Efficiency of a self-administered outpatient parenteral antimicrobial therapy (s-opat) for infective endocarditis within the context of a shortened hospital admission based on hospital at home program.

OBJECTIVE: This study aimed to evaluate the efficiency of treatment of infectious endocarditis (IE) via Self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) supported by a shortening hospital admission program in a hospitalization-at-home unit (HAH), including a short review of the literature. METHODS: Ambispective cohort study of 57 episodes of IE in 54 patients treated in an HAH unit between 1988 and 2014 who receive S-OPAT after prior intra-hospital clinical stabilization. Characteristics of each episode of IE, safety and efficiency of the care model, were analyzed. RESULTS: Forty-three (76%) patients were males with a median age of 61 years (SD = 16.5). A total of 37 (65%) episodes affected the native valve (42% the aortic valve). In 75%, a micro-organism was isolated, of which 88% were Gram-positive bacteria. No deaths occurred during HAH program, clinical complications appeared in 30% of episodes, only 6 patients were re-admitted to hospital although no patient died. In the 12 months' follow-up 3 cases had a recurrence. The average cost of a day stay in HAH was €174 while in traditional cardiology hospitalization was €1100. The total average cost of treatment of each episode of IE managed entirely in hospital was calculated as €54,723. Application of the S-OPAT model based on HAH meant a cost reduction of 32.72%. CONCLUSIONS: In suitably selected patients, treatment of IE based on S-OPAT supported by a shortening hospital admission care program by means of referral to a HAH unit is a safe and efficient care model which entails a significant cost saving for the public healthcare system.

Self-administered outpatient parenteral antimicrobial therapy (S-OPAT) for infective endocarditis: a safe and effective model.

The safety and efficacy of treatment of infectious endocarditis (IE) was evaluated within a program of hospital-in-home (HIH) based on self-administered outpatient parenteral antimicrobial therapy (S-OPAT). IE episodes (n=48 in 45 patients; 71% middle-aged males) were recruited into the HIH program between 1998 and 2012. Following treatment stabilization at the hospital they returned home for HIH in which a physician and/or a nurse supervised the S-OPAT. Safety and efficacy were evaluated as mortality, re-occurrence, and unexpected re-admission to hospital. Of the episodes of IE, 83.3% had comorbidities with a mean score of 2.3 on the Charlson index and 1.5 on the Profund index; 60.4% had pre-existing valve disease (58.6% having had surgical intervention); 8.3% of patients had suffered a previous IE episode; 62.5% of all episodes affected a native valve; 45.8% being mitral; 70.8% of infection derived from the community. In 75% of the episodes there was micro-organism growth, of which 83.3% were Gram positive. Overall duration of antibiotic treatment was 4.8 weeks; 60.4% of this time corresponding to HIH. Re-admission occurred in 12.5% of episodes of which 33.3% returned to HIH to complete the S-OPAT. No deaths occurred during HIH. One year after discharge, 2 patients had recurrence and 5 patients died, in 2 of whom previous IE as cause-of-death could not be excluded. In conclusion, the S-OPAT schedule of hospital-in-home is safe and efficacious in selected patients with IE.

Functional polymorphisms in genes of the Angiotensin and Serotonin systems and risk of hypertrophic cardiomyopathy: AT1R as a potential modifier.

BACKGROUND: Angiotensin and serotonin have been identified as inducers of cardiac hypertrophy. DNA polymorphisms at the genes encoding components of the angiotensin and serotonin systems have been associated with the risk of developing cardiovascular diseases, including left ventricular hypertrophy (LVH). METHODS: We genotyped five polymorphisms of the AGT, ACE, AT1R, 5-HT2A, and 5-HTT genes in 245 patients with Hypertrophic Cardiomyopathy (HCM; 205 without an identified sarcomeric gene mutation), in 145 patients with LVH secondary to hypertension, and 300 healthy controls. RESULTS: We found a significantly higher frequency of AT1R 1166 C carriers (CC+AC) among the HCM patients without sarcomeric mutations compared to controls (p = 0.015; OR = 1.56; 95%CI = 1.09-2.23). The AT1R 1166 C was also more frequent among patients who had at least one affected relative, compared to sporadic cases. This allele was also associated with higher left ventricular wall thickness in both, HCM patients with and without sarcomeric mutations. CONCLUSIONS: The 1166 C AT1R allele could be a risk factor for cardiac hypertrophy in patients without sarcomeric mutations. Other variants at the AGT, ACE, 5-HT2A and 5-HTT did not contribute to the risk of cardiac hypertrophy.

Endothelial dysfunction, measured by reactive hyperaemia using strain-gauge plethysmography, is an independent predictor of adverse outcome in heart failure.

AIMS: In congestive heart failure (CHF), arterial response is regulated by endothelial molecules. The aim of this study was to evaluate whether endothelial dysfunction (ED) was a predictor of outcome in a cohort of patients with heart failure. METHODS AND RESULTS: Endothelial function was assessed in 242 patients with CHF by forearm reactive hyperaemia measured with intermittent venous occlusion plethysmography using a mercury strain gauge. The main endpoints were: 'total events' (death, heart attack, angina, stroke, NYHA class IV, or hospitalization due to heart failure) analysed using Cox regression for repeated events and 'death'. Patients were followed-up for 5 years. Post-hyperaemia forearm blood flow (PHFABF) was an independent predictor of total events [P = 0.01; hazard ratio [Exp(B)] 0.665, standard error (SE) 0.182]. Risk stratification by basal forearm blood flow (BFABF) showed that patients with basal blood flow above the median (3.03 mL min(-1) 100 mL(-1)) benefited from an increase in PHFABF, whereas in patients with a BFABF below the median, the increase in PHFABF did not diminish the risk of events. There was no relation between variations in PHFABF and death. CONCLUSION: Post-hyperaemia forearm blood flow, as a measure of ED, is an independent predictor of major events in patients with CHF. A BFABF below the median is more predictive of an increased risk of complications.

Repeat mitral valve replacement: 30-years' experience.

Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%). In total, 369 patients needed a second operation (in-hospital mortality 8.1%), while 80 (age 59.8+/-11.4 years) needed a third. The reasons for the third intervention were structural deterioration (67.5%), paravalvular leak (20%) and endocarditis (6.3%). Some 15 patients died in hospital (18.8%). After a mean follow-up period of 17.8 years, 21 patients needed another intervention (i.e., a fourth intervention). The actuarial reoperation-free rate at 20 years was 40.1+/-13.8%. The late mortality rate was 58.5% (18-year survival rate 15.4+/-5.4%). Indications for repeat mitral valve replacement must be judged on an individual basis given the high risk associated with surgery.

Reintervenciones múltiples sobre la válvula mitral: 30 años de experiencia / Repeat mitral valve replacement: 30-years’ experience

La disfunción protésica es una enfermedad adquirida con significativo riesgo quirúrgico inmediato, aunque la historia natural a largo plazo es poco conocida. Entre 1974 y 2006 se realizaron 1.535 recambios mitrales aislados (mortalidad hospitalaria, 5%). Un total de 369 pacientes requirieron una segunda intervención (mortalidad hospitalaria, 8,1%) y 80, una tercera (59,8 ± 11,4 años). Las causas de la tercera intervención fueron deterioro estructural (67,5%), dehiscencia periprotésica (20%) y endocarditis (6,3%). La mortalidad hospitalaria fue 15 (18,8%) pacientes. Tras un seguimiento medio de 17,8 años, 21 pacientes precisaron nueva intervención (cuarta intervención) y la curva actuarial libre de reoperación fue del 40,1% ± 13,8% a 20 años. La mortalidad tardía fue del 58,5% (supervivencia a 18 años, 15,4% ± 5,4%). La indicación de una reintervención reiterativa mitral debe evaluarse de forma individualizada, dado el alto riesgo quirúrgico asociado (AU)

Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%). In total, 369 patients needed a second operation (in-hospital mortality 8.1%), while 80 (age 59.8[11.4] years) needed a third. The reasons for the third intervention were structural deterioration (67.5%), paravalvular leak (20%), and endocarditis (6.3%). Some 15 patients died in hospital (18.8%). After a mean follow-up period of 17.8 years, 21 patients needed another intervention (ie, a fourth intervention). The actuarial reoperation-free rate at 20 years was 40.1% [13.8%]. The late mortality rate was 58.5% (18-year survival rate 15.4% [5.4%]). Indications for repeat mitral valve replacement must be judged on an individual basis given the high risk associated with surgery (AU)

[Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy]. / Espectro mutacional de los genes sarcoméricos MYH7, MYBPC3, TNNT2, TNNI3 y TPM1 en pacientes con miocardiopatía hipertrófica.

INTRODUCTION AND OBJECTIVES: Mutation of a sarcomeric gene is the most frequent cause of hypertrophic cardiomyopathy. For each such gene, however, previous studies have reported a range of different mutation frequencies, and clinical manifestations have been highly heterogeneous, both of which limit the use of genetic information in clinical practice. Our aim was to determine the frequency of mutations in the sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in a cohort of Spanish patients with hypertrophic cardiomyopathy. METHODS: We used sequencing to analyze the coding regions of these five genes in 120 patients (29% with a family history) and investigated how the patient phenotype varied with the gene mutated. RESULTS: In total, 32 patients were found to have mutations: 10 in MYH7 (8%), 20 in MYBPC3 (16%), 2 in TNNT2, 1 in TPM1 and none in TNNI3. Overall, 61% of mutations had not been described before. Two patients had two mutations (i.e., double mutants). There was no difference in the mean age at diagnosis or the extent of the hypertrophy between those with MYH7 mutations and those with MYBPC3 mutations. CONCLUSIONS: Some 26% of patients had a mutation in one of the five sarcomeric genes investigated. More than half of the mutations had not been described before. The MYBPC3 gene was the most frequently mutated, followed by MYH7. No phenotypic differences were observed between carriers of the various mutations, which makes it difficult to use genetic information to stratify risk in these patients.

Espectro mutacional de los genes sarcoméricos MYH7, MYBPC3, TNNT2, TNNI3 y TPM1 en pacientes con miocardiopatía hipertrófica / Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy

Introducción y objetivos. Desarrollar un análisis coste-efectividad de un programa de cribado genético de familares de primer grado de pacientes con hipercolesterolemia familiar (HF), seguido de tratamiento cuando fuera necesario, frente a la alternativa de no cribar. Métodos. Se realiza un análisis coste-efectividad en el cual se modeló el efecto del tratamiento con estatinas en personas diagnosticadas de HF tras el cribado genético. La incertidumbre se trató mediante análisis de sensibilidad univariable y probabilístico. La estrategia alternativa considerada es no cribar. El análisis coste-efectividad considera como resultado sobre la salud los años de vida ganados (AVG) e incluye los costes del cribado, tratamiento con estatinas, visitas al especialista y hospitalizaciones. Asimismo, se calculó el valor esperado de la información perfecta, como complemento del análisis de sensibilidad. Resultados. En el caso base, el coste incremental por AVG del programa de cribado a pacientes directos asciende a 3.423 euros/AVG. Los resultados varían en el análisis de sensibilidad, pero las conclusiones son robustas frente a cambios en los parámetros considerados. El programa de cribado es óptimo frente a la alternativa considerada, con un 95% de probabilidad si la disposición a pagar, social o del decisor sanitario, fuera de al menos 7.400 euros/AVG. Conclusiones. El análisis señala que el programa de cribado genético más tratamiento en familiares directos de personas con HF presenta una buena relación incremental de coste-efectividad frente a la alternativa de no cribar (AU)

