Devices for Prevention of Atrial Tachyarrhythmias

Atrial fibrillation (AF) is the most frequent sustained cardiac arrhythmia in clinical practice and, although its importance has been underestimated even in recent years, we are now becoming aware of its clinical transcendence1,2,3. The classical treatment is pharmacological, but its efficacy is limited and it does have side effects4,5. Therefore, in recent years, there has been an increasing interest in other types of non-pharmacological treatments6,7. Physiologic cardiac pacing has proven to be more effective than VVI mode pacing to prevent the occurrence of AF during the follow-up of patients who have had a permanent pacemaker implanted 8,9,10. There are currently different lines of research that use different atrial pacing techniques to prevent and treat episodes of paroxysmal atrial fibrillation11,12. Techniques of multi-site pacing in the right atrium or both atria, new atrial pacing sites, prevention algorithms for paroxysmal atrial fibrillation episodes, and even high-frequency atrial tachyarrhythmia termination algorithms have all been proposed. In this article, we will try to synthesize the grounds for and findings of the different lines of research currently being developed

Prevalence of heart failure in the spanish general population aged over 45 years. the PRICE study

[Abstract] Introduction and objectives. Congestive heart failure is associated with substantial morbidity and mortality and both its incidence and prevalence are high. Nevertheless, comprehensive data on this condition in Spain are lacking. The aim of this study was to determine the prevalence of congestive heart failure in Spain. Methods. A demographic study which involved the participation of 15 healthcare centers throughout Spain was carried out. In each health area, a random sample was taken of the population aged 45 years or more. These individuals were examined by their primary care physicians, who made their diagnoses using Framingham criteria. Individuals who satisfied criteria for congestive heart failure were referred to a cardiologist for confirmation of the diagnosis and for echocardiography. Results. Overall, 1776 individuals were evaluated. Their mean age was 64±12 years (range, 45-100 years) and 44% were male. Of these, 242 were referred to a cardiologist. The weighted prevalence of congestive heart failure was 6.8% (95% confidence interval [CI] 4-8.7). The prevalence was similar in men (6.5%, 95% CI 4.7-8.4) and women (7%, 95% CI 4.4-9.6). When analyzed by age, the prevalence was 1.3% (0.4%-2.1%) in those aged 45-54 years, 5.5% (2.4%-8.5%) in those aged 55-64 years, 8% (4.2%-11.8%) in those aged 65-74 years, and16.1% (11%-21.1%) in those aged over 74 years. Conclusions. Prevalence of congestive heart failure in Spain is high, at about 7%-8%. The prevalence was similar in males and females, and appeared to increase with age.[Resumen] Introducción y objetivos. La insuficiencia cardiaca congestiva (ICC) tiene elevadas incidencia, morbilidad y mortalidad y una gran prevalencia. Sin embargo, no hay datos directos sobre este aspecto en nuestro país. El objetivo de nuestro estudio es evaluar la prevalencia de ICC en España. Métodos. Se diseñó un estudio poblacional en el que participaron 15 centros repartidos por toda España. Se seleccionó de forma aleatoria una muestra de la población de 45 o más años de edad atendida en cada área de salud, que fue estudiada por sus médicos de atención primaria. Se utilizaron los criterios de Framingham para el diagnóstico. Las personas con criterios de ICC fueron remitidas a una consulta de cardiología para confirmación diagnóstica y realización de ecocardiograma. Resultados. Se evaluó a 1.776 personas, con una media ± desviación estándar (intervalo) de edad de 64 ± 12 (45-100) años; eran varones el 44%. Se remitió a cardiología a 242 pacientes. La prevalencia ponderada de ICC fue del 6,8% (intervalo de confianza [IC] del 95%, 4%-8,7). La prevalencia fue similar en varones (6,5%; IC del 95%, 4,7-8,4) y en mujeres (7%; IC del 95%, 4,4-9,6). Por edades, la prevalencia fue del 1,3% (0,4%-2,1%) entre los 45 y 54 años; el 5,5% (2,4%-8,5%) entre 55 y 64 años; el 8% (4,2%-11,8%) entre 65 y 74 años, y el 16,1% (11%-21,1%) en personas de 75 o más años. Conclusiones. La prevalencia de ICC en España es alta, en torno a un 7-8%. La prevalencia es similar en varones y mujeres, y parece aumentar con la edad

Efecto de un programa de formación en atención primaria sobre la optimización del tratamiento con bloqueadores beta en pacientes ancianos con insuficiencia cardiaca

