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Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long‐term follow‐up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre–transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post–transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25–1.90]; P

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT‐proBNP at baseline in 499 patients. Left ventricular ejection fraction 2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT‐proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Background P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI. Methods and Results This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) before the intervention period (preintervention); (2) after the intervention period (postintervention); or (3) at the 8 hospitals not contacted (concurrent controls). The intervention consisted of 4 components: (1) P2Y12 inhibitor delivered to patients’ bedside after PCI; (2) education on importance of P2Y12 inhibitors; (3) automated reminder telephone calls to refill medication; and (4) outreach to patients if they delayed refilling P2Y12 inhibitor. The primary outcomes were as follows: (1) proportion of patients with delays filling P2Y12 inhibitor at hospital discharge and (2) proportion of patients who were adherent in the year after PCI using pharmacy refill data. Primary analysis compared intervention with preintervention control patients. There were 1377 (intent‐to‐treat) potentially eligible patients, of whom 803 (per protocol) were approached at intervention sites versus 5910 preintervention, 2807 postintervention, and 4736 concurrent control patients. In the intent‐to‐treat analysis, intervention patients were less likely to delay filling P2Y12 at hospital discharge (−3.4%; 98.3% CI, −1.2% to −5.6%) and more likely to be adherent to P2Y12 (4.1%; 98.3% CI, 1.0%–7.1%) at 1 year, but had more clinical events (3.2%; 98.3% CI, 2.3%–4.1%) driven by repeated PCI compared with preintervention patients. In post hoc analysis looking at myocardial infarction, stroke, and death, intervention patients had lower event rates compared with preintervention patients (−1.7%; 98.3% CI, −2.3% to –1.1%). Conclusions A 4‐component intervention targeting P2Y12 inhibitor adherence was difficult to implement. The intervention produced mixed results. It improved P2Y12 adherence, but there was also an increase in repeat PCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609842.

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core‐laboratory‐measured LV mass index, cTnT, and NT‐proBNP. LVH was defined by sex‐specific guideline cut‐offs and elevated biomarker levels were based on age and sex cut‐offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all‐cause death out to 5 years. Elevated cTnT and NT‐proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P

Background: There is a paucity of data regarding the relationship between overall hospital volumes for total aortic valve replacement (AVR; transcatheter AVR [TAVR] or surgical AVR [SAVR]) and patient outcomes., Methods and Results: We queried the 2019 Nationwide Readmission Database for patients undergoing AVR. Based on procedural volumes of TAVR or SAVR, we classified hospitals as high (≥50th percentile) or low (<50th percentile) volume centers and categorized hospitals as high TAVR/high SAVR, high TAVR/low SAVR, high SAVR/low TAVR, and low TAVR/low SAVR. Multivariable regression models were employed. The main study outcomes were in-hospital mortality and 30-day readmission after total AVR. Our final analysis included 72 123 patients undergoing AVR at 400 hospitals across the United States. The median (interquartile range) hospital procedural volumes for total AVR, TAVR, and SAVR were 137 (86-210), 82 (50-127), and 56 (31-87) procedures, respectively. There was an inverse correlation between hospital procedural volumes of AVR, TAVR, or SAVR and in-hospital mortality after total AVR but not with 30-day readmission. Using high TAVR/high SAVR hospitals as reference, there was higher in-hospital mortality after total AVR among low TAVR/low SAVR hospitals (adjusted odds ratio [OR], 1.29 [95% CI, 1.07-1.56]) but similar in-hospital mortality among high TAVR/low SAVR hospitals and low TAVR/high SAVR volumes. There was no difference in 30-day readmission rates after total AVR among the 4 hospital categories., Conclusions: Nationwide data revealed that in-hospital mortality after total AVR (SAVR or TAVR) is inversely related to hospital total volumes of AVR. Patients with aortic stenosis have better outcomes if they are managed among experienced centers with high case volumes of both TAVR and SAVR.

