Publications

BACKGROUND: Coronary access and neosinus washout are critical considerations following transcatheter aortic valve replacement (TAVR). However, the impact of transcatheter heart valve (THV) pathology on these factors remains unexplored.

OBJECTIVES: The aim of this study was to assess THV frame obstruction due to fibrotic tissue ingrowth and its potential impact on coronary access and neosinus flow.

METHODS: Thirty-four SAPIEN platform and 10 Evolut/CoreValve (EV/CV) platform explanted THVs were evaluated for frame cell obstruction. Patient data and clinical imaging were reviewed to assess relationships with frame fibrosis. Cannulation feasibility was assessed using 6-F catheter passage. Redo-TAVR was modeled using a SAPIEN 3 device implanted at EV/CV node 5. Histologic staining was performed to analyze endothelial-like cells, activated platelets, and fibrotic remodeling.

RESULTS: Across all explanted THVs, 79.5% of frame exhibited fibrotic ingrowth, with implant duration correlating with obstruction severity (P = 0.003). Fibrotic ingrowth was more commonly seen in the upper and lower regions of EV/CVs and in the upper cells adjacent to commissures in SAPIEN THVs. Fibrotic ingrowth prevented cannulation with a 6-F catheter in 13.0% of cells in areas of likely cannulation to achieve coronary access. Greater fibrotic ingrowth was associated with damage to native structure at THV explantation. Redo-TAVR models had reduced accessibility, with up to 76% unable to be fenestrated by a 6-F catheter. Frame adhesions were not detectable by standard clinical imaging. Histologic analysis demonstrated progressive granulation tissue formation, which became more organized in later explantations, with a median thickness of 0.5 mm.

CONCLUSIONS: Fibrotic THV frame ingrowth is a common phenomenon that may complicate THV explantation and impede neosinus washout and coronary access after TAVR.

BACKGROUND: Lower (<10 mm Hg) discharge echocardiographic mean gradients (MGs) following transcatheter aortic valve replacement with balloon-expandable valves are associated with lower ejection fraction and higher 5-year mortality compared with higher gradients. Using the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry, we studied the relationship between echocardiographic MG and patient prosthesis mismatch (PPM) following transcatheter aortic valve-in-valve replacement and clinical outcomes.

METHODS: Patients who underwent aortic valve-in-valve replacement with a balloon-expandable valve from July 2015 to December 2023 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were included. Adjusted Cox models with regression splines explored the relationship between MG and 5-year mortality. Kaplan-Meier estimates and adjusted hazard ratios compared the occurrence of 5-year mortality between gradient cutoffs and PPM presence.

RESULTS: A total of 13 054 patients were included; spline curves demonstrated a nonlinear relationship between discharge MG and 5-year mortality. Kaplan-Meier curves suggested higher 5-year mortality with MG <10 mm Hg compared with MG ≥10 mm Hg (hazard ratio, 1.15 [95% CI, 1.02-1.29]; P=0.024). MG <10 mm Hg was associated with lower ejection fraction compared with higher MG (50.4±13.9 versus 53.2±12.8; P<0.0001). Severe PPM and MG ≥20 mm Hg were not associated with worse 5-year outcomes compared with none/moderate PPM or MG ≤20 mm Hg, respectively.

CONCLUSIONS: Discharge MG <10 mm Hg is associated with lower ejection fraction and increased 5-year mortality following aortic valve-in-valve replacement compared with higher MG in a nonlinear fashion. Severe PPM and MG > 20 mm Hg were not associated with worse 5-year clinical outcomes. Incorporating data on ejection fraction with PPM and MG is important before determining the need for valve optimization.

Septal Scoring Along the Midline Endocardium (SESAME) is a recently developed electrosurgical, percutaneous myotomy technique. It was designed to prevent iatrogenic left ventricular outflow tract (LVOT) obstruction following transcatheter mitral valve replacement (TMVR) in patients with prohibitive surgical risk. SESAME can also be used to reduce LVOT obstruction in cases of obstructive hypertrophic cardiomyopathy (oHCM). Based on over 200 SESAME procedures at three experienced centers, we present a best practice step-by-step echocardiography-guided approach, emphasizing key anatomical and procedural features. Given the complexity of the electrosurgical approach, protocol-driven imaging is essential to ensure procedural safety and optimize outcomes.

BACKGROUND: Second-generation aldosterone-synthase inhibitors (ASIs) may offer a novel treatment for hypertension.

OBJECTIVES: The objective of the study was to assess the efficacy and safety of ASIs in this clinical setting.

METHODS: We searched major databases for randomized controlled trials (RCTs) assessing ASIs (baxdrostat, lorundrostat, and vicadrostat) in patients with hypertension. For efficacy outcomes, mean differences (MD) with 95% credible intervals (CrIs) were estimated using a Bayesian random-effects model. For adverse events, OR with 95% CrI were estimated using a Bayesian binomial-normal hierarchical model. The protocol was registered in Prospective Register of Systematic Reviews (CRD420251132306).

RESULTS: Eight RCTs were included (n = 3,369; 2,430 [72%] randomized to ASI). ASI reduced systolic blood pressure (SBP) (MD: -6.7 mm Hg; CrI: -8.78, -4.59; τ2 3.24), diastolic blood pressure (MD: -2.09 mm Hg; CrI: -3.68, -0.44; τ2 1.44), and hypertensive urgency (OR: 0.36; CrI: 0.13, 0.90; τ2 0.07) compared with placebo. There was no difference in all-cause mortality (OR: 0.45; CrI: 0.06, 3.20; τ2 0.10) or adrenal insufficiency (OR: 0.5; CrI: 0.1, 3.1; τ2 0.3) between groups. However, ASIs increased the odds of hyperkalemia (OR: 7.1; CrI: 3.56, 15.2; τ2 0.23), hyponatremia (OR: 2.6; CrI: 1.25, 5.98; τ2 0.1), and hypotension (OR: 3.28; CrI: 1.43, 8.16; τ2 0.1). In subgroup analysis, the probability of achieving a clinically meaningful reduction in SBP (MD < -5 mm Hg) was 87.5% with baxdrostat and 94.3% with lorundrostat.

CONCLUSIONS: Second-generation ASIs had a high likelihood of a clinically significant reduction in SBP compared with placebo. However, hyperkalemia, hyponatremia, and hypotension were more frequent with ASIs.

We discuss generalizability analyses under a partially nested trial design, where part of the trial is nested within a cohort of trial-eligible individuals, while the rest of the trial is not nested. This design arises, for example, when only some centers participating in a trial are able to collect data on non-randomized individuals, or when data on non-randomized individuals cannot be collected for the full duration of the trial. Our work is motivated by the Necrotizing Enterocolitis Surgery Trial, which compared initial laparotomy versus peritoneal drain for infants with necrotizing enterocolitis or spontaneous intestinal perforation. During the first phase of the study, data were collected from randomized individuals as well as consenting non-randomized individuals; during the second phase of the study, however, data were only collected from randomized individuals, resulting in a partially nested trial design. We propose methods for generalizability analyses with partially nested trial designs. We describe identification conditions and propose estimators for causal estimands in the target population of all trial-eligible individuals, both randomized and non-randomized, in the part of the data where the trial is nested while using trial information spanning both parts. We evaluate the estimators in a simulation study and provide an illustration using the Necrotizing Enterocolitis Surgery Trial study.