The validity and reliability of quadriceps twitch force as a measure of skeletal muscle fatigue while cycling.

The measurement of skeletal muscle fatigue in response to cycling exercise is commonly done in isometric conditions, potentially limiting its ecological validity, and creating challenges in monitoring the time course of muscle fatigue across an exercise bout. This study aimed to determine if muscle fatigue could be reliably assessed by measuring quadriceps twitch force evoked while pedaling, using instrumented pedals. Nine participants completed three laboratory visits: a step incremental test to determine power output at lactate threshold, and on separate occasions, two constant-intensity bouts at a power output 10% above lactate threshold. Femoral nerve electrical stimulation was applied to elicit quadriceps twitch force both while pedaling (dynamic) and at rest (isometric). The test-retest reliability of the dynamic twitch forces and the agreement between the dynamic and isometric twitch forces were evaluated. Dynamic twitch force was found to have excellent reliability in an unfatigued state (intraclass correlation coefficient (ICC) = 0.920 and mean coefficient of variation (CV) = 7.5%), and maintained good reliability at task failure (ICC = 0.846 and mean CV = 11.5%). When comparing dynamic to isometric twitch forces across the task, there was a greater relative decline in the dynamic condition (P = 0.001). However, when data were normalized to the 5 min timepoint when potentiation between conditions was presumed to be more similar, this difference disappeared (P = 0.207). The reliability of this method was shown to be commensurate with the gold standard method utilizing seated isometric dynamometers and offers a new avenue to monitor the kinetics of muscle fatigue during cycling in real time.

Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes.

Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds-Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin-derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related SIRT3 expression, and others reduced inflammatory TNFα expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.

Global longitudinal active strain energy density (GLASED): age and sex differences between young and veteran athletes.

BACKGROUND: Global longitudinal active strain energy density (GLASED) is an innovative method for assessing myocardial function and quantifies the work performed per unit volume of the left ventricular myocardium. The GLASED, measured using MRI, is the best prognostic marker currently available. This study aimed to evaluate the feasibility of measuring the GLASED using echocardiography and to investigate potential differences in the GLASED among athletes based on age and sex. METHODS: An echocardiographic study was conducted with male controls, male and female young athletes, and male and female veteran athletes. GLASED was calculated from the myocardial stress and strain. RESULTS: The mean age (in years) of the young athletes was 21.6 for males and 21.4 for females, while the mean age of the veteran athletes was 53.5 for males and 54.2 for females. GLASED was found to be highest in young male athletes (2.40 kJ/m3) and lowest in female veterans (1.96 kJ/m3). Veteran males exhibited lower values (1.96 kJ/m3) than young male athletes did (P < 0.001). Young females demonstrated greater GLASED (2.28 kJ/m3) than did veteran females (P < 0.01). However, no significant difference in the GLASED was observed between male and female veterans. CONCLUSION: Our findings demonstrated the feasibility of measuring GLASED using echocardiography. GLASED values were greater in young male athletes than in female athletes and decreased with age, suggesting possible physiological differences in their myocardium. The sex-related differences observed in GLASED values among young athletes were no longer present in veteran athletes. We postulate that measuring the GLASED may serve as a useful additional screening tool for cardiac diseases in athletes, particularly for those with borderline phenotypes of hypertrophic and dilated cardiomyopathies.

ß-adrenergic stimulation after rewarming does not mitigate hypothermia-induced contractile dysfunction in rat cardiomyocytes.