Introduction and objectives. The aim was to assess the cost-effectiveness of a genetic screening program for first-degree relatives of patients with familial hypercholesterolemia (FH), followed by treatment when necessary, compared with the alternative of no screening. Methods. The cost-effectiveness analysis modeled the effect of statin treatment on individuals who were diagnosed with FH after genetic screening. The impact of uncertainty was evaluated using univariate probabilistic sensitivity analysis. The alternate strategy considered was no screening. In the cost-effectiveness analysis, the number of life-years gained (LYG) was regarded as the health outcome and the costs of screening, statin treatment, specialist consultations and hospital visits were all included. In addition, the expected value of perfect information was calculated as part of the sensitivity analysis. Results. In the base case, the incremental cost of the screening program for close relatives was 3423 euros per LYG. Although the sensitivity analysis gave a range of results, the conclusions were not affected by changes in the parameters considered. The screening program was found to be better than the alternative considered at a probability level of 95% if the acceptable level of health-care costs was at least 7400 euros per LYG. Conclusions. This analysis indicates that a genetic screening program, supplemented by treatment, for the close relatives of individuals with FH is preferable to the alternative of no screening in terms of incremental cost-effectiveness (AU)

Soluble Fas ligand plasma levels are associated with forearm reactive hyperemia in subjects with coronary artery disease: a novel biomarker of endothelial function?

OBJECTIVES: Fas ligand expression by endothelial cells is downregulated under proinflammatory conditions, facilitating the vascular infiltration by circulating cells. We have analyzed whether the forearm vasodilatory response to reactive hyperemia is associated with soluble Fas ligand (sFasL) plasma concentrations in subjects with coronary artery disease (CAD). METHODS: Forearm blood flow to reactive hyperemia, an indicator of endothelial function, and forearm blood flow to nitroglycerin (endothelial-independent) were measured in 110 subjects with stable CAD. sFasL and C-reactive protein (CRP) concentrations were also determined. RESULTS: There was a linear trend for the increase of sFasL and forearm reactive hyperemia (p<0.001). In contrast, no association was observed between sFasL and forearm blood flow to nitroglycerine. sFasL was not related with the presence of cardiovascular risk factors. Partial correlation coefficient adjusted by age and gender remained significant between sFasL and forearm blood flow to reactive hyperemia (r=0.35; p<0.001). No association between CRP concentrations and forearm reactive hyperemia, forearm blood flow to nitroglycerin or sFasL plasma concentrations was noted. CONCLUSIONS: Our results are consistent with the hypothesis that sFasL levels could reflect endothelial function in subjects with CAD and suggest that sFasL plasma concentrations could be a potential biomarker of endothelial function.

Vasodilatory action of loop diuretics: a plethysmography study of endothelial function in forearm arteries and dorsal hand veins in hypertensive patients and controls.

INTRODUCTION: Intravenous administration of loop diuretics induces venodilation before the diuretic response. We investigated whether furosemide and torasemide exert a dilatory effect on arteries and veins mediated by endothelial release of nitric oxide. METHODS: We performed intermittent venous occlusion plethysmography to study forearm blood flow and dorsal hand-vein distension in response to furosemide and torasemide infusion in hypertensive patients and healthy controls. RESULTS: Furosemide increased venodilation from 0.56 +/- 0.09 to 0.88 +/- 0.06 (P=0.000) in control subjects and from 0.49 +/- 0.10 to 0.75 +/- 0.12 (P=0.000) in hypertensive patients. Torasemide increased venodilation from 0.46 +/- 0.06 to 0.70 +/- 0.11 (P=0.007) in control subjects and from 0.48 +/- 0.09 to 0.67 +/- 0.12 (P = 0.03) in hypertensive patients. Co-infusion of the Nitric Oxide Synthase Inhibitor (L-NMMA)-blocked this venodilation, and the action was reversed with L-arginine. There were no significant changes in the arterial bed. CONCLUSIONS: Furosemide and torasemide induce a similar dose-response curve venodilation, but they have no effect on the arterial bed. Hypertensive patients show a smaller venous endothelium-dependent response than healthy controls. The venodilation induced by both diuretics requires release of nitric oxide.

Prevalence and spectrum of mutations in the sarcomeric troponin T and I genes in a cohort of Spanish cardiac hypertrophy patients.

