Schaff, Hartzell

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.

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 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.

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.

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.

BACKGROUND: Pharmacological treatments for fibrocalcific aortic valve stenosis (FCAVS) have been elusive for >50 years. Here, we tested the hypothesis that reactivation of oxidized sGC (soluble guanylate cyclase), the primary receptor for nitric oxide, with ataciguat is a safe and efficacious strategy to slow progression of FCAVS. METHODS: We used quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry to characterize sGC signaling and the biological effects of ataciguat on signaling cascades related to nitric oxide, calcification, and fibrosis in excised human aortic valve tissue, aortic valve interstitial cells, and mouse aortic valves. We then conducted randomized, placebo-controlled phase I (14-day safety/tolerance) and phase II (6-month efficacy) trials in patients with moderate aortic valve stenosis. RESULTS: In excised human tissue, we found robust losses in sGC signaling despite upregulation of sGC subunits. In vitro, ataciguat increased sGC signaling and reduced BMP2 (bone morphogenetic protein 2) signaling in aortic valve interstitial cells. In mice with established FCAVS, treatment with ataciguat attenuated BMP signaling and slowed progression of valve calcification and dysfunction. In a phase I, randomized, placebo-controlled trial, treatment with ataciguat for 2 weeks was safe and well tolerated in patients with moderate FCAVS ( https://www.clinicaltrials.gov ; Unique identifier: NCT02049203). In a separate phase II, randomized, placebo-controlled trial, treatment with ataciguat for 6 months slowed the progression of aortic valve calcification and tended to slow the progression of valvular and ventricular dysfunction in patients with moderate FCAVS ( https://www.clinicaltrials.gov ; Unique identifier: NCT02481258). CONCLUSIONS: Collectively, this study highlights the therapeutic potential of the targeted restoration of the diseased/inactive form of sGC for treatment of FCAVS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02049203. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02481258.

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov ; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128. METHODS: A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128. RESULTS: At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years). CONCLUSIONS: In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04349072.