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.

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

La fibrilación auricular (FA) es un importante problema social y sanitario. Existe una amplia variación en la prevalencia de esta arritmia en los estudios que analizan a los pacientes en hemodiálisis (HD). OBJETIVO: Investigar la prevalencia, perfil clínico y manejo terapéutico de los pacientes con FA en HD en Andalucía. MÉTODOS: Solicitamos al sistema sanitario público de Andalucía el número de pacientes que estaban siendo tratados con HD. Pedimos a los nefrólogos responsables de todos los centros hospitalarios y extrahospitalarios de 5 de las 8 provincias de Andalucía que realizaran un electrocardiograma y cumplimentaran un cuestionario en pacientes seleccionados por un muestreo aleatorizado simple. RESULTADOS: Estaban en HD 2.348 pacientes en las 5provincias incluidas. El tamaño muestral estimado fue 285 pacientes. Obtuvimos electrocardiograma e información de 252 (88,4%). Edad media 65,3 ± 16 años; 40,9% mujeres. Tenían FA 63 pacientes (25%). De estos, 36 (14,3%) tenían FA en el registro realizado y en el resto había sido documentada previamente. En el análisis multivariante, mayor edad (OR: 1,071; IC 95%: 1,036-1,107; p = 0,000) y mayor tiempo en HD (OR: 1,009; IC 95%:1,004-1,014; p = 0,000) se asociaron de forma independiente con la FA. De los pacientes con FA, el 41,3% estaban en tratamiento anticoagulante en el momento del estudio y el 41,2% con antiagregantes. CONCLUSIONES: La FA en las unidades de diálisis es un importante hallazgo. Establecer la relación riesgo-beneficio del tratamiento anticoagulante constituye un auténtico reto. Son necesarios ensayos clínicos bien diseñados para establecer el uso racional del tratamiento antitrombótico

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

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.

Muerte súbita en pacientes con enfermedad renal crónica avanzada / Sudden death in patients with advanced chronic renal disease

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Calcificaciones valvulares en enfermedad renal crónica: ¿enfermedad mineral ósea o riesgo cardiovascular previo? Respuesta / Valvular calcifications in chronic kidney disease: Mineral and bone disease or previous cardiovascular risk? Response

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Factores que contribuyen a la reducida indicación de la cirugía de revascularización coronaria en España. ¿Seguimos las recomendaciones? Respuesta / Factors contributing to the low rate of surgical coronary revascularization in Spain. Are we following the recommendations? Response

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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.

Utilización de la cirugía de revascularización coronaria en nuestro medio. ¿Seguimos las recomendaciones de las guías? / The use of coronary artery bypass graft in our setting. Are we following the recommendations of the clinical guidelines?

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Las calcificaciones valvulares al inicio de diálisis predicen la aparición de eventos cardiovasculares en la evolución / Valvular calcification upon initiating dialysis predict the appearance of cardiovascular events in patient evolution

La calcificación valvular (CV) en la enfermedad renal crónica es frecuente, aunque la mayor parte de la información procede de pacientes prevalentes en diálisis. Son pocos los estudios que analicen la CV en los pacientes que inician diálisis. Objetivo: Analizar la presencia de CV al inicio de diálisis y su relación con eventos y/o muerte cardiovascular en la evolución. Métodos: Incluimos en el estudio los pacientes incidentes en diálisis entre nov/03 y sept/07. En el 1o mes de tratamiento analizamos la presencia de CV mediante Ecocardiograma-doppler, junto a factores demográficos y de riesgo cardiovascular, enfermedad coronaria, accidente cerebrovascular (ACV), fibrilación auricular (FA) y parámetros de electro y ecocardiográficos dimensionales y funcionales cardiacos. Los valores bioquímicos analizados fueron: hemoglobina, metabolismo calcio/fósforo/iPTH, colesterol y fracciones, triglicéridos, troponina I, albúmina, PCR y hemoglobina glicosilada. Analizamos la asociación de la CV con la presentación de infarto de miocardio (IAM), ACV y/o muerte cardiovascular hasta el trasplante, muerte, o fin del estudio (dic/2012). Resultados: De 256 pacientes incluidos (83% hemodiálisis, 17% diálisis peritoneal), 128 (50%) presentaban CV (mitral: 39, aórtica: 20, ambas: 69). En el análisis multivariante la CV se asoció a mayor edad (OR: 1,110; IC 95%: 1,073-1,148; p = 0,000) y menor albúmina (OR: 0,29; IC 95%: 0,14-0,61; p = 0,001). En un seguimiento de 42,1 ± 30,2 meses (898,1 pacientesaño), 68 pacientes presentaron IAM, ACV y/o murieron por causa cardiovascular. En el análisis de regresión de Cox, la mayor edad (HR: 1,028; IC 95%: 1,002-1,055; p = 0,037), la enfermedad coronaria y/o ACV (HR: 1,979; IC95%: 1,111-3,527; p = 0,021), la FA (HR: 2,474; IC 95%: 1,331-4,602; p = 0,004) y la presencia de CV antes de entrar en diálisis (HR: 1,996; IC 95%: 1,077-3,700; p = 0,028), fueron predictores independientes de la presentación de los eventos analizados. Conclusiones: La prevalencia de CV en el momento de iniciar diálisis es alta y su presencia predice la presentación de eventos y/o muerte cardiovascular en la evolución (AU)

