The absence of putative pathogenic bacteria in internal mammary arteries, which are known to be affected rarely by atherosclerotic changes, and their presence in a high percentage of atherosclerotic coronary arteries support the concept that periodontal organisms are associated with the development and progression of atherosclerosis.

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated. Methods: The Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR) trial is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm 2 with aortic jet velocity >4 m/s or a mean trans-aortic gradient ≥40 mm Hg), and with normal LV function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite endpoint of all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure, as compared to a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries. Results: Between June 2015 and September 2020, 157 patients (mean age 67 years, 57 % men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in conservative treatment group. In the early surgery group, 72 patients (92.3 %) underwent SAVR with operative mortality of 1.4 %. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite endpoint than those in the conservative arm (HR 0.46, 95 % CI 0.23-0.90, p=0.02). There was no statistical difference in secondary endpoints, including all-cause mortality, first heart failure hospitalizations, major bleeding or thromboembolic complications, but trends were consistent with the primary outcome. Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms.

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We thank both groups for their letters and interest in the AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis). 1 In response to Ennezat et al, individual components of the primary composite outcome were not statistically different among randomized groups. The trial was not adequately powered to detect the difference of each component of composite primary outcome. Individual analyses of all-cause mortality and heart failure hospitalizations showed a strong trend favoring early surgery (ES), making it hypothetically plausible that, if the number of enrolled patients was higher, the difference could reach statistical significance. We believe that the relatively high rates of sudden cardiac death (SCD) further point at the unpredictability of aortic stenosis (AS) and potential hazards of a watchful waiting strategy. Two patients randomly assigned to the conservative treatment group unfortunately had SCD several months after the surgery. Accordingly, the death of these patients should not be viewed in the context of the risk of SCD associated with untreated asymptomatic AS.Serial exercise testing (ET) during follow-up was not performed in our trial. As suggested, it would be the most optimal solution for adequate implementation of a watchful waiting strategy. It is unfortunate that ET is seldom performed in a real-world clinical setting for symptom evaluation for AS. 2 It is even more unlikely that serial ET could be performed for routine follow-up of asymptomatic patients. We performed ET in each patient for symptom evaluation at the beginning of the trial, and, to include truly asymptomatic patients with AS, each patient needed to reach the age-predicted heart rate followed by the implementation of regular clinical and echocardiographic follow-up per guidelines recommendations. 3 Although the exclusion criterion was a fall in systolic blood pressure ≥20 mm Hg, among those included, no patient experienced a fall in systolic blood pressure.