Genetic analysis in cardiovascular disease: a clinical perspective

Many forms of cardiovascular disease (CVD) demonstrate heritability and thus a genetic contribution is likely. This is most evident when considering the "simple" Mendelian traits such as hypertrophic cardiomyopathy. However, family history also influences our assessment of patients with complex traits such as coronary artery disease, hypertension, and common forms of hypercholesterolemia, as observed in clinical practice. Recent research has led to advances in our understanding of the genetic basis of both the simple and complex forms of CVD. This review presents the current state of knowledge regarding major gene disorders, as well as more common, complex forms of CVD such as coronary artery disease. It discusses the fundamental approaches being used to identify the genetic basis of the various disease states, as well as the practical implications of the discoveries to clinicians. It also focuses on our need to assess the extent by which genetic analysis can alter our calculation of an individual's risk of disease, and our ability to successfully target treatment that will modify this process.     

The direct thrombin inhibitor ximelagatran/melagatran: a systematic review on clinical applications and an evidence based assessment of risk benefit profile

The direct thrombin inhibitor, ximelagatran, and its active form, melagatran (X/M), have been compared against conventional anticoagulant therapy (CAT) in many clinical settings. Their risk-benefit profile drove large debate until withdrawal by the manufacturer. A systematic review of all published randomized trials has been performed and a meta-analysis of randomised controlled trial (RCT) of X/M versus CAT. Major medical databases were searched for RCTs. Major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, pulmonary embolism), major bleeds (MB), minor bleeds and the rate of hepatotoxicity (HT) were compared. In terms of efficacy, X/M was at least as effective as, or even superior to, CAT. In terms of safety, the overall risk of MAE, MB, minor bleeds and HT was not significantly different for X/M compared with CAT. According to individual clinical settings, X/M was associated with a lower risk of MB but a prohibitive higher risk of HT in those clinical settings requiring prolonged treatment.     

Diagnosis and management of patent foramen ovale

The foramen ovale is a slit-like anatomical structure located in the interatrial wall of the fetal heart that enables right-to-left shunting during fetal development. Although this hole generally closes completely shortly after birth due to shifting pressures in the atrial chambers, it remains open, or 'patent', in about 25% of cases representing a potential substrate for right-to-left shunting during adult life. A patent foramen ovale (PFO) is usually haemodynamically insignificant, even when large, but is the most common cause of right-to-left shunt. Large-diameter PFOs may act as a pathway for passage of thrombus, air, fat, vegetation or vasoactive substances from the venous to the arterial circulation, potentially causing paradoxical emboli and stroke, inappropriate decompression sickness in divers, platypnoea-orthodeoxia syndrome and aural migraine. Over the past two decades, the association between PFO and the occurrence of migraine and cryptogenic stroke, particularly in younger adults, has been subject to considerable controversy and debate. Currently, semi-invasive contrast-transoesophageal echocardiography is accepted as the gold standard to detect right-to-left shunt across a PFO, but other imaging modalities utilising contrast such as second-harmonic transthoracic echocardiogram, transcranial Doppler sonography, CT and cardiac MRI have been shown to have similar sensitivity and specificity in detecting a PFO when compared with transoesophageal echocardiography. In this review the authors discuss embryological origins, diagnostic measures and evidence-based treatment options for the prevention of PFO-related paradoxical embolism, with emphasis on cryptogenic stroke and migraine.     

Pneumopericardium masquerading as an acute myocardial infarction

We report a case of a 64-year-old woman with increasing shortness of breath due to massive pericardial effusion. Cardiac magnetic resonance imaging (CMRI) identified typical findings for pericarditis. Pericardectomy was needed due to suspicion of pericardial abscess formation. Histological examination of the resected tissue revealed an undifferentiated primary pericardial synovial sarcoma. The present case illustrates that pericardial tumours could be an important differential diagnosis to pericarditis, even if typical findings of pericarditis were present in CMRI.     

Left main coronary artery 'embolectomy' using a novel, straightforward technique

A 60-year-old man experienced catastrophic haemodynamic decompensation 3 days following coronary artery bypass grafting (CABG). Aspiration thrombectomy to remove a left main coronary artery saddle embolus resulted in immediate haemodynamic improvement with no requirement for angioplasty or repeat bypass grafting. Coronary thromboembolism should be considered in the differential diagnosis of haemodynamic collapse post CABG. Urgent coronary angiography and aspiration thrombectomy may result in significant improvement for this condition.