Confronto randomizzato tra ablazione circonferenziale delle vene polmonari e terapia antiaritmica in pazienti con fibrillazione atriale parossistica – Studio APAF (Ablation for Paroxysmal Atrial Fibrillation)

Il presente progetto di ricerca focalizza la sua attenzione su due aree di crescente interesse della cardiologia in generale e dell’aritmologia in particolare: la fibrillazione atriale e l’insufficienza cardiaca. Fibrillazione atriale e scompenso cardiaco sono due condizioni cliniche strettamente associate. Il meccanismo fondamentale alla base della loro co-prevalenza è che l’una condizione patologica determina e sostiene il meccanismo eziopatogenetico dell’altra. L’esempio più eclatante di questo rapporto di causalità diretta è rappresentato dalla cosiddetta tachicardiomiopatia, condizione clinica frequente in pazienti con funzione ventricolare normale al momento dell’insorgenza della FA e che successivamente sviluppano una cardiomiopatia dilatativa potenzialmente reversibile mediante efficace trattamento della FA. Un altro dato estremamente interessante rigurada il tasso di mortalità: il rischio di mortalità risulta di due volte più alto nei pazienti con HF che sviluppano successivamente FA e addirittura di tre volte in quelli con FA poi complicata da scompenso cardiaco. La comprensione ed il trattamento della fibrillazione atriale sono in evoluzione come mai prima d’ora grazie alla crescente disponibilità di nuove tecnologie e di nuovi farmaci. Sono pochi i dati attualmente disponibili circa l’evoluzione di malattia dal primo episodio di FA parossistica. In particolare non ci sono studi prospettici ed i soli dati di progressione della fibrillazione atriale disponibili in letteratura derivano da studi retrospettivi, che inoltre non valutano l’influenza della procedura di ablazione transcatetere mediante radiofrequenza (TC-RF) sulla progressione e sulle possibili complicanze della fibrillazione atriale. Il presente progetto di ricerca costituisce uno studio prospettico a lungo termine che ha tra i suoi obiettivi quello di individuare i principali predittori di progressione della FA dal primo episodio parossistico, non dovuto a cause reversibili, in soggetti con e senza comorbilità, indagando anche l’influenza potenziale dell’ablazione transcatetere sulla storia naturale di questa patologia. L’ablazione transcatetere mediante radiofrequenza è attualmente raccomandata in classe I (livello di evidenza A) per il trattamento di pazienti con FA parossistica e atrio sinistro di dimensioni normali o lievemente aumentate; tuttavia mancano dati di out-come a lungo termine per supportare tale raccomandazione ed i soli dati disponibili in letteratura dimostrano la superiorità dell’ablazione TC-RF rispetto alla terapia farmacologica antiaritmica convenzionale nella prevenzione delle recidive aritmiche di FA in un periodo di follow-up di un anno (Pappone e Coll. J Am Coll Cardiol 2006;48:2340-2347). Si tratta, ovviamente, di una finestra temporale piuttosto breve, specialmente se si tiene conto della natura di tale patologia, della sua progressione e delle complicazioni ad essa associate. Abbiamo quindi condotto un studio randomizzato (“Ablation for Paroxysmal Atrial Fibrillation”-APAF TRIAL) per determinare se l’ablazione circonferenziale delle vene polmonari fosse superiore alla terapia antiaritmica nel mantenimento del ritmo sinusale a quattro anni nei pazienti affetti da una lunga storia di FA parossistica. Il presente studio ha il più ampio numero di pazienti arruolati ed il follow-up più lungo tra tutti i trial randomizzati sul trattamento della fibrillazione atriale. In breve, i dati dello studio hanno mostrato come la strategia di impostare una terapia antiaritmica convenzionale e di ricorrere all’ablazione esclusivamente in caso di assenza di risposta alla terapia farmacologica sia assai meno efficace della ablazione mediante CPVA eseguita come approccio iniziale. L’ablazione transcatetere mediante radiofrequenza deve pertanto essere considerata come la strategia terapeutica di prima scelta in pazienti selezionati con fibrillazione atriale parossistica

