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Abstract Background and Aims Severe aortic stenosis (AS) is the guideline-based indication for aortic valve replacement (AVR), which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory and lack quantitative Doppler echocardiographic ascertainment. Methods All adults residents in Olmsted County (MN, USA) diagnosed over 20 years (1997–2016) with incident severe AS (first diagnosis) based on quantitatively defined measures (aortic valve area ≤ 1 cm2, aortic valve area index ≤ 0.6 cm2/m2, mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, Doppler velocity index ≤ 0.25) were counted to define trends in incidence, presentation, treatment, and outcome. Results Incident severe AS was diagnosed in 1069 community residents. The incidence rate was 52.5 [49.4–55.8] per 100 000 patient-year, slightly higher in males vs. females and was almost unchanged after age and sex adjustment for the US population 53.8 [50.6–57.0] per 100 000 residents/year. Over 20 years, severe AS incidence remained stable (P = .2) but absolute burden of incident cases markedly increased (P = .0004) due to population growth. Incidence trend differed by sex, stable in men (incidence rate ratio 0.99, P = .7) but declining in women (incidence rate ratio 0.93, P = .02). Over the study, AS clinical characteristics remained remarkably stable and AVR performance grew and was more prompt (from 1.3 [0.1–3.3] years in 1997–2000 to 0.5 [0.2–2.1] years in 2013–16, P = .001) but undertreatment remained prominent (>40%). Early AVR was associated with survival benefit (adjusted hazard ratio 0.55 [0.42–0.71], P < .0001). Despite these improvements, overall mortality (3-month 8% and 3-year 36%), was swift, considerable and unabated (all P ≥ .4) throughout the study. Conclusions Over 20 years, the population incidence of severe AS remained stable with increased absolute case burden related to population growth. Despite stable severe AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease lethality did not yet decline. These population-based findings have important implications for improving AS management pathways.

Introduction: Multiple Valvular Heart Disease (VHD), defined as at least moderate stenotic or regurgitant lesions in ≥2 valves, mixed VHD as combination of lesions in the same valve and mitral annular calcification (MAC) are common conditions. Association between multiple-mixed VHD (MMVHD), MAC and MACE in patients exposed to Radiation Therapy (RT) and/or chemotherapy (CT) who underwent Transcatheter Aortic Valve Replacement (TAVR) has not been studied. Aim: Assess the presence of MMVHD and MAC in cancer patients with prior RT and/or CT and their correlation with MACE (cardiovascular death, myocardial infarction, revascularization, stroke and hospitalization for heart failure) after TAVR. Methods: 544 patients were included and divided into 3 groups: 187 with prior chest RT and CT (RT/CT), 155 CT only, and 202 without CT/RT as controls (Table 1). Data was obtained from the pre-procedure echocardiogram and quantified in a 1-6 scale (none, mild, mild/moderate, moderate, moderate/severe and severe). Fisher’s exact test or chi-square were used to compare categorical. Multiple VHD-MACE correlation was evaluated through multivariable Cox analysis using a proportional hazards model. Results: The prevalence of Multiple VHD was 37.4% in RT/CT, 23.2% in CT, and 13.9% in controls p<0.001(Figure 1). The RT/CT group had a significantly higher prevalence of severe MAC. Multiple VHD predicted MACE at 18 months after TAVR in RT/CT (HR 3.42, CI 1.93-6.08, p<0.001) and in CT (HR 2.55, CI 1.39-4.66, p=0.002) (Table 2). In RT/CT, severe MAC also predicted MACE (HR 3.68, CI 2.13-6.37, p<0.001), while it was not a predictor in the other groups. Stenotic or regurgitant VHD was more prevalent in the RT/CT group (Figure 2). Conclusions: Multiple VHD was found higher in RT/CT and predicted MACE at 18 months post-TAVR, including CT only patients. Severe MAC was also a strong predictor of the outcome in RT/CT patients. Pre-TAVR evaluation of MMVHD lesions is crucial for optimal patient management.