The estimated frequency of cardiac valvular calcification (VC) in patients on dialysis is high, although the majority of studies published to date regarding the rate of VC have dealt with prevalent patients in dialysis. There are few studies of VC at the commencement of dialysis and its relationship to future events or cardiovascular mortality. Objective: To establish the prevalence of VC at the start of dialysis and the relationship between VC and the presentation of composite endpoints of acute myocardial infarction (MI), stroke or death from cardiovascular causes in the follow-up of incident dialysis patients. Methods: We conducted an analysis of dialysis patients (haemodialysis or peritoneal dialysis) who commenced dialysis between November 03 and September 07. VC was assessed by Doppler-echocardiography and its association with MI, stroke or cardiovascular mortality in the follow-up until death, transplant, or study end in December 2012 was analysed. Other variables assessed in the first month of dialysis were ECG, age, gender, smoking habit, diabetes, hypertension, previous ischemic stroke, coronary arterial disease and atrial fibrillation. Biochemical analyses included: haemoglobin, urea, creatinine, lipids, calcium, phosphorus, parathyroid hormone, albumin, troponin I, glycosylated haemoglobin and C-reactive protein. Results: Of 256 enrolled patients (83% Haemodialysis, 17% Peritoneal dialysis), 128 (50%) had VC at the commencement of dialysis (aortic 20, mitral 39, both 69). VC was associated with older age (OR: 1.110; CI 95%: 1.073-1.148; P=.000) and lower albumin levels (OR: 0.29; CI 95%: 0.14-0.61; P=.001). In a follow-up lasting a mean of 42.1±30.2 months (898.1 patient-years), 68 patients suffered an MI, a stroke or died from cardiovascular causes. The factors that predicted the presentation of the endpoint (Cox regression analysis) were older age (HR: 1.028; CI 95%: 1.002-1.055; P=.037), previous coronary arterial disease or stroke (HR: 1.979; CI 95%: 1.111-3.527; P=.021), atrial fibrillation (HR: 2.474; CI 95%: 1.331-4.602; P=.004) and VC at the start of dialysis (HR: 1.996; CI 95%: 1.077-3.700; P=.028). Conclusions: The prevalence of VC at the commencement of dialysis is very high and its presence is an independent predictor of event and cardiovascular mortality presentation in the course of follow-up (AU)

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.

Diferencias en la prevalencia de ateromatosis aórtica compleja según el tipo de accidente cerebrovascular / Differences in the Prevalence of Complex Aortic Atheromatosis by Type of Stroke

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Incidencia del infarto agudo de miocardio en la evolución de los pacientes en tratamiento con diálisis / Incidence of acute myocardial infarction in the evolution of dialysis patients

Introducción: Aunque la frecuencia de la enfermedad coronaria (EAC) en los pacientes en diálisis se estima muy elevada, existe una gran variabilidad en los estudios en la tasa de infarto agudo de miocardio (IAM). Objetivo: Establecer la incidencia IAM y analizar sus características y repercusión en la evolución de los pacientes incidentes en diálisis. Métodos: Estudiamos los pacientes incidentes en diálisis entre el 1/1/1999 y el 31/12/2007, y analizamos la presentación del primer IAM en diálisis. Valoramos diagnósticos previos de diabetes, hipertensión arterial, EAC (IAM o lesiones en coronariografía), accidente cerebrovascular isquémico, arteriopatía periférica avanzada y tabaquismo. Se analizaron urea, creatinina, hematocrito, calcio/fósforo, hormona paratiroidea intacta, lípidos y albúmina. El seguimiento fue hasta trasplante, muerte, pérdida o cierre del estudio el 31/12/2010. Resultados: De 576 pacientes incluidos (64,6 ± 16 años; 24,7% diabéticos; 82,3% hemodiálisis/17,7% diálisis peritoneal), 34 (5,9%) (..) (AU)

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 (..) (AU)

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.