Implementation of NICE Clinical Guideline 95 for assessment of stable chest pain in a rapid access chest pain clinic reduces the mean number of investigations and cost per patient

Objective In 2010, the National Institute for Health and Care Excellence (NICE) in the UK published Clinical Guideline 95 (CG95) advocating risk stratification of patients using ‘CADScore’ to guide appropriate cardiac investigations for chest pain of recent onset. Implementation of the guideline in the University College London Hospitals NHS Foundation Trust was evaluated to see if it led to a reduction in the average cost of the diagnostic journey per patient and fewer investigations per patient in order to confirm a diagnosis. Methods This was a single centre study at a Tertiary Centre in Central London. The investigative journey for each patient presenting to the Rapid Access Chest Pain Clinic (RACPC) at University College London Hospitals NHS Foundation Trust was recorded. Retrospective analysis on this data was performed. Results Data for 4968 patients presenting to the RACPC from 2004 to 2012 was analysed and a size-matched cohort of 1503 patients preimplementation and postimplementation of the guidelines was compared. The mean cost of investigations postimplementation was £291.83 as compared to £319.54 preimplementation of the guidelines despite higher costs associated with some of the recommended initial investigations. The mean number of tests per patient postguidelines was 0.78 compared to 0.97 for preguidelines. An approximate twofold increase in patients not requiring tests was seen post-CG95 implementation (245 pre-CG95 vs 476 post-CG95)

Remote preconditioning in normal and hypertrophic rat hearts

<p>Abstract</p> <p>Background</p> <p>The aim of our study was to investigate whether remote preconditioning (RPC) improves myocardial function after ischemia/reperfusion injury in both normal and hypertrophic isolated rat hearts. This is the first time in world literature that cardioprotection by RPC in hypertrophic myocardium is investigated.</p> <p>Methods</p> <p>Four groups of 7 male Wistar rats each, were used: Normal control, normal preconditioned, hypertrophic control and hypertrophic preconditioned groups. Moderate cardiac hypertrophy was induced by fludrocortisone acetate and salt administration for 30 days. Remote preconditioning of the rat heart was achieved by 20 minutes transient right hind limb ischemia and 10 minutes reperfusion of the anaesthetized animal. Isolated Langendorff-perfused animal hearts were then subjected to 30 minutes of global ischemia and reperfusion for 60 minutes. Contractile function and heart rhythm were monitored. Preconditioned groups were compared to control groups.</p> <p>Results</p> <p>Left ventricular developed pressure (LVDP) and the product LVDP × heart rate (HR) were significantly higher in the hypertrophic preconditioned group than the hypertrophic control group while left ventricular end diastolic pressure (LVEDP) and severe arrhythmia episodes did not differ. Variances between the normal heart groups were not significantly different except for the values of the LVEDP in the beginning of reperfusion.</p> <p>Conclusions</p> <p>Remote preconditioning seems to protect myocardial contractile function in hypertrophic myocardium, while it has no beneficial effect in normal myocardium.</p

Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion

Short non-lethal ischemic episodes administered to hearts prior to (ischemic preconditioning, IPC) or directly after (ischemic postconditioning, IPost) ischemic events facilitate myocardial protection. Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults. We propose that coronary IPC effluent contains hydrophobic cytoprotective mediators acting via PI3K/Akt-dependent pro-survival signaling at ischemic reperfusion. Ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. IPC effluent administered for 10 min prior to index ischemia attenuated infarct size by ≥55% versus control hearts (P < 0.05). Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05). The IPC effluent significantly increased Akt phosphorylation in un-preconditioned hearts when administered before ischemia or at reperfusion, while pharmacological inhibition of PI3K/Akt-signaling at reperfusion completely abrogated the cardioprotection offered by effluent administration. Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05). The total hydrophobic effluent fraction significantly reduced infarct size independently of temporal administration (before ischemia, at reperfusion or as remote postconditioning). In conclusion, the IPC effluent retains strong cardioprotective properties, containing hydrophobic mediator(s) < 30 kDa offering cytoprotection via PI3K/Akt-dependent signaling at ischemic reperfusion

Prevention of coronary microvascular obstruction by addressing the individual susceptibility

Another pathogenetic component of coronary microvascular obstruction (CMVO) is constituted by the individual susceptibility to microvascular dysfunction, probably related to the function, as well as to the structure and the density of the microcirculation. Common and uncommon cardiovascular risk factors can cause a pre-existing transient or permanent microvascular dysfunction, which contributes to the development and prognosis of acute coronary syndrome. Moreover, genetic factors may enhance the individual susceptibility of CMVO, affecting polymorphism of genes responsible of the onset, trigger and/or modulation of coronary microvascular dysfunction, as well as the resistance to the lysis. Finally, ischemic pre-conditioning may determine the individual susceptibility to CMVO, by protecting both the myocardium and the coronary microcirculation. This chapter summarizes the mechanisms, the effects, the prevention, and treatment of the single causes of individual susceptibility to CMVO

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure