Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents

During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discusse

Heart rate and blood pressure monitoring in heart failure.

It has been long known that incessant tachycardia and severe hypertension can cause heart failure (HF). In recent years, it has also been recognized that more modest elevations in either heart rate (HR) or blood pressure (BP), if sustained, can be a risk factor both for the development of HF and for mortality in patients with established HF. Heart rate and BP are thus both modifiable risk factors in the setting of HF. What is less clear is the question whether routine systematic monitoring of these simple physiological parameters to a target value can offer clinical benefits. Measuring these parameters clinically during patient review is recommended in HF management in most HF guidelines, both in the acute and chronic phases of the disease. More sophisticated systems now allow long-term automatic or remote monitoring of HR and BP and whether this more detailed patient information can improve clinical outcomes will require prospective RCTs to evaluate. In addition, analysis of patterns of both HR and BP variability can give insights into autonomic function, which is also frequently abnormal in HF. This window into autonomic dysfunction in our HF patients can also provide further independent prognostic information and may in itself be target for future interventional therapies. This article, developed during a consensus meeting of the Heart Failure Association of the ESC concerning the role of physiological monitoring in the complex multi-morbid HF patient, highlights the importance of repeated assessment of HR and BP in HF, and reviews gaps in our knowledge and potential future directions

Alternatives to Transplantation in the Treatment of Heart Failure: New Diagnostic and Therapeutic Insights

none4siThe aim of our current special issue was to present a series of original researches and reviews on recent advances in the diagnosis, medical therapy, and surgical approaches of heart failure. As reported in the introductive review of Agnetti et al., cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndromes are leading to an increasing number of “survivors” who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be o ered only to a small percentage of patients who could bene t from a new heart due to the limited availability of donor organs. e authors reported in this comprehensive review the evaluation of the safety and e cacy of innovative approaches in the diagnosis and treatment of patients refrac- tory to standard medical therapy and excluded from cardiac transplantation lists.mixedNicolini, Francesco; Piepoli, Massimo F.; Agnetti, Giulio; Siniscalchi, GiuseppeNicolini, Francesco; Piepoli, Massimo F.; Agnetti, Giulio; Siniscalchi, Giusepp

A multidisciplinary approach to prevention

Cardiovascular disease accounts for 17,500 deaths globally, representing nearly half of all non-communicable disease deaths. The World Health Organization has set nine lifestyle, risk factor and medicines targets to achieve by 2025 with the aim of reducing premature mortality from non-communicable diseases by 25%. In order to succeed in this, we need to equip our global health professional workforce with the skills to support patients and their families with making lifestyle changes and being in concordance with cardioprotective medication regimes at every opportunity. Success depends on collegiate working through effective interdisciplinary team-based care characterised by shared goals, clear roles, mutual trust, effective communication and measurable processes and outcomes, with the patient and family at the centre of care. Nurses are the largest sector of the health professional workforce and their role in prevention should be optimised. Nurse coordinated care is proven to be effective, especially where they work in an interdisciplinary way with other health professionals such as doctors, pharmacists and psychologists, who provide equally important expertise for supporting holistic care. Successful care models are those that comprehensively target all adverse lifestyles and risk factors that are responsible for the development of cardiovascular disease. These characteristics should be reflected in the standards and core components of prevention and rehabilitation programmes

MicroRNA co-expression networks exhibit increased complexity in pancreatic ductal compared to Vater’s papilla adenocarcinoma