Cardiac hybrid imaging: novel tracers for novel targets

Non-invasive cardiac imaging has explored enormous advances in the last few decades. In particular, hybrid imaging represents the fusion of information from multiple imaging modalities, allowing to provide a more comprehensive dataset compared to traditional imaging techniques in patients with cardiovascular diseases. The complementary anatomical, functional and molecular information provided by hybrid systems are able to simplify the evaluation procedure of various pathologies in a routine clinical setting. The diagnostic capability of hybrid imaging modalities can be further enhanced by introducing novel and specific imaging biomarkers. The aim of this review is to cover the most recent advancements in radiotracers development for SPECT/CT, PET/CT, and PET/MRI for cardiovascular diseases

Tracers for Cardiac Imaging: Targeting the Future of Viable Myocardium

Ischemic heart disease is the leading cause of mortality worldwide. In this context, myocar- dial viability is defined as the amount of myocardium that, despite contractile dysfunction, maintains metabolic and electrical function, having the potential for functional enhancement upon revascular- ization. Recent advances have improved methods to detect myocardial viability. The current paper summarizes the pathophysiological basis of the current methods used to detect myocardial viability in light of the advancements in the development of new radiotracers for cardiac imaging

Quantification of Coronary Artery Atherosclerotic Burden and Muscle Mass: Exploratory Comparison of Two Freely Available Software Programs

Abstract: Coronary artery calcification and sarcopenia may have a relevant prognostic impact in oncological and non‐oncological patients. The use of freeware software is promising for quantitative evaluation of these parameters after whole‐body positron emission tomography (PET)/computed tomography (CT) and might be useful for one‐stop shop risk stratification without additional radiation ionizing burden and further charges to health care costs. In this study, we compared two semiautomatic freeware software tools (Horos Medical Image software and LIFEx) for the assessment of coronary artery calcium (CAC) score and muscle mass in 40 patients undergoing whole‐body PET/CT. The muscle areas obtained by the two software programs were comparable, showing high correlation with Lin’s concordance coefficient (0.9997; 95% confidence intervals: 0.9995–0.9999) and very good agreement with Bland–Altman analysis (mean difference = 0.41 cm2, lower limit = −1.06 cm2, upper limit = 1.89) was also found. For CAC score, Lin’s concordance correlation coefficient was 0.9976 (95% confidence intervals: 0.9965–0.9984) and in a Bland–Altman analysis an increasing mean difference from 8 to 78 by the mean values (intercept = −0.050; slope = 0.054; p < 0.001) was observed, with a slight overestimation of Horos CAC score as compared to LIFEx, likely due to a different calculation method of the CAC score, with the ROI being equal for the two software programs. Our results demonstrated that off‐line analysis performed with freeware software may allow a comprehensive evaluation of the oncological patient, making available the evaluation of parameters, such as muscle mass and calcium score, that may be relevant for the staging and prognostic stratification of these patients, beside standard data obtained by PET/CT imaging. For this purpose, the Horos and LIFEx software seem to be interchangeable

Controlled Release of H2S from Biomimetic Silk Fibroin-PLGA Multilayer Electrospun Scaffolds

The possibility of incorporating H2S slow-release donors inside biomimetic scaffolds can pave the way to new approaches in the field of tissue regeneration and anti-inflammatory treatment. In the present work, GYY4137, an easy-to-handle commercially available Lawesson's reagent derivative, has been successfully incorporated inside biomimetic silk fibroin-based electrospun scaffolds. Due to the instability of GYY4137 in the solvent needed to prepare silk fibroin solutions (formic acid), the electrospinning of the donor together with the silk fibroin turned out to be impossible. Therefore, a multilayer structure was realized, consisting of a PLGA mat containing GYY4137 sandwiched between two silk fibroin nanofibrous layers. Before their use in the multilayer scaffold, the silk fibroin mats were treated in ethanol to induce crystalline phase formation, which conferred water resistance and biomimetic properties. The morphological, thermal, and chemical properties of the obtained scaffolds were thoroughly characterized by SEM, TGA, DSC, FTIR, and WAXD. Multilayer devices showing two different concentrations of the H2S donor, i.e., 2 and 5% w/w with respect to the weight of PLGA, were analyzed to study their H2S release and biological properties, and the results were compared with those of the sample not containing GYY4137. The H2S release analysis was carried out according to an "ad-hoc" designed procedure based on a validated high-performance liquid chromatography method. The proposed analytical approach demonstrated the slow-release kinetics of H2S from the multilayer scaffolds and its tunability by acting on the donor's concentration inside the PLGA nanofibers. Finally, the devices were tested in biological assays using bone marrow derived mesenchymal stromal cells showing the capacity to support cell spreading throughout the scaffold and prevent cytotoxicity effects in serum starvation conditions. The resulting devices can be exploited for applications in the tissue engineering field since they combine the advantages of controlled H2S release kinetics and the biomimetic properties of silk fibroin nanofibers

