Aung Myat

Reperfusion therapy for STEMI: is there still a role for thrombolysis in the era of primary percutaneous coronary intervention?

In the past ten years, primary percutaneous coronary intervention (PCI) has replaced thrombolysis as the revascularisation strategy for many patients presenting with ST-segment elevation myocardial infarction (STEMI). However, delivery of primary PCI within evidence-based timeframes is challenging, and health-care provision varies substantially worldwide. Consequently, even with the ideal circumstances of rapid initial diagnosis, long transfer delays to the catheter laboratory can occur. These delays are detrimental to outcomes for patients and can be exaggerated by variations in timing of patients presentation and diagnosis. In this Series paper we summarise the value of immediate out-of-hospital thrombolysis for STEMI, and reconsider the potential therapeutic interface with a contemporary service for primary PCI. We review recent trial data, and explore opportunities for optimisation of STEMI outcomes with a pharmacoinvasive approach.

Future treatment strategies in ST-segment elevation myocardial infarction

Over the past five decades, management of acute ST-segment elevation myocardial infarction (STEMI) has evolved substantially. Current treatment encompasses a systematic chain of network activation, antithrombotic drugs, and rapid instigation of mechanical reperfusion, although pharmacoinvasive strategies remain relevant. Secondary prevention with drugs and lifestyle modifications completes the contemporary management package. Despite a tangible improvement in outcomes, STEMI remains a frequent cause of morbidity and mortality, justifying the quest to find new therapeutic avenues. Ways to reduce delays in doing coronary angioplasty after STEMI onset include early recognition of symptoms by patients and prehospital diagnosis by paramedics so that the emergency room can be bypassed in favour of direct admission to the catheterisation laboratory. Mechanical reperfusion can be optimised by improvements to stent design, whereas visualisation of infarct size has been improved by developments in cardiac MRI. Novel treatments to modulate the inflammatory component of atherosclerosis and the vulnerable plaque include use of bioresorbable vascular scaffolds and anti-proliferative drugs. Translational efforts to improve patients outcomes after STEMI in relation to cardioprotection, cardiac remodelling, and regeneration are also being realised.

Renal Sympathetic Denervation Therapy for Resistant Hypertension: A Contemporary Synopsis and Future Implications

Resistant hypertension (RHTN) is defined as the failure to achieve goal blood pressure (BP), despite adherence to maximally tolerated doses of an appropriate regimen of 3 antihypertensive agents, including a diuretic.1,2 Interest surrounding its evaluation, diagnosis, and treatment has gained significant momentum for the following several reasons: (1) the recognition that patients with true RHTN appear to lie at the extreme end of an already high-risk cardiovascular (CV) morbidity and mortality continuum3–5; (2) the acceptance that accurate estimates of the incidence and prevalence of RHTN remain largely unknown5–8; (3) the need to establish robust prognostic associations to benchmark the degree of benefit gained from timely and consistent management; (4) the need to define the optimal pharmacotherapeutic regimen for RHTN; (5) evidence that RHTN may, at least in part, be mediated by chronic activation of the sympathetic nervous system (SNS)9; and (6) the subsequent emergence of percutaneous sympathetic denervation of the renal arteries—a novel intervention that could stimulate a paradigm shift in the way we manage not only treatment-resistant systemic HTN, but also a myriad of pathophysiological entities associated with chronically augmented SNS activation.10nnIn this review we focus on the evolution of renal sympathetic denervation (RSDN) therapy; its role in the management of RHTN; current trial data; the wider application of renal denervation in the treatment of heart failure (HF), arrhythmia, and the metabolic syndrome; and emerging technologies for this potential device-based standard of care.nnThe renal SNS comprises a dense network of postganglionic efferent fibers that run from the hypothalamus to the kidney via pre- and paravertebral sympathetic ganglia (T10–L2).11,12 Afferent renal sympathetic nerves emerge predominantly from the renal pelvic wall, where mechanoreceptors respond to stretch and chemoreceptors detect renal ischemia and alterations of the biochemical …