Victims of severe accidental hypothermia are frequently treated with catecholamines to counteract the hemodynamic instability associated with hypothermia-induced cardiac contractile dysfunction. However, we previously reported that the inotropic effects of epinephrine are diminished after hypothermia and rewarming (H/R) in an intact animal model. Thus, the goal of this study was to investigate the effects of Epi treatment on excitation-contraction coupling in isolated rat cardiomyocytes after H/R. In adult male rats, cardiomyocytes isolated from the left ventricle were electrically stimulated at 0.5 Hz and evoked cytosolic [Ca2+] and contractile responses (sarcomere length shortening) were measured. In initial experiments, the effects of varying concentrations of epinephrine on evoked cytosolic [Ca2+] and contractile responses at 37 °C were measured. In a second series of experiments, cardiomyocytes were cooled from 37 °C to 15 °C, maintained at 15 °C for 2 h, then rewarmed to 37 °C (H/R protocol). Immediately after rewarming, the effects of epinephrine treatment on evoked cytosolic [Ca2+] and contractile responses of cardiomyocytes were determined. At 37 °C, epinephrine treatment increased both cytosolic [Ca2+] and contractile responses of cardiomyocytes in a concentration-dependent manner peaking at 25-50 nM. The evoked contractile response of cardiomyocytes after H/R was reduced while the cytosolic [Ca2+] response was slightly elevated. The diminished contractile response of cardiomyocytes after H/R was not mitigated by epinephrine (25 nM) and epinephrine treatment reduced the exponential time decay constant (Tau), but did not increase the cytosolic [Ca2+] response. We conclude that epinephrine treatment does not mitigate H/R-induced contractile dysfunction in cardiomyocytes.

Air pollution induces morpho-functional, biochemical and biomechanical vascular dysfunction in undernourished rats.

Air pollution (gases and particulate matter -PM) and child undernutrition are globally recognized stressors with significant consequences. PM and its components breach the respiratory alveolar-capillary barrier, entering the vasculature transporting not only harmful particles and its mediators but, altering vascular paracrine and autocrine functions. The aim of this study was to investigate the effects of Residual Oil Fly Ash (ROFA), on the vasculature of young animals with nutritional growth retardation (NGR). Weanling rats were fed a diet restricted 20% (NGR) compared to ad libitum intake (control-C) for 4 weeks. Rats were intranasally instilled with 1 mg/kg BW of ROFA. After 24h exposure, histological and immunohistochemical, biochemical and contractile response to NA/ACh were evaluated in aortas. ROFA induced changes in the tunica media of the aorta in all groups regarding thickness, muscular cells and expression of Connexin-43. ROFA increased TGF-ß1 and decreased eNOs levels and calcium channels in C and NGR animals. An increment in cytokines IL-6 and IL-10 was observed in C, with no changes in NGR. ROFA exposure altered the vascular contractile capacity. In conclusion, ROFA exposure could increase the risk for CVD through the alteration of vascular biochemical parameters, a possible step of the endothelial dysfunction.

Immediate but not prolonged effects of submaximal eccentric vs concentric fatiguing protocols on the etiology of hamstrings' motor performance fatigue.

PURPOSE: Our study aimed to compare the immediate and prolonged effects of submaximal eccentric (ECC) and concentric (CON) fatiguing protocols on the etiology of hamstrings' motor performance fatigue. METHODS: On separate days, 16 males performed sets of 5 unilateral ECC or CON hamstrings' contractions at 80% of their 1 Repetition Maximum (1 RM) until a 20% decrement in maximal voluntary isometric contraction (MVC) torque was reached. Electrical stimulations were delivered during and after MVCs at several time points: before, throughout, immediately after (POST) and 24 h (POST 24) after the exercise. Potentiated twitch torques (T100 and T10, respectively) were recorded in response to high and low frequency paired electrical stimulations, and hamstrings' voluntary activation (VA) level was determined using the interpolated twitch technique. For statistical analysis, all indices of hamstrings' motor performance fatigue were expressed as a percentage of their respective baseline value. RESULTS: At POST, T100 (ECC: -13.3%; CON: -9.7%; p < 0.001), T10 (ECC: -5.1%; CON: -11.8%; p < 0.05) and hamstrings' VA level (ECC: -3.0%; CON: -2.4%; p < 0.001) were significantly reduced from baseline, without statistical differences between fatigue conditions. At POST24, all indices of hamstrings' motor performance fatigue returned to their baseline values. CONCLUSION: These results suggest that the contribution of muscular and neural mechanisms in hamstrings' motor performance fatigue may not depend on contraction type. This may have implications for practitioners, as ECC and CON strengthening could be similarly effective to improve hamstrings' fatigue resistance.

