Hazard Ratio Research Articles

Although there is general agreement on performing concomitant ablation of atrial fibrillation (AF) during left-sided heart valve surgery in low-risk patients due to its proven long-term clinical benefits, its role in reoperative cases remains debated because of perceived high risks. This study included 338 consecutive patients with AF who underwent redo surgery for left-sided valve disease between 2000 and 2015 at 2 tertiary referral centers. Among them, 143 patients underwent concomitant surgical ablation for AF (ablation group), while 195 did not (no-ablation group). To evaluate comparative long-term clinical outcomes between the 2 groups, inverse probability of treatment weighting was applied. Early mortality rates were 3.5% (4/143) in the ablation group and 9.2% (18/195) in the no-ablation group (p=0.064). At 5 years, the cumulative incidence of AF recurrence was 12.3%±0.1% in the ablation group and 85.2%±0.1% in the no-ablation group (p<0.001). During follow-up (median, 103 months), the ablation group demonstrated significantly lower risks of death (adjusted hazard ratio [aHR], 0.495; 95% confidence interval [CI], 0.312-0.784; p=0.003) and thromboembolic events (aHR, 0.212; 95% CI, 0.058-0.771; p=0.019) compared with the no-ablation group. Concomitant AF ablation during redo valve surgery was associated with improved rhythm outcomes, survival, and freedom from thromboembolic events, supporting its consideration as a reasonable option even in this high-risk group.

Background: Dietary risks, including energy intake, contribute to disease burden. We examined associations of energy intake with all-cause mortality in American adults with cardiometabolic diseases. Methods: This prospective cohort study used NHANES 1999-2018 data. Energy intake (kcal/kg/day) was calculated as daily calorie intake divided by ideal (IBW) or actual body weight. Cardiometabolic diseases included obesity, hypertension, diabetes, high cholesterol, heart failure, stroke, and coronary artery disease. Covariates included age, sex, race, education, smoking, drinking, body mass index (BMI), history of respiratory disease, and history of cancer. Cox models estimated adjusted hazard ratios (HRs) and 95% CIs across different age, sex, and physical activity (PA) level. Restricted cubic splines analyzed dose-response relationships. Results: Among 19,127 adults (mean follow-up: 8.88±0.11 years), energy intake and mortality showed a nonlinear relationship. Adjusted for IBW, 30-&lt;40 kcal/kg IBW/day had the lowest mortality risk (HR=0.792, 95% CI: 0.629–0.978, P=0.028). Subgroup analyses revealed heterogeneity: females had lower mortality at 20-&lt;30 (HR=0.702, P=0.005) and 30-&lt;40 kcal/kg IBW/day (HR=0.738, P=0.047), while males showed no association. Younger adults (&lt;60 years) had maximal protection at ≥40 kcal/kg IBW/day (HR=0.553, P=0.021), whereas older adults (≥60 years) benefited at 20-&lt;30 kcal/kg IBW/day (HR=0.781, P=0.030). Low-PA individuals mirrored overall trends (30-&lt;40 kcal/kg IBW/day: HR=0.804, P=0.037), but moderate-to-high PA subgroups showed no association. Actual weight-adjusted intake yielded similar results (optimal: 30-&lt;40 kcal/kg/day, HR=0.762, P=0.018). Younger adults required higher intake (≥40 kcal/kg/day: HR=0.488, P=0.002), while older adults benefited at 20-&lt;30 kcal/kg/day (HR=0.702, P=0.005). Dose-response analyses confirmed nonlinearity (P&lt;0.05) overall and in females, older adults, and low-PA subgroups. Conclusion: Energy intake exhibited a nonlinear relationship with all-cause mortality in cardiometabolic disease patients. Lowest risk occurred at 30-&lt;40 kcal/kg/day (ideal/actual weight). Subgroup heterogeneity underscores the need for personalized nutrition guidance over generalized recommendations.

Introduction: Malnutrition and frailty are highly prevalent among heart failure (HF) patients and have been shown to independently affect outcomes. However, these diagnoses are often overlooked during an acute decompensate HF (ADHF) hospitalization. In this retrospective analysis, we use data from a large, cardiac focused health system to assess the prognostic impact of baseline frailty and/or malnutrition on all-cause mortality at 30 days, 90 days, and 1 year following an ADHF hospitalization. Hypothesis: Baseline frailty and/or malnutrition will confer a higher mortality risk in patients admitted for ADHF. Methods: All Icahn Mount Sinai Health System patients were searched using TriNetX from 1/1/2005 through 4/30/2025. Patients aged &gt;18 years with pre-existing HF admitted for ADHF were included. Patients who did not meet the inclusion criteria or who died during the index event were excluded. The control HF cohort was composed of included patients who did not have either malnutrition or frailty. The cohorts were propensity matched and balanced for baseline characteristics (i.e. BMI, age, sex, etc.). Statistical analysis was performed via Cox regression using the built-in TriNetX calculator. Outcomes are reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: A total of 24,860 patients admitted for ADHF were included (Frailty n=2,770; malnutrition n=8,310; frailty + malnutrition n=1,350; control HF n=12,340). Baseline characteristics of the cohorts are reported in Table 1. There was a significant increase in the risk of all-cause mortality at 30 days, 90 days, and 1 year post-discharge seen with baseline frailty (30 days: HR 6.423 95% CI 5.487-7.518 p&lt;0.0001, 90 days: HR 5.783 95% CI 5.037-6.339 p=0.0002, 1 year: HR 4.856 95% CI 4.312-5.648 p&lt;0.0001), malnutrition (30 days: HR 3.231 95% CI 2.861-3.65 p&lt;0.0001, 90 days: HR 1.612 95% CI 1.345 - 1.933 p&lt;0.001, 1 year: HR 3.947 95% CI 3.617-4.308 p&lt;0.0001), or both (30 days: HR 9.826 95% CI 7.538-12.808 p&lt;0.0001, 90 days: HR 8.638 95% CI 6.91-10.799 p=0.0349, 1 year: HR 8.036 95% CI 6.612-9.766 p&lt;0.001). (Figure 1) Conclusion: Frailty and malnutrition are significant independent risk factors for mortality post-discharge for ADHF, with as high as a 9-fold increased risk when both are present. Future prospective studies looking at early assessment and interventions for ADHF patients with frailty and malnutrition are needed to address this vulnerable population with high morbidity and mortality.

