Ospedale Monaldi

Abstract Background Cardiac magnetic resonance (CMR) imaging is an important tool for diagnosis and morphological assessment of the heart in childhood HCM. Up to 20% of patients with childhood onset disease have an underlying RASopathy syndrome but to date no studies have reported the CMR findings in this population. Purpose To characterise CMR findings in RASopathy-associated HCM (RAS-HCM) investigate their role in prediction of major adverse cardiac events (MACE) in this population. Methods CMR findings from a multi-centre, retrospective, observational cohort of 47 children with RAS-HCM were compared with those of 85 children with s-HCM. Results Patients with RAS-HCM had a higher median indexed left ventricular mass (LVMi) (124g/m2 vs 105g/m2, p=0.027) but lower prevalence of left ventricular (LV) late gadolinium enhancement (LGE) (33.3% vs 55.6%, p<0.001). Patients with a RAF1 variant had a higher median maximal LV wall thickness (MLVWT; 23mm vs 12mm, p=0.029) and LVMi (160g/m2 vs 106g/m2, p=0.030), and a higher proportion of patients with hyperdynamic LV function (100% vs 58.3%, p=0.037) compared to PTPN11. Over a median follow up of 7.0 (IQR 3.5-12.0) years, 8 patients (17.0%) reached the MACE end point. On univariate regression analysis, LV end-diastolic volume (LVEDV) (HR 0.6, 95% CI 0.92-1, p=0.04), LV cardiac output (LVCO) (HR 0.43, 95% CI 0.19-0.97, p=0.04) and the presence of RVH (HR 0.09, 95% CI 0.01-0.86, p=0.04) emerged as potential predictors of MACE. Conclusions This multi-centre cohort study is, to our knowledge, the first that describes CMR features of pediatric RAS-HCM. Major findings include a lower prevalence of LV LGE compared to patients with sarcomeric HCM, with a higher LV indexed mass in patients with RAS-HCM, particularly those with RAF1 variants. These findings may have implications for the diagnosis and risk stratification of children with RAS-HCM.

Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) comprises a heterogeneous group of fibrosing lung disorders frequently complicated by progressive pulmonary fibrosis, a phenotype associated with accelerated lung function decline and increased mortality. Although antifibrotic therapies have improved clinical outcomes, significant unmet needs remain, particularly regarding treatment tolerability and integration with background immunosuppressive strategies. Preferential phosphodiesterase-4B (PDE4B) inhibition has emerged as a novel therapeutic approach targeting both inflammatory and fibrotic pathways through modulation of intracellular cyclic adenosine monophosphate signaling. This narrative review summarizes the biological rationale and emerging clinical evidence supporting nerandomilast, an oral preferential PDE4B inhibitor, in autoimmune-associated interstitial lung diseases. Preclinical data indicate that PDE4B inhibition may attenuate fibroblast activation, inflammatory signaling, and extracellular matrix deposition. Clinical trials conducted in progressive pulmonary fibrosis populations have demonstrated a reduction in lung function decline, with subgroup analyses suggesting potential benefit in autoimmune-related diseases, although evidence remains limited. The safety profile appears mainly characterized by gastrointestinal adverse events, with ongoing evaluation of neuropsychiatric safety and drug interactions in complex autoimmune populations. Overall, nerandomilast represents a promising investigational strategy bridging antifibrotic and immunomodulatory mechanisms, warranting further dedicated studies in SARD-ILD.

Spindle cell mesenchymal neoplasms comprise a heterogeneous group of tumors, with recent molecular advances uncovering novel pathogenic mechanisms. We report the case of a 22-year-old woman presenting with progressive dyspnea. A computed tomography (CT) scan revealed a solid mass located in the right cardiophrenic angle. Histological examination showed a spindle cell neoplasm composed of medium-sized, elongated cells with scant eosinophilic cytoplasm, arranged in storiform and whorled patterns. Immunohistochemical staining was negative for lineage-specific markers. Fluorescence in situ hybridization (FISH) detected an EWSR1 gene rearrangement in 15% of the neoplastic cells, and RNA sequencing demonstrated a novel EWSR1::HOXB8 fusion. This case highlights the relevance of EWSR1-driven fusions in spindle cell mesenchymal neoplasms and emphasizes the need for further exploration into their clinical and biological behavior. After 5 months of chemotherapy, the patient showed moderate clinical improvement.

Chronic obstructive pulmonary disease (COPD) is often associated with cardiovascular disease and the both conditions share common risk factors (smoke), associated pathophysiological mechanisms (pulmonary hyperinflation and vasoconstriction, systemic inflammation and sympathetic activation) and drug use (beta agonists and/or antagonists, steroids, amiodarone). Moreover, COPD is known to be linked to peripheral arterial disease (PAD), mainly represented by aneurysmal dilations. Overall, this chronic immune-inflammatory context might be related to the growth and expansion of malignant clones with specific and well-known biologic traits. Recent improvement in the knowledge of molecular basis of COPD, heart diseases and PAD have pointed out a strong, complex and fascinating relationship linking these conditions, not simply definable as comorbidities. From these premises, we here aim at discussing on the novel and emerging integrated therapeutic perspectives, in some instances exploited from immune-oncology, which strongly deserve a multidisciplinary clinical management.

To evaluate the retinal morphofunctional changes in patients with stage 2 age-related macular degeneration (AMD) following scleral iontophoresis for lutein delivery, and to assess its safety. In this prospective, non-randomized, single-arm pilot study, 30 stage 2 AMD patients (mean age 71.6 ± 10.88 years) received scleral iontophoresis with a liquid lutein formulation. Comprehensive ophthalmologic assessments-including best-corrected visual acuity (BCVA), macular pigment optical density (MPOD) via one-wavelength reflectometry, and microperimetry (mean sensitivity, mean defect, and fixation stability measured as BCEA)-were performed at baseline and at 6 months. Adverse events were monitored, and ocular surface health was assessed using the Ocular Surface Disease Index (OSDI). At 6 months, MPOD significantly increased from 0.169 ± 0.06 to 0.180 ± 0.075 density units (p = 0.0313). Mean sensitivity improved from 7.26 ± 5.13 dB to 8.18 ± 4.57 dB (p = 0.0179), and mean defect improved from -11.48 ± 4.90 dB to -10.27 ± 3.76 dB (p = 0.0207). Fixation stability, as measured by BCEA at 3 standard deviations, significantly decreased (p = 0.0107). No significant change was observed in BCVA, and OSDI scores remained stable. No adverse events were reported. Scleral iontophoresis of lutein is a safe and promising technique to enhance local MPOD and retinal sensitivity in intermediate AMD patients. Further studies with larger cohorts are warranted to confirm these preliminary findings.

The population of adult patients with congenital heart disease (ACHD) is rapidly growing thanks to advances in diagnostics and therapeutics. However, these patients now encounter new clinical and healthcare challenges. The ‘New perspectives in ACHD management’ session at the ACHD 2025 Congress highlighted the key areas of innovation aimed at improving prognosis and quality of life. The aging ACHD population places substantial demands on geriatric medicine, with significant implications for the healthcare system. Similarly, the increasing arrhythmic burden, in particular atrial fibrillation, requires specific preventive and therapeutic strategies, including ablation procedures tailored to the anatomical peculiarities of ACHD patients. Pulmonary hypertension is a major contributor to morbidity and mortality in ACHD, requiring precision medicine approaches, dedicated risk stratification, and multidisciplinary approach. A central role is played by adequate prevention of acquired cardiovascular diseases, whose incidence is higher and occur earlier than in the general population. Specific risk stratification tools and an integrated approach of lifestyle modification and innovative pharmacological therapy are necessary. Telemedicine offers new opportunities for remote monitoring, access to specialized expertise, and comprehensive support, particularly for frail patients or those living in remote areas. Lastly, emerging technologies such as 3D printing, virtual reality, computational modelling, and artificial intelligence are transforming treatment planning and enabling personalized care. A multidisciplinary and technologically advanced approach is essential for shifting the focus from merely prolonging survival to truly improving the quality of life of ACHD patients.

Abstract Background Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening form of heart failure (HF) occurring toward the end of pregnancy or in the months following delivery. Variable clinical presentations and progression have been reported worldwide. Purpose We conducted a national, multicenter, observational registry to characterize clinical, echocardiographic and circulating multi-omics features of PPCM patients in Italy, and report here results of clinical and echocardiographic evaluations. This study was founded by the European Union. Methods Women with history of PPCM or newly diagnosed cases were considered eligible. Inclusion criteria were (i) age ≥18 years; (ii) development of HF signs or symptoms in the last month of pregnancy or within 5 months of delivery, (iii) absence of an identifiable cause of HF; (iv) left ventricle ejection fraction (LVEF) ≤45 % (v) absence of recognizable heart disease before the last month of pregnancy. Data included clinical details, echocardiographic parameters, and blood samples to perform multi-omic profiling. Results Twenty-eight women with confirmed PPCM diagnosis were enrolled. The mean age at clinical onset was 33.9 ± 5.1 years. Six patients (21.4%) experienced hypertensive disorders of pregnancy and 14.3% pre-eclampsia. Overweight was observed in 25% of patients, and few of them (11%) had severe obesity. Two thirds of women presented with severe symptoms (NYHA class III/IV) within the first month after delivery, and 67% had an initial LVEF ≤35%. In fewer cases (25%) the clinical presentation consisted of an arrhythmic phenotype. A persistent severe LV dysfunction (LVEF<35%) was reported in 14% of patients, that required cardioverter-defibrillator implantation. Despite the initial severity, 50% of patients showed complete recovery of systolic function over an average follow-up of 11 ± 19 months, with no reported deaths. At transthoracic echocardiography, when categorized according to the subsequent LV systolic function, women with persisting LV dysfunction had more dilated LV (end-diastolic diameter 61.2±8.1 mm in LVEF<35% group vs 51.8±6.9 mm in 35%<EF< p="0.017), left"> Conclusions PPCM presents with heterogeneous clinical and imaging profiles. Though initial presentation is often severe, outcomes are favorable in many cases. Clinical and echocardiographic factors related to LVEF recovery are still unknown. These findings emphasize the need for increased awareness and further investigation, especially regarding underlying mechanisms and longitudinal outcomes through integrated multi-omics approaches.</EF<>

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring.

This retrospective study assessed the impact of SARS-CoV-2 infection on patients with interstitial lung disease (ILD) at two tertiary centers in Southern Italy between January 2022 and December 2023. The cohort included 282 ILD patients (mean age 69.6 years; 54.9% male), with common diagnoses such as idiopathic pulmonary fibrosis (33.3%) and connective tissue disease-associated ILD (18.7%). SARS-CoV-2 infection occurred in 130 patients (46%), mostly with mild or asymptomatic cases. Pneumonia developed in 18 cases, with 72.2% requiring hospitalization and 5 COVID-19-related deaths. Patients with pneumonia had higher rates of ILD progression (27.7%) and incidental post-infection ILD diagnoses (22.2%) than those with mild infection. Vaccination rates were high, correlating with favorable outcomes in most cases. Importantly, pneumonia cases were often associated with incomplete vaccination or complex comorbidities. Differentiating COVID-19-related lung changes from ILD progression proved challenging, highlighting the importance of specialized radiologic assessment. Excluding COVID-related deaths, mortality rates were similar regardless of infection status, suggesting a degree of resilience among ILD patients. The study concludes that with high vaccine coverage and careful follow-up, most ILD patients had stable outcomes after SARS-CoV-2 infection. However, pneumonia remains a risk factor for adverse outcomes, underscoring the need for long-term, specialized ILD care.

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO2max, higher VE/VCO2 slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman's rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22-2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00-1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable.