Oğuz, Didem

Introduction: A significant portion of patients with aortic stenosis (AS) have low-gradient AS (LGAS) defined as aortic valve area ≤ 1.0 cm 2 and a trans-aortic mean systolic gradient and peak velocity < 40 mmHg and < 4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Etiologies for LGAS include diastolic dysfunction, heart failure, other significant valvular disease, and atrial fibrillation (AF). AF is associated with worse outcomes compared to sinus rhythm (SR) in HGAS. AF is common in LGAS, but whether AF is associated with worse outcomes versus SR in LGAS has not been elucidated. Hypothesis: We hypothesize that AF is associated with higher mortality compared to SR in patients with LGAS. Methods: We retrospectively identified and reviewed charts of patients who were diagnosed with LGAS on transthoracic echocardiogram (TTE) from 2010-2020 at Mayo Clinic. Patient were classified according to rhythm at the time of TTE and history of AF was ascertained among those in SR. Patents were divided into 3 groups; SR without history of AF (group 1), SR with history of AF (group 2), and AF during TTE (group 3). Primary endpoints of overall mortality and cardiac mortality were ascertained. Results: A total of 3400 patients were included: n=2036 in group 1, n=519 in group 2, and n=845 in group 3. After adjusting for age, sex, and the Charlson index, group 2 and group 3 patient had significantly higher overall mortality (HR 1.22 and HR 1.52, respectively, p<0.0001 for both) and cardiac mortality (HR 1.37 and HR 2.05, respectively, p<0.0001 for both), Figure . Conclusions: In LGAS, AF is a significant prognostic indicator of overall mortality and cardiac mortality. LAGS associated with AF may need different management strategies given the higher mortality associated with the presence of AF.

Abstract Introduction Aortic stenosis (AS) is the most common significant valvular heart disease in developed countries. A significant portion of the AS populations have low-gradient AS (LGAS), defined as aortic valve area ≤1.0 cm2 and a trans-aortic mean systolic gradient and peak velocity &lt;40 mmHg and &lt;4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Atrial fibrillation (AF) is associated with LGAS and AF has been associated with worse outcomes compared to sinus rhythm (SR) in HGAS. The prognostic impact of AF in LGAS is not well described in previous literature. Hypothesis AF will be associated with worse clinical outcomes compared to SR in patients with LGAS. Methods 3400 patients diagnosed with LGAS from 2010–2020 were retrospectively identified and analyzed. Their electrical rhythm was analyzed at the time of their echocardiographic diagnosis of LGAS and patients were split into 3 separate groups: SR (n=2036), SR with history of AF (n=519), and AF (n=845). After adjustment for age, sex, and Charlson Comorbidity Index (CCI), primary endpoints of overall mortality and cardiac mortality were assessed for patients. Results Compared to those with SR, patients with AF and history of AF had significantly higher overall mortality (HR 1.52, p&lt;0.0001 and HR 1.22, p=0.004, respectively) and cardiac mortality (HR 2.05, p&lt;0.0001 and HR 1.37, p=0.03, respectfully) (Figure 1). On further sub group analysis, AF seemed to be most importantly associated with mortality and cardiac mortality in patients with preserved ejection fraction (EF &gt;50%, normal flow LGAS) compared to those patients with reduced EF (classical low-flow LGAS), where there was no statistically significant difference in outcomes between AF and SR (Figure 2). Conclusions Atrial fibrillation, compared to sinus rhythm, is associated with worse overall mortality and cardiac mortality in patients with LGAS and preserved EF. Specifically, this association was strongest in patients with preserved EF &gt;50%. Given these findings, the presence of AF should be factored into clinical decision making regarding LGAS management given the higher risk of age, sex, and CCI adjusted overall and cardiac mortality. Further research needs to be done to see if earlier aortic valve intervention in these patients would improve mortality compared to their SR counterparts. Funding Acknowledgement Type of funding sources: None.

