bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential echocardiographic profiles in immunoglobulin light chain and transthyretin amyloid cardiomyopathy: insights from speckle tracking analysis
Authors: Saijo Y , Yamada H , Zheng R , Takahashi T , Kawabata Y , Ueno R , Kadota M , Hara T , Matsuura T , Ise T , Yamaguchi K , Yagi S , Soeki T , Watkaysuki T , Sata M
Published: October 2024

Background

Amyloid cardiomyopathy is mainly caused by two main subtypes of amyloidosis; immunoglobulin light chains cardiomyopathy (AL-CM) and transthyretin cardiomyopathy (TTR-CM).

Purposes

The aim of the present study was to elucidate the differences in echocardiographic findings between AL-CM and TTR-CM using speckle tracking echocardiography.

Methods

The study included patients with a confirmed diagnosis of cardiac amyloidosis through cardiac biopsy and who underwent transthoracic echocardiography between March 2013 and October 2022. The relative apical sparing index (RASI) was calculated using speckle tracking echocardiography: mean apical strain value/(mean basal strain value + mean mid strain value).

Results

The final study population consisted of 50 patients with a confirmed diagnosis of cardiac amyloidosis diagnosed pathologically (AL-CM: 21 patients, TTR-CM: 29 patients). Mean age was 72 ± 11 years, 70% being male. AL-CM exhibited a lower left ventricular mass index compared to TTR-CM (124.5 ± 48.9 vs. 152.2 ± 39.2 g/m2, P = 0.001). In 35 patients available with longitudinal strain analysis, no significant difference was observed in left ventricular global longitudinal strain between the two subgroups (-9.9 ± 4.8 vs. -9.3 ± 2.4% , P = 0.63). However, RASI was significantly lower in AL-CM compared to TTR-CM as shown in Figure (0.92 ± 0.29 vs. 1.46 ± 0.53, P = 0.001). Receiver operating characteristic curve analysis shows a RASI cut-off value of <1.0 proved useful in differentiating the diagnosis of AL-CM from TTR-CM (sensitivity: 81%, specificity: 70%, AUC:0.82), and RASI <1.0 remained a significant association with the diagnosis of AL-CM, even after adjusted by conventional echocardiographic variables.

Conclusion

Apical sparing phenomenon was more remarkable in TTR-CM compared with AL-CM, although global longitudinal strain was comparable between the two groups. RASI was useful for the discrimination of cardiac amyloidosis subtypes.
Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction
Authors: Ricken K W L M , Panaou K , Al Ali L , Lenselink C , Van Dorp P , Pundziute G , Voors A A , Lipsic E
Published: October 2024

Background

Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI.

Purpose

To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI.

Methods

This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) >95 g/m2 for women and >115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI >95 g/m2 for women and >115 g/m2 for men with RWT >0.42. The different patterns in geometry were assessed at 4-months.

Results

Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p<0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p<0.001) and after 24 hours (1322 ng/l vs 784, p<0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991).

Conclusions

Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.
Prognostic value of echocardiographic parameters in predicting major adverse cardiac events one year following st-segment elevation myocardial infarction
Authors: Vishnevskaya I , Petyunina O , Kopytsya M
Published: October 2024

Approximately 50% of patients who survive an ST-segment elevation myocardial infarction (STEMI) experience irreversible damage to the heart muscle, which increases long-term risk of developing heart failure. Moreover, cardiovascular mortality constitutes half of all deaths.

This research aimed to determine the best combination of patient data collected during a one-year follow-up period to enhance the accuracy of outcome predictions for patients with STEMI.

Methods

In this study, 246 patients who experienced STEMI and older than 18 were prospectively monitored. All participants received primary percutaneous coronary intervention treatment. The study's primary outcomes, observed over the year following hospital discharge, included cardiovascular death, recurrent myocardial infarction, newly diagnosed heart failure, and arrhythmias or conduction issues. Of the patients, 18% of patients reached the primary outcomes. Two-dimensional transthoracic echocardiography was conducted 3-5 days after the initial event to assess left ventricular global longitudinal strain (GLS) using 2D speckle-tracking echocardiography on the apical four-chamber, two-chamber, and long-axis views. Left ventricular mechanical dispersion was calculated as the standard deviation of the time from the Q/R wave onset to peak GLS across 17 segments of the left ventricle.

Results

The findings revealed that the overall GLS was -10.70 (-12.61 to -8.40), but in patients who met the study's primary outcomes, GLS was significantly lower at -7.83 (-8.70 to -6.90), compared to -12.02 (-13.11 to -10.17) in those who did not, with a significant difference (p=0.00001). Mechanical dispersion was 40.24±26.56 in the entire cohort but significantly higher at 65.62±22.57 in the outcome group compared to 25.79±14.81 in the non-outcome group (p=0.00001). The ejection fraction averaged 48.97±7.69% across all patients, 47.22±7.16% in those with outcomes, and 49.92±7.84% in those without, with a statistically significant difference (p=0.039). Cox regression analysis identified key predictors of major adverse cardiac events (MACE) within one year after STEMI, including global longitudinal strain (p=0.0006), left atrium volume index (p=0.0448), left ventricular end-diastolic diameter (p=0.045), and mechanical dispersion (p<0.0001). A multivariate logistic regression analysis demonstrated that a combination of GLS, left ventricular end-systolic volume (LVESV), mechanical dispersion, and ejection fraction could predict 1-year MACE with high accuracy (χ2 = 85.18; p<0.0001, AUC=0.961 [0.903-0.989]).

In conclusion, this study identifies crucial metrics, such as global longitudinal strain, left ventricular end-systolic volume, mechanical dispersion, and ejection fraction, as predictive factors for MACE one year following STEMI. This predictive model is straightforward, reproducible, and can be easily implemented in cardiology practice.
Angina pectoris prevalence and sick leave burden one year after MINOCA
Authors: Welen K , Tornvall P , Lindahl B , Nordenskjold A , Jernberg T
Published: October 2024

Background

Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents approximately 5-10% of all myocardial infarctions (MI), with heterogenous etiologies and insufficient knowledge on symptom burden after the acute phase.

Purpose

To evaluate the prevalence of angina and sick leave in MINOCA, using individuals with MI due to coronary artery disease (MI-CAD) as control.

Methods

This observational study used prospectively collected data from the Swedish national quality register SWEDEHEART. All individuals with invasively assessed, first time MI between 2005 – 2022, available at one year follow-up were included and categorized as MINOCA (normal coronary arteries or <50% lumen obstruction) or MI-CAD (>50% lumen obstruction). We excluded subjects with previous coronary intervention, previous heart failure, tachy- or bradyarrhythmia at admission and not fully revascularized MI-CAD. Chest pain was assessed by a clinical nurse and angina graded according to the Canadian Cardiovascular Society, excluding non-ischemic chest pain. Occupational status was self-reported.

Results

We included N=46 428 individuals (mean age 62, 71% male; MINOCA n= 5281/MI-CAD n=41 157). Subjects with MINOCA were predominantly females, more commonly divorced or widowed, non-smoking and had a higher degree of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease, compared to fully revascularized MI-CAD. Angina prevalence was 11.6 % and 8.8% in MINOCA and MI-CAD respectively (p <0.001). After adjustment for background variables clinically relevantly associated to both MI type and anginal status OR was 1.21 [95% CI 1.10 – 1.34] (Figure 1). Sick leave was more common in MINOCA both at index care, and at one year (8.0 vs 5.6 % and 13.4 vs 10.9%, both p <0.001) (Figure 2).

Conclusion

MINOCA patients suffer significant distress, with higher levels of angina and sick leave compared to fully revascularized MI-CAD counterparts. Further research on causes of ischemic symptoms in this heterogenous condition is warranted.
Sex differences in atherogenic lipid profile following acute coronary syndrome
Authors: Yang J , Zhang R U I , Li S W , Li X I N
Published: October 2024

Background

Despite significant advancements in lipid-lowering therapy, the management of dyslipidemia remains challenging in patients with acute coronary syndrome (ACS). Significant differences are shown in lipid panels and management between different sexes following ACS.

Objective

To shed light on the alterations and characteristics of atherogenic lipoproteins and the characteristics of patients who achieve LDL-C targets after statin treatment, harnessing real-world data from electronic health records of patients with ACS after their discharge between sexes.

Methods

The data in the present study were derived from the iHeart program sponsored by the Chinese Cardiovascular Association. Eligible patients with a diagnosis of ACS from January 2014 to December 2021 during hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed the control of atherogenic lipid profiles between sexes. The primary outcome was the achievement of the LDL-C target, defined as LDL-C <1.8 mmol/L. A multivariable logistic regression model was used to assess the associations between patient characteristics and LDL-C achievement.

Results

Between 2012 and 2021, 4861 patients (1299 [26.7%] women) were hospitalised with a primary diagnosis of ACS (49.2% STEMI, 13.8% NSTEMI, and 33.8% UA). The mean age was 64.9 (12.4) years. In contrast to a higher proportion of AMI in men, more prevalence of UA was observed in women. Women had more cardiovascular comorbidities than men and were more likely to receive lipid-lowering therapies, blood pressure-lowering therapies, glucose-lowering therapies, and antiplatelet medications at discharge. In both men and women, TC, TG, LDL-C, ApoB, and non-HDL-C levels significantly decreased within 12 months (P<0.05). Women had less reduction in atherogenic lipid profile than men. The rate of LDL-C <1.8 mmol/L was similar between sexes (14.3% vs16.1%; P=0.136) at baseline, whereas within 12 months after discharge, women had a much lower achievement rate of LDL-C target than men (34.6% vs 45.6%; P<0.001). The risk factors for non-achievement of the LDL-C target in men were revascularisation, history of MI, atrial fibrillation, newly diagnosed MI, and high baseline LDL-C levels. For women, the risk factor was hypertension and diabetes.

