Daily Cardiology Research Analysis
Three studies advance structural and preventive cardiology: left atrial appendage occlusion (LAAO) during cardiac surgery reduced cardioembolic stroke features, disability, and 30-day mortality; a large multicenter TEER registry identified a postprocedural left atrial v-wave >25 mmHg as a strong predictor of 3-year mortality; and elevated lipoprotein(a) independently predicted stenotic structural valve degeneration of aortic bioprostheses with a dose–response relationship.
Summary
Three studies advance structural and preventive cardiology: left atrial appendage occlusion (LAAO) during cardiac surgery reduced cardioembolic stroke features, disability, and 30-day mortality; a large multicenter TEER registry identified a postprocedural left atrial v-wave >25 mmHg as a strong predictor of 3-year mortality; and elevated lipoprotein(a) independently predicted stenotic structural valve degeneration of aortic bioprostheses with a dose–response relationship.
Research Themes
- Perioperative stroke prevention via LAAO in atrial fibrillation
- Hemodynamic targets after mitral TEER (left atrial v-wave) and outcomes
- Biomarker-driven risk of bioprosthetic valve degeneration (lipoprotein(a))
Selected Articles
1. Stroke Mechanism and Severity After Left Atrial Appendage Occlusion: Insights From the LAAOS III Randomized Clinical Trial.
In a post hoc analysis of the LAAOS III RCT, adding surgical LAAO to standard cardiac surgery in AF patients reduced disability (lower mRS), 30-day post-stroke mortality, cortical infarcts, and presumed cardioembolic strokes among those who sustained an ischemic stroke. These data mechanistically support LAAO’s stroke prevention benefits beyond simple incidence reduction.
Impact: Clarifies that LAAO not only lowers stroke incidence but also shifts mechanism away from cardioembolism and improves early outcomes, reinforcing its role during concomitant cardiac surgery in AF.
Clinical Implications: For AF patients undergoing cardiac surgery, concomitant LAAO should be considered to reduce cardioembolic stroke features, disability, and early mortality. Stroke teams can anticipate fewer cortical, cardioembolic-phenotype infarcts after LAAO.
Key Findings
- LAAO reduced modified Rankin Scale scores at day 7/discharge (common OR 0.80, 95% CI 0.65-0.99).
- Lower 30-day mortality after stroke with LAAO (16.5% vs 20.1%; HR 0.55, 95% CI 0.31-0.97).
- Fewer cortical infarcts on imaging (46.2% vs 61.3%; −15.2%, 95% CI −26.7% to −3.7%).
- Lower proportion of presumed cardioembolic ischemic strokes (42.9% vs 57.9%; −15.1%, 95% CI −26.5% to −3.7%).
Methodological Strengths
- Secondary analysis nested in a large, multicenter randomized trial (LAAOS III) with adjudicated outcomes.
- Robust imaging-based phenotyping of stroke subtypes and standardized functional outcome (mRS).
Limitations
- Post hoc exploratory nature; not randomized for stroke severity endpoints.
- Findings limited to AF patients undergoing cardiac surgery; generalizability to percutaneous LAAO or non-surgical cohorts is uncertain.
Future Directions: Prospective, pre-specified analyses comparing LAAO vs no LAAO on stroke phenotypes; mechanistic imaging and embolic source studies; applicability to percutaneous LAAO populations.
IMPORTANCE: In the Left Atrial Appendage Occlusion Study III (LAAOS III), surgical occlusion of the LAA during cardiac surgery for patients with known history of atrial fibrillation (AF) substantially reduced the risk of stroke. OBJECTIVE: To assess the impact of LAAO on ischemic stroke subtype and outcome. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc exploratory analysis of the LAAOS III randomized clinical trial. Data were adjudicated from June 28, 2023, to November 29, 2023, and the main analyses took place from December 18, 2023, to April 29, 2024. The LAAOS III trial recruited participants from 105 centers in 27 countries between July 2012 and October 2018. Patients with AF and a CHA2DS2-VASc score of at least 2 undergoing cardiac surgery for other indications were included in the analysis. INTERVENTIONS: Surgical LAAO plus standard care vs standard care alone. MAIN OUTCOMES AND MEASURES: For strokes occurring during the trial, the functional outcome as measured by the modified Rankin Scale (mRS) score at day 7 or discharge, mortality, the presence of cortical infarcts, and the occurrence of infarcts of presumed cardioembolic origin were examined. RESULTS: Of 4811 participants in the LAAOS III trial followed up for 3.8 years, 273 had a first ischemic stroke. The mean (SD) age of participants at the time of the first ischemic stroke was 75 (7) years, 104 were female (38%), and 169 were male (62%). Participants allocated to receive LAAO had reduced (common odds ratio [OR], 0.80; 95% CI, 0.65-0.99) mRS scores at 7 days or discharge and a lower risk for mortality at 30 days (16.5% vs 20.1%; hazard ratio [HR], 0.55; 95% CI, 0.31-0.97) after a stroke event. Participants allocated to LAAO had fewer cortical infarcts on neuroimaging (46.2% vs 61.3%; difference in proportions: -15.2%; 95% CI, -26.7% to -3.7%), as well as a lower proportion of ischemic strokes of presumed cardioembolic etiology when compared with ischemic strokes in the no-LAAO group (42.9% vs 57.9%; difference in proportions: -15.1%; 95% CI, -26.5% to -3.7%). CONCLUSIONS AND RELEVANCE: This study found that LAAO in patients with AF undergoing cardiac surgery was associated with a decreased risk of presumed cardioembolic stroke, reduced disability, and mortality from stroke. These findings underscore the benefit of LAAO for patients with AF undergoing cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01561651.
2. Impact of Left Atrial v-Wave Following Mitral Edge-to-Edge Repair on Survival: The MITRA-PRO Registry.
In 1,487 TEER patients, increased postprocedural left atrial v-wave was associated with worse 3-year survival, with a threshold v-wave >25 mmHg predicting higher mortality. Patients achieving v-wave ≤25 mmHg had the lowest mortality, supporting v-wave as an actionable hemodynamic target during TEER optimization.
Impact: Defines a clear, measurable intraprocedural hemodynamic target (v-wave ≤25 mmHg) linked to long-term survival, enabling procedural guidance and residual MR assessment beyond imaging alone.
Clinical Implications: During TEER, aim to reduce the left atrial v-wave to ≤25 mmHg via clip optimization, adjunctive maneuvers, or addressing residual MR. Incorporate v-wave into multimodal residual MR assessment for risk stratification.
Key Findings
- Post-TEER increased v-wave associated with reduced 3-year survival.
- A v-wave threshold >25 mmHg predicted higher 3-year mortality by ROC analysis.
- Patients with postprocedural v-wave ≤25 mmHg had significantly lower 3-year mortality than those >25 mmHg.
Methodological Strengths
- Large-scale, multicenter registry with standardized hemodynamic assessment.
- Clear clinical endpoint (3-year mortality) and data-driven threshold identification.
Limitations
- Observational design precludes causal inference; residual confounding possible.
- Details of concomitant therapies and device iterations may influence v-wave and outcomes.
Future Directions: Prospective studies testing v-wave–guided TEER optimization strategies; integration with imaging and pulmonary vein flow to refine residual MR assessment; evaluate impact on hospitalization and quality of life.
BACKGROUND: Transcatheter edge-to-edge repair (TEER) for mitral regurgitation has been shown to affect left atrial pressure (LAP). However, the prognostic significance of postprocedural LAP changes remains a matter of debate. We aimed to evaluate the impact of v-wave on long-term survival after TEER. METHODS: A total of 1487 patients in the large-scale, multicenter MITRA-PRO (MITRAclip PROgnosis) registry with post-mitral TEER v-wave assessment were included in this study. RESULTS: After 3-years, survival was significantly reduced in patients with increased v-wave after mitral TEER, while patients with decreased v-wave showed the lowest 3-year mortality. A receiver operating characteristic analysis revealed a postprocedural v-wave >25 mm Hg as a relevant predictor of 3-year mortality following mitral TEER. Three-year mortality was significantly lower in patients with a v-wave ≤25 mm Hg indicating a postprocedural v-wave >25 mm Hg as a negative predictor of long-term survival (v-wave ≤25 mm Hg group: 34.2% versus v-wave >25 mm Hg group: 46.8%; CONCLUSIONS: A postprocedural v-wave >25 mm Hg is linked to reduced long-term survival. Multimodal residual mitral regurgitation assessment including v-wave supports the interventionalist in TEER guidance and optimizing procedural results aiming for decreasing v-wave to <25 mm Hg. REGISTRATION: URL: https://drks.de/search/en/trial/DRKS00012288; German Clinical Trials Register identifier: DRKS00012288.
3. Lipoprotein(a) and long-term structural valve degeneration of aortic bioprostheses.
In 174 patients after bioprosthetic AVR with 7.3 years median follow-up, elevated Lp(a) independently predicted long-term SVD, particularly stenotic/mixed phenotypes, with a linear dose–response (13% higher risk per 25 nmol/L). No association was seen with regurgitant SVD, positioning Lp(a) as a phenotype-specific biomarker and therapeutic target.
Impact: Links a modifiable biomarker to prosthetic valve stenotic degeneration with dose–response, generating a testable hypothesis for Lp(a)-lowering therapies to enhance bioprosthesis durability.
Clinical Implications: Consider measuring Lp(a) in patients receiving or following bioprosthetic AVR to refine long-term SVD risk, particularly for stenotic/mixed phenotypes, and to inform surveillance intensity and candidacy for emerging Lp(a)-lowering agents.
Key Findings
- Elevated Lp(a) (>125 nmol/L) associated with higher overall SVD risk (SHR 2.06, 95% CI 1.09-3.91).
- Stronger association with stenotic/mixed SVD phenotypes (adjusted SHR 3.00, 95% CI 1.48-6.07).
- No association with regurgitant SVD (SHR 0.85, 95% CI 0.19-3.92).
- Linear dose–response: each 25 nmol/L increase in Lp(a) conferred 13% higher risk.
Methodological Strengths
- Longitudinal follow-up with repeated echocardiography (1,372 studies) and VARC-3 SVD definitions.
- Competing risk modeling (Fine–Gray) and spline analyses capturing dose–response.
Limitations
- Single-center cohort with modest sample size; residual confounding possible.
- Observational design cannot confirm causality or therapeutic benefit of Lp(a) lowering.
Future Directions: Prospective multicenter validation and randomized trials testing Lp(a)-lowering therapies (e.g., antisense/siRNA) for preventing stenotic SVD; mechanistic imaging (CT calcium) and histopathology to link Lp(a) to leaflet calcification.
AIMS: Structural valve degeneration (SVD) is the leading cause of late bioprosthetic valve failure. Lipoprotein(a) [Lp(a)] contributes to native aortic valve calcification, but its role in SVD is unclear. We investigated whether elevated Lp(a) is associated with SVD after bioprosthetic aortic valve replacement (AVR), and whether this differs between stenotic and regurgitant phenotypes. METHODS AND RESULTS: We studied 174 bioprosthetic AVR patients with available Lp(a) levels over a median echocardiographic follow-up of 7.3 years (1,372 studies). SVD was defined by VARC-3 criteria, and associations were analyzed with Fine-Gray competing risk models. Lp(a) was evaluated categorically (≤ or > 125 nmol/L) and continuously using spline modeling. During follow-up, 40 patients developed SVD (22 stenotic, 9 mixed, 9 regurgitant). The 15-year cumulative incidence was 51% with median onset at 14.8 years. Elevated Lp(a) was associated with higher risk of overall SVD (62% vs 47%; SHR 2.06, 95% CI 1.09-3.91; p=0.026) and specifically with stenotic/mixed phenotypes (SHR 2.57, 95% CI 1.26-5.23; p=0.009). No association was observed with regurgitant phenotypes (SHR 0.85, 95% CI 0.19-3.92; p=0.84). After multivariable adjustment, elevated Lp(a) remained an independent predictor of stenotic/mixed SVD (adjusted SHR 3.00, 95% CI 1.48-6.07; p=0.002). Spline modeling showed a linear dose-response, with each 25 nmol/L increase in Lp(a) conferring 13% higher risk. CONCLUSION: Elevated Lp(a) is independently associated with long-term risk of stenotic/mixed SVD. These findings highlight Lp(a) as a promising biomarker of prosthetic valve vulnerability and support investigation of emerging Lp(a)-lowering therapies to improve valve durability.