bluuebunny/crossref_metadata_2025 huggingface dataset:
Gradually increased stress levels in the days leading to an acute myocardial infarction, detected by a new biomarker-based approach
Authors: Kosmas N , Zapantiotis D , Kitridis D , Kiouri E , Rallidis L S
Published: October 2022

Background

Stress has been recognized as a cardiovascular risk factor that aside from triggering acute coronary syndromes (acute stress), could also directly and indirectly mediate the pathophysiology of coronary artery disease (chronic stress). So far, there have been no quantitative indices available to study this relationship.

Purpose

We prospectively investigated stress levels for the days prior to the episode, on male patients with an acute myocardial infarction (AMI), by measuring the Hair Cortisol Concentration (HCC) which is indicative of cortisol blood levels.

Methods

A total of 95 consecutive male patients with AMI (ST-elevation MI and non-ST-elevation MI) wererecruited. Exclusion criteria were: age >80 years, presence of chronic inflammatory disease, endocrine/psychiatric disorder or malignancy. A small sample of hair was obtained from the patient's head and the hair segments were later analyzed for HCC, by an enzymatic analytical method that measures the amount of cumulative cortisol which was deposited from the bloodstream upon every piece, at the time when it was generated by the hair follicle.

Results

Results of mean HCC of patients, expressed as a percentage of the range detected were: 0 time: 75.41%, 15 days prior: 76.79%, 30 days prior: 72.88%, 45 days prior: 69.34%, 60 days prior: 69.43% and 75 days prior: 65.96%. Figure 1 shows HCC during 75 days prior to the day of AMI occurrence which is the day zero. The results are consistent with a gradual increase in HCC, which reflects stress levels, in the days before the AMI, which peaked 15 days before the episode.

Conclusions

Stress levels, as quantified by a new biomarker-based approach, are gradually increased in the days preceding an AMI, peaking at 15 days before the episode.

Funding Acknowledgement

Type of funding sources: None.
Autophagy biomarkers in patients with acute myocardial infarction
Authors: Kong M G , Suh J , Cho Y H , Lee N H , Park H W
Published: October 2022

Introduction

Acute myocardial infarction (AMI) is still one of leading cause for mortality and disability in cardiovascular disease [1]. Autophagy is an intracellular mechanism involved in the elimination and the recycling of proteins and organelles by lysosomes [2]. Autophagy has an important role of critical cellular process for the self-protective degradation mechanism and recycling of cellular components in ischemic events such as AMI and left ventricular remodeling [3]. However, very few studies are evaluated the activity of autophagy and the relationship between autophagy activity and prognosis in patients with AMI.

Purpose

We aimed to evaluate the activity of autophagy in patients with AMI. Moreover, our study evaluated the associations of autophagy biomarkers with traditional cardiac biomarkers such as CK-MB, Troponin T and NT-proBNP, and echocardiographic left ventricular ejection fraction (LVEF).

Methods

We prospectively enrolled AMI patients with urgent coronary revascularization and controls who underwent coronary angiography without significant coronary artery stenosis. We obtained the serum of patients from peripheral artery and coronary artery before coronary revascularization. Levels of LC3-II, ATG5, Beclin 1 and M30 were quantified by ELISA in the serum from 22 AMI patients and 19 controls. Associations between autophagy biomarkers and traditional cardiac biomarkers were analyzed by Spearman bivariate correlation analysis.

Results

There were no significant differences in age, gender, systolic blood pressure, diastolic blood pressure, heart rate and medical history including hypertension, diabetes, dyslipidemia and atrial fibrillation between two groups. AMI patients had significant higher concentrations of autophagy biomarkers such as LC3-II (218.2±47.1 vs. 117.2±28.0 ng/ml; 238.4±60.5 vs. 118.5±27.7 ng/ml; p<0.001), ATG5 (205.6±57.8 vs. 62.9±40.0 ng/ml; 199.5±56.3 vs. 68.4±54.7 ng/ml; p<0.001), and Beclin 1 (225.6±55.1 vs. 123.8±16.6 ng/ml; 222.1±51.4 vs. 115.4±21.4 ng/ml; p<0.001) in peripheral artery and coronary artery, both (Figure 1). M30 of apoptosis level was also significantly higher in AMI patients than in controls (262.0±78.6 vs. 148.4±57.7 ng/ml; 290.4±128.5 vs. 144.5±50.1 ng/ml; p<0.001). Especially, LC3-II and Beclin 1 in coronary artery had strong positive correlations with Troponin T (rho=0.630, p<0.001; rho=0.624, p<0.001, respectively).

Conclusions

Autophagy biomarkers such as LC3-II, ATG5 and Beclin 1 were significantly higher in AMI patients than in controls. Autophagy biomarkers had significant positive correlations with Troponin T and NT-proBNP as the traditional cardiac biomarkers and negative correlations with LVEF.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)
Direct oral anticoagulants compared to vitamin K-antagonists in patients with left ventricular thrombus
Authors: Seiler T , Vasiliauskaite E , Cioffi G M , Madanchi M , Attinger A , Staempfli S F , De Boeck B , Kobza R , Toggweiler S , Moccetti F , Wolfrum M , Suter Y , Grueter D , Cuculi F , Bossard M
Published: October 2022

Background/Introduction

In the setting of left ventricular thrombus (LVT), direct oral anticoagulants (DAOC) are poorly studied. Current European guidelines recommend treatment with Vitamin K antagonists (VKA) for 6 months. So far, several observational studies reported similar efficacity and safety of DOACs, compared to VKAs. Controversial findings were found in one big cohort, where higher stroke rates were reported among patients treated with DOAC compared to VKA, what raised concerns about the efficiency and safety to use DOACS in the setting of LVT.

Purpose

This retrospective multicenter study compared thrombus resolution and clinical outcomes of patients with LVT treated with DOACs or VKAs.

Methods

From an echocardiography database of three teaching hospitals in Switzerland, patients diagnosed with LVT between 2015 and 2021 were identified. All echocardiograms and outcomes were reviewed by independent physicians. Thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen.

Results

Overall, 101 patients (17.8% females, mean age 63.3±13.2 years) were included. Among those, 50.5% had a recent myocardial infarction, 38.6% chronic ischemic heart disease and 10.9% suffered from non-ischemic cardiomyopathy. At hospital discharge, 48 (47.5%) were treated with DOACs and 53 (52.5%) with VKAs. Initial left ventricular ejection fraction was 38±13%. 93.1% patients presented with apical wall motion abnormalities, mean wall motion score index was 1.91±0.39. Initial thrombus size was comparable in both groups (table 1).

Median follow-up was 799 (354; 1236) days and the clinical composite endpoint combining stroke, systemic embolism, bleedings, myocardial infarction and death was comparable in the VKA (22.6%) and DOAC (27.1%) group, respectively. There was no difference in major (4% vs. 6.3%) and minor (13.5% vs. 4.3%) bleeding events, neither for stroke and systemic thromboembolism (14.3% vs 14.9%) or death (11.3% vs 8.5%). Thrombus resolution rate after 1 year was similar in the VKA and DOAC group (75.5% vs. 76.7%), but early thrombus dissolution within the first month was faster in the VKA arm (p=0.049). In each group, 3 subjects had thrombus recurrence after cessation of anticoagulation.

Conclusion

Among patients with LVT, DOACs appear to be a safe and effective alternative to vitamin K antagonists, but thrombus seems to dissolve slower in the first month. An adequately powered randomized trial is needed to confirm these findings.

Funding Acknowledgement

Type of funding sources: None.
Platelet extracellular vesicles are superior to cardiac troponin to diagnose acute coronary syndrome with short symptom duration: LEMONADE trial
Authors: Gasecka A , Budzianowski J , Wawiorka M , Palucha K , Pieszko K , Hiczkiewicz J , Filipiak K J , Grabowski M , Falkema K , Van Der Pol E , Nieuwland R
Published: October 2022

Background

Acute coronary syndrome (ACS), which comprises acute myocardial infarction (AMI) and unstable angina pectoris (UAP), is one of the main causes of mortality worldwide. Cardiac troponin is the gold standard to diagnose AMI. Troponin has two main disadvantages: it is negative in patients with UAP but positive in other diseases. During ACS, activated platelets release extracellular vesicles (EVs), which promote coagulation and associate with fibrin, and contribute to thrombus formation. We hypothesized that the concentration and composition of circulating platelet EVs (1) change in blood of patients with ACS compared to patients with other causes of chest pain, and (2) thereby allow earlier diagnosis of ACS than cardiac troponin.

Purpose

We aimed to determine the diagnostic value of circulating platelet EVs as novel early biomarkers of developing ACS.

Methods

We conducted a prospective, multicentre trial enrolling 105 patients who presented to the emergency department with suspected ACS. Blood was collected at admission to measure the concentration of EVs and cardiac troponin. Flow cytometry (Apogee A60-Micro) was used to determine plasma concentrations of platelet EVs exposing P-selectin (CD61+/CD62p+) and fibrin (CD61+/fibrin+).

Results

Plasma concentrations of platelet EVs exposing fibrin was lower in patients with ACS, compared to patients with other causes of chest pain (p=0.023) and lower in patients with an occlusive thrombus compared to non-occlusive plaque (p=0.015). Fibrin exposing-EVs were independent predictors of ACS (OR 8.2, CI 1.3–16.4) in multivariate analysis, allowing to diagnose ACS with 75% sensitivity and 72% specificity. Among patients with pain onset less than 2 hours before presentation, fibrin-exposing EVs had substantially better diagnostic performance than troponin (area under the ROC curve 0.90 vs. 0.74, respectively). Regarding other causes of chest pain, fibrin-exposing EVs were the lowest in patients with ACS, higher in patients with other cardiological causes of chest pain, and the highest in patients with non-cardiological causes of chest pain (p=0.036).

Conclusions

Circulating fibrin-exposing EVs are early biomarkers of developing ACS, superior to cardiac troponin in patients with pain onset less than 2 hours before presentation. Incorporation of EV measurements into the ACS diagnostic algorithm might revolutionise thrombotic risk stratification in the emergency setting.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Specialised Research Fellowship, “Club 30” of the Polish Society of Cardiology
Post-myocardial infarction late diastolic left ventricular blood flow energetics are independently associated with left ventricular remodeling
Authors: Demirkiran A , Van Der Geest R J , Hopman L H G A , Robbers L F H J , Handoko M L , Nijveldt R , Greenwood J P , Plein S , Garg P
Published: October 2022

Background

Post-myocardial infarction (MI) left ventricular (LV) remodeling emerges as a compensatory mechanism and leads to complex pathophysiological changes in LV blood flow hemodynamics. The interplay, if any, between LV blood flow energetics and remodeling remains unknown. We hypothesized that LV blood flow energetics early after MI are independently related to the temporal changes in LV end-diastolic volume (LVEDV).

Methods

In this prospective cohort study, 69 patients with acute re-perfused ST-segment elevation MI (STEMI) were included. The patients underwent cardiovascular magnetic resonance (CMR) examination within 2 days of the index event and at 3-month. CMR examination included cine, late gadolinium enhancement, and whole-heart 4D flow acquisitions. LV volume-function, infarct size (indexed to body surface area), microvascular obstruction (MVO), mitral inflow, and 4D blood flow kinetic energy (KE) characteristics were obtained. LV mean and peak KEi (indexed to LVEDV) were quantified for all time parameters (entire cardiac cycle, during systole/diastole, at E- and A-waves).