Abstract Background Wild type transthyretin cardiac amyloidosis (wtATTR-CA) is increasingly recognized as a cause of heart failure with preserved ejection fraction (HFpEF) but prognosis is often limited due to late or misdiagnosis.Longitudinal left ventricular strain and biomarkers are established as markers of disease severity, but the role of RV free wall strain, reflecting RV contractility, is less well understood. Purpose We sought to determine whether RV free wall strain might add incremental prognostic value in wtATTR-CA. Methods Consecutive patients diagnosed with wtATTR-CA with tissue confirmation at Mayo clinic between 2013 and 2015 were included. Patients with TTR gene mutations were excluded. Baseline characteristics and transthoracic echocardiography measurements were obtained from the medical records. Speckle tracking RV free wall longitudinal 2D strain and peak LA longitudinal 2D strain were measured using Tom Tec Imaging System. Survival was determined using Kaplan Meier estimates and using the cox proportional hazard ratio, univariate and multivariable analysis were performed to identify predictors of mortality in patients with wtATTR. Results The study group comprised 139 patients (mean age 74.9±8.6, 92.8% male), of which 102 had adequate image quality for RV strain, and 99 for LA strain. Amongst these, 102 (73.3%) had AF and 118 patients (84.8%) had HF. During 3.23±2.0 years of follow up, 66 patients died. Both mean RV and LA strain were impaired at baseline: RV free wall strain was −14.7±4.9, and peak atrial longitudinal strain (PALS) was 13.2±8.8%. Using ROC analysis, RV strain of −16.8% was an independent predictor of all-cause mortality. In univariate modeling, higher levels of NT-proBNP (HR: 1.1 per 1000 pg.ml; 95%, CI 1.05–1.15, p&lt;0.001) and Troponin T (HR: 2.0 per 0.1ng/ml; 95% CI 1.49–2.61, p&lt;0.001) were associated with increased all-cause mortality. In addition, LV GLS (HR: 1.13 per 1%; 95% CI1.04–1.24, p=0.003), RV free wall LS (HR: 2.16 per 5%; 95%, CI 1.57–3.03, p&lt;0.0001), and PALS (HR: 0.91 per1%; 95% CI 0.85–0.96, p&lt;0.0001) were univariate predictors of all-cause mortality. In multivariate analysis using a stepwise regression model, RV free wall longitudinal strain (HR: 1.81; 95% CI 1.29–2.62, p&lt;0.001) and Troponin T (HR: 1.7; 95% CI 1.25–2.26, p=0.001) remained independent predictors. Kaplan-Meier survival analysis demonstrated a higher mortality rate above −16.8 RV strain cut-off (Wilcoxon &lt;0.0001). All stages were divided into two groups by −16.8% RV strain, and survival in individual stages analyzed. Stage 1 and 2 with &lt;−16.8 RV free wall strain value had higher mortality than ≤-16.8% RV strain (Stage 1: Wilcoxon = 0.0041 and Stage 2: Wilcoxon = 0.023). However, there was not a survival difference between two RV strain groups in stage3 (Wilcoxon = 0.34) Conclusion RV free wall strain is an independent predictor of survival in wtATTR patients and may add incremental prognostic value to NT-proBNP and Troponin. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier curve of all patientsKaplan-Meier curve of stages

Background: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mm Hg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS). Methods: One thousand five hundred forty-one patients with aortic valve area ≤1 cm 2 and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mm Hg) and LGAS (<40 mm Hg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed. Results: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mm Hg in AF-LGAS, all P ≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581–3462) AVCS were higher in AF-HGAS (2991 arbitrary units; IQR1978–4229, P =0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817–2810, P =0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945–1832, P <0.001); AVCS in AF-LGAS were higher when HS were present ( P =0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40–2.36], P <0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04–2.26], P =0.03) but not different in AF-LGAS without HS or SR-LGAS (both P =not significant). Conclusions: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present.