Introduction: Criteria for aortic valve intervention (AVI) in severe aortic stenosis (AS) rely on symptoms, left ventricular ejection fraction (LVEF) and AS severity. Computed tomography-based aortic valve calcification (CT-AVC) scores associated with severe AS also have prognostic value, but this remains unexplored in patients with non-severe AS. We aimed to assess the prognostic value of AVC in asymptomatic patients with nonsevere AS and preserved LVEF. Methods: We retrospectively identified 395 patients with ≥mild AS but less-than-severe AS by echocardiography, who had CT-AVC assessed within six months. AVCscore was quantified offline by Agatston method (TeraRecon software), and also indexed by LV outflow track area, i.e., AVCdensity. Patients were followed until AVI or death. The primary outcome was all-cause death under medical surveillance. Results: In 395 patients, mean age was 73±12 years, 61% were men, mean aortic valve area 1.2±0.3cm2, mean gradient 28±9 mmHg, peak velocity 3.4±0.5 m/s, LVEF 64±6%. During a follow-up of 2.2[0.74-4.94] years, 220 patients had AVI and 82 patients died. Both AVCscore and AVCdensity were associated with AVI-free survival and the best AVCscore thresholds associated with mortality were 853 in women and 1183 in men by log-rank test (both p<0.001). High AVCscore and high AVCdensity were associated with increased hazard for all-cause death in unadjusted and adjusted analyses (Figure), and after further adjustment for echocardiographic severity (all p ≤0.01). Conclusions: In asymptomatic patients with less-than-severe AS, sex-specific CT-AVC scores differentiate those at higher risk for death versus lower risk. Whether AVI could modify this risk remains to be proven.

Introduction: The association of echocardiographic measurements and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. Aim: To determine if transthoracic echocardiographic (TTE) measurements are associated with the subsequent development of LS-NVE in patients without recognized cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and recognized predisposing cardiac conditions were excluded. Patients with a TTE performed 6 months to 3 years before developing LS-NVE were included as cases. Controls were patients within the same Mayo Clinic location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson Comorbidity Index (CCI), and echocardiography date. Multivariate logistic-regression analyses adjusting significant variables between cohort's were performed. A p-value <0.05 was considered significant. Results: There were 148 cases and 431 matched controls. The median age was 63.8 (IQR: 53.6 - 74.6) years, and 329 (56.8%) patients were males. LS-NVE cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) when compared with controls (p<0.001 both). The median CCI score was 3 (IQR: 0-6) for cases and 2 (IQR: 0-6) for controls. After performing adjusted analyses, left ventricular outflow tract velocity (p=0.017), left ventricular ejection fraction (p=0.018), and E: e’ ratio (p=0.050) were associated with the development of LS-NVE ( Figure 1) . Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this preliminary investigation. A larger cohort of LS-NVE patients is needed to validate these findings.

