high risk of re-hospitalization, vericiguat might have a positive impact on healthcare costs for the management of HFrEF.

The role of iron deficiency in heart failure.

Iron is an essential micronutrient for several physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity observed in about 50% of patients with stable heart failure (HF) irrespective of the left ventricular function. The presence of ID is often as a multi-factorial condition, and it is associated with exercise intolerance, reduced quality of life, increased hospitalization rate, and mortality risk regardless of anaemia. The intravenous administration of iron to correct ID has emerged as a promising treatment in HF with reduced ejection fraction as it has been shown to alleviate symptoms, improve quality of life and exercise capacity, and reduce hospitalizations.

Effects of Concurrent, Within-Session, Aerobic and Resistance Exercise Training on Functional Capacity and Muscle Performance in Elderly Male Patients with Chronic Heart Failure.

BACKGROUND: The best format of exercise training (ET) in the setting of cardiac rehabilitation in patients with chronic heart failure (CHF) is still to be defined. Current guidelines recommend aerobic exercises, such as running and cycling, including some sessions per week of resistance exercise. AIM: The aim of this study was to address the effectiveness of a concurrent exercise training program utilizing a circuit of sequential endurance and resistance exercises on functional capacity and muscular strength in patients with CHF. METHODS: Ninety-five consecutive male patients (age 63.1 ± 6 years) with CHF (EF < 40%) in NYHA functional class II/III, were randomly assigned on 1:1 basis to a 12-week aerobic continuous training (AT) or concurrent CT), aerobic + resistance, training (CT), three times a week, with each session lasting 80 min. We used high quality, specifically designed ergometers, connected with each other and governed by a central console, and managed by a single physiotherapist. Before and after training all patients performed a symptoms-limited exercise test on a treadmill and a 6-min walking test (6MWT). Patients in the CT group also performed resistance exercises of upper and lower body. RESULTS: The 6MWT and exercise duration at ergometric test increased significantly in both AT and CT groups, with the increase being greater in CT group (p < 0.001; ES = 0.13; p < 0.01; ES = 0.07). Muscular strength increased significantly in the CT group, particularly in the lower body muscular districts (p < 0.001). Quality of life improved in both groups, with a significantly greater improvement in the CT group (p < 0.05). No side effects leading to discontinuation of training were observed. CONCLUSIONS: These findings indicate that concurrent, within-session training results in larger improvements in functional capacity, in addition to muscle performance, in patients with CHF, in comparison to single-mode aerobic training.

Assessing Genomic Mutations in SARS-CoV-2: Potential Resistance to Antiviral Drugs in Viral Populations from Untreated COVID-19 Patients.

Naturally occurring SARS-CoV-2 variants mutated in genomic regions targeted by antiviral drugs have not been extensively studied. This study investigated the potential of the RNA-dependent RNA polymerase (RdRp) complex subunits and non-structural protein (Nsp)5 of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to accumulate natural mutations that could affect the efficacy of antiviral drugs. To this aim, SARS-CoV-2 genomic sequences isolated from 4155 drug-naive individuals from southern Italy were analyzed using the Illumina MiSeq platform. Sequencing of the 4155 samples showed the following viral variant distribution: 71.2% Delta, 22.2% Omicron, and 6.4% Alpha. In the Nsp12 sequences, we found 84 amino acid substitutions. The most common one was P323L, detected in 3777/4155 (91%) samples, with 2906/3777 (69.9%) also showing the G671S substitution in combination. Additionally, we identified 28, 14, and 24 different amino acid substitutions in the Nsp5, Nsp7, and Nsp8 genomic regions, respectively. Of note, the V186F and A191V substitutions, affecting residues adjacent to the active site of Nsp5 (the target of the antiviral drug Paxlovid), were found in 157/4155 (3.8%) and 3/4155 (0.07%) samples, respectively. In conclusion, the RdRp complex subunits and the Nsp5 genomic region exhibit susceptibility to accumulating natural mutations. This susceptibility poses a potential risk to the efficacy of antiviral drugs, as these mutations may compromise the drug ability to inhibit viral replication.

Towards a More Individually Tailored Exercise Prescription for Promoting Cardiovascular Health.

The beneficial effects of exercise training (ET) in promoting cardiovascular health have been well established [...].