Conclusion

Substantial sex disparities were observed in the management of atherogenic lipids. Despite a higher likelihood of receiving guideline-recommended medical therapy at discharge, women had poorer lipid control compared to men, especially among those with NSTEMI.
Mortality related to left ventricular ejection fraction and obstructive coronary artery disease in non-ST-segment elevation myocardial infarction
Authors: Stoedkilde-Joergensen N , Olesen K K W , Gyldenkerne C , Thrane P G , Hansen M K , Noergaard B L , Nielsen R R , Maeng M
Published: October 2024

Background

Extent of coronary artery disease (CAD) and the severity of reduced left ventricular ejection fraction (LVEF) have both been associated with the prognosis after non-ST-segment elevation myocardial infarction (NSTEMI). However, the contemporary mortality associated with the extent of obstructive CAD over a range of LVEF remains uncertain.

Purpose

The aim of this study was to assess the impact of CAD and LVEF on all-cause death following a first-time NSTEMI.

Methods

We included consecutive first-time NSTEMI patients undergoing coronary angiography from 2010 to 2021 in Western Denmark. Patients were stratified by extent of obstructive vessel disease (VD; 1, 2, or 3VD) and LVEF (≥51%, 41-50%, or 10-40%). Patients with previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting were excluded. The primary outcome was all-cause death. We calculated 5-year cumulative incidence proportions (CIP) as a measure of absolute risk and adjusted hazard ratios (HR).

Results

A total of 8,770 patients with first-time NSTEMI and obstructive CAD were examined with coronary angiography. Two-thirds were male and median age was 68 years (Q1-Q3: 58-78). The increase in mortality associated with decreasing LVEF was greater than observed by extent of CAD (Table). Thus, the 5-year mortality increased stepwise by extent of CAD from 14% for 1VD to 31% for 3VD (adjusted HR 1.35, 95% CI:1.19-1.54), but from 12% for LVEF ≥51% to 40% for LVEF 10-40% (adjusted HR 2.32, 95% CI: 2.04-2.65). When combining LVEF and extent of CAD, an increase in 5-year mortality was found from 9% for 1VD and LVEF ≥51% to 46% for 3VD and LVEF 10-40% (risk difference of 37.1%; Figure). Correspondingly, using 1VD and LVEF ≥51% as reference, the adjusted HRs increased gradually with extent of CAD and decline in LVEF to 3.05 (95% CI: 2.51-3.70) for patients with 3VD and LVEF 10-40% (Table).

Conclusion

In a contemporary all-comers cohort of first-time NSTEMI patients, increasing extent of CAD and declining LVEF are both associated with a gradual increase in 5-year mortality. Our data suggest that the level of LVEF reduction was more strongly associated with 5-year mortality than CAD extent.
Association of contemporary hormonal contraception and the risk of arterial thrombosis
Authors: Yonis H , Kragholm K , Granger C B , Torp-Pedersen C , Meaidi A
Published: October 2024

Background

While contemporary hormonal contraception is effective in preventing unwanted pregnancies, its potential link to an increased risk of stroke and myocardial infarction raises safety concerns.

Purpose

This study aimed to investigate the association between the use of contemporary hormonal contraception and the occurrence of ischemic stroke and myocardial infarction.

Methods

A nationwide prospective cohort study was conducted, comprising of all Danish women aged 15-49 years without a history of arterial and venous thrombosis, thrombophilia, and cancer from 1996 to 2021. Data on hormonal contraception use, stroke and myocardial infarction diagnoses, and potential confounders were collected from nationwide registers. A Poisson regression analysis was performed adjusting for age, education level, calendar year, hypertension, statin use, diabetes, and atrial fibrillation.

Results

The study followed 2,205,794 women over 23,700,659 person-years. Weighted median age was 33 (interquartile range (IQR): 24-41) for non-users and 25 (20-34) for users. A total of 5,346 ischemic strokes (22.6 per 100,000 person-years) and 2,351 myocardial infarctions (9.9 per 100,000 person-years) occurred during the study period. When compared to no use, oral contraceptives containing ethinyl estradiol at a dose of 30 to 40 μg was associated with the following adjusted incidence rate ratios (and 95% confidence intervals) for ischemic stroke and myocardial infarction, according to progestin type: levonorgestrel, 1.9 (1.7 to 2.2) and 2.0 (1.7 to 2.4); norgestimate, 1.9 (1.5 to 2.3) and 1.9 (1.4 to 2.6); desogestrel, 2.4 (2.0 to 2.9) and 2.2 (1.6 to 3.0); gestodene, 1.9 (1.7 to 2.2) and 1.9 (1.5 to 2.2); drospirenone, 2.0 (1.6 to 2.5) and 1.8 (1.1 to 2.8); cyproterone acetate, 1.7 (1.2 to 2.3) and 2.1 (1.3 to 3.4), respectively.

