Ito, Saki

Abstract Aims Cardiogenic shock (CS) is characterized by impaired left ventricular (LV) mechanical performance and adverse remodelling. We evaluated whether transthoracic echocardiography (TTE)-derived modified cardiac efficiency (mCE), integrating stroke work and residual LV volume, is associated with short- and long-term mortality in CS and whether its prognostic value differs by shock aetiology. Methods and results In this retrospective cohort study, consecutive adults admitted with CS to the cardiac intensive care unit at Mayo Clinic (2007–2018) were included if TTE was performed within 24 h. mCE was calculated as (stroke volume × estimated LV end-systolic pressure) divided by LV end-systolic volume and categorized into quartiles. Primary outcome was in-hospital mortality; secondary outcome was 1-year mortality. Multivariable logistic and Cox models adjusted for illness severity, comorbidity burden, shock aetiology, cardiac arrest, vasoactive therapy, and mechanical circulatory support. Among 667 patients, median mCE was 48 mmHg (IQR 32–74). In-hospital mortality was 28% and increased stepwise across decreasing mCE quartiles. The lowest quartile had a 2.5-fold higher adjusted odds of in-hospital death (OR 2.53; 95%CI: 1.49–4.37; P < 0.001). One-year mortality was 41%; the lowest quartile had a two-fold higher adjusted hazard of death (HR 2.05; 95%CI: 1.45–2.89; P < 0.001). Associations were stronger in acute coronary syndrome-related CS (interaction P = 0.035 for in-hospital; P = 0.015 for 1-year). Within the lowest quartile, reduced systolic pressure further amplified mortality risk. Conclusion Early TTE-derived mCE was independently associated with short- and long-term mortality in CS, particularly in acute coronary syndrome-related CS, and captured the interaction between ventricular remodelling and mechanical performance underlying high-risk phenotypes.

Abstract A recent discussion that highlighted the differences between the reported effective orifice area and corresponding incidence of prosthesis-patient mismatch within the 1- and 7-year results of the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Trial of the Avalus valve has once again emphasized the instability of such measurements. The effective orifice area, calculated using the continuity equation through measurements of the left ventricular outflow tract diameter, is highly susceptible to measurement variability, as previously demonstrated in literature through both intra- and interobserver variability. To illustrate this problem, a simulation was performed in which the left ventricular outflow tract diameter was systematically altered by −2 mm, −1 mm, 0 mm, +1 mm, and +2 mm. Subsequently, the proportion of severe prosthesis-patient mismatch was recalculated and varied between 13.3%, 6.2%, 3.1% (original), 1.2%, and 0.3%, respectively. These findings demonstrate that small but clinically realistic variability in left ventricular outflow tract measurements can significantly affect the presence of prosthesis-patient mismatch. A measurement variability of 1 mm can nearly double or halve the prevalence of severe prosthesis-patient mismatch. This illustrates that prosthesis-patient mismatch, in its current form, is highly unstable and that indexed effective orifice area-based prosthesis-patient mismatch should not be used in isolation.

Abstract Aims Cardiogenic shock (CS) is a critical manifestation of severe cardiac dysfunction, necessitating precise evaluation of left ventricular (LV) function by transthoracic echocardiography. The prognostic value of global longitudinal strain (GLS) has not been examined in patients with CS. Therefore, we aimed to assess the prognostic significance of GLS in patients with CS. Methods and results This was a retrospective study of patients with CS from 2007 to 2018 who had a transthoracic echocardiography performed within 24 h of admission. GLS was measured, and conventional parameters were obtained. LV dysfunction was categorized by GLS: > 9.7% (Quartile 1), 7.0% < GLS ≤ 9.7% (Quartile 2), 5.0% < GLS ≤ 7.0% (Quartile 3), and ≤5.0% (Quartile 4). Outcomes included in-hospital and 1-year all-cause mortality. Among 623 patients with CS with the median LVEF of 31% [inter-quartile range (IQR): 24–41%] and the median GLS of 7.0% (IQR: 5.0–9.7%), in-hospital mortality was 29%. Mortality increased across GLS quartiles: Quartile 1: 17%; Quartile 2: 22%; Quartile 3: 35%; and Quartile 4: 42%. GLS remained the only independent echocardiographic predictor of in-hospital mortality after adjusting for clinical covariates (adjusted odds ratio: 1.23 per 1% decrease, 95% confidence interval: 1.04–1.46, P = 0.015). GLS independently predicted 1-year all-cause mortality (P < 0.001). The prognostic value of GLS was superior in cases with acute coronary syndrome. A classification and regression tree analysis identified GLS as the most important echocardiographic variable for predicting in-hospital mortality. Conclusion GLS independently predicted short- and long-term mortality in patients with CS, surpassing conventional echocardiographic parameters in prognostic value, supporting its potential role in risk stratification in this population.

