The 4q25 variant rs13143308T links risk of atrial fibrillation to defective calcium homoeostasis.

AIMS: Single nucleotide polymorphisms on chromosome 4q25 have been associated with risk of atrial fibrillation (AF) but the exiguous knowledge of the mechanistic links between these risk variants and underlying electrophysiological alterations hampers their clinical utility. Here, we tested the hypothesis that 4q25 risk variants cause alterations in the intracellular calcium homoeostasis that predispose to spontaneous electrical activity. METHODS AND RESULTS: Western blotting, confocal calcium imaging, and patch-clamp techniques were used to identify mechanisms linking the 4q25 risk variants rs2200733T and rs13143308T to defects in the calcium homoeostasis in human atrial myocytes. Our findings revealed that the rs13143308T variant was more frequent in patients with AF and that myocytes from carriers of this variant had a significantly higher density of calcium sparks (14.1 ± 4.5 vs. 3.1 ± 1.3 events/min, P = 0.02), frequency of transient inward currents (ITI) (1.33 ± 0.24 vs. 0.26 ± 0.09 events/min, P < 0.001) and incidence of spontaneous membrane depolarizations (1.22 ± 0.26 vs. 0.56 ± 0.17 events/min, P = 0.001) than myocytes from patients with the normal rs13143308G variant. These alterations were linked to higher sarcoplasmic reticulum calcium loading (10.2 ± 1.4 vs. 7.3 ± 0.5 amol/pF, P = 0.01), SERCA2 expression (1.37 ± 0.13 fold, P = 0.03), and RyR2 phosphorylation at ser2808 (0.67 ± 0.08 vs. 0.47 ± 0.03, P = 0.01) but not at ser2814 (0.28 ± 0.14 vs. 0.31 ± 0.14, P = 0.61) in patients carrying the rs13143308T risk variant. Furthermore, the presence of a risk variant or AF independently increased the ITI frequency and the increase in the ITI frequency observed in carriers of the risk variants was exacerbated in those with AF. By contrast, the presence of a risk variant did not affect the amplitude or properties of the L-type calcium current in patients with or without AF. CONCLUSIONS: Here, we identify the 4q25 variant rs13143308T as a genetic risk marker for AF, specifically associated with excessive calcium release and spontaneous electrical activity linked to increased SERCA2 expression and RyR2 phosphorylation.

Atrial fibrillation in patients on haemodialysis in Andalusia. Prevalence, clinical profile and therapeutic management. / Fibrilación auricular en los pacientes en hemodiálisis en Andalucía. Prevalencia, perfil clínico y manejo terapéutico.

Atrial fibrillation (AF) represents an important social and healthcare problem. There is wide variability in the prevalence of this arrhythmia in studies analysing patients on haemodialysis (HD). OBJECTIVE: To investigate the prevalence, clinical profile and therapeutic management of patients with AF on HD in Andalusia. METHODS: We asked the public healthcare system of Andalusia to provide us with the number of patients who were being treated with HD. We asked attending nephrologists from all hospital and outpatient centres in 5 of the 8 Andalusian provinces to perform an electrocardiogram and to fill out a questionnaire on patients selected by simple random sampling. RESULTS: A total of 2,348 patients were being treated with HD in the 5provinces included in the study. The estimated sample size was 285 patients. We obtained an electrocardiogram and information from 252 patients (88.4%); mean age 65.3±16 years; 40.9% women. Sixty-three patients (25%) had AF. Of these, 36 (14.3%) had AF in the recorded ECG and in the rest it had been documented previously. In the multivariate analysis, older age (OR: 1.071; 95% CI: 1.036-1.107; P=0.000) and greater time on HD (OR: 1.009; 95% CI: 1.004-1.014; P=0.000) were independently associated with the presence of AF. Of the patients with AF, 41.3% were on anticoagulant treatment at the time of the study; and 41.2% were on antiplatelet agents. CONCLUSIONS: AF in dialysis units is an important finding. Establishing the risk-benefit ratio of anticoagulant treatment constitutes a real challenge. Well-designed clinical trials are pivotal in order to define the rational use of antithrombotic drugs.

