Antioxidant vitamins in the prevention of atrial fibrillation: what is the evidence?

Atrial fibrillation (AF) is the most common sustained arrhythmia that is associated with significant morbidity and mortality. Current available therapies remain inadequate in symptom control and secondary prevention and are often associated with significant side effects. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. Recently, increasing evidence implicates oxidative stress and inflammation in the pathogenesis of AF. We searched the literature for evidence to support the use of antioxidant vitamins C and E in the prevention of AF. These vitamins, through their reactive-oxygen-species- (ROS-) scavenging effect, have shown a role in AF prevention in both animal and small clinical studies. The available evidence, however, is currently insufficient to support recommendations for their use in the wider patient population. Larger-scale clinical studies are required to confirm these preliminary results. Research is also required to further the understanding of the processes involved in the pathogenesis of AF and the role of antioxidant therapies to prevent the arrhythmia.

Platelet function in patients with diabetes mellitus: from a theoretical to a practical perspective.

Patients with diabetes mellitus have an increased prevalence of vascular disease. Pathologic thrombosis associated with atherosclerotic plaque rupture is a major cause of morbidity and mortality. Platelets are intimately involved in the initiation and propagation of thrombosis. Evidence suggests that platelets from patients with type 2 diabetes have increased reactivity and baseline activation compared to healthy controls. We review the pathophysiology of platelet hyperreactivity in DM patients and its implications in clinical practice, with particular focus on acute coronary syndromes, percutaneous coronary intervention, and novel antiplatelet agents.

Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part II: secondary prevention.

Fundamental research into molecular mechanisms of atrial fibrillation (AF) and improved understanding of processes involved in the initiation and maintenance of AF have transformed the traditional approach to its management by targeting only the electrical aspects, usually with antiarrhythmic drugs and, recently, by ablation. The antiarrhythmic potential of upstream therapies, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), statins, and n-3 (ω-3) polyunsaturated fatty acids, extends beyond the benefit of treating underlying heart disease to modifying the atrial substrate and intervening in specific mechanisms of AF. The key target is structural remodelling of the atria, particularly inflammation and fibrosis, although there is evidence to suggest the direct involvement at the ion channel level. Positive clinical reports supported by robust experimental data have suggested that upstream therapies can be valuable strategies for primary prevention of AF in selected patients and have resulted in several class IIA recommendations in the new European guidelines on AF. However, these results have not been consistently replicated in the secondary prevention setting, and several recent randomized controlled studies failed to demonstrate any effect of upstream therapies on AF burden or on major cardiovascular outcomes. Part II of the review summarizes the evidence base for the use of upstream therapies for secondary prevention of AF.

Tissue Doppler imaging of the tricuspid annulus and myocardial performance index in the evaluation of right ventricular involvement in the acute and late phase of a first inferior myocardial infarction.

BACKGROUND: Ischemic involvement of the right ventricle (RV) can complicate the early course of inferior ST elevation myocardial infarction (IMI) and has significant management implications but its diagnosis is difficult. This study assessed RV involvement in the acute and late phase of IMI by pulse-wave tissue Doppler (PW-TDI) and RV myocardial performance index (RVMPI). METHODS: We prospectively evaluated 38 patients with first IMI, of whom 14 had RV involvement and 24 no RV involvement, as defined by ST segment elevation ≥0.1 mV in lead V4R. Thirty age-matched healthy subjects served as controls. Echocardiographic assessment included PW-TDI measurements from the lateral tricuspid annulus with MPI evaluation and was repeated at 6-month follow-up. RESULTS: Peak systolic velocity of the tricuspid annulus, S', was significantly lower and RVMPI higher in patients with RVMI compared to patients without RVMI and controls. Patients with proximal RCA lesion had lower S' and higher RVMPI than patients with distal RCA or left coronary lesion. In the acute setting, the index S'/MPI < 17 was perfectly discriminatory for RV involvement and had moderate sensitivity and specificity (85%, 87%) for identifying proximal RCA disease. S'/MPI < 23 at 6 months had moderate-to-good sensitivity and specificity in identifying patients with previous RVMI. CONCLUSIONS: Echocardiographic assessment of the RV by PW-TDI of the lateral tricuspid annulus, with derivation of MPI is a sensitive and specific marker of RV involvement in first IMI and remains so 6 months after the ischemic event. The novel index of S'/MPI appears to have potentially improved diagnostic accuracy in identifying RV involvement and proximal RCA lesion.

