Global Cardiology Science and Practice - Volume 2015, Issue 3

The Cardiothoracic Surgery Trials Network has reported results of the one-year follow up of their randomized trial “Surgical Treatment of Moderate Ischemic Mitral Regurgitation”. They studied 301 patients with moderate ischemic mitral regurgitation (IMR) undergoing coronary artery bypass grafting (CABG) with or without mitral repair with the primary end-point of change in left ventricular end-diastolic volume index (LVEDVI) at one year and multiple clinical and echocardiographic secondary endpoints. Although their results were against repairing the mitral valve, the debate on surgical management of moderate IMR remains unsettled.

A disease that is associated with stroke and mortality, atrial fibrillation (AF) complicates 30 to 50% of mitral valve disease patients admitted for surgery.¹ Since the introduction of the Cox maze III procedure in 1992 many efforts have been made to come up with modified lesion sets and/or energy sources to surgically treat AF. This lead to the recently published American Heart Association (AHA)– American College of Cardiology (ACC)–Heart Rhythm Society (HRS) guidelines² stating that it is reasonable to perform atrial fibrillation ablation in selected patients undergoing other types of cardiac surgery. The effectiveness of different techniques in conversion to sinus rhythm and the clinical impact of freedom from AF remain a question. The CTS Trials Network have undertaken a trial to answer these questions. The first year results of their randomized trial comparing AF ablation at the time of mitral valve surgery with mitral valve surgery alone were published recently in The New England Journal of Medicine.³

Contrary to its central role in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) in stable ischemic heart disease (SIHD) remains largely restricted to patients in whom medical treatment fails to control symptoms, or those with a large area of myocardium at risk and/or high risk findings on non-invasive testing.^1,2 These recommendations are based on a number of studies – the largest of which is COURAGE – that failed to show any reduction in mortality or myocardial infarction (MI) with PCI compared to optimal medical therapy (OMT) in this group of patients.³ A possible limitation in these studies was relying on visual assessment of angiographic stenoses (which is now well-known to be imprecise) to determine lesions responsible for myocardial ischemia. Non-invasive stress testing – including imaging – may also be inaccurate in patients with multivessel coronary artery disease.^4,5 These limitations have inadvertently led to the inclusion of patients with non-ischemic lesions in these studies, which may have diluted any potential benefit with PCI. Given the superiority of fractional flow reserve (FFR) in identifying ischemic lesions compared to angiography, Fractional flow reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) investigators hypothesized that when guided by FFR, PCI plus medical therapy would be superior to medical therapy alone in patients with SIHD.

The Copenhagen City Heart Study, also known as “Østerbroundersøgelsen”, is a large prospective cardio-vascular population study of 20,000 women and men that was launched in 1975 by Dr Peter Schnohr and Dr Gorm Jensen together with statistician Jørgen Nyboe and Prof. A. Tybjærg Hansen. The original purpose of the study was to focus on prevention of coronary heart disease and stroke. During the years many other aspects have been added to the study: pulmonary diseases, heart failure, arrhythmia, alcohol, arthrosis, eye diseases, allergy, epilepsia, dementia, stress, vital exhaustion, social network, sleep-apnoe, ageing and genetics. In this review we highlight unique aspects of the Copenhagen City Heat Study (CCHS) and its outcome in investigations of clinical and molecular aspects of health and disease in the regional and global population. To increase the impact of population studies with a focus on risk and prevention of cardiovascular and related diseases and to maximize the likelihood of identifying disease causes and effective therapeutics, lessons learned from past research should be applied to the design, implementation and interpretation of future studies.

In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.¹ The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).² However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation.

A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.³ The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF.

One of the most intriguing aspects of cell biology is the state of pluripotency, where the cell is capable of self-renewal for as many times as deemed “necessary”, then at a specified time can differentiate into any type of cell. This fundamental process is required during organogenesis in foetal life and importantly during tissue repair in health and disease. Pluripotency is very tightly regulated, as any dysregulation can result in congenital defects, inability to repair damage, or cancer. Fuelled by the relatively recent interest in stem cell biology and tissue regeneration, the molecules implicated in regulating pluripotency have been the subject of extensive research. One of the important molecules involved in pluripotency, is NaNog, the subject of this article.