Short-term aerobic exercise prevents development of glucocorticoid myopathic features in aged skeletal muscle in a sex-dependent manner.

Older adults are vulnerable to glucocorticoid-induced muscle atrophy and weakness, with sex potentially influencing their susceptibility to those effects. Aerobic exercise can reduce glucocorticoid-induced muscle atrophy in young rodents. However, it is unknown whether aerobic exercise can prevent glucocorticoid myopathy in aged muscle. The objectives of this study were to define the extent to which sex influences the development of glucocorticoid myopathy in aged muscle, and to determine the extent to which aerobic exercise training protects against myopathy development. Twenty-four-month-old female (n = 30) and male (n = 33) mice were randomized to either sedentary or aerobic exercise groups. Within their respective groups, mice were randomized to either daily treatment with dexamethasone (DEX) or saline. Upon completing treatments, the contractile properties of the triceps surae complex were assessed in situ. DEX marginally lowered muscle mass and soluble protein content in both sexes, which was attenuated by aerobic exercise only in females. DEX increased sub-tetanic force and rate of force development only in females, which was not influenced by aerobic exercise. Muscle fatigue was higher in both sexes following DEX, but aerobic exercise prevented fatigue induction only in females. The sex-specific differences to muscle function in response to DEX treatment coincided with sex-specific changes to the content of proteins related to calcium handling, mitochondrial quality control, reactive oxygen species production, and glucocorticoid receptor in muscle. These findings define several important sexually dimorphic changes to aged skeletal muscle physiology in response to glucocorticoid treatment and define the capacity of short-term aerobic exercise to protect against those changes. KEY POINTS: There are sexually dimorphic effects of glucocorticoids on aged skeletal muscle physiology. Glucocorticoid-induced changes to aged muscle contractile properties coincide with sex-specific differences in the content of calcium handling proteins. Aerobic exercise prevents glucocorticoid-induced fatigue only in aged females and coincides with differences in the content of mitochondrial quality control proteins and glucocorticoid receptors.

Global Longitudinal Active Strain Energy Density (GLASED): A Powerful Prognostic Marker in a Community-Based Cohort.

BACKGROUND: Identifying the imaging method that best predicts all-cause mortality, cardiovascular adverse events and heart failure risk is crucial for tailoring optimal management. Potential prognostic markers include left ventricular myocardial mass, ejection fraction, myocardial strain, stroke work, contraction fraction, pressure-strain product and a new measurement called global longitudinal active strain density (GLASED). OBJECTIVES: This study sought to compare the utility of 23 potential left ventricular prognostic markers of structure and contractile function in a community-based cohort. METHODS: The impact of cardiovascular magnetic resonance image-derived markers extracted by machine learning algorithms was compared to the future risk of adverse events in a group of 44,957 UK Biobank participants. RESULTS: Most markers, including the left ventricular ejection fraction, have limited prognostic value. GLASED was significantly associated with all-cause mortality and major adverse cardiovascular events, with the largest hazard ratio, highest ranking and differentiated risk in all three tertiles (P ≤ 0.0003). CONCLUSIONS: GLASED predicted all-cause mortality and major cardiovascular adverse events better than conventional markers of risk and is recommended for assessing patient prognosis.

Quantifying myocardial active strain energy density: A comparative analysis of analytic and finite element methods for estimating left ventricular wall stress and strain.