Practice considerations of early aspirin administration following coronary artery bypass surgery.

Thrombotic occlusion of saphenous vein grafts (SVG), the conduits most commonly used in coronary artery bypass grafting (CABG) surgery, causes significant morbidity and mortality. There is class 1A evidence that early aspirin administration following CABG reduces thrombotic SVG occlusion, as well as overall morbidity and mortality. The American Heart Association/American College of Cardiology and the European Association of Cardiothoracic Surgeons have issued guidelines recommending that 150 to 325 mg aspirin be administered within 6 hours following CABG. We carried out a clinical audit of our practice to identify any reasons for deviation from these standards of care and to implement any corrective measures. We prospectively collected data on 200 consecutive patients who underwent CABG to assess both the compliance in prescribing and administering aspirin and the effect on blood loss and transfusion requirements. Sixty-nine percent of patients received an aspirin loading dose 6 hours postoperatively. The reasons for nonadministration of aspirin were postoperative bleeding (10%), lack of a prescription despite aspirin being clinically indicated (13%), and a prescription for aspirin but no administration (9%). Reasons included inadequate handover between clinical teams (4%), aspirin loading ≤24 hours preoperatively (2%), and administration after the first 6 hours (3%). Our audit showed that early aspirin administration did not cause further bleeding or increase blood or blood product transfusion. We followed the recommendations in the majority of cases, but there is scope for improvement in this practice and a need to address "gray areas" not covered by the guidelines.

Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention.

Atrial fibrillation (AF) is associated with significant morbidity and mortality. It is also a progressive disease secondary to continuous structural remodelling of the atria due to AF itself, to changes associated with ageing, and to deterioration of underlying heart disease. Current management aims at preventing the recurrence of AF and its consequences (secondary prevention) and includes risk assessment and prevention of stroke, ventricular rate control, and rhythm control therapies including antiarrhythmic drugs and catheter or surgical ablation. The concept of primary prevention of AF with interventions targeting the development of substrate and modifying risk factors for AF has emerged as a result of recent experiments that suggested novel targets for mechanism-based therapies. Upstream therapy refers to the use of non-antiarrhythmic drugs that modify the atrial substrate- or target-specific mechanisms of AF to prevent the occurrence or recurrence of the arrhythmia. Such agents include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, n-3 (ω-3) polyunsaturated fatty acids, and possibly corticosteroids. Animal experiments have compellingly demonstrated the protective effect of these agents against electrical and structural atrial remodelling in association with AF. The key targets of upstream therapy are structural changes in the atria, such as fibrosis, hypertrophy, inflammation, and oxidative stress, but direct and indirect effects on atrial ion channels, gap junctions, and calcium handling are also applied. Although there have been no formal randomized controlled studies (RCTs) in the primary prevention setting, retrospective analyses and reports from the studies in which AF was a pre-specified secondary endpoint have shown a sustained reduction in new-onset AF with ACEIs and ARBs in patients with significant underlying heart disease (e.g. left ventricular dysfunction and hypertrophy), and in the incidence of AF after cardiac surgery in patients treated with statins. In the secondary prevention setting, the results with upstream therapies are significantly less encouraging. Although the results of hypothesis-generating small clinical studies or retrospective analyses in selected patient categories have been positive, larger prospective RCTs have yielded controversial, mostly negative, results. Notably, the controversy exists on whether upstream therapy may impact mortality and major non-fatal cardiovascular events in patients with AF. This has been addressed in retrospective analyses and large prospective RCTs, but the results remain inconclusive pending further reports. This review provides a contemporary evidence-based insight into the role of upstream therapies in primary (Part I) and secondary (Part II) prevention of AF.