Abstract OBJECTIVES Safety, efficacy and durability are important considerations when selecting a bioprosthesis for aortic valve replacement (AVR). This study assessed 7-year clinical outcomes and haemodynamic performance of the Avalus bioprosthesis. METHODS Patients indicated for surgical AVR were enrolled in this prospective, nonrandomized trial, conducted across 39 sites globally. The primary end-point of this analysis was freedom from surgical explant or percutaneous valve-in-valve reintervention due to structural valve deterioration (SVD) at 7 years of follow-up, determined using Kaplan–Meier (KM) analysis. We also evaluated a composite end-point of SVD and/or severe haemodynamic dysfunction requiring reintervention. Survival, valve-related safety events and haemodynamic performance were assessed. Deaths and safety events were adjudicated by an independent clinical events committee. RESULTS A total of 1132 patients underwent surgical AVR. Mean age was 70 years; 854 patients (75%) were men. The mean STS risk of mortality was 2.0 ± 1.4%, and 659 patients (58%) had a New York Heart Association classification of I/II. One or more concomitant procedures were performed in 577 patients (51%). At 7 years, the Kaplan–Meier rate of freedom from SVD/severe haemodynamic dysfunction requiring reintervention was 1.2% (0.5–2.5%) with no cases adjudicated as SVD. The survival rate was 82.6% (79.5–85.0%). The KM event rate was 5.7% (4.3–7.7%) for reintervention, 6.3% (4.9–8.3%) for endocarditis and 0.4% (0.1–1.1%) for valve thrombosis. Mean aortic gradient, dimensionless velocity index and effective orifice area were 13.8 ± 5.9 mmHg, 0.42 ± 0.09 and 1.99 ± 0.53 cm2, respectively. CONCLUSIONS This analysis demonstrated excellent durability of the Avalus valve with good clinical outcomes and stable haemodynamic performance through 7 years of follow-up.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis, but data are limited on younger, low-risk patients. This analysis compares outcomes in low-surgical-risk patients aged <75 years receiving TAVR versus surgery. METHODS: The Evolut Low Risk Trial randomized 1414 low-risk patients to treatment with a supra-annular, self-expanding TAVR or surgery. We compared rates of all-cause mortality or disabling stroke, associated clinical outcomes, and bioprosthetic valve performance at 3 years between TAVR and surgery patients aged <75 years. RESULTS: In patients <75 years, 352 were randomized to TAVR and 351 to surgery. Mean age was 69.1±4.0 years (minimum 51 and maximum 74); Society of Thoracic Surgeons Predicted Risk of Mortality was 1.7±0.6%. At 3 years, all-cause mortality or disabling stroke for TAVR was 5.7% and 8.0% for surgery ( P =0.241). Although there was no difference between TAVR and surgery in all-cause mortality, the incidence of disabling stroke was lower with TAVR (0.6%) than surgery (2.9%; P =0.019), while surgery was associated with a lower incidence of pacemaker implantation (7.1%) compared with TAVR (21.0%; P <0.001). Valve reintervention rates (TAVR 1.5%, surgery 1.5%, P =0.962) were low in both groups. Valve performance was significantly better with TAVR than surgery with lower mean aortic gradients ( P <0.001) and lower rates of severe prosthesis-patient mismatch ( P <0.001). Rates of valve thrombosis and endocarditis were similar between groups. There were no significant differences in rates of residual ≥moderate paravalvular regurgitation. CONCLUSIONS: Low-risk patients <75 years treated with supra-annular, self-expanding TAVR had comparable 3-year all-cause mortality and lower disabling stroke compared with patients treated with surgery. There was significantly better valve performance in patients treated with TAVR. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02701283.