At a dose of 20 μg of ethinyl estradiol, the incidence rate ratios for ischemic stroke and myocardial infarction varied based on the type of progestin as follows: desogestrel, 1.9 (1.6 to 2.2) and 1.4 (1.0 to 1.9); gestodene, 1.7 (1.4 to 2.0) and 1.7 (1.2 to 2.4); drospirenone, 1.4 (0.7 to 2.6) and 1.1 (0.3 to 4.4); For transdermal patch, the incidence rate ratio was 3.4 (1.4 to 8.2) and 0.0 (0.0 to 0.0); for vaginal ring, 2.2 (1.4 to 3.3) and 3.2 (1.7 to 6.3); for intrauterine device, 1.1 (0.9 to 1.2) and 1.1 (0.9 to 1.3); for implant, 2.0 (1.2 to 3.5) and 1.3 (0.4 to 3.9); for injection, 1.9 (0.9 to 3.8) and 0.6 (0.1 to 4.0).

Conclusion

Use of contemporary hormonal contraception appeared to be associated with ischemic stroke and myocardial infarction when compared to non-users. The incidence rate ratios varied across type of hormonal contraception, estrogen dose, progestin type and route of administration. The findings underscore the importance of informed decision-making when considering contraceptive options, with implications for public health and individual health choices.FlowchartAdjusted incidence rate ratios
Prevalence and temporal trends of risk factors among young patients with acute myocardial infarction - a nationwide cohort study
Authors: Simonsson M , Reitan C , Andell P
Published: October 2024

Background

Cardiovascular disease, including acute myocardial infarction (AMI) is the leading cause of death globally.(1) While the risk of AMI is higher with increasing age, the consequences of AMI can be more severe in younger individuals, causing larger loss-of-life-expectancy and imposing burdens for society in terms of healthcare costs and premature retirements. Description of the young AMI cohort is of greatest interest to identify modifiable risk factors and/or other predisposing factors that may be optimized.

Aims

To describe the prevalence and temporal trend of risk factors among young individuals with AMI.

Methods

We used data from the SWEDEHEART registry, the National Patient Registry, the Drug Prescription registry and the Swedish Population registry. Adult young patients, defined as 18-59 years, admitted with a first AMI from January 2003 to January 2022 were included. Prevalence of the potentially modifiable risk factors; hypertension, diabetes, hyperlipidemia, smoking and obesity was defined on admission. In the analyses the cohort was further divided into two age groups 18-44 and 45-59 years.

Results

From January 2003 to January 2022, 249 735 patients were admitted with a first AMI and among these, 50 281 (20.1% of the total AMI cohort) were classified as young and included in the study. 44 243 (88.0%) patients were 45-59 years and 6038 (12%) were 18-44 years. The overall prevalence of risk factors was substantial, with higher rates observed in women compared to men (Table 1a) and in the older age group, except for obesity, which was more common in the younger age group (Table 1b). While the prevalence of diabetes and hyperlipdemia remained unchanged over time, smoking decreased and hypertension slightly increased. Notably, the prevalence of obesity more than doubled (Figure 1).

Conclusion

Among young AMI patients the prevalence of modifiable risk factors was substantial with an even higher prevalence in women than in men. The increasing prevalence of obesity especially in the younger age group may indicate a potential future rising health care risks.Figure 1
Association of culprit lesions with in-hospital mortality in patients with acute coronary syndrome complicated by cardiogenic Shock
Authors: Matsushita S , Sawayama Y , Fujita M , Oka S , Taninobu N , Sasaki K , Osakada K , Kadota K
Published: October 2024

Background/Introduction

The Society for Cardiovascular Angiography and Interventions (SCAI) shock stage is useful for stratifying short-term prognosis in patients with acute coronary syndrome (ACS). However, the impact of culprit lesion location for ACS on prognostic stratification by the SCAI shock stage remains insufficiently elucidated.

Purpose

This study aims to investigate the association between culprit lesion location for ACS and shock severity on in-hospital mortality.

Methods

We retrospectively investigated consecutive ACS patients who underwent percutaneous coronary intervention at a single center between January 2014 and October 2023. Patients were classified into five groups (No risk, Stage A, Stage B, Stage C, and Stage E) based on data at arrival in the emergency department using SCAI classification. The following culprit lesions were included in this analysis: left main coronary artery (LMCA), proximal right coronary artery (RCA), proximal left anterior descending artery (LAD), and proximal left circumflex artery (LCX).

Results

Of 1,665 patients included in the analysis, the mean age was 72±12 years, and females accounted for 26% overall. The distribution of SCAI shock stages by culprit lesions is shown in Figure 1. The proportion of stage B or higher in the LMCA, RCA, LAD, and LCX was 41%, 23%, 24%, and 24%, respectively. The corresponding in-hospital mortality was 20%, 3%, 5%, and 3%, respectively. The trend of in-hospital mortality stratified by shock severity and culprit lesions is demonstrated in Figure 2. LMCA and LAD showed increased in-hospital mortality with progressing shock severity. In contrast, this trend was not observed for RCA and LCX.

Conclusions

Except for LMCA, the proportion of shock stage B or higher was comparable. SCAI shock stage classification was useful in stratifying in-hospital mortality in patients where culprit lesions for ACS were LMCA and proximal LAD. Conversely, its validity in those with proximal RCA and LCX may be limited.
Machine-learning based calculator for personalized risk following ST-elevation myocardial infarction
Authors: Kodesh A , Bental T , Loebl N , Kornowski R , Perl L
Published: October 2024

Background

Despite recent advancements in the management of patients with ST-elevation myocardial infarction (STEMI), a high risk for adverse events remains during the first year following the event. There are several risk scores which estimate the risk of major adverse cardiac events (MACE) following STEMI. However, the most established risk scores are not contemporary, their diagnostic accuracy ranges across populations, and they are far from being personalized.

Purpose

We aimed to develop a machine learning (ML)-based calculator to provide patients and physicians with a personalized prognostic tool based on modern-world data to determine outcomes for patients following STEMI. Our goal was to predict mortality within 1-year post-STEMI and contribute personalized recommendations to reduce the risk of events. Additionally, we aimed to have the calculator provide a personalized risk assessment for each independent variable.

Methods

We included patients from two large tertiary care centers in Israel and Italy. 2888 patients who suffered STEMI between the years of 2000 – 2020 were included in our training model. Our calculator leveraged CatBoost for supervised machine learning, utilizing gradient boosting on decision trees. The model was subsequently tested on 321 patients from the Israeli center and 132 patients from the Italian center.

Results

The calculator was able to accurately predict 1-year mortality (96.5% accuracy, ROC 0.97 in the Israeli center and 93.2% accuracy, ROC 0.89 in the Italian center). In the full cohort, left ventricular ejection fraction (LVEF) post-STEMI demonstrated the strongest contribution towards predicted outcome with a mean Shapley value (SHAP) of 0.978, with lower EFs correlating to higher likelihood of one-year mortality (figures 1 and 2). Other strong contributing factors were identified, including glomerular filtration rate (GFR), age, and Killip classification, with mean SHAPs of 0.580, 0.571, and 0.563, respectively. Importantly, the algorithm was designed to also output a personalized assessment of risk for each patient based on their individual variables.

Conclusion

ML-derived STEMI calculators can determine which risk factors and variables provide highest predictive value in determining outcomes in a personalized manner. They can be leveraged for high-accuracy prognostication and provide guidance for physicians and patients after STEMI.
Ethnic disparity in the care and management of non-ST-segment elevation myocardial infarction and its impact on short-term and long-term survival: a long-term study of a national registry
Authors: Yera H , Weight N , Moledina S M , Mamas M A
Published: October 2024

Background

Previous examination of data from the United Kingdom indicates no apparent ethnic disparity in the treatment of patients hospitalised with non-ST-segment elevation myocardial infarction (NSTEMI). However, it remains uncertain whether this lack of disparity results in similar long-term survival outcomes among ethnic minority groups, particularly those with multiple underlying risk factors for coronary artery disease, when compared to White patients.

Purpose

To assess the impact of quality of care on short-term and long-term survival among NSTEMI patients while examining disparities based on ethnicity.

Methods

We analysed records of 252,964 individuals diagnosed with NSTEMI from the Myocardial Ischaemia National Audit Project database spanning 2005 to 2019, alongside Office of National Statistics data for mortality. Among them, 233,158 were identified as White patients, while 19,806 were categorised as belonging to ethnic minority groups (Asian, Black, and mixed ethnicity). Propensity score matching was used to compare average treatment effects between cohorts while survival was compared using Cox regression model.

Results

Ethnic minorities were younger (median age in years) (66 vs. 73, P < 0.001), predominantly male (70% vs. 63%, P < 0.001), and exhibited a higher prevalence of cardiovascular risk factors such as diabetes (52% vs. 24%, P < 0.001), hypertension (67% vs. 54%, P < 0.001), hypercholesterolemia (49% vs. 34%, P < 0.001), and chronic renal dysfunction (13% vs. 8%, P < 0.001). Ethnic minorities more frequently underwent invasive coronary angiography (80% vs. 68%, P < 0.001), percutaneous coronary intervention (53% vs. 44%, P < 0.001), and coronary artery bypass grafting (5% vs. 4%, P < 0.001). After conducting propensity score matching, both cohorts had no significant differences in in-hospital all-cause mortality [odds ratio (OR) 1.13, confidence interval (CI) 0.89 – 1.43; P = 0.268], cardiac mortality (OR 1.20, CI 0.89 – 1.54; P = 0.209), one-year mortality (OR 1.01, CI 0.89 – 1.13; P = 0.893) and major adverse cardiovascular events (OR 1.21, CI 0.95 – 1.48; P = 0.108). However, upon conducting a five-year survival analysis, ethnic minorities had better survival rates than their White counterparts (Hazard ratio (HR) 0.89, CI 0.86-0.92; P < 0.001).

