Abstract Background Benign thymic cysts are a rare clinical entity, representing approximately 3% of all mediastinal masses and can be congenital or acquired. We report a case of a 58–year–old female with a giant benign thymic cyst which entered in differential diagnosis with pericardial cyst and pericardial effusion. Case presentation: A 58–year–old female was brought to our hospital due to new onset dyspnoea and fatigue. She had a history of a mediastinal liquid mass incidentally discovered 9 years before which was interpreted at that time as a loculated pericardial effusion (Fig. 1). An echocardiogram was performed and it revealed increased size of the known lesion without any signs of hemodynamic compromise (Fig. 2). A magnetic resonance showed a voluminous liquid lesion that originated from the anterior mediastinum, extending caudally to the diaphragm with maximum dimension on the right hemithorax of 16 x 12 x 9 cm and on the left hemithorax of 10 x 5 x 13 cm (antero–posteriorly, transversely and cranio–caudally respectively) (Fig. 3). It was initially interpreted as a pericardial cyst. All the findings were then collegially reviewed and it was suspected of being a giant thymic cyst especially due to its rapid growth and spatial evolution over time. The cyst was surgically removed using a thoracoscopic approach. Histological examination confirmed the thymic origin of the cyst and excluded malignancy. At three month follow up, the patient presented no symptoms, and the echocardiogram was normal. Discussion The echocardiographic features of mediastinal cysts are not specific for the type of cystic lesion, so the origin and location of the cyst can be used for differential diagnosis. Computed tomography has the best spatial resolution, while the magnetic resonance has better capacity to differentiate the content of the cyst, especially when it is not a homogeneous liquid lesion. In our case, the growth over nine years was a crucial hint to suspect the thymic origin of the lesion. On the other hand, the sole evaluation of the last imaging exam would have made the diagnosis more challenging because of its huge dimensions, which made the exact site of origin almost impossible to identify. Conclusion Our case is a rare example of a giant thymic cyst which was extremely difficult to differentiate from other paracardiac cystic lesions and required integrated imaging and discussion by a team of experts of different specialties to make the correct diagnosis.

BACKGROUND The ventricular ectopic QRS interval (VEQSI) has been shown to identify structural heart disease and predict mortality. In arrhythmogenic right ventricular cardiomyopathy (ARVC), early diagnosis is difficult using current methods, and life-threatening arrhythmias are common and difficult to predict.OBJECTIVE The purpose of this study was to assess the utility of ventricular ectopic indices including VEQSI in ARVC diagnosis.METHODS We studied 70 patients with ARVC [30 with definite disease (age 47 +/- 12 years; 60% male), 40 with incomplete disease expression (age 44 +/- 18 years; 44% male)], 116 healthy controls (age 40 +/- 15 years; 56% male), and 26 patients with normal heart right ventricular outflow tract (RVOT) ectopy (age 46 17 years; 27% male). The duration of the broadest ventricular ectopic beat during 12-lead Hotter monitoring was recorded as VEQSI max.RESULTS VEQSI max was associated with age and gender, but not with conducted QRS duration. Adjusted VEQSI max was greater in ARVC patients than in control groups. In healthy males (44.5 years), estimated VEQSI max was 163 ms (95% confidence interval [CI] 159-167 ms); in definite ARVC 212 ms (95% CI 206-217 ms); in incompletely expressed ARVC 204 ms (95% CI 199-210 ms); and in normal heart RVOT ectopy 171 ms (95% CI 165-178 ms). VEQSI max >180 ms had 98% sensitivity and specificity for diagnosis of ARVC (area under the curve 0.99, 95% CI 0.980-0.998). In our incompletely expressed ARVC patients, VEQSI max >180 ms identified 88% as affected.CONCLUSION VEQSI max distinguishes ARVC patients, including those with incomplete disease expression, from healthy controls and patients with normal heart RVOT ectopy.

BACKGROUND:Primary cardiac angiosarcoma is extremely aggressive; however, it is often misdiagnosed because of its rarity. For locally advanced tumors, doxorubicin-based chemotherapy regimens are the standard of treatment, even if the gain in term of progression-free survival is limited and is no longer than 5 months.CASE PRESENTATION:We report the case of a Caucasian 23-year-old man with locally advanced cardiac angiosarcoma who underwent radical surgical resection after a prolonged response to weekly docetaxel and complementary radiotherapy.CONCLUSION:Combined treatment with weekly docetaxel and radiotherapy may be a valid alternative for the treatment of locally advanced cardiac angiosarcoma; the combination can lead to radical surgical resections, avoiding the cumulative cardiotoxicity of antracycline-based regimens.

Randomized trials showed that mTOR inhibitors prevent early development of cardiac allograft vasculopathy (CAV). However, the action of these drugs on CAV late after transplant is controversial, and their effectiveness for CAV prevention in clinical practice is poorly explored. In this observational study we included 143 consecutive heart transplant recipients who underwent serial intravascular ultrasound (IVUS), receiving either everolimus or mycophenolate as adjunctive therapy to cyclosporine. Ninety-one recipients comprised the early cohort, receiving IVUS at weeks 3–6 and year 1 after transplant, and 52 the late cohort, receiving IVUS at years 1 and 5 after transplant. Everolimus independently reduced the odds for early CAV (0.14 [0.01–0.77]; p = 0.02) but it did not appear to influence late CAV progression. High-dose statins were found to be associated with reduced CAV progression both early and late after transplant (p ≤ 0.05). Metabolic abnormalities, such as high triglycerides, were associated with late, but not with early CAV progression. By highlighting a differential effect of everolimus and metabolic abnormalities on early and late changes of graft coronary morphology, this observational study supports the hypothesis that everolimus may be effective for CAV prevention but not for CAV treatment, and that risk factors intervene in a time-dependent sequence during CAV development.