iRNA expression abnormalities in adenocarcinoma arising from pancreatic ductal system (PDAC) and Vater’s papilla (PVAC) could be associated with distinctive pathologic features and clinical cancer behaviours. Our previous miRNA expression profiling data on PDAC (n=9) and PVAC (n=4) were revaluated to define differences/ similarities in miRNA expression patterns. Afterwards, in order to uncover target genes and core signalling pathways regulated by specific miRNAs in these two tumour entities, miRNA interaction networks were wired for each tumour entity, and experimentally validated target genes underwent pathways enrichment analysis. One hundred and one miRNAs were altered, mainly over-expressed, in PDAC samples. Twenty-six miRNAs were deregulated in PVAC samples, where more miRNAs were down-expressed in tumours compared to normal tissues. Four miRNAs were significantly altered in both subgroups of patients, while 27 miRNAs were differentially expressed between PDAC and PVAC. Although miRNA interaction networks were more complex and dense in PDAC than in PVAC, pathways enrichment analysis uncovered a functional overlapping between PDAC and PVAC. However, shared signalling events were influenced by different miRNA and/or genes in the two tumour entities. Overall, specific miRNA expression patterns were involved in the regulation of a limited core signalling pathways in the biology landscape of PDAC and PVAC

New Insights in the Diagnosis and Treatment of Heart Failure

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists

Achievement of multiple therapeutic targets for cardiovascular disease prevention. Retrospective analysis of real practice in Italy

Background: Pharmacological therapy in patients at high cardiovascular (CV) risk should be tailored to achieve recommended therapeutic targets. Hypothesis: To evaluate individual global CV risk profile and to estimate the control rates of multiple therapeutic targets for in adult outpatients followed in real practice in Italy. Methods: Data extracted from a cross-sectional, national medical database of adult outpatients in real practice in Italy were analyzed for global CV risk assessment and rates of control of major CV risk factors, including hypertension, dyslipidemia, diabetes, and obesity. CV risk characterization was based on the European SCORE equation and the study population stratified into 3 groups: low risk ( 40 (males)/>50 (females) mg/dL (OR: 0.926, 95% CI: 0.895–0.958), triglycerides <160 mg/dL (OR: 0.925, 95% CI: 0.895–0.957), and BMI <25 kg/m2(OR: 0.888, 95% CI: 0.851–0.926), even after correction for diabetes, renal function, pharmacological therapy, and referring physicians (P < 0.001). Conclusions: Despite low prevalence and optimal medical therapy, individuals with high to very high SCORE risk did not achieve recommended therapeutic targets in a real-world practice

Indexed maximal left atrial volume predicts response to cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) has shown morbidity and mortality benefits in patients with advanced congestive heart failure (HF). Since about one-third of the patients did not appear to respond to CRT, it would seem reasonable to try to identify patients more accurately before implantation. Left atrial (LA) dimension has been proposed as a powerful outcome predictor in patients with heart disease. Accordingly, the aim of this study is to prospectively assess the predictive value of LA for selecting CRT responders. Methods Fifty two consecutive patients with refractory HF, sinus rhythm and left bundle branch block were enrolled in the study and planned for CRT implantation. Clinical and echocardiographic evaluations were performed before CRT implantation and after 6 months. Three LA volumes indexed to body surface area (iLAV) were computed to evaluate the LA complexity: maximal LAV (iLAVmax), LAV just before atrial systole (iLAVpre), and minimal LAV (iLAVpost). CRT responders were defined as those who presented a reduction of &gt; 10% in LVESVi at 6-month follow-up. Results Responders (63%) and nonresponders (37%) had similar baseline clinical characteristics and pre-implantation LV volumes. However, baseline LA volumes were significantly associated with the extent of LV reverse remodeling: in particular, baseline iLAVmax was remarkably lower in responders than in nonresponders (50.2 ± 14.1 ml/m2 vs 65.8 ± 15.7 ml/m2, p = 0.001) resulting predictive for CRT response. Conclusion Patients with small iLAV result as better responders to CRT than larger one. iLAVmax is an independent predictor of LV reverse remodeling and allows to indentify the best candidates for CRT. © 2013 Elsevier Ireland Ltd

Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA–miRNA and miRNA–miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non- tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional back- bone was fulfilled by tight micro-societies of miR- NAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signalling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA–RNA crosstalk, which mechanistically modulates several signalling path- ways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis