NPY and cardiac diseases

Hypertension-induced left ventricular hypertrophy (LVH), along with ischemic heart disease, result in LV remodeling as part of a continuum that often leads to congestive heart failure. The neurohormonal model has been used to underpin many treatment strategies, but optimal outcomes have not been achieved. Neuropeptide Y (NPY) has emerged as an additional therapeutic target, ever since it was recognised as an important mediator released from sympathetic nerves in the heart, affecting coronary artery constriction and myocardial contraction. More recent interest has focused on the mitogenic and hypertrophic effects that are observed in endothelial and vascular smooth muscle cells, and cardiac myocytes. Of the six identified NPY receptor subtypes, Y-1, Y-2, and Y-5 appear to mediate the main functional responses in the heart. Plasma levels of NPY become elevated due to the increased sympathetic activation present in stress-related cardiac conditions. Also, NPY and Y receptor polymorphisms have been identified that may predispose individuals to increased risk of hypertension and cardiac complications. This review examines what understanding exists regarding the likely contribution of NPY to cardiac pathology. It appears that NPY may play a part in compensatory or detrimental remodeling of myocardial tissue subsequent to hemodynamic overload or myocardial infarction, and in angiogenic processes to regenerate myocardium after ischemic injury. However, greater mechanistic information is required in order to truly assess the potential for treatment of cardiac diseases using NPY-based drugs.

Challenges in secondary prevention of cardiovascular diseases: A review of the current practice

With the changing demography of populations and increasing prevalence of co-morbidity, frail patients and more complex cardiac conditions, the modern medicine is facing novel challenges leading to rapid innovation where evidence and experiences are lacking. This scenario is also evident in cardiovascular disease prevention, which continuously needs to accommodate its ever changing strategies, settings, and goals. The present paper summarises actual challenges of secondary prevention, and discusses how this intervention should not only be effective but also efficient. By this way the paper tries to bridge the gaps between research and real-world findings and thereby may find ways to improve standard care.

Heart Disease

Chapter describes some of the more common cardiac conditions in neonates

Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes

Whilst the decision regarding defibrillator implantation in a patient with a familial sudden cardiac death syndrome is likely to be most significant for any particular individual, the clinical decision-making process itself is complex and requires interpretation and extrapolation of information from a number of different sources. This document provides recommendations for adult patients with the congenital Long QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although these specific conditions differ in terms of clinical features and prognosis, it is possible and logical to take an approach to determining a threshold for implantable cardioveter-defibrillator implantation that is common to all of the familial sudden cardiac death syndromes based on estimates of absolute risk of sudden death. Published on behalf of the European Society of Cardiology. © The Author 2010.

Surgical optimisation and characterisation of a minimally invasive aortic banding procedure to induce cardiac hypertrophy in mice

Left ventricular pressure overload in response to aortic banding is an invaluable model for studying progression of cardiac hypertrophy and transition to heart failure. Traditional aortic banding has recently been superceded by minimally invasive transverse aortic banding (MTAB) which does not require ventilation so is less technically challenging. Although the MTAB procedure is superior, few laboratories have documented success and minimal information on the model is available. The aim of this study was to optimise conditions for MTAB and to characterise the development and progression of cardiac hypertrophy. Isofluorane proved the most suitable anaesthetic for MTAB surgery in mice and one week after surgery MTAB animals showed significant increases in systolic blood pressure (110±6 v's 78±3(mmHg), MTAB v's sham, n=7,p

Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial-mesenchymal transition

Objectives: This study sought to investigate the effect of endothelial dysfunction on the development of cardiac hypertrophy and fibrosis.
Background: Endothelial dysfunction accompanies cardiac hypertrophy and fibrosis, but its contribution to these conditions is unclear. Increased nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) activation causes endothelial dysfunction.
Methods: Transgenic mice with endothelial-specific NOX2 overexpression (TG mice) and wild-type littermates received long-term angiotensin II (AngII) infusion (1.1 mg/kg/day, 2 weeks) to induce hypertrophy and fibrosis.
Results: TG mice had systolic hypertension and hypertrophy similar to those seen in wild-type mice but developed greater cardiac fibrosis and evidence of isolated left ventricular diastolic dysfunction (p < 0.05). TG myocardium had more inflammatory cells and VCAM-1-positive vessels than did wild-type myocardium after AngII treatment (both p < 0.05). TG microvascular endothelial cells (ECs) treated with AngII recruited 2-fold more leukocytes than did wild-type ECs in an in vitro adhesion assay (p < 0.05). However, inflammatory cell NOX2 per se was not essential for the profibrotic effects of AngII. TG showed a higher level of endothelial-mesenchymal transition (EMT) than did wild-type mice after AngII infusion. In cultured ECs treated with AngII, NOX2 enhanced EMT as assessed by the relative expression of fibroblast versus endothelial-specific markers.
Conclusions: AngII-induced endothelial NOX2 activation has profound profibrotic effects in the heart in vivo that lead to a diastolic dysfunction phenotype. Endothelial NOX2 enhances EMT and has proinflammatory effects. This may be an important mechanism underlying cardiac fibrosis and diastolic dysfunction during increased renin-angiotensin activation.

Systematic review of the use of behaviour change techniques (BCTs) in home-based cardiac rehabilitation programmes for patients with cardiovascular disease-protocol

BACKGROUND: Cardiovascular diseases (CVDs), including myocardial infarction, heart failure, peripheral arterial disease and strokes, are highly prevalent conditions and are associated with high morbidity and mortality. Cardiac rehabilitation (CR) is an effective form of secondary prevention for CVD but there is a lack of information regarding which specific behaviour change techniques (BCTs) are included in programmes that are associated with improvements in cardiovascular risk factors. This systematic review will describe the BCTs which are utilised within home-based CR programmes that are effective at reducing a spectrum of CVD risk factors.

METHODS/DESIGN: The review will be reported in line with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidance. Randomised and quasi-randomised controlled trials of home-based CR initiated following a vascular event (myocardial infarction, heart failure, peripheral arterial disease and stroke patients) will be included. Articles will be identified through a comprehensive search of MEDLINE, Embase, PsycINFO, Web of Science and Cochrane Database guided by a medical librarian. Two review authors will independently screen articles retrieved from the search for eligibility and extract relevant data, identifying which specific BCTs are included in programmes that are associated with improvements in particular modifiable vascular risk factors.

DISCUSSION: This review will be of value to clinicians and healthcare professionals working with cardiovascular patients by identifying specific BCTs which are used within effective home-based CR. It will also inform the future design and evaluation of complex health service interventions aimed at secondary prevention in CVD.

The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study

OBJECTIVES: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy.

DESIGN: We carried out a descriptive epidemiological analysis of population-based data.

SETTING: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country.

RESULTS: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p<0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal β-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n=3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n=11) compared with cardiac controls.

CONCLUSIONS: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.