Comparing the prognostic value of stress myocardial perfusion imaging by conventional and cadmium-zinc telluride single-photon emission computed tomography through a machine learning approach

We compared the prognostic value of myocardial perfusion imaging (MPI) by conventional- (C-) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride- (CZT-) SPECT in a cohort of patients with suspected or known coronary artery disease (CAD) using machine learning (ML) algorithms. A total of 453 consecutive patients underwent stress MPI by both C-SPECT and CZT-SPECT. The outcome was a composite end point of all-cause death, cardiac death, nonfatal myocardial infarction, or coronary revascularization procedures whichever occurred first. ML analysis performed through the implementation of random forest (RF) and k-nearest neighbors (KNN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for KNN) was greater than that of C-SPECT (88% for RF and 53% for KNN). A preliminary univariate analysis was performed through Mann-Whitney tests separately on the features of each camera in order to understand which ones could distinguish patients who will experience an adverse event from those who will not. Then, a machine learning analysis was performed by using Matlab (v. 2019b). Tree, KNN, support vector machine (SVM), Naïve Bayes, and RF were implemented twice: first, the analysis was performed on the as-is dataset; then, since the dataset was imbalanced (patients experiencing an adverse event were lower than the others), the analysis was performed again after balancing the classes through the Synthetic Minority Oversampling Technique. According to KNN and SVM with and without balancing the classes, the accuracy (p value = 0.02 and p value = 0.01) and recall (p value = 0.001 and p value = 0.03) of the CZT-SPECT were greater than those obtained by C-SPECT in a statistically significant way. ML approach showed that although the prognostic value of stress MPI by C-SPECT and CZT-SPECT is comparable, CZT-SPECT seems to have higher accuracy and recall

The role of myocardial scintigraphy in the assessment of coronary artery disease

Single photon emission computed tomography (SPECT) for the assessment of myocardial perfusion was introduced in the early 1970s, following pioneer studies of Gould et al. It has rapidly become one of the most used noninvasive technique for the assessment of myocardial ischemia. Thanks to the current technetium based tracers that allow electrocardiogram gated synchronization, it is possible to assess the regional ventricular systolic function and the evaluation of myocardial perfusion as well. In the last twenty years, beyond its diagnostic role, myocardial SPECT has become also a prognostic technique. Indeed, it has acquired a role for the short-term prediction of major coronary events in a large cohort with known or suspected coronary artery disease (CAD). The aim of this review is to give an update of the correct use and interpretation of myocardial SPECT in patients with known or suspected CAD and without left ventricular dysfunction

The effect of iterative model reconstruction on coronary artery calcium quantification

Coronary artery calcium (CAC) scoring with computed tomography (CT) is an established tool for quantifying calcified atherosclerotic plaque burden. Despite the widespread use of novel image reconstruction techniques in CT, the effect of iterative model reconstruction on CAC score remains unclear. We sought to assess the impact of iterative model based reconstruction (IMR) on coronary artery calcium quantification as compared to the standard filtered back projection (FBP) algorithm and hybrid iterative reconstruction (HIR). In addition, we aimed to simulate the impact of iterative reconstruction techniques on calcium scoring based risk stratification of a larger asymptomatic population. We studied 63 individuals who underwent CAC scoring. Images were reconstructed with FBP, HIR and IMR and CAC scores were measured. We estimated the cardiovascular risk reclassification rate of IMR versus HIR and FBP in a larger asymptomatic population (n = 504). The median CAC scores were 147.7 (IQR 9.6-582.9), 107.0 (IQR 5.9-526.6) and 115.1 (IQR 9.3-508.3) for FBP, HIR and IMR, respectively. The HIR and IMR resulted in lower CAC scores as compared to FBP (both p < 0.001), however there was no difference between HIR and IMR (p = 0.855). The CAC score decreased by 7.2 % in HIR and 7.3 % in IMR as compared to FBP, resulting in a risk reclassification rate of 2.4 % for both HIR and IMR. The utilization of IMR for CAC scoring reduces the measured calcium quantity. However, the CAC score based risk stratification demonstrated modest reclassification in IMR and HIR versus FBP