Background: Pulmonary valve (PV) endocarditis is a frequent complication during follow-up in patients with repaired right ventricular outflow tract (RVOT) obstruction and poses relevant diagnostic and treatment challenges. We aimed to describe in details the possible different clinical presentations of this rare condition and to highlight the role of both transthoracic and transoesophageal echocardiography which, in experienced hands, may provide comprehensive useful information for the clinicians. Case summary: We below describe the clinical presentation and the echo findings of three cases of pulmonary valve endocarditis complicating disease course after different repair modalities of congenital right ventricular outflow tract obstruction. Discussion: The present case series outlines the diagnostic challenges of this increasingly frequent complication during follow-up of patients with congenital RVOT dysfunction after both surgical and percutaneous repair. Despite the diffusion of multimodality imaging, echocardiography with PV-dedicated views play a pivotal role in diagnosing such condition and guiding clinical management. Furthermore, this case series highlight that the suspicion of infective endocarditis should be raised whenever a sudden increase in transvalvular gradient is found during follow-up.

Background: Sacubitril/valsartan has been proved to reduce mortality in heart failure and reduced ejection fraction (EF) and is currently recommended as first-line therapy. However, effects in patients with a systemic right ventricle (sRV) have not been systematically investigated yet. Purpose: We aimed to assess safety and efficacy of sacubitril/valsartan in patients with a sRV Methods: From September 2020 to April 2021, all patients with congenitally corrected transposition of the great arteries (TGA) or TGA after Senning/Mustard repair attending our tertiary centre were prospectively enrolled. Inclusion criteria were: age ≥18 years, 3-months of optimal medical therapy including ACEi/ARB and sRV EF≤40%. Patients with univentricular physiology, systolic blood pressure (SBP) <90 mmHg, glomerular filtration rate (GFR) 5.5 mEq/L were excluded. SBP and blood samples were obtained at 1-month of treatment. Other clinical and echocardiographic variables were reassessed at 6 and 12-month follow-up and the medication was progressively up-titrated to the highest tolerated dose. Results: Fifty-one patients (38±11 years, 60% male, 34% ccTGA) were included. Up to March 2022, 48 (92%) patients were reviewed after 6 months of therapy and 35 (68%) completed the first year of follow-up. Baseline patients' characteristics are summarized in Table 1. At 1 month, treatment did not impact on the serum potassium values (4.5±0.3 vs 4.4±0.3 mEq/L, p=0.9) and GFR (112±33 vs 112±31 ml/min, p=0.3), while SBP dropped significantly (119±13 vs 108±18 mmHg, p=0.003). Two patients ceased the treatment due to symptomatic hypotension during the first month. One patient developed a nephrotic syndrome at 4 months of follow-up, which was likely unrelated to the treatment. No other major adverse events were reported. One patient was lost to follow-up after 3 months. Despite no significant change in the NYHA class (p=0.9), the 6-minute walking distance increased significantly at 6-month (Table 2). Nt pro BNP values were significantly decreased at 6-month, and returned to baseline at 12-month. Improved sRV systolic function was demonstrated at 6 and 12-month by significant increase in fractional area change, RV global longitudinal strain and sRV EF measured with 3D echocardiography. Conclusions: Our mid-term results showed that sacubitril/valsartan is well tolerated in patients with a sRV and leads to signficant improvement of sRV systolic function, supporting its use in this complex population. Funding Acknowledgement: Type of funding sources: None.

Background: Heart failure (HF) is a major cause of morbidity in adults with congenital heart disease (ACHD), who may also have limited access to transplant. Intermittent levosimendan has shown benefit in advanced HF due to acquired heart disease, but currently there are no data in ACHD. Methods: We conducted a retrospective analysis of ACHD patients aged >18 years with advanced HF who received ≥3 intermittent levosimendan infusions between March 2020 and January 2026 at a tertiary ACHD centre. Clinical outcomes during follow-up were compared with those in the year preceding treatment. Primary endpoints included safety and HF-related adverse events, particularly HF hospitalizations. Secondary endpoints included changes in New York Heart Association (NYHA) class, NT-proBNP levels, and ventricular systolic function assessed by echocardiography. Results: Twelve patients (median age 44.6 years, 25% female) were included, with heterogeneous congenital diagnoses and advanced HF. Five patients had a systemic right ventricle (sRV) and one had a single ventricle with previous Fontan palliation. During a median follow-up of 1.3 years, intermittent levosimendan was generally well tolerated, with no treatment-limiting adverse events. HF hospitalization incidence significantly decreased from 0.83 events/person-year before treatment to 0.20 events/person-year during follow-up (p=0.03). NYHA functional class improved significantly (p=0.005). While no significant changes were observed in NT-proBNP or left ventricular ejection fraction, patients with an sRV demonstrated a significant improvement in right ventricular fractional area change (27±7.4% to 30.6±7%, p=0.02). Two deaths occurred, consistent with the severity of underlying disease and not directly attributable to levosimendan. Conclusions: In this real-world cohort of ACHD patients with advanced HF, intermittent levosimendan administration was safe and associated with improved symptoms, reduced HF hospitalizations, and enhanced systemic right ventricular function. These findings support the potential role of intermittent levosimendan as a therapeutic option in selected ACHD patients and underscore the need for prospective, adequately powered studies to confirm efficacy and define optimal patient selection.

Background: Adults with congenital heart disease (ACHD) are a vulnerable population. Routine vaccination is the only strategy to prevent a life-threatening infection. However, concerns on the cardiac safety and efficacy of COVID-19 vaccines have been raised. Aim: To assess safety and efficacy of available COVID-19 vaccines in ACHD patients. Methods: Data on COVID-19 infection and vaccines including booster doses and any suspected or confirmed adverse events were prospectively collected for all ACHD patients attending our tertiary centre from the beginning of the vaccination campaign (March 2021). A group of 75 healthy volunteers, matched per age and sex, was included for comparison. Antispike IgG titre was routinely obtained at the ACHD clinic. Patients' attitude towards COVID-19 was explored with a questionnaire. Results: As of February 2022, 498 ACHD patients (36.7±16 years, 54% male,69% with moderate-complex defects, 48% with advanced physiological stage) were enrolled. Four hundred and sixty-one (92%) were fully vaccinated: the type of vaccine was Pfizer-BioNTech for 399 (86%) patients, Moderna for 20 (4%) and AstraZeneca for 26 (6%), 9 received a mixed vaccine regimen (2%). Forty-two (9%) had a history of previous COVID-19 infection and therefore received only one dose. Two-hundred and sixty-nine (58%) patients received a booster dose. Adverse events were mainly mild and transient. One patient complaining of chest pain following administration of mRNA-based vaccination was diagnosed with acute pericarditis, which made full remission after appropriate therapy. Two patients reported a non-specific increment of inflammatory markers. No other severe adverse events were reported. Thirty-seven (7%) refused COVID-19 vaccination being scared of potential cardiac/extra-cardiac adverse events. Among those not-vaccinated, 9 (24%) had a history of previous mild COVID-19 infection. IgG titre was measured in 243 patients at 1915 [835–5934] BAU/ml, which was significantly higher compared to controls (1196 [827–2048] BAU/ml, p=0.002). Three ACHD patients contracted COVID-19 infection after the first dose, while 65 (14%) fully vaccinated patients tested positive for COVID-19, all with mild to moderate symptoms. COVID-19 symptoms duration was significantly longer in case of infection before vaccination (10 [2.7–15] vs 3 [1.2–7], p=0.03). One Fontan patient was tested positive for COVID-19 twice, before and after COVID-19 vaccination, requiring hospitalization in both cases. Four hundred and seven patients completed the questionnaire: 128 (31%) declared to be scared of potential cardiac effects of the vaccine and that the discussion with the ACHD cardiologist was crucial to decide to undergo COVID-19 vaccination. Conclusions: Our data provide real-world evidence on COVID-19 vaccines safety and efficacy in ACHD patients. Patients' education from the ACHD team may play a key role in vaccine acceptance in this vulnerable population. Funding Acknowledgement: Type of funding sources: None.

Background and Objective: Heart failure (HF) is a major cause of morbidity in adults with congenital heart disease (ACHD), who may also have limited access to transplant. Intermittent levosimendan administration has shown benefit in advanced HF due to acquired heart disease, but currently, there are no data on ACHD. We aimed to evaluate the effects of this treatment in ACHD patients with advanced heart failure, focusing on both clinical status and objective outcome measures. Materials and Methods: We conducted a single-center retrospective analysis of ACHD patients aged >18 years with advanced HF who received ≥ three intermittent levosimendan infusions (either 12.5 mg once monthly or 6.25 mg every two weeks over a 6 h infusion) between March 2020 and January 2025 at a tertiary ACHD center. Clinical outcomes during follow-up were compared with those in the year preceding treatment. Primary endpoints included safety and HF-related adverse events, particularly HF hospitalizations. Secondary endpoints included changes in New York Heart Association (NYHA) class, nt-pro-B-natriuretic peptide (nt-proBNP) values, and ventricular systolic function assessed by echocardiography. Results: Twelve patients (median age 44.6 years, 25% female) were included, with heterogeneous congenital diagnoses and advanced HF. Five patients had a systemic right ventricle (sRV) and one had a single ventricle with previous Fontan palliation. During a median follow-up of 1.3 years, intermittent levosimendan was well-tolerated, with no treatment-limiting adverse events. Two patients (16%) required hospitalization for HF during follow-up compared with 8 (66%) in the year preceding treatment. The incidence of HF hospitalizations decreased from 0.83 to 0.20 events per person-year during follow-up (p = 0.03), although findings should be interpreted cautiously given the small sample size and retrospective design. NYHA functional class improved significantly (p = 0.005). While no significant changes were observed in NT-proBNP or left ventricular ejection fraction, patients with a systemic right ventricle (sRV) showed an increase in right ventricular fractional area change (27 ± 7.4% to 30.6 ± 7%, p = 0.02); however, this observation should be regarded as exploratory given the limited sample size. Two deaths occurred, consistent with the severity of the underlying disease and not directly attributable to levosimendan and the Fontan patient received a successful heart and liver transplant. Conclusions: In a small, real-world cohort of ACHD and advanced HF, intermittent levosimendan administration was safe and associated with improved symptoms, reduced HF hospitalizations, and signals of enhanced systemic right ventricular function. These hypothesis-generating findings may help inform future multicenter studies in ACHD patients with advanced HF, suggesting a potential role for intermittent levosimendan in selected patients, while highlighting the need for prospective, adequately powered studies to confirm its efficacy and better define optimal patient selection.