Citations

Abstract: Cardiovascular disease (CVD) remains the leading cause of death worldwide. While advances in treatment have improved outcomes, the greatest gains in public health will come from primary prevention. Risk stratification is the foundation of CVD prevention. Traditional tools, such as pooled cohort equations (PCEs) and SCORE2, do not capture non-traditional risk factors and individual variability, driving efforts to refine existing approaches. We critically discuss emerging risk determinants for primary CVD prevention. Coronary artery calcium scoring can reclassify CVD risk but has limitations related to cost, access, and unvalidated improvements in clinical endpoints. Biomarkers such as apolipoprotein B and lipoprotein(a) may identify residual risk beyond LDL-C, particularly in patients with lipid discordance, but remain underused due to uncertain thresholds and the lack of prospective triallevel outcome data. Trials of colchicine in primary prevention have yielded mixed results, making the role of targeting inflammation unclear in CVD prevention. Polygenic risk scores can stratify genetic risk but face challenges in sensitivity, specificity, and generalizability. Multiomics approaches, while offering the promise of deeper phenotyping, lack established clinical applications and consensus on when their use is appropriate. Artificial intelligence may allow better prediction across cohorts but requires broader validation. Clonal hematopoiesis of indeterminate potential, a marker of inflammation and age-related CVD risk, lacks evidence supporting routine screening or intervention in younger, asymptomatic individuals. The proliferation of new risk stratification tools poses a key challenge: determining when additional data meaningfully alter clinical decisions. Until robust outcome-based evidence emerges, risk enhancers should guide, but not dictate, therapy in selected patients.

ABSTRACT Background Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤ 1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3‐month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR = 1.28, p < 0.001) and HFpEF (HR = 1.21, p = 0.02), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re‐do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. Conclusions Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke, HF hospitalization and mortality rates were similar, suggesting earlier ablation may enhance rhythm control over other outcomes.

Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. Conclusions: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival.

11pt, fleqn, a4paper, ]LegrandOrangeBook Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. CONCLUSIONS: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival. Condensed Abstract Delayed atrial fibrillation (AF) ablation was associated with higher (AF) recurrence in both HFrEF and HFpEF. In HFrEF, delayed ablation led to increased use of re-do ablation, cardioversion and antiarrhythmic drugs (AADs). In HFpEF, only AAD use was significantly higher with delayed ablation. Stroke and mortality rates were similar between early and delayed ablation groups.

Cardiac amyloidosis (CA) is a progressive condition resulting from the deposition of amyloid fibrils in the heart, which leads to severe diastolic dysfunction and restrictive cardiomyopathy. The disease has two main subtypes: light-chain and transthyretin (TTR) CA, with the latter subdivided into wild-type and hereditary forms. Despite advances in diagnostic imaging, early detection remains a challenge due to non-specific symptoms that mimic other cardiac conditions. Treatment has evolved significantly with targeted therapies like TTR stabilizers, gene silencers, and RNA interference, showing promise in altering disease progression. However, barriers such as high costs, limited availability of genetic testing, and inadequate multidisciplinary care continue to impede comprehensive management. Future strategies should focus on integrating novel gene-editing therapies, expanding access to diagnostics, and enhancing multidisciplinary care models to improve outcomes. Overall, early diagnosis, equitable access to therapies, and personalized management plans are crucial to advancing care for CA patients.

Background Patient‐reported outcome measures have been shown to have important prognostic value after various cardiac interventions. We assessed the association between the change in Kansas City Cardiomyopathy Questionnaire 12 (KCCQ‐12) score after transcatheter aortic valve replacement and mortality. Methods and Results We included patients who underwent transcatheter aortic valve replacement at Mayo Clinic between February 2012 to June 2022 and who completed a KCCQ‐12 before and 30 to 45 days after the procedure. Patients were categorized into 3 groups: those who experienced significant (>+19 points; group 1), modest (1–19 points; group 2), and no (≤0 points; group 3) improvement. A total of 1124 patients were included: 60.8% men; 97.6% White. Mean age was 79.4±8.3 years, baseline KCCQ‐12 score was 53.9±24.5, and median Society of Thoracic Surgeons score was 4.9% (interquartile range, 3.1–8.0). At 45 days, the mean change in KCCQ‐12 score was 19±24 points; 46.3% (n=520) of patients had a significant improvement in their KCCQ‐12 score, while 33.4% (n=375) and 20.4% (n=229) had modest and no improvement, respectively. Median survival was higher in group 1 (5.7±0.2 years) compared with groups 2 and 3 (5.1±0.3 and 4.1±0.4 years, respectively; P <0.001). Compared with patients in group 1, those in groups 2 and 3 had higher long‐term risk‐adjusted mortality (adjusted hazard ratios, 1.54 [95% CI, 1.20–1.96], and 2.30 [95% CI, 1.74–3.04], respectively). Conclusions Patients who experience modest or no improvement in KCCQ‐12 score after transcatheter aortic valve replacement have substantially higher long‐term mortality. Delta KCCQ‐12 is a cost‐effective, efficient tool that can identify patients at increased risk of death at long‐term follow‐up post‐transcatheter aortic valve replacement.

AbstractObjectivesThe aim of this study was to describe the use pattern and outcomes of protamine administration for heparin reversal among sites performing percutaneous left atrial appendage occlusion (LAAO).MethodsWe identified 45,135 patients who underwent LAAO at 243 hospitals participating in Vizient® Clinical Database between January 1, 2016 and December 31, 2021. Patients were stratified according to protamine administration after the procedure. Outcomes of interest included vascular complications, major bleeding, ischemic events, and same‐day discharge.ResultsA total of 40,278 patients were included in the propensity‐matched comparison, of whom 50% received protamine after the LAAO procedure. The use of protamine varied across hospitals, with 88 hospitals (36.2%) using protamine in >75% of cases and 32 hospitals (13.1%) not using protamine at all. Major bleeding occurred less frequently in the protamine group compared with the control group (2.4% vs. 2.8%, p = 0.03). Major vascular complications and pericardial tamponade were rare but slightly higher in the protamine group (0.8% vs. 0.6%, p = 0.04) and (1.0% vs. 0.8%, p = 0.01), respectively. There were no differences in the rates of ischemic or hemorrhagic stroke, all‐cause mortality, or the rate of any major adverse event between the two groups. Same‐day discharge was more frequent in the protamine group (12.3% vs 9.4%, p ≤ 0.001).ConclusionsProtamine is used in approximately 50% of LAAO procedures and is associated with lower bleeding events and higher rates of same‐day discharge. The higher vascular complication and tamponade is likely due to its ad‐hoc use as a reversal agent in these patients.

AbstractBackgroundImprovement in left atrial pressure (LAP) during transcatheter edge‐to‐edge repair (TEER) is associated with improved outcomes. We sought to investigate the predictors of optimal hemodynamic response to TEER.MethodsWe identified patients who underwent TEER at Mayo Clinic between May 2014 and February 2022. Patients with missing LAP data, an aborted procedure, and those undergoing a concomitant tricuspid TEER were excluded. We performed a logistic regression analysis to identify predictors of optimal hemodynamic response to TEER (defined as LAP ≤ 15 mmHg).ResultsA total of 473 patients were included (Mean age 78.5 ± 9.4 years, 67.2% males). Overall, 195 (41.2%) achieved an optimal hemodynamic response after TEER. Patients who did not achieve an optimal response had higher baseline LAP (20.0 [17–25] vs. 15.0 [12–18] mmHg, p < 0.001), higher prevalence of AF (68.3% vs. 55.9%, p = 0.006), functional MR (47.5% vs. 35.9%, p = 0.009), annular calcification (41% vs. 29.2%, p = 0.02), lower left ventricular EF (55% vs. 58%, p = 0.02), and more frequent postprocedural severe MR (11.9% vs. 5.1%, p = 0.02) and elevated mitral gradient >5 mmHg (30.6% vs. 14.4%, p < 0.001). In the multivariate logistic regression analysis, AF (OR = 0.58; 95% CI = 0.35–0.96; p = 0.03), baseline LAP (OR = 0.80; 95% CI = 0.75–0.84; p < 0.001) and postprocedural mitral gradient <5 mmHg (OR = 0.35; 95% CI = 0.19–0.65; p < 0.001), were independent predictors of achieving an optimal hemodynamic response. In the multivariate model, residual MR was not independently associated with optimal hemodynamic response.ConclusionsOptimal hemodynamic response is achieved in 4 in 10 patients undergoing TEER. AF, higher baseline LAP, and higher postprocedural mitral gradient were negative predictors of optimal hemodynamic response after TEER.

Background The management of severe mitral regurgitation (MR) after transcatheter edge‐to‐edge repair (TEER) remains a clinical conundrum. Considering the growing volume of TEER, more outcomes data for mitral surgery in this cohort are needed. Methods and Results Symptomatic patients with persistent or recurrent severe MR after TEER evaluated between May 2014 and June 2021 were included. The primary outcome was all‐cause mortality in patients who were treated with surgery versus medical therapy. The Kaplan–Meier and Cox regression methods were used to report risk‐adjusted survival analyses. Among the 142 included patients, 44 (31.0%) underwent mitral surgery. Patients who underwent surgery were younger than those treated medically (74.1±8.9 versus 78.6±10.5 years, P =0.01). Major comorbidities were similar except obesity, sleep apnea, left ventricular dimensions, and ejection fraction. Society of Thoracic Surgeons Predicted Risk of Operative Mortality was 9.0±4.7 versus 7.9±4.9 in the surgical versus medical therapy groups, respectively, P =0.22. Time from TEER to detection of severe MR was similar in both groups (median [interquartile range] 97.5 [39.5–384] versus 93.5 [40–389] days in the surgical versus medical groups, respectively [ P >0.05]). In the surgical group, valve replacement was performed in all patients. Operative mortality was 4.5% (observed/expected ratio 0.55), and major complications were uncommon. After risk‐adjustment, surgery was associated with significantly lower all‐cause mortality (adjusted hazard ratio, 0.33 [95% CI, 0.12–0.92], P =0.001) compared with medial therapy. Conclusions Compared with medical therapy, mitral surgery in patients with severe persistent or recurrent MR after TEER is associated with lower mortality despite the high‐risk profile of these patients. Patients with severe MR after TEER should be considered for surgery at a referral mitral surgical center.