AIMS: This study compared commonly used methods for calculating left ventricular wall stress with the finite element analysis and evaluated different approaches to strain estimation. We sought to improve the accuracy of contractance estimation by developing a novel stress equation. BACKGROUND: Multiple methods for calculating LV contractile stress and strain exist. Contractance is derived from stress and strain information and is a measure of myocardial work per unit volume of muscle. Precise stress and strain information are essential for its accurate evaluation. METHODS AND RESULTS: We compared widely used methods for stress and strain calculations across diverse clinical scenarios representing distinct types of left ventricular myocardial disease. Our analysis revealed significant discrepancies in both the stress and strain values obtained with different methods. However, a newly developed modified version of the Mirsky equation demonstrated close agreement with the finite element analysis results for circumferential stress, while the Lamé method produced results close to those of finite element analysis for longitudinal stress and improved contractance accuracy. CONCLUSION: This study highlights significant inconsistencies in stress and strain values calculated using different methods, emphasising the potential impact on contractance calculations and subsequent clinical interpretation. We recommend adopting the Lamé method for longitudinal stress assessment and the modified Mirsky equation for circumferential stress analysis. These methods offer a balance between accuracy and feasibility, making them advantageous for clinical practice. By adopting these recommendations, we can improve the accuracy of LV wall stress and strain estimates, leading to more dependable contractance calculations, better prognostication and improved clinical decisions. CLINICAL AND TRANSLATIONAL IMPACT STATEMENT: Accurately estimating myocardial stress and strain is of paramount significance in clinical practice because the calculation of the contractance, defined and quantified by myocardial active strain energy density, necessitates correct stress and strain data. Contractance, which assesses myocardial work per unit muscle volume, has emerged as a promising indicator of contractile function and a predictor of future risk. The new recommendations for calculating myocardial stress improve the reliability of calculating contractance and enhance the understanding of myocardial diseases.

BeatProfiler: Multimodal In Vitro Analysis of Cardiac Function Enables Machine Learning Classification of Diseases and Drugs.

Goal: Contractile response and calcium handling are central to understanding cardiac function and physiology, yet existing methods of analysis to quantify these metrics are often time-consuming, prone to mistakes, or require specialized equipment/license. We developed BeatProfiler, a suite of cardiac analysis tools designed to quantify contractile function, calcium handling, and force generation for multiple in vitro cardiac models and apply downstream machine learning methods for deep phenotyping and classification. Methods: We first validate BeatProfiler's accuracy, robustness, and speed by benchmarking against existing tools with a fixed dataset. We further confirm its ability to robustly characterize disease and dose-dependent drug response. We then demonstrate that the data acquired by our automatic acquisition pipeline can be further harnessed for machine learning (ML) analysis to phenotype a disease model of restrictive cardiomyopathy and profile cardioactive drug functional response. To accurately classify between these biological signals, we apply feature-based ML and deep learning models (temporal convolutional-bidirectional long short-term memory model or TCN-BiLSTM). Results: Benchmarking against existing tools revealed that BeatProfiler detected and analyzed contraction and calcium signals better than existing tools through improved sensitivity in low signal data, reduction in false positives, and analysis speed increase by 7 to 50-fold. Of signals accurately detected by published methods (PMs), BeatProfiler's extracted features showed high correlations to PMs, confirming that it is reliable and consistent with PMs. The features extracted by BeatProfiler classified restrictive cardiomyopathy cardiomyocytes from isogenic healthy controls with 98% accuracy and identified relax90 as a top distinguishing feature in congruence with previous findings. We also show that our TCN-BiLSTM model was able to classify drug-free control and 4 cardiac drugs with different mechanisms of action at 96% accuracy. We further apply Grad-CAM on our convolution-based models to identify signature regions of perturbations by these drugs in calcium signals. Conclusions: We anticipate that the capabilities of BeatProfiler will help advance in vitro studies in cardiac biology through rapid phenotyping, revealing mechanisms underlying cardiac health and disease, and enabling objective classification of cardiac disease and responses to drugs.

Short-Chain Fatty Acid Butyrate Is an Inotropic Agent With Vasorelaxant and Cardioprotective Properties.

