Ángel González Pinto

Periannular extension of infective endocarditis

OBJECTIVES This prospective study was designed to assess the current clinical course, risk factors, microbiologic profile and echocardiographic findings of patients with left-sided endocarditis and perivalvular complications. BACKGROUND Periannular complications worsen the prognosis of patients with endocarditis. The relation between these complications and the clinical and microbiologic data has not been clearly defined. METHODS In this clinical cohort study, 211 patients with left-sided endocarditis, according to the Duke criteria, were prospectively recruited. All patients underwent conventional and transesophageal echocardiography. The mean follow-up interval was 151 days. RESULTS Perivalvular complications were detected in 78 patients (37%). The incidence of periannular extension of infection in native and prosthetic valves was 29% and 55%, respectively. The presence of prosthesis (relative risk [RR] 1.88, 95% confidence interval [CI] 1.35 to 2.64) and previous endocarditis (RR 1.78, 95% CI 1.16 to 2.7) were the only pre-existing heart conditions associated with perivalvular complications. Aortic infection (RR 1.8, 95% CI 1.23 to 2.66) and the development of atrioventricular (AV) block (RR 2.55, 95% CI 1.91 to 3.41) were related with the existence of these complications. Coagulase-negative staphylococci were very common in patients with perivalvular complications (RR 1.77, 95% CI 1.21 to 2.59), and small vegetations were more frequent in these patients (RR l.45, 95% CI 0.95 to 2.22). An operation was more frequently performed in patients with perivalvular complications, but mortality was similar in patients with and without these complications. CONCLUSIONS Aortic infection, prosthetic endocarditis, new AV block and coagulase-negative staphylococci were independent risk factors of periannular complications. The period between symptom onset and diagnosis, the incidence of pericardial effusion and persistent signs of infection were similar between patients with and without perivalvular complications. Patients with perivalvular complications did not demonstrate a difference in the presence or size of vegetations or the frequency of embolism. An operation was more frequently performed in these patients, but mortality was similar in both groups.

A Proteomic Focus on the Alterations Occurring at the Human Atherosclerotic Coronary Intima

Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries.

Nitric Oxide Increases Cardiac IK1 by Nitrosylation of Cysteine 76 of Kir2.1 Channels

Rationale: The cardiac inwardly rectifying K+ current (IK1) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential. Objective: This study aims to analyze the effects of nitric oxide (NO) on human atrial IK1 and on Kir2.1 channels, the major isoform of inwardly rectifying channels present in the human heart. Methods and Results: Currents were recorded in enzymatically isolated myocytes and in transiently transfected CHO cells, respectively. NO at myocardial physiological concentrations (25 to 500 nmol/L) increased inward and outward IK1 and IKir2.1. These effects were accompanied by hyperpolarization of the resting membrane potential and a shortening of the duration of phase 3 of the human atrial action potential. The IKir2.1 increase was attributable to an increase in the open probability of the channel. Site-directed mutagenesis analysis demonstrated that NO effects were mediated by the selective S-nitrosylation of Kir2.1 Cys76 residue. Single ion monitoring experiments performed by liquid chromatography/tandem mass spectrometry suggested that the primary sequence that surrounds Cys76 determines its selective S-nitrosylation. Chronic atrial fibrillation, which produces a decrease in NO bioavailability, decreased the S-nitrosylation of Kir2.1 channels in human atrial samples as demonstrated by a biotin-switch assay, followed by Western blot. Conclusions: The results demonstrated that, under physiological conditions, NO regulates human cardiac IK1 through a redox-related process.

