An Unusual Case of Ascending Aorta Dissection 4 Years after Perceval Sutureless Bioprosthesis Implantation: Easier Access to Diagnosis through the Right Parasternal Longitudinal Echocardiographic Window.

Sutureless bioprostheses are more frequently used for the surgical treatment of elderly patients with high burden of comorbidity, who are candidates to aortic valve replacement (AVR). Among the sutureless bioprostheses, the Perceval valve has shown a good midterm durability, with very few reports of valve deterioration and low risk of complications. Herein, we present an unusual case of ascending aorta dissection which occurred 4 years after AVR with a Perceval sutureless pericardial bioprosthesis, likely related to the peculiar prosthetic design. A high right parasternal longitudinal view of the aorta in the right lateral decubitus allowed to suspect the acute aortic syndrome, thus accelerating the subsequent diagnostic and therapeutic iter.

Comparison of clinical scoring to predict mortality risk in mild-to-moderate idiopathic pulmonary fibrosis.

BACKGROUND: During the last decade, a number of clinical scores, such as Gender-Age-Physiology (GAP) Index, TORVAN Score and Charlson Comorbidity Index (CCI), have been separately used to measure comorbidity burden in idiopathic pulmonary fibrosis (IPF). However, no previous study compared the prognostic value of these scores to assess mortality risk stratification in IPF patients with mild-to-moderate disease. METHODS: All consecutive patients with mild-to-moderate IPF who underwent high-resolution computed tomography, spirometry, transthoracic echocardiography and carotid ultrasonography at our Institution, between January 2016 and December 2018, were retrospectively analyzed. GAP Index, TORVAN Score and CCI were calculated in all patients. Primary endpoint was all-cause mortality, whereas secondary endpoint was the composite of all-cause mortality and rehospitalizations for all-causes, over medium-term follow-up. RESULTS: Seventy IPF patients (70.2±7.4 yrs, 74.3% males) were examined. At baseline, GAP Index, TORVAN Score and CCI were 3.4±1.1, 14.7±4.1 and 5.3±2.4, respectively. A strong correlation between coronary artery calcification (CAC) and common carotid artery (CCA) intima-media thickness (IMT) (r=0.88), CCI and CAC (r=0.80), CCI and CCA-IMT (r=0.81), was demonstrated in the study group. Follow-up period was 3.5±1.2 years. During follow-up, 19 patients died and 32 rehospitalizations were detected. CCI (HR 2.39, 95% CI: 1.31-4.35) and heart rate (HR 1.10, 95% CI: 1.04-1.17) were independently associated with primary endpoint. CCI (HR 1.54, 95% CI: 1.15-2.06) predicted secondary endpoint, also. A CCI ≥6 was the optimal cut-off for predicting both outcomes. CONCLUSIONS: Due to the increased atherosclerotic and comorbidity burden, IPF patients with CCI ≥6 at an early-stage disease have poor outcome over medium-term follow-up.

The influence of pectus excavatum on cardiac kinetics and function in otherwise healthy individuals: A systematic review.

BACKGROUND: A number of anterior chest wall deformities, most notably pectus excavatum (PE), may have a detrimental effect on cardiac motion and function. Interpretation of transthoracic echocardiography (TTE) and speckle-tracking echocardiography (STE) results may be hampered by the possible influence of PE on cardiac kinetics. METHODS: A comprehensive search of all articles assessing cardiac function in PE individuals was carried out. Inclusion criteria were: 1) individuals aged >10 years; 2) studies providing objective assessment of chest deformity (Haller index). Studies that measured myocardial strain parameters in PE patients were also included. RESULTS: The search (EMBASE and Medline) yielded a total of 392 studies, 36 (9.2%) of which removed as duplicates; a further 339 did not meet inclusion criteria. The full-texts of 17 studies were then analyzed. All studies concordantly reported impaired right ventricular volumes and function. With respect to left ventricle (LV), TTE studies uniformly demonstrated a significant impairment in conventional echoDoppler indices in PE individuals, whereas STE studies provided conflicting results. Importantly, LV functional alterations promptly reverted upon surgical correction of chest defect. In subjects with PE of mild-to-moderate severity, we observed that degree of anterior chest wall deformity, as noninvasively assessed by modified Haller index (MHI), was strongly associated with myocardial strain magnitude, in heterogenous cohorts of otherwise healthy PE individuals. CONCLUSIONS: Clinicians should be aware that in PE individuals, TTE and STE results may not always be indicative of intrinsic myocardial dysfunction, but may be, at least in part, influenced by artifactual and/or external chest shape determinants.