BACKGROUND: The heart can metabolize the microbiota-derived short-chain fatty acid butyrate. Butyrate may have beneficial effects in heart failure, but the underlying mechanisms are unknown. We tested the hypothesis that butyrate elevates cardiac output by mechanisms involving direct stimulation of cardiac contractility and vasorelaxation in rats. METHODS AND RESULTS: We examined the effects of butyrate on (1) in vivo hemodynamics using parallel echocardiographic and invasive blood pressure measurements, (2) isolated perfused hearts in Langendorff systems under physiological conditions and after ischemia and reperfusion, and (3) isolated coronary arteries mounted in isometric wire myographs. We tested Na-butyrate added to injection solutions or physiological buffers and compared its effects with equimolar doses of NaCl. Butyrate at plasma concentrations of 0.56 mM increased cardiac output by 48.8±14.9%, stroke volume by 38.5±12.1%, and left ventricular ejection fraction by 39.6±6.2%, and lowered systemic vascular resistance by 33.5±6.4% without affecting blood pressure or heart rate in vivo. In the range between 0.1 and 5 mM, butyrate increased left ventricular systolic pressure by up to 23.7±3.4% in isolated perfused hearts and by 9.4±2.9% following ischemia and reperfusion, while reducing myocardial infarct size by 81.7±16.9%. Butyrate relaxed isolated coronary septal arteries concentration dependently with an EC50=0.57 mM (95% CI, 0.23-1.44). CONCLUSIONS: We conclude that butyrate elevates cardiac output through mechanisms involving increased cardiac contractility and vasorelaxation. This effect of butyrate was not associated with adverse myocardial injury in damaged hearts exposed to ischemia and reperfusion.

[Evaluation of Contractile Function Using Human iPS Cell-derived Cardiomyocytes].

Cardiotoxicity induced by anti-cancer drugs is a significant concern for patients undergoing cancer treatment. Some anti-cancer drugs can damage cardiac muscle cells directly or indirectly, potentially leading to severe heart failure. Various risk factors, including the type and dosage of chemotherapy agents as well as patient background, contribute to the development of cardiotoxicity. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which enable patient-specific toxicity prediction, hold great promise in this regard. However, the practical implementation of hiPSC-CMs-based prediction of anti-cancer drug-induced cardiotoxicity still faces hurdles. One major challenge involves establishing and optimizing experimental systems for evaluating contractile dysfunction, the ultimate output of heart failure, using hiPSC-CMs. Such efforts are currently underway globally, focusing on tailoring functional evaluation systems to the characteristics of hiPSC-CMs. In this paper, we provide an overview of the contraction mechanisms of cardiac cells and introduce a method of measuring contraction that we have developed, and discuss the current status of contractile function evaluation methods using hiPSC-CMs.

Elevated levels of alcohol dehydrogenase aggravate ethanol-evoked cardiac remodeling and contractile anomalies through FKBP5-yap-mediated regulation of ferroptosis and ER stress.

Alcohol intake provokes severe organ injuries including alcoholic cardiomyopathy with hallmarks of cardiac remodeling and contractile defects. This study examined the toxicity of facilitated ethanol metabolism in alcoholism-evoked changes in myocardial morphology and contractile function, insulin signaling and various cell death domains using cardiac-selective overexpression of alcohol dehydrogenase (ADH). WT and ADH mice were offered an alcohol liquid diet for 12 weeks prior to assessment of cardiac geometry, function, ER stress, apoptosis and ferroptosis. Alcohol intake provoked pronounced glucose intolerance, cardiac remodeling and contractile anomalies with apoptosis, ER stress, and ferroptosis, the effects were accentuated by ADH with the exception of global glucose intolerance. Hearts from alcohol ingesting mice displayed dampened insulin-stimulated phosphorylation of insulin receptor (tyr1146) and IRS-1 (tyrosine) along with elevated IRS-1 serine phosphorylation, the effect was augmented by ADH. Alcohol challenge dampened phosphorylation of Akt and GSK-3ß, and increased phosphorylation of c-Jun and JNK, the effects were accentuated by ADH. Alcohol challenge promoted ER stress, FK506 binding protein 5 (FKBP5), YAP, apoptosis and ferroptosis, the effects were exaggerated by ADH. Using a short-term ethanol challenge model (3 g/kg, i.p., twice in three days), we found that inhibition of FKBP5-YAP signaling or facilitated ethanol detoxification by Alda-1 alleviated ethanol cardiotoxicity. In vitro study revealed that the ethanol metabolite acetaldehyde evoked cardiac contractile anomalies, lipid peroxidation, and apoptosis, the effects of which were mitigated by Alda-1, inhibition of ER stress, FKBP5 and YAP. These data suggest that facilitated ethanol metabolism via ADH exacerbates alcohol-evoked myocardial remodeling, functional defects, and insulin insensitivity possibly through a FKBP5-YAP-associated regulation of ER stress and ferroptosis.

Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.

AIM: Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment. METHODS: The HF-REVERT (Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction after Myocardial Infarction) evaluates the efficacy and safety of CDR132L in HF patients post-acute MI (n = 280), comparing the effect of 5 and 10 mg/kg CDR132L, administered as three single intravenous doses 28 days apart, in addition to standard of care. Key inclusion criteria are the diagnosis of acute MI, the development of systolic dysfunction (LV ejection fraction ≤45%) and elevated N-terminal pro-B-type natriuretic peptide. The study consists of a 6-month double-blinded treatment period with the primary endpoint LV end-systolic volume index and relevant secondary endpoints, followed by a 6-month open-label observation period. CONCLUSION: The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF.

Development of a Mechanism-Based Next-Generation Therapeutic for Heart Failure Derived From the Dark Genome.

The ability of nucleic acids for intramolecular interactions opens manifold opportunities for novel medicines that have the potential to treat intractable human disorders, including heart disease. In this context, microRNAs have been identified as pleiotropic regulators of disease pathways and consequently as powerful therapeutic targets. With antisense oligonucleotides novel drug modalities are available to specifically inhibit as well as correct derailed microRNAs including pathological downstream pathways potentially restoring hallmarks of disease. However, only a handful of microRNA-targeting drugs underwent clinical testing so far, and none in the cardiovascular field. In this paper, the authors introduce the first-ever microRNA-based therapy that entered clinical trials in heart disease and present the previous development from target identification to first-in-human studies.

Plantar Flexor Weakness and Pain Sensitivity Cannot Be Assumed in Midportion Achilles Tendinopathy.

Introduction/Purpose: The purpose of this study was to determine the following in persons with midportion Achilles tendinopathy (AT): 1) maximal strength and power; 2) neural drive during maximal contractions and contractile function during electrically evoked resting contractions; and 3) whether pain, neural drive, and contractile mechanisms contribute to differences in maximal strength. Methods: Twenty-eight volunteers (14 AT, 14 controls) completed isometric, concentric, and eccentric maximal voluntary contractions (MVCs) of the plantar flexors in a Biodex™ dynamometer. Supramaximal electrical stimulation of the tibial nerve was performed to quantify neural drive and contractile properties of the plantar flexors. Pain sensitivity was quantified as the pressure-pain thresholds of the Achilles tendon, medial gastrocnemius, and upper trapezius. Results: There were no differences in plantar flexion strength or power between AT and controls (isometric MVC: P = 0.95; dynamic MVC: P = 0.99; power: P = 0.98), nor were there differences in neural drive and contractile function (P = 0.55 and P = 0.06, respectively). However, the mechanisms predicting maximal strength differed between groups: neural drive predicted maximal strength in controls (P = 0.02) and contractile function predicted maximal strength in AT (P = 0.001). Although pain did not mediate these relationships (i.e., between maximal strength and its contributing mechanisms), pressure-pain thresholds at the upper trapezius were higher in AT (P = 0.02), despite being similar at the calf (P = 0.24) and Achilles tendon (P = 0.40). Conclusions: There were no deficits in plantar flexion strength or power in persons with AT, whether evaluated isometrically, concentrically, or eccentrically. However, the mechanisms predicting maximal plantar flexor strength differed between groups, and systemic pain sensitivity was diminished in AT.