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University Dagmar Marshalls Fond. Background The assessment of left ventricular (LV) function through transthoracic echocardiography (TTE) is essential for guiding diagnosis and treatment in cases of cardiogenic shock (CS). Myocardial global longitudinal strain (GLS) provides an objective and reproducible measure of systolic function, independently predicting outcomes in acute heart failure, regardless of left ventricular ejection fraction (LVEF). However, whether assessment of GLS can predict mortality in patients with CS remains unknown. Purpose In this study, we aimed to evaluate the prognostic significance of GLS in patients with CS. Methods Data from cardiac intensive care unit (CICU) patients admitted between 2007 and 2018 with CS who received vasoactive agents and/or mechanical circulatory support were analysed. GLS (as absolute values) and biplane LVEF were measured via TTE performed within 24 hours of CICU admission. Patients with CS were categorised based on the GLS quartile: mild (GLS &gt;9.7%), moderate (7.0% &lt; GLS &lt;9.6%), severe (5.0% &lt; GLS &lt; 6.9%), and very severe (GLS ≤ 4.9%). CICU and in-hospital mortality were compared across GLS categories, and the relationship between GLS and mortality was assessed using multivariable logistic regression. Results The study included 626 patients with a median age of 68.6 years, a median LVEF of 31% (IQR 24 to 40%), and a median GLS of 7.0% (IQR 5.0 to 9.7%). In-hospital mortality was 29.1%. As GLS deteriorated, there was an increasing need for vasopressors (P&lt;0.001). Patients with progressively lower GLS exhibited significantly higher CICU and in-hospital mortality across the GLS quartiles (Figure A; P&lt;0.001). Patients in the severe (adjusted OR 2.67; p&lt;0.001) and very severe category (adjusted OR 3.54; P&lt;0.001) had significantly increased risk of in-hospital death compared with mild category. In multivariable analysis, every 1% decrease in GLS corresponded to a 14% higher risk of in-hospital mortality (P&lt;0.001). Finally, GLS outperformed LVEF for discrimination of in-hospital mortality (P=0.002), and when both measurements were included in the same multivariable model, only GLS remained significant. When patients were divided according to whether they had GLS and/or LVEF below the median value, patients with low GLS had higher mortality irrespective of the LVEF (Figure B). Conclusion In patients with CS, GLS assessment surpasses LVEF in its prognostic value and improves risk stratification. Routine evaluation of GLS should be considered for patients with CS.Figure AFigure B

Abstract OBJECTIVES The objective of this analysis was to assess the normal haemodynamic performance of contemporary surgical aortic valves at 1 year postimplant in patients undergoing surgical aortic valve replacement for significant valvular dysfunction. By pooling data from 4 multicentre studies, this study will contribute to a better understanding of the effectiveness of surgical aortic valve replacement procedures, aiding clinicians and researchers in making informed decisions regarding valve selection and patient management. METHODS Echocardiograms were assessed by a single core laboratory. Effective orifice area, dimensionless velocity index, mean aortic gradient, peak aortic velocity and stroke volume were evaluated. RESULTS The cohort included 2958 patients. Baseline age in the studies ranged from 70.1 ± 9.0 to 83.3 ± 6.4 years, and Society of Thoracic Surgeons risk of mortality was 1.9 ± 0.7 to 7.5 ± 3.4%. Twenty patients who had received a valve model implanted in fewer than 10 cases were excluded. Ten valve models (all tissue valves; n = 2938 patients) were analysed. At 1 year, population mean effective orifice area ranged from 1.46 ± 0.34 to 2.12 ± 0.59 cm2, and dimensionless velocity index, from 0.39 ± 0.07 to 0.56 ± 0.15. The mean gradient ranged from 8.6 ± 3.4 to 16.1 ± 6.2 mmHg with peak aortic velocity of 1.96 ± 0.39 to 2.65 ± 0.47 m/s. Stroke volume was 75.3 ± 19.6 to 89.8 ± 24.3 ml. CONCLUSIONS This pooled cohort is the largest to date of contemporary surgical aortic valves with echocardiograms analysed by a single core lab. Overall haemodynamic performance at 1 year ranged from good to excellent. These data can serve as a benchmark for other studies and may be useful to evaluate the performance of bioprosthetic surgical valves over time. Clinical trial registration number NCT02088554, NCT02701283, NCT01586910 and NCT01531374.