Concurrent Aerobic Plus Resistance Training Elicits Different Effects on Short-Term Blood Pressure Variability of Hypertensive Patients in Relation to Their Nocturnal Blood Pressure Pattern.

Background and Objectives: The purpose of this study was to investigate the effects of a 12-week concurrent training (CT) (i.e., aerobic plus resistance exercise) on short-term blood pressure variability (BPV) and BP values in hypertensive patients with non-dippper BP nocturnal pattern and underlying coronary artery disease. Material and Methods: The study included 72 consecutive patients who were divided into two groups according to the nocturnal BP pattern: dipping pattern (33 pts) and non-dipping (39 pts). Before starting CT and at 12 weeks, patients underwent the six minute walk test, ergometric test, assessment of 1-repetiton maximum (1 RM), and 24/h BP monitoring (24-h ABPM). Results: After CT, exercise capacity increased in both groups in a similar fashion. Twenty-four/h systolic BPV and daytime systolic BPV decreased significantly in the dipping group while they were unchanged in the non-dipping group (between groups changes: -1.0 ± 0.4 mmHg and -1.3 ± 0.9 mmHg; p = 0.02 and p = 0.006, respectively). Twenty-four/h systolic BP and daytime systolic BP decreased significantly in the dipping group while they were unchanged in the non-dipping group (between groups changes: -7.1 ± 2.6 mmHg and -7.8 ± 2.4 mmHg; p = 0.004 and p = 0.002, respectively). Nighttime systolic BP and BPV was unchanged in both groups. Twenty-four/h diastolic BP presented small but not significant changes in both groups. Conclusions: The effects of CT on BPV and BP were blunted in hypertensive subjects with a non-dipping BP pattern.

Relationship between aerobic fitness and metabolic power metrics in elite male soccer players.

The aim was to assess the relationship between aerobic fitness and metabolic power metrics in elite male soccer players, and the possible differences that playing positions might impose during match play over new metabolic power metrics. Sixty-two elite professional male soccer players (13 central backs, 13 side backs, 22 midfielders, and 14 forwards) took part in the study. Players were monitored during eleven months of full training (including pre-season and in-season) and over all official matches (Serie A matches, Italy Cup matches). Aerobic fitness tests were conducted one week after the start of the preseason, and 8, 24 and 36 weeks after the beginning of the Championship. Players' aerobic fitness and metabolic power metrics were considered as the mean of all seasonal testing and of pooling data of 38 championship matches and 3 or 6 Italy Cup matches for all the calculations respectively. The velocity at 4 mmol·L-1 (VL4) was significantly related to metabolic power metrics match variables with correlation ranging from trivial to very large (r = 0.32 to r = 0.89). Receiver-operating-characteristic (ROC) analysis showed that speed at VL4 was sensitive in detecting high metabolic power distance (HMPD) changes in all but central back players as revealed by area under the curve (central back .78, 95%CI .47 to .95; full back .93, 95%CI .64 to 0.99; midfielder .88, 95%CI .67 to 0.98; forward .90, 95%CI .62 to 0.99). This study's findings provide further evidence for the ecological validity of aerobic fitness in elite male soccer players. Players having a HMPD cut-off equal to or higher than > 1450 m for central backs, > 1990 m for full backs, > 2170 m for midfielders and > 1670 m for forwards may be considered as possessing superior aerobic fitness status. In light of this study's findings, the VL4 test may be considered a valid test to evaluate meaningful information for direct generic aerobic training in soccer players.

Ideal P2Y12 Inhibitor in Acute Coronary Syndrome: A Review and Current Status.

Dual antiplatelet therapy (DAPT) has remained the cornerstone for management of acute coronary syndrome (ACS) over the years. Clopidogrel has been the quintessential P2Y12 receptor (platelet receptor for Adenosine 5' diphosphate) inhibitor for the past two decades. With the demonstration of unequivocal superior efficacy of prasugrel/ticagrelor over clopidogrel, guidelines now recommend these agents in priority over clopidogrel in current management of ACS. Cangrelor has revived the interest in injectable antiplatelet therapy too. Albeit the increased efficacy of these newer agents comes at the cost of increased bleeding and this becomes more of a concern when combined with aspirin. Which P2Y12i is superior over another has been intensely debated over last few years after the ISAR-REACT 5 study with inconclusive data. Three novel antiplatelet agents are already in the pipeline for ACS with all of them succeeding in phase II studies. The search for an ideal antiplatelet remains a need of the hour for optimal reduction of ischemic events in ACS.

