Øvrehus, Kristian Altern

Objectives To explore the outcomes among patients treated with TAVI (transcatheter aortic valve implantation) in the COMPARE-TAVI 1 trial by age groups and sex. Design Cohort study. Setting Three Danish university hospitals. Participants Patients treated with TAVI in the COMPARE-TAVI 1 trial (N=1030), 60 (5.8%), 337 (32.7%), 592 (57.5%) and 41 (4.0%) were in the four age groups, < 70, 70–79, 80–89 and 90+ years while 414 (40.2%) and 616 (59.8%) were of female and male sex. Interventions Transfemoral TAVI with balloon-expandable valves (Sapien or Myval) performed between June 2020 and November 2023. Outcome measures Post hoc analyses of trial secondary outcomes that include end-point committee-adjudicated outcomes. Results In the four age groups, 1-year mortality rates were 8.3%, 5.6%, 5.6% and 7.3% while it was 5.8% in both sexes. Across the four age groups, 1-year stroke rates were 6.7%, 1.8%, 3.2% and 4.9%, and 5.1% among females and 4.7% among males. In the four age groups, 1-year new pacemaker rates were 7.5%, 15%, 19% and 13% while it was 15% among females and 18% among males. Females had smaller annuli than males and their gradients were higher and the effective orifice area lower after TAVI but their frequency of prosthesis-patient mismatch was similar at 1 year. Conclusion While comorbidity levels varied between groups, clinical outcomes were similar across age groups and between sexes. Trial registration number NCT04443023 .

Abstract Aims This study aimed to identify clinical factors associated with AVC in individuals with T2D. Methods and results This cross-sectional study is a pre-specified substudy of the multicentre randomized Steno INTEN-CT trial (Clinical Trials—INTEN-CT). Participants were eligible if they had T2D without ischaemic heart disease and were aged between 55–69 years (men) or 60–74 years (women). All participants underwent non-contrast cardiac computed tomography. AVC was measured in Agatston Units and categorized as 0, 0–300, ≥ 300. Of the 4570 participants, 46% had AVC &gt; 0. With increasing AVC, patients were older, predominantly males, and with significantly more comorbidities. In multivariable ordered logistic regression age (OR per SD 1.54, 95% CI 1.43–1.66), BMI (OR per SD 1.18, 95% CI 1.11–1.25), hypertension (OR 1.21, 95% CI 1.05–1.40), and chronic kidney disease (OR 1.18, 95% CI 1.03–1.36) were associated with higher AVC. Statin use was also associated with higher AVC (OR 1.50, 95% CI 1.27–1.78). Higher LDL cholesterol showed stronger associations with AVC in men than women (OR 1.39, 95% CI 1.24–1.56 vs. OR 1.16, 95% CI 1.02–1.31, P for interaction = 0.025). T2D severity (Haemoglobin A1c, T2D duration, and number of antidiabetic drugs) was not associated with AVC. Conclusion In individuals with T2D without cardiovascular disease, AVC is prevalent in nearly half of all individuals. Higher AVC was associated with T2D-related comorbidities, but not T2D severity.

Abstract Aims We aimed to compare procedural, echocardiographic, and clinical outcomes within the first year after transcatheter aortic valve implantation (TAVI) among inhospital and subacute patients to elective patients in the COMPARE-TAVI 1 cohort. Methods and results Among 1030 patients treated with TAVI, 927 (90%) had an elective procedure, 63 (6.1%) had a subacute procedure, and 40 (3.9%) had an inhospital procedure. Procedural characteristics and outcomes were comparable. Among elective, subacute, and inhospital patients, mortality at 30 days was 15 (1.6%), 0 (0%), and 0 (0%) and at 1 year 54 (5.8%), 4 (6.3%), and 2 (5.0%). Stroke at 30 days was 28 (3.0%), 0 (0%), and 3 (7.5%) and at 1 year 42 (4.5%), 5 (7.9%), and 3 (7.5%). New pacemaker at 30 days was 119 (14%), 12 (21%), and 6 (17%) and at 1 year 130 (16%), 14 (25%), and 7 (19%). Elective, subacute, and inhospital patients with LVEF ≤40%, improved their LVEF from 33% (28–37), 33% (27–37), and 28% (22–33) before TAVI to 46% (35–60), 43% (33–52), and 42% (33–55) at 30-days, and 54% (45–62), 53% (43–61), and 49% (39–63) at 1-year. Differences between the groups were not statistically significant. Conclusion After transfemoral TAVI with balloon-expandable valves in COMPARE-TAVI 1, procedural, echocardiographic, and clinical outcomes were comparable among elective, subacute, and inhospital patients within the first year.

