Myocardial stress perfusion scintigraphy for outcome prediction in patients with severe left ventricular systolic dysfunction

Abstract: Coronary angiography has been recommended in all patients with suspected chronic coronary syndrome and left ventricular ejection fraction (LVEF) ≤35%. The role of ischemia testing, for example, through stress-rest myocardial perfusion scintigraphy (MPS), for risk prediction is not well established. Methods: We evaluated 1576 consecutive patients referred to MPS and stratified into 3 LV ejection fraction (LVEF) categories: ≤35%, 36–49%, and ≥ 50%. Results: Patients with LVEF ≤35% were oldest, most often men, and with the highest likelihood of prior early (elective or urgent) coronary revascularization. They had also the highest values or summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS), as well as the highest frequency of significant coronary artery disease, and a greater number of diseased vessels. Follow-up: In this subgroup, 32 cardiovascular death or non-fatal myocardial infarction (MI) (21%), 35 all-cause deaths (22%), and 37 cardiovascular deaths, non-fatal MI, or late revascularizations (27%) were recorded with the shortest survival among all LVEF classes. SRS, SSS, and SDS had very low area under the curve values for the prediction of the 3 endpoints, with very high cut-offs, respectively. SRS and SSS cut-offs predicted a worse outcome in Cox regression models including the number of diseased vessels and early revascularization. Conclusions: In patients with LVEF ≤35%, SRS and SSS are less predictive of outcome than in patients with better preserved systolic dysfunction, but their cut-offs retain independent prognostic significance from the number of vessels with significant stenoses and from early revascularization

T-786→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy

Background: Insulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T-786→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T-786→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy.Method: A group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T-786→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index > 2.5) were determined in all patients.Results: Genotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p < 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p < 0.04).Conclusions: T-786→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease. © 2012 Vecoli et al.; licensee BioMed Central Ltd

Propaedeutic study for the delivery of nucleic acid-based molecules from PLGA microparticles and stearic acid nanoparticles

We studied the mechanism governing the delivery of nucleic acid-based drugs (NABD) from microparticles and nanoparticles in zero shear conditions, a situation occurring in applications such as in situ delivery to organ parenchyma. The delivery of a NABD molecule from poly(DL-lactide-co-glycolide) (PLGA) microparticles and stearic acid (SA) nanoparticles was studied using an experimental apparatus comprising a donor chamber separated from the receiver chamber by a synthetic membrane. A possible toxic effect on cell biology, as evaluated by studying cell proliferation, was also conducted for just PLGA microparticles. A mathematical model based on the hypothesis that NABD release from particles is due to particle erosion was used to interpret experimental release data. Despite zero shear conditions imposed in the donor chamber, particle erosion was the leading mechanism for NABD release from both PLGA microparticles and SA nanoparticles. PLGA microparticle erosion speed is one order of magnitude higher than that of competing to SA nanoparticles. Finally, no deleterious effects of PLGA microparticles on cell proliferation were detected. Thus, the data here reported can help optimize the delivery systems aimed at release of NABD from micro- and nanoparticles

Structural abnormalities of the coronary arterial wall - in addition to luminal narrowing - Affect myocardial blood flow reserve

Multislice CT provides information on coronary luminal narrowing and on the structural abnormalities of the coronary arterial wall using densitometric analysis. We sought to investigate the effects of coronary luminal narrowing, structural abnormalities of the coronary arterial wall, and cardiovascular risk factors on regional and global myocardial blood flow (MBF) reserve. Methods: We studied 68 patients (mean age ± SD, 61 ± 10 y; 41 men, 27 women) with an intermediate probability of coronary artery disease. We measured the severity of coronary stenoses and the fibroadipose, fibromuscular, and calcium components of the coronary arterial wall by 64-row multislice CT coronary angiography. We also measured regional and global MBF reserve by PET using 13N-ammonia as a flow tracer at rest and after dipyridamole. Results: One or more significant coronary stenoses (≥50% luminal narrowing) was present in 32 patients (47%), and nonsignificant stenoses were present in 15 patients (22%). Regional MBF reserve was significantly different in the territories perfused by normal coronary arteries, nonsignificant coronary stenoses, and significant coronary stenoses (P < 0.001). Calcium content was higher in the coronary arteries with significant or nonsignificant stenoses (0.95% ± 1.08% and 0.73% ± 0.93%, respectively) than in those without stenoses (0.11% ± 0.38%, P < 0.001). Significant coronary stenosis (P = 0.047) and calcium content (P = 0.017) were the only independent determinants of impaired regional MBF reserve using multivariate analysis. At multiple logistic regression analysis, the Framingham risk score, an index of global cardiovascular risk burden, was the only significant determinant of global MBF reserve (P = 0.028). Conclusion: Coronary stenoses and coronary calcium content independently affect regional MBF reserve. Framingham risk score is the only significant determinant of global MBF reserve. Copyright © 2011 by the Society of Nuclear Medicine, Inc

Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis

BACKGROUND: The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. METHODS AND RESULTS: We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. CONCLUSIONS: Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

Translation and cross-cultural adaptation of the protocol of orofacial myofunctional evaluation with scores for Italian Language

RESUMO O protocolo de avaliação miofuncional orofacial com escores (protocolo AMIOFE) é um instrumento validado para o diagnóstico de distúrbios miofuncionais orofaciais que pode ser utilizado por fonoaudiólogos em sua prática clínica. O presente estudo foi desenvolvido porque não há um instrumento validado para esta finalidade em língua Italiana. Objetivos: traduzir e realizar a adaptação transcultural do protocolo AMIOFE para a língua italiana e determinar os valores dos escores de normalidade em um grupo de jovens e adultos italianos. Métodos: o protocolo AMIOFE foi traduzido da língua inglesa para a italiana por três indivíduos bilíngues. A partir dessas traduções, uma versão de consenso foi preparada por um comitê de pesquisa (três fonoaudiólogos e um médico) e submetida a um comitê de juízes, composto por oito fonoaudiólogos italianos experientes na área. Os autores da versão original verificaram e aprovaram a versão italiana do protocolo. O instrumento foi testado por meio de avaliações de 40 sujeitos italianos jovens e adultos (faixa etária entre 18 e 56 anos de idade), realizadas por dois fonoaudiólogos. O ponto de corte, previamente descrito, foi usado para determinar as médias e desvios-padrão. Resultados: a etapa de tradução e a versão final da versão italiana do protocolo AMIOFE foram apresentadas, bem como as médias dos escores para os sujeitos com e sem distúrbio miofuncional orofacial. Conclusão: a versão italiana do protocolo AMIOFE foi desenvolvida, traduzida e adaptada transculturalmente. Valores de normalidade para sujeitos italianos jovens e adultos foram apresentados

Study on Polymer-Surfactant Interactions for the Improvement of Drug Delivery Systems Wettability

One of the possible causes of failure of the mechanochemical activation of poorly soluble drugs relies on the scarce drug wettability. Indeed, the mechanochemical process comports the disposition of drug nano-crystals and amorphous drug, generated by the destruction of original drug macro-crystals, on the surface of the carrier (acting as stabiliser), usually represented by crosslinked polymeric particles. Accordingly, the scarce drug wettability can reduce the beneficial action of mechanochemical activation (nano-crystals and amorphous drug are characterised by a higher solubility with respect to the original macro-crystals). In this light, this paper is focussed on the use of surfactants for the increase of delivery system (drug plus carrier) wettability. In particular, the surfactant-polymer systems are characterised for what concerns their bulk and surface properties. This allows to select the best surfactant and to experimentally verify its effect on the release kinetics of a poorly soluble and wettable drug