Ravn, Emil Johannes

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 > 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.

BACKGROUND Patients with severe aortic stenosis (AS) exhibit heterogeneous flow-gradient hemodynamics and ventricular remodeling, which may influence symptomatic, functional, and structural responses to transcatheter aortic valve implantation (TAVI). Thus, we evaluated differences in functional recovery and reverse remodeling after transfemoral TAVI across flow-gradient phenotypes. METHODS In this sub-study of the COMPARE-TAVI 1 trial, 975 patients undergoing transfemoral TAVI were classified as classical low-flow low-gradient (cLFLG, 9.1%), paradoxical low-flow low-gradient (pLFLG, 7.7%), low-flow high-gradient (24.7%), normal-flow low-gradient (NFLG, 13.0%), and normal-flow high-gradient (45.4%). The primary functional outcome was longitudinal change in six-minute walk test distance (6MWTD) from baseline to 1 year follow-up. Secondary endpoints included changes in NYHA functional class and reverse remodeling from baseline to 1 year follow-up along with the incidence and risk of all-cause death and a composite MACE-endpoint. RESULTS Mean 6MWTD increased by 59±4 meters at 1-month (p=0.000) with no additional improvement at 1-year, but with heterogeneity between groups (p=0.000). Improvements among NFLG, cLFLG and low-flow high-gradient AS were comparable with normal-flow high-gradient AS, while pLFLG AS exhibited significantly increments at 1-year (−28±15 meters, p=0.007). Patients with NFLG, cLFLG and pLFLG were more symptomatic at baseline (NYHA ≥III: 40.5%, 57.3% and 50.6%, respectively, p=0.000). NYHA improved in all groups at 1-year follow-up (p=0.000), although persistent symptoms at 1-year were most frequent in pLFLG (NYHA ≥II; 38.7%, p=0.012). Reverse remodeling was also comparable between normal-flow high-gradient AS and NFLG, cLFLG, and low-flow high-gradient AS, respectively, but attenuated in pLFLG AS in both unadjusted and adjusted analyses. No differences were observed in the incidence and risk of all-cause death or the composite MACE-endpoint. CONCLUSION TAVI associates with functional recovery across all flow-gradient phenotypes, although with heterogeneous responses. Patients with NFLG showed comparable functional recovery and reverse remodeling at 1-year follow-up compared with normal-flow high-gradient AS, whereas pLFLG demonstrated attenuated benefits across all parameters.

Abstract Objectives The study aimed to compare long-term outcomes of the David and Yacoub valve-sparing aortic root replacement (VSARR) procedures in a nationwide, low-volume setting. Methods All patients undergoing elective VSARR in Denmark between January 2010 and April 2022 were identified using the Danish registries. The primary end-point was all-cause death. Secondary end-points included stroke, reoperation, a composite of death or reoperation, and long-term echocardiographic outcomes. Analyses were performed in both crude and propensity score-matched (PSM) populations and compared with outcomes from a control group comprised of all elective composite root replacement procedures performed at the contributing centres in the study period. Results A total of 160 patients underwent VSARR (median age; David vs Yacoub; 49.7 [SD 14.1] years vs 51.5 [SD 14.3] years; P = .42) with the David (n = 92, 57.5%; median follow-up 8.2 [SD 3.6] years) or Yacoub (n = 68, 42.5%; median follow-up 7.1 [SD 2.4] years) procedure. Ten-year all-cause death was similar (David 9.3% [95% CI: 2.3-15.2] vs Yacoub 8.8% [95% CI: 3.6-20.6]; log-rank P = .54). Reoperation rates (log-rank P = .12), stroke incidence (P = .41), and the composite end-point of death or reoperation (log-rank P = .63) were comparable, with consistent findings in the PSM cohort. Long-term echocardiographic follow-up demonstrated no difference in recurrent regurgitation, stenosis, or valve-related complications. Compared to elective composite root replacement (CRR) (n = 486), VSARR demonstrated lower rate of all-cause death (P = .027) and stroke (P = .026), while reoperation rate was higher (13.8% vs 4.3%; P < .001). However, the risk of reoperation was comparable between procedures when accounting for competing risk of death (log-rank P = .17). Conclusions Long-term outcomes following elective VSARR using the David and Yacoub procedure were comparable. VSARR was associated with lower risk of all-cause death and stroke compared to elective CRR, supporting the two VSARR procedures as durable options when performed in experienced centres with careful patient selection, even in low-volume settings.

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 > 0 (n=1502 with 0 < AVC < 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 < AVC < 300: n = 1217 (81%), AVC ≥ 300: n = 163 (85%), p = 0.009). Higher body mass index (OR: 1.03 (1.02-1.04), p < 0.001), statin use (OR: 1.49 (1.24-1.80), p <0.001), low-density lipoprotein (OR: 1.24 (1.12 - 1.37), p < 0.001), and kidney dysfunction, measured as urine albumine-creatinine ratio (OR: 1.00 (1.00-1.00), p <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.

Background The hemodynamic profile and remodeling patterns of paradoxical low‐flow, low‐gradient aortic stenosis are well understood. However, some patients with severe aortic stenosis exhibit eccentric remodeling with enlarged left ventricular cavities, enabling a normal flow, low ejection fraction ( NF ‐ LEF ) phenotype. We assessed the prevalence, hemodynamic characteristics, and post‐transcatheter aortic valve implantation outcomes of NF ‐ LEF . Methods In this substudy of the COMPARE‐TAVI 1 trial, 979 patients undergoing transfemoral transcatheter aortic valve implantation were stratified by left ventricular ejection fraction (LVEF) (< or ≥50%) and stroke volume index (< or ≥35 mL/m 2 ) into 4 groups: normal flow, normal LVEF, NF‐LEF, low flow, normal ejection fraction, and low flow, low ejection fraction. Results NF‐LEF was observed in 10.7% of patients. Reduced LVEF was associated with previous myocardial infarction, pacemakers, New York Heart Association class >2, atrial fibrillation, moderate or worse mitral regurgitation, and larger left ventricular cavities ( P <0.001) with eccentric hypertrophy ( P =0.004). Compared with low‐flow, low‐ejection fraction, patients with NF‐LEF more frequently had moderate or worse aortic regurgitation ( P =0.007), whereas low flow, low ejection fraction showed poorer diastolic indices, suggesting diastolic dysfunction with high left ventricular filling pressures. Patients with low flow, normal ejection fraction were the most symptomatic and showed less improvement in 6‐minute walk distance at 1 year compared with normal flow, normal ejection fraction. During follow‐up, both low‐flow groups demonstrated significant increases in stroke volume index ( P <0.001), whereas LVEF also improved among patients with reduced LVEF ( P <0.001). Conclusions NF‐LEF is a prevalent aortic stenosis phenotype characterized by preserved flow despite reduced LVEF, likely driven by eccentric remodeling with moderate or worse aortic regurgitation and more favorable diastolic properties, with similar survival and time‐to‐event outcomes across phenotypes after transcatheter aortic valve implantation at long‐term follow‐up. Despite higher comorbidity burdens, patients with NF‐LEF showed functional and clinical improvements comparable with normal flow, normal ejection fraction, indicating a severe aortic stenosis phenotype.

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.