Atrial contractile function and fibrosis in patients with paroxysmal atrial fibrillation in sinus rhythm / Función contráctil auricular y fibrosis en pacientes con fibrilación auricular paroxística en ritmo sinusal

Abstract Objectives: The aim of the study was to investigate atrial contractile function in patients with paroxysmal atrial fibrillation (AF) in sinus rhythm using transthoracic echocardiography (EchoCG). Methods and results: Thirty-five patients with paroxysmal AF and arterial hypertension (mean age 62 ± 10 years, 43% male) in sinus rhythm were enrolled in the study. The control group was composed of comparable patients with arterial hypertension without heart rhythm disturbances. EchoCG was performed during sinus rhythm according to an extended protocol, which included the ejection fraction (EF) of the left atrium (LA) and tissue Doppler measurements. Myocardial fibrosis was assessed quantitatively by videodensitometry in intraventricular and intraatrial (IAS) septa using an original image post-processing algorithm. We found a significant decrease in the left atrial contraction function during sinus rhythm in patients with AF when compared to controls. LA EF (34 ± 14 vs. 54 ± 17, p = 0.03) and A' velocity (0.17 ± 0.04 vs. 0.22 ± 0.04, p = 0.008) decreased while A/A' ratio (2.7 ± 0.2 vs. 1.9 ± 0.1, p = 0.006) increased. Peak A velocity was not affected. Videodensitometric analysis revealed a 2.3-fold increase in IAS fibrosis fraction in AF patients compared with controls (p = 0.01). Conclusion: Patients with AF in sinus rhythm have markedly depressed atrial contractile function. Videodensitometry of IAS has the potential to be used as inexpensive method of atrial fibrosis assessment in patients with AF.

Resumen Objetivo: El objetivo del estudio fue investigar la función contráctil auricular en pacientes con fibrilación auricular paroxística (FA) en ritmo sinusal mediante una ecocardiografía transtorácica (EchoCG). Material y métodos: Treinta y cinco pacientes con FA paroxística e hipertensión arterial (edad media de 62 ± 10 años, el 43% varones) se inscribieron en el estudio en ritmo sinusal. El grupo de control estaba compuesto por pacientes comparables con hipertensión arterial sin alteraciones del ritmo cardíaco. Se realizó una ecocardiografía durante el ritmo sinusal, según el protocolo extendido, incluidas la fracción de eyección (FE) de la aurícula izquierda (AI) y las mediciones Doppler tisulares. La fibrosis miocárdica se evaluó cuantitativamente mediante una videodensitometría de los septos interventricular e interauricular (IAS) utilizando un algoritmo de posprocesamiento de imágenes originales. Resultados: Encontramos una disminución significativa en la función de contracción de la aurícula izquierda durante el ritmo sinusal en pacientes con FA en comparación con el grupo de control. Cabe destacar que la FE de la AI (34 ± 14 vs. 54 ± 17, p = 0.03) y la velocidad A' disminuyeron (0.17 ± 0.04 vs. 0.22 ± 0.04, p = 0,008) mientras que la relación A/A' aumentó (2,7 ± 0,2 vs. 1.9 ± 0.1, p = 0,006). La velocidad pico A no se vio afectada. El análisis videodensitométrico reveló que la fracción de fibrosis IAS en pacientes con FA fue 2.3 veces mayor que en el grupo de control (p = 0.01). Conclusiones: Incluso en ritmo sinusal, los pacientes con FA tienen una función contráctil auricular marcadamente deprimida. La videodensitometría de IAS tiene el potencial de utilizarse como método económico de diagnóstico de la fibrosis auricular en pacientes con FA.

Clinical predictors of improvement in left ventricular ejection fraction in U.S. veterans with heart failure.