We sequenced the coding exons of the cardiac troponins T (TNNT2) and I (TNNI3) genes in 115 Spanish HCM-patients (32% with a family history of the disease). Only two (2%) had mutations in the TNNT2 (Arg278>Cys and Arg92>Lys). These mutations were associated with variable clinical outcomes. No patient had TNNI3-mutation. We also genotyped these patients and 320 healthy controls for a 5 bp insertion/deletion (I/D) polymorphism in intron 3 of TNNT2. DD-homozygotes for the 5 bp I/D polymorphism were significantly more frequent among the patients (OR=1.83, 95% CI=2.10-5.16).

[Aspergillus fumigatus endocarditis in a patient with a biventricular pacemaker]. / Endocarditis por Aspergillus fumigatus en un marcapasos bicameral.

Aspergillus fumigatus endocarditis is one of the rarest and severest complications in cardiological patients. We describe a patient with an intracardial pacemaker who was diagnosed as having Aspergillus fumigatus endocarditis. Postmortem examination showed a large, Aspergillus-infected thrombus encased in the right ventricle, pulmonary trunk and main pulmonary branches.

Endocarditis por Aspergillus fumigatus en un marcapasos bicameral / Aspergillus fumigatus endocarditis in a patient with a biventricular pacemaker

La endocarditis por Aspergillus fumigatus es una de las complicaciones más raras y severas que puede presentar un paciente cardiológico. Presentamos el caso de una paciente portadora de marcapasos endocavitario diagnosticada de endocarditis por Aspergillus. El estudio postmortem mostró un trombo infectado por Aspergillus que ocupaba el ventrículo derecho, así como la arteria y las ramas de la arteria pulmonar (AU)

Aspergillus fumigatus endocarditis is one of the rare stand severest complications in cardiological patients. We describe a patient with an intracardial pacemaker who was diagnosed as having Aspergillus fumigatus endocarditis .Postmortem examination showed a large, Aspergillus-infected thrombus encased in the right ventricle, pulmonary trunk and main pulmonary branches (AU)

Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease.

OBJECTIVE: To demonstrate that nitroglycerin improves biological markers of arterial inflammation in patients with peripheral vascular disease. BACKGROUND: Atherosclerosis is an inflammatory disease in which there is an increase in active inflammation markers such as C-reactive protein and other factors released by endothelial cells. Nitroglycerin acts by a chemical liberation of nitric oxide. We have previously published the results from several controlled clinical trials confirming an anti-inflammatory action of nitroglycerin. METHODS: Forty patients with peripheral vascular disease entered a randomized, double-blind, placebo-controlled pilot study for 6 weeks. Twenty-one patients were treated with continuous application of a transdermal nitroglycerin patch (15 mg/24 hours) on the anterior face of the thigh. Venous blood samples were obtained before treatment and 2 and 6 weeks after. We measured plasma levels of C-reactive protein, cGMP (also intraplatelet cGMP), E-selectin, ICAM, VCAM-1, IL-6, and nitrites/nitrates. RESULTS: No biological parameter was modified in the placebo group. On the contrary, nitroglycerin significantly reduced plasma levels of C-reactive protein and sE-selectin and increased the levels of intraplatelet cGMP. CONCLUSIONS: The results of this preliminary study show that nitroglycerin has an anti-inflammatory action in patients with peripheral vascular disease. This may provide a new therapeutic approach to understanding the efficacy of nitrovasodilators in the improvement of atherosclerotic syndromes.

[Reproducibility of C-reactive protein analyses]. / Reproducibilidad de los análisis de proteína C reactiva.

The aim of this study was to measure the reliability of different nephelometric techniques for measuring C-reactive protein (CRP). One hundred and twenty samples were obtained from 40 patients. All 120 samples were divided in three parts to measure CRP using three different methods. Reliability was determined by the kappa index and intraclass correlation coefficient. The intraclass correlation coefficient ranged from 0.78 to 0.94. When CRP values were categorized in four groups, the kappa index reached 75-86% and percentage of agreement varied from 95% to 97%. When CRP values were divided into two groups, the kappa index was 73% to 78% and the percentage of agreement was 86% to 89%. We found that CRP determinations with different nephelometric methods were highly reproducible, even when different analysts were involved. Ultrasensitive techniques are needed only if the clinical objective is to obtain a CRP measurement under 0.3 mg/dl.