Background: The role of echocardiography in deriving transvalvular mean gradients from transaortic velocities in aortic stenosis (AS) and in structural valve degeneration (SVD) is well established. However, reports following surgical aortic valve replacement, post-transcatheter aortic valve replacement (TAVR), and valve-in-valve-TAVR (ViV-TAVR) have cautioned against the use of echocardiography-derived mean gradients to assess normal functioning bioprosthesis due to discrepancy compared with invasive measures in a phenomenon called discordance., Methods: In a multicenter study, intraprocedural echocardiographic and invasive mean gradients in AS, SVD, post-native TAVR, and post-ViV-TAVR were compared, when obtained concomitantly, and discharge echocardiographic gradients were recorded. Absolute discordance (intraprocedural echocardiographic - invasive mean gradient) and percent discordance (intraprocedural echocardiographic - invasive mean gradient/echocardiographic mean gradient) were calculated. Multivariable regression analysis was performed to determine variables independently associated with elevated postprocedure invasive gradients ≥20 mm Hg, absolute discordance >10 mm Hg, and discharge echocardiographic mean gradient ≥20 mm Hg., Results: A total of 5,027 patients were included in the registry: 4,725 native TAVR and 302 ViV-TAVR. Intraprocedural concomitant echocardiographic and invasive mean gradients were obtained pre-TAVR in AS (n = 2,418), pre-ViV-TAVR in SVD (n = 101), in post-ViV-TAVR (n = 77), and in post-TAVR (n = 823). Echocardiographic and invasive mean gradients demonstrated strong correlation (r = 0.69) and agreement (bias, 0.11; 95% CI, -0.4-0.62) in AS, moderate correlation (r = 0.56) and agreement (bias, 1.08; 95% CI, -2.53 to 4.59) in SVD, moderate correlation (r = 0.61) and weak agreement (bias, 6.47; 95% CI, 5.08-7.85) post-ViV-TAVR, and weak correlation (r = 0.18) and agreement (bias, 3.41; 95% CI, 3.16-3.65) post-TAVR. Absolute discordance occurs primarily in ViV-TVR and is not explained by sinotubular junction size and increases with increasing echocardiographic mean gradient. Percent discordance in AS and SVD (1.3% and 4%, respectively) was lower compared with post-TAVR/ViV-TAVR (66.7% and 100%, respectively). Compared with self-expanding valves, balloon expanding valves were independently associated with elevated discharge echocardiographic but lower invasive mean gradient (odds ratio = 3.411, 95% CI, 1.482-7.852, P = .004; vs odds ratio = 0.308, 95% CI, 0.130-0.731, P = .008, respectively)., Conclusions: Post-TAVR/ViV-TAVR, echocardiography is discordant from invasive mean gradients, and absolute discordance increases with increasing echocardiographic mean gradient and is not explained by sinotubular junction size. Percent discordance is significantly higher post-TAVR/ViV-TAVR than in AS and SVD. Post-TAVR/ViV-TAVR, poor correlation and wide limits of agreement suggest echocardiographic and invasive mean gradients may not be used interchangeably and a high residual echocardiographic mean gradient should be confirmed invasively before considering any additional procedure to "correct" the gradient. Transcatheter aortic valve replacement valve types have variable impact on echocardiographic and invasive mean gradients., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of data regarding the comparative efficacy and safety of Mitral valve transcatheter edge-to-edge repair (MTEER) using the PASCAL or MitraClip systems for patients with mitral regurgitation (MR)., Methods: An electronic search was conducted for MEDLINE, COCHRANE, and EMBASE, through February 2023, for studies comparing the clinical outcomes of MTEER using PASCAL versus MitraClip systems among patients with severe MR. The primary study outcome was residual MR ≤ 2 at discharge. Data were pooled using a random-effects model., Results: The final analysis included six studies with a total of 1581 patients, with a weighted follow-up period of 3.5 months. Two studies only included patients with degenerative MR, while the remaining studies included both degenerative and functional MR. There was no significant difference in procedure duration between MTEER with the PASCAL or MitraClip systems. There was no difference in residual MR ≤ 2 at discharge (94.7% vs. 91.9%; odds ratio [OR]: 1.44; 95% confidence interval [CI]: 0.92-2.27) or residual MR ≤ 2 at the mid-term follow-up (94.6% vs. 91.0%, p = 0.05) among the PASCAL versus MitraClip systems. There was no difference between both groups in residual MR ≤ 1 at discharge (73.1% vs. 63.8%, p = 0.12), while there was greater incidence of residual MR ≤ 1 at midterm follow-up with the PASCAL system (71.3% vs. 56.2%, p < 0.001). There was no difference between the PASCAL and MitraClip MTEER systems in technical success (97.0% vs. 97.9%, p = 0.15), procedural success (89.1% vs. 87.1%, p = 0.78), single leaflet detachment (1.8% vs. 1.4%, p = 0.55), or all-cause mortality (3.6% vs. 4.6%, p = 0.71)., Conclusion: In this meta-analysis, we demonstrated comparable efficacy and safety between the PASCAL and MitraClip MTEER systems at short- and mid-term assessments. Randomized trials are warranted to evaluate the comparative long-term outcomes between both MTEER systems., (© 2023 Wiley Periodicals LLC.)