Percutaneous Circulatory Assist Devices for High-Risk Coronary Intervention

A unifying definition of what constitutes high-risk percutaneous coronary intervention remains elusive. This reflects the existence of several recognized patient, anatomic, and procedural characteristics that, when combined, can contribute to elevating risk. The relative inability to withstand the adverse hemodynamic sequelae of dysrhythmia, transient episodes of ischemia-reperfusion injury, or distal embolization of atherogenic material associated with coronary intervention serve as a common thread to tie this patient cohort together. This enhanced susceptibility to catastrophic hemodynamic collapse has triggered the development of percutaneous cardiac assist devices such as the intra-aortic balloon pump, Impella (Abiomed Inc., Danvers, Massachusetts), TandemHeart (CardiacAssist, Inc., Pittsburgh, Pennsylvania), and extracorporeal membranous oxygenation to provide adjunctive mechanical circulatory support. In this state-of-the-art review, we discuss the physiology underpinning their application. Thereafter, we examine the results of several randomized multicenter trials investigating their use in high-risk coronary intervention to determine which patients would benefit most from their implantation and whether there is a signal to delineate whether they should be used in an elective pre-procedure, standby, rescue, or routine post-procedure fashion.

What is the optimum adjunctive reperfusion strategy for primary percutaneous coronary intervention

Acute ST-segment elevation myocardial infarction (STEMI) is a dynamic, thrombus-driven event. As understanding of its pathophysiology has improved, the central role of platelets in initiation and orchestration of this process has become clear. Key components of STEMI include formation of occlusive thrombus, mediation and ultimately amplification of the local vascular inflammatory response resulting in increased vasoreactivity, oedema formation, and microvascular obstruction. Activation, degranulation, and aggregation of platelets are the platforms from which these components develop. Therefore, prompt, potent, and predictable antithrombotic therapy is needed to optimise clinical outcomes after primary percutaneous coronary intervention. We review present pharmacological and mechanical adjunctive therapies for reperfusion and ask what is the optimum combination when primary percutaneous coronary intervention is used as the mode of revascularisation in patients with STEMI.

Diabetes, incretin hormones and cardioprotection

In 2012 an estimated 371 million people had diabetes and of those about a half were undiagnosed. That number is set to expand to 552 million by 2030. Type 2 diabetes mellitus (T2DM) constitutes 85–95% of all diabetes in high income nations and may account for an even greater proportion in their low and middle income counterparts (figure 1). As a global pandemic, diabetes claimed the lives of 4.8 million people in 2012, half of whom were below the age of 60u2005years.w1 The predominant cause of morbidity and mortality in diabetes is cardiovascular disease, with at least a twofold excess risk of developing a multitude of vascular pathologies including ischaemic heart disease, different stroke subtypes, peripheral arterial disease, and heart failure.w2 w3 Indeed, as many as 80% of T2DM patients will develop and possibly die from macrovascular complications.w3 Such stark findings have led many to regard diabetes as a coronary heart disease risk equivalent, to a level at which non-diabetic individuals with a previous history of acute coronary syndrome (ACS) would reside.nnnnFigurexa01 nThe International Diabetes Federation Diabetes Update 2012. Diabetes has become a truly global pandemic. Urbanisation, changes in lifestyle, and improvements in healthcare systems combine to increase an individuals risk of acquiring the condition. Reproduced with permission from the International Diabetes Foundation.nnnnFor many years this enhanced cardiovascular risk was thought to be a solely atherosclerosis driven process characterised by endothelial cell dysfunction, oxidative stress, vessel remodelling, impaired vasodilatation, and subendothelial plaque formation. Latterly the concept of the vulnerable patient emerged to highlight the complex interplay between a constellation of deleterious processes spearheaded not only by the vulnerable vessel/plaque but also by vulnerable blood constituents and a vulnerable myocardium; together these processes shift an individual towards a greater susceptibility to developing cardiovascular complications.w4 w5 It …

Is bleeding a necessary evil? The inherent risk of antithrombotic pharmacotherapy used for stroke prevention in atrial fibrillation

Current European atrial fibrillation (AF) guidelines have assigned a strong recommendation for the initiation of antithrombotic therapy to prevent thromboembolism in all but those AF patients at low risk (or with contraindications). Furthermore, the selection of antithrombotic therapy is based on the absolute risks of thromboembolism and bleeding, and the relative risk and benefit for a given patient. By their very mechanism of action, antithrombotic agents used for stroke prevention in AF will potentially increase the risk of bleeding events. Moreover, the introduction of novel oral anticoagulation agents have introduced new, hitherto ill-defined, deficiencies in the authors’ knowledge with respect to anticoagulation monitoring, availability of direct antidotes, drug–drug interactions and the ability to appropriately control and reverse their actions if bleeding events occur. The authors present a comprehensive review on all aspects of bleeding related to currently licensed antithrombotic agents used for stroke prevention in patients with AF.