Valvular calcifications at the start of dialysis predict the onset of cardiovascular events in the course of follow-up.

OBJECTIVE: To analyse the presence of VC at the start of dialysis and its relationship with events and/or death from cardiovascular causes in the course of follow-up. METHODS: In the study, we included patients who started dialysis between November 2003 and September 2007. In the first month of treatment, we assessed the presence of VC by Doppler echocardiography, along with demographic factors and risk factors for cardiovascular disease, coronary artery disease, stroke, atrial fibrillation (AF), and cardiac dimensional and functional electrocardiographic and echocardiographic parameters. The biochemistry values assessed were: haemoglobin, calcium/phosphorous/iPTH metabolism, cholesterol and fractions, triglycerides, troponin I, albumin, CRP and glycosylated haemoglobin. We analysed the association between VC and the presence of myocardial infarction (MI), stroke and/or death from cardiovascular causes up to transplantation, death or the end of the study (December 2012). RESULTS: Of 256 enrolled patients (83% haemodialysis, 17% peritoneal dialysis), 128 (50%) had VC (mitral: 39, aortic: 20, both: 69). In the multivariate analysis, VC was associated with older age (OR: 1.110; 95% CI: 1.073-1.148; p = 0.000) and lower albumin levels (OR: 0.29; 95% CI: 0.14-0.61; p = 0.001). In a follow-up lasting 42.1 ± 30.2 months (898.1 patient-years), 68 patients suffered MI, stroke and/or died from cardiovascular causes. In the Cox regression analysis, older age (HR: 1.028; 95% CI: 1.002-1.055; p = 0.037), coronary artery disease and/or stroke (HR: 1.979; 95% CI: 1.111-3.527; p = 0.021), AF (HR: 2.474; 95% CI: 1.331-4.602; p = 0.004), and the presence of VC at the start of dialysis (HR: 1.996; 95% CI: 1.077-3.700; p = 0.028) were the predictor variables for the occurrence of the analysed events. CONCLUSIONS: The prevalence of VC at the start of dialysis is high and its presence predicts the occurrence of events and/or cardiovascular death in the course of follow-up.

Resolution of left ventricular thrombus by rivaroxaban.

Intracardiac thrombus is a potentially life-threatening condition, with a high risk of embolic complications. Although vitamin K antagonists have been traditionally used for the treatment of intracardiac thrombus, they have relevant disadvantages that limit their use. Rivaroxaban is a once daily oral anticoagulant, currently indicated for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, and for the prevention and treatment of venous thromboembolism. We present the case of a 78-year-old man with nonvalvular atrial fibrillation, heart failure and creatinine clearance of 40 ml/min, anticoagulated with rivaroxaban 15 mg/day as the patient had very difficult access to hematologic controls. The transthoracic echocardiogram showed dilated left ventricle, severe left ventricular dysfunction and two images of thrombus, which disappeared after 4 weeks of treatment with rivaroxaban. To our knowledge, this is the first case reported regarding the resolution of left ventricular thrombosis with rivaroxaban.

Incidence of acute myocardial infarction in the evolution of dialysis patients.

BACKGROUND: Although the estimated frequency of coronary artery disease (CAD) in patients on dialysis is very high, there is considerable variation in the studies published to date regarding the rate of acute myocardial infarction (AMI) in these patients. OBJECTIVE: To establish the incidence of AMI and to analyse the characteristics and consequences of this entity on the clinical progression of incident dialysis patients. METHODS: We recorded AMI in the patients treated in our dialysis unit between 01/01/1999 and 31/12/07. The variables assessed were: prior diagnosis of diabetes, hypertension, CAD (AMI or lesions observed in coronary angiography), ischaemic cerebrovascular accident, advanced peripheral artery disease (PAD), atrial fibrillation and tobacco use. Biochemical analyses included: urea, creatinine, haematocrit, calcium, phosphorous, iPTH, lipids and albumin. Follow-up lasted until transplant, death, loss to follow-up or study end in Dec. 2010. RESULTS: Of the 576 patients recruited (aged 64.6 ± 16 years), 24.7% had diabetes, 82.3% were on haemodialysis (17.7% on peritoneal dialysis), and 34 (5.9%) had a previous diagnosis of CAD. In a follow-up lasting a mean of 40.2 ± 32 months (1931.5 patient-years), 40 patients (6.9%) suffered an AMI. The incidence was 2.13/100 patient-years. The patients without CAD had an incidence of 1.84/100 patient-years and those with a previous diagnosis of CAD had an incidence of 7.53/100 patient-years. In 22.5% of patients, AMI happened in the first 3 months of dialysis, and 37.5% in the 1st year. Of the 40 AMI, 15 were with ST-segment elevation (incidence: 0.79/100 patient-years) and 25 were non ST-segment elevation (incidence: 1.33/100 patient-years). The factors that predicted the occurrence of AMI in dialysis were older age (OR: 1.037; 95% CI: 1.009-1.067; P=.011), previous CAD (OR: 3.35; 95% CI: 1.48-7.16; P=.004), and diabetes as a cause of nephropathy (OR: 2.96; 95% CI: 1.49-5.86; P=.002). In-hospital mortality was 30%, with 72.5% of deaths occurring in the 1st year and 82.5% in the 2nd; 80% of the patients who underwent a coronary angiography had multi-vessel disease. CONCLUSIONS: The incidence of AMI in incident dialysis patients is high. In previous coronary disease patients, the incidence is 3-fold higher. Post-infarction mortality is very high and multi-vessel disease is very frequent.

[Prevalence of and predisposing factors for bundle branch block in patients starting dialysis]. / Análisis de la prevalencia y los factores predisponentes de los bloqueos de rama en los pacientes que inician diálisis.

INTRODUCTION AND OBJECTIVES: Although bundle branch block (BBB) is regarded as a frequent finding, data on its prevalence are scarce in the general population and nonexistent in patients on dialysis. The aims of this study were to determine the prevalence of complete BBB in patients starting dialysis, to identify factors associated with its presence and, secondarily, to explore its association with mortality and the occurrence of cardiovascular events. METHODS: The study involved patients who started dialysis at our institution between November 1, 2003 and December 31, 2006. All underwent cardiological evaluation at the start of treatment. The presence of BBB was determined and its relationship with clinical factors and biochemical and echocardiographic parameters was examined. Patients were followed up until November 30, 2007. RESULTS: The study included 211 patients (age 65.05+/-15.7 years; 56.4% male). Of these, 24 (11.4%) presented with BBB: 6 (2.8%) with left BBB and 18 (8.5%) with right BBB. Age (odds ratio [OR]=1.05; 95% confidence interval [CI], 1.008-1.113; P=.02) and body mass index (OR=1.12; 95% CI, 1.019-1.234; P=.02) were independently associated with BBB. During a mean follow-up period of 23.7+/-12.9 months, patients who presented with left BBB showed a clear trend towards a poorer outcome than those without a conduction defect. CONCLUSIONS: The prevalence of BBB was high in patients starting dialysis and greater than that observed in the general population. Its presence was independently associated with older age and obesity. During the mean follow-up period of 2 years, patients with left BBB demonstrated a trend towards a poor prognosis.

[Analysis of the frequency of cardiac arrhythmias and conduction disturbances from a health-care perspective]. / Análisis de la frecuencia de las arritmias cardíacas y de los trastornos de conducción desde una perspectiva asistencial.

INTRODUCTION AND OBJECTIVES: Over the last few years, our understanding of the mechanisms underlying cardiac arrhythmias has increased substantially. However, few data on their prevalence exist. Our objectives were to analyze the prevalence of cardiac arrhythmias and conduction disturbances in cardiology clinic outpatients and to determine the number of patients with a class-I or -IIa recommendation for electrophysiological studies (EPS). PATIENTS AND METHOD: We investigated cardiac arrhythmias and conduction disturbances in 2045 patients and determined their prevalence in those seen for the first time. Specific conditions investigated included supraventricular and ventricular arrhythmias, ischemic disease with an ejection fraction (EF) <30%, second-degree or higher atrioventricular (AV) block, intraventricular block, and sick sinus syndrome. RESULTS: In total, 798 (39%) of all patients and 153 of the 704 (22%) seen for the first time presented with 1 or more of the specified conditions. Their distribution in all patients was: atrial fibrillation, 524 (26%); atrial flutter, 34 (2%); narrow-QRS tachycardia, 58 (3%); ventricular arrhythmias or EF<30% due to ischemic disease or both, 46 (2%); AV block or sinus dysfunction, 68 (3%); intraventricular block, 157 (8%); and other conditions, 4 (0.2%). Some 7% (143/2045) of all patients and 3.5% (25/704) of those seen for the first time had an indication for EPS. CONCLUSIONS: a) Almost 40% of all patients seen in a cardiology outpatient clinic and 1 in 4 of those seen for the first time presented with a cardiac arrhythmia or conduction disturbance; and b) more than 3% of patients seen for the first time had an indication for EPS.

[Patterns of clinical presentation of atrial fibrillation in hospitalized patients]. / Patrones clínicos de presentación de la fibrilación auricular en los pacientes hospitalizados.

INTRODUCTION AND OBJECTIVES: The ACC/AHA/ESC 2001 guidelines for the management of atrial fibrillation (AF) establish 4 categories: first episode, paroxysmal, persistent and permanent. The aim of this study was to analyze the frequency of the different clinical patterns of presentation of AF in hospitalized patients. PATIENTS AND METHOD: We analyzed the pattern of AF in 300 hospitalized patients, 200 of whom were admitted to the cardiology and 100 to the internal medicine department. We determined the clinical profile and evaluated the factors influencing therapeutic management. RESULTS: The permanent form was present in 30% of the patients admitted to the cardiology department and in 51% if those admitted to the internal medicine department. The first episode pattern was the most frequent in cardiology department patients (41%). In patients hospitalized the in cardiology the percentage use of anticoagulants (57.9% vs. 41%; p < 0.01) and beta blockers was greater than in internal medicine patients, and digitalis use was lower. In the multivariate analysis, admission to the cardiology department was an independent predictor of treatment with beta blockers (OR = 3.8; 95% CI, 1.3-11.1; p < 0.05), and discharge from the hospital with AF was a predictor of anticoagulant prescription (OR = 4.8; 95% CI, 2.5-9.2; p < 0.001). CONCLUSIONS: a) Atrial fibrillation is an arrhythmia with a heterogeneous clinical pattern that varies depending on the type of care provided; b) on admission to cardiology, only 30% of the patients present with permanent arrhythmia, and the most frequent clinical pattern is first episode; and c) discharge from the hospital with AF was the principal determinant of therapeutic management.

[Changes in the clinical profile of patients treated with oral anticoagulants in the 1990's]. / Cambios en el perfil clínico de los pacientes anticoagulados durante la década de los noventa.

INTRODUCTION: During the last few years the efficacy of oral anticoagulant treatment in the prevention of thromboembolic complications among patients with cardiac diseases has been well established. This has determined an increase in the number of patients undergoing this therapy and a change in the clinical profile of these patients. OBJECTIVE: To determine the number and the changes in the clinical characteristics of patients treated with oral anticoagulants during the last decade. PATIENTS AND METHOD: The charts of 5,771 hospitalized patients between January 1, 1991 and December 31, 1999, were retrospectively reviewed. We analyzed the number of patients discharged with anticoagulant treatment, the clinical profile and the evolution during the decade. RESULTS: 761 (13.1%) patients were discharged with anticoagulants. The therapy was prescribed to 7.4% of the patients from 1991-1993 and to 15.1% of the patients from 1998-1999. The mean age of the patients was 60.4 from 1991-1993 and 67.1 from 1998-1999 (p < 0.001). At the beginning of the decade, 90% of the patients had prosthetic valves, suffered from rheumatic heart disease or had had thromboembolic phenomena previously. At the end of the decade, only 49% could be included in these groups. CONCLUSIONS: a) The use of oral anticoagulants among our hospitalized patients has been duplicated during the past ten years; b) the clinical profile has changed, patients are now older and with different morbidity; c) the rheumatic heart disease and the prosthetic valves are no longer the predominant indications, and d) the use of therapy as secondary prevention has decreased significantly.