Prognostic role of CHA2DS2-VASc score for mortality risk assessment in non-advanced idiopathic pulmonary fibrosis: a preliminary observation.

During the last decade, the CHA2DS2-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA2DS2-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA2DS2-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA2DS2-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA2DS2-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA2DS2-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA2DS2-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.

Coronary artery calcium score is a prognostic factor for mortality in idiopathic pulmonary fibrosis.

BACKGROUND: Cardiovascular diseases are frequent in idiopathic pulmonary fibrosis (IPF) and impact on survival. We investigated the association of coronary artery calcium (CAC) score at IPF diagnosis and during mid-term follow-up, with adverse cardiovascular events and all-cause mortality. METHODS: Consecutive patients with IPF were retrospectively analyzed. Demographic data, smoking history, comorbidities and pulmonary function tests (PFTs) were recorded. All patients had at least two chest high resolution computed tomography (HRCT) performed 2 years apart. The total CAC score and visual fibrotic score were calculated and all clinically significant cardiovascular events and deaths were reported. RESULTS: The population consisted of 79 patients (57 male, mean age 74.4 ± 7.6 years); 67% of patients had a history of smoking, 48% of hypertension, 37% of dyslipidemia and 22.8% of diabetes. The visual score was 21.28 ± 7.99% at T0 and 26.54 ± 9.34% at T1, respectively (T1-T0 5.26 ± 6.13%, p< 0.001). CAC score at T0 and at T1 was 537.93 ± 839.94 and 759.98 ± 1027.6, respectively (T1-T0 224.66 ± 406.87, p< 0.001). Mean follow-up time was 2.47±1.1 years. On multivariate analysis, male sex (HR 3.58, 95% CI 1.14-11.2) and CAC score at T0 (HR 1.04, 95% CI 1.01-1.07) correlated with mortality and cardiovascular events. CAC score at T0 ≥405 showed 82% sensitivity and 100% specificity for predicting mortality and adverse cardiovascular events. CONCLUSIONS: IPF patients with a CAC score at diagnosis ≥405 have a poor prognosis over a midterm follow-up. A higher CAC score is associated with mortality and cardiovascular events.

Modified Haller index validation and correlation with left ventricular strain in a cohort of subjects with obesity and without overt heart disease.

The present study was primarily designed to validate the modified Haller index (MHI), the ratio of chest transverse diameter over the distance between sternum and spine, measured by a ruler and transthoracic echocardiography (TTE), respectively, in a cohort of subjects with obesity, but otherwise healthy, by comparing the results to the conventional Haller index (HI) measured on chest X-ray (CXR). 100 consecutive subjects with body mass index (BMI) ≥ 30 kg/m2 and 60 matched controls with BMI < 30 kg/m2, who underwent a two-plane CXR for any clinical indication, were prospectively examined over a 6-month period. All participants underwent MHI assessment, TTE and speckle-tracking analysis of left ventricular (LV) global longitudinal strain (GLS). Bland-Altman analysis was used to compare the radiological and nonradiological techniques. Second, independent predictors of subclinical myocardial dysfunction, defined as LV-GLS less negative than - 20%, were evaluated. Bland-Altman analysis revealed a bias of - 4.91 cm for latero-lateral thoracic diameter, of - 0.74 cm for antero-posterior (A-P) thoracic diameter and of - 0.22 for HI assessment, suggesting a systematic overestimation of the nonradiological methodology in comparison to that radiological. Despite normal LV systolic function on TTE, LV-GLS resulted impaired in 76% of subjects with obesity. Waist circumference (OR 1.13, 95%CI 1.04-1.22) and nonradiological A-P thoracic diameter (OR 0.51, 95%CI 0.28-0.93) were the main independent predictors of subclinical myocardial dysfunction in subjects with obesity. The impairment in LV myocardial strain detected in subjects with obesity appears to be primarily related to extrinsic abdominal and thoracic compressive phenomena, rather than intrinsic myocardial dysfunction.

An unusual case of painless type A aortic dissection.

