The Different Pathways of Epicardial Adipose Tissue across the Heart Failure Phenotypes: From Pathophysiology to Therapeutic Target

Epicardial adipose tissue (EAT) is an endocrine and paracrine organ constituted by a layer of adipose tissue directly located between the myocardium and visceral pericardium. Under physiological conditions, EAT exerts protective effects of brown-like fat characteristics, metabolizing excess fatty acids, and secreting anti-inflammatory and anti-fibrotic cytokines. In certain pathological conditions, EAT acquires a proatherogenic transcriptional profile resulting in increased synthesis of biologically active adipocytokines with proinflammatory properties, promoting oxidative stress, and finally causing endothelial damage. The role of EAT in heart failure (HF) has been mainly limited to HF with preserved ejection fraction (HFpEF) and related to the HFpEF obese phenotype. In HFpEF, EAT seems to acquire a proinflammatory profile and higher EAT values have been related to worse outcomes. Less data are available about the role of EAT in HF with reduced ejection fraction (HFrEF). Conversely, in HFrEF, EAT seems to play a nutritive role and lower values may correspond to the expression of a catabolic, adverse phenotype. As of now, there is evidence that the beneficial systemic cardiovascular effects of sodium-glucose cotransporter-2 receptors-inhibitors (SGLT2-i) might be partially mediated by inducing favorable modifications on EAT. As such, EAT may represent a promising target organ for the development of new drugs to improve cardiovascular prognosis. Thus, an approach based on detailed phenotyping of cardiac structural alterations and distinctive biomolecular pathways may change the current scenario, leading towards a precision medicine model with specific therapeutic targets considering different individual profiles. The aim of this review is to summarize the current knowledge about the biomolecular pathway of EAT in HF across the whole spectrum of ejection fraction, and to describe the potential of EAT as a therapeutic target in HF

The coherent dynamics of photoexcited green fluorescent proteins

The coherent dynamics of vibronic wave packets in the green fluorescent protein is reported. At room temperature the non-stationary dynamics following impulsive photoexcitation displays an oscillating optical transmissivity pattern with components at 67 fs (497 cm-1) and 59 fs (593 cm-1). Our results are complemented by ab initio calculations of the vibrational spectrum of the chromophore. This analysis shows the interplay between the dynamics of the aminoacidic structure and the electronic excitation in the primary optical events of green fluorescent proteins.Comment: accepted for publication in Physical Review Letter

Hypertensive response to exercise, hypertension and heart failure with preserved ejection fraction (HFpEF)-a continuum of disease?

INTRODUCTION Heart failure with preserved ejection fraction (HFpEF) has been shown to be a long-term consequence of uncontrolled arterial hypertension (aHT). Other than that, hypertensive response to exercise (HRE) precedes aHT. We aim to evaluate the available evidence for a continuum of HRE, aHT and HFpEF. METHODS A literature search on PubMed was conducted to assembly the most recent data on the topic. After collecting the data, a qualitative analysis was instrumented. RESULTS 10 studies including 16,165 subjects were analyzed with respect to the association between HRE and the future risk of developing aHT. With the exception of one study, all reported on a positive association between HRE and the future development of aHT despite methodological issues related to different definitions for HRE. Furthermore, HRE was associated with an increased risk of coronary artery disease. Moreover, we analysed 6 studies including overall 1366 subjects investigating the association between HRE and HFpEF. In these studies, increased left atrial volume index (LAVI), elevated E/e' (as surrogate parameters of increased LV end-diastolic filling pressure and of diastolic dysfunction) and higher LV mass index have been proposed as independent predictor of HRE in patients with no known HFpEF diagnosis. DISCUSSION AND CONCLUSION The literature search revealed suggestive data on a connection of HRE, aHT and HFpEF. HRE seems to be an independent risk factor for aHT and aHT in turn is one of the main risk factors for HFpEF. However, further research is needed to improve our knowledge of a possible continuum of disease

Hypertensive Response to Exercise in Athletes: Unremarkable Finding or Relevant Marker for Future Cardiovascular Complications?

BACKGROUND In the general population, hypertensive response to exercise (HRE) predicts new-onset resting hypertension or other cardiovascular diseases. METHODS PubMed was searched for English articles published between January 1st 2000 and April 30th 2020. Additional studies were identified via reference lists of included studies. 92 papers were selected for full text analysis, finally 30 studies were included. RESULTS The results from 5 follow-up studies suggested an association between HRE and the risk of developing hypertension, while 10 studies reported a link with adverse cardiovascular events in the general population. Another study showed an association between HRE and future hypertension in athletes after a follow-up of 7 years. HRE in athletes was associated with left ventricular hypertrophy in three studies. Two other studies showed a link between HRE and focal myocardial fibrosis in triathletes and myocardial injury, respectively. One study found lower Apoliprotein-1 serum levels in athletes with HRE leading to a higher risk for cardiovascular disease. Only in one study no association with cardiovascular dysfunction in athletes with HRE was found. CONCLUSIONS Based on current evidence, HRE is not a normal finding in athletes. If detected, it should be interpreted as a risk factor for future cardiovascular complications. Future research should address the adequate follow-up and management of athletes with HRE

Feasibility of Muscle Synergy Outcomes in Clinics, Robotics, and Sports: A Systematic Review

In the last years, several studies have been focused on understanding how the central nervous system controls muscles to perform a specific motor task. Although it still remains an open question, muscle synergies have come to be an appealing theory to explain the modular organization of the central nervous system. Even though the neural encoding of muscle synergies remains controversial, a large number of papers demonstrated that muscle synergies are robust across different tested conditions, which are within a day, between days, within a single subject and between subjects that have similar demographic characteristics. Thus, muscle synergy theory has been largely used in several research fields, such as clinics, robotics and sports. The present systematical review aims at providing an overview on the applications of muscle synergy theory in clinics, robotics and sports; in particular, the review is focused on the papers that provide tangible information for: (i) diagnosis or pathology assessment in clinics; (ii) robot-control design in robotics; and (iii) athletes’ performance assessment or training guidelines in sports

Arrhythmic Manifestations of Cardiac Amyloidosis: Challenges in Risk Stratification and Clinical Management

Amyloidosis is a systemic disease characterized by extracellular deposits of insoluble amyloid in various tissues and organs. Cardiac amyloidosis is a frequent feature of the disease, causing a progressive, restrictive type of cardiomyopathy, and is associated with adverse clinical outcomes and increased mortality. The typical clinical presentation in patients with cardiac amyloidosis is heart failure (HF) with preserved ejection fraction. Most patients present with typical symptoms and signs of HF, such as exertional dyspnea, pretibial edema, pleural effusions and angina pectoris due to microcirculatory dysfunction. However, patients may also frequently encounter various arrhythmias, such as atrioventricular nodal block, atrial fibrillation and ventricular tachyarrhythmias. The management of arrhythmias in cardiac amyloidosis patients with drugs and devices is often a clinical challenge. Moreover, predictors of life-threatening arrhythmic events are not well defined. This review intends to give a deepened insight into the arrhythmic features of cardiac amyloidosis by discussing the pathogenesis of these arrhythmias, addressing the challenges in risk stratification and strategies for management in these patients

Linking sediment supply variations and tectonic evolution in deep time, source-to-sink systems—The Triassic Greater Barents Sea Basin

Triassic strata in the Greater Barents Sea Basin are important records of geodynamic activity in the surrounding catchments and sediment transport in the Arctic basins. This study is the first attempt to investigate the evolution of these source areas through time. Our analysis of sediment budgets from subsurface data in the Greater Barents Sea Basin and application of the BQART approach to estimate catchment properties shows that (1) during the Lower Triassic, sediment supply was at its peak in the basin and comparable to that of the biggest modern-day river systems, which are supplied by tectonically active orogens; (2) the Middle Triassic sediment load was significantly lower but still comparable to that of the top 10 largest modern rivers; (3) during the Upper Triassic, sediment load increased again in the Carnian; and (4) there is a large mismatch (70%) between the modeled and estimated sediment load of the Carnian. These results are consistent with the Triassic Greater Barents Sea Basin succession being deposited under the influence of the largest volcanic event ever at the Permian-Triassic boundary (Siberian Traps) and concurrent with the climatic changes of the Carnian Pluvial Event and the final stages of the Northern Ural orogeny. They also provide a better understanding of geodynamic impacts on sedimentary systems and improve our knowledge of continental-scale sediment transport. Finally, the study demonstrates bypass of sediment from the Ural Mountains and West Siberia into the adjacent Arctic Sverdrup, Chukotka, and Alaska Basins in Late Carnian and Late Norian time.publishedVersio

Value of troponin T versus I in the diagnosis of immune checkpoint inhibitor-related myocarditis and myositis: rechallenge?

A 54-year old patient with metastatic melanoma presented with asymptomatic myositis and myocarditis after combined immune checkpoint inhibitors (ICI) therapy (anti-programmed cell death receptor-1, anti-lymphocyte activating gene-3, and anti-indoleamine 2,3-dioxygenase-1). The diagnosis was based on the typical time window after ICI, recurrence upon re-challenge, elevations of CK, high-sensitive troponin T (hs-TnT) and I (hs-TnI), mild NT-proBNP increase, and positive magnetic resonance imaging criteria. Notably, hsTnI was found to more rapidly increase and fall and to be more heart-specific than TnT in the context of ICI-related myocarditis. This led to ICI therapy withdrawal and switch to a less effective systemic therapy. This case report highlights the differential value of hs-TnT and hs-TnI for diagnosis and monitoring of ICI-related myositis and myocarditis