Cardiac sympathetic dysfunction in pulmonary arterial hypertension: Lesson from left-sided heart failure

Sympathetic nervous system hyperactivity has a well-recognized role in the pathophysiology of heart failure with reduced left ventricular ejection fraction. Alterations in sympathetic nervous system have been related to the pathophysiology of pulmonary arterial hypertension, but it is unclear whether cardiac sympathetic nervous system is impaired and how sympathetic dysfunction correlates with hemodynamics and clinical status in pulmonary arterial hypertension patients. The aim of this study was to evaluate the cardiac sympathetic nervous system activity by means of 123Iodine-metaiodobenzylguanidine nuclear imaging in pulmonary arterial hypertension patients and to explore its possible correlation with markers of disease severity. Twelve consecutive pulmonary arterial hypertension patients (nine women, median age 56.5 (17.8), eight idiopathic and four connective tissue-associated pulmonary arterial hypertension) underwent cardiac 123Iodine-metaiodobenzylguanidine scintigraphy. The results were compared with those of 12 subjects with a negative history of cardiovascular or pulmonary disease who underwent the same nuclear imaging test because of a suspected paraganglioma or pheochromocytoma, with a negative result (controls), and 12 patients with heart failure with reduced left ventricular ejection fraction. Hemodynamics, echocardiography, six-minute walking distance, cardiopulmonary exercise testing, and N-terminal pro brain natriuretic peptide were collected in pulmonary arterial hypertension patients within one week from 123Iodine-metaiodobenzylguanidine scintigraphy. Cardiac 123Iodine-metaiodobenzylguanidine uptake, assessed as early and late heart-to-mediastinum ratio, was significantly lower in pulmonary arterial hypertension compared to controls (p = 0.001), but similar to heart failure with reduced left ventricular ejection fraction. Myocardial 123Iodine-metaiodobenzylguanidine turnover, expressed as washout rate, was similar in pulmonary arterial hypertension and heart failure with reduced left ventricular ejection fraction and significantly higher compared to controls (p = 0.016). In the pulmonary arterial hypertension group, both early and late heart-to-mediastinum ratios and washout rate correlated with parameters of pulmonary arterial hypertension severity including pulmonary vascular resistance, right atrial pressure, tricuspid annular plane systolic excursion, N-terminal pro brain natriuretic peptide, and peak VO2. Although we evaluated a small number of subjects, our study showed a significant impairment in cardiac sympathetic nervous system in pulmonary arterial hypertension, similarly to that observed in heart failure with reduced left ventricular ejection fraction. This impairment correlated with indices of pulmonary arterial hypertension severity. Cardiac sympathetic dysfunction may be a contributing factor to the development of right-sided heart failure in pulmonary arterial hypertension

Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients

Although there have been many improvements in prognosis for patients with cancer, anticancer therapies are burdened by the risk of cardiovascular toxicity. Heart failure is one of the most dramatic clinical expressions of cardiotoxicity, and it may occur acutely or appear years after treatment. This article reviews the main mechanisms and clinical presentations of left ventricular dysfunction induced by some old and new cardiotoxic drugs in cancer patients, referring to the most recent advances in the field. The authors describe the mechanisms of cardiotoxicity induced by anthracyclines, which can lead to cardiovascular problems in up to 48% of patients who take them. The authors also describe mechanisms of cardiotoxicity induced by biological drugs that produce left ventricular dysfunction through secondary mechanisms. They outline the recent advances in immunotherapies, which have revolutionised anticancer therapies

Cognitive abilities in siblings of children with autism spectrum disorders

The aim of the present study was to assess the cognitive profiles of children with autistic spectrum disorder and of their healthy siblings (Siblings). With the term cognitive profile, we indicate the relationship extant among the values of verbal and performance subtests of the Wechsler Intelligence Scale. The conducted statistical analyses indicated that, although siblings showed a normal intelligent quotient and did not differ in this aspect from typically developing group, their cognitive profile was amazingly similar to that of their relatives affected by autism. A k-means clustering analysis on the values of single subtests further confirmed this result, showing a clear separation between typically developing children on the one side, and autistics and their siblings on the other. We suggest that the common cognitive profile observed in autistic children and their siblings could represent a marker of liability to autism and, thus, a possible intermediate phenotype of this syndrome

Spatiotemporal dynamics in understanding hand-object interactions

It is generally accepted that visual perception results from the activation of a feed-forward hierarchy of areas, leading to increasingly complex representations. Here we present evidence for a fundamental role of backward projections to the occipitotemporal region for understanding conceptual object properties. The evidence is based on two studies. In the first study, using highdensity EEG, we showed that during the observation of how objects are used there is an early activation of occipital and temporal areas, subsequently reaching the pole of the temporal lobe, and a late reactivation of the visual areas. In the second study, using transcranial magnetic stimulation over the occipital lobe, we showed a clear impairment in the accuracy of recognition of how objects are used during both early activation and, most importantly, late occipital reactivation. These findings represent strong neurophysiological evidence that a top-down mechanism is fundamental for understanding conceptual object properties, and suggest that a similar mechanism might be also present for other higher-order cognitive functions

Segmentation agreement and the reliability of radiomics features

Radiomics features extracted from medical images have been shown to correlate with tumor histological biomarkers and patient clinical information. An accurate selection of reliable features is crucial for an efficient prediction/stratification analysis in clinical applications. This work introduces a computational method for evaluating the reliability of radiomics features with respect to image segmentation. To do so, we define four reliability scores that link segmentation variability to feature quality, consistency, robustness and instability. These scores can be used to establish a ranking that helps identifying the best features to employ for the application at hand, allowing an a-priori evaluation of radiomics reliability in clinical applications. We show the performance of the method with Magnetic Resonance images of meningioma patients. In this case, we identified three main groups of features displaying similar behaviors with respect to image segmentation variability

New drugs, therapeutic strategies, and future direction for the treatment of Pulmonary Arterial Hypertension

Despite recent advances in pulmonary arterial hypertension (PAH) treatment, this condition is still characterized by an extremely poor prognosis. In this review, we discuss the use of newly-approved drugs for PAH treatment with already known mechanisms of action (macitentan), innovative targets (riociguat and selexipag), and novel therapeutic approaches with initial up-front combination therapy. Secondly, we describe new potential signalling pathways and investigational drugs with promising role in the treatment of PAH