Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study

OBJECTIVE—To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation.
DESIGN—Prospective, randomised, single blind, placebo controlled study.
SETTING—Tertiary cardiac referral centre.
PATIENTS—186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation.
INTERVENTIONS—65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated.
MAIN OUTCOME MEASURES—Recurrence of atrial fibrillation or side effects.
RESULTS—In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side effects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side effects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol).
CONCLUSIONS—Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects.


Keywords: amiodarone; sotalol; atrial fibrillation     

Ischaemic cardiomyopathy. Pathophysiological insights,diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology

Ischaemic cardiomyopathy (ICM) represents an important cardiovascular condition associated with substantially increased morbidity and mortality. It is characterised from a broad spectrum of clinical manifestations and pathophysiological substrates and its diagnosis is based on the demonstration of significant left ventricular dysfunction in the context of significant epicardial coronary artery disease. Contemporary management aims at improving prognosis through evidence‐based pharmacotherapy and device therapy, where indicated. Whilst the beneficial role of revascularisation remains clear in patients with strong indications such as those with symptoms and/or acute coronary syndromes, for those patients that are asymptomatic and suffer from stable ischaemic heart disease the impact of revascularisation on hard outcomes remains less well defined and currently its adoption is hampered by the lack of robust randomised data. The aim of this review is therefore to provide a constructive appraisal on the pathophysiology of ICM, the role of the various non‐invasive imaging techniques in the diagnosis of ICM and the differentiation between viable and non‐viable myocardium and finally discourse the potential role of revascularisation and contemporary device therapy in the management of patients with ICM.     

The Heart Failure Association Atlas: rationale,objectives, and methods

Heart failure (HF) constitutes the growing cardiovascular burden and the major public health issue, but comprehensive statistics on HF epidemiology and related management in Europe are missing. The Heart Failure Association (HFA) Atlas has been initiated in 2016 in order to close this gap, representing the continuity directly rooted in the European Society of Cardiology (ESC) Atlas of Cardiology. The major aim of the HFA Atlas is to establish a contemporary dataset on HF epidemiology, resources and reimbursement policies for HF management, organization of the National Heart Failure Societies (NHFS) and their major activities, including education and HF awareness. These data are gathered in collaboration with the network of NHFS of the ESC member and ESC affiliated countries. The dataset will be continuously improved and advanced based on the experience and enhanced understanding of data collection in the forthcoming years. This will enable revealing trends, disparities and gaps in knowledge on epidemiology and management of HF. Such data are highly needed by the clinicians of different specialties (aside from cardiologists and cardiac surgeons), researchers, healthcare policy makers, as well as HF patients and their caregivers. It will also allow to map the snapshot of realities in HF care, as well as to provide insights for evidence‐based health care policy in contemporary management of HF. Such data will support the ESC/HFA efforts to improve HF management ant outcomes through stronger recommendations and calls for action. This will likely influence the allocation of funds for the prevention, treatment, education and research in HF.     

Increased Mobilization of Mesenchymal Stem Cells in Patients With Essential Hypertension: The Effect of Left Ventricular Hypertrophy

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45−/CD34−/CD90+ cells and also as a population of CD45−/CD34−/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45−/CD34−/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45−/CD34−/CD105+ cells was found between hypertensive patients'' and normotensive patients'' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45−/CD34−/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target.

In recent years there has been growing interest in the role of adult stem cells in the pathophysiology of cardiovascular diseases. Although it used to be believed that mammalian cardiomyocytes cease replication soon after birth and that the subsequent growth of the heart was attributable only to cardiomyocyte hypertrophy, newer studies have demonstrated a small degree of cardiogenesis and cardiomyocyte turnover that occurs throughout life.¹, ² These findings led to further research into the contribution of stem cells to the pathophysiology of cardiovascular disorders that has raised the hope of developing new therapeutic approaches. Stem cells have the potential for self‐renewal and differentiation and are the origin cells of various mature cells.Mesenchymal stem cells (MSCs) are also known to have a highly plastic differentiation potential that includes not only adipogenesis, osteogenesis, and chondrogenesis, but also endothelial, cardiovascular,³ and neovascular differentiation.⁴, ⁵, ⁶ Although present in only very small numbers in peripheral blood, in recent years stem and progenitor cells have been implicated in ventricular remodeling and are thought to be of great clinical significance in the pathophysiology of heart failure and atheromatosis. Previous studies have indicated that MSCs derived from peripheral blood, apart from their multilineage potential, can also be used for cellular and gene therapies.⁷ Human MSCs isolated from adult bone marrow provide a model for the development of stem cell therapeutics and could find application in the cardiovascular system—although this is still under investigation.⁸ Under normal conditions, endogenous cardiac progenitor cells are responsible for homeostasis in the heart.⁹ However, it appears that under conditions of stress, this may change, with stem cells from extra‐cardiac sources also playing a role. An interesting experimental study has shown that an increase in preload results in the mobilization of progenitor cells from the bone marrow for use in neovascularization, which plays an important role in cardiac hypertrophy.¹⁰ There are indications that the recruitment of bone marrow–derived cells is involved in cardiac myocyte hypertrophy and maintenance of function in response to pressure overload.¹¹ A recent study from our department has shown increased expression of myocardin and GATA4 genes in the peripheral blood mononuclear cell fraction of hypertensive patients, implying the presence of mesenchymal progenitor cells in the peripheral blood that could possibly be intended to differentiate into cells of the cardiac series.¹² Interestingly, in the patients in that study, myocardin and GATA4 expression was associated with both blood pressure (BP) levels and left ventricular hypertrophy (LVH).To date, most published reports concerning the cardiovascular applications of stem cells have focused on their role in myocardial infarction and in heart failure. Very little work has been done on arterial hypertension, and most has concerned endothelial progenitor cells. The role and behavior of MSCs in patients with essential hypertension is unknown. In a recent animal study, it was shown that the degree to which angiotensin II increased neointima formation was statistically correlated with the increased incorporation of fluorescent bone marrow–derived smooth muscle cells, and that this was inhibited by angiotensin‐1 receptor antagonism.¹³ Based on the hypothesis that MSCs participate in pathophysiological processes that contribute to hypertension, and on the assumption that the behavior of MSCs is altered in hypertensive patients, we carried out the first flow cytometric analysis of CD45−/CD34−/CD90+ and CD45−/CD34−/CD105+ in the peripheral blood of those patients compared with healthy individuals.     

Coronary Vasomotion One Year after Drug-Eluting Stent Implantation: Comparison of Everolimus-Eluting and Paclitaxel-Eluting Coronary Stents

First-generation drug-eluting stents (DES) have been associated with impaired localized coronary vasomotion and delayed endothelialization. We aimed to compare coronary vasomotion after implantation of a newer-generation everolimus-eluting stent (EES), with a first-generation paclitaxel-eluting stent (PES). Coronary vasomotion was studied in 19 patients with EES and 13 with PES. Vasomotor response was measured proximally and distally to the stent and in a remote vessel (reference segment). Quantitative coronary angiography was performed offline. Endothelium independent vasomotion did not differ significantly between the two groups. EES showed significant vasodilatation while PES showed vasoconstriction at both proximal (+4.5?±?3.6 vs ?4.2?±?6.9, p?<?0.001) and distal (+4.6?±?7.9 vs ?4.8?±?9.3, p?=?0.003) segments. The reference segment did not show any significant difference in vasodilatation between the two groups (+9.8?±?6.4 vs +7.2?±?5.2, p?=?0.17). Endothelium-dependent vasomotion at adjacent stent segments is relatively preserved after EES implantation while vasoconstriction was observed after PES implantation.     

Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered?

The hypothesis testing of inappropriate fast, irregular, or asynchronous myocardial contraction provoking cardiomyopathy has been the primary focus of numerous research efforts, especially during the last few decades. Rapid ventricular rates resulting from supraventricular arrhythmias and atrial fibrillation (AF), irregularity of heart rhythm-basic element of AF-and asynchrony, as a consequence of right ventricular pacing, bundle branch block, or frequent premature ventricular complexes, have been established as primary causes of arrhythmia-induced cardiomyopathy. The main pathophysiological pathways involved have been clarified, including neurohumoral activation, energy stores depletion, and abnormalities in stress and strain. Unfortunately, from a clinical point of view, patients usually seek medical advice only when symptoms develop, while the causative arrhythmia may be present for months or years, resulting in myocardial remodelling, diastolic, and systolic dysfunction. In some cases, making a definite diagnosis may become a strenuous exercise for the treating physician, as the arrhythmia may not be present and, additionally, therapy must be applied for the diagnosis to be confirmed retrospectively. The diagnostic process is also hardened due to the fact that strict diagnosing criteria are still a matter of discrepancy. Therapy options include pharmaceutical agents trials, catheter-based therapies and, in the context of chronic ventricular pacing, resynchronization. For the majority of patients, partial or complete recovery is expected, although they have to be followed up thoroughly due to the risk of recurrence. Large, randomized controlled trials are more than necessary to optimize patients' stratification and therapeutic strategy choices.     

Plasma Levels of Nitrites/Nitrates in Patients with Chronic Atrial Fibrillation are Increased after Electrical Restoration of Sinus Rhythm

Introduction: Patients with persistent atrial fibrillation (AF) have hemodynamic changes, which impair endothelial cell function resulting in decreased nitric oxide (NO) production. The aim of this work was to assess endothelial function in AF patients before and at various time points after cardioversion. Methods: Forty-two patients with AF and 21 normal and age-adjusted healthy controls were studied. Nitrites and nitrates (NO _x ) and von Willebrand factor (vWf) concentrations were measured on blood samples taken just before cardioversion and over a 30 day period after the procedure. Results: Plasma levels of NO _x in AF were significantly lower compared to healthy controls (p < 0.001), but after cardioversion gradually increased to approach to those of the healthy controls by the end of the first month of sustained sinus rhythm (p = 0.004). Interestingly plasma levels of NO _x were negatively correlated to left atrial volume measured by ultrasonography (r = –0.34, p < 0.05). Plasma levels of vWf in AF patients were significantly higher compared to the healthy controls (p < 0.01) but with sustained sinus rhythm decreased (p = 0.02). Conclusion: The parallel normalization of the NO _x titers and vWf levels suggests that vascular endothelial function improves after 30 days of normal sinus rhythm.     

Atrial fibrillation: A progressive atrial myopathy or a distinct disease?

Atrial fibrillation is a complex arrhythmia with multiple possible mechanisms. A lot of experimental and clinical studies have shed light on the pathophysiological mechanisms of arrhythmia, especially on molecular basis. Electrical, contractile and structural remodeling, calcium handling abnormalities, autonomic imbalance and genetic factors seem to play a crucial role in atrial fibrillation initiation and maintenance. However, the exact pathophysiological mechanisms of atrial fibrillation are not completely understood and whether atrial fibrillation is an unclassified cardiomyopathy or a distinct disease still remains to be answered. This review highlights proarrhythmic and pathophysiological mechanisms of atrial fibrillation and approaches the molecular basis underlying atrial fibrillation susceptibility.