Background: Our understanding of the factors associated with improvement of LVEF and a heart failure with improved EF (HFimpEF) phenotype remains incomplete. Methods: We conducted a retrospective study using a national database of patients followed in the Veterans Affairs (VA) health system with serial assessment of left ventricular ejection fraction (LVEF) by echocardiography. We identified US veterans with a new diagnosis of heart failure with: (i) LVEF of <40 % in the 12 months prior to diagnosis, and (ii) follow-up LVEF assessment at least 6 months after their diagnosis. We defined HFimpEF as a final LVEF of ≥40 %. Results: Among the 106,414 US veterans with an initial LVEF of <40 % in this analysis, 39,994 (37.6 %) had a final EF of >40 % after a median follow up of 5 years. Multivariate regression analysis identified several factors that were independently associated with LVEF improvement including female sex, younger age, higher BMI, and a history of specific comorbid conditions such as hypertension, valve disease, atrial fibrillation, connective tissue disease, liver disease, and malignancy (p < 0.001). Conversely, a history of ischemic heart disease and peripheral arterial disease, as well as specific racial backgrounds (Black and Hispanic) were associated with lower rates of LVEF improvement. The model c-statistic for predicting LVEF improvement was 0.70. Conclusions: This large, detailed dataset facilitated an analysis of a large number of variables that significantly associated with HFimpEF; however, their combined discriminatory value for LVEF improvement remained modest, underscoring the complexity of the gene-environment-treatment interactions that govern LV function.

Left atrial size and contractile function in healthy dogs and dogs with chronic mitral valve disease / Tamanho e função sistólica atrial esquerda em cães sadios e com doença valvar crônica de mitral

In humans, left atrial enlargement and reduced contractile functions are associated with adverse cardiovascular events and a poor prognosis in many dilatation of the left atrium occurs with the gradual evolution of chronic mitral valve disease and is well diseases. The left atrium is the most compromised cardiac chamber in dogs with chronic mitral valve disease (CMVD). Therefore, this study aimed to compare the main parameters of left atrial enlargement (left atrium/aorta ratio, left atrial diameter and volume indices) and contractile function (transmitral flow peak velocity A wave and time velocity integral, atrial fraction, and atrial ejection force) at different stages of valve disease, and correlate the left atrial diameter, volume, and contractile function indices with echocardiographic variables predictive of heart failure in dogs (transmitral flow peak velocity E wave, E wave/IVRT ratio, E wave/E´wave ratio, and E wave/A wave ratio). The results showed that progressive characterized by the left atrium/aorta ratio and left atrium volume index. The left atrial diameter and volume indices and left atrium/aorta ratio correlated positively with the transmitral flow peak velocity E wave and E wave/IVRT ratio, which are important indices of diastolic function. The left atrial contractile function indices increased as CMVD evolved. Except for the atrial fraction, the left atrial contractile function indices correlated with the left ventricular filling pressure indices.(AU)

O tamanho e a função atrial esquerda estão relacionados em humanos com eventos cardiovasculares adversos e prognóstico nas principais cardiopatias. Na doença valvar crônica de mitral (DVCM) em cães, o átrio esquerdo é a câmara cardíaca mais comprometida. Portanto, os objetivos deste estudo foram comparar os principais parâmetros de aumento atrial esquerdo (relação átrio esquerdo/aorta, índice do diâmetro atrial esquerdo e índice do volume atrial esquerdo) e função contrátil de átrio esquerdo (velocidade máxima e integral de velocidade da onda A do fluxo transvalvar mitral, fração atrial e força de ejeção atrial) nos diferentes estágios da doença valvar; correlacionar diâmetro e volume atrial esquerdo e os índices de função contrátil atrial esquerda com as variáveis ecocardiográficas preditivas de insuficiência cardíaca em cães (velocidade máxima da onda E do fluxo transvalvar mitral, relação E/TRIV, relação E/E'par e relação E/A). Os resultados mostraram que com a evolução progressiva da doença valvar crônica de mitral, ocorre dilatação progressiva do átrio esquerdo, bem caracterizada pela relação átrio esquerdo/aorta e pelo índice de volume atrial esquerdo. O índice do diâmetro atrial esquerdo, o índice de volume atrial esquerdo e a relação átrio esquerdo/aorta correlacionam-se, positivamente, com a velocidade da onda E e com a relação E/TRIV, que são importantes índices de função diastólica. Os índices de função contrátil do átrio esquerdo aumentam à medida que a DVCM evolui. Os índices de função contrátil do átrio esquerdo apresentam correlação positiva com os índices de pressão de enchimento ventricular esquerdo, exceção feita à fração atrial.(AU)