BACKGROUND: Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard for evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. The aim of this observational study was to describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%. METHODS: Patients with aortic valve area ≤1.5 cm 2 underwent right heart catheterization at rest and during maximal exercise, measuring pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and the PCWP/CO-slope. Patients were stratified into 3 groups: discordant LG AS (aortic valve area ≤1.0 cm 2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm 2 ); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm 2 and mean gradient ≥40 mm Hg). RESULTS: Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) HG severe AS. The median PCWP/CO-slope was significantly steeper in discordant LG (3.3 [interquartile range, 2.1–4.3] mm Hg/L/min) and HG severe AS (2.7 [1.9–3.4] mm Hg/L per minute) compared with moderate AS (1.9 [0.7–2.8] mm Hg/L per minute), P =0.004. In a regression model adjusted for age, sex, and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO-slope. Furthermore, patients with discordant LG AS had a leftward-upward shift in the PCWP/CO-curve. CONCLUSIONS: Discordant LG and HG severe AS had similar hemodynamic responses to exercise with steeper PCWP/CO-slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left upwards shift in PCWP/CO-curve for discordant LG compared with HG severe AS indicates that this group also has heart failure with preserved ejection fraction physiology. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04913870 and NCT02395107.

Abstract Background While type 2 diabetes (T2DM) is a known risk factor for aortic valve calcification (AVC) and aortic stenosis (AS), the specific mechanisms remain unclear. The aim of this study was to determine early factors associated with AVC in patients with T2DM. Methods This cross-sectional study is a pre-specified substudy of an ongoing multicenter randomized controlled trial, the STENO INTEN-CT trial (Screening and Intervention for Subclinical Coronary Artery Disease in Patients With Type 2 Diabetes). Eligibility criteria are patients with diagnosed T2DM without prior ischemic heart disease, and age between 55-69 years (male) and 60-74 years (female). All patients underwent a non-contrast cardiac computed tomography scan and AVC was measured in Agatston units. Results Of the 3635 patients included in this study, nearly half (n = 1694) demonstrated an AVC &gt; 0 (n=1502 with 0 &lt; AVC &lt; 300 and n = 192 with AVC ≥ 300). With increasing AVC, patients were elder, predominantly males, and had significantly more comorbidities (obesity, hypertension, chronic obstructive pulmonary disease, and kidney dysfunction). Patients with higher AVC were more likely to be treated with statins (AVC = 0: n = 1509 (78%), 0 &lt; AVC &lt; 300: n = 1217 (81%), AVC ≥ 300: n = 163 (85%), p = 0.009). Higher body mass index (OR: 1.03 (1.02-1.04), p &lt; 0.001), statin use (OR: 1.49 (1.24-1.80), p &lt;0.001), low-density lipoprotein (OR: 1.24 (1.12 - 1.37), p &lt; 0.001), and kidney dysfunction, measured as urine albumine-creatinine ratio (OR: 1.00 (1.00-1.00), p &lt;0.001), were independently associated with increasing AVC (Figure 1). However, T2DM severity, measured as the duration of T2DM, HbA1c levels, and the number of antidiabetic drugs used, was not associated with increasing AVC severity (Figure 1+2). Conclusion AVC is highly prevalent, affecting nearly half of patients with T2DM. However, early factors driving AVC are not associated with T2DM severity, but rather to diabetes-related comorbidities and complications.

Abstract Aims Aortic valve-sparing root replacement is recommended over composite root replacement for aortic root aneurysms, especially in younger patients, but long-term outcomes in low-volume nationwide settings remain unclear. The objectives are to compare long-term survival, stroke, and reoperation rates between the two procedures in a low-volume national setting. Methods and results Patients were identified from the Western Danish Heart Registry and the Danish Heart Registry. Cases were validated by review of operative descriptions. The primary outcome was long-term survival from all-cause mortality; secondary outcomes included stroke, reoperation, recurrent aortic regurgitation, and aortic stenosis. Groups were balanced using propensity score matching. Echocardiographic data were provided for the matched cohort. We identified 760 patients treated with composite root replacement and 179 patients with aortic valve-sparing root replacement between January 2010 and April 2022. Mean follow-up was 6.5 years. Composite root replacement patients were younger [50.7 years (SD 14.1) vs. 55.2 (SD 13.5), P &lt; 0.001], but more comorbid with a median EuroSCOREII of 5.5 [interquartile range (IQR): 3.3–11.7] vs. 3.4 (IQR: 2.6–5.0) (P &lt; 0.001). After matching 157 patients per group, aortic valve-sparing root replacement showed improved 10-year survival [91.2%, 95% confidence interval (CI) 82.3–95.8 vs. 80.4%, 95% CI 70.0–87.5, log-rank P = 0.026], with lower 10-year stroke risk (4.9%, 95% CI 1.8–13.0 vs. 18.9%, 95% CI 11.7–29.9, log-rank P = 0.007). Risk of reoperation was nonsignificant (log-rank P = 0.12), which was consistent in the crude population when accounting for competing risk of death (log-rank P = 0.09). Conclusion In this nationwide study, aortic valve-sparing root replacement was associated with better long-term survival and lower stroke risk, supporting its role as a durable surgical option for selected patients.

Abstract Aims In aortic stenosis (AS), estimation of left ventricular (LV) contractility is difficult as most markers of systolic LV function are load-dependent. The ratio of LV ejection fraction (LVEF) to end-systolic wall stress (ESWS), has been widely accepted as a marker of contractility. However, no studies have evaluated if this ratio is affected by loading conditions. The study describes changes in ESWS and ESWS corrected LVEF after transcatheter aortic valve replacement (TAVR). Methods and results In this prospective study, 41 patients with severe AS underwent echocardiography, LV catheterisation, and computed tomography (CT) before and immediately after TAVR. ESWS was estimated from echocardiography alone (ESWSEcho), combining CT LV dimensions and echocardiographic gradients (ESWSCT + echo) and combining CT LV dimensions and invasively measured LV end-systolic pressure (ESWSCT + Invasive). ESWSecho, ESWSCT + echo and ESWSCT + Invasive all decreased significantly after TAVR (89 ± 48 vs. 57 ± 37 Kdynes/cm2, P &lt; 0.01; 69 ± 8 vs. 51 ± 8 Kdynes/cm2, P &lt; 0.01, and 197 ± 69 vs. 137 ± 48 Kpa/cm2, P &lt; 0.01, respectively). We observed weak to moderate associations between the methods. After TAVR, LVEF corrected to ESWSecho, ESWSCT + echo and ESWSCT + Invasive increased (0.93 ± 0.07 vs. 1.91 ± 2.1, P = 0.013; 0.36 ± 0.19 vs. 0.58 ± 0.33, P &lt; 0.01, and 0.3 ± 0.02 vs. 2.5 ± 1.5, P &lt; 0.01, respectively). Conclusion ESWSecho, ESWSCT + echo and ESWSCT + Invasive decreased significantly after TAVR suggesting they reflect afterload, but independent of method, ESWS corrected LVEF increased slightly post-TAVR, indicating load dependency.

Abstract Aims This study aims to describe the prevalence of discordant mild/moderate aortic stenosis (AS) in a population-based study and to identify the mechanisms that lead to reduced stroke volume (SV) and discordant moderate AS. Methods and results Discordant high-gradient (HG)-mild AS, defined as AVA &gt; 1.5 cm2 and mean pressure gradient (MG) of 20–40 mmHg, and discordant low-gradient (LG) moderate AS, defined as AVA 1.0–1.5 cm2 and MG &lt; 20 mmHg, were assessed in 883 individuals from the DANCAVAS screening study with aortic valve calcification and 257 individuals form the PROGRESSA study excluding those with left ventricular (LV) ejection fraction &lt; 50%. In the DANCAVAS cohort, 150 men had mild/moderate AS of which 34% had discordance between MG and AVA, representing 66% with moderate AS. Among 262 patients in the combined cohort, 39% had discordant LG-moderate AS and 6% discordant HG-mild AS. Compared with concordant mild and moderate AS, individuals with discordant LG-moderate AS were more likely to present with LV concentric remodelling geometry (26 vs. 33 vs. 45%, P &lt; 0.001), increased valvulo-arterial impedance (3.3 ± 0.7 vs. 3.6 ± 0.5 vs. 4.1 ± 0.7 mmHg/mL/m2, P &lt; 0.001), and reduced systemic arterial compliance (SAC) (0.74 ± 0.22 vs. 0.81 ± 0.22 vs. 0.64 ± 0.18 mL/m2/mmHg, P &lt; 0.001). Factors associated with SV index were relative wall thickness, LV end-diastolic diameter index, SAC, and LV remodelling pattern. Conclusion Discordant moderate AS is common, accounting for two-thirds of patients with moderate AS in the general male population. Patients with discordant LG-moderate AS have predominantly a concentric remodelling pattern with reduced SV. Reduced SV index was associated with signs of reduced vascular compliance, suggesting that altered vascular properties drive differences in remodelling patterns and discordant moderate AS.