BACKGROUND: Cyclosporine nephrotoxicity negatively impacts long-term outcome after heart transplantation (HT). We previously reported 1-year results from a randomized study showing that cyclosporine-lowering strategies based on everolimus or mycophenolate mofetil (MMF) are equally effective for reducing progression of renal dysfunction. It is unknown whether this efficacy could be maintained over the long term.METHODS: Thirty-four recipients 1 to 4 years after HT and with 25 to 60 ml/min of creatinine clearance (CrCl) were randomized to everolimus with a very low dose (C-0: 50 to 90 ng/ml, n = 17) or MMF with low dose of cyclosporine (C-0: 100 to 150 ng/ml, n = 17). Follow-up was prolonged up to 3 years, and calculated CrCl was the main efficacy measure.RESULTS: Cyclosporine was maintained at 70% and 30% lower than baseline in the everolimus and MMF arms, respectively, throughout the 3-year study period. CrCl remained stable in the everolimus patients (+7% from baseline; p = 0.7), but improved in the MMF patients (+20% from baseline; p < 0.01), with a trend toward improved values compared with everolimus patients (46 +/- 12 vs 56 +/- 15 ml/min; p = 0.06). Subgroup analysis revealed that baseline proteinuria markedly influenced the renal function response to everolimus: whereas in patients with baseline proteinuria CrCl significantly worsened (-20%; p = 0.04), it improved in those without (+15%; p = 0.03). Safety was comparable between the two study arms.CONCLUSIONS: Cyclosporine nephrotoxicity improved after a prolonged dose reduction in patients receiving MMF. The everolimus-based strategy provided a similar benefit only to patients without baseline proteinuria. While raising caution against the universal use of everolimus for kidney protection, our long-term results support the need for customized approaches in the management of drug toxicities in maintenance HT recipients. J Heart Lung Transplant 2012;31:565-70 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.

Coronary allograft vasculopathy (CAV) is the main cause of graft failure after heart transplantation (HT). Clinical trials showed that everolimus (EVE) prevents early CAV. However, if this property can be replicated in clinical practice and on long-term CAV progression is unexplored.

Pulmonary hypertension (PH) in heart transplant (HT) candidates is associated with increased post-transplant mortality, and may represent a contraindication to HT. Vasorectivity studies test PH reversibility, but how their results match post-HT outcome is unexplored. In addition, data guiding organ allocation in recipients with PH are lacking.

BACKGROUND: Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold.METHODS: This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters.RESULTS: Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02).CONCLUSIONS: Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries. J Heart Lung Transplant 2011;30:1305-11 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.

Cyclosporine (CsA) nephrotoxicity negatively impacts long-term management of heart transplant (HT) recipients. Thus, we designed the SHIRAKISS randomized study to compare two CNI lowering strategies on the progression of renal dysfunction (NCT00420537). Herein we report the 24 months outcome of the patients initially randomized in the study.

Cancer is a leading cause of death in adult heart transplant (HT) recipients. Whereas large registries identified several risk factors involved in the development of post-transplant malignancies, data about factors influencing the outcome after malignancy onset are lacking.

Coronary allograft vasculopathy (CAV) is the main cause of graft failure after heart transplantation (HT). Clinical trials showed that everolimus (EVE) prevents early CAV. However, its effect in a ...

Antisense-mediated exon skipping has proven to be efficacious for subsets of Duchenne muscular dystrophy mutations. This approach is based on targeting specific splicing motifs that interfere with the spliceosome assembly by steric hindrance. Proper exon recognition by the splicing machinery is thought to depend on exonic splicing enhancer sequences, often characterized by purine-rich stretches, representing potential targets for antisense-mediated exon skipping. We identified and functionally characterized two purine-rich regions located within dystrophin intron 11 and involved in splicing regulation of a pseudo-exon. A functional role for these sequences was suggested by a pure intronic DMD deletion causing X-linked dilated cardiomyopathy through the prevalent cardiac incorporation of the aberrant pseudo-exon, marked as Alu-exon, into the dystrophin transcript. The first splicing sequence is contained within the pseudo-exon, whereas the second is localized within its 3' intron. We demonstrated that the two sequences actually behave as splicing enhancers in cell-free splicing assays because their deletion strongly interferes with the pseudo-exon inclusion. Cell-free results were then confirmed in myogenic cells derived from the patient with X-linked dilated cardiomyopathy, by targeting the identified motifs with antisense molecules and obtaining a reduction in dystrophin pseudo-exon recognition. The splicing motifs identified could represent target sequences for a personalized molecular therapy in this particular DMD mutation. Our results demonstrated for the first time the role of intronic splicing sequences in antisense modulation with implications in exon skipping-mediated therapeutic approaches.

Statin therapy reduces cardiac allograft vasculopathy (CAV) development and cardiovascular events in heart transplant (HT) recipients. However, the optimal lipid target to be aimed at in these patients is unknown. In addition, safety concerns regarding the interaction between statins and immunosuppressive drugs may limit the use of high statins doses, potentially reducing the efficacy of this therapy. This randomized study aims to assess safety and efficacy of a fixed high dose of fluvastatin (80mg) vs. a low-density-lipoproteins (LDL)-driven approach based on low dose (20mg) adjustments targeting 100mg/dl.