Abstract Background Atrial fibrillation (AF) is associated with increased risk of incident tricuspid regurgitation (TR), but types of incident TR in AF versus sinus rhythm (SR) are not well-defined. Purpose We aimed to compare the risk of the different types of incident ≥moderate TR in AF and SR. Methods Adults first diagnosed with AF (2010-2021) who had a transthoracic echocardiogram (TTE) within 30 days after AF and adults with no diagnosis of AF who had a TTE in the same period were identified. Patients with previous cardiac surgeries, congenital heart disease, cardiomyopathy, cardiac devices, primary valve disease, previous or current ejection fraction (EF) &lt;50%, severe diastolic dysfunction (SDD), ≥moderate left-sided valve disease (LVD), right ventricular systolic pressure (RVSP) ≥50 mmHg, ≥moderate TR, any tricuspid stenosis, or with no follow-up TTE ≥6 months from baseline were excluded. Patients were followed for the development of ≥moderate TR, the type of which was identified in a hierarchal order: 1) pacemaker-associated TR, 2) LVD-associated TR in the setting of ≥moderate LVD, 3) low EF or SDD-related TR, 4) pulmonary hypertension (PH)-associated TR if RVSP was ≥50 mmHg, 5) other ventricular functional TR (VFTR) if there was &gt;mild RV enlargement or dysfunction, and 6) atrial functional TR (AFTR) when none of the previous was present. Patients were also followed for the occurrence of risk factors for TR (pacemaker insertion, ≥moderate LVD, low EF or SDD, PH, &gt;mild RV enlargement or dysfunction) in a hierarchal order, and both the prevalence and future risk of the corresponding type of ≥moderate TR was determined at the onset of these conditions in AF and SR. Results Overall, 1,360 patients with new-onset AF (median age 67 years, 34% females) and 20,438 patients in SR (median age 60 years; 54% females) were included. Over median 3.8 (IQR 1.8-6.6) years, incident ≥moderate TR occurred in 110 patients with new-onset AF [2.13 per 100-person years] compared to 378 patients in SR [0.41 per 100-person years, p &lt;.001]. All types of incident ≥moderate TR occurred more frequently in AF (p &lt;.001 for all). The distribution and incidence of each type of TR in AF and SR are shown in Figure 1. The incidence of risk factors associated with the development of TR was higher in the AF group, except for pre-capillary PH, Figure 2A. At time of diagnosis or occurrence of these conditions, the prevalence of the corresponding TR types was higher in AF, except for pacemaker-TR, Figure 2B. The incidence of the corresponding TR type after occurrence of TR risk factors was higher in the AF group for LVD-TR and low EF/SDD-associated TR (p ≤0.03); although numerically higher in AF, the association was only borderline for PH-TR (p =0.05), Figure 2C. Conclusion Incident ≥moderate TR of all types occurred more frequently in patients with AF vs. SR and the distribution of TR types differed by rhythm. Patients with AF may benefit from a closer follow-up.Distribution and incidence rates of TRIncidence of TR risk factors & TR after

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’&gt;14; and left ventricular ejection fraction &lt;50%); stage 2 (left atrial volume index &gt;34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension&gt; 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p&lt;0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p &lt;0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p&lt;0.001, CT HR 4.49 CI (2.27 – 8.89) p&lt;0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage &gt;3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p&lt;0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Objective CT aortic valve calcium score (AVCscore) and density (AVCdensity) thresholds have been recommended for aortic stenosis (AS) severity assessment in tricuspid aortic valve (TAV). We aimed to compare AVCscore and AVCdensity in bicuspid aortic valve (BAV) versus TAV. Methods Retrospective single-centre study of patients with echocardiographic AS-severity and CT-AVC assessments within 6 months, and left ventricular ejection fraction ≥50%, all referred for clinical AS evaluation. Severe AS was defined as aortic valve area (AVA) ≤1 cm2 or indexed AVA ≤0.6cm2/m2 plus mean gradient ≥40 mm Hg or peak velocity ≥4 m/s. AVC was assessed by Agatston method. Results Of the 1957 patients, 328 had BAV and 1629 had TAV, age 65±11 vs 80±9 years (p<0.001), men 65% vs 56% (p=0.006), respectively. BAV morphology was associated with higher AVCscore and AVCdensity independent of age, comorbidities and AS severity (p<0.001) in men only (sex and BAV interaction p<0.001). In patients with severe AS, mean AVCscore and AVCdensity were higher in BAV-men than that in TAV-men (both p<0.001), but similar in BAV-women and TAV-women (both p≥0.4). Such patterns remained the same after adjustment for clinical covariates and AS severity. Best thresholds for severe AS diagnosis in BAV-men were 2916 AU by AVCscore and 600 AU/cm2 by AVCdensity which were higher than the guideline-recommended thresholds, while thresholds in BAV-women (1036 AU and 282 AU/cm2) were similar to guideline-recommended ones. Conclusion Valve calcification in AS differs according to valve morphology and sex. BAV-men with severe AS exhibit greater AVCscore and AVCdensity than TAV-men. This presents a diagnostic challenge to the current guidelines, which needs confirmation in larger studies.

Abstract Background and aims Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. Methods A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. Results The TRI-SCORE was low (≤3) in 32%, intermediate (4–5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P &lt; .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). Conclusions Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.