Results

In univariable linear regression analysis, peak KEi (R-R interval), mean systolic KEi, A-wave KEi, MVO presence were all associated with the relative change (%) of LVEDV (p=0.03, p=0.01, p<0.01, P=0.03, respectively). In multivariable linear regression analysis, A-wave KEi was identified as the only independent marker for association with the relative change of LVEDV (p=0.02). In another univariable linear regression analysis, A-wave KEi, infarct size, and MVO presence were all associated with the absolute change of LVEDV (p=0.03, p=0.04, p=0.04, respectively). In multivariable linear regression analysis, A-wave KEi was determined as the only independent marker for association with the absolute change of LVEDV (p=0.02). No significant association was observed between mitral inflow characteristics and relative and absolute change of LVEDV.

Conclusion

Late diastolic LV blood flow energetics early after acute MI are independently associated with both absolute and relative longitudinal changes in LVEDV and may provide incremental value over infarct and mitral inflow characteristics to be associated with post-MI LV remodeling.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation
Association of ischemic and bleeding events with mortality in patients with a recent acute myocardial infarction
Authors: Simonsson M , Alfredsson J , Szummer K , Jernberg T , Ueda P
Published: October 2022

Background/Introduction

Duration and intensity of antithrombotic treatment after myocardial infarction should be individualized based on a patient's ischemic and bleeding risk [1,2]. While such strategies are typically based on calculations that give equal weight to both types of events, uncertainty remains regarding their relative importance.

Purpose

To describe the incidence of ischemic and bleeding events in patients with a recent myocardial infarction, to compare the association of an ischemic vs bleeding event with mortality and to assess whether this association had changed over the past two decades.

Methods

Patients with acute myocardial infarction enrolled in the SWEDEHEART registry and discharged alive with antithrombotic treatment (aspirin, P2Y12 inhibitor, or oral anticoagulant) from January 2012 to December 2017 were followed from discharge until an ischemic event (recurrent myocardial infarction or ischemic stroke) or bleeding event. Cox regression adjusted for demographic factors, comedications and comorbidities, was used to estimate hazard ratios (HR) for time to death after an ischemic and bleeding event as compared with no event (in a model using time-varying exposure definition) and for an ischemic vs bleeding event in a direct comparison. We then assessed whether the adjusted HR for mortality of an ischemic vs bleeding event had changed across three time-periods (1997–2000, 2001–2011 and 2012–2017) by using an interaction term between time period and type of event.

Results

From January 2012 until December 2017 86, 736 patients were discharged alive with antithrombotic treatment after a myocardial infarction. Of these, 4,039 patients experienced a first ischemic event (incidence rate 5.7 events per 100 person-years), and 3,399 a first bleeding event (incidence rate 4.8 events per 100 person-years). As compared with no event, both ischemic events (adjusted HR 4.16, 95% CI 3.91 to 4.43) and bleeding events (adjusted HR 3.43, 95% CI 3.17 to 3.71) were associated with an increased risk of death. In the direct comparison, ischemic events were associated with a higher risk of death than bleeding events (adjusted HR 1.27, 95% CI 1.15 to 1.40). There was no evidence of a change in the aHR across the three time periods (aHR; 1.17, 95% CI 1.02 to 1.35 in 1997–2000 and 1.18, 95% CI, 1.11 to 1.27 in 2001–2011, p for interaction between time period and type of event ≥0.646).

Conclusion

In this nationwide study of patients with a recent MI, post-discharge ischemic events were more common and associated with higher mortality risk as compared with bleeding events.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung FoundationSwedish Diabetes Foundation
Temporal trends in the management and outcome of obese patients with an acute coronary syndrome – the ACSIS registry 2000–2018
Authors: Gurevitz C , Mohsen J , Ovdat T , Zwas D R , Fluk Gmach S , Beigel R , Eisen A
Published: October 2022

Introduction

Obesity has been increasing in epidemic proportions over many decades, and is clearly associated with major cardiovascular (CV) risk factors [1–2]. We aimed to examine temporal trends in the management and clinical outcomes of obese patients with an acute coronary syndrome (ACS).

Methods

Data from the ACSIS registry including all obese patients (calculated BMI of 30 or above) between the years 2000–2018. Patients were stratified by BMI to obesity classes: Class 1 – BMI 30–34; class 2 – BMI 35–39 and class 3 – BMI 40 and above. Clinical endpoints included 30d MACE and 1-year mortality. Temporal trends were examined in the late (2010–2018) vs. the early period (2000–2008).

Results

Among the 13,816 patients from the ACSIS registry with available BMI data, of whom 3567 were defined as obese, 2670 were in obesity class 1, 679 were in class 2, and 218 were defined as class 3. Patients in higher obesity classes had more CV risk-factors including dyslipidemia, hypertension, and diabetes mellitus (p<0.01 for all interactions). Overall, invasive and pharmacological treatment has improved during time in all obesity classes. The rates of 30-day MACE were numerically higher among patients in class 3 (11.6% in class 1, 11.3% in class 2, and 15.6% in class 3, p-trend= 0.3), and so was the rate of 1-year mortality (7.3%, 7.3%, and 10.9%, respectively, p-trend = 0.1) Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in class 1 and 2, but has remained unchanged in class 3. Similarly, 1-year mortality has not changed during the years among patients in class 3, but has decreased among patients in classes 1 and 2 (8.6% to 5.8%, p=0.007, and 9.3% to 5.5%, p=0.08, respectively) [Figure 1].