Introduction: Rate of aortic stenosis (AS) progression in patients with concurrent atrial fibrillation (AF) has not been previously described. Objectives: To describe changes over time in aortic valve area (AVA) and associated hemodynamics during AS progression in patients in AF versus sinus rhythm (SR). Methods: Patients with AVA ≤ 1 cm 2 and preserved left ventricular ejection fraction ≥50% were identified from the Mayo Clinic Echocardiographic Laboratory Database. Serial echocardiograms prior to the development of AVA ≤ 1 cm 2 (Time 0) were examined. Inverse probability weighting was used for statistical analysis. Results: A total of 166 patients were included (SR=79 and AF=87), mean age 78.1 ± 7.8 years, females 31%. The rates of AVA reduction (-0.14±0.01 vs -0.12±0.01 cm2/year, p=0.31) and increase in trans-aortic peak velocity (+0.23 ± 0.02 vs +0.22 ± 0.02 m/sec, p=0.55) and mean gradient (MG) (3.9 ± 0.3 vs 3.8 ± 0.4 mmHg, p=0.83) did not differ between AF and SR (Figure 1). However, AF was associated with systematically lower forward stroke volume index (SVi), peak velocity and MG for the same AVA compared to SR (p<0.04 for all) throughout AS progression. When AVA reached 1 cm 2 , SVi (38.8±6.6 vs 45.7 ±8.9, p=0.02), peak velocity (3.9 ± 0.6 vs 4.1 ± 0.6 m/sec, p=0.04) and MG (36.6±10.9 vs 41±12.8 mmHg, p=0.03) were lower in AF compared to SR. Conclusions: The rate of AS progression was not different in AF versus SR. However, forward flow was systematically lower in AF resulting in discordant AS during AS progression and when AVA reached 1 cm 2 . Doppler velocity and MG criteria for severe AS appear to be lower in AF versus SR which has implications for timely diagnosis of severe AS and patient management.

Objective To evaluate whether transcatheter or surgical aortic valve replacement (TAVR or SAVR) affects clinical and haemodynamic outcomes in symptomatic patients with moderately-severe aortic stenosis (AS). Methods Echocardiographic evidence of severe AS for enrolment in the Evolut Low Risk trial was based on site-reported measurements. For this post hoc analysis, core laboratory measurements identified patients with symptomatic moderately-severe AS (1.0<aortic valve area (AVA)<1.5 cm2, 3.0<peak velocity<4.0 m/s and 20≤mean gradient (MG) <40 mm Hg). Clinical outcomes were reported through 2 years. Results Moderately-severe AS was identified in 113 out of 1414 patients (8%). Baseline AVA was 1.1±0.1 cm2, peak velocity 3.7±0.2 m/s, MG 32.7±4.8 mm Hg and aortic valve calcium volume 588 (364, 815) mm3. Valve haemodynamics improved following TAVR (AVA 2.5±0.7 cm2, peak velocity 1.9±0.5 m/s and MG 8.4±4.8 mm Hg; p<0.001 for all) and SAVR (AVA 2.0±0.6 cm2, peak velocity 2.1±0.4 m/s and MG 10.0±3.4 mm Hg; p<0.001 for all). At 24 months, the rates of death or disabling stroke were similar (TAVR 7.7% vs SAVR 6.5%; p=0.82). Kansas City Cardiomyopathy Questionnaire overall summary score assessing quality of life improved from baseline to 30 days after TAVR (67.0±20.6 to 89.3±13.4; p<0.001) and SAVR (67.5±19.6 to 78.3±22.3; p=0.001). Conclusions In symptomatic patients with moderately-severe AS, AVR appears to be beneficial. Determination of the clinical and haemodynamic profile of patients who can benefit from earlier isolated AVR needs further investigation in randomised clinical trials.

Abstract Aims An artificial intelligence-enabled electrocardiogram (AI-ECG) is a promising tool to detect patients with aortic stenosis (AS) before developing symptoms. However, functional, structural, or haemodynamic components reflected in AI-ECG responsible for its detection are unknown. Methods and results The AI-ECG model that was developed at Mayo Clinic using a convolutional neural network to identify patients with moderate–severe AS was applied. In patients used as the testing group, the correlation between the AI-ECG probability of AS and echocardiographic parameters was investigated. This study included 102 926 patients (63.0 ± 16.3 years, 52% male), and 28 464 (27.7%) were identified as AS positive by AI-ECG. Older age, atrial fibrillation, hypertension, diabetes, coronary artery disease, and heart failure were more common in the positive AI-ECG group than in the negative group (P &lt; 0.001). The AI-ECG was correlated with aortic valve area (ρ = −0.48, R2 = 0.20), peak velocity (ρ = 0.22, R2 = 0.08), and mean pressure gradient (ρ = 0.35, R2 = 0.08). The AI-ECG also correlated with left ventricular (LV) mass index (ρ = 0.36, R2 = 0.13), E/e′ (ρ = 0.36, R2 = 0.12), and left atrium volume index (ρ = 0.42, R2 = 0.12). Neither LV ejection fraction nor stroke volume index had a significant correlation with the AI-ECG. Age correlated with the AI-ECG (ρ = 0.46, R2 = 0.22) and its correlation with echocardiography parameters was similar to that of the AI-ECG. Conclusion A combination of AS severity, diastolic dysfunction, and LV hypertrophy is reflected in the AI-ECG to detect AS. There seems to be a gradation of the cardiac anatomical/functional features in the model and its identification process of AS is multifactorial.