Schaff, Hartzell V.

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.

Importance Current guidelines recommend consideration of surgical treatment for asymptomatic patients with severe mitral valve regurgitation, but the long-term prognosis and optimal treatment of those with moderate mitral regurgitation (MR) remain uncertain. Objective To evaluate the long-term prognostic value of baseline MR severity and the association of surgery with survival outcomes in asymptomatic patients. Design, Setting, and Participants This was a prospective cohort study with extended follow-up among 449 asymptomatic patients with holosystolic degenerative MR enrolled between January 1991 and November 2000 and followed up with through May 2025 (median [IQR] follow-up, 26 [14-29] years; maximum, 34 years) at a single tertiary referral center (the Mayo Clinic, Rochester, Minnesota). Exposure Baseline MR severity quantified by effective regurgitant orifice area (ERO). Patients were monitored under medical therapy and, when applicable, after subsequent surgical correction. Main Outcomes and Measures All-cause mortality, assessed according to baseline ERO using Cox proportional hazards models adjusted for cardiovascular risk factors. Results Among the 449 patients included, the mean (SD) age was 64 (14) years, and 278 participants (62%) were male. At baseline, 127 patients (28%) had ERO &amp;lt;20 mm 2 , 128 (28%) had ERO 20-39 mm 2 , and 194 (43%) had ERO ≥40 mm 2 . During follow-up, 254 patients (57%) underwent mitral valve surgery. Ten-year cumulative incidence of surgery was 18% for ERO &amp;lt;20 mm 2 , 64% for 20-39 mm 2 , and 88% for ≥40 mm 2 . Survival of medically treated patients declined progressively with increasing ERO category (5-year rate: 88% [&amp;lt;20 mm 2 ], 72% [20-39 mm 2 ], and 55% [≥40 mm 2 ]; P = .01), and multivariable analysis confirmed the incremental risk of higher ERO on a continuous scale (adjusted hazard ratio per IQR increase, 2.53; 95% CI, 1.30-4.93; P = .01). When extending the analysis through subsequent surgical follow-up, the survival difference between patients who did vs did not undergo operation widened with ERO (χ 2 3 = 8.4; interaction P = .04), starting at values above 30 mm 2 . Conclusions and Relevance In this 25-year follow-up cohort study, increasing ERO was associated with an increase in risk of mortality under medical therapy. Patients with upper-moderate MR (ERO 30-39 mm 2 ) at baseline demonstrated a significant association between surgical treatment and improved long-term survival.

Abstract Objectives This study examined the indications, frequency, and outcomes of cardiac surgery following transcatheter aortic valve replacement (TAVR) at a single institution. As TAVR volumes increase, understanding the nature and outcomes of subsequent cardiac operations is critical, particularly as the procedure expands to younger, lower-risk populations. Methods We analysed outcomes of 61 patients who underwent cardiac surgery after TAVR at our institution from August 2011 to September 2023, excluding periprocedural complications and staged procedures. Patients were stratified into 2 groups: those requiring surgical aortic valve replacement (SAVR) with or without concomitant procedures (n = 33) and those undergoing non-SAVR cardiac operations (n = 28). Data were collected from a prospectively maintained cardiovascular surgery database and electronic health records. Indications for surgery, operative characteristics, and outcomes were analysed, with survival assessed using Kaplan-Meier estimates. Results The median interval between TAVR and cardiac surgery was 19 months. Indications for SAVR included infective endocarditis (36%), non-structural valve deterioration (36%), structural valve deterioration (12%), and valve thrombosis (6%). Non-SAVR operations primarily addressed mitral valve disease (43%) and coronary artery disease (29%). Operative mortality was 6.6%, with no deaths in the endocarditis subgroup. Postoperative complications included prolonged mechanical ventilation (18%), new-onset renal failure (7%), and stroke (2%). Kaplan-Meier survival estimates were 83% at 1 year and 50% at 5 years. Conclusions Although complex, cardiac operations in patients who have undergone TAVR can be performed with acceptable mortality rates. Structural valve deterioration, paravalvular leak, and endocarditis were the primary indications for SAVR, while mitral valve and coronary artery disease predominated in non-SAVR cases. These findings highlight the importance of considering nonaortic valve pathologies in TAVR planning, particularly as the procedure expands to younger, lower-risk populations.

Abstract Myocardial bridging is the most common congenital coronary anomaly, characterized by an intramyocardial course of a segment of an epicardial coronary artery, with considerable variability in its depth and length. In most cases, MB is a benign anatomical variant without clinical significance, often asymptomatic and not requiring treatment. However, with the increasing use of coronary computed tomography angiography for coronary assessment, myocardial bridging is now more frequently identified during non-invasive imaging. It can also be diagnosed via invasive coronary angiography, where it appears as a dynamic systolic compression of the tunnelled artery segment, and further anatomical characterization can be enhanced by intravascular ultrasound or optical coherence tomography. Growing recognition of myocardial bridging’s role in ischaemia with non-obstructive coronary arteries has heightened clinical interest in its prevalence, diagnostic strategies, and management approaches. As such, this narrative review provides clinicians with an updated, evidence-based guide to the diagnosis and therapeutic management of myocardial bridging, while also addressing ongoing controversies and areas of uncertainty.

Background: Several studies have described anteroapical displacement of the anterolateral papillary muscle (PM) in patients with hypertrophic cardiomyopathy (HCM), implying a role in left ventricular outflow tract obstruction. Some surgeons address PM position during myectomy, but no quantitative imaging measures of abnormal versus normal PM anatomy exist. Objective: To quantify PM anatomy in HCM using cardiac magnetic resonance imaging (CMR) and determine if differences in PM anatomy alter myectomy outcomes. Methods: 143 patients with HCM (median age 58 (IQR 48-65) years, 64% male) who had undergone CMR were compared to 50 healthy controls (median age 32 (IQR 28-50) years, 40% male). The HCM cohort included 50 patients with non-obstructive HCM, 50 with obstructive HCM requiring transaortic myectomy, and 43 with obstructive HCM requiring transapical myectomy. Six independent measurements of PM anatomy were performed (Figure), comprising both established and novel measurements. Intergroup comparisons were made, and correlative analysis of PM measurements was performed using echocardiographic data and surgical outcomes. Results: There was significant variability in PM anatomy in all patients. The SXAd measurement was smaller (26.76 +/- 6.10 mm vs 32.10 +/- 4.85 mm, p < 0.001) in HCM patients versus controls. The 4Cd measurement was smaller in patients with apical HCM than in all other groups (p < 0.001). D_PM, d_apex, and the ratio between these measurements were consistent among all groups. No PM quantification in HCM patients correlated to pre-, intra-, or postoperative LVOT obstruction, NYHA class, or postoperative length of stay. Conclusions: Although there were some statistically significant differences between healthy patients and those with HCM, analysis of six different PM measurements yielded no associations with LVOT obstruction or outcomes of septal myectomy.

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.

Myocardial Bridging (MB) is typically a benign congenital coronary anomaly. MB can infrequently result in complications such as myocardial ischemia, arrhythmias, and sudden cardiac death. Recent studies suggest an underlying genetic component for MB involving DES, FBN1, SCN2B, or NOTCH1. The role of percutaneous coronary intervention (PCI) in managing MB, compared to optimal medical therapy (OMT), remains uncertain. Our study used the National Inpatient Sample (NIS) Database to identify patients aged 18 or older with myocardial bridging who were managed with PCI versus medical therapy. We compared the outcomes between both groups including in-hospital mortality, the trend of management of MB and other in-hospital outcomes or complications. Our results showed no statistically significant difference between both subgroups when comparing in-hospital mortality and secondary outcomes of cardiac arrest and the development of an acute kidney injury (AKI). Patients with myocardial bridging treated with PCI had a higher risk of developing cardiogenic shock, requiring LVAD, and requiring the use of intra-aortic balloon pump (IABP) compared to the medical therapy subgroup. Our study suggests the decision to perform PCI in myocardial bridging patients should be individualized such as in patients with refractory symptoms despite medical therapy or those with known high-risk features.