Conclusions

In obese patients admitted with an ACS, the rates of 30-day MACE and 1-year mortality are numerically higher among patients who are extremely obese. During 2 decades, 30-day MACE and 1-year mortality have decreased among obesity classes 1 and 2, but remained unchanged among patients in class 3. Extremely obese patients admitted with an ACS are a particularly high-risk group and future efforts should examine treatment modalities in order to curtail this increased risk.

Funding Acknowledgement

Type of funding sources: None.
Added value of left atrial strain in outcome prediction after myocardial infarction. SWEDEHEART-registry based echocardiographic study
Authors: Sjolen L , Lenell J , Lindahl B , Baron T
Published: October 2022

Background

Left ventricular function parameters, such as ejection fraction and global longitudinal strain are widely accepted prognostic parameters after myocardial infarction. Left atrial strain has been suggested as a novel risk parameter in this population.

Objective

To investigate whether left atrial (LA) deformation parameters (LA reservoir strain, LARS) can improve prognostic value of traditional echo parameters in prediction of heart failure and dead in patients after myocardial infarction. Moreover, to study relationship between LARS and established LV function parameters, and test its reproducibility between the readers.

Method

A total of 380 patients with myocardial infarction, hospitalized at our university hospital between 2008–2014, underwent echocardiography during hospital stay. The collected images was reanalyzed with respect to left atrial strain. Patients were followed up within the Swedish myocardial infarction registry (SWEDEHEART).

Results

To the final analysis a total of 253 patients (64 years of age, 81% men) were included, and followed up over median of 4.9 years. Among the parameters tested in the univariate analysis, LARS was able to predict long-term risk of heart failure admissions and death in patients with myocardial infarction (HR 0.95, 95% CI 0.91–0.99 for combined end-point). LARS below 27.2% identifies patients with higher risk of combined endpoint with AUC 0.68 (p=0.001). After adjustment for background characteristics and established LV function measures, LARS has lost significance, meaning that it provides no additional information in this population. LARS correlates moderately with LV GLS (r=−0.52, p<0.001) and weakly with LVEF (r=0.31, p<0.001), to a moderate extent and to a small extent with LAVI and LVEF, respectively. LARS shows moderate to perfect agreement between reviewers.

Conclusions

LARS is a good prognosticator of death and heart failure hospitalizations after myocardial infarction, but not independent of the established LV function parameters. We showed a good correlation between LARS and LV strain parameters and its near perfect inter-reader reproducibility.

Funding Acknowledgement

Type of funding sources: None.
Cardiovascular or renal disease (CVRD) complication and mortality incidence for type 2 diabetics with a single or without CVRD comorbidity: a 5-year SNDS nationwide claims database cohort study
Authors: Jourdain P , Blin P , Zaoui P , Guiard E , Sakr D , Dureau-Pournin C , Bernard M A , Lassalle R , Thomas-Delecourt F , Bineau S , Moore N , Droz-Perroteau C , Joubert M A
Published: October 2022

Background

Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal disease (CVRD) complications for type 2 diabetes (T2D). However, for those with a single CVRD comorbidity, the incidence of a new CVRD complication and death is not well known.

Purpose

To assess the 5-year CVRD complication and mortality incidence for T2D patients with a single CVRD comorbidity or without CVRD at baseline.

Methods

A cohort study of all T2D patients with a single CVRD or without CVRD (disease-free) at baseline (January 1st, 2014) identified and followed-up for 5 years within the French SNDS nationwide claims database. Incidence rates were estimated for 5 years and the risk of all-cause death was compared to the disease-free population using Cox proportional hazards risk model: hazard ratio (HR) with [95% confidence interval].

Results

From about 2 million T2D patients without cancer or transplantation at baseline, 76.5% were disease-free, 7.9% with a single CVRD and the others having several CVRD comorbidities history. Five-year CVRD complication and mortality incidence rates for 1,000 patient-years are presented in the table. CKD and HF were the most frequent CVRD complications for the disease-free and all CVRD comorbid populations, far ahead of MI, stroke and PAD, except PAD complication for PAD population and to a lesser degree stroke complication for stroke population. The incidence rate of all-cause death was the highest for HF+CKD patients, followed by HF patients, then PAD, stroke and CKD patients. Compared to disease-free patients with same sex and age, the HR of death was 4.3 [4.2–4.5] higher for HF+CKD patients, 2.7 [2.7–2.8], 2.1 [2.0–2.1], 2.1 [2.0–2.1], 1.9 [1.9–1.9] and 1.4 [1.3–1.4] for HF, CKD, PAD, stroke and MI patients, respectively.

Conclusions

While MI, stroke and PAD comorbidities remain major risks of complications for T2D patients, HF and CKD nowadays represent a clearly higher risk of CVRD complications and death, that needs improved preventive strategies.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Study performed with unconditional funding from AstraZeneca
Heart rate and mortality in myocardial infarction: incremental or bimodal correlation?
Authors: Biasco L , Foster-Witassek F , Radovanovic D , Dittli P , Tersalvi G , Rickli H , Roffi M , Eberli F , Jeger R , Erne P , Pedrazzini G B
Published: October 2022

Introduction

Risk prediction scores adopted in acute coronary syndromes use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, a non-linear, bimodal relationship, with higher event rates at low or high HR, has been described, potentially hampering risk prediction accuracy.

Purpose

Our aim was to assess the prognostic impact of bradycardia, defined as admission HR <50 bpm, in myocardial infarction (MI) among patients enrolled in a large nationwide registry.

Methods

Data of patients enrolled between 1999 and 2021 stratified by admission HR were retrospectively analysed. The primary endpoint was in-hospital mortality. The secondary endpoint was a composite of death, cerebrovascular event, and reinfarction. Associations between HR and outcomes were assessed at univariate and multivariable logistic regression analyses, then verified after sequential propensity-score matchings among HR groups.

Results

51001 patients (median age 66 years, IQR 56–76) were included. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. Association of HR <50 bpm with mortality was recognised only at primary multivariable logistic regression analysis (OR 1.49; 95% CI 1.01–2.13 p=0.038) but not at multiple sensitivity analyses after exclusion of patients on negative chronotropic therapy. Three sequential propensity-score matching were performed among patients with HR <50 bpm at admission and those with HR 50–75 bpm, HR 76–100 bpm and HR >100 bpm at admission, identifying 1159, 1159 and 1158 matched pairs, respectively. After propensity-score matching, rates of primary and secondary endpoints equalled among groups with HR <100 bpm.

Conclusions

Bradycardia (HR <50 bpm) at admission in patients with MI identified a group with higher crude rate of adverse events. Nonetheless, the signal supporting an independent association between bradycardia at admission and short-term mortality is weak and was not confirmed after correction for relevant baseline differences by propensity score matching. These findings support the hypothesis that lower HR might not be causative for the worse outcomes, but rather serves as a marker of underlying morbidity.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The AMIS Plus registry is funded by unrestricted grants from the Swiss Heart Foundation and from Abbot AG, Amgen AG, AstraZeneca AG, Bayer (Schweiz) AG, Biotronik AG, Boston Scientific AG, B. Braun Medical AG, Daiichi-Sankyo/Lilly AG, Cordis Cardinal Health GmbH, Medtronic AG, Novartis Pharma Schweiz AG, Sanofi-Aventis (Schweiz) AG, SIS Medical AG, Terumo AG, Vascular Medical GmbH, all in Switzerland, and the Swiss Working Group for Interventional Cardiology. The sponsors did not play any role in the design, data collection, analysis, or interpretation of data.
Prevalence and outcomes of peripheral artery disease in a real-world cohort of patients with acute coronary syndrome: insights from the prospective SPUM registry
Authors: Denegri A , Magnani G , Kraler S , Wenzl F , Raeber L , Gencer B , Mach F , Nanchen D , Matter C M , Luescher T F
Published: October 2022

Background

Despite substantial improvement in secondary preventive therapy, the burden of recurrent cardiovascular (CV) events remains high. Peripheral artery disease (PAD), is a potential marker of increased residual ischemic risk in acute coronary syndrome (ACS) patients suggesting greater net clinical benefit from intensified individualized therapy.

Purpose

We aimed to assess the prevalence and cardiovascular (CV) outcomes of peripheral arterial disease (PAD) in 4'787 patients with acute coronary syndromes (ACS) in the Swiss prospective multicenter SPUM study.

Methods

PAD was defined according to international guidelines. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), i.e., stroke, myocardial infarction (MI) and death at 1 year. Adjusted Cox proportional hazards regression models were used to estimate the risk associated with PAD and outcomes.

Results

Out of 4'787 ACS patients, 285 patients (6.0%) had PAD. These patients were older (70.1±10.6 vs 63.3±12.4, p<0.001), presented all traditional CV risk factors (all p<0.001) and were more likely to have a complex history of CV disease, such as previous MI (24.3% vs 11.4%, p<0.001), prior percutaneous (32.3% vs 13.8%, p<0.001) or surgical (12.6% vs 3.5%, p<0.001) coronary revascularization. PAD-patients presented also higher levels of inflammatory biomarkers, such as hs-CRP, and GRACE 2.0 score (all p<0.001). At 1 year, patients with PAD had a higher rate of MACCE compared to those presenting without PAD. Rates of the individual components of the primary endpoint and CV-death were all significantly higher in patients with PAD (all p<0.001), except for a numerical increase in MI (5.3% vs 3.3%, p=0.060). This enhanced risk persisted after adjustment for differences in baseline characteristics, with a 53% (Adj. HR 1.53, CI95% 1.14–2.08, p=0.005) increase in MACCE. In spite of high-intensity anti-thrombotic therapy, PAD patients presented the same rate (Adj. HR 1.03, CI95% 0.68–1.54, p=0.901) of major bleeding events at 1 year.

Conclusions

Among a real-world cohort of ACS patients, the coexistence of PAD, a very-high CV risk phenotype, is associated with significantly increased rates of MACCE, but no difference in major bleeding events. These observations might help clinicians to further stratify this very-high risk population and to identify patients who may derive the greatest benefit from more intense secondary prevention therapies.

Funding Acknowledgement

Type of funding sources: None.
Prognostic impact of aborted cardiac arrest in patients with acute myocardial infarction
Authors: Presume J , Gomes D , Strong C , Tralhao A , Aguiar C , Trabulo M , Almeida M , Ferreira J , Mendes M
Published: October 2022

Background

Aborted cardiac arrest (ACA) during the acute ischaemic phase is a relatively frequent but often undervalued complication of acute myocardial infarction (AMI). The aim of this study was to evaluate the clinical and prognostic impact of aborted cardiac arrest in AMI patients and investigate its correlation with infarct size.

Methods

We conducted a single-centre retrospective study enrolling consecutive patients admitted for AMI, from January 2016 to December 2018. ACA was defined as the need for advanced life support measures and defibrillation, either out-of-hospital or in-hospital, up until culprit vessel revascularisation. Infarct size was estimated using peak serum troponin T, impact on left ventricular ejection fraction (LVEF ≤50%) and echocardiographic wall motion index (WMI). Clinical outcomes included cardiogenic shock (SCAI C or more), need for mechanical circulatory support (MCS), major bleeding events (BARC ≥3) during in-hospital phase and all-cause mortality during follow-up.

