Global Cardiology Science and Practice - Volume 2014, Issue 2

Carotid sinus syndrome (CSS) is a disease of the autonomic nervous system presenting with syncope, especially in older males who often have cardiovascular disease. The aetiology is unknown and epidemiological data is limited. Forty new patients/million population have been estimated to require pacing for CSS and these patients represent ∼9% of those presenting syncope to a specialist facility. CSS is defined as a response to carotid sinus massage (CSM) that includes reproduction of spontaneous symptoms. Cardioinhibitory CSS shows 3s asystole on CSM and vasodepressor CSS shows >50 mmHg fall in blood pressure (BP), there are mixed forms. The methodology of CSM requires correct massage in the supine and upright with continuous ECG and BP. Assessment of the vasodepressor component implies the ‘method of symptoms’ using atropine to prevent asystole. Carotid sinus hypersensitivity (CSH) is a related condition where CSM is positive in an asymptomatic patient. CSH cannot be assumed to respond to pacing. CSS patients present syncope with little or no warning. If no cause is revealed by the initial evaluation, CSM should be considered in all patients >40 years. CSM carries a small risk of thromboembolism. Therapy for cardioinhibitory CSS is dual chamber pacing, which is most effective in patients with a negative tilt test. Syncope recurrence is ∼20% in 5 years in paced patients. Therapy for the vasodepressor component of CSS, as pure vasodepression or mixed, where tilt testing will likely be positive, is often unrewarding: alternative therapeutic measures may be needed including discontinuation/reduction of hypotensive drugs.

The heart is a mechanically-active organ that dynamically senses its own mechanical environment. This environment is constantly changing, on a beat-by-beat basis, with additional modulation by respiratory activity and changes in posture or physical activity, and further overlaid with more slowly occurring physiological (e.g. pregnancy, endurance training) or pathological challenges (e.g. pressure or volume overload). Far from being a simple pump, the heart detects changes in mechanical demand and adjusts its performance accordingly, both via heart rate and stroke volume alteration. Many of the underlying regulatory processes are encoded intracardially, and are thus maintained even in heart transplant recipients. Over the last three decades, molecular substrates of cardiac mechanosensitivity have gained increasing recognition in the scientific and clinical communities. Nonetheless, the processes underlying this phenomenon are still poorly understood. Stretch-activated ion channels (SAC) have been identified as one contributor to mechanosensitive autoregulation of the heartbeat. They also appear to play important roles in the development of cardiac pathologies – most notably stretch-induced arrhythmias. As recently discovered, some established cardiac drugs act, in part at least, via mechanotransduction pathways suggesting SAC as potential therapeutic targets. Clearly, identification of the molecular substrate of cardiac SAC is of clinical importance and a number of candidate proteins have been identified. At the same time, experimental studies have revealed variable–and at times contrasting–results regarding their function. Further complication arises from the fact that many ion channels that are not classically defined as SAC, including voltage and ligand-gated ion channels, can respond to mechanical stimulation. Here, we summarise what is known about the molecular substrate of the main candidates for cardiac SAC, before identifying potential further developments in this area of translational research.

Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the history of clinical trials in PAH being the largest and longest clinical study conducted thus far in PAH patients with morbidity and mortality events as primary endpoint. SERAPHIN trial investigated whether long-term treatment with the new endothelin receptor antagonist macitentan would reduce the risk of mortality and morbidity in PAH patients.

Stimulators of soluble guanylate cyclase (sCG) are novel pharmacological agents that directly stimulate sGC. Ongoing research on sGC stimulators led to the development of the more potent and more specific sGC stimulator, riociguat.

Recently, the US Food and Drug Administration has approved riociguat to treat pulmonary arterial hypertension in adults. Support for the approval of riociguat comes from the recently published PATENT-1 (Pulmonary Arterial Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1) study.

Extrinsic compression of airways is one the most important causes of respiratory insufficiency in the perioperative period in children with congenital heart disease. This is especially true of pathologies that involve surgery of the aortic arch or conduit replacement of the right ventricular outflow tract. However bronchial obstruction is uncommon in the setting of bidirectional cavopulmonary shunt alone.

We report the case of an infant with a functionally univentricular heart who had a bidirectional superior cavopulmonary shunt and disconnection of the main pulmonary artery from the ventricular mass with oversewing of pulmonary valve. Post-operatively the patient desaturated due to compression of left main bronchus by the left pulmonary artery anteriorly and the descending aorta posteriorly. This was clearly defined by CT based on 3D-modelling of the airways and great vessels. The child was managed conservatively by ventilator support, selective bronchial suctioning and systemic steroids with a successful outcome.

The St Vincent's Screening TO Prevent Heart Failure (STOP-HF) study is a recently published trial that assessed the use of brain natriuretic peptide (BNP) as a screening tool for HF in an at-risk population in reducing newly-diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction. The study provides an excellent model to the global community on how to integrate primary care simple screening with secondary and tertiary level targeted diagnostic and therapeutic system. This integration includes screening of high-risk groups, use of a sensitive screening tool, early diagnostic modalities, early therapeutic interventions, and proper assessment of the hard clinical outcomes. However, more studies are needed across multiple sites around the world with different levels of health care services and variable biomarkers to identify higher-risk groups.

Obesity and metabolic syndrome frequently co-exist and are major health problems worldwide. Prior research has questioned whether obesity without cardiometabolic abnormalities “metabolically healthy obesity” (MHO), has adverse effects on overall cardiovascular disease risk (CVD). The association between MHO and the first development of acute myocardial infarction and heart failure (HF) was evaluated in the second HUNT (Nord-Trøndelag Health).

The use of anticoagulant therapy in patients with pulmonary arterial hypertension (PAH) has been controversial for decades. Recommendations for anticoagulation in these patients are often derived from small, retrospective, and single centre studies without any placebo-controlled randomized study. Furthermore, uncertainties exist regarding a number of issues such as patient selection, risk stratification for bleeding, the intensity of anticoagulation, appropriateness of anticoagulation in different types of PAH, and the potential use of new oral anticoagulants.

Recently, the database of the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) has been analyzed to assess the effect of anticoagulation on the long-term outcome of patients with various forms of PAH. This analysis is the largest to date to assess anticoagulant therapy in PAH patients in a prospective design with long observation period. The results of COMPERA lend support to current recommendations for the use of anticoagulant therapy in patients with idiopathic PAH, but not in other forms of PAH. Also, the study confirmed the previously reported concern that anticoagulant therapy may be harmful in patients with scleroderma-associated PAH.

Radiofrequency ablation (RFA) for the treatment of paroxysmal Atrial Fibrillation (pAF) has a class 1 indication in patients who have not tolerated or responded to antiarrhythmic medications. Antiarrhythmic medications (AAM) are, however, limited not only by modest efficacy, but also by significant side effects. Discontinuation rates for AAM range from 11-40% in trials. The RAAFT-2 trial evaluates the use of RFA as a first line treatment for pAF compared to optimal pharmacological management (1).

Data from the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial⁶ and 5-year results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI)⁷ are evaluated for further evidence on the effectiveness and safety of a pharmacoinvasive approach for patients presenting with acute ST-segment elevation myocardial infarction (STEMI).

Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH.

MicroRNAs (miRNAs) have emerged as potent modulators of mammalian gene expression, thereby broadening the spectrum of molecular mechanisms orchestrating human physiological and pathological cellular functions. Growing evidence suggests that these small non-coding RNA molecules are pivotal regulators of cardiovascular development and disease. Importantly, multiple miRNAs have been specifically implicated in the onset and progression of heart failure, thus providing a new platform for battling this multi-faceted disease. This review introduces the basic concepts of miRNA biology, describes representative examples of miRNAs associated with multiple aspects of HF pathogenesis, and explores the prognostic, diagnostic and therapeutic potential of miRNAs in the cardiology clinic.

In his quest to comprehend his existence, Man has long been exploring his outer world (macro-cosmos), as well as his inner world (micro-cosmos). In modern times, monmental advances in the fields of physics, chemistry, and other natural sciences have reflected on how we understand the anatomy and physiology of the human body and circulation. Yet, humanity took a long and winding road to reach what we acknowledge today as solid facts of cardiovascular physiology. In this article, we will review some of the milestones along this road.

The atrioventricular (AV) valves are complex anatomical structures which perform sophisticated functions.¹ A wide spectrum of malformations of these valves can occur in patients with AV septal defects. We here describe the anatomic and functional abnormalities of a rare form of the disease, where two valves connected the right atrium to both the right and left ventricles, in addition to a third valve that connected the left atrium to the left ventricle, with no evidence of regurgitation or cyanosis in spite of the relatively large communication between the right atrium and the left ventricle. In addition, the patient had severe subaortic stenosis. The pathophysiology, hemodynamics and method of repair of the condition are discussed.