Discussion

In this cohort of patients with adult CHD treated in a tertiary adult CHD centre, infective endocarditis is still associated with significant morbidity and mortality. Surgery was often necessary (40%) and the in-hospital mortality was 10.5%, associated with heart failure and a non-surgical approach.

In our study, the lesions most frequently affected by endocarditis were ventricular septal defect and bicuspid aortic valve, followed by tetralogy of Fallot and complex defects as pulmonary atresia and univentricular hearts. These results were consistent with a higher prevalence of infective endocarditis in the same defects in the total population of patients followed in our centre’s outpatient clinic.

Risk in CHD has been traditionally classified into three groups, being high-speed shunts and non-operated native aortic valve disease considered a moderate risk group, opposing to high-risk cyanotic heart disease, patients with previous infective endocarditis, valve prostheses, heart disease operated on with residual lesions, and during the 6 postoperative months. ^{Reference Di Filippo14}

Other authors had previous demonstrated the increase risk of infective endocarditis in non-repair simple lesions in left ventricular outflow tract and ventricular septal defect, although infective endocarditis prophylaxis in these conditions is no longer recommend. ^{Reference Habib, Plonska-Gosciniak and Price6,Reference Li and Somerville15–Reference Niwa, Nakazawa, Tateno, Yoshinaga and Terai17} In a nationwide NHS study, the authors also found higher incidence of infective endocarditis in those with acyanotic congenital valve anomalies than those with cyanotic CHD and a similar risk compare to other “high-risk” conditions. ^{Reference Thornhill, Jones and Prendergast18}

For an adult CHD patient with unrepaired ventricular septal defect, is estimated that the lifetime risk for infective endocarditis at age 30 years is ∼10% and by the end of life is 12%, ^{Reference Knirsch and Nadal16} while in bicuspid aortic valve more recent data estimates an infective endocarditis risk of 0.3–2% per year. ^{Reference Siu and Silversides10} Shear stress of the endothelium caused by turbulent flow can alter cell shape and cytoskeletal organisation, and increases leukocytes and bacteria adhesion to the endothelium. ^{Reference Knirsch and Nadal16} Even more, it is thought that the high velocity of the stream immediately beyond the orifice in a high-speed shunt lesion, as a ventricular septal defect, is associated with a marked drop in lateral pressure with subsequent reduction in perfusion of the intima of this segment, with increasing risk for infective endocarditis during episodes of bacteraemia. ^{Reference Dodo and Child7} This suggests these lesions carry innate risk or are present in patients with conditions that place them at particularly high risk (for instance, their lifestyle).

However, motivated by lack of robust data of the effectiveness of antibiotic prophylaxis, potential hazards of antibiotic use (anaphylaxis and antibiotic resistance) and recognition of the importance of bacteraemias from routine daily activities in causing infective endocarditis, European guidelines now limit antibiotic prophylaxis to the highest-risk patients undergoing the highest-risk procedures and emphasise the role of primary prevention. ^{Reference Habib, Plonska-Gosciniak and Price6,Reference Mulder19}

While right-side CHD and atrial septal defects are at the lowest infective endocarditis risk, the hazard of endocarditis in patients with other simple lesions considered as moderate risk and left out of the European prophylaxis recommendations could be underestimated. In fact, in our cohort and in the study of Moore et al., the highest mortality rate was seen in simple lesions, which can be related, in part, to a higher delay in diagnosis. ^{Reference Moore, Cao, Kotchetkova and Celermajer20} The Japanese Circulation Society infective endocarditis guidelines recognises this problem and still recommends antibiotic prophylaxis in moderate-risk groups (class of recommendation IIa) since they have a high incidence of infective endocarditis in national surveys in Japan, although with documented lower morbidity and mortality comparing to high-risk groups. ^{Reference Nakatani, Ohara and Ashihara21}

On the other hand, the high prevalence of infective endocarditis noted in patients after repair of tetralogy of Fallot and pulmonary atresia are probable related with residual lesions, valve-containing prosthetics, conduits and subsequent interventions, namely transcatheter pulmonary valve replacement that has recognised increased risk of infective endocarditis. ^{Reference Kuijpers, Koolbergen and Groenink8,Reference McElhinney, Sondergaard and Armstrong22,Reference Egbe, Vallabhajosyula, Akintoye and Connolly23}

Although safety, efficacy, and cost-effectiveness data are lacking regarding antibiotic prophylaxis, it is likely that there are patients that may benefit from prophylaxis, particularly those at high-risk of adverse outcomes, ^{Reference Mylotte, Rushani and Therrien2} what can include ventricular septal defect and bicuspid aortic valve lesions. Put it all together, there is an urgent need for models that can better predict the risk of developing IE and its complications in individual patients with adult CHD. ^{Reference Montanaro, Dimopoulos and Shore24}

A study of Bauer et al. showed also important knowledge gaps regarding infective endocarditis and antibiotic prophylaxis in adult CHD patients which highlight the importance of discussion these subjects during regular clinical contacts. ^{Reference Bauer, Helm and Diller5} Patients with ventricular septal defect, bicuspid aortic valve and other well-known high-risk lesions should be targeted for tailored intensified medical surveillance and educational counselling on proper daily dental and skin care, and regarding signs or symptoms of IE. ^{Reference Verheugt, Uiterwaal and van der Velde1}

Concerning the microbiological characteristics of infective endocarditis, although the incidence of staphylococcal disease and health-care associated infection are increasing, in our cohort streptococcus is still the leading causative agent in CHD patients, as it was showed in a United Kingdom study. ^{Reference Cahill, Jewell and Denne3} In 20% of cases, blood culture reports were not available. In the remaining cases, blood cultures were only positive in 79%, which suggests the early identification and collection of cultural exams prior to the onset of antibiotics is still a current problem, along with difficulty of isolating unusual organisms.

On the other hand, echocardiography is important in identifying the site of infection and related complications. Even though we reported a good diagnostic capacity of ultrasonographic methods, previous reports showed lower accuracy due to poor echo windows and frequent infections outside the heart, as on shunts, collaterals and conduits, that are difficult to demonstrate by transthoracic or transesophageal echocardiography. ^{Reference Li and Somerville15,Reference Niwa, Nakazawa, Tateno, Yoshinaga and Terai17} Other imaging methods as 18F-FDG-PET/CT could be a useful diagnostic tool in the complex group of adult patients with CHD. ^{Reference Pizzi, Dos-Subirà and Roque25}

Regarding infective endocarditis treatment, no specific recommendations has been made for surgical indication in CHD, but it is usually required in over one-third of cases. ^{Reference Tutarel, Alonso-Gonzalez and Montanaro12,Reference Murakami, Niwa, Yoshinaga and Nakazawa26} ‘Removing’ the cardiac lesion could be indicated as soon as infective endocarditis is cured, because of possible recurrence after the first episode. ^{Reference Di Filippo14} However, and according to what we observed (less surgical approach in cyanotic patients), surgical repair is not an option in complex heart disease, and these patients remain lifelong exposed to infective endocarditis risk.