The pathogenesis of acute aortic dissection (AAD) is not fully elucidated yet, but it was recently shown that inflammation contributes to the occurrence and development of both Stanford type A and type B AAD. We describe a rare case of a painless type A aortic dissection that occurred in an 85-year-old male, with moderate calcified aortic stenosis and a moderately dilated ascending aorta in 6-month clinical and echocardiographic follow-up. A chronic calculous cholecystitis with neutrophilic leukocytosis and severely increased C reactive protein was diagnosed in the last 3 months. In this patient, a chronic systemic inflammatory state might have contributed to generate the intimal entry tear in the aortic root. In particular, a neutrophil mobilization might have played a causative role in aortic rupture.

A New modified anthropometric haller index obtained without radiological exposure.

To validate a new modified method for measuring the anthropometric Haller index (HI), obtained without radiological exposure. This new method was based on the use of a rigid ruler and of a 2.5 MHz ultrasound transducer for the assessment of latero-lateral and antero-posterior chest diameters, respectively. We enrolled 100 consecutive patients (mean age 67.9 ± 14.5 years, 55% males), who underwent a two-plane CXR, for any clinical indication, over a four-month period. In all patients, the same radiologist calculated the conventional radiological HI (mean value 1.93 ± 0.35) and the same cardiologist used the above described new technique to measure the modified HI (mean value 1.99 ± 0.26). The Bland-Altman analysis showed tight limits of agreement (+ 0.37; - 0.51) between the two measurement methods, with a mild systematic overestimation of the new method as compared to the standard radiological HI. The Pearson's correlation analysis highlighted a strong correlation between the two methods (r = 0.81, p < 0.0001), while the Student's t test demonstrated a not statistically difference between the means (p = 0.12). The modified HI might allow a quick description of the chest conformation without radiological exposure and a more immediate comprehension of its possible influence on the cardiac kinetics and function, as assessed by echocardiography or other imaging modalities.

HTLV-1 Tax protein cooperates with Ras in protecting cells from apoptosis.

Tax protein of the human T-cell leukemia virus type 1 (HTLV-1) plays a critical role in HTLV-I-correlated diseases through its ability to deregulate the expression of a vast array of cellular genes. We have previously shown that Tax counteracts apoptosis induced by stimuli triggering mitochondria apoptotic pathway, most likely by activating CREB-mediated transcription and affecting the phosphorylation levels of CREB at Ser-133. Here, we report data that indicate the oncoprotein Ras as a possible mediator of Tax-induced apoptosis protection and suggest a possible role of Tax in Ras activation. In addition, using inhibitors of down stream effectors of Ras, we found that ERK signaling is the most relevant for Tax-mediated apoptosis protection. As a whole, our findings provide intriguing evidence of a possible link between Ras signaling and Tax capability to counteract apoptosis and to enhance P-CREB levels, and implicates a potential role for Ras in HTLV-1-induced diseases.

Antiapoptotic effect of human T-cell leukemia virus type 1 tax protein correlates with its creb transcriptional activity.

Defects in the regulation of programmed cell death play a fundamental role in the development of neoplasia and neurological disorders, both of which are linked to the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection. We previously showed that the HTLV-1 Tax protein protects from apoptosis induced by serum starvation by preventing cytochrome c release and Bax relocation to mitochondria, two early events in the mitochondrial apoptotic pathway. As a natural extension of these findings, and to better define the action of Tax, in the present study, we investigated the outcome of Tax and two mutants which are inactive in CREB/ATF (M47) or NF-kappaB (M22) pathways, in the control of apoptosis induced by the proapoptotic Bax protein. We found that activation of CREB, rather than NF-kappaB, is a key phenomenon in preventing apoptosis. Furthermore, the importance of CREB activation is strengthened by experiments with CREB mutants, treatment with forskolin, and in situ analysis of P-CREB status in cells transfected with Tax or its nonprotecting M47 mutant. Considered together, these results underscore a primary role of CREB in preventing apoptosis triggered by Bax, and suggest that Tax might act by affecting the phosphorylation state of CREB.

Antioxidant defences in cybrids harboring mtDNA mutations associated with Leber's hereditary optic neuropathy.

Oxidative stress and imbalance between free radical generation and detoxification may play a pivotal role in the pathogenesis of Leber's hereditary optic neuropathy (LHON). Mitochondria, carrying the homoplasmic 11778/ND4, 3460/ND1 and 14484/ND6 mtDNA point mutations associated with LHON, were used to generate osteosarcoma-derived cybrids. Enhanced mitochondrial production of reactive oxygen species has recently been demonstrated in these cybrids [Beretta S, Mattavelli L, Sala G, Tremolizzo L, Schapira AHV, Martinuzzi A, Carelli V & Ferrarese C (2004) Brain 127, 2183-2192]. The aim of this study was to characterize the antioxidant defences of these LHON-affected cells. The activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutases (SOD) and catalase, and the amounts of glutathione (GSH) and oxidized glutathione (GSSG) were measured in cybrids cultured both in glucose-rich medium and galactose-rich medium. The latter is known to cause oxidative stress and to trigger apoptotic death in these cells. In spite of reduced SOD activities in all LHON cybrids, and of low GPx and GR activities in cells with the most severe 3460/ND1 and 11778/ND4 mutations, GSH and GSSG content were not significantly modified in LHON cybrids cultured in glucose medium. In contrast, in galactose, GSSG concentrations increased significantly in all cells, indicating severe oxidative stress, whereas GR and MnSOD activities further decreased in all LHON cybrids. These data suggest that, in cells carrying LHON mutations, there is a decrease in antioxidant defences, which is especially evident in cells with mutations associated with the most severe clinical phenotype. This is magnified by stressful conditions such as exposure to galactose.

Relevance of CREB phosphorylation in the anti-apoptotic function of human T-lymphotropic virus type 1 tax protein in serum-deprived murine fibroblasts.

The human T-cell leukemia virus type 1 (HTLV-1) Tax transactivator is thought to play a primary role in the development of HTLV-1-mediated diseases. Using a murine fibroblast model, we previously showed that Tax reduces apoptosis induced by serum starvation by preventing cytochrome c release from the mitochondria. As Tax can enhance the transcriptional activity of nuclear factor NF-kB and cAMP-responsive element binding protein/activating transcription factor-1 (CREB/ATF-1), we investigated the relevance of these routes in the anti-apoptotic effects of Tax. Results showed that a Tax mutant retaining CREB/ATF-1 transactivating activity protects murine fibroblasts from serum-depletion-induced apoptosis, while two CREB/ATF-1-defective mutants did not. Treatment with forskolin, an activator of CREB, significantly attenuated cytochrome c release and Bax translocation in response of serum deprivation. In analogy to forskolin treatment, Tax expression results in sustained phosphorylation of CREB at Ser(133) during serum starvation. Considered together, these results underscore a primary role of CREB transcriptional activation in preventing apoptosis triggered by growth factor withdrawal, and suggest that Tax might in part function by affecting the phosphorylation state of CREB.

[Imaging of living donor liver transplantation].

PURPOSE: This paper presents our experience in the evaluation of 23 potential living liver donors examined from January 2001 to December 2002. MATERIALS AND METHODS: Between January 2001 and December 2002, a total of 23 potential living liver donors were evaluated (20 men, 3 women; mean age 30 years) with MSCT and MR. Vascular reconstructions (MIP and Thin MIP) and volumetric evaluation of liver "in toto" and of the right hepatic lobe to be harvested were obtained with CT. MR was performed with in- and out-of-phase GE acquisitions in order to detect liver steatosis and with SSFSE T2 weighted thick-slab (50 mm) coronal acquisitions to obtain MR cholangiography. MR cholangiography was also obtained with post-contrast (Gd-BOPTA 90 min) 3D GE thin (1.5 mm) coronal sequences. Ten potential living liver donors also underwent angiography. RESULTS: The radiological examinations demonstrated abnormalities of the portal vein bifurcation in 7/23 potential living liver donors, variants of the arterial anatomy in 5/23 and abnormalities of the biliary anatomy in 20/23. One case showed gallbladder dysmorphism. The MR examinations led to the exclusion from the transplantation of one potential living liver donor owing to the detection of liver steatosis that was subsequently confirmed by biopsy. 7/23 potential living liver donors were considered eligible for the surgical procedure and underwent preoperative colour Doppler sonography and intraoperative cholangiography. CONCLUSIONS: The diagnostic protocols used at our centre provide the clinician with important information and an exhaustive picture of the hepatic anatomy to evaluate the inclusion of potential living liver donors in the transplantation program.