Chronic Atrial Fibrillation Increases MicroRNA-21 in Human Atrial Myocytes Decreasing L-Type Calcium Current

Background—Atrial fibrillation is characterized by progressive atrial structural and electrical changes (atrial remodeling) that favor arrhythmia recurrence and maintenance. Reduction of L-type Ca2+ current (ICa,L) density is a hallmark of the electrical remodeling. Alterations in atrial microRNAs could contribute to the protein changes underlying atrial fibrillation–induced atrial electrical remodeling. This study was undertaken to compare miR-21 levels in isolated myocytes from atrial appendages obtained from patients in sinus rhythm and with chronic atrial fibrillation (CAF) and to determine whether L-type Ca2+ channel subunits are targets for miR-21. Methods and Results—Quantitative polymerase chain reaction analysis showed that miR-21 was expressed in human atrial myocytes from patients in sinus rhythm and that its expression was significantly greater in CAF myocytes. There was an inverse correlation between miR-21 and the mRNA of the &agr;1c subunit of the calcium channel (CACNA1C) expression and ICa,L density. Computational analyses predicted that CACNA1C and the mRNA of the &bgr;2 subunit of the calcium channel (CACNB2) could be potential targets for miR-21. Luciferase reporter assays demonstrated that miR-21 produced a concentration-dependent decrease in the luciferase activity in Chinese Hamster Ovary cells transfected with CACNA1C and CACNB2 3′ untranslated region regions. miR-21 transfection in HL-1 cells produced changes in ICa,L properties qualitatively similar to those produced by CAF (ie, a marked reduction of ICa,L density and shift of the inactivation curves to more depolarized potentials). Conclusions—Our results demonstrated that CAF increases miR-21 expression in enzymatically isolated human atrial myocytes. Moreover, it decreases ICa,L density by downregulating Ca2+ channel subunits expression. These results suggested that this microRNA could participate in the CAF-induced ICa,L downregulation and in the action potential duration shortening that maintains the arrhythmia.

Implantación percutánea de prótesis valvular aórtica: experiencia inicial en España

Los pacientes con estenosis aortica sintomatica tienen un pronostico ominoso con tratamiento medico. En pacientes con contraindicacion quirurgica, se ha propuesto la implantacion percutanea como alternativa. Presentamos la experiencia inicial en Espana de la implantacion percutanea de protesis valvular aortica. Analizamos los resultados hospitalarios y a corto-medio plazo de 4 pacientes a quienes se implanto, de forma percutanea, una protesis valvular aortica de Cribier-Edwards. Las cuatro protesis valvulares se implantaron con exito por via percutanea a traves de la arteria femoral. El procedimiento fue guiado por angiografia y ecocardiografia transesofagica. Los pacientes fueron dados de alta entre 3 y 5 dias despues del procedimiento y siguen en buena situacion clinica a los 3 meses. En conclusion, la experiencia inicial en Espana de implantacion percutanea de protesis valvular aortica de Cribier-Edwards apunta en la direccion de una alternativa valida en pacientes con contraindicacion o alto riesgo para la sustitucion quirurgica.

Heart Valves Should Not Be Routinely Cultured

ABSTRACT Heart valve (HV) culture is one of the major Duke criteria for the diagnosis of definite infectious endocarditis (IE). However, previous series suggest that heart valve culture does not have good sensitivity (7.8 to 17.6%) and may be contaminated during manipulation. Our goal was to establish the value of routine cultures of heart valves in patients with and without IE. From 2004 to 2006, resected heart valves were systematically cultured according to standard procedures. The definition and etiology of IE were based on the Duke criteria and on valve PCR of specimens from blood culture-negative patients. Bacterial and fungal broad-range PCR was performed. A total of 1,101 heart valves were studied: 1,030 (93.6%) from patients without IE and 71 (6.4%) from patients with IE (42 patients). Overall, 321 (29.2%) cultures were positive (28/71 [39.4%] IE cases and 293/1,030 [28.4%] non-IE). All IE patients with negative heart valve cultures had received antimicrobial therapy. The yield of culture of heart valves for IE diagnosis was as follows: sensitivity, 25.4%; specificity, 71.6%; positive predictive value (PPV), 5.8%; and negative predictive value, 93.3%. Because of its poor sensitivity and PPV, valve cultures should not be performed for patients without a clinical suspicion of IE. For patients with confirmed IE, heart valve cultures should be interpreted with caution.

Aortic Intramural Hematoma During Coronary Angioplasty: Insights into the Pathogenesis of Intramedial Hemorrhage

We report a case of a 74-year-old woman who had an aortic intramural hematoma as a complication of percutaneous coronary angioplasty. Transesophageal echocardiography enabled the diagnosis of aortic intramural hematoma and was very useful in the patients management and follow-up.

Chronic Atrial Fibrillation Up-regulates β1-adrenoceptors Affecting Repolarizing Currents and Action Potential Duration

AIMS β-adrenergic stimulation has profound influence in the genesis and maintenance of atrial fibrillation (AF). However, the effects of β-Adrenoceptor stimulation on repolarizing currents and action potential (AP) characteristics in human atrial myocytes from left (LAA) and right atrial appendages (RAA) obtained from sinus rhythm (SR) and chronic atrial fibrillation (CAF) patients have not been compared yet. METHODS AND RESULTS Currents and APs were recorded using whole-cell patch-clamp in RAA and LAA myocytes from SR and CAF patients. Isoproterenol concentration-dependently decreased the Ca(2+)-independent 4-aminopyridine-sensitive component of the transient outward current (I(to1)) and the inward rectifying current (I(K1)). CAF significantly enhanced this inhibition, this effect being more marked in the left than in the right atria. CAF dramatically enhanced β-Adrenoceptor-mediated increase in the slow component of the delayed rectifier current (I(Ks)), whose density was already markedly increased by CAF. Conversely, the ultrarapid component of the delayed rectifier current (I(Kur)) of both SR and CAF myocytes was insensitive to low isoproterenol concentrations. As a consequence, stimulation of β1-Adrenoceptors in SR myocytes lengthened, whereas in CAF myocytes shortened, the AP duration. Quantitative PCR revealed that CAF up-regulated β1-Adrenoceptor expression, preferentially in the left atria. CONCLUSION The present results demonstrate that CAF increases the effects of β1-Adrenoceptor stimulation on repolarizing currents by means of a chamber-specific up-regulation of the receptors. This, together with the ion channel derangements produced by CAF, could contribute to the long-term stabilization of the arrhythmia by shortening the AP duration.

Pitx2c increases in atrial myocytes from chronic atrial fibrillation patients enhancing IKs and decreasing ICa,L

AIMS Atrial fibrillation (AF) produces rapid changes in the electrical properties of the atria (electrical remodelling) that promote its own recurrence. In chronic AF (CAF) patients, up-regulation of the slow delayed rectifier K(+) current (IKs) and down-regulation of the voltage-gated Ca(2+) current (ICa,L) are hallmarks of electrical remodelling and critically contribute to the abbreviation of action potential duration and atrial refractory period. Recent evidences suggested that Pitx2c, a bicoid-related homeodomain transcription factor involved in directing cardiac asymmetric morphogenesis, could play a role in atrial remodelling. However, its effects on IKs and ICa,L are unknown. METHODS AND RESULTS Real-time quantitative polymerase chain reaction analysis showed that Pitx2c mRNA expression was significantly higher in human atrial myocytes from CAF patients than those from sinus rhythm patients. The expression of Pitx2c was positively and negatively correlated with IKs and ICa,L densities, respectively. Expression of Pitx2c in HL-1 cells increased IKs density and reduced ICa,L density. Luciferase assays demonstrated that Pitx2c increased transcriptional activity of KCNQ1 and KCNE1 genes. Conversely, its effects on ICa,L could be mediated by the atrial natriuretic peptide. CONCLUSION Our results demonstrated for the first time that CAF increases Pitx2c expression in isolated human atrial myocytes and suggested that this transcription factor could contribute to the CAF-induced IKs increase and ICa,L reduction observed in humans.

[Percutaneous closure of pseudoaneurysm of the mitral-aortic intervalvular fibrosa].

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is an uncommon event, which is usually secondary to endocarditis of the aortic valve. Its clinical evolution is variable and potentially serious complications can occur. Therefore, surgical treatment is usually recommended. To the best of our knowledge, this is the first description of percutaneous treatment of this disease.