Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study

In idiopathic dilated cardiomyopathy, there are scarce data on the influence of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance on left ventricular (LV) remodeling

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Inquadramento clinico e prognostico della cardiomiopatia dilatativa: ruolo della risonanza magnetica cardiaca.

Obiettivi: obiettivo dello studio è stato quello di analizzare il valore prognostico aggiuntivo dei parametri di risonanza magnetica cardiovascolare (magnetic resonance imaging, MRI) rispetto alla caratterizzazione clinica e strumentale tradizionale in pazienti con cardiomiopatia dilatativa non-ischemica (CMD). Metodi: è stata arruolata una coorte prospettica di 342 pazienti con CMD (236 maschi, età 55±15 anni, media ± deviazione standard) con disfunzione sistolica ventricolare sinistra confermata alla MRI (frazione di eiezione<55%, media 33±11%), senza (stadio B, n=158) o con storia di sintomi da insufficienza cardiaca (stadio C, n=184, classe NYHA I-III). I pazienti in aggiunta alla caratterizzazione clinica ed elettrocardiografica convenzionale, sono stati sottoposti ad una MRI cardiaca per studiare i volumi e la funzione biventricolare e la fibrosi miocardica con sequenze post-contrasto (delayed enhancement, DE). In una sottopopolazione di 143 pazienti (93 maschi, età 60 ± 14 anni, frazione di eiezione 33±11%), sono stati effettuati anche un test da sforzo cardiopolmonare, un ECG secondo Holter, un ecocardiogramma ed una valutazione bioumorale completa. L’end-point era costituito dalle morti per causa cardiovascolare, gli shock appropriati del defibrillatore impiantabile e le ospedalizzazioni per scompenso cardiaco. Risultati: durante un follow-up mediano di 20,7 mesi, i pazienti con DE miocardico (n=142, 42%; estensione mediana 6,2% della massa ventricolare sinistra) hanno avuto un numero maggiore di eventi (n=24, 17%) rispetto ai pazienti senza DE (n=14, 7% P<0,01-all’analisi di Kaplan-Meier). Inoltre i pazienti con DE presentavano peggiori indici di rimodellamento e di funzione sistolica biventricolare. All’analisi uni variata, la frazione di eiezione ventricolare sinistra (HR 0.97, 95% CI 0.94-1.00, p=0.03), la frazione di eiezione ventricolare destra (HR 0.97, 95% CI 0.95-0.99, p=0.01), l’area dell’atrio sinistro (HR 1.06, 95%CI 1.03-1.09, p<0.01), l’area dell’atrio destro (HR 1.07, 95%CI 1.03-1.12, p<0.01), la presenza di DE (HR 2.58, 95%CI 1.33-4.99, p<0.01) e la creatininemia (HR 2.98, 95%CI 1.13-7.89, p=0.03) sono risultati predittori significativi dell’evento composito. All’analisi multivariata, solo la presenza di DE (HR 3.36, 95%CI 1.30-8.64, p=0.01) e la frazione di eiezione ventricolare destra (HR 0.96, 95% CI 0.93-0.98, p=0.01) sono risultati predittori significativi di eventi. Nella sottopopolazione di 143 pazienti, sia il DE sia la disfunzione ventricolare destra rimanevano significativi predittori di eventi all’analisi univariata, oltre alla disfunzione diastolica ventricolare sinistra, alla ipertensione polmonare, alle aritmie ventricolari, ai peptidi natriuretici cardiaci ed alla noradrenalina plasmatica. In particolare il DE risultava associato alle aritmie ventricolari, mentre la disfunzione sistolica ventricolare sinistra risultava associata ad un ridotto consumo di ossigeno e ad un’iperattivazione neuroendocrina. Conclusioni: nei pazienti con CMD sia la fibrosi miocardica sia la disfunzione ventricolare destra sono risultati predittori indipendenti di eventi cardiovascolari, fornendo utili informazioni aggiuntive per la stratificazione clinico-prognostica dei pazienti con CMD

Big gamma-glutamyltransferase is associated with epicardial fat volume and cardiovascular outcome in the general population

Aims: Gamma-glutamyltransferase (GGT) has been recognized as a cardiovascular risk factor, and its highest molecular weight fraction [big GGT (b-GGT)] is found in vulnerable atherosclerotic plaques. We explored the relationship between b-GGT, computed tomography findings, and long-term outcomes in the general population. Methods and results: Between May 2010 and October 2011, subjects aged 45-75 years living in a Tuscan city and without known cardiac disease were screened. The primary endpoint was a composite of cardiovascular death or acute coronary syndrome requiring urgent coronary revascularization. Gamma-glutamyltransferase fractions were available in 898 subjects [median age 65 years (25th-75th percentile 55-70), 46% men]. Median plasma GGT was 20 IU (15-29), and b-GGT was 2.28 (1.28-4.17). Coronary artery calcium (CAC) score values were 0 (0-60), and the volume of pro-atherogenic epicardial fat was 155 mL (114-204). In a model including age, sex, low-density lipoprotein (LDL) cholesterol, current or previous smoking status, hypertension, diabetes, obesity, b-GGT independently predicted epicardial fat volume (EFV) (r = 0.162, P &lt; 0.001), but not CAC (P = 0.198). Over a 10.3-year follow-up (9.6-10.8), 27 subjects (3%) experienced the primary endpoint. We evaluated couples of variables including b-GGT and a cardiovascular risk factor, CAC or EFV. Big GGT yielded independent prognostic significance from age, LDL cholesterol, current or previous smoking status, hypertension, diabetes, obesity, but not CAC or EFV. Conversely, GGT predicted the primary endpoint even independently from CAC and EFV. Conclusion: Big GGT seemed at least as predictive as the commonly available GGT assay; therefore, the need for b-GGT rather than GGT measurement should be carefully examined

Diagnostic performance of a Lattice Boltzmann-based method for CT-based fractional flow reserve

AIMS: Fractional flow reserve (FFR) estimated from coronary computed tomography angiography (CT-FFR) offers non-invasive detection of lesion-specific ischaemia. We aimed to develop and validate a fast CT-FFR algorithm utilising the Lattice Boltzmann method for blood flow simulation (LBM CT-FFR). METHODS AND RESULTS: Sixty-four patients with clinically indicated CTA and invasive FFR measurement from three institutions were retrospectively analysed. CT-FFR was performed using an onsite tool interfacing with a commercial Lattice Boltzmann fluid dynamics cloud-based platform. Diagnostic accuracy of LBM CT-FFR ≤0.8 and percent diameter stenosis >50% by CTA to detect invasive FFR ≤0.8 were compared using area under the receiver operating characteristic curve (AUC). Sixty patients successfully underwent LBM CT-FFR analysis; 29 of 73 lesions in 69 vessels had invasive FFR ≤0.8. Total time to perform LBM CT-FFR was 40±10 min. Compared to invasive FFR, LBM CT-FFR had good correlation (r=0.64), small bias (0.009) and good limits of agreement (-0.223 to 0.206). The AUC of LBM CT-FFR (AUC=0.894, 95% confidence interval [CI]: 0.792-0.996) was significantly higher than CTA (AUC=0.685, 95% CI: 0.576-0.794) to detect FFR ≤0.8 (p=0.0021). Per-lesion specificity, sensitivity, and accuracy of LBM CT-FFR were 97.7%, 79.3%, and 90.4%, respectively. CONCLUSIONS: LBM CT-FFR has very good diagnostic accuracy to detect lesion-specific ischaemia (FFR ≤0.8) and can be performed in less than one hour

Prognostic significance of myocardial extracellular volume fraction in nonischaemic dilated cardiomyopathy

In nonischaemic dilated cardiomyopathy (NICM), replacement myocardial fibrosis as detected by late gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR) is associated with poor prognosis. We investigated the as-yet unexplored prognostic significance of interstitial fibrosis in NICM, using T1-mapping CMR

3D-Flair sequence at 3T in cochlear otosclerosis

Purpose: To assess the capability of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences in detecting signal alterations of the endolabyrinthine fluid in patients with otosclerosis. Materials and methods: 3D-FLAIR before and after (-/+) gadolinium (Gd) administration was added to the standard MR protocol and acquired in 13 patients with a clinical/audiological diagnosis of severe/profound hearing loss in otosclerosis who were candidates for cochlear implantation and in 11 control subjects using 3-T magnetic resonance imaging (MRI) equipment. The MRI signal of the fluid-filled cochlea was assessed both visually and calculating the signal intensity ratio (SIR = signal intensity cochlea/brainstem). Results: We revealed no endocochlear signal abnormalities on T1-weighted –/+ Gd images for either group, while on 3D-FLAIR we found bilateral hyperintensity with enhancement after Gd administration in eight patients and bilateral hyperintensity without enhancement in one patient. No endocochlear signal abnormalities were detected in other patients or the control group. Conclusion: Using 3-T MRI equipment, the 3D-FLAIR -/+ Gd sequence is able to detect the blood-labyrinth barrier (BLB) breakdown responsible for alterations of the endolabyrinthine fluid in patients with cochlear otosclerosis. We believe that 3D-FLAIR +/- Gd is an excellent imaging modality to assess the intra-cochlear damage in otosclerosis patients. Key Points: • Gd-enhanced T1-weighted MRI has limited application to detect intra-cochlear damage.• 3D-FLAIR is less sensitive to flux artefacts and allows multiplanar reconstruction.• Post-Gd 3D-FLAIR is advantageous as it may highlight the BLB breakdown.• Using 3D-FLAIR -/+ Gd, we were able to identify intra-cochlear signal hyperintensities.• 3D-FLAIR might be applied for monitoring disease progression and treatment response