[Abstract] Introduction and objectives. Underuse of beta-blockers may contribute to elevated mortality in chronic heart failure. The aim of this study was to determine whether a specific interventional training program for primary care physicians would help optimize the use of beta-blockers in elderly chronic heart failure patients. Methods. This randomized comparative study included 627 patients aged 70 years or more who were discharged consecutively from 53 Spanish hospitals with a principal diagnosis of chronic heart failure. In total, 292 health-care centers in the catchment areas of these hospitals were randomly assigned to two groups: one group of 146 centers carried out an interventional training program on beta-blocker use for primary care physicians belonging to the centers assigned to training, and 146 centers served as a control group. The main outcome variable was the percentage of patients who were receiving a beta-blocker at the maximum or maximum tolerated dose 3 months after hospital discharge. Results. The patients’ mean age was 78±5 years and 42% were women. There was no difference between the groups in demographic characteristics, clinical care, or treatment at discharge. The percentage of patients who received beta-blockers at the maximum tolerated dose 3 months after discharge was greater in the training group (49% vs. 38%; P=.014). Being treated in the training group was an independent predictor of receiving a beta-blocker at the MTD (odds ratio=2.46; 95% confidence interval, 1.29-4.69; P<.001). Conclusions. Implementation of an interventional training program on beta-blocker treatment for primary care physicians improved the use of these medications in elderly chronic heart failure patients.[Resumen] Introducción y objetivos. La infrautilización de bloqueadores beta puede influir en la elevada mortalidad de la insuficiencia cardiaca. El objetivo de nuestro estudio es evaluar si un programa específico de intervención sobre médicos de atención primaria permite optimizar el uso de bloqueadores beta en pacientes ancianos con insuficiencia cardiaca. Métodos. Se diseñó un estudio aleatorizado y comparativo en el que se incluyó a 627 pacientes de 70 o más años, dados de alta de forma consecutiva con el diagnóstico principal de insuficiencia cardiaca en 53 hospitales españoles. Se realizó una asignación aleatoria de los 292 centros de salud de las áreas de esos hospitales a dos grupos (formación, 146 centros, y control, 146 centros), para impartir un programa de intervención y formación sobre bloqueadores beta a los médicos pertenecientes a los centros del grupo formación. La variable principal fue el porcentaje de pacientes que recibían la dosis máxima o máxima tolerada de bloqueadores beta a los 3 meses del alta. Resultados. La edad de los pacientes era de 78 ± 5 años; el 42% eran mujeres. No hubo diferencias entre ambos grupos en sus características demográficas, clínicas o en el tratamiento al alta. El porcentaje de pacientes que recibían la dosis máxima tolerada de bloqueadores beta a los 3 meses del alta fue mayor en el grupo formación (el 49 frente al 38%; p = 0,014); pertenecer al grupo formación fue predictor independiente de recibir la dosis máxima tolerada de bloqueadores beta (odds ratio = 2,46; intervalo de confianza del 95%, 1,29-4,69; p < 0,001). Conclusiones. Un programa de formación sobre bloqueadores beta en atención primaria mejora su uso en pacientes ancianos con insuficiencia cardiaca

Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci

Background: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects — for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. Results: We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, Pempirical = 0.0004) and at chromosome 18 (18q21.2, Pempirical = 0.0005). Conclusions: In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHDThis study was supported by the grants from the Instituto de Salud Carlos III (08–1363 and 11–0699) of the Spanish Ministry of Health and by grant Str643/4-1 of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)

Diferencias en el pronóstico de la insuficiencia cardiaca con función sistólica conservada o deprimida en pacientes mayores de 70 años que toman bloqueadores beta

[Abstract] Introduction and objectives. Most studies have shown that prognosis of heart failure with preserved systolic function is as poor as that of heart failure with depressed systolic function, although these results may be biased by the fact that these types of heart failure have different characteristics (age, comorbidity, treatment), which can influence prognosis. Our aim was to determine whether short-term morbidity and mortality differed in these 2 subgroups of heart failure patients when they were comparable in terms of age, associated comorbidity, and therapy. Methods. We analyzed 2 groups of patients aged >70 years who were candidates to receive beta blockers (preserved systolic function, 245; depressed systolic function, 374), consecutively discharged from 53 participating Spanish hospitals with a diagnosis of heart failure, and compared cardiovascular morbidity and mortality 3 months after discharge. Results. Mean age was similar (77.5 ± 4.8 vs 78.2 ± 5.5 years). Left ventricular ejection fraction was 56.2% ± 8.1% vs 33% ± 6.9% (P<.001). The combined event rate (death, hospitalization for heart failure, acute coronary syndrome, or stroke) at 3 months after discharge was lower in patients with heart failure and preserved systolic function (13.4% vs 20.6%; P=.026). Depressed systolic function was an independent predictor of greater incidence of events (odds ratio=1.732; P=.048). Conclusions. In patients of similar age and receiving similar treatment, short-term prognosis is better in patients with heart failure and preserved systolic function than in those with depressed systolic function.[Resumen] Introducción y objetivos. La mayoría de los trabajos han puesto de manifiesto que el pronóstico de la insuficiencia cardiaca con función sistólica conservada es tan malo como el de la insuficiencia cardiaca con función sistólica deprimida, aunque estos resultados pueden estar sesgados debido a que estos dos tipos de insuficiencia cardiaca tienen características distintas (edad, comorbilidades, tratamiento) que pueden influir en el pronóstico. Nuestro objetivo es evaluar si la morbimortalidad a corto plazo es distinta en estos dos subgrupos de insuficiencia cardiaca, con pacientes homogéneos en cuanto a edad, comorbilidad y tratamiento recibido. Métodos. Analizamos dos grupos de pacientes mayores de 70 años y que pudieran recibir bloqueadores beta, dados de alta consecutivamente tras un ingreso por insuficiencia cardiaca en 53 hospitales españoles (función sistólica deprimida, 245; función sistólica conservada, 374), y se comparó la morbimortalidad cardiovascular a los 3 meses del alta. Resultados. Las medias de edad fueron similares (77,5 ± 4,8 frente a 78,2 ± 5,5 años). La fracción de eyección ventricular izquierda fue de 56,2 ± 8,1% frente a 33 ± 6,9% (p < 0,001). La incidencia del evento combinado (muerte, ingreso por insuficiencia cardiaca, síndrome coronario agudo o ictus) a los 3 meses del alta fue menor en los pacientes con insuficiencia cardiaca y función sistólica conservada (el 13,4 frente al 20,6%; p = 0,026). Tener la función sistólica deprimida fue predictor independiente de mayor incidencia de eventos (odds ratio = 1,732; p = 0,048). Conclusiones. En pacientes de edad similar que reciben el mismo tratamiento, el pronóstico a corto plazo es mejor en los pacientes con insuficiencia cardiaca y función sistólica conservada que en aquellos con función sistólica deprimida

Usefulness of genetic testing in hypertrophic cardiomyopathy. An analysis using real-world data.

Aims: This study sought to determine the usefulness of genetic testing to predict evolution in hypertrophic cardiomyopathy (HCM) and to assess the role of genetic testing in clinical practice. Methods and Results: Genetic results of 100 HCM patients tested for mutations in ≥10 HCM-causing genes were evaluated. Patients were classified as with poor (Group A) or favourable(Group B) clinical course. Forty-five pathogenic mutations (PM) were identified in 28 patients (56%) from Group A and in 23 (46%) from Group B (p=0.317). Only 40 patients (40%) exhibited PM that had been previously reported and only 15 (15%) had PM reported in ≥10 individuals. PM associated with poor prognosis were identified in just 5 patients from Group A (10%). Conclusion: Genetic findings are not useful to predict prognosis in most HCM patients. By contrast, real-world data reinforce the usefulness of genetic testing to provide genetic counselling and to enable cascade genetic screening.pre-print298 K

Clinical characteristics of wild-type transthyretin cardiac amyloidosis – Disproving myths.

Aims: Wild-type transthyretin amyloidosis (ATTRwt) is mostly considered a disease predominantly of elderly male, characterised by concentric LV hypertrophy, preserved LVEF and low QRS voltages. We sought to describe the characteristics of a large cohort of ATTRwt patients to better define the disease. Methods and Results: Clinical findings of consecutive ATTRwt patients diagnosed at 2 centres were reviewed. ATTRwt was diagnosed histologically or non-invasively (LV hypertrophy 12mm, intense cardiac uptake at 99mTc-DPD scintigraphy and AL exclusion). Mutations in TTR were excluded in all cases. The study cohort comprised 108 patients (78.68 years); 67 (62%) diagnosed invasively and 41 (38%) non-invasively. Twenty patients (19%) were females. An asymmetric hypertrophy pattern was observed in 25 (23%) patients. Mean LVEF was 5214%, with 39 patients (37%) showing a LVEF<50%. Atrial fibrillation (56%) and a pseudo-infarct pattern (63%) were the commonest ECG findings. Only 22 patients fulfilled QRS low-voltage criteria while 10 showed LV hypertrophy on ECG. Although heart failure was the most frequent profile leading to diagnosis (68%), 7% of individuals presented with atrioventricular block and 11% were diagnosed incidentally. Almost one third (35; 32%) were previously misdiagnosed. Conclusion: The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.pre-print833 K

Parathormone levels add prognostic ability to N-terminal pro-brain natriuretic peptide in stable coronary patients

Aims: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. Methods and results: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52–72) years. Median glomerular filtration rate was 80.4 (65.3–93.1) mL/min/1.73 m2. One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021–1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012–1.028]; P 85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. Conclusions: Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT-proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (Fondo Europeo de Desarrollo Regional) European Union (PI05/0451, PI14/1567, PI17/01615, and PI17/01495); Spanish Society of Cardiology; Spanish Society of Arteriosclerosis; RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) (RD06/0014/0035); and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the spanish post–heart transplant tumour registry

[Abstract] Background. Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods. This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results. Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions. Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively