Quantifying the Survival Loss Linked to Late Therapeutic Indication in High-Gradient Severe Aortic Stenosis.

Background: International guidelines recommend aortic valve replacement (AVR) as Class I triggers in high-gradient severe aortic stenosis (HGSAS) patients with symptoms and/or left ventricular ejection fraction (LVEF) <50%. The association between waiting for these triggers and postoperative survival penalty is poorly studied. Objectives: The purpose of this study was to examine the impact of guideline-based Class I triggers on long-term postoperative survival in HGSAS patients. Methods: 2,030 patients operated for HGSAS were included and classified as follows: no Class I triggers (no symptoms and LVEF >50%, n = 853), symptoms with LVEF >50% (n = 965), or LVEF <50% regardless of symptoms (n = 212). Survival was compared after matching (inverse probability weighting) for clinical differences. Restricted mean survival time was analyzed to quantify lifetime loss. Results: Ten-year survival was better without any Class I trigger than with symptoms or LVEF <50% (67.1% ± 3% vs 56.4% ± 3% vs 53.1% ± 7%, respectively, P < 0.001). Adjusted death risks increased significantly in operated patients with symptoms (HR: 1.45 [95% CI: 1.15-1.82]) or LVEF <50% (HR: 1.47 [95% CI: 1.05-2.06]) than in those without Class I triggers. Performing AVR with LVEF >60% produced similar outcomes to that of the general population, whereas operated patients with LVEF <60% was associated with a 10-year postoperative survival penalty. Furthermore, according to restricted mean survival time analyses, operating on symptomatic patients or with LVEF <60% led to 8.3- and 11.4-month survival losses, respectively, after 10 years, compared with operated asymptomatic patients with a LVEF >60%. Conclusions: Guideline-based Class I triggers for AVR in HGSAS have profound consequences on long-term postoperative survival, suggesting that HGSAS patients should undergo AVR before trigger onset. Operating on patients with LVEF <60% is already associated with a 10-year postoperative survival penalty questioning the need for an EF threshold recommending AVR in HGSAS patients.

3D histopathology of stenotic aortic valve cusps using ex vivo microfocus computed tomography.

Background: Calcific aortic stenosis (AS) is the most prevalent heart valve disease in developed countries. The aortic valve cusps progressively thicken and the valve does not open fully due to the presence of calcifications. In vivo imaging, usually used for diagnosis, does not allow the visualization of the microstructural changes associated with AS. Methods: Ex vivo high-resolution microfocus computed tomography (microCT) was used to quantitatively describe the microstructure of calcified aortic valve cusps in full 3D. As case study in our work, this quantitative analysis was applied to normal-flow low-gradient severe AS (NF-LG-SAS), for which the medical prognostic is still highly debated in the current literature, and high-gradient severe AS (HG-SAS). Results: The volume proportion of calcification, the size and number of calcified particles and their density composition was quantified. A new size-based classification considering small-sized particles that are not detected with in vivo imaging was defined for macro-, meso- and microscale calcifications. Volume and thickness of aortic valve cusps, including the complete thickness distribution, were also determined. Moreover, changes in the cusp soft tissues were also visualized with microCT and confirmed by scanning electron microscopy images of the same sample. NF-LG-SAS cusps contained lower relative amount of calcifications than HG-SAS. Moreover, the number and size of calcified objects and the volume and thickness of the cusps were also lower in NF-LG-SAS cusps than in HG-SAS. Conclusions: The application of high-resolution ex vivo microCT to stenotic aortic valve cusps provided a quantitative description of the general structure of the cusps and of the calcifications present in the cusp soft tissues. This detailed description could help in the future to better understand the mechanisms of AS.

18F-Sodium Fluoride PET/CT in Assessing Valvular Heart and Atherosclerotic Diseases.