Churg-Strauss presenting as acute coronary syndrome: sometimes it's zebras.

A 53-year-old patient presented to our institution with troponin-positive chest pain and new-onset peripheral oedema. A week prior, while abroad, he had developed visual disturbances and fever in conjunction with an elevated troponin. Coronary angiography had revealed minor coronary artery disease and he was treated for acute coronary syndrome and occult infection. On arrival to our coronary care unit, further review elicited a history of recently diagnosed and worsening severity asthma with nasal polyposis. A mononeuritis and a vasculitic rash were noted and blood screen showed hypereosinophilia and immunoglobulin E (IgE) elevation. A clinical diagnosis of Churg-Strauss syndrome was made and the patient was treated urgently and successfully with immunosuppressants. The case illustrates a fulminant presentation mode of this rare vasculitis and the importance of seeking a unifying diagnosis in cases presenting with apparently disparate symptoms and findings.

Right ventricular myocardial infarction: pathophysiology, diagnosis, and management.

Right ventricular (RV) ischaemia complicates up to 50% of inferior myocardial infarctions (MIs), though isolated RV myocardial infarction (RVMI) is extremely rare. Although the RV shows good long term recovery, in the short term RV involvement portends a worse prognosis to uncomplicated inferior MI, with haemodynamic and electrophysiologic complications increasing in-hospital morbidity and mortality. Acute RV shock has an equally high mortality to left ventricular (LV) shock. Identification of RV involvement, particularly in the setting of hypotension, can help anticipate and prevent complications and has important management implications which are distinct from the management of patients presenting with LV infarction. Reperfusion therapy, particularly by primary percutaneous coronary intervention, hastens and enhances RV functional recovery that occurs to near normality in most patients. The diagnostic methods for RVMI are discussed, including clinical, electrocardiographic, and various imaging modalities as well as the RV pathophysiology that underpins the specifics of RVMI management.

Anomalous unilateral pulmonary vein in a patient with aortic coarctation.

A 34-year-old woman with previous aortic coarctation repair at the age of 5 years was referred for review. She was in good health. On clinical examination, there was no blood pressure difference between the arms, but pedal pulses were weak. A contrast-enhanced 64-slice thoracic CT scan was performed to assess the coarctation repair.

Conventional second-line salvage chemotherapy regimens are not warranted in patients with malignant lymphomas who have progressive disease after first-line salvage therapy regimens.

This study aimed to determine the outcome of patients with relapsed or refractory lymphoma who have an inadequate response to first-line salvage therapy (1 degrees ST) and who subsequently receive a second-line salvage regimen (2 degrees ST) with the intention of ultimately proceeding to high-dose therapy. The outcome of 57 patients [Hodgkin's Lymphoma 17, histologically-aggressive non-Hodgkin's Lymphoma (NHL) 26, histologically-indolent NHL 14] who received more than one modality of conventional-dose salvage therapy was analysed. Sixteen patients had a partial response (PR) to 1 degrees ST, but subsequently received 2 degrees ST because the PR was judged to be inadequate (iPR) because of persisting disease bulk or marrow infiltration. Of these 16 patients, 10 (63%) continued to respond to 2 degrees ST. Of the 15 patients who had stable disease following 1 degrees ST, 5 (33%) responded to 2 degrees ST. Only one of the 24 (4%) with progressive disease (PD) following 1 degrees ST, responded to 2 degrees ST. 25 of the 57 patients ultimately underwent stem cell transplantation. The 2-year progression-free survival (PFS) and the 3-year overall survival (OS) for all patients was 24% and 31%, respectively. Long-term survival was highly dependent on response to 1 degrees ST (P = 0.0001); in patients with PD following 1 degrees ST, the PFS and OS at 3 years was only 4%. This analysis indicates that patients with malignant lymphomas, who have PD on 1 degrees ST, are not rescued by subsequent salvage regimens. They should either be treated palliatively or novel approaches should be explored.