Effects of Concurrent Aerobic Plus Resistance Training on Blood Pressure Variability and Blood Pressure Values in Patients with Hypertension and Coronary Artery Disease: Gender-Related Differences.

The purpose of this study was to compare changes in blood pressure variability (BPV) and blood pressure (BP) values occurring in response to concurrent training (CT) between the two genders. A total of 35 males and 20 women aged 55-80 years, with hypertension and coronary artery disease, were included. They underwent a 12-week CT program. The aerobic component of CT was performed according to the rate of perceived exertion while the intensity of the resistance component was set at 60% of 1 repetition maximum for the first 4 weeks and then increased to 80%. BP and BPV were evaluated at baseline and at the end of the CT program through 24 h ambulatory blood pressure monitoring. After 12-weeks, 24 h and daytime systolic BPV decreased in both men and women without significant between-groups differences. Twenty-four-hour daytime and nighttime diastolic BPV decreased in both genders with a significantly greater decrease in women compared to men. Twenty-four-hour daytime systolic and 24 h diastolic BP decreased in men while they were unchanged in women. In conclusion, CT induced similar reductions of systolic BPV in men and women and a greater decrease in diastolic BPV in women. Conversely, CT decreased BP values in males but not in females. CT appears to be an effective intervention for reducing BPV in both genders.

Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects.

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.

Acute Left Atrial Response to Different Eccentric Resistance Exercise Loads in Patients with Heart Failure with Middle Range Ejection Fraction: A Pilot Study.

In this study, we aimed to assess acute changes occurring on atrial function following single bouts of eccentric resistance exercise (ECC-RE) performed at two different loads. Twenty-five patients with chronic heart failure with middle range ejection fraction (HFmrEF) participated in three experimental sessions in a randomized order and on separate days: two sessions of ECC RE at 20% (ECC-20) of one-repetition maximum (1-RM) and 50% (ECC-50) 1-RM, and one session of control, without exercise. Each session lasted three minutes. Before and immediately after the sessions, patients underwent echocardiography and blood pressure and heart rate measurement. Peak atrial longitudinal strain (PALS) and peak atrial contractile strain (PACS) significantly increased after both ECC-20 (+16.3%) and ECC-50 (+18.1%) compared to control (between sessions p = 0.022). Peak atrial contractile strain (PACS) significantly increased after ECC-50 (+28.4%) compared to ECC-20 (+17.0%) and control (between sessions p = 0.034). The ratio of transmitral and annular velocities (E/E') increased significantly after ECC-20 (+10.4%) and ECC-50 (+19.0%) compared to control (between groups p = 0.003). EF, left ventricular longitudinal strain, and stroke volume did not change after ECC-RE sessions compared to control. Cardiac output increased significantly after ECC-20 and ECC-50 compared to control, (between groups p = 0.025). In conclusion, both ECC-RE sessions were well tolerated, and LA functional reserve was properly mobilized in response to ECC-RE in patients with HFmrEF. Cardiac output increased at the cost of an increased LV filling pressure, but no detrimental changes of LV function occurred.

L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19 Pandemic.

Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-arginine is the substrate used by nitric oxide (NO) synthase to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy one bottle containing 1.66 g of L-arginine or one bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT), and their Borg modified 0-10 rating of perceived exertion (BRPE) was assessed before starting and at the end of the treatment. Seventy-five patients receiving L-arginine, and 35 receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-arginine group compared with both baseline and placebo (P < 0.0001). Additionally, we observed a significant improvement in the BRPE in patients treated with L-arginine but not in the placebo group. Taken together, our data indicate that L-arginine potentiates the response to CR independently of age, sex, baseline functional capacity, and comorbid conditions. SIGNIFICANCE STATEMENT: This study shows for the first time that oral supplementation of L-arginine potentiates the response to cardiac rehabilitation after myocardial infarction and cardiac revascularization. Indeed, we observed a significant improvement in two fundamental parameters, namely, the 6-minute walking test and the Borg modified 0-10 rating of perceived exertion. Strikingly, the beneficial effects of L-arginine were independent of age, sex, comorbid conditions, and baseline functional capacity.