Cardiovascular Outcomes In Patients Research Articles

High intensity statin-ezetimibe combination therapy reduces mortality in patients with ischaemic heart disease and elevated Lipoprotein(a)

Abstract Background Early and prompt reduction of low-density lipoprotein cholesterol concentrations (LDL-C) using combination lipid-lowering therapy (LLT) is recommended to lower cardiovascular risk in patients with ischaemic heart disease (IHD) and elevated LDL-C. Lowering LDL-C is also an important cardiovascular risk mitigation strategy in patients with elevated lipoprotein(a) [Lp(a)]. However, it is unknown if combination LLT reduces mortality in patients with elevated Lp(a). Aim To undertake an observational study to investigate the effect of combination LLT using high intensity statin with ezetimibe on cardiovascular outcomes in patients with and without elevated Lp(a). Methods Serum Lp(a) concentrations were measured in 520 consecutively recruited patients with IHD admitted to hospital, half of whom were admitted for acute myocardial infarction. Patients treated with high intensity statin and ezetimibe within the 1st year from admission to hospital (‘HI statin-ezetimibe group’, n=157) were compared with the rest of patients who had less intensive lipid lowering regimen (‘Others group’, n=363) for cardiovascular outcomes. Results During the 2-year follow-up period, 14.6%, 6.5%, and 53.1% of patients had all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) respectively. Median age was 63.5 years and 82.3% were male. Multivariable Cox regression showed that baseline Lp(a) ≥70 nmol/L was associated with increased risk of all-cause mortality (HR 1.97, 95% CI 1.20-3.22, P=0.007). Compared with a less intensive regimen, HI statin-ezetimibe was associated with reduced risk of all-cause mortality (HR 0.44 [0.21-0.89], P=0.023) and MACE (HR 0.71 [0.52-0.95], P=0.027), with no statistically significant effect on cardiovascular mortality (HR 0.43, P=0.142). Notably, the cardiovascular benefits of HI statin-ezetimibe were more pronounced in patients with elevated Lp(a); a greater reduction in risk of MACE was seen for patients with Lp(a) ≥70 nmol/L (HR 0.51, P=0.007) or Lp(a) ≥100 nmol/L (HR 0.36, P=0.009), and in all-cause mortality risk for those with Lp(a) ≥70 nmol/L (HR 0.24, P=0.025). Although LDL-C reduction >50% was associated with reduced risk of all-cause mortality (p=0.027), this could not fully explain the overall cardiovascular benefit of HI statin-ezetimibe use in patients with or without elevated Lp(a). Conclusion Intensification of lipid-lowering therapy with high-intensity statin and ezetimibe improves cardiovascular outcomes in patients at very high cardiovascular risk, particularly those with elevated Lp(a). Larger studies are required to confirm our findings that this cardiovascular benefit is partially independent of LDL-C lowering.

ABLE-SCORE: a simplified risk score for major adverse cardiovascular outcomes in patients with left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with life-threatening complications and variable prognosis [1,2]. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVNC is comparatively complex for clinical practice [3,4]. Purpose To develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVNC. Methods This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVNC patients between January 2009 and December 2020 at a single national-level medical center (derivation cohort n=300; internal validation cohort n=129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort n=95). The derivation/internal validation cohorts and the multicenter external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors for MACE in the multivariable Cox regression predictive model, and underwent both internal and external validation to confirm its discrimination (Harrell’s C-index), calibration (calibration plots), and clinical applicability (decision curve analysis). Results A total of 524 LVNC patients (43.5 ± 16.6 years, 65.8% male) were included in the study. At the end of the follow-up, 97 (32.3%), 38 (29.5%), and 20 (21.1%) individuals in the derivation, internal validation, and external validation cohort experienced at least one endpoint of MACE. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement and left ventricular ejection fraction≤40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell’s C-index of 0.821 (95%CI 0.772-0.869), 0.786 (95%CI 0.703-0.869), and 0.750 (95%CI 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVNC. According to decision curve analysis, the ABLE-SCORE displayed greater net benefit than the currently existing risk score for MACE in LVNC [3], indicating its strength in clinical applicability. Conclusions Derived from readily available laboratory and echocardiographic variables, a simplified and efficient risk score for MACE was developed and validated using a large LVNC cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVNC.Development of the ABLE-SCOREValidation of the ABLE-SCORE

Dapagliflozin versus empagliflozin and major adverse cardiovascular events in type 2 diabetes: a nationwide cohort study

Abstract Background Large randomized clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus (T2DM) at high risk of atherosclerotic cardiovascular disease. Whether these effects might differ between individual SGLT2-inhbitors remain unclear given the lack of head-to-head comparisons. Purpose To examine the association between treatment with dapagliflozin versus empagliflozin and the long-term rate of major adverse cardiovascular events (MACE) in patients with T2DM. Methods Using nationwide registries, all Danish residents with T2DM, who initiated treatment with dapagliflozin or empagliflozin from 2015 to 2020, were identified. Only treatment with dapagliflozin or empagliflozin was considered in the present analysis, since approximately 3% initiated treatment with other SGLT2-inhibitors (i.e., canagliflozin and ertugliflozin). Patients were followed from date of the first claimed prescription of dapagliflozin or empagliflozin until the outcome of interest, emigration, death, or end of study (December 31, 2021). The primary outcome was a composite endpoint of major adverse cardiovascular events (i.e., time to first heart failure hospitalisation, acute myocardial infarction (AMI), stroke, or all-cause mortality). The primary outcome was compared between the dapagliflozin and empagliflozin group, overall and in prespecified subgroups of interest, with multivariable Cox proportional hazards regression models. Results In total, 61,031 patients with T2DM initiated treatment with dapagliflozin (N=21,028; 34.5%) or empagliflozin (N=40,003; 65.5%). The median age of study population was 62.6 years (25th-75th percentile, 54.2-70.8 years), and 62.6% were men. There were no clinically significant differences between the dapagliflozin and empagliflozin group with respect to age, sex, and clinical characteristics. The median follow-up was 3.1 years (25th-75th percentile, 1.9-4.5 years). The adjusted long-term hazard ratios of the primary outcome, overall and in prespecified subgroups of interest, are displayed in the Figure. Compared with empagliflozin, treatment with dapagliflozin was not associated with a significantly different rate of the primary outcome (HR 1.02 [95% CI, 0.97-1.07]). The observed association was consistent across clinically relevant subgroups, including in patients with and without heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease. Conclusion In a large, nationwide cohort of patients with T2DM, treatment with dapagliflozin was associated with a similar rate of major adverse cardiovascular outcomes compared with empagliflozin, and this association was consistent across clinically relevant subgroups. These findings suggest that the benefits of SGLT2-inhibitors can be characterized as a class-effect.

Left atrial strain is associated with cardiovascular outcomes in children with congenitally corrected transposition of the great arteries

Abstract Background The assessment of the systemic right ventricular (sRV) function in congenitally corrected transposition of the great arteries (ccTGA) by echocardiography is restricted by its complex geometry. Purpose To determine the utility of left atrial strain (LAS) and sRV longitudinal strain (sRV-LS) in the prediction of outcomes in children with ccTGA. Methods This nested case-control study included all patients <21 years old with unrepaired ccTGA at our tertiary pediatric institution who had an echocardiogram prior to cardiovascular outcomes (milrinone-dependent heart failure, ventricular assistant device, heart transplant or death). LAS (both R wave and P wave references) and sRV-LS were measured using TomTec AutoStrain. To account for potential confounders, cases and controls were matched (1 cases vs 3 controls) by age ± 1 year and tricuspid regurgitation (TR) severity (none/mild vs. moderate/severe). Univariable conditional logistic regression was employed to assess the association between LAS and sRV-LS with outcomes among matched patients. Results Of 101 patients (64% male) with echocardiogram performed at 1.78 years old (IQR 0.02, 9.80), 14 (14%) developed an outcome. Baseline characteristics, LAS, and sRV-LS are depicted in Table 1. LAS and sRV-LS were not discriminative between age-matched cases and controls. In the matched cases and controls for TR severity, each unit-increase in LAS conduit phase (LAScd R and LAScd P) was associated with 18% and 22% higher odds of outcomes respectively, although these did not achieve statistical significance (LAScd R OR 1.2, 95% CI 1.0-1.4, p=0.09; LAScd P OR 1.2, 95% CI 1.0-1.5, p=0.08, Table 2). Conclusions After controlling for TR severity as a potential confounding factor, the conduit phase of LAS by both R wave and P wave references may have clinical implications as predictors of cardiovascular outcomes in patients with ccTGA. Larger and more well-powered studies are needed to further evaluate this association and studying longitudinal changes in LAS may provide insight in the development of outcomes in this population.

Echocardiographic predictors of cardiovascular outcome in heart failure with preserved ejection fraction

Abstract Background The optimal echocardiographic predictors of cardiovascular outcome in heart failure with presereved ejection fraction (HFpEF) are unknown. Purpose We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF. Methods Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and heart failure (HF) hospitalization were pooled using a random effects meta-analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e’, pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models. Results Forty-six studies totalling 20,056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: Decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10-1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13-1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07-1.25) per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e’, moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust. Conclusion Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models.