Introduction: Air and noise pollution are recognized public health concerns. However, their long-term impact on valvular heart disease (VHD) remains unclear. Methods: This study analyzed 453,413 participants from the UK Biobank. Air pollution was quantified using the air pollution score based on PM 2.5 , PM 2.5-10 , PM 10 , NO x , and NO 2 levels. Road traffic noise (L den and L night ) exposure was estimated based on baseline residential addresses. Participants were categorized into quintiles (Q1-Q5) of exposure. VHD diagnoses were identified from hospitalization and cause-of-death records. Multivariable Cox proportional hazard models were used to assess the association between pollution exposures and VHD risk, presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: During a median follow-up of 13.9 years, 18,806 cases of VHD were recorded. Participants exposed to the highest levels of pollution exposures had a significantly increased risk of developing VHD compared to those in the lowest exposure group (Q5 vs. Q1: air pollution score [HR 1.73, 95% CI 1.61-1.87], PM 2.5 [HR 1.69, 95% CI 1.57-1.82], PM 2.5-10 [HR 1.43, 95% CI 1.34-1.53], PM 10 [HR 1.29, 95% CI 1.22-1.36], NO 2 [HR 1.59, 95% CI 1.47-1.71], NO X [HR 1.64, 95% CI 1.53-1.77], L den [HR 1.66, 95% CI 1.56-1.77], and L night [HR 1.67, 95% CI 1.57-1.78]). These associations persisted significantly regardless of the genetic risk to VHD and extended across all VHD subtypes, including non-rheumatic, rheumatic, aortic, mitral, tricuspid, and pulmonary valve diseases. Conclusion: This study demonstrates a significantly positive association between long-term exposure to air and noise pollution and increased VHD risk.

Background: There is no definite consensus on the best treatment option for atrial fibrillation (AF) in heart failure (HF) with preserved ejection fraction (HFpEF) population. Aim: This study aims to systematically review the prognostic effects of catheter ablation (CA) in patients with HFpEF and AF and provide quantitative pooled analysis where applicable. Methods: A systematic search of PubMed/Medline, Web of Science, Embase, ClinicalTrials.gov, Cochrane, Scopus, and Google Scholar was conducted for observational and randomized clinical trial studies on HFpEF patients published up to March 15, 2025. Studies were included if they evaluated the clinical prognostic utility for CA in AF patients with at least 6 months of follow-up. Pooled estimates and 95% CI for CA hazard ratio (HR) or mean difference (MD)/standardized MD (SMD) in each outcome were calculated using a random effects model by RStudio 2025.05.1 software. Results: Twelve studies with 38,237 participants (mean age 69.6) underwent descriptive analysis, and 11 eligible studies were included in the meta-analysis. CA was associated with a lower risk of HF hospitalization (HR: 0.61, 95% CI: 0.39-0.84, I 2 : 83%, p&lt;0.01), cardiovascular (CV) hospitalization (HR: 0.78, 95% CI: 0.55-1.01, I 2 : 42%, p&lt;0.01), all-cause hospitalization (HR: 0.83, 95% CI: 0.68-0.97, I 2 : 42%, p&lt;0.01), CV mortality (HR: 0.43, 95% CI: 0.22-0.84, I 2 : 22%, p:0.01), and all-cause mortality (HR: 0.61, 95% CI: 0.37-0.86, I 2 : 75%, p&lt;0.01). Similarly, the risk for composite outcome (death or HF hospitalization; HR: 0.62, 95% CI: 0.36-0.89, I 2 : 84%, p&lt;0.01), AF recurrence (HR: 0.64, 95% CI: 0.26-1.03, I 2 : 99%, p&lt;0.01), and stroke/transient ischemic (TIA) attacks (HR: 0.66, 95% CI: 0.59-0.73, I 2 : 0%, p&lt;0.01) decreased significantly in the CA group. Moreover, CA was linked to a statistically significant decrease in NT-proBNP level (MD: -500.16; SMD: -0.53, 95% CI: -0.71 to -0.35, I 2 : 0%, p&lt;0.01) and a clinically negligible increase in ejection fraction (MD: 5.34; SMD: 0.4, 95% CI: 0.21-0.59, I 2 : 0%, p&lt;0.01). Meta-regression results showed that CA was associated with greater long-term reduction in HF hospitalization, with risk decreasing over time compared to the usual anti-arrhythmic drugs approach, which can suggest the reverse remodeling potential of CA in the long term. Conclusion: The results indicated that CA is linked with better prognosis in the patients with HFpEF and AF, with more prominent benefits in long-term follow-ups.

Background: Cardiovascular disease is a leading cause of death globally, with type 2 diabetes (T2DM) and obesity as major contributors.GLP-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefits in patients with T2DM.More recent evidence suggests similar benefits in obese individuals without diabetes.However, no meta-analysis has directly compared cardiovascular safety of GLP-1 RAs between diabetic and non-diabetic populations. Hypothesis: We hypothesized that GLP-1 receptor agonists reduce cardiovascular events irrespective of baseline glycemic status,with comparable benefit in individuals with and without T2DM. Methods: We conducted a meta-analysis of randomized controlled trials comparing GLP-1 receptor agonists with placebo in adults with T2DM or obesity without diabetes.Eligible trials reported major adverse cardiovascular events and related outcomes,were phase 3 or 4,parallel-group,placebo-controlled,and conducted between 2008 and 2025.A systematic search of PubMed,Embase,and ClinicalTrials.gov was performed.The primary outcome was MACE; secondary outcomes included cardiovascular death,myocardial infarction,stroke,and heart failure hospitalization.Data were pooled using random-effects models and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated.Subgroup analyses were performed based on glycemic status.Risk of bias was assessed using Cochrane RoB 2 tool. Results: Seven RCTs were included (N = 69,433).GLP-1 RAs significantly reduced MACE (HR 0.84; 95% CI,0.79–0.89,p &lt; 0.001).Risk reductions were consistent in both diabetic (HR 0.85; 95% CI,0.80–0.91) and non-diabetic populations (HR 0.80; 95% CI, 0.72–0.89),with no statistically significant difference between glycemic subgroups (p= 0.37).GLP-1 RAs also significantly reduced all-cause mortality (HR 0.90), hospitalization for heart failure (HR 0.90),cardiovascular death (HR 0.88),non-fatal myocardial infarction (HR 0.89), and non-fatal stroke (HR 0.82),with consistent effects across trials.A dose-response pattern suggested that higher doses are associated with greater cardiovascular risk reductions. Conclusion: GLP-1 RAs reduced major cardiovascular events in both T2DM and obesity without diabetes.The similar efficacy across indications supports a paradigm shift toward broader therapeutic use of GLP-1 RAs as cardioprotective agents in high-risk individuals regardless of glycemic status and underscores the need for updated clinical guidelines inclusive of non-diabetic populations.

Background: Cognitive impairment is a frequent and debilitating comorbidity in older adults with heart failure (HF). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve HF-related outcomes, but their effect on cognitive outcomes is not well established. Research Question: Does treatment with the SGLT2i empagliflozin or dapagliflozin reduce the incidence of cognitive impairment in older adults with HF? Methods: We conducted a retrospective, propensity score-matched cohort study using TriNetX, a global electronic health records database. Adults ≥60 years of age with a diagnosis of HF between July 1, 2020, and March 31, 2023, were included ( Figure 1 ). Patients with pre-existing dementia, type 1 diabetes or chronic kidney disease were excluded. A total of 50,188 SGLT2i users (empagliflozin n=32,761 [65.3%]; dapagliflozin n=17,427 [34.7%]) were propensity score–matched 1:1 to non-user controls based on demographic and clinical variables. Outcomes were assessed over a 2-year follow-up, and included incident diagnosis of Alzheimer’s disease (AD), vascular dementia (VD), mild cognitive impairment (MCI), unspecified dementia, and drugs related to AD. Cox proportional hazards models were used to estimate hazard ratios (HRs). Results: The matched cohorts had a mean age of 72.0 years (empagliflozin) and 71.5 years (dapagliflozin); approximately 58–59% were male and 43–49% had diabetes mellitus. Baseline characteristics were adequately matched ( Table 1 ). Empagliflozin use was associated with significantly reduced risk of AD (HR 0.61, 95% CI 0.48–0.77, p&lt;0.001), VD (HR 0.56, 95% CI 0.44–0.71, p&lt;0.001), unspecified dementia (HR 0.59, 95% CI 0.52–0.67, p&lt;0.001), and initiation of drugs related to AD (HR 0.73, 95% CI 0.62–0.85, p&lt;0.001) ( Table 2 ) Dapagliflozin showed similar protective associations with VD (HR 0.48, 95% CI 0.33–0.68, p&lt;0.001), unspecified dementia (HR 0.65, 95% CI 0.54–0.77, p&lt;0.001), initiation of drugs related to AD (HR 0.76, 95% CI 0.61–0.96, p=0.021), and MCI (HR 0.76, 95% CI 0.60–0.97, p=0.028). Conclusion: In a real-world study of older adults with heart failure, empagliflozin and dapagliflozin use was associated with a lower risk of incident cognitive impairment. While mechanisms such as improved cerebral perfusion, attenuation of neuroinflammation or modulation of metabolic and vascular pathways implicated in neurodegeneration are plausible, prospective studies are needed to confirm these associations and elucidate causal pathways.

Background: Atrial fibrillation (AFib) is common in kidney transplant recipients and may adversely affect outcomes. In the general population, AFib increases thromboembolism, bleeding, and cardiovascular risk, but its impact post-transplant is less defined. Research Question/Hypothesis: We hypothesized that pre-existing AFib is independently associated with adverse outcomes in kidney transplant recipients. Goals/Aims: To assess the long-term impact of pre-existing AFib on clinical outcomes in kidney transplant recipients over 5 years. Methods: Using the TriNetX Research Network (103 healthcare organizations), we identified adult kidney transplant recipients with (n=8,939) and without AFib (n=43,606), defined by ICD-10-CM and ICD-10-PCS codes. Propensity score matching (1:1) was done for demographics and comorbidities including heart failure, diabetes, hypertension, obesity, and coronary artery disease. Matched cohorts included 8,464 patients each. The index event was the transplant date. Outcomes were assessed over 5 years using Kaplan-Meier analysis, log-rank testing, hazard ratios (HR), risk ratios, odds ratios, and absolute risk differences. Primary outcomes included all-cause mortality, 3-point major adverse cardiovascular events (MACE), acute heart failure, graft rejection/failure, bleeding, hospital admission, kidney graft infections, and other infections. Results: After matching, AFib patients had higher 5-year all-cause mortality (21.0% vs. 10.4%; HR 2.23; 95% CI: 2.06–2.42; p&lt;0.001), MACE (16.1% vs. 8.2%; HR 2.17; 95% CI: 1.96–2.40; p&lt;0.001), acute heart failure (10.9% vs. 4.4%; HR 2.75; 95% CI: 2.42–3.13; p&lt;0.001), and bleeding (6.8% vs. 3.5%; HR 2.13; 95% CI: 1.84–2.46; p&lt;0.001). Infectious complications were also more common (54.8% vs. 47.8%; HR 1.27; 95% CI: 1.22–1.32; p&lt;0.001). No significant differences were seen in graft failure/rejection (73.2% vs. 74.7%; HR 0.98; 95% CI: 0.95–1.02; p=0.271) or kidney graft infection (11.8% vs. 11.5%; HR 1.11; 95% CI: 1.02–1.21; p=0.022). Although cumulative hospital admission was slightly lower in AFib patients (84.1% vs. 86.2%), time to first admission was shorter (HR 0.91; 95% CI: 0.88–0.94; p&lt;0.001). Conclusion: Pre-existing AFib is linked to significantly worse 5-year cardiovascular and infectious outcomes after kidney transplantation, though not to graft failure or rejection. These findings highlight the need for focused pre-/post-transplant care, including CV risk management and tailored anticoagulation.

Background: Patients undergoing coronary revascularization (CR), including percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), are at increased risk of repeat CR. This risk often overlaps with factors predisposing patients to coronary artery disease based on their polygenic risk score (PRS). Methods: We conducted a retrospective analysis using UK Biobank data (03/13/2006–06/12/2023). Adults (≥18 years) who underwent index CR after recruitment were included. The primary outcome was repeat CR risk. Outcomes were assessed across three PRS categories for coronary artery disease: high (&gt;80th percentile), intermediate (20th–80th percentile), and low (&lt;20th percentile). Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, with statistical significance set at p&lt;0.05. Results: The study included 12,288 patients with a history of CR. The average age at diagnosis of CR was 66.89 years [95% CI: 66.76–67.02], with high-risk PRS patients presenting at a younger age than those at low risk [65.51 vs. 68.15 years; p&lt;0.001]. A higher proportion of females was observed in the high-risk PRS group compared to the low-risk group [30.88% vs. 20.36%; p&lt;0.001]. The risk of repeat CR after index procedure was significantly higher in high-risk PRS patients [HR: 1.73; 95% CI: 1.39–2.14; p&lt;0.001] and intermediate-risk patients [HR: 1.30; 95% CI: 1.08–1.57; p=0.01] compared to low-risk PRS patients (Figure 1). High PRS risk was also associated with an increased risk of cardiovascular-related mortality [HR: 1.32; 95% CI: 1.08–1.62; p=0.01]. The risk of major adverse cardiovascular events [HR: 0.96; 95% CI: 0.88–1.04; p=0.31], all-cause mortality [HR: 1.09; 95% CI: 0.93–1.28; p=0.28], and non-fatal ischemic stroke [HR: 1.35; 95% CI: 0.96–1.91; p=0.08] were comparable between high- and low-risk PRS groups. Subgroup analysis showed that patients who underwent index PCI had a higher risk of repeat CR in the high-risk vs. low-risk PRS group [HR: 1.90; 95% CI: 1.53–2.37; p&lt;0.001]. In contrast, repeat CR risk was similar across PRS groups for those undergoing CABG [HR: 1.25; 95% CI: 0.95–1.65; p=0.10]. Conclusion: Patients with a high PRS for coronary artery disease had an increased likelihood of repeat CR and cardiovascular-related mortality after the index procedure. The strategic use of PRS models may aid in identifying those who would benefit from routine monitoring and/or intensive management following the index procedure.

Background: Heart failure with preserved ejection fraction (HFpEF) in patients with type 2 diabetes and obesity is common and associated with high morbidity. Glucagon like peptide 1 receptor agonists (GLP-1 RAs) improve weight and glycemic control, but their impact on clinical outcomes in HFpEF remains uncertain. Research Question: Does adding GLP1 RAs to standard of care (SoC) pharmacotherapy reduce 3-year all-cause death and hospitalization compared with SoC alone in adults with HFpEF? Methods: A retrospective cohort study was conducted using the TriNetX U.S. Collaborative Network (69 HCOs). Adults ≥18 years with HFpEF (LVEF ≥50%), type 2 diabetes, and BMI ≥30 kg/m2 initiating a GLP1 RA between January 2016 and January 2025 were identified. The comparison cohort received SoC therapies without GLP-1 RAs. A one-year look-back period captured baseline comorbidities; outcomes were evaluated for 3 years post-index. One-to-one propensity score matching balanced demographics and 24 comorbidities. Cox proportional-hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Results: After 1:1 propensity matching (N = 5,474/group; mean age 70 ± 11 y; 57% women), GLP1 RA therapy produced fewer all cause deaths than SoC alone (8.9% vs 14.7%; HR 0.56, 95 % CI 0.51–0.63, p &lt; 0.001) and fewer hospitalizations (49.1% vs 66.2%; HR 0.54, 95% CI 0.51–0.56, p &lt; 0.001). GLP-1 RAs also lowered the risk of AKI (HR 0.70, 95% CI 0.63–0.79, p &lt; 0.001), atrial fibrillation/flutter (HR 0.59, 95% CI 0.51–0.69, p &lt; 0.001), AMI (HR 0.63, 95% CI 0.54–0.73, p &lt; 0.001), and progression to dialysis (HR 0.61, 95% CI 0.54–0.68, p &lt; 0.001). ER visits fell modestly (HR 0.85, 95 % CI 0.81–0.89, p = 0.001), whereas ED encounters increased (HR 2.00, 95 % CI 1.82–2.21, p &lt; 0.001). Median follow-up was 2.3 y (IQR 1.9–3.0), and proportional-hazards assumptions held. Conclusions: Among U.S. adults with HFpEF, diabetes, and obesity, adding a GLP-1 RA to guideline pharmacotherapy was associated with a 43% relative reduction in all-cause mortality and a 47% reduction in hospitalization over three years. Significant decreases were also observed in AKI, atrial arrhythmias, AMI, and progression to dialysis, while ED visits increased. These findings support incorporating GLP-1 RAs into comprehensive HFpEF management and underline the need to clarify mechanisms driving emergency HF visits.

Background: Takotsubo cardiomyopathy (TCM), a transient myocardial disorder, is increasingly recognized to involve heightened inflammatory activation. Elevated inflammatory markers have been associated with worse outcomes in TCM. Colchicine, an anti-inflammatory agent, may have therapeutic potential in TCM, but supporting evidence remains limited. Hypothesis: We hypothesized that Colchicine therapy in TCM is associated with reduced mortality, cardiovascular events, and renal complications compared to no Colchicine treatment. Methods: A retrospective cohort study was conducted using the Global Collaborative Network, a large multi-institutional electronic health record database. Adults aged 15–70 years diagnosed with TCM who received colchicine (n=1,149) were 1:1 propensity score–matched to TCM patients who did not receive colchicine (n=1,149), balancing on demographics, comorbidities, cardiac risk factors, medications, inflammatory biomarkers, and other labs. Outcomes were assessed over 12 months. The primary endpoint was all-cause mortality. Secondary outcomes included heart failure (HF) exacerbations, major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, arrhythmias, acute kidney injury (AKI), and renal replacement therapy (RRT). Hazard ratios (HRs), 95% confidence intervals (CIs), and absolute risk reductions (ARRs) were calculated. Results: Colchicine was associated with significantly lower all-cause mortality (10.4% vs. 17.0%; HR 0.61 [95% CI: 0.49–0.76]; ARR −6.6%; p&lt;0.001), HF exacerbations (46.2% vs. 52.2%; HR 0.89; ARR −6.0%; p=0.004), and MACE (27.6% vs. 32.5%; HR 0.85; ARR −4.9%; p=0.011). MI risk was reduced (23.2% vs. 27.2%; HR 0.85; p=0.027), as was RRT use (2.5% vs. 4.5%; HR 0.54; p=0.008). Stroke (HR 0.87), AKI (HR 0.91), and arrhythmias showed non-significant trends favoring Colchicine. LVEF recovery was more common in the Colchicine group (7.3% vs. 9.3% unrecovered; HR 0.79; p=0.082). Conclusion: In this large, matched real-world cohort, Colchicine use in TCM was associated with improved survival and cardiovascular outcomes. These findings raise the possibility of a therapeutic benefit, given the role of inflammation in TCM. Prospective studies and randomized trials are warranted to further explore its clinical utility and mechanistic impact in this unique cardiomyopathy.

Background: Atrial fibrillation (AF) is a common comorbidity in hypertrophic cardiomyopathy (HCM), yet its incremental impact on clinical outcomes remains incompletely defined. We leveraged a large, federated electronic health record network to quantify 1-year risks associated with AF in HCM. Methods: Using TriNetX’s US Collaborative Network, we identified adults (≥18 years) with HCM. Two cohorts were formed: HCM + AF (n = 54 852) and HCM without AF (n = 130,250). After 1:1 propensity score matching for demographics and comorbidities (yielding 51,750 patients per cohort), we assessed 1-year outcomes commencing 1 day post–index date. Outcomes included all-cause mortality, ischemic stroke, heart failure (HF) hospitalization, ventricular arrhythmias, sudden cardiac arrest (SCA), pacemaker/implantable cardioverter-defibrillator (ICD) implantation, and left atrial appendage occlusion (LAAO). Hazard ratios (HRs) with 95% confidence intervals (CIs) were generated using Kaplan-Meier and Cox analyses. Results: In matched cohorts (mean age 72 years, 45% female), HCM + AF was associated with significantly higher 1-year mortality (9.8% vs. 5.1%; HR 1.92 [1.84–2.02]; p &lt; 0.0001). AF conferred a 1.61-fold increase in stroke risk (2.9% vs. 1.8%; HR 1.61 [1.48–1.76]; p &lt; 0.0001) and a 2.21-fold higher risk of HF hospitalization (14.4% vs. 6.7%; HR 2.21 [2.10–2.32]; p &lt; 0.0001). Ventricular arrhythmias were more frequent in HCM + AF (5.7% vs. 2.2%; HR 2.66 [2.48–2.87]; p &lt; 0.0001), as was SCA (1.3% vs. 0.6%; HR 2.38 [2.08–2.74]; p &lt; 0.0001). Device interventions—including pacemaker (3.1% vs. 1.1%; HR 2.70 [2.45–2.97]; p &lt; 0.0001), ICD implantation (1.2% vs. 0.4%; HR 2.95 [2.51–3.45]; p &lt; 0.0001), and LAAO (1.0% vs. 0.05%; HR 19.58 [13.20–29.04]; p &lt; 0.0001)—were significantly more common in the AF cohort. Conclusions: Among HCM patients, AF nearly doubles 1-year mortality risk and substantially increases thromboembolic, heart failure, and arrhythmic events, as well as device/procedural interventions. These findings underscore the necessity for vigilant AF surveillance and tailored management strategies in HCM.

