Correlazione tra iFR e test di imaging non invasivi per la diagnosi di ischemia miocardica inducibile

Nei pazienti con malattia coronarica, la presenza di ischemia miocardica inducibile è un fattore di rischio importante per un evento clinico avverso. Il ripristino del flusso sanguigno attraverso la rivascolarizzazione coronarica risulta in una maggiore riduzione di ischemia miocardica rispetto alla sola terapia medica. Tuttavia, per i pazienti con arterie coronariche stenotiche che non inducono ischemia miocardica, il beneficio della rivascolarizzazione è meno chiaro. Dopo 5 anni di follow-up in pazienti con una singola stenosi non determinante ischemia, non vi è alcun vantaggio di rivascolarizzazione da Percutaneous Coronary Intervention (PCI) rispetto alla terapia medica. Stress test non invasivi per l'individuazione di ischemia miocardica sono stati attuati nelle linee guida per la diagnosi e il trattamento della malattia coronarica. Di questi test, la perfusione nucleare è il più utilizzato. L'imaging nucleare, combinato con lo stress da esercizio fisico o farmacologicamente indotto è più preciso nella rilevazione e localizzazione ischemia miocardica del test da sforzo con elettrocardiografia. Molti studi clinici sulla rivascolarizzazione usano l’angiografia coronarica anche come il "gold standard" per definire il significato di una stenosi coronarica. la valutazione visiva della gravità della stenosi angiografica predice male suo il significato funzionale, mentre la presenza di ischemia miocardica inducibile relativa a tale stenosi dovrebbe essere il "trigger" per la rivascolarizzazione. Nello studio FAME, la misurazione di routine dell’importanza fisiologica di una lesione mediante la determinazione della riserva frazionale di flusso (FFR) è stata confrontata con l’angiografia per guidare la PCI nei pazienti con malattia coronarica multivasale. Questo studio ha dimostrato che l'angiografia è imprecisa nel valutare il significato funzionale di una stenosi coronarica rispetto a FFR. La riserva frazionale di flusso è un indice molto accurato e specifico per indicare se una particolare stenosi di un segmento coronarico può essere ritenuta responsabile d’ischemia o no, facilitando in tal modo la rivascolarizzazione coronarica ischemia-guidata in molti pazienti nel laboratorio di Emodinamica. L’instantaneous wave-free ratio o Instant Flow Reserve (iFR) è un nuovo strumento invasivo per valutare la presenza di ischemia miocardica attraverso la misura del rapporto tra la pressione distale ad una stenosi coronarica e la pressione aortica durante l'ultima fase della diastole. La iFR ha dimostrato di correlare molto bene con la FFR, che è stata validata come un mezzo per la diagnosi di ischemia miocardica inducibile attraverso il confronto con la scintigrafia miocardica (Single Photon Emission Computed Tomography, SPECT) e la PET (Positron Emission Tomography). Ad oggi, non sono disponibili dati sul grado di correlazione di iFR con i test non invasivi di ischemia miocardica. Lo scopo del nostro studio è stato quello di confrontare l'accuratezza diagnostica e l’instantaneous wave-free ratio (iFR) nella rilevazione d’ischemia miocardica nei pazienti con malattia coronarica stabile (SCAD) o con sindromi coronariche acute a basso rischio senza sopraslivellamento del segmento ST (NSTEACS) che mostrano almeno una stenosi coronarica intermedia (50-80% di diametro) e che sono stati sottoposti ad almeno due test non invasivi di stress imaging del miocardio. Uno dei test non invasivi sarà la SPECT, che è considerato il gold standard per la diagnosi di ischemia miocardica inducibile; gli altri test eseguiti sono stati l’ecocardiografia da sforzo, l'ecocardiografia da stress farmacologico

Lack of a relationship between circulating gamma-glutamyltransferase levels and carotid intima media thickness in hypertensive and diabetic patients