Results

A total of 571 patients were included (65±13 years old, 72% male). Overall, 237 had anterior STEMI, 39 patients (6,8%) suffered ACA (21 out of hospital), 60 progressed into cardiogenic shock throughout the hospitalisation, 7 needed MCS, and 52 had BARC ≥3 bleeding. During a mean follow-up of 32 months, 96 patients died.

ACA was significantly associated with higher peak serum troponin T (4802 [1950; 9420] vs 2659 [555; 6708] ng/L – p=0.004), higher proportion of patients with reduced or mildly reduced LVEF (60% vs. 36.5%, p=0.018) and higher WMI (1.7 [1.4; 2.3] vs. 1.5 [1.2; 1.8], p=0.016). Moreover, ACA was also associated with higher risk of cardiogenic shock occurrence (64.1% vs. 6.6%, p<0.001 – OR 25.357 (12.115–53.073)), higher need for MCS (7.9% vs 0.8%, p<0.001 – OR 11.271 (2.427–52.343)) and higher incidence of BARC ≥3 bleeding events (28.2% vs. 8.4%, p<0.001 – OR 4.705 (2.185–10.128)) – Table 1.

On univariate Cox regression, ACA showed significant association with all cause death, which remained highly significant after multivariable adjustment (OR 2.431 (1.181; 5.002); p=0.016).

Conclusion

The occurrence of aborted cardiac arrest in patients with AMI was associated with increased morbidity and mortality. This may be driven by a larger area of arrhythmia prone ischemic myocardium.

Funding Acknowledgement

Type of funding sources: None.
Prognostic and diagnostic impact of new pathophysiology-based categorization of type 1 and type 2 myocardial infarction: data from the French RICO survey
Authors: Yao H , Putot A , Chague F , Maza M , Bichat F , Cottin Y , Zeller M
Published: October 2022

Background

A new classification of type 1 and 2 myocardial infarction (MI) derived from the fourth universal definition of MI (UDMI) has been recently proposed, based on pathophysiology of coronary artery disease (CAD),. We assessed the impact of this new MI categorization on epidemiology and outcomes.

Methods

Retrospective study including all consecutive patients hospitalized for an acute MI in a multicenter database (RICO). MI was defined according to current UDMI. Rates and outcomes of T1MI and T2MI were addressed according to the new classification.

Results

Among the 4573 patients included on our study, 3710 patients (81.1%) were initially diagnosed with T1M1 and 863 (18.9%) with T2MI. After reclassification, 96 T2MI patients were moved into the T1MI category. Out of the remaining 767 patients with T2MI, 567 underwent coronary angiography, and were adjudicated as type 2A MI (68.6%) with obstructive CAD, and type 2B MI (31.4%) without obstructive CAD.

When compared with T1MI and T2BMI, T2AMI patients had worse in-hospital outcomes, including heart failure (p<0.001), recurrent infarction (p<0.048) and mechanical complications such as mitral insufficiency (p=0.001). The 3 groups (T1AMI, T2AMI and T2BMI) had similar all-cause and cardiovascular death rates, with a trend for a higher all-cause mortality in T2AMI patients.

Kaplan-Meier one-year survival curves showed higher all-cause and cardiovascular causes mortality in T2AMI patients compared to T1MI and T2BMI (p<0.001). In multivariate Cox regression, type of MI was independent predictor of death.

Conclusion

Our large observational multicenter study shows major disparities in mortality according to type of MI and support the relevance of the new MI classification to improve risk classification. Our findings may will help identifying specific phenotypes and considering personalized diagnostic and management strategies.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Agence Régionale de Santé (ARS) de Bourgogne Franche-ComtéRegional Council of Bourgogne Franche-Comté.
Prognostic impact of newly diagnosed atrial fibrillation and episode characteristics in patients with acute coronary syndrome
Authors: Bor W L , Azzahhafi J , Di Maio N , Van Der Sangen N M R , Rayhi S , Chan Pin Yin D R P P , Peper J , Ten Berg J M
Published: October 2022

Background/Introduction

Newly diagnosed atrial fibrillation (AF) frequently occurs during acute coronary syndrome (ACS). In contrast to known AF, little is known about the prognostic and therapeutic implications of new AF.

Purpose

To evaluate the prognostic impact of newly diagnosed and known AF in patients with ACS. Furthermore, we evaluated the association of episode characteristics of new AF with clinical outcomes: early vs late occurrence, short vs long duration, post-CABG occurrence, and OAC treatment.

Methods

This analysis was performed within the prospective, multicentre, FORCE-ACS registry which studies ACS patients in the Netherlands. All ECGs during index ACS admission were retrospectively examined for the occurrence of AF. Patients were classified as no, new, or known AF. New AF episodes were described regarding early or late occurrence, duration of the episode, and post-CABG occurrence, and OAC prescription at discharge was evaluated. The primary outcome was MACE, a composite of death, myocardial infarction and stroke. Secondary outcomes include the separate MACE components and bleeding. Crude and adjusted outcomes were evaluated by univariable and multivariable Cox regression.

Results

3902 patients were included of which 299 (10.2%) had new and 367 (9.4%) had known AF. Major adverse cardiac events happened significantly more in both new and known AF patients than in patients without AF (22.2%, 17.4%, and 9.2%, p<0.001). Ischemic stroke occurred significantly more in new AF but not in known AF patients, compared to patients without AF (3.5% vs 0.9% vs 1.1%). After one year follow-up, a total of 234 patients (6.3%) deceased, of whom 138 in the group without AF (4.6%), and significantly more in the groups with new AF (n=59, 15.9%), and known AF (n=37, 10.8%). The timing of onset of the AF episode showed no significant association with clinical outcomes. Longer duration of the episode, however, was associated with increased MACE (HR 2.0, 95% CI 1.2–3.1) and all-cause mortality (HR 2.0, 95% CI 1.2–3.4). Episodes of new AF that occurred post-CABG were associated with less MACE (HR 0.31, 95% CI 0.14–0.67) and all-cause mortality (HR 0.20, 95% CI 0.07–0.55). No significant association between OAC treatment and MACE nor any of its separate components was found.

Conclusion

Newly diagnosed atrial fibrillation in acute coronary syndromes is associated with worse clinical outcomes than known or no atrial fibrillation. Longer episodes were associated with worse outcomes than short episodes. Post-operative new AF was associated with better outcomes than non-post-operative new AF.

Funding Acknowledgement

Type of funding sources: None.
Glycated haemoglobin and the association with long-term survival among patients evaluated for stable angina – a prospective Norwegian cohort
Authors: Svingen G , Pedersen E K R , Meyer K , Softeland E , Tell G , Ueland P M , Nygaard O K
Published: October 2022

Background and methods

Recent guidelines have included glycated haemoglobin (HbA1c) ≥48 mmol/L as a diagnostic criterion for diabetes mellitus (DM) in addition to plasma glucose (PG) concentrations, mainly based on the relationship between hyperglycemia and microvascular disease [1]. However, increased HbA1c may stem not only from hyperglycemia, and the risk association between HbA1c and long-term survival in patients with stable coronary heart disease and HbA1c ≥48 mmol/L but no previous DM according to PG is uncertain. We explored the relationship between HbA1c and survival among patients with and without DM who were evaluated for stable angina in the period 2000–2004. Endpoints were obtained from the Norwegian Cause of Death Registry.

Results

In total, 4164 patients were evaluated by cardiac cathetherization, of whom 576 patients (13.8%) had DM (median HbA1c 55 mmol/L) according to self-report and/or baseline PG concentrations. Of the remaining 3588 patients 1026 had HbA1c ≥48 mmol/L; however, HbA1c did not correlate with the HOMA2 insulin resistance index or fasting PG in these patients. During median (25–75 percentile) follow-up time of 14.0 (12.1–15.4) years a total of 1328 patients (31.9%) died, of whom 582 from cardiovascular causes. In patients with DM according to PG, HbA1c trended towards positive associations with all-cause and CVD mortality when adjusted for age and gender (HRs (95% CIs) 1.13 (0.99–1.28) and 1.16 (0.98–1.39) per 1SD, respectively). However, HbA1c was not associated with survival in either the group of patients without DM and HbA1c <48 mmol/L (median HbA1c 38 mmol/L) (HRs (95% CIs) 0.99 (0.92–1.06) and 0.96 (0.86–1.08) for all-cause and CVD mortality, respectively) or patients without DM but having HbA1c ≥48 mmol/L (median HbA1c 53 mmol/L) (HRs (95% CIs) 0.99 (0.88–1.12) and 1.04 (0.88–1.22)).

Conclusion

In patients evaluated for stable angina pectoris about two decades ago, almost a third of patients with no history of DM according to PG still had HbA1c concentrations indicating DM according to current guidelines. Including these patients in the DM category yielded similar percentages of patients with DM as observed in recent populations with stable coronary disease [2]. However, as opposed to what we observed in patients with DM, HbA1c did not show any association with very long-term survival among patients without DM. Our findings therefore question the use of HbA1c in the diagnosis of DM, especially in terms of risk assessment for longevity among patients with chronic coronary syndrome.

Funding Acknowledgement

Type of funding sources: None.
0/1h-algorithm using a new high-sensitivity cardiac troponin I assay for early diagnosis of myocardial infarction
Authors: Koechlin L , Boeddinghaus J , Lopez-Ayala P , Nestelberger T , Wussler D , Twerenbold R , Zimmermann T , Wildi K , Miro O , Martin-Sanchez J , Keller D , Christ M , Buser A , Rubini Gimenez M , Mueller C
Published: October 2022

Background

The clinical performance of the novel high-sensitivity cardiac troponin I EXL (hs-cTnI-EXL) assay is unknown so far.

Purpose

We aimed to validate the clinical performance of the hs-cTnI-EXL assay and to derive and validate an hs-cTnI-EXL-specific 0/1h-algorithm for the early diagnosis of myocardial infarction (MI).

Methods

This multicenter study included patients presenting to the emergency department with symptoms suggestive of myocardial infarction. Central adjudication of final diagnoses was performed by two independent cardiologists using all clinical information including cardiac imaging twice: first, using serial hs-cTnI-Architect (primary analysis) and second, using serial hs-cTnT-Elecsys (secondary analysis) concentrations in addition to those clinically used (hs)-cTn. Hs-cTnI-EXL was measured at presentation and at 1h. The primary objective was to directly compare diagnostic accuracy quantified by the area under the receiver-operating-characteristic curve (AUC) of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys. Secondary objectives included the derivation and validation of an hs-cTnI- EXL-specific 0/1h-algorithm.

Results

MI was the adjudicated final diagnosis in 204/1454 (14%) patients. At presentation, the AUC for hs-cTnI-EXL was 0.94 (95% CI, 0.93–0.96), being comparable to hs-cTnI-Architect (0.95; 95% CI, 0.93–0.96) and hs-cTnT-Elecsys (0.93; 95% CI, 0.91–0.95; Figure 1). In the derivation cohort (n=813), an optimal hs-cTnI-EXL-0/1h-algorithm was rule-out of MI with <9ng/L if onset of chest pain >3h or <9ng/L & 0h-1h-change <5ng/L, and rule-in with ≥160ng/L or 0h-1h-change ≥100ng/L. In the validation cohort (n=345), this hs-cTnI-EXL-0/1h-algorithm also performed well: rule-out in 56% of patients, negative predictive value 99.5% (95% CI, 97.1–99.9), sensitivity 97.8% (95% CI, 88.7–99.6), rule-in in 9% of patients, positive predictive value 83.3% (95% CI, 66.4–92.7), specificity 98.3% (95% CI, 96.1–99.3; Figure 2). Secondary analyses confirmed the findings using adjudication including serial measurements of hs-cTnT-Elecsys.

Conclusions

Hs-cTnI-EXL has comparable diagnostic performance to the currently best-validated hs-cTnT/I assays.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swiss National Foundation, Swiss Heart Foundation
Soluble suppression of tumorigenicity associated to post-procedural no-or-slow-reflow phenomenon in ST-elevation myocardial infarction
Authors: Sondergaard F , Beske R , Frydland M , Helgestad O , Jensen L O , Holmvang L , Engstroem T , Moeller J E , Hassager C
Published: October 2022

Background

Over the last decades, the prognosis for patients with ST-elevation myocardial infarction (STEMI) has improved due to primary percutaneous coronary intervention (pPCI). However, no-or-slow-reflow phenomenon after pPCI constrains this benefit. Suppression of tumorigenicity (sST2) is released from vascular endothelial cells in response to myocyte stretch and increased sST2 level in the initial phase of STEMI is a useful prognostic biomarker for predicting mortality and heart failure (HF).

Purpose

To explore the association of sST2 with post-procedural no-or-slow-reflow phenomenon in patients with STEMI.

Method

During a 1-year period in 2015/2016, the study included consecutive STEMI patients from two heart centers who underwent acute coronary angiography (CAG). Blood samples including sST2 levels were collected at admission and before angiography and/or revascularization. Post-procedural coronary flow was assessed according to thrombolysis in myocardial infarction (TIMI) classification for STEMI. We divided patients into two groups: TIMI 0,1 and 2 as no-or-slow-reflow, and TIMI 3 as normal reflow. Both troponin I and troponin T were used and therefore combined and grouped into 10th percentile levels. The association between sST2 and TIMI flow was explored using multiple logistic regression adjusted for age, gender, hypercholesterolemia, diabetes, hypertension, cardiogenic shock, time from onset of symptoms to CAG, and troponin levels.

Results

In total, 1,789 consecutive patients with verified STEMI and available TIMI flow classification were included in the analysis. Of these, 1,693 (94.6%) classified as normal reflow and 96 (5.4%) as no-or-slow-reflow. The proportion of male sex was similar (1,253 (74%) vs 67 (70%), p=0.36) in the two groups. No-or-slow-reflow patients were older (median 68 years (IQR 57–75) vs median 63 years (IQR 54–72), p=0.02) and more likely to develop cardiogenic shock (22 (23%) vs 146 (8.6%), p<0.001). The troponin level was similar in the two groups (no-reflow: 5.50 (2.00, 8.00) vs normal reflow: 5.00 (3.00, 7.00), p=0.38). In the regression model, sST2 was independently associated with post-procedural no-or-slow-flow (two-fold sST2 increase: OR 1.37 (1.09, 1.70, p=0.006)).

Conclusion

In patients with STEMI, sST2 level at admission before coronary angiography is associated with the post-procedural no-or-slow-reflow phenomenon.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Righospitalets Forskningsfond AND Lundbeck Foundation
Prognostic implication of platelet reactivity according to disease entity after drug eluting stent implantation: results from the PTRG-DES consortium
Authors: Hyun Woong P , Jeong J Y H , Kim K B K , Joo J H J , Park P Y , Chang C K , Song S Y B , Ahn A S G , Suh S J W , Lee L S Y , Cho C J R , Kim H S K , Kim K M H , Shin S E S
Published: October 2022

Background

Relationship between the level of antiplatelet effect and clinical event appears weak in East Asian patients. In addition prognostic implication of platelet reactivity may differ according to index presentation of disease entity (AMI vs. non-AMI).

Methods

PTRG-PFT consortium was established to determine the linkage of platelet function with long-term clinical outcome during DAPT (aspirin+clopidogrel) in DES-treated East Asian patients (n=11,714). Platelet reactivity was measured using the VerifyNow P2Y12 assay and its level was divided according to quartile distribution (≤168, 169–220, 221–271, ≥272 P2Y12 reaction unit [PRU]). Primary endpoints were incidences of major adverse cardiac and cerebrovascular events (MACCE) post-PCI.

Results

Impact of platelet reactivity on MACCE occurrence appeared proportionally increased irrespective of type of disease entity, but their relationship was relatively stronger in the AMI vs. non-AMI group (Figure 1A and B). The cutoff of high-risk platelet reactivity was lower in the AMI group compared with the non-AMI group (225 vs. 245 PRU), and the cutoff of low-risk platelet reactivity (immunity zone) was similar between the groups (175 vs. 170 PRU). In the AMI patients (28.5%), 3rd and 4th quartiles significantly increased MACCE rate (HRadjusted 2.19 and 2.24) (Figure 1C and D). However, 4th quartile only was significantly associated with increased risk of MACCE among the non-AMI patients (71.5%) (HRadjusted 2.19).

Conclusion

Close associations between platelet reactivity and MACCE occurrence were observed irrespective of type of disease entity. In addition, the targeted antiplatelet level to prevent platelet-centric events appeared similar between the AMI and non-AMI patients.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Korean Society of Intervention Cardiology