Current Cardiology Reviews - Volume 10, Issue 4, 2014

Advances in the therapy of atrial fibrillation (AF) have not come easily or quickly, despite the recognized need for significantly better antiarrhythmic agents for AF termination and prevention as well as for more user-friendly anticoagulants for the prevention of emboli in patients with AF. Rather, the road has been only slowly progressive and bumpy. This manuscript will introduce the recent issues with dronedarone, the complex development story for vernakalant, and the appearance of the new oral anticoagulants. Each of these three considerations will then be explored in more depth by the invited experts for this “mini-Thematic issue” in Current Cardiology Reviews.

Patients with non-valvular atrial fibrillation (AF) face an increased risk of stroke compared with those in normal sinus rhythm. The vitamin K antagonist warfarin, available for over half a century, is highly effective in reducing the risk of stroke in patients with AF, but it is a difficult drug to use properly. As a result, it is challenging to keep the anticoagulant effect of warfarin in the desired range. Newer oral anticoagulants (NOACs) that directly inhibit Factor IIa (thrombin) or Factor Xa provide reliable anticoagulation when administer in fixed oral doses without routine coagulation monitoring. This manuscript will review in detail the pivotal trials of these NOACs that led to their approval as well as comment on the factors that should influence their selection.

Dronedarone is an amiodarone analog that differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These modifications reduce thyroid and other end-organ adverse effects and makes dronedarone less lipophilic, with a shorter half-life. Dronedarone has been shown to prevent atrial fibrillation/ flutter (AF/AFl) recurrences in several multi-center trials. In addition to its rhythm control properties, dronedarone has rate control properties. In patients with decompensated heart failure, dronedarone treatment increased mortality and cardiovascular hospitalizations. When dronedarone was used in elderly high risk AF/AFl patients, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. The results of the PALLAS trial suggest that dronedarone should not be used in the long-term treatment of patients with permanent AF. Post-marketing data have demonstrated rare hepatic toxicity to be associated with dronedarone use. Updated practice and regulatory guidelines have positioned dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, the drug should not be used in patients with advanced heart failure and in patients who develop permanent AF.

The sudden onset of atrial fibrillation (AF) is often associated with rapid irregular palpitations, chest pain, shortness of breath and considerable anxiety. If a patient presents shortly after the onset of the arrhythmia the physician may adopt initially an expectant “wait and see” policy, perhaps with the help of mild sedation and drug therapy to reduce the ventricular rate. If the arrhythmia does not terminate spontaneously and has been present for less than 24-48 hours restoration of sinus rhythm by cardioversion should be considered. This manuscript reviews the option of electrical cardioversion versus pharmacologic and the data for, the role of, and the status of vernakalant with respect to the latter.

The authors of this Mini-Hot-Topic collection of review manuscripts have provided an outstanding review of the development and current status of several of our most recently developed agents in the fight against atrial fibrillation (AF). They have also given the readers a glimpse into the difficulty of drug development and the contrasts that can exist with the same product in different geographies. For their efforts they have my deepest appreciation. It is my hope that these articles will assist those of you who are clinicians in your care of patients and those of you who are investigators in your appreciation of the drug development process and its hurdles. More specifically, this Mini-Hot-Topic symposium has reviewed for you: (1) the evidence supporting the new novel oral anticoagulants (NOACs) as first-line therapy for prevention of stroke and systemic embolism in patients with “nonvalvular” atrial fibrillation (NVAF); (2) the winding path taken by dronedarone in reaching its current place in our antiarrhythmic armamentarium – in which it still has a role; and (3) the contrasting decisions made with respect to the marketing of vernakalant in Europe versus the United States. Now, in this last manuscript of the collection, I will echo for emphasis some of their highlights and I will also bring you further up to date with respect to a possible future role for dronedarone, as hinted at by the HARMONY trial.

Peripartum cardiomyopathy (PPCM) is a form of idiopathic dilated cardiomyopathy affecting women in late pregnancy or early puerperium. Although initially described in the late 1800s, it has only recently been recognized as a distinct cardiac condition. The reported incidence and prognosis varies according to geography. The clinical course varies between complete recovery to rapid progression to chronic heart failure, heart transplantation or death. In spite of significant improvements in understanding the pathophysiology and management of the PPCM many features of this unique disease are poorly understood, including incidence, etiology, epidemiology, pathophysiology, predictors of prognosis and optimal therapy. The present article revisits these concepts and recent advances in PPCM.

Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke.