AbstractBackgroundThe predictors and clinical significance of increased Doppler‐derived mean diastolic gradient (MG) following transcatheter edge‐to‐edge mitral valve repair (MVTEER) remain controversial.ObjectiveWe sought to examine baseline correlates of Doppler‐derived increased MG post‐MVTEER and its impact on intermediate‐term outcomes.MethodsPatients undergoing MVTEER were analyzed retrospectively. Post‐MVTEER increased MG was defined as >5 mmHg or aborted clip implantation due to increased MG intraprocedurally. Baseline MG and 3D‐guided mitral valve area (MVA) by planimetry were retrospectively available in 233 and 109 patients.Results243 patients were included; 62 (26%) had MG > 5 mmHg post‐MVTEER or aborted clip insertion, including 7 (11%) that had aborted clip implantation. Mortality occurred in 63 (26%) during a median follow up of 516 days (IQR 211, 1021). Increased post‐MVTEER MG occurred more frequently in females (44% vs. 16%, p < 0.001), those with baseline MVA <4.0 cm2 (71% vs. 16%), baseline MG ≥4 mmHg (61% vs. 20%), or multiple clips implanted (33% vs. 21%, p = 0.04). Increased post‐MVTEER MG was associated with increased subsequent mortality compared to those with normal gradient (HR 1.91 95% CI 1.15–3.18 p = 0.016) as was aborted clip insertion compared to all others (HR 5.23 95% CI 2.06–13.28 p < 0.001).ConclusionsSmaller baseline MVA and increased baseline MG are associated with increased MG post‐MVTEER and patients with a Doppler‐derived post‐MVTEER MG >5 mmHg suffered excess subsequent mortality. In high risk patients considered for MVTEER, identification of those at risk of iatrogenic mitral stenosis with MVTEER is important as they may be optimally treated with alternate surgical or transcatheter therapies.

Abstract Aims Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. Methods and results Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5–5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1–2.9 cm2) in SR, P &lt; 0.001. Maximal MA area was observed within 30–70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5–3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3–1.7 cm2) in SR, P &lt; 0.001. Maximal TA area was observed within 60–100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. Conclusion MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.

Background: The aim of this aortic stenosis registry was to investigate the changes of routine echocardiographic indices and strain in patients with moderate-to-severe aortic stenosis over a 6-month follow-up period. Methods: Our aortic stenosis registry is observational, prospective, multicenter registry of nine countries, with 197 patients with aortic valve area less than 1.5 cm 2 . The enrolment took place from January to August 2017. We excluded patients with uncontrolled atrial arrhythmias, pulmonary hypertension or cardiomyopathies, as well as those with hemodynamically significant valvular disease other than aortic stenosis. We included patients who did not require intervention and who had a complete follow-up study. Results: In patients with preserved ejection fraction, left ventricular mass has significantly increased between baseline and follow-up studies (218 ± 34 grams vs 253 ± 29 grams, p = 0.02). However, when indexed to body surface area, there was no significant difference. Left ventricular global longitudinal strain significantly decreased (-19.7 ± -4.8 vs (-16.4 vs -3.8, p = 0.01). Left atrial volume was significantly higher at follow-up (p = 0.035). Right ventricular basal diameter and mid-cavity diameter were greater at the follow-up (p = 0.04 and p = 0.035, respectively). Patients with low-flow low-gradient aortic stenosis had significantly lower global longitudinal strain (-12.3% ± -3.9% vs -19.7% ± -4.8%, p = 0.01). Conclusion: Left atrial dilatation is one of the first changes to take place in low-flow low-gradient aortic stenosis patients even when left ventricular dimensions and function remains intact. Global longitudinal strain is an important determinant of left ventricular systolic and diastolic dysfunction and right ventricular function is an important parameter of aortic stenosis assessment. Accordingly, our registry has further shed the light on these indices role as multisite follow-up of aortic stenosis.

Abstract Background Transcatheter edge-to-edge mitral valve repair (TMVR; MitraClip, Abbott Vascular) is clinically approved for treatment of severe, symptomatic mitral regurgitation (MR) in high or prohibitive surgical risk patients. Iatrogenic mitral stenosis is a known complication of TMVR, but determinants of increased post-procedure mean diastolic gradient are not well defined. Purpose We aimed to investigate the determinants of increased mitral mean diastolic gradient after TMVR. Methods We retrospectively reviewed 59 patients. 2D and 3D TEE data sets acquired before and immediately after procedure were analyzed. 4D Cardio-View and 4D MV-Assessment (TomTec, Germany) were used for the analysis of the 3D volume data set. Quantitative mitral valve analysis was done at the end of systole. Increased mitral mean diastolic gradient after TMVR was correlated with pre-procedure 2D and 3D echocardiographic data. Results 34 patients had primary MR, 25 patients had mixed/secondary MR. Baseline mean mitral diastolic gradient was 2.0 ± 0.9mmHg and increased to 3.9 ± 1.8mmHg post-TMVR and the mean 3D planimetric mitral valve area decreased from 5.3 ± 1.5cm2 to 2.6 ± 1.0cm2. Implantation of multiple clips was performed less frequently in patients with smaller baseline mitral valve area; 8% vs 47% in the lowest quartile vs all others (p = 0.006). 12(20%) of patients had a mean diastolic gradient &gt;5mmHg post-TMVR and 15(25%) of patients had a post-TMVR mitral valve area &lt;2.0 cm2. There was no significant difference in post-procedure heart rate between patients with mean diastolic gradient ≤5mmHg vs &gt;5mmHg (p = 0.08). Patient characteristics according to post-TMVR mean diastolic gradient are shown in the Table. Post-TMVR mean diastolic gradient &gt;5mmHg was more common in patients with increased pre-procedure mean diastolic gradient(p = 0.006), post-TMVR mitral valve area &lt;2.0 cm2(40% vs 14%, p = 0.03), and ≥moderate residual mitral regurgitation(38% vs 11%, p = 0.02). Post-TMVR mitral valve area &lt;2.0cm2 was present in 50% vs 19% of patients with vs without a mean gradient &gt;5mmHg(p = 0.04). Conclusions Elevated post-TMVR mean diastolic gradient is multifactorial and related to mitral stenosis, but residual mitral regurgitation also appears to be an important contributor to increased gradients in some patients. Larger cohorts are likely needed to assess the concurrent impact of mitral annular calcification, leaflet calcification, and other variables on post-TMVR mean gradient. Abstract P1798 Figure. 2D and 3D Echocardiographic Parameters

Abstract Funding Acknowledgements Mayo Clinic Background Variability in Doppler signals is common in patients with atrial fibrillation (AF) and AF is common in low-gradient AS (LGAS). Presence of high single beat Doppler signals (peak velocity ≥4m/s or mean gradient ≥40mmHg) is not factored into decision-making in low-gradient aortic stenosis (LGAS). Objective Determine prevalence of at least one high Doppler signal in AF LGAS and its relationship to computed tomography aortic valve calcium score (AVCS) versus sinus rhythm (SR) high-gradient aortic stenosis (HGAS). Methods Consecutive patients with aortic valve area ≤1cm2 and left ventricular ejection fraction ≥50% during echo were identified (January 1, 2012-December 31, 2016). At least three consecutive Doppler signals were averaged in sinus rhythm (SR) and five in atrial fibrillation (AF). Results Of 1,854 patients, age 76± 11 years, male 52%, 301/1,854 (16%) were in AF and LGAS was present in 122/301 (41%). At least one high Doppler signal in AF LGAS was present in 43/122 (35%). AVCS within 1 year of echo was available for 36% of patient with SR HGAS and 34% of AS LGAS. Median AVCS was not different in SR HGAS 2424 (IQR 1623, 3445) vs AF LGAS with at least one high Doppler signal 2509 [IQR1547, 3119], p =0.10 AVCS threshold for severe AS (men &gt;2000 women &gt;1200) was met in 80% SR HGAS vs 86% AF LGAS with high signals. Conclusions High Doppler signals in AF LGAS are associated with high AVCS more frequently exceeding thresholds for severe AS. Single-beat high Doppler signals instead of the average correlate better with AVCS and classic HGAS.