The Role of Mineralocorticoid Receptor Antagonists in Patients with Acute Myocardial Infarction: Is the Evidence Reflective of Modern Clinical Practice?

Heart failure (HF) and ischaemic heart disease (IHD) are among the leading causes of death globally [1,2]. Despite improvements in the prevention and management of IHD, it remains the commonest cause of HF [2,3]. The prognosis, once a diagnosis of HF is established, is limited with only 50% surviving to 5 years and 10% to 10 years [2]. It is therefore critical that interventional cardiologists not only focus on appropriate revascularisation strategies but also optimal medical therapy to prevent and/or treat HF. Spironolactone, the first available mineralocorticoid receptor antagonist (MRA), has been available for over 50 years when it was used solely in states of hyperaldosteronism [4]. Since then the class has expanded and their role in the medical management and prevention of HF has been firmly established [4]. However, despite the recommendations of both the European Society of Cardiology (ESC) and the American Heart Association (AHA) to initiate eplerenone early after acute myocardial infarction (AMI) associated with left ventricular systolic dysfunction, there are concerns that there is a mismatch between the evidence base behind these recommendations and contemporary management of patients with AMI particularly with regard to revascularisation and speed of discharge [5–7].

In people with atrial fibrillation receiving antithrombotics, short-term non-steroidal anti-inflammatory drug exposure increases risk of serious bleeding

Commentary on: Lamberts M, Lip GYH, Hansen ML, et al. Relation of non-steroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy Ann Intern Med 2014;161:690–8.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]nnnnSince the discovery of salicylic acid from willow bark in the mid-19th century, a multitude of NSAIDs have been developed. They are widely used for their anti-inflammatory and analgesic properties, good tolerability and speed of action. Conversely their use can increase the risk of gastrointestinal bleeding, kidney injury, …nn [1]: {openurl}?query=rft.jtitle%253DAnn%2BIntern%2BMed%26rft.volume%253D161%26rft.spage%253D690%26rft_id%253Dinfo%253Adoi%252F10.7326%252FM13-1581%26rft_id%253Dinfo%253Apmid%252F25402512%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actxn [2]: /lookup/external-ref?access_num=10.7326/M13-1581&link_type=DOIn [3]: /lookup/external-ref?access_num=25402512&link_type=MED&atom=%2Febnurs%2F19%2F1%2F11.atomn [4]: /lookup/external-ref?access_num=000347245600026&link_type=ISI

Appraisal of the Clinical Trial Data on Renal Denervation for the Management of Resistant Hypertension

Over the past decade several national and international societies/regulatory bodies have proposed definitions of resistant hypertension (RHTN) (Table 5.1). There are subtle differences between these definitions, but treatment-resistant systemic HTN can be described as a blood pressure (BP) that remains uncontrolled (i.e., seated office BP >140/90 mmHg) despite adherence to treatment with at least three complementary antihypertensive agents (one of which is a diuretic) already taken at optimal or best-tolerated doses [1, 3, 11, 12]. In the UK, the National Institute for Health and Care Excellence (NICE) Clinical Guideline 127 [13] (Table 5.1) has been more proscriptive with their definition by suggesting that the three antihypertensives would usually be a regimen of an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) plus a calcium channel blocker plus a thiazide-type diuretic (i.e., A+C+D regimen), in accordance with the NICE treatment algorithm (http://guidance.nice.org.uk/CG127). The NICE guidance has also suggested that RHTN should only be diagnosed after confirming inadequate BP control by use of ambulatory blood pressure monitoring (ABPM – i.e., mean daytime BP >135/85), thereby excluding so-called “white coat” hypertension. The optimal target BP in patients treated for RHTN is widely accepted to be <140/90 mmHg, although lower targets might be appropriate in those with diabetes and/or chronic kidney disease (CKD) (Table 5.1) [11]. Furthermore, it should be remembered that an individual whose BP is controlled by the incorporation of a 4th line agent continues to be labelled as having RHTN. Likewise, RHTN should not be confused with uncontrolled HTN, the latter being an umbrella term to include all those individuals unable to achieve adequate BP targets, including that due to non-adherence, despite therapeutic intervention.