Activation of soluble guanylate cyclase (sGC), a key downstream target of nitric oxide (NO) signaling, is reduced in valve tissue from patients with fibrocalcific aortic valve stenosis (FCAVS). We hypothesized that restoring NO signaling pathway using Ataciguat (ATA)—an activator of oxidized sGC—would slow progression of aortic valve calcification. To determine whether Ataciguat attenuates bone morphogenetic protein (BMP2) signaling in vitro, we treated mouse aortic valve interstitial cells with exogenous BMP2(200ng/ml) with or without ATA(10nm), and demonstrated that ATA significantly reduced canonical BMP2 signaling by more than 50% (p< 0.01). To determine whether Ataciguat slows progression of FCAVS in vivo , ldlr -/- /apoB 100/100 mice were assigned to one of two groups:1) 9 months of western diet feeding (WD), or 2) 6 months of WD followed by 3 months of WD + ATA (5mg/kg ATA). In this model, Ataciguat attenuated BMP signaling in aortic valve tissue (p < 0.05), reduced aortic valve calcification (p < 0.05), and prevented progression of aortic valve dysfunction (p < 0.05). Finally, to determine whether ATA slows progression of calcification in humans, we treated patients with mild-to-moderate FCAVS with placebo or ATA (200 mg/day) for 6 months. In this Phase II clinical trial, ATA significantly slowed progression of aortic valve calcification (computed tomography imaging; p = 0.05) and also tended to slow progressive reductions in aortic valve area and valvular stenosis. Collectively, we believe this is the first study to demonstrate the pre-clinical and clinical utility of pharmacologically stimulating sGC to attenuate osteogenic signaling and slow progression of aortic valve disease in mice and humans, and creates a unique opportunity for larger trials focused on the effectiveness of this strategy to delay or prevent surgery in FCAVS.

BACKGROUND: Bioprosthetic valve dysfunction and reoperations/reinterventions are common after aortic valve replacement (AVR) with bioprosthetic valves, leading to cycles of left ventricular (LV) pressure overload and unloading. The purpose of this study was to compare postoperative changes in LV structure and function and their relationship to clinical outcomes in young patients who underwent AVR with bioprosthetic valves (Bio_AVR group) versus mechanical prosthetic valves (Mech_AVR group). METHODS: Retrospective study of adults with congenital heart disease who underwent AVR at Mayo Clinic (2003–2023). The Bio_AVR group was matched 1:2 to the Mech_AVR group. LV indices (LV mass index, relative wall thickness, LV global longitudinal strain, averaged e′, and averaged E/e′) and clinical indices (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and New York Heart Association class) were assessed preoperatively, and at 1, 5, and 10 years post-AVR. RESULTS: We studied 151 and 302 patients in the Bio_AVR and Mech_AVR groups, respectively (age 38±16 years, 58% males). Both groups had similar LV and clinical indices at baseline and 1 year post-AVR. However, the Bio_AVR group had higher LV mass index, relative wall thickness, and averaged E/e′, and lower averaged e′ and LV global longitudinal strain at 5 and 10 years post-AVR. Of 51 patients from the Bio_AVR group who underwent a second AVR, there was less robust improvement in LV indices and clinical indices after the second AVR compared with the first AVR. CONCLUSIONS: AVR with a bioprosthetic valve was associated with progressive LV hypertrophy and dysfunction, and worsening clinical status compared with mechanical prosthetic valves. This provides further evidence against the use of bioprosthetic AVR in young patients.