Global Cardiology Science and Practice - Volume 2014, Issue 1

It is increasingly recognised that lipoprotein(a) [Lp(a)], an inherited, genetically-determined form of LDL-cholesterol, is an independent cardiovascular risk factor and predictor of adverse cardiovascular outcomes. Lp(a) is felt to increase cardiovascular risk via its pro-thrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is currently the most effective treatment for raised Lp(a). There is a growing body of evidence suggesting that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although much more research is required in this field.

Angina which is refractory to conventional medical therapy and revascularisation, is extremely challenging to manage. Treatment options for such patients remain very limited. We describe the case of a patient with refractory angina and raised lipoprotein(a) in whom aggressive reduction of Lp(a) with lipoprotein apheresis successfully ameliorated the progression of coronary stenosis and provided effective and durable relief of angina symptoms. In our centre, we are currently conducting a prospective, randomised controlled cross-over study of patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis or ‘sham’ apheresis with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised phospholipids and their antibodies, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment.

The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these ‘omic’ approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population.

Atrial fibrillation (AF) is a common disorder with a complex and incompletely understood pathophysiology. Genetic approaches to understanding the pathophysiology of AF have led to the identification of several biological pathways important in the pathogenesis of the arrhythmia. These include pathways important for cardiac development, generation and propagation of atrial electrical impulses, and atrial remodeling and fibrosis. While common and rare genetic variants in these pathways are associated with increased susceptibility to AF, they differ substantially among patients with lone versus typical AF. Furthermore, how these pathways converge to a final common clinical phenotype of AF is unclear and might also vary among different patient populations. Here, we review the contemporary knowledge of AF pathogenesis and discuss how derangement in cardiac development, ion channel dysfunction, and promotion of atrial fibrosis may contribute to this common and important clinical disorder.

The use of bivalirudin during primary percutaneous coronary intervention (PPCI) is perceived to be associated with less bleeding compared to unfractionated heparin (UFH). However, evidence supporting this observation is confounded by the frequent co-administration of glycoprotein IIb/IIIa inhibitors in the UFH arm in the majority of previous large trials. The “How Effective Are Antithrombotic Therapies in Primary PCI (HEAT-PPCI)” trial was conducted to test the efficacy and safety of UFH vesrus bivalirudin in patients undergoing PPCI when GP IIb/IIIa inhibitors are used selectively.

Diabetes mellitus (DM) and obesity are associated with significant morbidity and mortality. Recent large-scale trials of intensive medical management for obesity and diabetes have been disappointing. Observational studies and small-scale trials of bariatric surgery on DM patients have shown promising results. The effects of sleeve gastrectomy and gastric bypass in a larger cohort of patients with DM and obesity was tested in the STAMPEDE trial over a 3-year follow-up.

The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70–90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve.

The introduction of transcatheter aortic valve implantation (TAVI) has resulted in a paradigm shift in the treatment of patients with severe aortic stenosis. Data from the recent U.S CoreValve Trial suggest, for the first time, that TAVI is associated with a significantly higher rate of survival at one year compared to surgical aortic valve replacement (SAVR) in the treatment of high-risk patients affected by severe aortic stenosis. The present review discusses this study and the current evidence about TAVI, for the treatment of severe aortic stenosis, from major trials and real world registries.

Resistant hypertension is, by definition, a challenge to most physicians treating hypertension. Renal sympathetic denervation has shown promising early results in treating this condition. The SYMPLICITY HTN-3 is the most recent trial to report the effects of this technique on resistant hypertension. This review discusses this study and its surprising neutral results before ending with an overview of key lessons learned.