Cesare Quarto

Thoracic endovascular aortic repair (TEVAR) in proximal (type A) aortic dissection: Ready for a broader application?

Objective: Thoracic endovascular aortic repair (TEVAR) has demonstrated encouraging results and is gaining increasing acceptance as a treatment option for aortic aneurysms and dissections. Yet, its role in managing proximal aortic pathologies is unknown—this is important because in proximal (Stanford type A) aortic dissections, 10% to 30% are not accepted for surgery and 30% to 50% are technically amenable for TEVAR. We describe our case series of type A aortic dissections treated by using TEVAR. Methods: Between year 2009 and 2016, 12 patients with acute, subacute, or chronic type A aortic dissection with the proximal entry tear located between the coronaries and brachiocephalic artery were treated with TEVAR at 3 centers. Various stent‐graft configurations were used to seal the proximal entry tear in the ascending aorta under rapid pacing. Results: A total of 12 patients (9 male, 3 female), mean age 81 ± 7 years, EuroSCORE II 9.1 ± 4.5, underwent TEVAR for the treatment of type A aortic dissection. Procedural success was achieved in 11 of 12 patients (91.7%). There was 1 minor stroke and 1 intraprocedural death. No additional deaths were reported at 30 days. At 36 months, there were 4 further deaths (all from nonaortic causes). The mean survival of these 4 deceased was 23 months (range 15‐36 months). Follow‐up computed tomography demonstrated favorable aortic remodeling. Conclusions: TEVAR is feasible and reveals promising early results in selected patients with type A aortic dissection who are poor candidates for surgical repair. The current iteration of stent‐graft technology, however, needs to be adapted to features specific to the ascending aorta.

Expression profiles in surgically-induced carotid stenosis: a combined transcriptomic and proteomic investigation.

Vascular injury aimed at stenosis removal induces local reactions often leading to restenosis. The aim of this study was a concerted transcriptomic‐proteomics analysis of molecular variations in a model of rat carotid arteriotomy, to dissect the molecular pathways triggered by vascular surgical injury and to identify new potential anti‐restenosis targets. RNA and proteins extracted from inbred Wistar Kyoro (WKY) rat carotids harvested 4 hrs, 48 hrs and 7 days after arteriotomy were analysed by Affymetrix rat microarrays and by bidi‐mensional electrophoresis followed by liquid chromatography and tandem mass spectrometry, using as reference the RNA and the proteins extracted from uninjured rat carotids. Results were classified according to their biological function, and the most significant Kyoro Encyclopedia of Genes and Genomes (KEGG) pathways were identified. A total of 1163 mRNAs were differentially regulated in arteriotomy‐injured carotids 4 hrs, 48 hrs and 7 days after injury (P < 0.0001, fold‐change ≥2), while 48 spots exhibited significant changes after carotid arteriotomy (P < 0.05, fold‐change ≥2). Among them, 16 spots were successfully identified and resulted to correspond to a set of 19 proteins. mRNAs were mainly involved in signal transduction, oxidative stress/inflammation and remodelling, including many new potential targets for limitation of surgically induced (re)stenosis (e.g. Arginase I, Kruppel like factors). Proteome analysis confirmed and extended the microrarray data, revealing time‐dependent post‐translational modifications of Hsp27, haptoglobin and contrapsin‐like protease inhibitor 6, and the differential expression of proteins mainly involved in contractility. Transcriptomic and proteomic methods revealed functional categories with different preferences, related to the experimental sensitivity and to mechanisms of regulation. The comparative analysis revealed correlation between transcriptional and translational expression for 47% of identified proteins. Exceptions from this correlation confirm the complementarities of these approaches.

Basal lamina structural alterations in human asymmetric aneurismatic aorta

Basal lamina (BL) is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation. We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens. We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study. We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RT-PCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin alpha2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type IV is more evident in the concavity and Tenascin in the convexity.

Statins Improve Outcome in Isolated Heart Valve Operations: A Propensity Score Analysis of 3,217 Patients

BACKGROUND Whether statins can improve postoperative outcome in patients without coronary artery disease undergoing heart valve operations was assessed. METHODS Data for 3,217 patients undergoing isolated valve procedures at 2 institutions between May 2003 and May 2009 were reviewed. Clinical follow-up was completed. Two propensity-matched cohorts of 1,104 patients each were identified. Multivariable regression and Kaplan-Meyer survival analysis were performed to investigate risk factors correlated with death, stroke, myocardial infarction, and cardiac arrhythmias. RESULTS The overall 30-day mortality rate was 2.7%, and 2,096 of 2,149 hospital survivors were alive at a median follow-up of 27 months. Preoperative statin treatment was independently associated with a significant reduction in the risk of hospital death (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32 to 0.89; p=0.001), postoperative cardiac arrhythmias (OR, 0.76; 95% CI, 0.62 to 0.93; p<0.006), and stroke (OR, 0.54; 95% CI, 0.32 to 0.92; p=0.02) but was not independently associated with a reduced risk of postoperative myocardial infarction. At follow-up, Kaplan-Meyer survival analysis showed statistically significant lower rates of mortality (χ2, 4.41; hazard ratio [HR], 1.59; 95% CI, 1.13 to 2.27; p=0.03), stroke (χ2, 11.42; HR, 2.15; 95% CI, 1.37 to 3.27; p=0.0007), cardiac arrhythmias (χ2, 19.9; HR, 2.13; 95% CI, 1.81 to 2.72; p<0.0001), and major adverse cardiac and cerebrovascular events (χ2, 3.74; HR, 1.37; 95% CI, 0.99 to 1.74; p=0.05) in patients receiving statin treatment. No statistically significant difference was found between groups in myocardial infarction incidence at follow-up. CONCLUSIONS Statin therapy is associated with a lower rate of adverse cardiovascular events after isolated heart valve operations.

Metabolically Active Brown Fat Mimicking Pericardial Metastasis on PET/CT: The Discriminating Role of Cardiac Magnetic Resonance Imaging.

Metabolically active mediastinal brown adipose tissue may be mistakenly diagnosed as a malignancy on 18F-fluoro-2-deoxy-D-glucose (FDG)/positron emission tomography (PET). We report the case of a patient with locally recurrent breast carcinoma in which staging PET/CT revealed a suspicious pericardial lesion for which the patient was referred to our centre. The novelty of this case resides in the fact that by tissue characterization, cardiac magnetic resonance imaging allowed the determination that the lesion corresponded to brown fat, a reassuring finding with important impact on management, because the presence of pericardial metastasis would have disqualified this patient for curative resection of her cancer recurrence.

Injury to rat carotid arteries causes time-dependent changes in gene expression in contralateral uninjured arteries

Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. Although extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. The aim of the present study was to analyse changes occurring in contralateral uninjured rat carotid arteries in the acute phase following unilateral injury. WKY (Wistar-Kyoto) rats were subjected to unilateral carotid arteriotomy. Contralateral uninjured carotid arteries were harvested from 4 h to 7 days after injury. Carotid arteries were also harvested from sham-operated rats and uninjured rats. Carotid morphology and morphometry were examined. Affymetrix microarrays were used for differential analysis of gene expression. A subset of data was validated by real-time RT-PCR (reverse transcription-PCR) and verified at the protein level by Western blotting. A total of 1011 genes were differentially regulated in contralateral uninjured carotid arteries from 4 h to 7 days after arteriotomy (P<0.0001; fold change, >or=2) and were classified into 19 gene ontology functional categories. To a lesser extent, mRNA variations also occurred in carotid arteries of sham-operated rats. Among the changes, up-regulation of members of the RAS (renin-angiotensin system) was detected, with possible implications for vasocompensative mechanisms induced by arteriotomy. In particular, a selective increase in the 69 kDa isoform of the N-domain of ACE (angiotensin-converting enzyme), and not the classical somatic 195 kDa isoform, was observed in contralateral uninjured carotid arteries, suggesting that this 69 kDa isoenzyme could influence local AngII (angiotensin II) production. In conclusion, systemic reactions to injury occur in the vasculature, with potential clinical relevance, and suggest that caution is needed in the choice of controls during experimental design in vivo.

A single-stage hybrid approach for the management of severely stenotic bicuspid aortic valve, ascending aortic aneurysm, and coarctation of the aorta with a literature review

The combination of aortic stenosis in the context of bicuspid aortic valve, aneurysmal dilatation of the ascending aorta, and coarctation is not uncommon. This condition has conventionally been addressed either by a complex open surgical approach or by staged hybrid approach combining open surgery of the ascending aorta with subsequent endovascular stenting of the coarctation. So far, the risk of a complex open approach for the aortic valve and ascending aorta and the cumulative risk of a staged second procedure for management of the coarctation are unknown; and similarly, the risk of a complex single-staged surgical procedure as an option instead of a single-staged hybrid approach is unknown. For the first time, we present a case of a patient with bicuspid aortopathy and concomitant coarctation who was simultaneously managed with both stenting of the coarctation and subsequent surgical replacement of the aortic valve and ascending aorta in one session. This new strategy has potential to become a future standard of care with various advantages. <Learning objective: Endovascular techniques are more frequently being used in the management of coarctation of the aorta, especially when associated with other cardiac pathologies. The definitive role of these techniques is still to be defined. A review of the risks and benefits of different management strategies may be beneficial with regard to making the right choice for each patient and a hybrid technique may be superior to purely surgical management, especially in a high-risk patient.>.

Histological validation of a new CMR T1-mapping-based protocol to improve accuracy for fibrosis assessment in patients with aortic stenosis

Histological validation of a new CMR T1-mappingbased protocol to improve accuracy for fibrosis assessment in patients with aortic stenosis Vassilis Vassiliou, Katharina Wassilew, George Asimakopoulos, Anthony de Souza, Cesare Quarto, Ee Ling Heng, Claire E Raphael, Bruce S Spottiswoode, Andreas Greiser, Evangelia Nyktari, Francisco Alpendurada, David Firmin, Andrew Jabbour, John Pepper, Dudley J Pennell, Peter Gatehouse, Sanjay Prasad