Marco Nuti, Paolo Spontoni, Chrysanthos Grigoratos, Giulia Dell'Omo, Alberto Balbarini, Roberto PedrinelliDipartimento Cardio Toracico e Vascolare, Università di Pisa, Pisa, ItalyBackground: By increasing the intracellular prooxidant burden, gamma-glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That noxious influence may be reflected by circulating enzyme levels, a correlate of cardiovascular risk factors, and a predictor of incident events. To evaluate this hypothesis, we tested the association between circulating GGT and common carotid intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic involvement, in a large and well-characterized group of patients at risk of cardiovascular disease (CVD).Patients: This study analyzed 548 patients with hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with known hepatic disease and abnormal GGT values were excluded.Methods: CIMT (B-mode ultrasonography) values were the mean of four far-wall measurements at both common carotids. Metabolic syndrome (MetS) was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent sex-related differences in GGT levels, the data were analyzed separately in males and females in samples dichotomized by the median.Results: The age-adjusted CIMT values did not differ by GGT levels in males or females. In contrast, the carotid wall was consistently thicker in patients with a history of CVD and MetS independent of age and concurrent GGT values. In both sexes, GGT was associated with key components of the MetS such as triglycerides, fasting plasma glucose, and body mass index.Conclusion: The data collected in this mixed group of hypertensive and/or diabetic patients with widely prevalent history of CVD do not support the concept of a direct pathophysiological link between GGT levels within reference limits and atherosclerotic involvement.Keywords: gamma-glutamyltransferase, carotid intima-media thickness, atherosclerosis, metabolic syndrom

Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes

<p>Abstract</p> <p>Background</p> <p>Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.</p> <p>Methods</p> <p>Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured.</p> <p>Results</p> <p>After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP.</p> <p>Conclusions</p> <p>Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.</p

A meta-analysis of MitraClip combined with medical therapy vs. medical therapy alone for treatment of mitral regurgitation in heart failure patients

Aims: Survival benefit of percutaneous mitral valve repair with the MitraClip over conservative treatment of functional mitral regurgitation (MR) remains unclear. The purpose of this meta-analysis is to compare survival outcomes of MitraClip with those of medical therapy in patients with functional MR. Methods and results: A comprehensive literature search of PubMed, MEDLINE, and Google Scholar was conducted including studies evaluating MitraClip vs. medical therapy with multivariate adjustment and with &gt;80% of patients with functional MR. Death from any cause was the primary endpoint, while freedom from readmission was the secondary one, evaluated with random effects. These analyses were performed at study level and at patient level including only functional MR when available, evaluating the effect of MitraClip in different subgroups according to age, ischaemic aetiology, presence of implantable cardioverter defibrillator/cardiac resynchronization therapy, and left ventricular ejection fraction and volumes. We identified six eligible observational studies including 2121 participants who were treated with MitraClip (n&nbsp;=&nbsp;833) or conservative therapy (n&nbsp;=&nbsp;1288). Clinical follow-up was documented at a median of 400&nbsp;days. At study-level analysis, MitraClip, when compared with medical therapy (P&nbsp;=&nbsp;0.005), was associated with significant reduction of death (P&nbsp;=&nbsp;0.002) and of readmission due to cardiac disease. At patient-level analysis, including 344 patients, MitraClip confirmed robust survival benefit over medical therapy for all patients with functional MR and among the most important subgroups. Conclusions: Compared with conservative treatment, MitraClip is associated with a significant survival benefit. Importantly, this superiority is particularly pronounced among patients with functional MR and across all the main subgroups

Evaluation of a Novel Method Using Computed Tomography to Predict New Onset of Atrial Fibrillation or Embolic Events after Transcatheter Aortic Valve Implantation: the Role of Hounsfield Unit Density Ratio in the Left Atrial Appendage

Backgrounds: Evaluation of left atrial appendage (LAA) with angio-computed tomography (CCTA) in order to predict new onset of atrial fibrillation (AF) or embolic events is a new upcoming topic. No previous reported studies are available in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: We analyzed pre-procedural CCTA scans of 325 patients who underwent TAVI performing a linear coefficient of attenuation analyses with Hounsfield units (HU) in LAA. HU in LAA distal and proximal was calculated, as well as the ratio. A sensibility and specificity analyses was conducted in order to identify the optimal cutoff to predict new onset AF or embolic events after TAVI. Results: Patients were divided into 4 groups according to the presence of AF. Baseline clinical and echocardiographic features were similar except for a significantly higher STS score and mitral regurgitation severity in PRE-TAVI AF group (p=0.003 and p=0.002 respectively). HU analyses showed a statistical difference in measure performed in LAA distal and in the HU LAA distal/Proximal ratio, with the lowest value in patients with pre-TAVI AF (p&lt;0.001 and p&lt;0.001 respectively). The ROC analyses found 0.84 as the cut-off for to predict the composite endpoint of new AF or embolic events, with sensitivity of 51% and specificity of 52% (p=0.008). Conclusion: In patients with aortic stenosis (AS), use of LAA assessment with CCTA to predict embolic events or new onset AF is no efficacy and cannot be substituted clinical indications for prevention and therapy of embolic events

Cellule progenitrici endoteliali: ruolo nel trattamento interventistico endovascolare della stenosi carotidea

E’ noto dalla letteratura che le cellule progenitrici endoteliali (EPC) derivano dal midollo osseo, sono coinvolte nella riparazione del danno endoteliale e contribuiscono all’angiogenesi nelle aree ischemiche. Tali cellule sono identificabili nel sangue periferico per la presenza di specifici antigeni di superficie. I principali stimoli alla mobilizzazione delle EPC dal midollo osseo sono l’ischemia e il trauma vascolare. Evidenze cliniche mostrano come l’angioplastica coronarica, eseguita in pazienti affetti da cardiopatia ischemica, sia in grado di determinare una variazione dei livelli circolanti di questi progenitori in ragione dell’insulto endoteliale prodotto. Lo scopo del nostro studio è quello di valutare l’effetto della procedura di stenting carotideo(CAS) sia sulle cellule progenitrici circolanti(PC, CD34+) che sulle cellule progenitrici endoteliali(EPC, CD34+/KDR+). Sono stati arruolati 16 pazienti(10 maschi e 6 femmine, di età media pari a 71±7 anni) afferiti presso il nostro dipartimento per sottoporsi a CAS. Abbiamo eseguito prelievi ematici all’ammissione in reparto(t0), a 24 ore(t1), a 7 giorni(t7) e a 30 giorni (t30) dalla procedura interventistica, al fine di valutare, oltre i principali parametri ematochimici, la proteina C-reattiva ad alta sensibilità(hs-CRP), il VEGF(tramite metodo ELISA), le PC ed EPC(mediante analisi citofluorimetrica). Il follow-up clinico, condotto anche attraverso l’esame ecococolorDoppler, non ha evidenziato complicanze periprocedurali (entro 1 mese), mentre nel più lungo periodo sono insorti un IMA e un TIA. I risultati ottenuti mostrano una diminuzione di PC ed EPC al t1 rispetto al basale(t0); al tempo t7 abbiamo un incremento di entrambi i tipi cellulari, che si mantiene anche a distanza di un mese. La hs-CRP aumenta al t1, si mantiene elevata al t7 e assume valori simil-basali al t30. Il VEGF mostra un andamento in costante crescita da t0 a t7. Il transitorio decremento delle cellule progenitrici al t1 potrebbe essere dovuto al cosiddetto ”effetto homing”, mentre l’incremento al t7 e al t30 potrebbe essere legato al prolungato stato infiammatorio e al tardivo rilascio di VEGF. E’ necessario disporre di una più ampia casistica per comprendere se le EPC possano assumere un ruolo come biomarkers di prognosi, capaci di identificare pazienti ad elevato rischio di eventi cardiovascolari una volta sottoposti a procedura interventistica endovascolare

Au-Pd/AC as catalysts for alcohol oxidation: effect of reaction parameters on catalytic activity and selectivity

The oxidation of different alcohols with molecular oxygen in water has been investigated using a range of activated carbon-supported Au-Pd bimetallic catalysts. The effect of the Au-Pd ratio on the conversion and selectivity was observed and a synergistic effect is present in a large range of the Au-Pd ratio, being maximized for Au80-Pd20 composition instead of Au90-Pd10 shown in glycerol oxidation [1]. Moreover the enhancement of conversion observed by adding a base resulted greater for gold-rich catalysts rather than for palladium-rich ones. The effect of the alcohol concentration and the metal/substrate ratio in the presence or the absence of the base was also studied revealing substantial differences in terms of both activity and selectivity. At 1 M concentration under biphasic conditions benzyl alcohol has been selectively oxidized to benzaldehyde (S90=98%) even in the presence of NaOH with a TOF of 18000h-1 using Au60-Pd40/AC as the catalyst