Microparticles, in the context of this review, are defined as plasma membrane derived-particles shed by various types of vascular and blood cells in response to different stimuli. They were first described as products of platelet activation or “platelet dust”, however microparticles are now ascribed prominent roles in cardiovascular diseases and contribute to the regulation of pathophysiological processes including, endothelial function, inflammation, coagulation, angiogenesis, and cellular remodelling. Furthermore, microparticles serve as cell-cell messengers by transfer of biological information to target cells in pathophysiological settings and have proven to be prominent biomarkers for health and physiology assessments for both diagnostic and risk stratification purposes. This review describes the mechanisms of microparticles formation, release and clearance, and their detection by currently available and applicable methods. It also discusses the role of microparticles in the development of cardiovascular diseases, as well as their role as biomarkers and cell effectors in the cardiovascular system.

Recent technological advances in cardiology have resulted in new guidelines for the diagnosis, treatment and prevention of diseases. Despite these improvements, sudden death remains one of the main challenges to clinicians because the majority of diseases associated with sudden cardiac death are characterized by incomplete penetrance and variable expressivity. Hence, patients may be unaware of their illness, and physical activity can be the trigger for syncope as first symptom of the disease. Most common causes of sudden cardiac death are congenital alterations and structural heart diseases, although a significant number remain unexplained after comprehensive autopsy. In these unresolved cases, channelopathies are considered the first potential cause of death. Since all these diseases are of genetic origin, family members could be at risk, despite being asymptomatic. Genetics has also benefited from technological advances, and genetic testing has been incorporated into the sudden death field, identifying the cause in clinically affected patients, asymptomatic family members and post-mortem cases without conclusive diagnosis. This review focuses on recent advances in the genetics of channelopathies associated with sudden cardiac death.

Background: Although essentially disappeared from the industrialized world, rheumatic heart disease (RHD) is still prevalent in developing countries, with 300,000 new cases identified each year. In Aswan, Egypt, RHD affects about 2.3% of children with over 90% of the cases being subclinical. Secondary prophylaxis has proved to be an effective method of preventing the progression of RHD. However, its efficacy is limited by low patient adherence. A systematic, generalizable tool is necessary to outline, and ultimately address these barriers. Methods: A 43-item semi-structured questionnaire was developed based on the three domains outlined by Fishbein (capability, intention, and health care barriers). A preliminary evaluation of the barriers to RHD prophylaxis use in Aswan, Egypt was carried out as a pilot study using this tool. Participants were local school children diagnosed with RHD or flagged as high-risk (as per a set of echocardiographic criteria developed by the Aswan Heart Centre) through a previous screening program of randomly selected 3,062 school children in Aswan. Results: 29 patients were interviewed (65.5% adherent to RHD prophylaxis). Compared to non-adherent patients, adherent patients had better understanding of the disease (68.4% versus 20% in the non-adherent group, p = 0.021), and were more aware of the consequences of missing prophylaxis doses (79% versus 40% of non-adherent patients, p = 0.005). Furthermore, 90% of non-adherent patients consciously choose to miss injection appointments (as compared to 31.6% of adherent patients, p = 0.005). Clinic wait time was the most frequently reported deterrent for both groups. Conclusion: A standardized tool that systematically outlines barriers to prophylaxis is a necessary first step to improving adherence to penicillin. Although individually developed tools exist for specific populations, a generalizable tool that takes into account the demographic and cultural differences in the populations of interest will allow for more reliable data collection methodology. Application of this tool will be used to further explore barriers to prophylaxis adherence and inform the basis for the design of future KT interventions.

Given the increasing numbers of cardiac device implantations worldwide, it is important to determine whether permanent endocardial leads across the tricuspid valve can promote tricuspid regurgitation (TR). Virtually all current data is retrospective, and indicates a signal of TR being increased after permanent lead implantation. However, the precise incidence of moderate or greater TR post-procedure, the exact mechanisms (mechanical, traumatic, functional), and the hemodynamic burden and clinical effects of this putative increase in TR, remain uncertain. We have therefore designed a multicenter, international, prospective study of 300 consecutive patients (recruitment completed, baseline data presented) who will undergo echocardiography and clinical assessment prior to, and at 1-year post device insertion. This prospective study will help determine whether cardiac device-associated TR is real, what are its potential mechanisms, and whether it has an important clinical impact on cardiac device patients.

Pulmonary arterial hypertension (PAH) is a serious complication of congenital heart disease, causing an increase in morbidity and mortality. The progressive and irreversible pulmonary vascular disease is more often the consequence of a significant, uncorrected, left-to-right shunt. The rise in pulmonary vascular resistance may lead to the reversal of the shunt and cyanosis, condition known as Eisenmenger syndrome. The management of this population is challenging and requires specific expertise both for diagnosis and follow-up. The progress in the understanding of the underlying pathophysiology of this condition has promoted recent pharmacological trials. New therapeutic options are now available that could improve the long-term prognosis and the quality of life of these patients, but several controversial points still remain and need to be addressed.