bluuebunny/crossref_metadata_2025 huggingface dataset:
Which is better for predicting and discriminating cardiovascular events: a traditional risk score, a calcium score or a genetic risk score?
Authors: Sousa F , Mendonca M I , Serrao M , Sa D , Abreu G , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Ornelas I , Drumond A , Sousa A C , Palma Dos Reis R
Published: October 2024

Background

The most effective approach to prevent coronary artery disease (CAD) in the general population remains to quantify the individual risk of CAD followed by controlling risk factors. There has been a lot of curiosity to investigate several scores individually for improving risk prediction. However, whether one would be better than the other in the same population is still unclear.

Aim

To evaluate the performance of the three individual scores, European SCORE2, Coronary artery calcium score (CACS) and a Genetic risk score (GRS), in predicting and discriminating cardiovascular (CV) events in an asymptomatic Portuguese population.

Methods

Prospective, observational population-based study, including 1002 asymptomatic subjects (mean age 53.1±6.8 years, 73.8% male) selected from a normal Portuguese population, without apparent CAD and diabetes at baseline. Data were recorded at the end of an extended follow-up (average 6.5±4.9 years). The European SCORE2, a computed tomography CACS, and a GRS were created to evaluate CV events’ predictive and discriminative ability through Receiver Operating Characteristics (ROC) analysis and Harrell’s C-statistics.

Results

ROC curve analysis showed 0.723 for SCORE2, 0.815 for CACS and 0.649 for GRS. Harrell’s C-statistics were 0.731 in the SCORE2, 0.785 for CACS and 0.684 for GRS.

Conclusion

The CAC score was the best individual score to predict and discriminate CV events in our asymptomatic population. Its capacity to identify high-risk individuals and those asymptomatic with subclinical atherosclerosis may improve CV risk management strategies to prevent future cardiovascular events. This result can be explained because CAC score, more than a risk marker, represents the existence of disease in the vessel wall.
Pre-discharge prediction of long-term prognosis in patients after ST-segment elevation myocardial infarction - the ValAMI-P risk score
Authors: Merenciano-Gonzalez H , Marcos Garces V , Bertolin-Boronat C , Perez N , Gavara J , Rios-Navarro C , De Dios E , Molina-Garcia T , Iraola-Viana D , Minguez Diaz De Alda S , Aulet-Manuel S , Canoves J , Nunez J , Sanchis J , Bodi V
Published: October 2024

Background

Despite contemporary management of ST-segment elevation myocardial infarction (STEMI) patients, cardiovascular death (CV death) and re-admission for acute heart failure (aHF) are frequent complications during follow-up. Several clinical, electrocardiographic, and echocardiographic variables have been identified as risk factors of major adverse cardiovascular events (MACE) in this setting. We aim to study the usefulness of a risk score using universally available clinical, electrocardiographic, and echocardiographic variables at discharge to stratify the risk of MACE during follow-up.

Methods

We prospectively included 712 patients treated with primary percutaneous coronary intervention after STEMI. We registered clinical, ECG and echocardiography-derived pre-discharge data. Left ventricular ejection fraction (LVEF) was categorized according to current recommendations. The primary endpoint was time to first MACE, defined as CV death or aHF, whichever occurred first. We created a risk score (ValAMI-P) including variables independently associated with MACE in multivariable analysis. Patients were classified in three groups (low, intermediate, and high risk) according to the ValAMI-P score.

Results

Mean age was 60±12 years, most patients (78.5%) were male, and smoking was the most prevalent risk factor (54.4%). During an 8.1-year median follow-up, 154 MACE (21.6%) were registered. In multivariable analysis, age (HR 1.03 [1.01-1.05], p=0.001), previous hypertension (HR 1.49 [1.04-2.12], p=0.029), GRACE score (HR 1.01 [1.01-1.02], p<0.001), mildly reduced LVEF (41-49%; HR 1.92 [1.18-3.11], p=0.008), reduced LVEF (≤40%; HR 5.2 [3.53-7.65], p<0.001) and the number of leads with Q-wave and residual ST-segment elevation at pre-discharge ECG (Q-STE; HR 1.13 [1.03-1.25], p=0.013) associated with long-term MACE. After classification according to the ValAMI-P risk score, patients with intermediate (8-13 points) and high (≥14 points) score depicted an increased risk of MACE (31% and 50%, respectively) compared to patients with low ValAMI-P risk score (≤7 points; 13%; p<0.001 for all comparisons).

Conclusions

The ValAMI-P risk score, which comprises widely available clinical, ECG and echocardiographic variables at discharge, can identify patients at increased long-term risk of MACE after STEMI.ValAMI-P risk score after STEMI
Dynamics and prognostic role of persistent angina in chronic coronary syndrome with clinical, angiographic and stress CMR evidence of ischemia
Authors: Merenciano-Gonzalez H , Perez N , De Dios E , Monmeneu J V , Lopez-Lereu M P , Gavara J , Rios-Navarro C , Marcos Garces V , Moratal D , Bayes-Genis A , Sanz-Sanchez J , Martinez-Dolz L , Sanchis J , Nunez J , Bodi V
Published: October 2024

Background

In patients with established chronic coronary syndrome (CCS), the significance of myocardial ischemia is a controversial issue. Persistent angina within the first year after treatment intervention has ranged widely in previous studies and its association with subsequent hard clinical events is unclear. We aim to evaluate the long-term dynamics of angina class and the prognostic role of persistent angina in symptomatic chronic coronary syndrome (CCS) patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiography.

Methods

We analyzed 486 CCS patients with Canadian Cardiovascular Society angina class ≥2, perfusion deficit in stress CMR and severe lesions in angiography submitted to treatment intervention (medical therapy plus, if feasible, CMR-guided revascularization). The dynamics and association of persistent angina at 6 months post-intervention with subsequent cardiac death, myocardial infarction, and admission for heart failure were investigated.

Results

All patients displayed angina class ≥2 (mean: 2.7±0.7), abnormal stress CMR (mean ischemic burden: 6.2±3 segments) and severe angiographic lesions. Most underwent CMR-guided revascularization (n=392, 81%). The angina resolution rate was 78% at 6 months, and 79%, 77%, and 75% at 1, 2, and 5 years respectively. Compared with medical treatment alone, CMR-guided revascularization was associated with less persistent angina (19% vs. 35%; HR 0.42 [0.2–0.7]; p=0.003). During an 8.3-year median follow-up, persistent angina was independently associated with higher subsequent cardiac death rates (18% vs. 4%; HR 10.9 [4.1–29.2]; p<0.001), myocardial infarction (24% vs. 6%; HR 5.8 [3.2–10.4]; p<0.001), and admission for heart failure (31% vs. 14%; HR 2.7 [1.7–4.2]; p<0.001).

Conclusions

In CCS patients with robust diagnostic evidence by symptoms, stress CMR and angiography, sustained improvement of anginal symptoms can be achieved in most patients after treatment intervention. Angina resolution is more frequent in patients treated with CMR-guided revascularization and is associated with fewer cardiac events.Central Figure.Persistent angina and MACE risk
Chronic Coronary Syndromes with/without obstructive coronary arteries: are there differences in ongoing chest pain?
Authors: La S , Tavella R , Wu J , Spertus J , Pasupathy S , Girolamo O , Zeitz C , Worthley M , Arstall M , Sinhal A , Beltrame J
Published: October 2024

Background

Stable coronary artery disease (CAD) is the archetype chronic coronary syndrome, clinically manifesting as angina with obstructive CAD on angiography and managed via evidence-based guidelines. In contrast, patients with Angina with Non-Obstructive Coronary Arteries (ANOCA) are often diagnosed with ‘non-specific chest pain’ and not appropriately managed.

Purpose

To compare the Seattle Angina Questionnaire (SAQ) responses and 3-year rates of chest pain hospital presentations in patients with ANOCA compared to Stable CAD.

Methods

Consecutive angina patients undergoing elective coronary angiography enrolled in the CADOSA (Coronary Angiogram Database of South Australia) Registry between 2012-18 were included. Consenting patients participated in a longitudinal health status assessment utilising the SAQ. In-hospital clinical data was extracted from CADOSA and mortality and hospitalisation data over 12-months was extracted via administrative records.

Results

Of 6,372 consecutive patients undergoing elective angiography for the investigation of chest pain 2,287 had ANOCA and 4,085 Stable CAD. ANOCA patients were younger (61±11 vs 66±11, p<0.05) and more often female (59% vs 27%, p<0.05) compared to Stable CAD. The SAQ health status assessment was completed at baseline, 1 and 12-months for 377 patients (ANOCA n=156, Stable CAD n=221). At 12-month follow-up, there were no differences in SAQ scores amongst all domains (physical limitation- 92±16 vs 92±15, angina stability- 64±25 vs 62 ±24, angina frequency- 91±17 vs 92±16, treatment satisfaction- 94±13 vs 94±13 and quality of life- 78±22 vs 81±21) between ANOCA and Stable CAD, all p>0.05. However, in the 12-month follow-up, ANOCA patients were less likely to have a chest pain hospital emergency department presentation (10% vs 15%, p<0.001) or admission (6% vs 12%, p<0.005) compared to the Stable CAD cohort.

Conclusion

Although patient-reported outcomes were identical between Stable CAD and ANOCA patients, the latter were less likely to present to emergency department or be admitted to hospital than their Stable CAD counterparts, reflecting the clinical nihilism encountered in the ANOCA patient journey.
Prognostic impact of the presence and absence of angina on mortality and cardiovascular outcomes in the ISCHEMIA trial
Authors: Singh A , Rodman J C S , Brown D L
Published: October 2024

Introduction

Patients with chronic coronary syndromes (CCS) manifested by myocardial ischemia may present with typical angina or with no anginal symptoms. It is unclear whether symptom status affects prognosis in these patients.

Purpose

To assess whether the risk of all-cause mortality and other cardiovascular (CV) outcomes varied according to the presence or absence of angina in patients with CCS and moderate to severe myocardial ischemia in the ISCHEMIA trial.

Methods

The ISCHEMIA data set was obtained from the National Heart, Lung, and Blood Institute under a data use agreement. Subjects were divided into quartiles by baseline Seattle Angina Questionnaire Angina Frequency (SAQ AF) score. Quartile (Q)1 included patients with SAQ AF scores from 1-70 whereas all patients in Q4 had SAQ AF scores of 100, indicating no angina at baseline. Categorical variables were compared using the chi-squared or Fisher’s exact test. Continuous variables were compared using the student T-test or Wilcoxon rank sum test. The cumulative incidence rate of outcomes up to five years was estimated with the Kaplan-Meier method and the rate curves were compared using the log-rank test. Multivariable Cox regression models were used to estimate hazard ratios (HRs) with potential confounders from baseline characteristics, clinical history, and angiographic characteristics included. All tests were two-sided and P<0.05 was considered statistically significant.

Results

Of the 5,179 patients with CCS and at least moderate ischemia on stress testing, 1,434 were in Q1 and 1,635 were in Q4. Compared to Q1, patients in Q4 were older (66.4 (9.0) vs. 62.8 (9.6); P<0.001), more often male (82% vs. 73%; P<0.001), more often diabetic (43% vs. 38%; P=0.006) and less often current smokers (12% vs. 15%; P=0.001). The estimated glomerular filtration rate was lower in Q4 (82(22) vs. 86 (38); P=0.002). Fewer patients in Q4 had NYHA class II heart failure (37% vs. 62%) and more had Class I symptoms (63% vs. 38%) (P<0.001). Q4 patients had a lower ejection fraction (59% vs. 60%; P=0.002), a lower Duke jeopardy score (4.9(3.5) vs. 5.5 (3.3); P<0.001), less often had severe ischemia (47% vs. 56%), and more often had moderate ischemia (40% vs. 32 %) (P<0.001). The cumulative 5-year event rates for Q4 vs. Q1 were: all-cause death, 10.6% and 6.4% (P=0.002); CV death/MI, 16.3% vs. 13.7% (P=0.97); CV death, 7% vs. 3.7% (P=0.009); MI, 11.4% vs. 11.4% (P=0.2). On multivariable Cox regression, angina quartile (Q4 vs. Q1) was not independently associated with all-cause death (HR 1.34, 95% CI: 0.76-2.31; P=0.33), CV death/MI (HR 0.77, 95% CI: 0.52-1.14; P=0.19), CV death (HR 1.10, 95% CI: 0.50-2.43; P=0.82), or MI (HR 0.70; 95% CI: 0.45-1.08; P=0.11).

Conclusion

In the ISCHEMIA trial, patients with CCS and moderate to severe myocardial ischemia are at elevated risk for all-cause mortality and other major CV outcomes. This risk is not modified by the presence or absence of angina.
Long-term clinical implications of routine follow-up coronary angiography of asymptomatic patients with long-duration diabetes mellitus after percutaneous coronary intervention in drug-eluting stent e
Authors: Kim H J , Jung Y S , Kim S O , Jung J C , Jung Y J , Park J I , Choi K U , Nam J H , Lee C H , Son J W , Kim U , Park J S
Published: October 2024

Background

Diabetes mellitus (DM) is a major risk factor for coronary artery disease (CAD), significantly contributing to mortality in affected patients. There are concerns about the adequacy of clinical follow-up for post-percutaneous coronary intervention (PCI) surveillance, especially in uncontrolled DM, due to potential asymptomatic CAD. This study assesses whether routine follow-up coronary angiography (FUCAG) offers a surveillance advantage over clinical follow-up in uncontrolled DM post-PCI.

Methods

From 2014 to 2020, a study was conducted on patients with DM who underwent PCI at our university medical. Poorly controlled DM was defined as a mean HbA1c of 9 or higher during the index PCI and follow-up period. Out of a total of 2,864 individuals, after excluding 538 individuals with a follow-up period of less than 4 years and 232 individuals who experienced an event within a year, a total of 2,094 was enrolled. Follow-up coronary angiography (FUCAG) was defined as angiography performed between 6- and 18-months post-index PCI for lesion evaluation. To adjust for any differences in baseline characteristics between the groups, propensity score matching (PSM) was implemented. The primary outcome was defined as Major Adverse Cardiac Events (MACE), comprising all-cause death, myocardial infarction, and target-lesion revascularization.

Results

PSM was conducted to correct the difference in baseline characteristics between the two groups. In the Kaplan-Meier analysis, there was no difference between FUCAG and clinical follow-up for MACE (Log-rank: P=0.770). Cox proportional regression analysis revealed a hazard ratio (HR) of 0.77 with a 95% confidence interval (CI) of 0.70-1.63, indicating no statistically significant difference.

Conclusions

Even in poorly controlled DM patients, there was no apparent clinical benefit of FUCAG compared to clinical follow-up. Particularly considering concerns such as renal function deterioration in DM patients, post-PCI surveillance through clinical follow-up may be advantageous.
Machine-learning based prediction of obstructive coronary artery disease using integrated submodules of clinical information, chest x-ray, and electrocardiography
Authors: Heo R , Park S J , Lim Y H
Published: October 2024

Background

The early diagnosis of obstructive coronary artery disease (CAD) is critical. However, delays in diagnosis may occur due to subsequent high-cost tests, contributing to substantial medical expenses. A more insightful interpretation of fundamental diagnostic tools, such as chest x-ray (CXR) and electrocardiography (ECG), could mitigate medical costs and facilitate a timely diagnosis.

Purpose

This study explores the application of machine learning to interpret each modality and create a consolidated prediction model for significant CAD, aiming to construct a diagnostic model based on primary tests, including CXR, ECG, and clinical information.

Methods

Clinical information-ECG-CXR paired data were generated from 19,140 patients, with CAD confirmed through coronary angiography (CAG). Machine learning (ML) was employed to develop submodules for each modality, and various integration methods were explored. The area under the curve (AUC) served as the outcome metric for predicting obstructive CAD.

Results

The development set comprised data from 17,976 patients, with CAG-confirmed obstructive CAD observed in approximately 60% of patients. The obstructive CAD group exhibited characteristics such as advanced age, male predominance, a higher prevalence of chest pain, and more risk factors. The ML model, incorporating clinical information, CXR, and ECG with submodules, demonstrated the optimal prediction of obstructive CAD (AUC 0.722). This model significantly outperformed the model without submodules (0.722 vs. 0.638, p<0.0001) in obstructive CAD prediction.

Conclusions

Through the integration of submodules encompassing clinical information and basic tests, leveraging a high-quality database, the integrated ML algorithm offers improved prediction capabilities for CAG-confirmed obstructive CAD. This underscores the potential role of machine learning in clinical decision-making based on diverse modalities with distinct characteristics.
Prognostic value of combined myocardial performance index in patients with acute ST-elevation myocardial infarction
Authors: Hayrapetyan H G , Petrosyan H H , Kristosturyan A A , Tavaratsyan A R , Hayrapetyan L H , Kalantaryan V A
Published: October 2024

Background

Myocardial performance index (MPI) also known as Tei index is a unique echocardiographic parameter which can estimate both systolic and diastolic performances of left and right ventricles. We previously suggested the echocardiographic parameter combined MPI (CMPI) as a new predictor of the prognosis of acute ST-elevation myocardial infarction (STEMI). The CMPI is the sum of left ventricular (LV) MPI and right ventricular (RV) MPI (CMPI = LV MPI + RV MPI). We supposed that CMPI might be a better predictor in STEMI, because it reflects both ventricular systolic and diastolic functions.

Objectives

The purpose of this study is to assess the prognostic value of a new echocardiographic parameter CMPI in STEMI patients calculated in acute phase.

Methods

240 STEMI patients who underwent primary PCI have been included in the study. Echocardiography (EchoCG) was performed, and LV MPI and RV MPI were assessed within 24 hours after the symptom onset, prior to primary PCI. The MPI was calculated as the sum of isovolumic contraction time (ICT) and isovolumic relaxation time (IRT), divided by the ejection time (ET): MPI = (ICT + IRP) / ET. 50 % of the patients had anterior STEMI. 30 patients (12.5%) had concomitant RV myocardial infarction (MI). Patients were divided into two groups: Group 1 – CMPI > 0.9 (110 patients), Group 2 – CMPI ≤ 0.9 (130 patients). Baseline demographic and clinical characteristics were similar in both groups. Also, there were no differences in LV MI localization and concomitant RV MI between the groups. Primary endpoints were in-hospital and the one-year cardiovascular mortality rates. The secondary endpoint was the one-year heart failure hospitalization rate.

Results

In Group 1 the in-hospital mortality rate was 9.1%, and 3.1% in Group 2 (p = 0.0489). One-year cardiovascular mortality rate was 12.7% in and 5.4%, respectively (p = 0.0465). One-year heart failure hospitalization was also significantly lower in Group 2 (22.7% vs. 12.3%, p = 0.0332).

Conclusion

CMPI can be offered as a new predictor for the in-hospital and one-year cardiovascular mortality and one-year heart failure hospitalization rate in patients with acute STEMI.
Real world data after the implementation of coronary computed tomography angiography in Swedish primary care to rule out coronary artery disease, a cross-sectional study based on pre-test probability
Authors: Stertman E , Gabro F , Sandstedt M , Sysoev O , Sederholm Lawesson S , Engvall J , Nilsson S , Iredahl F
Published: October 2024

Background

In primary care, most patients with of non-acute chest pain will neither receive a heart related diagnosis nor be referred to a cardiologist. Studies indicate a better cardiovascular prognosis in chest pain patients referred to Coronary Computed Tomography Angiography (CCTA) as compared to risk stratification solely based on risk prediction instruments(1). CCTA is recommended since 2019 for low to intermediate cardiovascular (CV) risk patients(2). In the study setting, the primary care has implemented CCTA as first line test for patients with suspected obstructive coronary artery disease (CAD) and a Pre-Test Probability (PTP) of <15% and any CV risk factor, with PTP mandatorily entered in the referral letters.

Purpose

To study the outcome of CCTA based on referred PTP values categorised into <5%, 5-15% and >15%. We hypothesized that the presence of significant stenosis would be on par with the mean PTP.

Methods

In this cross-sectional retrospective cohort study, all consecutive clinical referrals for a CCTA from primary health care centres with a catchment area of ~470 000 inhabitants in the country of Sweden between 1 June 2021 and 7 Dec. 2022, with PTP estimates and completed CCTA were included. CCTA findings were stratified as normal, atheromatosis, or significant stenosis (≥50% coronary lumen obstruction). Patient baseline characteristics routinely registered on the day of CCTA was retrieved from a nationwide quality registry, SWEDEHEART(3). Pearsons’s Chi2 and one-way ANOVA was used to test differences in group distributions.

Results

During the study period, 381 patients with a PTP had obtained CCTA, of which 75% (n=286) had PTP <15%. The mean age was 60 years (standard deviation [SD] 11), 70% were female, 30% were prescribed lipid-lowering medication and 47% anti-hypertensives (Table 1).

In total, the mean PTP was 12.4% (SD 8.7) and in 18% a suspected significant stenosis was identified. (Figure 1). Among patients referred with PTP 5-15%, the presence of suspected significant stenosis was 12% and cardiology consultation was less frequently described than for PTP <5 or ≥15% (14% vs 33% vs 44%, p < 0.001).

Conclusions

This study indicates that PTP is an efficient means to select patients for CCTA in primary care. In total, about 1/5 had a suspected significant stenosis, which often requires further investigations, and about 4/5 could be reassured that symptoms were not due to coronary artery disease. In 31% atheromatosis was identified, potentially facilitating counselling on CV prevention. We conclude that CCTA is a clinically effective option for primary care physicians to rule out CAD in patients with low PTP.Figure 1Table 1
Association of vasospastic angina with myocardial bridging and pericoronary adipose tissue attenuation on computed tomography angiography
Authors: Mineo T , Usui E , Kanaji Y , Hada M , Nagamine T , Ueno H , Nogami K , Setoguchi M , Tahara T , Yonetsu T , Sasano T , Kakuta T
Published: October 2024

Background

Recent studies have suggested that vasospastic angina (VSA) is associated with myocardial bridging (MB). The relationship between VSA and pericoronary adipose tissue (PCAT) inflammation has also been reported but still remains to be determined.

Purpose

We investigated clinical and coronary computed tomography angiographic (CCTA) features in patients with VSA diagnosed by spasm provocation test (SPT).

Methods

We retrospectively studied patients with clinically suspected VSA who underwent both SPT with intracoronary acetylcholine administration and CCTA within three months before SPT at Tsuchiura Kyodo General Hospital. PCAT inflammation was evaluated on CCTA images by fat attenuation index (FAI) which has been recently used as a novel biomarker of coronary inflammation. In FAI analysis, we measured FAI of the proximal segments not only for 4mm (FAI4mm) but also for the inner and thinner 2mm pericoronary adipose tissue layer from the vessel wall (FAI2mm), since FAI2mm has been reported to provide better discriminating efficacy for VSA diagnosis than FAI4mm. We also evaluated the presence or absence of MB and its features including length, depth and location on CCTA images.

Results

A total of 172 patients were studied and VSA was diagnosed in 39.0% (67/172) of patients by SPT according to the latest guideline. Male (74.6% vs 49.5%, P=0.001), smoking history (74.6% vs 48.6%, P=0.001) were more frequent, and prevalence of CCTA-defined MB (47.8% vs 34.3%, P=0.082) and RCA-FAI2mm (-68.73 HU vs -73.35 HU, P<0.001) were higher in patients with versus without VSA. In multivariable analysis, presence of CCTA-defined MB (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.26-5.19, P=0.0095), RCA-FAI2mm (OR 1.05, 95% CI 1.01-1.09, P=0.025), and smoking (OR 3.40, 95% CI 1.57-7.36, P=0.0019) were independently associated with VSA. A combination of high RCA-FAI2mm (≥-68.93HU, the best cut-off obtained by ROC analysis with AUC of 0.64, 95% CI 0.551 - 0.728), smoking history and existence of MB could predict VSA with 73.7% of probability, while an absence of all 3 covariates could exclude VSA with 85.3% of probability.

Conclusion

CCTA-defined MB, high RCA-FAI2mm and smoking were independently predictive of VSA.
How to predict myocardial injury in patients with large ischaemic burden identified during stress echocardiography?
Authors: Vakalis K , Berrill M , Jimeno M , Barron A , Rahman Haley S , Baltabaeva A
Published: October 2024

Background/Introduction

Stress echocardiography (SE) is well established diagnostic tool in coronary artery disease (CAD) with broadly agreed consensus for the indications and protocols. There is, however, no clear non-invasive SE parameter in identifying high risk features in patients with large burden of inducible regional wall motion abnormalities (RWMA) that would require prompt treatment or urgent admission.

Purpose

To identify high risk features during SE associated with myocardial injury following a positive SE with large amount of RWMA.

Methods

All consecutive patients referred for SE from June 2019 to November 2022 to diagnose coronary artery disease were assessed for inducible RWMAs using a hybrid protocol (low dose Dobutamine and exercise on supine bike with 3 min increments of workload of 25W). Those with ≥4/17 segments of inducible RWMAs underwent measurement of Troponin level 1 hour after the test termination. Somatometric characteristics, risks factors, symptoms, haemodynamic pre- and during SE and results of subsequent coronary angiography were recorded.

Results

631 patients were referred for assessment of CAD. 87 patients had ≥4/17 inducible RWMAs out of 152 patients with positive SE. 61/87 who had Troponin measurements were included in the analysis. Mean age was 65 ± 13 yo, 61% were male. There was high prevalence of known CAD (77%) and cardiovascular risks factors as hypertension (59%) and hyperlipidaemia (61%). The median exercise time was 9 minutes, 46% developed chest pain (CP), 49% - ECG changes, 39% - left ventricular (LV) dilatation and 74% - reduction in LVEF. Troponin was positive in 25/61 patients.

Invasive coronary angiography confirmed clinical CAD in 51/61 patients. 5 patients had either normal angiogram or non-obstructive CAD, 5 patients were awaiting diagnostic test. The severity of CAD appears to be associated with magnitude of Troponin release (1 vessel disease - 16.5 ng/L, 2 vessels disease - 39.9 ng/L, 3 vessels disease – 58.2 ng/L). All patients (6/61) with higher troponin values (>90ng/L) had multivessel disease involving the left anterior descending (LAD) artery. Interestingly, 2/5 patients without CAD had elevated Troponin suggesting possible ongoing myopathic process.

The only non-invasive SE parameters that were significantly related to troponin increase were recovery time (P=0.001) and exercise time (P<0.05) whereas symptoms, BP response and LVEF reduction showed a trend which did not achieve significance.

Conclusions

In patient with positive SE with large burden of inducible RWMAs prolonged recovery time and low threshold for ischaemia appear to be the most reliable characteristic to identify patients with potential myocardial injury and should be used as a triaging tool for admission or early invasive assessment.
Methylome of circulating cell free DNA as a novel biomarker tool: from acute coronary syndrome to broader risk stratification of cardiovascular disease
Authors: Kratzer A , Giral H , Cuadrat R , Blume A , Mauno T , Moobed M , Hartung J , Meteva D , Fuereder L , Haghikia A , Akalin A , Landmesser U
Published: October 2024

Background

Cell death during tissue injury leads to release of chromosomal DNA which is promptly degraded. However, short DNA fragments wrapped around nucleosomes survive longer in the bloodstream and can be isolated as circulating cell-free DNA (ccfDNA). Oncology field pioneered the use of cfDNA as clinical biomarker by identifying sequence modifications induced in cancer cells. Importantly, ccfDNA also retains the same epigenetic information as the tissue of origin. Despite major advances for disease diagnosis and therapy, coronary artery diseases (CAD) and associated conditions such acute myocardial infarction (AMI) or heart failure (HF) are responsible for leading number of deaths worldwide. Preventive and surveillance strategies with non-invasive testing are needed.

Purpose

Evaluation of ccfDNA methylation profiles as prognostic non-invasive biomarker for risk stratification of acute coronary syndromes and their potential application in preventive and surveillance strategies in other cardiovascular disorders.

Methods

CcfDNA isolated from citrate-plasma collected from our discovery cohort, comprising healthy controls, STEMI, NSTEMI and unstable angina (UA) patients, was analyzed applying Whole Genome Bisulfite Sequencing (WGBS) using a low-input BS-seq (PBAT) protocol. Computational analysis generated differentially methylated regions (DMRs) by tiling CpG areas and setting a threshold of minimal 25% methylation difference compared to the healthy group. To assess the validity of our findings, a selection of disease-specific DMRs were tested using targeted methylation sequencing protocol in a new set of patients. This procedure consisted in enzymatic conversion of ccfDNA methylated sites followed by probe-specific enrichment libraries and sequencing at a Novaseq 6000 platform.

Results

The study identified a total of 1941 DMRs and from those 486 were STEMI, 223 NSTEMI and 684 UA specific. From the identified DMRs, 74.13% from STEMI, 72.68% from NSTEMI and 61.62% from UA annotated with heart-related diseases using DisGeNET gene-disease associations. Interestingly, most of identified DMRs located within intronic regions (~60%) and also annotated as enhancers and lncRNAs. The independent validation with targeted methylation sequencing identified 566, 306 and 248 DMRs, respectively, and reduced the number of disease-specific DMRs to 171 in STEMI, 115 in NSTEMI and 82 in UA.

Conclusion and Future Approaches

Methylation profiles of ccfDNA showed potential as a biomarker to stratify the severity of acute coronary syndromes, a novel non-invasive detection methodology that could be extrapolated to risk stratification in other cardiovascular disease such as heart failure or coronary artery disease.
Multi-modality deep learning model for prediction of chronic obstructive coronary artery disease
Authors: Trivedi R , Chiu I , Ouyang D
Published: October 2024

Background/Introduction

The incidence of coronary artery disease (CAD) is on the rise with an increasing burden of stable ischemic heart disease (SIHD) and high prevalence of obesity, diabetes, hyperlipidemia, and other cardiovascular risk factors. Pre-test probability estimation for CAD based on demographic features and characterization of chest pain is insufficient to accurately assess whether further evaluation for CAD is warranted.

Purpose

To develop and validate a deep learning (DL) algorithm utilizing electrocardiogram (ECG) waveforms and clinical features to predict obstructive CAD.

Methods

Clinical data from subjects undergoing invasive angiography over a 4-year period at a quaternary care center exclusive of subjects who had concern for acute coronary syndromes were used for model training. ECGs obtained up to 5 years prior to angiography were included; ECGs were partitioned 8:1:1 for training, validation, and test datasets. Obstructive CAD was defined as receiving percutaneous coronary intervention during elective angiography. Convolutional neural network models were developed for ECG waveforms alone (DL-ECG), clinical features from standard risk scores (DL-Clinical), and the combination of ECG waveforms and clinical features (DL-ECG+Clinical); a commonly used pre-test probability estimation tool derived from the CAD Consortium study was used as a comparison (PTP). The models were evaluated based on area under the curve receiver operating characteristics (AUC). Shapley additive explanations (SHAP) analysis was performed to understand feature importance in the DL models.

Results

A total of 40,602 ECGs and 8,361 coronary angiograms from 7,201 patients were included in the analysis. The median age was 66 (IQR 56-75), 71.9% were men, 34.9% had hypertension, 30.6% had diabetes mellitus, and 39.0% had dyslipidemia. The PTP model (AUC 0.733 [0.717-0.750]) had similar performance as the DL-Clinical model (AUC 0.762 [0.746-0.778]). The DL-ECG model (AUC 0.741 [0.726-0.758]) had similar performance as both the clinical feature models. The DL-ECG+Clinical model (AUC 0.807 [0.793-0.822]) trained on ECG waveforms and clinical features had a superior performance (Figure 1). SHAP analysis for the DL-ECG+Clinical model revealed that ECG waveforms had the largest influence on the model’s output followed by age and chest pain type (Figure 2).

Conclusions

Multi-modality DL model utilizing ECG and commonly used features can improve prediction of obstructive CAD in SIHD compared to traditional pre-test probability estimates. Prospective research is warranted to determine whether incorporation of DL methods to ECG analysis effectively improves diagnosis and outcomes in obstructive CAD.Figure 1.Figure 2.
Non-invasive imaging to guide percutaneous coronary revascularization in chronic total occlusion: a systematic review and meta-analysis
Authors: Bisaccia G , Greenwood J P , Berry C , Mccann G P , Wong J , Ricci F , Gallina S , Liu L , Wang Y , Hill J , Curzen N , Bucciarelli-Ducci C
Published: October 2024

Background and aims

Whether recanalization of coronary chronic total occlusions (CTO) leads to improved patient outcomes is uncertain. We set out to investigate the use of noninvasive imaging modalities to guide patient selection for percutaneous recanalization of coronary chronic total occlusions (CTO-PCI) and its association with outcomes.

Methods

Systematic review and meta-analysis of studies involving patients undergoing CTO-PCI to detail use of preprocedural non-invasive imaging, change in clinical endpoints and the occurrence of clinical events in these patient cohorts. PubMed and Embase, the Cochrane Database of Systematic Reviews, the PROSPERO database and the Clinical Trials Registry were searched for relevant randomized and observational studies up to May 2023. This study is registered with PROSPERO. The study primary endpoint was a composite of all-cause death and nonfatal myocardial infarction (MI), with a secondary composite endpoint of cardiovascular death, nonfatal MI and target vessel revascularization (TVR). Additional endpoints were individual components of the composite endpoints along with changes in angina burden, LV ejection fraction, ischemic burden, and infarct extent after PCI.

Results

Of 1264 publications retrieved, 31 studies (26 observational and 5 randomized) were finally included for a total of 7260 patients. Guidance to CTO-PCI varied greatly among included studies, with only a minority implementing routine preprocedural inducible ischemia and myocardial viability assessment. At a median of 3.1 years (range 1-5 years), the primary endpoint occurred at a rate of 3.1 events per 100 patient-years (95%CI: 2.4-3.7). When non-invasive imaging was used to guide CTO-PCI, patients with myocardial ischemia and/or viability, a reduced risk for the primary endpoint was observed (OR 0.3 95%CI 0.2-0.5) compared to CTO-PCI without evidence of myocardial ischemia and/or viability.

CTO-PCI was associated with improvements in SAQ summary score, LVEF, reduction of ischemic burden, improvement in myocardial perfusion (all P-values < 0.01), with no change in the burden of myocardial scarring. At meta-regression analysis, a greater improvement in LVEF was observed in studies enrolling patients with lower average baseline LVEF (≤ 45%) (R2 = 63%, p < 0.0001).

Conclusions

CTO-PCI led to a significant improvement in symptom status (reduction of chest pain) and LV ejection fraction. CTO-PCI guided by the presence of ischemia and/or viability was associated with improved patient outcomes compared with CTO-PCI in the absence of ischemia and/viability, or in patients where non-invasive imaging testing was not performed. Future randomized clinical trials testing whether ischemia and viability-guided CTO-PCI improves clinical outcomes are lacking and warranted.PRISMA Flow diagramGraphical abstract
Number of inflamed coronary vessels in prediction of cardiac death and MACE among patients undergoing routine CCTA: the Oxford Risk Factors And Non-Invasive Imaging (ORFAN) Study
Authors: Chan K , Wahome E , Nicol E , Mittal T K , Adlam D , Rodrigues J , Greenwood J , Desai M , Patel P , Tomlins P , Neubauer S , Channon K M , Blankstein R , Deanfield J , Antoniades C
Published: October 2024

Background

Coronary inflammation can be assessed by the changes in perivascular adipose tissue on routine coronary CT angiograms (CCTA). Fat attenuation index score (FAI Score) quantifies the degree of inflammation in each epicardial coronary artery, and adjusts for age, sex, scan technical parameters, biological and anatomical factors. Coronary inflammation assessment in a single coronary artery was previously shown to be predictive of cardiac events in the CRISP-CT study. However, the impact of inflammation in multiple coronary arteries on clinical outcome remains unclear.

Purpose

To evaluate the prognostic value of the number of inflamed coronary arteries with high inflammation in the risk of cardiac death, and major adverse cardiac events (MACE).

Methods

In a nested cohort within the Oxford Risk Factors And Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality, and MACE (including myocardial infarction, new onset heart failure, cardiac mortality). FAI Score was calculated for each of the 3 epicardial coronary arteries.

Results

The number of inflamed arteries (FAI Score >75th centile) showed an additive impact on cardiac mortality compared with no inflamed arteries (all vessels FAI Score <25th centile), with hazard ratio 29.8 (95% CI 13.9-63.9, p<0.001) for 3 inflamed arteries, HR 20.4 (95% CI 9.4-44.7, p<0.001) for 2 inflamed arteries, and HR 13.0 (95% CI 5.9-28.8, p<0.001) for 1 inflamed artery. (Panel A) Similarly, patients with multiple inflamed arteries showed progressively higher risk for MACE (HR 7.2, 8.3 and 12.6 for 1-, 2- and 3-inflamed arteries respectively compared to patients with no inflamed artery). (Panel B) Patients with no inflamed arteries showed very low event rates for cardiac mortality and MACE. In patients with no obstructive CAD (n=2,651), similar trends were observed whereby patients with 3-inflamed arteries showed highest risk for cardiac mortality (Panel C) and MACE (Panel D), with intermediate risk for those with 1 or 2 inflamed arteries.

Conclusion

The number of coronary arteries with high inflammation, measured by FAI Score from routine CCTA, is associated with adverse cardiovascular events and cardiac mortality in an additive dose-response manner.
Impact of coronary CT angiography on the hospital outcome among patients admitted with AMI undergoing revascularization procedures in theUS
Authors: Shoar S , Allencherril J
Published: October 2024

Background

Coronary CT angiography (CCTA) is gaining popularity as a diagnostic modality for risk stratification among patients hospitalized with acute myocardial infarction (AMI). However, its impact on the hospital outcomes among this population of patients remains to be determined.

Methods

Using national inpatient sample database, admission cases with a diagnosis of AMI who underwent revascularization procedures were identified from 2016-2020. The prevalence of CCTA was determined among the patient population and stratified based on the type of AMI (STEMI vs. NSTEMI) and revascularization procedure (PCI vs. CABG). Hospital outcomes were compared among the study strata.

Results

A total of 862,064 admission cases for STEMI and 3,586,944 admission cases for NSTEMI were identified out of which 661,958 cases underwent revascularization procedures. The utilization of CCTA was roughly 10 times higher among AMI cases undergoing PCI than those undergoing CABG (0.5% vs. 0.06%, p<0.0001). Prior CCTA increased the odds of receiving PCI by 79.3 times and the odds of undergoing CABG by 2.8 times. Among STEMI patients undergoing PCI, prior CCTA was associated with a lower mortality rate and non-home disposition (13.8% vs. 21.2%, p<0.0001) compared to no CCTA (3% vs. 5.5%, p=0.01). For NSTEMI patients undergoing PCI, CCTA was associated with a lower non-home disposition (16.5% vs. 20.6%, p=0.003) but not a significantly lower mortality rate. CCTA did not demonstrate any statistically significant differences for AMI patients undergoing CABG. On the other hand, CCTA increased the cost of hospitalization by $15,130.7 for STEMI patients undergoing PCI, length of stay (9 days) and hospital cost for STEMI patients undergoing CABG ($302,802), and total hospital cost for NSTEMI patients undergoing PCI by $8,705.

Conclusions

Using CCTA helps in risk stratifying AMI patients for revascularization procedures, allocating PCI to those admitted with STEMI and CABG to those with NSTEMI. Although CCTA reduces the risk of death and non-home disposition among STEMI patients undergoing PCI, it also increases hospital charges for patients receiving revascularization procedures.
Relationship between coronary artery calcium score and plaque vulnerability in patients with established coronary artery disease
Authors: Fujimoto D , Niida T , Kinoshita D , Suzuki K , Lee H , Mcnulty I , Kakuta T , Jang I K
Published: October 2024

Introduction

Coronary artery calcium (CAC) score is widely used for risk stratification. However, in patients with established coronary artery disease (CAD), its clinical implication and relationship with plaque vulnerability have not been fully investigated.

Purpose

We sought to investigate the relationship between CAC score and plaque vulnerability assessed by optical coherence tomography (OCT).

Methods

Patients with CAD who had both CAC score and OCT prior to percutaneous coronary intervention were included. The patients with a prior history of coronary revascularization were excluded. Patients were divided into five groups based on CAC score; CAC score of 0, 1-99, 100-399, 400-999, and over 1000. Vulnerable features in culprit plaque assessed by OCT were compared among these five groups.

Results

In 460 patients, the prevalence of lipid-rich plaque, macrophage, and cholesterol crystal significantly differed among the five groups: lowest in the patients with a CAC score of zero. The prevalence of thin-cap fibroatheroma (TCFA) tended to be lower in those with a CAC score of zero (Figure). In the two-group comparison between the group with a CAC score of zero and the other four groups, the prevalence of lipid-rich plaque (60.5 vs. 85.9%, p < 0.001), macrophage (48.8 vs. 74.1%, p < 0.001), TCFA (16.3 vs. 35.0%, p = 0.013), and cholesterol crystal (11.6 vs. 32.9%, p = 0.004) was significantly lower in the patients with CAC score of zero. No significant difference in vulnerable features was observed among the four groups with CAC scores > 0. CAC score of zero was independently negatively associated with the lipid-rich plaque (odds ratio [OR] 0.246, p < 0.001), macrophage (OR 0.348, p = 0.003), TCFA (OR 0.285, p = 0.006), and cholesterol crystal (OR 0.273, p = 0.010) after adjustment with patient characteristics.

Conclusion

This is the first study that investigated the relationship between CAC score and plaque vulnerability assessed by OCT in patients with known CAD. Patients with CAC score of zero have a significantly lower prevalence of vulnerable plaque features compared to those with CAC score > 0.
Impact of the distribution of calcification around the left main coronary artery bifurcation on prognosis after percutaneous coronary intervention
Authors: Sasaki K , Sawayama Y , Ikuta A , Osakada K , Kubo S , Tada T , Tanaka H , Fuku Y , Kadota K
Published: October 2024

Backgrounds

The presence of true bifurcation lesions (TBL) by Medina classification at the left main coronary artery (LMCA) bifurcation is known to be associated with cardiovascular events after percutaneous coronary intervention (PCI). However, the prognostic impact of the distribution of calcification at LMCA bifurcation has not been adequately investigated.

Methods

This retrospective study consisted of consecutive patients who were implanted with a second or subsequent generation drug-eluting stent for LMCA bifurcation at a single center from 2014 to 2018. We excluded patients with a protected LMCA and those in whom calcification or stenosis of the LMCA bifurcation could not be assessed. With reference to the Medina classification, the region was divided into three segments (LM, LAD, and LCX). Each segment was assigned a value of 0 (for less than moderate calcification) or 1 (for more than moderate calcification) and expressed as calc (X.X.X). Calc (1.1.1), calc (1.0.1), and calc (0.1.1) were defined as true bifurcation calcification (TBC). The primary endpoint was 3-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization.

Results

Of 498 patients in this analysis, the mean age was 73 years, males accounted for 78% overall, acute coronary syndrome 31% overall, and TBL 42% overall. Moderate or severe calcification at any site around the LMCA bifurcation was observed in 184 (37%). In order of frequency, calc (1.1.0) in 70 (14%), calc (1.1.1) in 58 (12%), calc (0.1.0) in 43 (9%), calc (0.1.1) in 11 (2%), and calc (1.0.1) in 2 (0.4%), while calc (1.0.1) and calc (1. 0.0) were not present. TBC accounted for 14% overall. Patients with TBC at LMCA bifurcation had a higher incidence of 3-year TLF (Log-rank P <0.001; Figure1). Multivariable logistic regression, including age, acute coronary syndrome, maintenance hemodialysis, SYNTAX score ≥33, TBL, and TBC in the model as covariates, TBC was significantly associated with the primary endpoint (adjusted odds ratio 3.4, 95% confidence interval 1.6-7.2, P=0.013). In contrast, a significant association between TBL and the primary endpoint was not observed (adjusted odds ratio 1.5, 95% confidence interval 0.8-2.8, p=0.206).

Conclusion

Even after adjusting the presence of TBL at LMCA bifurcation, the presence of TBC at LMCA bifurcation was significantly associated with the 3-year TLF.