Aortic valve stenosis is the most common valvular disease in Western countries, while atherosclerotic cardiovascular disease is the foremost cause of death and disability worldwide. Valve degeneration and atherosclerosis are mediated by inflammation and calcification and inevitably progress over time. Computed tomography can visualise the later stages of macroscopic calcification but fails to assess the early stages of microcalcification and cannot differentiate active from burnt out disease states. Molecular imaging has the ability to provide complementary information related to disease activity, which may allow us to detect disease early, to predict disease progression and to monitor preventive or therapeutic strategies for in both aortic stenosis and atherosclerosis. PET/CT is a non-invasive imaging technique that enables visualization of ongoing molecular processes within small structures, such as the coronary arteries or heart valves. 18F-sodium fluoride (18F-NaF) binds hydroxyapatite deposits in the extracellular matrix, with preferential binding to newly developing deposits of microcalcification, which provides an assessment of calcification activity. In recent years, 18F-NaF has attracted the attention of many research groups and has been evaluated in several pathological cardiovascular processes. Histologic validation of the 18F-NaF PET signal in valvular disease and atherosclerosis has been reported in multiple independent studies. The selective high-affinity binding of 18F-NaF to microscopic calcified deposits (beyond the resolution of µCT) has been demonstrated ex vivo, as well as its ability to distinguish between areas of macro- and active microcalcification. In addition, prospective clinical studies have shown that baseline 18F-NaF uptake in patients with aortic stenosis and mitral annular calcification is correlated with subsequent calcium deposition and valvular dysfunction after a follow-up period of 2 years. In patients with surgical bioprosthetic aortic valves but without morphological criteria for prosthetic degeneration, increased 18F-NaF uptake at baseline was associated with subsequent bioprosthetic degeneration over time. Similar data were obtained in a cohort of patients with transcatheter aortic valve implantation. Furthermore, several studies have confirmed the association of coronary 18F-NaF uptake with adverse atherosclerotic plaque features, active disease and future disease progression. 18F-NaF uptake is also associated with future fatal or nonfatal myocardial infarction in patients with established coronary artery disease. The link between 18F-NaF uptake and active atherosclerotic disease has not only been demonstrated in the coronary arteries, but also in peripheral arterial disease, abdominal aortic aneurysms and carotid atherosclerosis. It can be assumed that 18F-NaF PET/CT will strengthen the diagnostic toolbox of practitioners in the coming years. Indeed, there is a strong medical need to diagnose degenerative valvular disease and to detect active atherosclerotic disease states. Finally, the use of 18F-NaF as a biomarker to monitor the efficacy of drug therapies in preventing these pathological processes is attractive. In this review, we consider the role of 18F-NaF PET/CT imaging in cardiac valvular diseases and atherosclerosis.

Prognostic Implications of Discordant Low-Gradient Severe Aortic Stenosis: Comprehensive Analysis of a Large Multicenter Registry.

Background: Up to 30% of patients with severe aortic stenosis (SAS) (indexed aortic valve area [AVAi] <0.6 cm2/m2) exhibit low-transvalvular gradient despite normal ejection fraction. There is intense debate regarding the prognostic significance of this entity. Objectives: The purpose of this study was to compare the outcome of patients with discordant low-gradient SAS (DLG-SAS) vs moderate aortic stenosis (MAS) and high-gradient SAS (HG-SAS). Methods: We used the BEL-F-ASt (Belgium-France-Aortic Stenosis) registry including consecutive patients with AS. Survival was compared overall and after matching (inverse probability weighting and propensity-score matching) for clinical and imaging variables. The analysis was first performed in the overall population (n = 2,582) and then in the population of unoperated patients (n = 1,812). Results: After-inverse probability weighting-matching, the 3 groups were balanced. Five-year survival was better in MAS than in DLG-SAS and HG-SAS-patients (58.9% vs 47% vs 41.2%, P < 0.001). Similar results were obtained in unoperated patients (54.1% vs 37.9% vs 28.1%, P < 0.001). To explore the impact of MG (≤40 vs >40 mmHg) and AVAi (<0.6 vs ≥0.6 cm2/m2) on outcomes, survival of propensity score-matched cohorts of HG-vs DLG-SAS and MAS vs DLG-SAS were compared. After matching for MG, survival was better in MAS than in DLG-SAS (52% vs 40%, P < 0.001). After matching for AVAi, survival was better in DLG-SAS than in HG-SAS patients (45% vs 33%, P < 0.001). Conclusions: Survival of DLG-SAS is better than that of HG-SAS and worse than that of MAS patients. At comparable MG, the lower the AVAi, the worse the prognosis, whereas at comparable AVAi, the higher the MG, the worse the prognosis. These data argue that DLG-SAS is an intermediate form in the disease continuum.

The Management between Comorbidities and Pain Level with Physical Activity in Individuals with Hip Osteoarthritis with Surgical Indication: A Cross-Sectional Study.

Background and Objectives: The degenerative pathology of the hip joint appears in young age groups, related to fem-oroacetabular impingement, and in advanced age, due to other inflammatory causes, with greater potential for severity in the presence of comorbidities. Objectives: To evaluate the participation of the main causes of osteoarthritis in relation to physical activities, s Body Mass Index (BMI) and television time (TV). Materials and Methods: 54 patients with surgical indication treated at an orthopedic referral university hospital were stratified into groups (Impact: I, Osteonecrosis/rheumatic: II, Infectious/traumatic: III), and the influence of comorbidities on physical activity performance, relative to BMI and TV time. Results: It was observed that the impact group was the most frequent (51.8%), with 79.6% under the age of 60 years. This group followed the general mean (p < 0.05), using the variables of comorbidity and the level of physical activity. Pain intensity, TV time, BMI showed no correlation with physical activity. Conclusion: Morphostructural changes (group I) represented the most frequent etiological group, and severe pain was common in almost the entire sample. Unlike BMI, comorbidity showed a significant relationship with the level of physical activity.