A great bulk of evidence supports the concept that regular exercise training can reduce the incidence of coronary events and increase survival chances after myocardial infarction. These exercise-induced beneficial effects on the myocardium are reached by means of the reduction of several risk factors relating to cardiovascular disease, such as high cholesterol, hypertension, obesity etc. Furthermore, it has been demonstrated that exercise can reproduce the “ischemic preconditioning” (IP), which refers to the capacity of short periods of ischemia to render the myocardium more resistant to subsequent ischemic insult and to limit infarct size during prolonged ischemia. However, IP is a complex phenomenon which, along with infarct size reduction, can also provide protection against arrhythmia and myocardial stunning due to ischemia-reperfusion. Several clues demonstrate that preconditioning may be directly induced by exercise, thus inducing a protective phenotype at the heart level without the necessity of causing ischemia. Exercise appears to act as a physiological stress that induces beneficial myocardial adaptive responses at cellular level. The purpose of the present paper is to review the latest data on the role played by exercise in triggering myocardial preconditioning.

In the stent era, in addition to restenosis, there are many important consequences deserving more attention. Firstly described in peripheral vascular interventions, it took several years for stent fracture to be known as an appreciable complication of coronary intervention. Especially with the introduction of drug eluting stents and the use of coronary stents in more complex cases, its prevalence has raised and new data have been published concerning its mechanism, predictors, diagnosis, clinical course and treatments. This review will discuss the available literature about stent fracture.

Cardiovascular diseases are the leading cause of deaths. Also, cardiovascular risk factors start the atherosclerotic process, which leads to cardiovascular diseases. Nowadays, periodontal disease can also be considered another cardiovascular risk factor. It involves inflammatory, immunological and humoral activities, which induce the production of proinflammatory cytokines and the destruction of the epithelium. This allows the entry of endotoxins and exotoxins in the bloodstream, which may contribute to atherogenesis and thromboembolic events. There is also direct invasion of the vessel wall by oral pathogens, triggering an inflammatory response that produces endothelial dysfunction. In hypertension, changes in microcirculation can cause ischemia in the periodontium, which favors periodontal disease. Moreover, endothelial dysfunction promotes the formation of atherosclerotic plaque and the development of lesions in target organs. Periodontitis has also been associated with insulin resistance and a higher risk for the metabolic syndrome, which is characterized by oxidative stress. This seems to act as a common link to explain the relationship between each component of the metabolic syndrome (including hypertension) and periodontitis. This article will discuss clinical and experimental evidence, as well as possible pathophysiologic mechanisms and links involved in the relationship among periodontal disease, hypertension and cardiovascular disease.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with relevant morbidity and mortality. Besides hypertension, valvular disease and cardiomyopathy, mainly ischemic and dilated, also other conditions like obesity, alcohol abusus, genetic factors and obstructive sleep apnea (OSA) are discussed to contribute to the progression from paroxysmal to persistent AF. The prevalence of OSA among patients with AF is 40-50%. OSA is characterized by periodic or complete cessation of effective breathing during sleep due to obstruction of the upper airways. Obstructive respiratory events result in acute intrathoracic pressure swings and profound changes in blood gases together leading to atrial stretch and acute sympatho-vagal dysbalance resulting in acute apnea related to electrophysiological and hemodynamic alterations. Additionally, repetitive obstructive events in patients with OSA may lead to sympathetic and neurohumoral activation and subsequent structural and functional changes in the atrium creating an arrhythmogenic substrate for AF in the long run. This review focuses on the acute and chronic effects of negative thoracic pressure swings, changes in blood pressure and sympatho-vagal dysbalance induced by obstructive respiratory events on atrial electrophysiology and atrial structure in patients with obstructive sleep apnea.

In cardiology, optical coherence tomography (OCT) is an invasive imaging technique based on the principle of light coherence. This system was developed to obtain three-dimensional high resolution images to examine coronary artery normal and/or pathological structure. This technique replaces the ultrasound used by its main alternative procedure, intravascular ultrasound, by a near-infrared light source. Acute coronary syndromes due to atherosclerotic vascular disease are the leading cause of mortality in developed and developing countries. As a consequence, intravascular imaging systems became an important area of research and 1991 marks the first use of OCT in coronary artery observations. Since its first appearance in invasive cardiology, OCT maintains a strong presence in the research environments for the identification of vulnerable plaques, as it is able to overcome difficulties presented by other techniques such as virtual intravascular ultrasound, near-infrared spectroscopy, and histology. Moreover, OCT is increasingly being used in the clinical practice as a guide during coronary interventions and in the assessment of vascular response after coronary stent implantation. This review focuses on the relevance of OCT in research and clinical applications in the field of invasive cardiology and discusses the future directions of the field.