Wenliang Che

Background: Left bundle branch area pacing (LBBAP) with atrioventricular node (AVN) ablation has emerged as a promising therapy for patients with atrial fibrillation (AF) and symptomatic heart failure (HF). However, it remains unclear which patients are likely responders and which may derive limited benefit. Objective: This study aimed to identify predictors of unfavorable therapeutic outcomes following this ‘ablate and pace’ therapy. Methods: In this retrospective analysis, consecutive patients with successful LBBAP and AVN ablation were included. Baseline characteristics and long-term outcomes were assessed. Multivariable Cox regression and reclassification analysis were used to evaluate the predictors of heart failure hospitalization (HFH). Results: Ninety-eight patients (age 73.1 ± 8.9 years; ventricular rate 93.6 ± 18.7 bpm; 41.8% male) were enrolled. During 43.9 ± 19.4 months of follow-up, 19 (19.4%) patients experienced HFH. Three independent risk factors were identified for HFH: impaired renal function (eGFR ≤ 60 mL/min/1.73 m²; HR: 7.9), left atrial enlargement (LAD ≥ 50 mm; HR: 4.8), and male sex (HR: 3.9). A risk stratification model incorporating these factors effectively discriminated patients with minimal versus high HFH risk. All patients with three risk factors experienced HFH within 2 years, whereas none of the 25 patients without any risk factors experienced the endpoint during 113 patient years of follow-up. Conclusions: The eGFR ≤ 60 mL/min/1.73 m², LAD ≥ 50 mm, and male sex were likely predictors of poor therapeutic outcomes to ‘ablate and pace’ therapy in patients with AF and HF. Patients without any of these risk factors had minimal HFH risk, whereas ≥2 risk factors showed a markedly higher risk. This may help to identify potential patients who are less likely to benefit from this combined approach, although prospective validation is needed before clinical application.

In this exploratory diagnostic study, although our previous study demonstrated the strong prognostic value of CZT-SPECT-derived stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR) in patients with ischemia and non-obstructive coronary artery disease (INOCA), their diagnostic value and optimal cut-off values for coronary microvascular dysfunction (CMD) remain unclear. We prospectively recruited 56 INOCA patients referred from cardiovascular medicine to nuclear medicine. Each underwent CZT-SPECT and coronary angiography-derived index of microcirculatory resistance (caIMR) within one week. CMD was defined as caIMR > 25 U. Bonferroni correction was applied for multiple comparisons of regional coronary physiological parameters. Based on caIMR, CMD was present in 42 INOCA patients (75%). After correction, regional MFR (LAD: 2.9 ± 0.9 vs. 3.7 ± 0.7, p =0.02; LCX: 2.8 ± 1.0 vs. 4.0 ± 1.5, p = 0.02; RCA: 2.9 ± 1.1 vs. 3.9 ± 0.7, p = 0.04) and global MFR (3.0 ± 0.9 vs. 3.9 ± 0.8, p < 0.01) were significantly lower in the CMD group, while no significant difference was observed in regional sMBF. Only global sMBF (r=-0.43, p < 0.01) and global MFR (r=-0.32, p = 0.02) showed moderate inverse correlations with caIMR. The optimal diagnostic cut-offs were global sMBF ≤ 3.8 mL/min/g (AUC = 0.68, 95%CI 0.55-0.80, p = 0.02) and global MFR ≤ 2.9 (AUC = 0.80, 95%CI 0.68-0.90, p < 0.01). DeLong test showed no statistically significant difference in diagnostic efficacy between the two parameters (95%CI for AUC difference: -0.06 to 0.30, p = 0.19). Conclusions These preliminary results demonstrate that CZT-SPECT-derived global sMBF and MFR provide modest diagnostic accuracy for identifying CMD in INOCA patients. This non-invasive approach may support identification of CMD and help guide clinical decision-making. ChiCTR2000037112. Registered 27 August 2022, https://www.chictr.org.cn/.

Background: Metabolic disturbances in lipid and glucose metabolism underlie coronary microvascular dysfunction (CMD) in chronic coronary syndromes (CCS), yet a practical biomarker integrating this metabolic risk is lacking. Methods: In this single-center retrospective cohort, 421 CCS patients undergoing coronary angiography were included. CMD was defined by caIMR ≥ 25 U. C-reactive protein-triglyceride-glucose index (CTI), triglyceride-glucose index (TyG), and C-reactive protein (CRP) were measured. Associations with CTI and major adverse cardiovascular events (MACE) in CMD patients were analyzed using Cox regression, mediation, and ROC analyses. Results: CTI was independently associated with CMD after full adjustment (Q4 vs. Q1: OR: 2.28, 95% CI: 1.16–4.49, p = 0.017), outperforming TyG and CRP. Over a median 35-month follow-up, higher CTI predicted increased MACE risk (fully adjusted HR for Q4: 2.62, 95% CI: 1.25–5.51, p = 0.011), especially in CMD patients (fully adjusted HR: 2.84, 95% CI: 1.06–7.62, p = 0.039). CTI demonstrated a superior predictive accuracy for CMD-related MACE compared with TyG (DeLong test p = 0.020). Conclusion: CTI is a robust and independent predictor of both CMD and MACE in patients with CCS, supporting its use for early risk stratification and personalized management in patients with suspected or confirmed microvascular dysfunction.

Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spectrum in hypertensive adults. We evaluated ten IR indices, three insulin-based [homeostasis model assessment of insulin resistance (HOMA-IR), McAuley index, and quantitative insulin sensitivity check index (QUICKI)] and seven non-insulin-based [triglyceride-glucose index (TyG), stress hyperglycemia ratio (SHR), cardiometabolic index (CMI), atherogenic index of plasma (AIP), estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR), and lipid accumulation product (LAP)], for all-cause mortality (ACM) and cardiovascular mortality (CVM) by glycemic status. This prospective cohort study included 7,548 hypertensive adults from NHANES 1999-2018, classified as normoglycemia (n = 1,869), prediabetes (n = 3,389), and diabetes (n = 2,290). Mortality data were collected through December 31, 2019. Associations were analyzed using Cox models with three levels of adjustment. Dose-response relationships were modeled with restricted cubic splines. Over a mean follow-up of 8.7 ± 5.3 years, 1,752 ACM events (23.2%) and 499 CVM events (6.6%) occurred. In fully adjusted models, HOMA-IR independently predicted ACM (per-unit HR 1.017; Q4 HR 1.165) and CVM (per-unit HR 1.012). eGDR showed the strongest overall associations: ACM: per-unit HR 0.807; Q4 HR 0.559; CVM: per-unit HR 0.774; Q4 HR 0.538. TyG predicted ACM (per-unit HR 1.158; Q4 HR 1.233) and CVM per-unit (HR 1.160). In glycemic-stratified analyses, HOMA-IR was the only index with per-unit ACM significance across all three strata (normoglycemia: HR 1.085; prediabetes: HR 1.039; diabetes: HR 1.012). eGDR showed per-unit and Q4 ACM significance in prediabetes and diabetes, and demonstrated significant quartile-level protection for CVM in both prediabetes (Q4 HR 0.465) and diabetes (Q4 HR 0.463), whereas per-unit associations with CVM were observed only in diabetes. TyG was significantly associated with ACM in diabetes (per-unit HR 1.147; Q4 HR 1.337) and with CVM in diabetes (Q4 HR 1.595). In hypertensive adults, HOMA-IR was the only fasting-insulin-based index independently associated with ACM across all three glycemic strata. eGDR demonstrated the most consistent non-insulin-based associations with ACM and CVM, particularly in prediabetes and diabetes. TyG provided additional prognostic value for ACM and CVM, particularly in patients with diabetes. These findings support selecting IR indices based on glycemic phenotype and data availability.

Aims: Coronary microvascular dysfunction (CMD) is a crucial prognostic indicator in chronic coronary syndrome (CCS) patients. The stress hyperglycemia ratio (SHR), a novel biomarker of acute hyperglycemia, has demonstrated predictive value for adverse outcomes in various diseases. However, its association with CMD remains unclear. This study aims to evaluate the prognostic role of SHR in predicting CMD outcomes in CCS patients. Methods: CCS patients who underwent coronary angiography (CAG) were included. Microvascular function was assessed using coronary angiography-derived index of microcirculatory resistance (caIMR), with CMD defined as caIMR > 25U. Patients were divided into three groups based on SHR values: T1 (SHR < 0.73), T2 (SHR 0.73–0.80), and T3 (SHR≥0.80). The primary endpoint was major adverse cardiac events (MACE). Results: 379 CCS patients were included, among which 196 were identified with CMD. The CMD group exhibited higher SHR levels. During a mean follow-up of 32.9 months, 53 MACE events occurred in CMD patients, with a higher incidence in the T3 group compared to the T1/T2 groups (37.681% vs. 16.667% vs. 26.230%, P = 0.023). SHR was identified as an independent predictor of CMD (OR 7.379, 95% CI: 1.305–41.725, P = 0.024). The T3 group demonstrated a 2.325-fold increased risk of MACE (HR 2.325, 95% CI: 1.228–5.033, P = 0.011), with a non-linear relationship observed between SHR and MACE (P for non-linear < 0.001). Conclusions: Elevated SHR is associated with adverse outcomes and predicts MACE in CMD patients with CCS. These results highlight the potential of SHR as a valuable tool for early risk stratification and prevention in CMD management. Trial Registration: ClinicalTrials.gov, NCT06698432 (Registration Date: November 19, 2024)

Sprouting angiogenesis requires endothelial cells (ECs) to transition into specialized tip and stalk cells, a process influenced by metabolic regulation. ATP-citrate lyase (ACLY), which generates acetyl-CoA from citrate, is markedly activated in proliferating ECs (PECs) but less so in quiescent ECs (QECs). However, it remains elusive whether ACLY-derived acetyl-CoA fuels angiogenesis. Here, we demonstrate the critical role of ACLY in angiogenesis. ACLY depletion impaired EC proliferation, migration, tube formation, and sprouting, while EC-specific Acly-knockout mice showed reduced physiological and pathological angiogenesis, including in oxygen-induced retinopathy (OIR). Mechanistically, ACLY fuels glycolysis, boosts acetyl-CoA production, and enhances histone acetylation at key angiogenic gene loci. Intriguingly, acetate supplementation restored acetyl-CoA levels and rescued defective angiogenesis in ACLY-deficient models. In addition, pharmacological inhibition of ACLY suppressed neovascularization in OIR models. These findings establish ACLY as a previously unrecognized metabolic and epigenetic regulator of angiogenesis, highlighting its potential as a therapeutic target for pathological neovascularization.

Background: Plant-based diets have been demonstrated to be associated with lower risk of several chronic diseases. However, a comprehensive assessment of plant-based diet quality and its association with heart failure (HF) is limited. This study aimed to investigate whether healthful and unhealthful plant-based dietary patterns are associated with overall HF risk among middle-aged and older adults in the United Kingdom. Methods: We included a total of 190,092 UK Biobank participants without HF at baseline. Three plant-based diet indices were calculated using 24-h dietary recalls based on 17 food groups: the overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). Multivariable Cox regression models were applied to assess the association between these indices and incident HF. Results: Over a median follow-up of 13.04 years, 4,351 cases of new-onset HF were recorded. Compared to the lowest tertile, the multivariable-adjusted hazard ratios (HRs) with 95% confidence interval (CI) for HF in the highest tertile were 0.94 (0.88–1.02) for overall PDI, 0.84 (0.78–0.91) for hPDI, and 1.11 (1.03–1.19) for uPDI. Conclusion: A higher intake of healthful plant-based diets was associated with a lower risk of HF, while follow unhealthful plant-based diet was linked to a higher overall HF risk. Adhering to a high-quality diet primarily based on healthy plant-based foods may be helpful prevent HF.