Background: Atrial fibrillation (AF) and mitral valve regurgitation (MVR) often co-occur in clinical settings, with the temporal sequence of their diagnoses potentially influencing cardiovascular outcomes. This study aimed to compare major cardiovascular event risks in patients diagnosed first with MVR followed by AF (MVR→AF) versus those with the reverse sequence (AF→MVR). Methods: A retrospective comparative outcomes analysis was conducted using the TriNetX Global Collaborative Network, encompassing data from 135 healthcare organizations. Two cohorts were defined post–propensity score matching using demographic, comorbidities, procedures and treatment: Cohort 1 (MVR→AF; n = 111,391) and Cohort 2 (AF→MVR; n = 111,391). Patients were balanced across demographics and comorbidities to isolate outcome differences. Cardiovascular outcomes were compared via later Cox models to obtain the hazard ratios (HRs) with 95% confidence intervals (CIs) (table 2). Results: Despite similar baseline characteristics, the MVR→AF group exhibited significantly higher incidence rates of all evaluated cardiovascular outcomes. Major Adverse Cardiovascular Events (MACE) occurred in 28.3% of MVR→AF patients compared to 21.0% in the AF→MVR cohort (HR 1.30; 95% CI: 1.28–1.33; p &lt; 0.0001) (Figure 1). This trend persisted across subcategories including ischemic heart disease (HR 1.18), heart failure (HR 1.38), myocardial infarction (HR 1.41), and cerebrovascular outcomes such as cerebral infarction (HR 1.35) and TIA (HR 1.31). The most notable disparity was observed in acute coronary disease (HR 1.65; p = 0.028). Cardiogenic shock and cardiac arrest, while elevated in the MVR→AF group, did not reach statistical significance (table 2). Conclusion: Patients with MVR preceding AF diagnosis are at significantly higher risk for adverse cardiovascular outcomes compared to those with AF diagnosed prior to MVR. These findings underscore the need for heightened surveillance and potential early intervention strategies in the MVR→AF population to mitigate downstream cardiovascular morbidity.

Background: Diabetes mellitus is a known risk factor for adverse cardiovascular outcomes, particularly in patients with atrial fibrillation. While left atrial appendage occlusion (LAAO) has emerged as a viable alternative to long-term anticoagulation, the influence of glycemic control on post-procedural outcomes remains inadequately defined. This study aimed to evaluate cardiovascular outcomes among nondiabetic (NDM), well-controlled diabetic (WCDM; HbA1c &lt;7%), and poorly controlled diabetic (PCDM; HbA1c ≥7%) patients undergoing LAAO. Research Question: Does diabetes and its glycemic control status affect adverse cardiovascular outcomes following LAAO in atrial fibrillation patients? Methods: Using the TriNetX Global Collaborative Network, we identified adult AF patients who underwent LAAO between 2018 and 2024. Patients were stratified into three comparisons: Diabetics vs NDM, WCDM vs NDM, and PCDM vs NDM. Propensity score matching (PSM) was employed to balance 26 baseline covariates across cohorts. Outcomes including major adverse cardiovascular events (MACE), stroke and all-cause mortality were assessed over a 5-year follow-up. Risk analysis and Kaplan-Meier survival curves were used to derive hazard ratios (HR) and 95% confidence intervals (CI). Results: In the overall analysis, major adverse cardiovascular events (MACE) occurred in 13.4% of diabetics versus 9.0% of non-diabetics (HR, 1.44; 95% CI, 1.28–1.62) and all-cause mortality in 15.2% versus 12.3% (HR, 1.15; 95% CI, 1.05–1.25). Stroke occurred in 5.1% versus 3.6% (HR, 1.30; 95% CI, 1.09–1.54), pulmonary embolism in 2.8% versus 2.1% (HR, 1.25; 95% CI, 1.02–1.54), and ventricular fibrillation in 1.0% versus 0.5% (HR, 1.81; 95% CI, 1.22–2.70). In the HbA1c &gt;7% subgroup, MACE risk was further elevated (HR, 1.59; 95% CI, 1.25–2.00), whereas diabetics with HbA1c &lt;7% still experienced increased risk (HR, 1.39; 95% CI, 1.21–1.60) compared with non-diabetics. Conclusion: Poor glycemic control (HbA1c ≥7%) in diabetic patients with atrial fibrillation undergoing LAAO is associated with a significantly increased long-term risk of MACE, stroke, and mortality. Notably, both suboptimal and even controlled glycemic states appear to confer elevated cardiovascular risk, underscoring the complex interplay between diabetes and outcomes post-LAAO. These findings highlight the critical importance of individualized glycemic management and comprehensive cardiovascular risk reduction strategies in this high-risk population.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy is an innovative treatment for hematologic malignancies. However, its long-term cardiovascular safety profile remains understudied. Understanding its impact on cardiovascular outcomes is essential for holistic survivorship care. We aimed to evaluate the 5-year incidence of MACE and other cardiovascular outcomes in patients with hematologic malignancies who received CAR-T therapy compared to those who did not, using real-world data. Methods: A retrospective cohort study was conducted using the TriNetX network. Adult patients with hematologic malignancies were identified and categorized based on CAR-T exposure using relevant ICD-10 CM codes. Propensity score matching (1:1) was used to balance baseline demographics and comorbidities. The primary outcome was 5-year MACE. Secondary outcomes included myocardial infarction (MI), heart failure, arrhythmias, cardiac arrest, and all-cause mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. A two-tailed p less than 0.05 was considered statistically significant. Results: After matching (N=1,382 in each group), baseline characteristics were balanced. Statistically significance were seen in Major Adverse Cardiac Cerebrovascular Events (MACCE) (HR 1.623, 95% CI 1.414-1.862), all cause mortality (HR 1.680, 95% CI 1.466-1.924), new Heart Failure (HR 1.366, 95% CI 1.063-1.755), Major Adverse Kidney Events (HR 2.022, 95% CI 1.670-2.448). No statistical significance were seen in MI (HR 1.147, 95% CI (O.761-1.730), cardiac arrest (HR 1.729, 95% CI 0.973-3.072), new Afib/flutter (HR 1.575, 95% CI 1.214-2.043). Conclusions: CAR-T therapy was associated with a significantly increased 5-year risk of MACCE, mortality, heart failure, MAKE rates. Ongoing cardiovascular monitoring may be warranted in long-term CAR-T survivors.

Background: Current clinical guidelines underscore the importance of rhythm control using catheter ablation but lack guidance regarding the timing of atrial fibrillation (AF) ablation in relation to the diagnosis time. Purpose: This study aims to assess the impact of diagnosis-to-ablation time (DAT) on clinical outcomes in patients with AF who underwent their first catheter ablation. Methods: This study utilized the TriNetX database (January 2016 to April 2022). We identified 62,548 adult patients (≥18 years) with AF who underwent their first catheter ablation. Our primary outcome was the recurrence of AF at a three-year follow-up following a three-month blanking period. All outcomes were evaluated at three-year follow-up using the hazard ratio (HR) and 95% confidence interval (CI). Results: Our study included 32,449 patients with DAT &lt; 1 year, 13,662 patients with DAT 1–3 years, and 16,437 patients with DAT &gt; 3 years. Compared to DAT &lt; 1 year, DAT 1–3 years was significantly associated with an increased risk of AF recurrence (HR: 1.326, 95% CI [1.285, 1.368], p &lt; 0.001). However, DAT &gt; 3 years was significantly associated with an even greater risk of AF recurrence (HR: 1.532, 95% CI [1.488, 1.576], p &lt; 0.001). Compared to DAT &lt; 1 year, both DAT 1–3 years and DAT &gt; 3 years were significantly associated with an increased risk of ischemic stroke (HR: 1.395, 95% CI [1.274, 1.528], p &lt; 0.001) and (HR: 1.400, 95% CI [1.285, 1.526], p &lt; 0.001), respectively. Additionally, compared to DAT &lt; 1 year, DAT 1–3 years was significantly associated with an increased risk of all-cause mortality (HR: 1.393, 95% CI [1.259, 1.541], p &lt; 0.001). However, DAT &gt; 3 years was significantly associated with an even greater risk of all-cause mortality (HR: 1.617, 95% CI [1.475, 1.772], p &lt; 0.001). Moreover, compared to DAT &lt; 1 year, both DAT 1–3 years and DAT &gt; 3 years were significantly associated with an increased risk of new-onset heart failure, bleeding complications, pericardial complications, cardiac-related hemodynamic instability, and all-cause hospitalizations. Conclusion: Delayed ablation was significantly associated with an increased risk of AF recurrence, new-onset heart failure, ischemic stroke, bleeding complications, pericardial complications, cardiac-related hemodynamic instability, all-cause hospitalizations, and all-cause mortality. This underscores the importance of early ablation within one year of AF diagnosis.

Background: Lipoprotein (a) (Lp(a)) and diabetes mellitus (DM) are both established risk factors for the development of cardiovascular disease. However, there is limited data regarding the impact of DM on cardiovascular outcomes in patients with elevated Lp(a). Purpose: This study aims to investigate the impact of DM on cardiovascular outcomes among patients with elevated Lp(a). Methods: This study utilized the TriNetX database (January 2016 to April 2022). A total of 19,942 adult patients (≥18 years) diagnosed with elevated Lp(a) were identified. Propensity score matching (PSM) (1:1) was conducted based on baseline characteristics. Our primary outcome was major adverse cardiovascular events (MACE) (a composite of incident acute myocardial infarction, ischemic stroke, and all-cause mortality) at a three-year follow-up. All outcomes were assessed using the hazard ratio (HR) and 95% confidence interval (CI). Results: Our study included 5,968 patients with elevated Lp(a) and DM, as well as 13,974 patients with elevated Lp(a) without DM. After PSM, there were 4,822 patients in each group. DM was significantly associated with a higher risk of MACE (HR: 1.430, 95% CI [1.229, 1.664], p &lt; 0.001), atherosclerotic cardiovascular disease (HR: 1.151, 95% CI [1.081, 1.227], p &lt; 0.001), new-onset heart failure (HR: 1.463, 95% CI [1.230, 1.739], p &lt; 0.001), cardiac-related hemodynamic instability (HR: 1.836, 95% CI [1.278, 2.640], p = 0.001), all-cause hospitalizations (HR: 1.405, 95% CI [1.263, 1.563], p &lt; 0.001), and all-cause mortality (HR: 1.343, 95% CI [1.117, 1.615], p = 0.002). However, there was no significant difference between the presence of DM and its absence in new-onset atrial fibrillation and new-onset aortic valve stenosis. Conclusions: The presence of DM in patients with elevated Lp(a) levels was significantly associated with an increased risk of MACE, atherosclerotic cardiovascular disease, new-onset heart failure, cardiac-related hemodynamic instability, all-cause hospitalizations, and all-cause mortality. However, there was no significant difference between the presence of DM and its absence in new-onset atrial fibrillation and new-onset aortic valve stenosis.

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardiovascular benefits in randomized trials, including reductions in mortality and heart failure hospitalizations. However, real-world evidence on their effectiveness across the population with valvular heart disease (VHD) remains limited. Methods: We analyzed two matched cohorts from a federated health research network. We identified all the population VHD (excluding those who have received valve replacement or repair, those with congenital heart disease, and those with systolic heart failure). Then we divided them into those with SGLT2i prescription (n = 107,607) and those without (n = 107,607). Propensity score matching was performed on 38 variables encompassing demographics, comorbidities, medications, and laboratory covariates. Outcomes were assessed between 30 and 365 days post-index SGLT2i prescription, and those with outcomes prior to the analysis were excluded. Risk estimates, Kaplan-Meier survival analysis, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results: SGLT2i use was associated with a significantly lower risk of all-cause mortality (2.8% vs. 5.7%; HR: 0.433, 95% CI: 0.414–0.452; p&lt;0.001). Survival at one year was higher in the SGLT2i group (96.93% vs. 93.12%). No significant differences were observed for atrial fibrillation (4.3% vs. 3.6%; HR: 1.014, 95% CI: 0.965–1.065; p=0.586) or ED visits (7.5% vs. 6.3%; HR: 1.036, 95% CI: 0.992–1.083; p=0.111). Rates of hospital admissions (0.01% vs. 0.01%; HR: 2.638, 95% CI: 0.714–9.746; p=0.459), ICU admissions (0.09% vs. 0.10%; HR: 0.845, 95% CI: 0.640–1.117; p=0.415), and cardiogenic shock (0.20% vs. 0.21%; HR: 0.836, 95% CI: 0.693–1.009; p=0.08) were similar between groups. Conclusion: Among the population with VHD, SGLT2i use was associated with a 57% relative reduction in all-cause mortality. Other outcomes, including atrial fibrillation, ED visits, ICU admissions, and cardiogenic shock, showed no significant differences. These findings support the need for further research.

Introduction: In patients with type 2 diabetes (T2D) at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been shown to reduce major adverse cardiovascular events. However, patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been largely excluded from randomized trials. Hypothesis: We investigated whether GLP1-RA use is associated with improved one-year cardiovascular outcomes in patients with T2D undergoing TAVI. Methods: We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with T2D who underwent TAVI between 2015 and 2023 were included and stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). The primary outcome was a composite of all-cause mortality or hospitalization at 1 year. Secondary outcomes included acute heart failure (HF) exacerbation, acute myocardial infarction (AMI), cardiac arrest, and ischemic stroke. Outcomes were assessed from 1 month to 1 year after TAVI. Survival probabilities were estimated using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Results: Among 20,454 patients with T2D undergoing TAVI from 2015-2023, 937 received GLP1-RAs. After PSM, 930 patients were included in each cohort, with a mean age of 73 years and 37% female. The mean follow-up duration was 342 days for GLP1-RA users and 325 days for non-users. GLP1-RA cohort exhibited a higher 1-year survival probability (93.8%) compared to non-users (89.5%) (HR 0.573 [95% CI, 0.410-0.801]; p=0.001). GLP1-RA use was also associated lower rates of all-cause hospitalization (HR 0.762 [95% CI, 0.652-0.891]; p=0.001), acute HF exacerbation (HR 0.687 [95% CI, 0.566-0.834]; p&lt;0.001), and cardiac arrest (HR 0.452 [95% CI, 0.213-0.960]; p=0.034). No differences were observed in AMI (HR 1.033 [95% CI, 0.750-1.423]; p=0.844), or ischemic stroke (HR 0.875 [95% CI, 0.659-1.162]; p=0.356). Conclusions: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiovascular outcomes, including reductions in acute HF exacerbation, all-cause hospitalization, and cardiac arrest. These findings highlight the need for prospective clinical trials to confirm these results.

Background: Type 2 diabetes mellitus (T2DM) significantly increases the risk of cardiovascular events, particularly in high-risk patients—those with coexisting cardiovascular disease (CVD) or chronic kidney disease (CKD). Oral semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated strong efficacy in glycemic control and potential cardiovascular benefits in T2DM. However, its impact on cardiovascular outcomes in T2DM patients with coexisting CVD or CKD remains to be fully elucidated. Methods: A comprehensive literature search of PubMed, Cochrane Library, and ClinicalTrials.gov was conducted to identify randomized, placebo-controlled trials (RCTs) evaluating oral semaglutide in T2DM patients aged over 50 years with either CVD or CKD. Primary outcomes included all-cause mortality, major cardiovascular events, non-fatal myocardial infarction (MI), cardiovascular death, and non-fatal stroke. The secondary outcomes assessed were adverse events of special interest, such as malignant neoplasms and acute pancreatitis. A random-effects model using the Mantel-Haenszel method was used to calculate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Four RCTs comprising 19,663 patients (9,831 in the semaglutide group; 9,832 in the placebo group) were included. Oral semaglutide significantly reduced all-cause mortality (HR: 0.87; 95% CI: 0.78–0.95; p = 0.004), major cardiovascular events (HR: 0.81; 95% CI: 0.75–0.88; p &lt; 0.00001), and non-fatal MI (HR: 0.79; 95% CI: 0.67–0.93; p = 0.005) compared to placebo. No significant differences were observed for cardiovascular death (HR: 0.80; 95% CI: 0.64–1.01), non-fatal stroke (HR: 0.88; 95% CI: 0.67–1.15), or heart failure hospitalization (HR: 0.91; 95% CI: 0.76–1.09). All adverse events of special interest, including malignant neoplasms (RR: 1.08; p = 0.17) and acute pancreatitis (RR: 0.89; p = 0.60), did not differ significantly between groups. Conclusion: Oral semaglutide is associated with significant reductions in all-cause mortality, major cardiovascular events, and non-fatal myocardial infarction in high-risk T2DM patients with CVD or CKD, supporting its role as a cardioprotective agent in this population. Importantly, semaglutide did not increase the risk of serious adverse events, underscoring its safety. These findings support broader consideration of oral semaglutide in cardiovascular risk management for high-risk T2DM patients.