Comparison of cardiovascular outcomes in patients with diabetes treated with tirzepatide versus semaglutide: a multi-institutional analysis

Abstract Introduction Glucagon-like-peptide-1 (GLP-1) receptor agonists have been demonstrated to have cardiovascular benefits in patients with diabetes. Two of the most prescribed medications in this class are tirzepatide and semaglutide. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, while semaglutide is a selective GLP-1 receptor agonist. Tirzepatide and semaglutide have previously been directly compared to assess efficacy in glycemic control as the primary endpoint. However, there is limited data directly comparing cardiovascular outcomes between the two medications in patients with diabetes. This retrospective cohort study compares the incidence of major adverse cardiovascular events (MACE) in patients with diabetes treated with tirzepatide or semaglutide. Purpose The purpose of this study is to identify differences in cardiovascular outcomes between patients with diabetes treated with tirzepatide as compared to semaglutide. Materials and Methods The TriNetX research network was used for this study. Two patient cohorts were generated using International Classification of Disease 10 (ICD-10) codes and medication codes in the TriNetX system. Both cohorts of patients had a history of diabetes (E08-E13) and no prior history of cerebral vascular accident (I63) or myocardial infarction (I21). One cohort received semaglutide and the other tirzepatide. Each cohort was prohibited from receiving the other agent. The cohorts were balanced for age, race, gender, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm resulting in 36,212 patients in each arm. They were then evaluated for the 3-year outcomes of major adverse cardiovascular events (myocardial infarction, cerebral vascular accident, and death). Results Tirzepatide was associated with statistically significantly fewer MACE outcomes compared to semaglutide for each of the individual endpoints as well as the overall composite endpoint over the 3 year follow up period. Table 1. MACE events for semaglutide and tirzepatide. Table 2. Relative risks for semaglutide MACE endpoints compared to tirzepatide. Conclusions In this retrospective cohort study, tirzepatide was associated with a lower incidence of major adverse cardiovascular events compared to semaglutide in patients with diabetes. These findings suggest that tirzepatide offers superior cardiovascular protection for primary prevention compared to semaglutide and warrant further investigation in future studies and clinical trials.Table 1Table 2

Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients

Abstract Background A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease. Methods This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT. Results A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT. Conclusion Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.

Effect of catheter ablation vs medical therapy on cardiovascular outcomes in hypertrophic cardiomyopathy with atrial fibrillation

Abstract Background Atrial fibrillation (AF) increases the risks of stroke and mortality. AF ablation in patients with heart failure (HF) was associated with a lower risk of death and hospitalisation for worsening HF. Whether AF ablation is beneficial to improve cardiovascular outcomes in patients with concomitant hypertrophic cardiomyopathy (HCM) and AF remains unclear. Objective To investigate whether AF ablation is more effective than conventional medical therapy for improving outcomes in HCM. Methods 2,281 patients with HCM and AF undergoing catheter ablation or medical therapy (antiarrhythmic drugs or rate control drugs) in 2005–2015 were identified from the Korean National Health Insurance Service database. The primary composite outcome of death from cardiovascular causes, ischaemic stroke, hospitalization for worsening HF, or acute myocardial infarction was compared between catheter ablation and medical therapy using propensity score overlap weighting. The time-at-risk was counted from the first medical therapy, and catheter ablation was analysed as a time-varying exposure. Results Of the included (41.1% female; median age: 66 years), 145 (6.1%) underwent catheter ablation for AF during the study period. During a mean follow-up of 3.1 (IQR 1.3–5.8) years, a total of 831 composite outcomes occurred including 292 cardiovascular deaths and 401 strokes. Catheter ablation, compared with medical therapy, was associated with lower risks of the primary composite outcome (weighted incidence rate: 3.84 vs. 6.43 per 100 person-years; weighted HR 0.61, 95% CI 0.38–0.96) and ischaemic stroke (weighted HR 0.43, 95% CI 0.19–0.97). The association between ablation and a lower risk of composite outcome was more pronounced in cases of ablation success whereas no significant difference was observed in cases of ablation failure. Conclusions In patients with AF and HCM, catheter ablation was associated with a lower risk of adverse cardiovascular outcomes than medical therapy.

Gender-differences in Polyvascular disease: implications for lipid-lowering management and cardiovascular outcomes

Abstract Background Polyvascular disease (PolyVD) exhibits extensive atherosclerotic disease in multiple vascular beds. Despite lowering LDL-C with a statin, patients with PolyVD still present elevated risks of subsequent atherosclerotic cardiovascular events, suggesting the need to better understand pathophysiology of PolyVD. Female gender has been reported to mitigate severity of atherosclerotic disease and future events’ risks. However, whether this gender-difference exists in patients with PolyVD remains to be fully elucidated yet. Purpose To characterize gender-differences in cardiovascular outcomes in patients with and without PolyVD, respectively. Methods The on-going multi-center registry enroll patients with CAD receiving intravascular imaging-guided PCI. The current study included 679 patients with CAD. PolyVD was defined as the concomitance of other atherosclerotic cardiovascular disease (stroke and/or LEAD). In patients with PolyVD (n=185) and Non-PolyVD (n=494), clinical characteristics and major cardiovascular outcomes (MACE) were compared between men and women, respectively. MACE was defined as a composite of cardiovascular death, non-fatal MI, ischemic stroke, LEAD and coronary revascularization. Results The proportion of women was 21% and 18% in Non-PolyVD and PolyVD subjects, respectively. In patients with non-PolyVD, women were more likely to be older (75 vs. 68 years, p<0.001) and exhibit a lower BMI (22.3 vs. 24.0 kg/m2, p<0.001) with a lower frequency of previous myocardial infarction (13.5 vs. 24.9%, p=0.01). LDL-C levels did not differ between the two groups [102 (76-130) vs. 93 (71-120) mg/dL, p=0.06). However, during the observational period (median=3 years), women were associated with a lower frequency of MACE compared to men (HR=0.31, 95%CI=0.13-0.78, p=0.012, Figure, Table). In patients with PolyVD, BMI, and the frequency of established risk factors and previous myocardial infarction were comparable between men and women. Despite the use of high-intensity statin in over 40% of study subjects (44 vs. 36%, p=0.41), women still exhibited an elevated level of LDL-C [103 (74-122) vs. 82 (64-103) mg/dL, p=0.04]. Furthermore, in contrast to Non-PolyVD patients, similar cardiovascular outcomes were observed in both men and women with PolyVD (Figure). On multivariate analysis adjusting clinical characteristics, women were not a significant factor associated with a reduced risk of MACE (Table). Conclusion 18% of PolyVD were women who presented a higher LDL-C level. While women with Non-PolyVD exhibited better cardiovascular outcomes compared to men, this gender-difference did not exist in patients with PolyVD. Our findings indicate that female PolyVD did not necessarily show better outcomes but similar cardiovascular event’s risks compared to men. Further intensified anti-atherosclerotic managements are required in both men and women with PolyVD.

Implementation of sodium-glucose co-transporter 2 inhibitors in patients with heart failure through a new digital strategy (EMAIL-HF): a randomised clinical trial study design

Abstract Introduction Delayed implementation of new medical discoveries remains a global healthcare challenge and is mainly due to the complexity of cross-institutional patient care. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors is the latest medical discovery in heart failure (HF) and have recently been added to clinical guidelines as they have proven to reduce the risk of adverse cardiovascular outcomes in patients with HF across the ejection fraction spectrum. Whether a new digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients living with HF is of great importance for public health. Purpose To evaluate whether a new and streamlined digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients with HF. Design and methods: The trial is a multicentre, parallel group, register-based randomised clinical study, evaluating the effect and potential of a new digital strategy to implement new guideline therapies to patients living with a chronic disease, specifically SGLT2 inhibitors to patients with HF (figure 1). The setup employs data from nationwide health registers and official digital letters to inform patients about the new therapy option and invite them to have their eligibility evaluated by a HF specialist and start therapy. A total of ~10,000 patients with HF across the ejection fraction spectrum (with and without diabetes), who have not yet been started on SGLT2 inhibitors, are identified through Danish nationwide health registers, and randomised 1:1 to receive the digital letter (figure 2). The primary outcome is the proportion of patients redeeming a prescription of a SGLT2 inhibitor within six months. Secondary outcome is a composite HF endpoint consisting of all-cause death or HF hospitalisation. Other outcome measures are renal failure, stroke and myocardial infarction, safety outcomes, adherence to therapy and proportion of vulnerable patient groups initiating therapy including immigrants, elderly, frail patients, patients with lower socioeconomic level and lower educational level. A total of 4689 patients have been randomised (February 2024) and data will be presented in 2025. Conclusions The trial will determine the efficacy and safety of a new and streamlined digital strategy to implement SGLT2 inhibitors to patients with chronic HF. The setup has the potential to be used in a broad spectrum of patients living with chronic diseases and is expected to be highly cost-effective.Figure 1.Study hypothesisFigure 2.Study design

Comparative efficacy of colchicine and intensive LDL-C lowering in patients with ASCVD receiving statins: a network meta-analysis of randomised controlled trials

Abstract Background Adding intensive low-density lipoprotein cholesterol (LDL-C) lowering treatments or colchicine to statins resulted in additional cardiovascular benefits. However, the relative efficacy and priority of these agents are unclear. Purpose We aimed to compare the effects of these supplementary agents on cardiovascular outcomes in patients with atherosclerotic cardiovascular diseases (ASCVD) receiving statins. Methods We performed a systematic review and frequentist network meta-analysis on randomized controlled trials. The primary efficacy endpoint was the main adverse cardiovascular event (MACE), and the secondary efficacy endpoints were myocardial infarct, stroke, coronary revascularization, cardiovascular death and all-cause mortality. The safety endpoints were treatment discontinuation and non-cardiovascular death. Colchicine was used as reference treatment. Random-effects model was used in case of high heterogeneity, the fixed-effects model was preferred otherwise. We ranked the comparative effects of all drugs with surface under the cumulative ranking (SUCRA) probabilities. Results 17 trials totaling 85823 participants treated with colchicine, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, Niemann-Pick C1-like 1 protein (NPC1L1) inhibitor and ATP citrate lyase (ACL) inhibitor were included. Compared with colchicine, NPC1L1 inhibitor was associated with increased risk of MACE (risk ratio [RR]: 1.39, 1.21-1.59), stroke (RR: 1.81, 1.09-3.00) and coronary revascularization (RR: 1.36, 1.11-1.68), and PCSK9 inhibitor was associated with increased risk of MACE (RR: 1.27, 1.10-1.46). However, NPC1L1 inhibitor (RR: 0.68, 0.48-0.96) and PCSK9 inhibitor (RR: 0.64, 0.44-0.93) were associated with reduced risk of non-cardiovascular death in comparison to colchicine. PCSK9 inhibitors had a lower risk of MACE (RR: 0.91, 95% CI: 0.85-0.98) and coronary revascularization (RR: 0.89, 95% CI: 0.81-0.97) compared with NPC1L1 inhibitor. Although no regimen prolonged survival, colchicine had the lowest rank at non-cardiovascular death and the worse performance on all-cause mortality. Conclusions In patients with ASCVD receiving statins, inflammation-inhibiting with colchicine seems to be superior to intensive LDL-C lowering therapy with PCSK9 inhibitor or NPC1L1 inhibitor in cardiovascular prevention. However, using colchicine as an alternative to intensive lipid-lowering therapy may need to be weighed against the greater cardiovascular benefits and the potential harms of higher non-cardiovascular death. Given the worse performance of colchicine on survival based on current evidence, colchicine may be more appropriate for patients who have been treated with intensive LDL-C-lowering agents but still have recurrent cardiovascular events.Forest plots of included agentsRadar plot of treatments based on SUCRA

Unique regional risk profiles and cardiovascular outcomes of patients with acute coronary syndrome in the absence of standard modifiable risk factors: a systematic review and meta-analysis

Abstract Background With differences in prevalence, risk profile, cardiovascular complications, and mortality of patients with acute coronary syndrome (ACS) in the absence of standard modifiable risk factors (SMuRF-less) worldwide, this study examines the regional differences and the unique risk profiles of this often-understudied group of patients. Purpose We hypothesize that differences in non-traditional risk factor profiles may lead to unique ACS-related presentations, complication rates, and secondary preventative strategies across regions. Hence this study was undertaken to assess the cross-regional comparisons of patient characteristics, risk profile, angiographic characteristics that may provide insights into disparate cardiovascular outcomes observed in the SMuRF-less ACS population. Methods Medline and Embase databases were searched in November 2022 to identify relevant literature relating to the prevalence of risk factors in SMuRF-less patients with ACS. A single-arm meta-analysis of proportion and means was conducted on baseline and presentation characteristics, outcomes and complications, management, and risk factors in SMuRF-less ACS patients, stratified according to geographical region (Asia-Pacific, Europe, and North America). Risk of bias was assessed using the Newcastle-Ottawa scale. Results A total of 25 studies comprising of 1,393,184 individuals with ACS were included, of which 242,929 patients were SMuRF-less. Within this SMuRF-less ACS group, mortality rates were similar across the regions (Asia-Pacific:15.8%, Europe:17.5%, p=0.861), cardiac arrest (6.3%, 95%CI:2.3% to 16.3%, p=0.001) and major bleeding (5.2%, 95%CI:2.9% to 9.2%, p=0.001) were more prevalent in Asia-Pacific, and heart failure more common in Europe (21.7%, 95%CI:18.2% to 25.7%, p<0.001). Prevalence of chronic obstructive lung disease (21.4%, 95%CI:21.2% to 21.6%, p<0.001) and peripheral artery disease (3.8%, 95%CI:3.1% to 4.7%, p=0.001) were highest in SMuRF-less ACS patients from North America, chronic liver disease most prevalent in those from Asia-Pacific (3.5%, 95%CI:2.2% to 5.6%, p<0.001) and family history of coronary artery disease highest in SMuRF-less ACS patients from Europe (25.2%, 95%CI:24.8% to 25.7%, p=0.024). Significantly lower rates of guideline-directed medical therapy prescriptions were observed for SMuRF-less ACS patients in Asia-Pacific compared to other regions. Conclusion This regional analysis highlights the different risk profiles, cardiovascular outcomes, and specific needs of individuals presenting with ACS in the absence of cardiovascular risk factors, across Asia-Pacific, Europe, and North America. Whilst unravelling novel pathomechanistic pathways of atherosclerosis will prove beneficial on a global scale, understanding the unique regional profile of these individuals will aid policymakers strategize effective and tailored clinical pathways in the management of SMuRF-less ACS.Graphical AbstractKey Outcomes

Scalable enzymatic lactate sensor for continuous monitoring in interstitial fluid

Abstract Elevated lactate levels have been shown to be an indicator of poor outcome in cardiovascular patients [1]. Moreover, continuous monitoring of lactate may be more clinically valuable than the absolute value of lactate for risk stratification [2]. A promising approach involves the implementation of a lactate monitoring system inspired by advanced continuous glucose monitoring [3] to provide real-time measurements of lactate in interstitial fluid (ISF) based on miniaturized lactate sensors with submillimeter dimensions. The proposed amperometric lactate sensor employs Pt electrodes (WE = 0.785 mm²) on which the enzyme lactate oxidase is immobilized to selectively detect lactate. The sensing mechanism, shown in Fig. 1a, is based on the conversion of lactate to hydrogen peroxide, which then undergoes oxidation at the electrode surface, generating a current proportional to the concentration of lactate. Amperometric measurements are performed with an applied potential of 0.5 V, a sample volume of 2 µL and a flow rate of 1 µL/min, respecting real-life conditions. The response of the sensor towards lactate is shown in Fig. 1c, demonstrating excellent reversibility, long-term stability over 8 hours and negligible cross sensitivity to glucose (G), ascorbic acid (AA) and uric acid (UA). In addition, the sensor linear range can be extended by 10x by incorporating an outer Nafion layer, acting as a diffusion-limiter. As shown in Fig. 1d, by adjusting the thickness of Nafion layer, the linear range increases up to 20 mM lactate, as per ICU specifications. The physiological challenges associated with ISF extraction prompted us to develop a minimally invasive, submillimeter-sized sensor for direct placement inside the body. To address the most critical step of miniaturization, we have successfully fabricated a three-electrode platform on a Si ribbon measuring 300x1500 µm² and a thickness of 100 µm (Fig. 2a). The sensor is also drastically scaled down, with smallest design having a total sensing area of 200x500 µm² (WE = 0.026 mm², Fig. 2b). Its response to lactate is displayed in Fig. 2c, confirming a reliable functionality. Fig. 2d presents the calibration curves obtained from sensors with different sizes, indicating that the reduction in size does not affect the sensitivity. The developed lactate sensor demonstrates excellent performance: high sensitivity, excellent reversibility, and high stability. In addition, the linear range of the sensor is tunable by integrating an outer Nafion membrane. Finally, we demonstrate the successful fabrication and characterization of submillimeter-sized sensors, opening up their potential for minimally invasive in-vivo measurements.Working principle and characterizationCharacterization miniaturized sensors

The obesity paradox in patients with hypertrophic cardiomyopathy: A Korean nationwide cohort study

Abstract Background In cardiomyopathies, obesity is known to affect the cardiac remodeling and is associated with a poor prognosis. However, in hypertrophic cardiomyopathy, which is included in the category of heart failure with preserved ejection fraction, the risk of underweight has been suggested, and its impact in practice is controversial. Purpose The aim of this study was to investigate the potential relationship between obesity and cardiovascular outcomes in patients diagnosed with hypertrophic cardiomyopathy. Methods We conducted a retrospective national cohort study from 2013 to 2020 utilizing administrative claims data and health check-up database from the Korean National Health Insurance Service. Patients newly diagnosed with hypertrophic cardiomyopathy from January 2015 to December 2019 were included. Body mass index was stratified into five groups based on the World Health Organization's recommended criteria for Asian populations, and patients were followed until the date of each outcome or the end of the study period. Predefined clinical outcomes included heart failure hospitalization events, fatal arrest events, all-cause death, and composite clinical outcomes. Results A total of 6,361 patients were included in the study, with a mean age was 60 ± 13 years and 32.6% female. During a median follow-up of 3.0 years (interquartile range, 1.8 to 4.3), 921 heart failure hospitalization, 185 fatal arrest, and 340 deaths occurred. The underweight group had higher adjusted hazard ratios for heart failure hospitalization, fatal arrest, all-cause death, and the composite outcome compared to the normal range body mass index group (HR 1.69, 95% CI 1.16-2.47; HR 2.29, 95% CI 1.06-4.93; HR 2.74, 95% CI 1.77-4.24; HR 1.77, 95% CI 1.28-2.45). In addition, the adjusted hazard ratios for the composite outcome were lower in the overweight and obese I group compared to the normal range (HR 0.80, 95% CI 0.68-0.95; HR 0.84, 95% CI 0.72-0.98). Conclusions Among patients with hypertrophic cardiomyopathy, those classified as underweight had an increased risk of heart failure hospitalization, fatal arrest, all-cause death, and composite outcomes compared with normal weight patients, while those classified as overweight and obese had a decreased risk of composite outcomes.

Prognostic impact of SGLT2-inhibitor therapy on survival in patients with transthyretin amyloid cardiomyopathy

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) significantly improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction. Recently published data indicates the safety and tolerability of SGLT2i therapy in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, there is a lack of evidence regarding the impact of SGLT2i therapy on clinical outcomes in those patients. Purpose This study aims to investigate the association between SGLT2i therapy and clinical outcomes in patients with ATTR-CM. Methods This is an analysis of a prospective registry conducted at an expert center for hypertrophic cardiomyopathies. We included all participants with a confirmed diagnosis of ATTR-CM, who were enrolled until December 2022. Prior and concomitant SGLT2i treatment was systemically assessed according to the patient interview and medical records. Patients’ outcomes were retrieved from local medical and health insurance records. Results We enrolled 116 patients, of whom 7 patients (6%) were treated with SGLT2i at inclusion and 44 patients (38%) were started on SGLT2i therapy during the observational period while 65 patients (56%) were SGLT2i-naïve. There were no significant differences in baseline characteristics between groups, as shown in the table. Median (interquartile range) age was 80 (76-82) years with 15% females. Median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 2844 (1519-5033) pg/ml, median estimated glomerular filtration rate (eGFR) 58 (46-69) ml/min/1,73m2, and median troponin T 56 (34-83) pg/ml. During a median follow-up of 2.6 (1.8-3.7) years, 28 patients (24%) died, of whom 6 patients (5%) were in the treatment group and 22 patients (19%) in the control group. In univariate Cox-regression analysis, SGLT2i treatment was significantly associated with a lower mortality (HR 0.325, 95%CI 0.132-0.802, p=0.015). This association persisted after adjusting for age and sex (HR 0.347, 95%CI 0.139-0.867, p=0.023). However, when treatment initiation time was considered, the benefit did not remain statistically significant. No significant associations between SGLT2i treatment and worsening heart failure hospitalizations or cardiovascular death were observed. Conclusion In a prospective registry-based cohort of patients with ATTR-CM, SGLT2i therapy was associated with significantly better survival, with a potential treatment initiation time bias. These results suggest that SGLT2i may exert beneficial effects in patients with ATTR-CM and warrant a randomized controlled trial.

Ten-year outcomes in patients with hypertension and primary hyperaldosteronism undergoing surgical adrenalectomy versus medical therapy: data from the multinational collaborative network TriNetX

Abstract Background Surgical adrenalectomy for resection of adenomas has been the standard approach for treating patients with secondary hypertension due to primary hyperaldosteronism. However, few studies explored long-term outcomes in patients treated with adrenalectomy when compared to patients treated with conservative management. Purpose To compare ten-year mortality and cardiovascular outcomes in patients with primary hyperaldosteronism treated with surgical adrenalectomy versus patients with primary hyperaldosteronism treated with medical therapy alone. Methods This retrospective cohort study used real-world data from healthcare organizations participating in the global health research collaborative network TriNetX. We performed propensity score matching for demographic and clinical characteristics and calculated hazard ratios, comparing 2.397 patients in each group. The outcomes were all-cause death, heart failure, and the composite endpoint ischemic stroke, hemorrhagic stroke, myocardial infarction, unstable angina, and aorta aneurysm or dissection (major adverse vascular events) during the 10-year follow-up. Results Patients undergoing surgical adrenalectomy had a lower incidence of all-cause death (3.0%) when compared with patients in medical therapy (5.0%) ( hazard ratio 0.60, 95% CI 0.45-0.81). Patients in the surgical group had a 4.6% incidence of heart failure and the medical therapy had an 8.6% incidence of heart failure (hazard ratio 0.54, 95% CI 0.42-0.69). The incidence of major adverse vascular events was lower in the surgical group (10.9%) compared to the medical therapy group (14. 1%) ( hazard ratio 0.76, 95% CI 0.65-0.90). Conclusion In patients with hypertension and primary hyperaldosteronism, surgical adrenalectomy was associated with lower 10-year mortality, heart failure, and major adverse vascular events compared to medical therapy alone.

Association of cardiac amyloidosis with cardiovascular outcomes after aortic valve replacement in patients with severe aortic stenosis: a systematic review and meta-analysis

Abstract Introduction Aortic stenosis (AS) and cardiac amyloidosis (CA) frequently coexist and is commonly observed in older individuals referred for aortic valve replacement (AVR). However, the association of CA with adverse outcomes after AVR has not been well established. Purpose This meta-analysis aimed to evaluate the association of CA with adverse cardiovascular outcomes in patients with severe AS after undergoing AVR. Methods A literature search was performed for studies evaluating patients with severe AS undergoing AVR, comparing clinical endpoints on follow-up for patients with and without CA. The clinical endpoints included all-cause mortality and heart failure (HF) hospitalization. Databases searched included Ovid MEDLINE, Embase, and Web of Science. Subgroup analysis was performed for short term (<30 days) and long term (>30 days) mortality. The search was not restricted to time or publication status. Results Five studies including 1,105 patients with severe AS (111 with concurrent CA, 904 without CA) met inclusion criteria. The mean follow-up duration was 24.6 months, mean age was 81.2 years and 55.4% were men. Mean echocardiographic aortic valve parameters included valve area of 0.715cm2, mean gradient of 41.8 mmHg, and peak velocity of 4.2m/s. The mean left ventricular ejection fraction was 58%. All except 1 study included only patients with ATTR CA while excluding other causes of CA. There was no statistically significant difference in all-cause mortality between patients with and without CA following AVR, both in short-term (OR 0.94; 95% CI 0.17-5.31; p=0.95) and long-term (OR 1.72; 95% CI 0.75-3.91; p=0.20) follow-up. However, patients without CA demonstrated a significantly lower risk of heart failure hospitalization post-AVR compared to those with CA (OR 2.49; 95% CI 1.18–5.23; p = 0.02). Conclusion In the context of patients with severe AS undergoing AVR, the presence of CA does not appear to significantly impact short-term or long-term all-cause mortality. Notably, patients without CA exhibited a lower risk of heart failure hospitalization following AVR. These findings underscore the importance of considering cardiac amyloidosis in the clinical management of severe AS and highlight potential differences in outcomes based on its presence or absence. Additional studies are needed to elucidate outcome differences for CA patients who undergo surgical versus transcatheter AVR.Figure 1

The long-term usage of statin prevents adverse events in patients with atrial fibrillation

Abstract Background The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Purpose Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF. Methods This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined. Results We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p < 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p < 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p < 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories. Conclusions Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.

Effect of physical activity level on the association of LBBB, heart failure, and mortality

Abstract Background The beneficial effect of physical activity (PA) on adverse cardiovascular outcomes in patients with heart failure (HF) and left bundle branch block (LBBB) is well established. Yet, the impact of PA on individuals with LBBB without evident HF remains unexplored. Our objective is to investigate how PA modifies the outcomes of new-onset LBBB patients concerning HF-related hospitalizations and mortality. Methods Among the UK Biobank participants without a diagnosis of HF, we identified individuals with new-onset LBBB and available PA quantification. Patients were dichotomized into normal QRS and LBBB groups, following by stratification according to summed minutes of PA per week. The primary outcome was all-cause mortality, and HF-related hospitalizations. Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results The final cohort comprised 367,934 individuals, with a mean age of 56.6±8.2 years and 47% male. Among them, 3,427 (0.9%) developed new-onset LBBB, characterized by advanced age, male predominance, and higher rates of comorbidities. Median summed PA minutes per week were 100 (IQR: 125-180), with no significant difference between normal QRS and LBBB patients. Over a median follow-up of 13.8 years (IQR: 13-14.5), 26,304 patients (7.15%) died. Kaplan-Meier analysis revealed higher mortality risk with reduced PA level and/or LBBB (log-rank p<0.001 for both). Multivariate Cox analysis adjusted for age, sex, and comorbidities showed LBBB patients had over 3.5-fold increased risk of death (HR 3.67, 95% CI 3.39-3.97, p<0.001) compared to normal QRS. The association of LBBB with mortality was modified by weekly PA minutes; those with <150 minutes had nearly 40% higher risk compared to those with ≥150 minutes (HR 3.78, 95% CI 3.43–4.15, p<0.001; HR 3.4, 95% CI 2.93–3.95, p<0.001; p for interaction=0.035). The protective effect of PA was 6% among normal QRS patients, compared to 22% among individuals with LBBB (HR 0.94, 95% CI 0.91 – 0.96, p<0.001 vs. HR 0.78, 95% CI 0.66 – 0.93, p=0.004). Similar findings were observed for HF hospitalizations. Conclusions Although the correlation between LBBB and adverse cardiovascular outcomes remained consistent across both levels of physical activity (PA), it was more pronounced among patients with low PA levels. When assessing the risk in patients with newly diagnosed LBBB, particular attention should be directed towards their PA status.

Body mass index may alter cardiovascular outcomes in patients with newly-diagnosed atrial fibrillation and previous stroke: an interaction analysis using longitudinal data from the GLORIA-AF registry

Abstract Background Patients with new onset atrial fibrillation (AF) and previous stroke (PS) are at higher risk of cardiovascular (CV) outcomes. An obesity paradox, where overweight or obese patients have better outcomes, has been seen. Whether body mass index (BMI) modify the risks of cardiovascular (CV) events and mortality in AF patients with PS remains uncertain. Purpose To ascertain whether BMI of AF patients with PS events alters risks of CV outcomes. Methods A cohort from phase III of the prospective GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) was included. Risks of Major Adverse Cardiovascular Events (MACE), CV death, and all-cause mortality were analysed using COX proportional hazard regression with interaction terms added between PS and the BMI characteristics. Results Data from 17482 patients [median age: 71.0 (IQR: 64.0–78.0) years; 45.3% female] with newly-diagnosed AF were analysed and included in risk models. At baseline, 1840 (10.5%) patients with AF had PS in which 1694 (9.7%) and 170 (0.97%) patients had one (1 PS) and ≥2 (2 PS) respectively. After a median follow-up of 3.0 (IQR: 2.9–3.1) years, 1111 MACE, 562 CV deaths, and 1266 all-cause deaths were recorded. In a multivariate COX regression model, interaction between BMI and PS was significant in predicting risk of CV death (Pint =0.019). BMI was also associated with increased risk of CV death among AF patients with ≥1 PS. The interaction between PS and BMI was borderline significant in predicting MACE (Pint=0.063) and all-cause death (Pint=0.057). Figure 1 showed the different risks associated with different BMI statuses. Conclusion The risks of adverse CV outcomes were higher in AF patients with higher BMI and previous stroke. An obesity paradox was not evident in AF patients with previous stroke.Figure 1