Danesh, Sina

Background Diastolic dysfunction is common in patients with aortic stenosis and may influence outcomes following surgical aortic valve replacement. We aimed to examine the association of preoperative artificial intelligence (AI)‐generated diastolic function grades with early and late outcomes following aortic valve replacement and how postoperative progression influence prognosis. Methods We identified 5503 patients undergoing aortic valve replacement between 2000 and 2023. Diastolic function was assessed using a validated deep‐learning AI model applied to 12‐lead ECGs done preoperatively and on postoperative follow‐up. Diastolic grades were classified by AI into Grades 1 to 3. Longitudinal trend analyses and multivariable regression models were used to assess study end points. Results Among 5503 patients (mean age 72.4±10.8 years; 39% female), higher AI ECG diastolic grades were associated with greater comorbidity burden, including diabetes, renal disease, and heart failure. AI ECG diastolic Grade 3 was independently associated with higher in‐hospital mortality (odds ratio, 2.5; P =0.007) and other complications. At 5‐year follow‐up, patients with Grade 3 showed the least improvement in diastolic function by both ECG and echocardiography. Grades 2 and 3 diastolic function at baseline were independently associated with increased late mortality (hazard ratio, 1.3 and 2.45, respectively; both P <0.001). Additionally, lack of improvement in AI ECG diastolic grade by 1 year was also independently associated with late mortality. Conclusions AI ECG–derived diastolic function grades strongly correlates with early complications and long‐term mortality and diastolic progression after aortic valve replacement. AI ECG provides a powerful, noninvasive tool for risk stratification and longitudinal monitoring of patients with aortic stenosis.

Background: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) is an increasingly preferred strategy for managing failed surgical bioprosthetic valves, especially in high-risk patients. However, limited data exist comparing outcomes between balloon-expandable (BE) and self-expandable (SE) transcatheter heart valves (THVs) in this setting. The influence of aortic annular area on outcomes by valve type remains poorly understood. This study evaluated the impact of annular area on clinical outcomes following ViV-TAVR with BE vs. SE valves. Methods: We conducted a retrospective, single-center analysis of 353 patients who underwent ViV-TAVR between 2012 and 2024. All had prior surgical bioprosthetic AVR and received either BE (n=267) or SE (n=86) valves. Preprocedural multidetector CT was used to quantify aortic annular area. Transthoracic echocardiography was performed before and after the procedure to assess transvalvular gradients and hemodynamics. The primary endpoint was all-cause mortality. Penalized spline regression was used to model the nonlinear relationship between annular area and mortality and assess interaction by valve type. Results: Median age was 79 (IQR: 72–83) in the BE group and 80 (IQR: 76–85) in the SE group (p=0.07). Female sex was more common in the SE group (32% vs. 22%, p=0.047). Median annular area was 374 mm2 (IQR: 316–440) for BE and 365 mm2 (IQR: 308–432) for SE (p=0.081). Preprocedural gradient and effective orifice area index were 36 mm Hg (IQR: 28–46) and 0.6 cm2/m2 (IQR: 0.5–0.9), respectively, with no significant differences. Median hospital stay was 2 vs. 3 days (p=0.68). Thirty-day mortality was low (1 per group, p=0.36). Median follow-up was 4.0 years (IQR: 1.6–6.4). One- and 5-year survival rates were 94.75% and 61.7%, respectively (p=0.20). Penalized spline analysis showed a nonlinear association between annular area and mortality. The hazard ratio for BE valves declined with increasing annular area and fell below SE valves beyond ~400 mm2. Conclusion: ViV-TAVR is a safe and effective treatment for failed surgical bioprostheses. Smaller annular areas were associated with higher mortality. Outcomes with BE valves improved in larger annuli, suggesting annular area could guide valve selection. Further studies are warranted to validate these observations.

Background Postoperative atrial fibrillation occurs in ~40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We evaluated the association of preoperative MRA use with postoperative atrial fibrillation and investigated atrial cell types modulated by MRAs during cold preservation. Methods We studied 19 042 cardiac surgery patients at Mayo Clinic. Propensity 1:3 matching identified 298 MRA users and 894 non‐users. A subgroup analysis of patients on any preoperative diuretic was performed to isolate cardiac‐specific effects of MRAs, matching 298 MRA users to 894 non‐MRA diuretic users. AF recurrence was assessed for up to 6‐years. Single‐nucleus RNA sequencing (snRNA‐seq) was performed on human donor atria exposed to canrenone (a water‐soluble MRA) during cold preservation with ex‐vivo reperfusion, and expression profiles were compared with atria from patients with AF. Results After matching, preoperative MRA use was associated with a lower incidence of postoperative atrial fibrillation (19.8% versus 31.8%, P <0.001). In the diuretic‐only subgroup, MRA users also had lower postoperative atrial fibrillation (19.8% versus 33.2%, P <0.001). MRA use was associated with a reduced incidence of paroxysmal and chronic AF at 6‐years. snRNA‐seq identified a cardiomyocyte subpopulation, CM2, with high mineralocorticoid receptor expression where canrenone suppressed cold preservation‐induced mineralocorticoid receptor target gene expression, which was conversely elevated in chronic AF. Canrenone also attenuated stress‐response in atrial macrophages and pericytes. Conclusions Preoperative MRAs were associated with reduced postoperative and long‐term AF after cardiac surgery. Mechanistically, our ex‐vivo human atrial model revealed that MRAs suppress mineralocorticoid receptor ‐driven atrial stress responses, particularly in conduction‐relevant cardiomyocytes.

Abstract Background New postoperative atrial fibrillation (POAF) occurs in about 40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We examined the impact of preoperative MRA use on POAF and also examine the atrial cell type impacted by MRA treatment during cold cardiac preservation. Methods Retrospective study of 19,042 patients who underwent cardiac surgery at Mayo Clinic in Minnesota, and performed 1:3 propensity matching to obtain 298 patients on preoperative MRA matched to 894 who were not. We also separately matched patients using preoperative diuretics. Single-nuclei RNA sequencing (snRNA-seq) examined MRA’s effects on different atrial cell types in canrenone (water soluble MRA) treated human donor hearts undergoing cold preservation followed by ex-vivo reperfusion and compared gene expression to the atria of patients with AF. Results Propensity matched preoperative MRA group had less new onset POAF (19.8% vs 31.5%, P<0.001). To account for the possibility that preoperative diuretic use and volume reduction may impact POAF, we propensity matched 298 preop diuretic users that included MRA use to another 894 patients who used a non-MRA diuretic preoperatively. Those who used preoperative MRA similarly had a lower incidence of POAF (19.8% vs 33.2%, P<0.001). No survival difference was present between the propensity matched groups that used preoperative diuretics (P=0.079). Preoperative MRA use also reduced the development of paroxysmal and chronic AF at 6 years of follow up. From our snRNA-seq data, we identified a subpopulation of atrial cardiomyocytes (CM2) that had high MR expression where canrenone suppressed the increase in MR target gene expression associated with cold preservation-reperfusion. These MR targets were conversely elevated in patients with chronic AF. Canrenone also suppressed other cardiac preservation associated genes that show elevated expression in atrial macrophages and pericytes from chronic AF atria. Conclusions Our studies show that preoperative MRA use is associated with 40% reduction in POAF as well as lowering long standing AF development by about 41%. Our cold cadiac preservation-reperfusion model showed that canrenone reduced expression of MR target genes associated with chronic AF, particular in cardiomyocytes with important roles in electrical conduction. Clinical Perspective What is New? This study shows that preoperative use of mineralocorticoid receptors antagonists (MRA) is associated with a reduced incidence of new onset perioperative atrial fibrillation after cardiac surgery utilizing cardiopulmonary bypass. We show that preoperative MRA use is associated with a lower incidence of developing more chronic paroxymal or sustained atrial fibrillation. Addition of canrenone, a clinically utilized water soluble MRA, to cardioplegia solution used during cardiac preservation can attenuate atrial inflammatory reponses and reduce signaling through molecular pathways that promote atrial fibrillation. What are the clinical implications? Perioperative use of MRAs may be considered to reduce early postoperative atrial fibrillation as well as lowering the risk of developing more chronic atrial arrhythmias. These findings support pursuing a clinical trial to determine the impact of MRA use on atrial arrhythmias following cardiac surgery in the setting of cardiopulmonary bypass with cold cardiac preservation.