Global and Regional Ventricular Repolarization Study by Body Surface Potential Mapping in Patients with Left Bundle-Branch Block and Heart Failure Undergoing Cardiac Resynchronization Therapy

Background: The controversial effects promoted by cardiac resynchronization therapy (CRT) on the ventricular repolarization (VR) have motivated VR evaluation by body surface potential mapping (BSPM) in CRT patients. Methods: Fifty-two CRT patients, mean age 58.8 +/- 12.3 years, 31 male, LVEF 27.5 +/- 9.2, NYHA III-IV heart failure with QRS181.5 +/- 14.2 ms, underwent 87-lead BSPM in sinus rhythm (BASELINE) and biventricular pacing (BIV). Measurements of mean and corrected QT intervals and dispersion, mean and corrected T peak end intervals and their dispersion, and JT intervals characterized global and regional (RV, Intermediate, and LV regions) ventricular repolarization response. Results: Global QTm (P < 0.001) and QTcm (P < 0.05) were decreased in BIV; QTm was similar across regions in both modes (P = ns); QTcm values were lower in RV/LV than in Intermediate region in BASELINE and BIV (P < 0.001); only RV/Septum showed a significant difference (P < 0.01) in the BIV mode. QTD values both of BASELINE (P < 0.01) and BIV (P < 0.001) were greater in the Intermediate than in the LV region. CRT effect significantly reduced global/regional QTm and QTcm values. QTD was globally decreased in RV/LV (Intermediate: P = ns). BIV mode significantly reduced global T peak end mean and corrected intervals and their dispersion. JT values were not significant. Conclusions: Ventricular repolarization parameters QTm, QTcm, and QTD global/regional values, as assessed by BSPM, were reduced in patients under CRT with severe HF and LBBB. Greater recovery impairment in the Intermediate region was detected by the smaller variation of its dispersion.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload

Objectives: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Methods: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB+AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Results: Contractile performance was significantly improved in the PAB+AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB+AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor beta genes. Conclusions: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. (J Thorac Cardiovasc Surg 2012;144:1494-501)

The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat

The modulation played by reactive oxygen species on the angiotensin II-induced contraction in type I-diabetic rat carotid was investigated. Concentration-response curves for angiotensin II were obtained in endothelium-intact or endothelium-denuded carotid from control or streptozotocin-induced diabetic rats, pre-treated with tiron (superoxide scavenger), PEG-catalase (hydrogen peroxide scavenger), dimethylthiourea (hydroxyl scavenger), apocynin [NAD(P) H oxidase inhibitor], SC560 (cyclooxygenase-1 inhibitor), SC236 (cyclooxygenase-2 inhibitor) or Y-27632 (Rho-kinase inhibitor). Reactive oxygen species were measured by flow cytometry in dihydroethidium (DHE)-loaded endothelial cells. Cyclooxygenase and AT1-receptor expression was assessed by immunohistochemistry. Diabetes increased the angiotensin II-induced contraction but reduced the agonist potency in rat carotid. Endothelium removal, tiron or apocynin restored the angiotensin II-induced contraction in diabetic rat carotid to control levels. PEG-catalase, DMTU or SC560 reduced the angiotensin II-induced contraction in diabetic rat carotid at the same extent. SC236 restored the angiotensin II potency in diabetic rat carotid. Y-27632 reduced the angiotensin II-induced contraction in endothelium-intact or -denuded diabetic rat carotid. Diabetes increased the DHE-fluorescence of carotid endothelial cells. Apocynin reduced the DHE-fluorescence of endothelial cells from diabetic rat carotid to control levels. Diabetes increased the muscular cyclooxygenase-2 expression but reduced the muscular AT1-receptor expression in rat carotid. In summary, hydroxyl radical, hydrogen peroxide and superoxide anion-derived from endothelial NAD(P) H oxidase mediate the hyperreactivity to angiotensin II in type I-diabetic rat carotid, involving the participation of cyclooxygenase-1 and Rho-kinase. Moreover, increased muscular cyclooxygenase-2 expression in type I-diabetic rat carotid seems to be related to the local reduced AT1-receptor expression and the reduced angiotensin II potency. (C) 2011 Elsevier B. V. All rights reserved.

Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome

Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA repair pathway. To understand the role of this molecular pathway in a pluripotent cell and the impact of CSB mutation during human cellular development, we generated induced pluripotent stem cells (iPSCs) from CSB skin fibroblasts (CSB-iPSC). Here, we showed that the lack of functional CSB does not represent a barrier to genetic reprogramming. However, iPSCs derived from CSB patients fibroblasts exhibited elevated cell death rate and higher reactive oxygen species (ROS) production. Moreover, these cellular phenotypes were accompanied by an up-regulation of TXNIP and TP53 transcriptional expression. Our findings suggest that CSB modulates cell viability in pluripotent stem cells, regulating the expression of TP53 and TXNIP and ROS production.

Clinical Usefulness of Coronary Angiography in Patients with Left Ventricular Dysfunction

Background: Performing a coronary angiography in patients with heart failure of unknown etiology is often justified by the diagnostic assessment of ischemic heart disease. However, the clinical benefit of this strategy is not known. Objective: To evaluate the prevalence of ischemic heart disease by angiographic criteria in patients with heart failure and reduced ejection fraction of unknown etiology, as well as its impact on therapy decisions. Methods: Consecutive outpatients with heart failure and systolic dysfunction, who had an indication for coronary angiography to clarify the etiology of heart disease were assessed from 1 January 2009 to December 31, 2010. Patients diagnosed with coronary artery disease, positive serology for Chagas disease, congenital heart disease, valve disease or patients undergoing cardiac transplantation were excluded from the analysis. The sample was divided into two groups according to the indication for catheterization. Group-1: Symptomatic due to angina or heart failure. Group-2: Presence of >= 2 risk factors for coronary artery disease Results: One hundred and seven patients were included in the analysis, with 51 (47.7%) patients in Group 1 and 56 (52.3%) in Group 2. The prevalence of ischemic heart disease was 9.3% (10 patients), and all belonged to Group 1 (p = 0.0001). During follow-up, only 4 (3.7%) were referred for CABG; 3 (2.8%) patients had procedure-related complications. Conclusion: In our study, coronary angiography in patients with heart failure and systolic dysfunction of unknown etiology, although supported by current guidelines, did not show benefits when performed only due to the presence of risk factors for coronary artery disease. (Arq Bras Cardiol 2012;98(5):437-441)

Left ventricular free wall impeding rupture in post-myocardial infarction period diagnosed by myocardial contrast echocardiography: Case report

Abstract Background: Left ventricular free wall rupture occurs in up to 10% of the in-hospital deaths following myocardial infarction. It is mainly associated with posterolateral myocardial infarction and its antemortem diagnosis is rarely made. Contrast echocardiography has been increasingly used for the evaluation of myocardial perfusion in patients with acute myocardial infarction, with important prognostic implications. In this case, we reported its use for the detection of a mechanical complication following myocardial infarction. Case presentation: A 50-year-old man with acute myocardial infarction in the lateral wall underwent myocardial contrast echocardiography for the evaluation of myocardial perfusion in the third day post-infarction. A perfusion defect was detected in lateral and inferior walls as well as the presence of contrast extrusion from the left ventricular cavity into the myocardium, forming a serpiginous duct extending from the endocardium to the epicardial region of the lateral wall, without communication with the pericardial space. Magnetic resonance imaging confirmed the diagnosis of impending rupture of the left ventricular free wall. While waiting for cardiac surgery, patient presented with cardiogenic shock and died. Anatomopathological findings were consistent with acute myocardial infarction in the lateral wall and a left ventricular free wall rupture at the infarct site. Conclusion: This case illustrates the early diagnosis of left ventricular free wall rupture by contrast echocardiography. Due to its ability to be performed at bedside this modality of imaging has the potential to identify this catastrophic condition in patients with acute myocardial infarction and help to treat these patients with emergent surgery.

Invasive candidiasis and oral manifestations in premature newborns

Objective: To investigate prevalence of invasive candidiasis in a Neonatal Intensive Care Unit and to evaluate oral diseases and Candida spp. colonization in low birth weight preterm newborns. Methods: A descriptive epidemiological study performed in two stages. First, prevalence of candidiasis was analyzed in a database of 295 preterm patients admitted to hospital for over 10 days and birth weight less than 2,000g. In the second stage, oral changes and Candida spp. colonization were assessed in 65 patients weighing less than 2,000g, up to 4 week-old, hospitalized for over 10 days and presenting oral abnormalities compatible with fungal lesions. Swab samples were collected in the mouth to identify fungi. Results: Prevalence of candidiasis was 5.4% in the database analyzed. It correlated with prolonged hospital length of stay (p<0.001), in average, 31 days, and 85% risk of developing infection in the first 25 days. It correlated with low birth weight (p<0.001), with mean of 1,140g. The most frequent alterations were white soft plaques, detachable, in oral mucosa and tongue. Intense oral colonization by Candida spp was observed (80%). Conclusions: The frequency of invasive candidiasis was low and correlated with low birth weight and prolonged hospital stay. The most common oral changes were white plaques compatible with pseudomembranous candidiasis and colonization by Candida spp. was above average.

Residual stresses in Y-TZP crowns due to changes in the thermal contraction coefficient of veneers

Objective. To test the hypothesis that the difference in the coefficient of thermal contraction of the veneering porcelain above (˛liquid) and below (˛solid) its Tg plays an important role in stress development during a fast cooling protocol of Y-TZP crowns. Methods. Three-dimensional finite element models of veneered Y-TZP crowns were developed. Heat transfer analyses were conducted with two cooling protocols: slow (group A) and fast (groups B–F). Calculated temperatures as a function of time were used to determine the thermal stresses. Porcelain ˛solid was kept constant while its ˛liquid was varied, creating different ˛/˛solid conditions: 0, 1, 1.5, 2 and 3 (groups B–F, respectively). Maximum ( 1) and minimum ( 3) residual principal stress distributions in the porcelain layer were compared. Results. For the slowly cooled crown, positive 1 were observed in the porcelain, orientated perpendicular to the core–veneer interface (“radial” orientation). Simultaneously, negative 3 were observed within the porcelain, mostly in a hoop orientation (“hoop–arch”). For rapidly cooled crowns, stress patterns varied depending on ˛/˛solid ratios. For groups B and C, the patterns were similar to those found in group A for 1 (“radial”) and 3 (“hoop–arch”). For groups D–F, stress distribution changed significantly, with 1 forming a “hoop-arch” pattern while 3 developed a “radial” pattern. Significance. Hoop tensile stresses generated in the veneering layer during fast cooling protocols due to porcelain high ˛/˛solid ratio will facilitate flaw propagation from the surface toward the core, which negatively affects the potential clinical longevity of a crown.

Utilidade clínica da angiografia coronariana em pacientes com disfunção ventricular esquerda

FUNDAMENTO: A realização da angiografia coronariana na insuficiência cardíaca sem etiologia definida é frequentemente justificada para avaliação diagnóstica de cardiopatia isquêmica. Porém, o benefício clínico dessa estratégia não é conhecido. OBJETIVO: Avaliar a prevalência de cardiopatia isquêmica mediante critérios angiográficos em pacientes com insuficiência cardíaca e fração de ejeção reduzida sem etiologia, assim como o seu impacto na decisão terapêutica. MÉTODOS: Foram avaliados pacientes ambulatoriais consecutivos com insuficiência cardíaca e disfunção sistólica, que tiveram a angiografia coronariana indicada para esclarecimento etiológico da cardiopatia, no período de 1º de janeiro de 2009 a 31 de dezembro de 2010. Os pacientes com diagnóstico de doença arterial coronariana, sorologia positiva para doença de Chagas, cardiopatia congênita, valvopatia grave ou pacientes submetidos a transplante cardíaco foram excluídos da análise. A amostra foi dividida em dois grupos conforme a indicação do cateterismo. Grupo-1: Sintomáticos em razão de angina ou insuficiência cardíaca refratária. Grupo-2: Presença de > 2 fatores de risco para doença arterial coronariana RESULTADOS: Cento e sete pacientes foram incluídos para análise, sendo 51 (47,7%) pacientes pertencentes ao Grupo-1 e 56 (52,3%), ao Grupo-2. A prevalência de cardiopatia isquêmica foi de 9,3% (10 pacientes), e todos pertenciam ao Grupo-1 (p = 0,0001). Durante o seguimento, apenas 4 (3,7%) tiveram indicação de revascularização miocárdica; 3 (2,8%) pacientes apresentaram complicações relacionadas ao procedimento. CONCLUSÃO: Em nosso trabalho, a realização da angiografia coronariana em pacientes com insuficiência cardíaca e disfunção sistólica sem etiologia, apesar de embasada pelas atuais diretrizes, não evidenciou benefício quando indicada apenas pela presença de fatores de risco para doença arterial coronariana.