Conclusions

Despite ethnic minorities being at a higher risk for coronary artery disease, our findings indicate that they experience better five-year survival rates than White patients. This suggests equitable access to care and potentially a more aggressive treatment approach in this relatively young patient cohort.
Sex-specific models to predict 5-year mortality after ST-elevation myocardial infarction using machine learning: insight from FAST-MI registry
Authors: Singh M , Hamzi K , Toupin S , Dillinger J G , Henry P , Cayla G , Schiele F , Ferrieres J , Simon T , Danchin N , Pezel T
Published: October 2024

Background

Most prognostic stratification tools in acute myocardial infarction (AMI) have been derived from populations including both women and men and including only a small proportion of women.

Purpose

Using supervised machine learning (ML), we examined the performance of 2 models assessing 5-year mortality after AMI, one derived from a population of women only and one from a population of men only, to determine whether sex-specific models improved outcome prediction.

Methods

This cohort study used the French registry on acute ST-elevation and non-ST-elevation myocardial infarction (FAST-MI) 2010 and 2015 surveys. This multicentric registry led in more than 200 French hospitals, enrolled all consecutive patients with acute myocardial infarction during a 1-month recruitment period. Our analysis included all men and women presenting STEMI who underwent invasive coronary angiography (ICA). To build and validate the models, the data set were split with a 70%/30% ratio into training and testing sets. The primary outcome was 5-year all-cause mortality. Then, 52 clinical, laboratory, ECG, echocardiographic, and ICA parameters were evaluated for feature selection using Boruta algorithm. Different supervised machine learning algorithms, including random forest (RF), were assessed for model building, and their performance were compared in women and men. To compare prediction accuracy according to sex, we evaluate the performance of the women-based ML model in men from the same cohort.

Results

1,189 consecutive women and 3,685 men with STEMI (mean age 61±13 and 69±15 years, respectively) were recruited; 12% of men and 20% of women experienced 5-year all-cause mortality. Using Boruta algorithm, the 10 most important variables for prediction were selected (Figure 1). For women-based ML model building, the RF algorithm exhibited the best performance to predict mortality with an area under the receiver-operating characteristic curve (ROC-AUC) of 0.82 (95% CI: 0.77 – 0.88), an area under the precision-recall curve (PR-AUC) of 0.59 (95% CI: 0.54 – 0.64); and a F1-score of 0.58. The women-based ML model exhibited lower performance in men (ROC-AUC: 0.78; PR-AUC: 0.43; Figure 2). Conversely, the men-based model exhibited better accuracy in men than in women.

Conclusion

In a large multicentric cohort of STEMI patients, a women-based ML-model exhibited a good accuracy to predict 5-year all-cause mortality in women, but a drop of accuracy when applied to men. In mirror, the accuracy of the men-based model was lower in women. This suggests that sex-specific models might be superior to general models to predict mortality after AMI.Features selection and ML model buildingML model performance according to sex
Rapid rule-out of acute myocardial infarction using the 0/1-hour algorithm for cardiac troponins in emergency primary care: the OUT-ACS implementation study
Authors: Johannessen T R , Vallersnes O M , Atar D , Halvorsen S , Larstorp A C K , Nilsen B , Ruud S E
Published: October 2024

Background

Acute chest pain in primary care often results in defensive and unnecessary hospital referrals due to the limited ability to rule out an acute myocardial infarction (AMI) outside of hospital. In a previous prospective observational study (OUT-ACS; One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome), we demonstrated that the ESC 0/1-hour algorithm for high-sensitivity cardiac troponin T (hs-cTnT) would be safe and cost-effective if implemented to assess low-risk patients with chest pain in emergency primary care.

Purpose

We evaluated the real-world applicability, personnel adherence, and disposition of low-risk patients with chest pain following the implementation of the ESC 0/1-hour algorithm in emergency primary care.

Methods

In April 2023, the ESC 0/1-hour algorithm for hs-cTnT was implemented at a large emergency primary care clinic in Norway. The clinic is located close to a hospital, enabling the patient to wait at the clinic while blood samples are analysed for hs-cTnT at the hospital laboratory. For the following six months, all patients ≥18 years with acute non-traumatic chest discomfort, offered hs-cTnT measurements at the clinic, were anonymously registered, including their discharge diagnoses and disposition from the clinic. By applying the ESC 0/1-hour algorithm, patients were assigned to rule-out, rule-in or further observation. Patients in the observation group were offered a 4-hour hs-cTnT measurement before a final decision.

Results

During the six-month period, 10.3% (n=3,053/29,631) of the clinic's consultations involved chest complaints. Hs-cTnT measurements were conducted in 32.6% (n=995/3,053) with a median age of 58 years (IQR 45-68), 50.6% being female. A single hs-cTnT <5 ng/L, sampled ≥3 hours since symptom onset, triaged 24.1% (n=240/995) of the patients towards the rule-out group, increasing to 63.8% after adding a 1-hour measurement. In the rule-in group (n=42/995, 4.2%), 16 patients were diagnosed with an AMI. The intermediate observation group (n=318/995, 32.0%, 4 AMIs) was reduced to 23.0 % after a 4-hour hs-cTnT measurement. Healthcare personnel adhered well to the algorithm, with a median sampling interval of 63 minutes (IQR 60-66) and 4.5 hours (IQR 4.1-5.5) for the 1- and 4-hour measurements, respectively. The algorithm was misinterpreted or overruled in 8.8% of the cases. Ultimately, only 14.8% required hospital transfer following troponin assessment at the clinic. The remaining patients were sent home or managed in the outpatient setting.

Conclusions

The OUT-ACS strategy, utilizing a 0/1/4-hour algorithm for hs-cTnT measurements in emergency primary care, is safe, effective and applicable, and the strategy contributes to reduced hospital referrals for low-risk patients with chest pain.0/1/4-hour algorithm for hs-cTnTDisposition
Identifying low-risk chest pain in out-of-hours primary care: the diagnostic performance of preHEAR and preHEART scores based on two European cohorts
Authors: Johannessen T R , Melessen I M , Vallersnes O M , Manten A , Halvorsen S , Atar D , Harskamp R E
Published: October 2024

Background

Distinguishing cardiac from non-cardiac acute chest pain presents a diagnostic challenge. Risk stratification tools, such as the HEART score, have been developed for decision support for hospital-based settings. For prehospital settings, the preHEART score was developed as an alternative to the HEART score, with refinements made to meet prehospital conditions, as illustrated in Figure 1. While promising for use by emergency medical services, the diagnostic performance in primary care is unknown.

Purpose

In this study, we aim to evaluate the preHEART score (with and without high-sensitivity cardiac troponin (hs-cTn)) as a risk stratification tool to rule out acute myocardial infarction (MI) in patients evaluated in out-of-hours primary care.

Methods

We relied on retrospective data from two cohorts, namely, the OUT-ACS study involving 1,711 consecutive patients (47.7% female, median age: 56 (25th-75th percentiles: 45-68)) evaluated at a Norwegian primary care emergency centre from 2016-2018; and the TRACE study involving 664 consecutive patients (56.9% female, median age: 48 (25th-75th percentiles: 32-67) from a Dutch primary care emergency centre in 2017. We evaluated the preHEAR (OUT-ACS & TRACE without hs-cTn) and preHEART scores (OUT-ACS). The threshold of ≤3 points was considered low-risk and previously determined as optimal for rule-out purposes. The primary outcome was the diagnostic performance for ruling out MI at the index episode, and the secondary outcome was the composite of 90-day all-cause death or MI.

Results

In the OUT-ACS cohort, 61 (3.6%) patients were diagnosed with an MI; for the TRACE study, MI was diagnosed in 20 (3.0%) patients. The percentage of patients deemed at low risk by preHEAR was 49.3% (n=843) and 82.7% (n=549) for OUT-ACS and TRACE, respectively. For preHEART, only 33.6% (n=575) of OUT-ACS patients were deemed low-risk. As shown in Figure 2, the corresponding sensitivity/specificity indices for index MI were 63.9%/49.8% (OUT-ACS) and 65.0%/84.2% (TRACE) for preHEAR and 93.4%/34.6% for preHEART. Positive predictive values were low (preHEAR 5.0-11.3%, preHEART 5.0%), whereas negative predictive values were high (preHEAR 97.4-98.7%, preHEART 99.3%). For the secondary outcome, similar diagnostic performance metrics were found. All missed MI cases (n=4) in the low-risk preHEART group were female.

Conclusion

The preHEAR and preHEART scores did not result in adequate rule-out safety for an emergency primary care setting despite a low a priori MI risk. Moreover, the score appears to underestimate the risk for MI in females.preHEAR(T) risk scoresPerformance of the risk scores
Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD
Authors: Apple F , Mills N L , Vasile V C , Schulz K , Sexter A , Jaffe A S
Published: October 2024

Background/Introduction

The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome.

Methods

In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay.

Results

Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from <2 to <7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days.

Conclusions

Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.
Multi-biomarker approach for predicting cardiac magnetic resonance parameters at 30 days after ST-segment elevation myocardial infarction
Authors: Horbach T , Wenzl F A , Manka R , Raeber L , Pedrazzini G , Carballo D , Keller T , Sossalla S , Von Eckardstein A , Matter C M , Ruschitzka F , Luescher T F , Staehli B E , Klingenberg R
Published: October 2024

Background

Prior data showed associations of circulating Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9) and inflammatory/anti-fibrotic Cellular Communication Network factor 1 (CCN1) at index ST-segment elevation acute myocardial infarction (STEMI) with left ventricular ejection fraction at 6 and 12 months, respectively and for CCN1 also with infarct size.

Purpose

PCSK-9, CCN1 and reference biomarkers high-sensitivity Troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NTproBNP) were measured in patients from the CLEVER-ACS trial (clinicaltrials.gov NCT01529554) at presentation with STEMI and correlated with clinically relevant cardiac magnetic resonance (CMR) parameters at 30 days.

Methods

Associations between baseline biomarkers (PCSK-9, CCN1, hsTNT, NTproBNP) and CMR parameters at 30 days were evaluated using Spearman correlation and linear regression analysis (dichotomised at their median). Receiver operating characteristic (ROC) and area under the curve (AUC) were determined for significant values based on correlation analysis; AUC > 0,7 considered relevant. CMR parameters comprised left ventricular structural and functional parameters including scar mass and microvascular obstruction.

Results

We identified 56 STEMI patients (mean age 61.7 ± 11.2 (SD) years) who completed 30 days follow-up with biomarker data. Among biomarkers, significant associations with CMR parameters were only found for hsTNT, and NTproBNP. The strongest associations were found for left ventricular ejection fraction (LVEF; hsTNT RSp =-0.66; NTproBNP RSp =-0.57), left ventricular scar (LVSCAR; hsTNT RSp =0.58; NTproBNP RSp =0.56) and scar mass (SM; hsTNT RSp =0.65; NTproBNP RSp =0.55). Conversely, left ventricular end-diastolic volume index (LVEDVI; hsTNT RSp =0.47; NTproBNP RSp =0.32), left ventricular end-systolic volume index (LVESVI; hsTNT RSp =0.51; NTproBNP RSp =0.39) and microvascular obstruction (MVO; hsTNT RSp =0.34; NTproBNP RSp =0.34) were significantly, albeit only modestly associated.

ROC and AUC analysis yielded relevant associations of biomarkers with CMR parameters LVEF (hsTNT=0.79; NTproBNP=0.81), LVSCAR (hsTNT=0.84; NTproBNP=0.76) and scar mass (hsTNT=0.83; NTproBNP=0.78). Furthermore, relevant associations of biomarkers with CMR were found for LVEDVI (hsTNT=0.79; NTproBNP=0.72), LVESVI (hsTNT=0.84; NTproBNP=0.72) and MVO (hsTNT=0.72; NTproBNP=0.71).

Conclusion

Baseline levels of hsTNT and NT-proBNP are strong predictors for functional and dimensional CMR parameters of the left ventricle including clinically relevant imaging surrogates of myocardial injury shortly after STEMI.ROC LVEF
Circulating nucleases degrade high-molecular-weight cell-free DNA in coronary vessels during acute myocardial infarction
Authors: Artner T , Ondracek A S , Hofbauer T M , Scherz T , Sharma S , Rinderer J , Panzenboeck A , Testori C , Beitzke D , Mangold A , Lang I M
Published: October 2024

Introduction

Extracellular cell-free DNA (cfDNA) originates from various biological processes, including cell turnover, apoptosis, necrosis, NETosis, and other forms of cell death. In healthy individuals, highly fragmented cfDNA is elevated in the bloodstream due to infection, cancer, inflammation and thrombosis. In thrombotic vascular diseases, neutrophils release elongated, high-molecular-weight DNA with bioactive and prothrombotic properties in a process termed NETosis. Circulating nucleases are thought to counteract pathogenic properties of NETs. However, attempts to connect total cfDNA concentration to nuclease activity have failed.

Purpose

We aimed to elucidate the in vivo connection between extracellular DNA and circulating nucleases in thrombotic vascular diseases by investigating DNA length as a potential novel biomarker in cardiovascular disease.

Methods

Citrated plasma from healthy volunteers (n=363) and from ST-elevation myocardial infarction (MI) coronary aspirates (n=59) and peripheral arterial sites (n=96) were analyzed for DNA concentration, length, and nuclease activity. Total DNA concentration was measured with a fluorescent DNA binding dye, and elongated DNA assessed using qPCR and Agilent bioanalyzer high-sensitivity DNA chip. Nuclease activity was measured by single radial enzyme-diffusion (SRED) assay. Cardiac MRI assessed infarct size acutely and six months after the event.

Results

Coronary aspirates exhibited an elevation in total DNA, with a significant rise in high-molecular weight cell-free DNA in addition to an increase in sub-nucleosome fragmentation (Figure 1). Peripheral and coronary plasma samples from individuals with myocardial infarction (MI) showed elevated levels of total and elongated cfDNA. When compared to healthy individuals, the integrity of cfDNA was lower in peripheral samples and higher in coronary aspirates. During myocardial infarction, circulating nuclease activity was elevated systemically but low at the coronary culprit lesion site. Elongated high-molecular-weight cfDNA accumulates primarily in coronary vessels but is also elevated systemically. In coronary aspirates, nuclease activity negatively correlated with elongated DNA and DNA integrity (rs=0.6255, p<0.0001).

Conclusions

Elongated DNA accumulates during MI at the culprit lesion site. Its inverse correlation with nuclease activity underscores the role of nucleases in cleaving elongated DNA to shorter, soluble fragments. This study establishes DNA length and integrity as novel biomarkers in thrombotic cardiovascular disease.Figure 1:Coronary cfDNA lengthFigure 2:Nuclease activity and cfDNA
Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy
Authors: Batra G , Wassberg C , Westerbergh J , Lindback J , Lopes R D , Leonardi S , Mahaffey K W , Harrington R A , Held C , Wallentin L
Published: October 2024

Background

Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS).

Purpose

To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events.

Methods

The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics.

Results

The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p<0.001). The results were consistent across the different components of the composite endpoint.

Conclusions

The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome