Luis Alonso-Pulpón

Prevalencia de la insuficiencia cardiaca en la población general española mayor de 45 años. Estudio PRICE

Introduccion 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 pais. El objetivo de nuestro estudio es evaluar la prevalencia de ICC en Espana. Metodos Se diseno un estudio poblacional en el que participaron 15 centros repartidos por toda Espana. Se selecciono de forma aleatoria una muestra de la poblacion de 45 o mas anos de edad atendida en cada area de salud, que fue estudiada por sus medicos de atencion primaria. Se utilizaron los criterios de Framingham para el diagnostico. Las personas con criterios de ICC fueron remitidas a una consulta de cardiologia para confirmacion diagnostica y realizacion de ecocardiograma. Resultados Se evaluo a 1.776 personas, con una media ± desviacion estandar (intervalo) de edad de 64 ± 12 (45-100) anos; eran varones el 44%. Se remitio a cardiologia 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 anos; el 5,5% (2,4%-8,5%) entre 55 y 64 anos; el 8% (4,2%-11,8%) entre 65 y 74 anos, y el 16,1% (11%-21,1%) en personas de 75 o mas anos. Conclusiones La prevalencia de ICC en Espana es alta, en torno a un 7-8%. La prevalencia es similar varones y mujeres, y parece aumentar con la edad.

Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction

AIMS Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Wild-type transthyretin (TTR) amyloidosis (ATTRwt) is an underdiagnosed cause of HFpEF that might benefit from new specific treatments. ATTRwt can be diagnosed non-invasively by (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy. We sought to determine the prevalence of ATTRwt among elderly patients admitted due to HFpEF. METHODS AND RESULTS We prospectively screened all consecutive patients ≥60 years old admitted due to HFpEF [left ventricular (LV) ejection fraction ≥50%] with LV hypertrophy (≥12 mm). All eligible patients were offered a (99m)Tc-DPD scintigraphy. The study included 120 HFpEF patients (59% women, 82 ± 8 years). A total of 16 patients (13.3%; 95% confidence interval: 7.2-19.5) showed a moderate-to-severe uptake on the (99m)Tc-DPD scintigraphy. All patients with a positive scan underwent genetic testing of the TTR gene, and no mutations were found. An endomyocardial biopsy was performed in four patients, confirming ATTRwt in all cases. There were no differences in age, gender, hypertension, diabetes, coronary artery disease, or atrial fibrillation between ATTRwt patients and patients with other HFpEF forms. Although patients with ATTRwt exhibited higher median N-terminal pro-brain natriuretic peptide (6467 vs. 3173 pg/L; P = 0.019), median troponin I (0.135 vs. 0.025 µg/L; P < 0.001), mean LV maximal wall thickness (17 ± 3.4 vs. 14 ± 2.5 mm; P = 0.001), rate of pericardial effusion (44 vs. 19%; P = 0.047), and rate of pacemakers (44 vs. 12%; P = 0.004), clinical overlap between ATTRwt and other HFpEF forms was high. CONCLUSION ATTRwt is an underdiagnosed disease that accounts for a significant number (13%) of HFpEF cases. The effect of emerging TTR-modifying drugs should be evaluated in these patients.

Malignancy After Heart Transplantation: Incidence, Prognosis and Risk Factors

The Spanish Post‐Heart‐Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984–2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post‐HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post‐HT (from respectively 5.2 and 8.9 per 1000 person‐years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R‐blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post‐HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post‐HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre‐HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five‐year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

RADIAL: A novel primary graft failure risk score in heart transplantation

BACKGROUND Primary graft failure (PGF) is the leading cause of early mortality after heart transplantation (HT). Our aim is to propose a working definition of PGF and to develop a predictive risk score. METHODS PGF was defined by four criteria reflecting significant myocardial dysfunction, severe hemodynamic impairment, early onset after HT, and absence of secondary causes of graft dysfunction. We identified independent risk factors for PGF in a derivation series of 621 HTs and constructed a predictive model. After proving its internal consistency we tested the model in a prospective validation series. RESULTS The incidence and lethality of PGF in our series were 9% and 80%, respectively. We identified 6 multivariate risk factors for PGF (Right atrial pressure ≥ 10 mm Hg, recipient Age ≥ 60 years, Diabetes mellitus, Inotrope dependence, donor Age ≥ 30 years, Length of ischemic time ≥ 240 minutes--i.e., RADIAL). Analysis of isolated right ventricular failure showed similar predictors. The RADIAL score was obtained by adding 1 point for each of these factors present in a given HT. PGF incidence increased significantly as the RADIAL score increased (p < 0.001 for trend). Rates of actual and predicted PGF incidence for RADIAL subgroups showed a good correlation (C-statistic = 0.74). In a prospective validation cohort, RADIAL score kept its predictive ability. CONCLUSIONS PGF as defined by these criteria showed a high impact on early post-HT mortality in our series. The RADIAL score showed good ability to predict the development of PGF, and could be useful in the prevention and early treatment of this complication.

A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation : SIMCOR study

Background. Antilymphocytic antibodies have been long used for the prevention of acute rejection early after heart transplantation (HTx), but their adverse effects have limited their widespread use. Our aim was to evaluate the safety, tolerability, and efficacy of the novel anti-CD25 antibody basiliximab (BAS) compared with muromonab (OKT3). Patients and methods. In this multicenter study, 99 patients were randomly assigned to receive either BAS or OKT3 in the early post-HTx period. The primary endpoint was safety and tolerability. Specific safety variables were predefined for a better comparison of adverse effects. Secondary endpoints concerning anti-rejection efficacy were also evaluated. Results. No adverse events related to study medication were found in the BAS group, whereas 23 were observed among patients receiving OKT3 (P<0.0001). The proportion of patients with predefined adverse events day 4 post-HTx was much higher with OKT3 than with BAS (43% vs. 4%; P<0.0001). Fever, acute pulmonary edema, hypotension, and other complications accounted for most of the difference. At 1-year follow-up, biopsy-proven rejection episodes grade ≥3A had occurred in 39.6% of BAS patients versus 40.4% of OKT3 patients (P=0.87). There were no differences in terms of severity and timing of acute rejection episodes. The number of infectious episodes, complications not related to study medication, and actuarial survival were similar in both groups. Conclusion. In this HTx study, induction therapy with BAS was safer and better tolerated than OKT3, without significant differences in efficacy outcomes.

Evaluation of a Telemedicine Service for the Secondary Prevention of Coronary Artery Disease

PURPOSE: Efficient ways are needed to implement the secondary prevention (SP) of coronary heart disease. Because few studies have investigated Web-based SP programs, our aim was to determine the usefulness of a new Web-based telemonitoring system, connecting patients provided with self-measurement devices and care managers via mobile phone text messages, as a tool for SP. METHODS: A single-blind, randomized controlled, clinical trial of 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. All patients received lifestyle counseling and usual-care treatment. Patients in the telemonitoring group (TMG) sent, through mobile phones, weight, heart rate, and blood pressure (BP) weekly, and capillary plasma lipid profile and glucose monthly. A cardiologist accessed these data through a Web interface and sent recommendations via short message service. Main outcome measures were BP, body mass index (BMI), smoking status, low-density lipoprotein-cholesterol (LDL-c), and glycated hemoglobin A1c (HbA1c). RESULTS: At 12-month followup, TMG patients were more likely (RR = 1.4; 95% CI = 1.1−1.7) to experience improvement in cardiovascular risk factors profile than control patients (69.6% vs 50.5%, P = .010). More TMG patients achieved treatment goals for BP (62.1% vs 42.9%, P = .012) and HbA1c (86.4% vs 54.2%, P = .018), with no differences in smoking cessation or LDL-c. Body mass index was significantly lower in TMG (−0.77 kg/m2 vs +0.29 kg/m2, P = .005). CONCLUSIONS: A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.

Genetic basis of end‐stage hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterized by a heterogeneous presentation and clinical course. A minority of HCM patients develop end‐stage HCM and require cardiac transplantation. The genetic basis of end‐stage HCM is unknown but small series, isolated case reports and animal models have related the most aggressive heart failure course with the presence of multiple mutations.

Conferencia de Consenso de los Grupos Españoles de Trasplante Cardiaco

La Seccion de Insuficiencia Cardiaca, Trasplante Cardiaco y otras Alternativas Terapeuticas de la Sociedad Espanola de Cardiologia desarrollo en Sevilla, en junio de 2005, una Conferencia de Consenso sobre trasplante cardiaco (TC) a la que fueron invitados a participar todos los grupos espanoles de TC. El objetivo fue determinar, discutir y consensuar los aspectos mas relevantes y/o controvertidos de diferentes areas del TC en la actualidad: organizacion, seleccion del receptor, donantes, rechazo, inmunosupresion, enfermedad vascular del injerto, complicaciones a largo plazo y TC pediatrico. Este documento reune las recomendaciones del grupo de trabajo incluyendo el grado de evidencia con que se respalda cada una.

A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li–Fraumeni-like families

Cardiac angiosarcoma (CAS) is a rare malignant tumour whose genetic basis is unknown. Here we show, by whole-exome sequencing of a TP53-negative Li–Fraumeni-like (LFL) family including CAS cases, that a missense variant (p.R117C) in POT1 (protection of telomeres 1) gene is responsible for CAS. The same gene alteration is found in two other LFL families with CAS, supporting the causal effect of the identified mutation. We extend the analysis to TP53-negative LFL families with no CAS and find the same mutation in a breast AS family. The mutation is recently found once in 121,324 studied alleles in ExAC server but it is not described in any other database or found in 1,520 Spanish controls. In silico structural analysis suggests how the mutation disrupts POT1 structure. Functional and in vitro studies demonstrate that carriers of the mutation show reduced telomere-bound POT1 levels, abnormally long telomeres and increased telomere fragility.

Prevalence of Heart Failure in the Spanish General Population Aged Over 45 Years. The PRICE Study

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, and 16.1% (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.