bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic outcome of ACS in HTX patients after PCI
Authors: Ayoub M , Rudolph V , Elbinger L
Published: October 2024

Background

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide, particularly in countries with limited access to healthcare [1,2]. Acute coronary syndrome is a collective term for several clinical conditions resulting from narrowing or occlusion of the coronary arteries [3,4]. Another group of patients affected by cardiovascular disease are those who have undergone heart transplantation. Long-term survival after transplantation is limited by cardiac allograft vasculopathy, a condition that affects the coronary arteries of the donor heart and causes diffuse narrowing [5,6]. Our retrospective analysis aims to compare the prognostic outcomes of HTX patients with ACS who underwent PCI with patients without a history of HTX.

Results

A total of 3194 patients with ACS were enrolled, of whom 1.16% (37) had a previous heart transplant. Patients with prior transplantation were on average younger (52.54 ± 15.13 vs. 69.76 ± 12.16, p < 0.001), had less dyspnea (p < 0.001) and a different distribution of ACS types (p < 0.001), as shown in Figure 1. There were no differences in sex (p = 0.287), BMI (p = 0.123), hypertension (p = 0.557), diabetes mellitus (p = 0.188) and previous myocardial infarction (p = 0.681). The majority of HTX patients were diagnosed with ISHLT CAV III (58.54%) and the average time to PCI was 12 years after transplantation. Multi-vessel disease was more common in HTX patients (p < 0.001). In addition, calcification was less frequent in the HTX group than in the control group (p < 0.001), and the lesion morphology was more diffuse in the HTX group (p < 0.001). On the other hand, there was no difference in the distribution of target vessels (p = 0.424), with the left anterior descending being the most frequently treated coronary artery, followed by the left circumflex and right coronary arteries. HTX patients received more stents (p < 0.001). There was also a difference in post-procedural TIMI flow achieved (p = 0.047), with less TIMI 3 flow achieved after PCI in the HTX group (80% vs. 93.59%). Technical success was less likely to be achieved in the HTX group (62.50% vs. 96.29%, p < 0.001), as was procedural success (47.06% vs. 89.68%, p < 0.001). There was no difference in the incidence of complications, which include perforation and bleeding (p = 0.284). All-cause mortality at three years (39.02% vs. 17.50%, p < 0.001), stroke (7.32% vs. 1.59%, p = 0.035) and myocardial infarction (p = 0.026) were higher in the HTX group. Over a period of three years, MACCE was more likely to occur in the HTX sub-group, which is shown graphically in Figure 2.

Conclusion

Interventional treatment of ACS in HTX patients is an option with a complication rate comparable to non-HTX patients and with a lower technical and procedural success - partly due to the diffuse nature of CAV and the involvement of distal and microvascular vessels. Overall MACCE and survival are inferior to the control population.Figure 1Figure 2
Persistent angina following revascularization for chronic coronary syndromes: a systematic review and meta-analysis of randomized controlled trials
Authors: Singh A , Brown D L
Published: October 2024

Introduction

Recent randomized clinical trials (RCTs) have demonstrated that revascularization plus optimal medical therapy for patients with chronic coronary syndromes (CCS) results in greater reduction in angina than medical therapy alone. However, the frequency of persistent angina following revascularization for CCS is not well understood.

Purpose

To quantify the frequency of persistent angina following revascularization in contemporary RCTs of revascularization plus medical therapy vs. medical therapy alone among patients with CCS.

Methods

A literature search through January of 2024 was conducted in PubMed and Cochrane Central Register of Controlled Trials for contemporary RCTs reporting angina frequency following randomization to revascularization plus medical therapy vs. medical therapy alone. The primary outcome of interest was the frequency of persistent angina in the revascularization arms of these studies at early (3-12 months) and late (3-5 years) time points. A random effects model was used to combine results from individual studies.

Results

From a total of 5287 citations, the search yielded 7 RCTs that met inclusion criteria. These studies randomized 5719 patients to an invasive or revascularization strategy. Revascularization was exclusively by percutaneous coronary intervention (PCI) in 4 studies and by coronary artery bypass grafting or PCI in 3 studies. At the early time point, the combined frequency of persistent angina was 39.6% (95% CI: 30.6-49.4). For the two blinded, sham-controlled studies, the rate of persistent angina was significantly greater at 67.2% (95%CI: 54.9-77.4) compared to 30.5% (95% CI: 23.1-39) in the unblinded studies (P<0.001). In the 5 studies with 3-5 years of follow-up, the frequency of persistent angina was 33.3% (95% CI: 19.2-51.2).

Conclusion

Persistent angina is common after revascularization for CCS and suggests alternative causes and treatments of residual angina should be considered.
Estimated impact of inclisiran treatment on hyperlipidemia prevalence and cardiovascular disease events in NHANES dataset
Authors: Li H , Zhao S , Wu J , Zhang Y
Published: October 2024

Background

Inclisiran, administered subcutaneously every 6 months, will result in the reduction of LDL-cholesterol levels of approximately 50%. We estimated the eligibility of the US population for Inclisiran treatment and its impact on blood lipids and CVD events.

Methods

We applied ORION trial eligibility criteria to US adults aged ≥ 18 years in the US NHANES 1999-2018 to estimate the US eligible population. Blood lipid alterations in ORION 10 were applied to estimate the impact on LDL-C levels and hyperlipidemia prevalence in the ASCVD population sample. We also used the Framingham CVD risk scores to estimate 10-year CVD risks in the ASCVD high-risk population sample based on ORION 11. The difference in estimated risks with and without Inclisiran administration, multiplied by the eligible population from NHANES data, represented the potentially preventable CVD events.

Results

We identified 651 ASCVD persons (projected to 5.55 million) who fit ORION 10 trial eligibility criteria and 359 ASCVD high-risk persons (projected to 2.53 million) who fit ORION 11 trial eligibility criteria for our analysis. We then analyzed the changes in these populations after Inclisiran treatment. Firstly, we estimated that approximately 3.9 million (72.8%) individuals would experience ≥50% LDL-C reductions. Secondly, we estimated that among the ASCVD patients, 5.07 million (91.3%) with elevated LDL-C, 0.25 million (22.8%) with reduced HDL-C, 1.24 million (95.2%) with elevated TC, and 0.65 million (32.4%) with elevated TG would potentially achieve a more reasonable blood lipid level. Finally, among those without CVD, the estimated 10-year CVD risks were 19% before and 13.8% after Inclisiran treatment, reflecting a 5.2% absolute (and 27.4% relative) reduction in risk translating to potentially 130,000 preventable CVD events over 10 years.

Conclusion

Inclisiran treatment in eligible US adults may substantially reduce hyperlipidemia prevalence and CVD events.core graphics
Assessing the utility of the increased wall thickness score in diagnosing ATTR cardiomyopathy: a validation study
Authors: Sobral Domingues M , Carvalho R , Lima R , Maltes S , Rocha B , Ferreira A , Aguiar C , Ribeiras R , Freitas P
Published: October 2024

Introduction

Cardiac amyloidosis due to transthyretin deposition (ATTR-CM) is often underdiagnosed. An increased left ventricular wall thickness (LVWT) should raise the suspicion for ATTR-CM, but it is a very frequent and non-specific finding. In order to improve diagnostic certainty, an echocardiographic score (Increased Wall Thickness [IWT] score) was recently proposed.

The aim of our study was to assess the diagnostic performance of the IWT score in an independent population with increased LVWT.

Methods

We conducted a retrospective analysis of 295 consecutive patients studied at our centre for increased LVWT. All patients with severe aortic stenosis (AS) had ATTR-CM excluded by endomyocardial biopsy (EMB), during aortic valve replacement. ATTR-CM was considered as per the ESC algorithm. To be included, patients with Hypertrophic Cardiomyopathy (HCM) performed cardiac magnetic resonance and required a sarcomeric mutation for definite diagnosis.

The echocardiographic IWT score was calculated for all patients, and categorized as certain (IWT≥8), unlikely (IWT ≤1) or indeterminate (1 < IWT < 8) for ATTR-CM diagnosis.

Results

A total of 295 patients were included (median age of 75 years [69-81], 61% men). Overall, 230 (70%) patients had hypertension and 164 (56%) chronic kidney disease (CKD). The median LVWT was 16 mm [IQR 15-19] and the median LVEF was 57% [IRQ 50-62%].

After diagnostic workup, 97 patients (33%) had confirmed ATTR-CM, 129 (44%) had isolated severe AS and 71 (24%) had hypertrophic cardiomyopathy (HCM). Fifteen patients had both severe AS and ATTR-CM.

The median IWT score was 4 (IQR 2-7), with 21% of patients (n=64) showing an IWT score ≤1, 19% an IWT score ≥8, and 60% of patients (n=176) having an "indeterminate" value between 2 and 7. Despite this, on a continuous scale, the IWT showed good discriminative value (area under ROC curve 0.86, 95% 0.82-0.90, p<0.001). The criteria of IWT score ≥8 showed a positive predictive value of 82% (95% CI 72-89%), while an IWT score ≤ 1 yielded a negative predictive value of 92% (95% CI 84-97%) - Figure.

Conclusions

Even though the IWT score provides "indeterminate" results in a large proportion of patients, values at the ends of the spectrum showed good negative and positive predictive values for the diagnosis of ATTR-CM. Our findings provide external validation for this echocardiographic score, and support its use in the diagnostic workup of patients with increased wall thickness and suspected ATTR-CM.
Association of ticagrelor vs clopidogrel with net adverse clinical events in STEMI patients with mild thrombocytopenia
Authors: Jiang C , Zhang Y K , Gu T S , Hu S T , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Backgrounds

Current guidelines advocate for aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing STEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L.

Purpose

This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in STEMI patients with a platelet count of 100~150×109/L.

Methods

A retrospective cohort study was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023.The study included STEMI-patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (either clopidogrel or ticagrelor) All STEMI patients with a platelet count of 100~150×109/L were included in the analysis with a follow-up of at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was utilized to balance observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, including ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes were cardiac death, recurrent myocardial infarction, and ischaemic stroke.

Results

The study cohort consisted 2941 participants with median age of 69 years, and 21.0% were female. Following adjustment using the inverse probability of treatment weighting, ticagrelor and clopidogrel demonstrated similar NACE (aHR, 0.86; 95%CI, 0.60-1.23). Cardiac death (aHR, 0.69; 95%CI, 0.36-1.31), recurrent myocardial infarction (aHR, 0.94; 95%CI, 0.50-1.78), and ischaemic stroke (aHR, 0.62; 95%CI, 0.34-1.14) did not significantly differ between the two groups.

Conclusion

In routine clinical practice, among STEMI patients with a platelet count of 100~150×109/L ticagrelor compared with clopidogrel, was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this particular patient population.
Prevalence, type, severity and determinants of sleep disordered breathing in acute myocardial infarction patients: the AMI-Sleep study
Authors: Balagny P , D'ortho M P , Sauze D , Rousseau A , Vidal-Petiot E , Drouet E , Gourmelen J , Durand-Zaleski I , Simon T , Steg P G
Published: October 2024

Background

Sleep Disordered Breathing (SDB) is highly prevalent in patients with ischemic heart disease and often remains undiagnosed.

Purpose

We aimed to assess the prevalence, type, severity and determinants of SDB in patient hospitalized for acute myocardial infarction (AMI).

Methods

We prospectively enrolled a subset of patients hospitalized for AMI of the French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry included from January 2019 and December 2022 in the 16 AMI-Sleep-trained centers. Baseline and in-hospital information were collected through the FRENCHIE registry. A simplified polygraphy through ApneaLink Air+ was performed overnight during the initial hospitalization before discharge. Data were scored in centralized manner at a single center where trained physicians ascertained SDB characteristics (central or obstructive) and severity based on Apnea-Hypopnea index (AHI). SDB was defined by an AHI≥15/h. Multivariable logistic regression (adjusted for age, sex, diabetes, hypertension, smoking, body mass index, severity of the coronary artery disease, left ventricular ejection fraction [LVEF] at admission [or at discharge if missing] and use of Ticagrelor) was used to analyze the associations between characteristics of the patients at inclusion and SDB.

Results

Among 1752 patients, 955 (54.5 [52.1;56.9] %) had an AHI≥15/h. The prevalences of mild (AHI= 5-14.9), moderate (AHI=15-29.9) and severe (AHI≥30) SDB were 30.9%, 24.2% and 30.3% respectively. SDB characterization was technically possible in 712 patients (74.6%), and was found central in 72.2% of cases, obstructive in 12.9% and mixed in 15.4%. Male sex, age, BMI, diabetes, degree of severity of CAD, LVEF≤40% and treatment with Ticagrelor were independently associated with SDB.

Conclusion

More than half of the patients hospitalized for AMI had at least moderate SDB with a majority of them characterized as central. SDB diagnosis should be considered in this setting and particularly in very high cardiovascular risk patients with severe CAD.SDB determinants in AMI patients
Prognostic significance of type 4a myocardial infarction and periprocedural myocardial injury in NSTEMI patients
Authors: Bodega F , Armillotta M , Bergamaschi L , Sansonetti A , Angeli F , Amicone S , Bertolini D , Fedele D , Canton L , Suma N , Impellizzeri A , Tattilo F P , Cavallo D , Casella G , Pizzi C
Published: October 2024

Background

Type 4a myocardial infarction (MI) and periprocedural myocardial injury (PMI) might occur in patients with non-ST-elevation MI (NSTEMI) after percutaneous coronary intervention (PCI) procedures.

Purpose

This study investigated the incidence and prognostic relevance of type 4a MI and PMI, according to current definitions, in NSTEMI patients undergoing PCI. The best cardiac troponin (cTn) threshold of PMI for prognostic stratification is also identified.

Methods

In this observational cohort study, we enrolled consecutive NSTEMI patients undergoing PCI with stable or falling pre-PCI cTn levels. According to the 4th Universal Definition of Myocardial Infarction (UDMI), we stratified the study population into three subgroups: those experiencing 1) type 4a MI; 2) PMI; 3) no periprocedural ischemic events. The primary endpoint was 1-year all-cause mortality. The secondary endpoint consisted in a composite of major adverse cardiovascular events (MACE) at 1-year, including all-cause mortality, non-fatal reinfarction, urgent revascularization, non-fatal ischemic stroke and hospitalization for heart failure.

Results

Among 1412 NSTEMI patients undergoing PCI with stable or falling cTn levels at baseline, 240 (17.0%) experienced type 4a MI, 288 (20.4%) PMI, and 884 (62.6%) no periprocedural ischemic events. Patients with type 4a MI had the highest 1-year all-cause mortality and MACE rates. PMI defined by the 4th UDMI (post-PCI delta cTn >20%) did not show significant associations with primary and secondary endpoints. PMI redefined as post-PCI delta cTn >40% was significantly correlated with 1-year all-cause mortality and MACE.

Conclusion

Periprocedural ischemic events are common in NSTEMI patients undergoing PCI and influence patient outcomes. Type 4a MI and PMI redefined as post-PCI delta cTn >40% are strongly associated with 1-year death and MACE. This study highlights the importance of identifying periprocedural ischemic events to aid risk stratification and management of NSTEMI patients.PMI and type 4a MI: mortality 1-yearPMI and type 4a MI: MACE 1-year
Soluble amyloid precursor protein-alpha mediates post-ischemic neovascularization after myocardial infarction
Authors: Kawase H , Liu S , Kurz S , Wietelman A , Looso M , Banicevic M , Wettschureck N , Mueller U , Offermanns S
Published: October 2024

Background

Amyloid precursor protein (APP) gives rise to amyloid-β peptides and thus has a key role in the pathogenesis of Alzheimer´s disease. APP is also highly expressed outside the brain including cells of the cardiovascular system, in particular endothelial cells (1). However, the role of APP and its proteolytic fragments in cardiovascular function and disease remains unknown.

Purpose

The main purpose of this study was to understand the function APP and the close homologue, amyloid precursor-like protein 2 (APLP2) in endothelial cells.

Methods

To test the potential role of endothelial APP and APLP2 in vivo, we generated inducible endothelium-specific APP/APLP2-double deficient mice (EC-APP/APLP2-KO) by crossing App fl/fl; Aplp2 fl/fl mice with the Cdh5-CreERT2 line. Animals were analyzed after exposure to myocardial infarction (MI). Human umbilical vein endothelial cells were used to study the mechanisms underlying APP/APLP2-mediated endothelial function in vitro.

Results

APP and APLP2 were found to be upregulated in cardiac endothelial cells after MI both in mice and humans. Loss of APP and APLP2 in endothelial cells had no effect on the basal heart function in mice. But, when subjected to MI, approximately 40 % of the EC-APP/APLP2-KO mice died within 3 weeks after MI in contrast to control animals, where hardly any death occurred. Survival of endothelium-specific APP- or APLP2-single knockouts was indistinguishable from that of control animals after MI. The surviving EC-APP/APLP2-KO mice showed larger infarct scars than the control animals. Magnetic resonance imaging and echocardiography at 3 weeks after MI revealed that EC-APP/APLP2-KO had more severe contractile dysfunction than the control mice (left ventricular ejection fraction 32.8 % vs. 44.9 %, respectively). As the underlying cause of this we identified a strong impairment of post-ischemia neovascularization in the absence of endothelial APP and APLP2.

We found that soluble APP-α (APPsα) generated by non-amyloidogenic processing was the predominant form of APP in cardiac endothelial cells after MI. We therefore tested whether the expression of APPsα was able to rescue the observed phenotype of EC-APP/APLP2-KO after MI. Indeed, APPsα knock-in mice that solely express APPsα and no other APP fragments or cell surface APP showed the same phenotype as wild-type animals, indicating that APPsα is sufficient to mimic the function of APP. Under in vitro conditions, we found that APPsα was able to promote tube formation of cultured endothelial cells. APPsα also induced downstream signalling events such as AKT, ERK, and p38 activation which are reminiscent of growth factor induced signaling processes.

Conclusions

APPsα mediates post-ischemia neovascularization in the heart by exerting growth factor-like activity in endothelial cells, thereby protecting against cardiac injury.
Hair cortisol concentration, a biomarker of stress, is gradually increased in patients with acute myocardial infarction before the acute episode
Authors: Kosmas N , Simitsis P , Zapantiotis D , Rallidis L S
Published: October 2024

Background/Introduction

Chronic stress is considered to be an important element of residual cardiovascular risk and modern guidelines recommend its systematic assessment and treatment. Its pathophysiologic contribution, however, in acute myocardial infarction (AMI) was not, until recently, easy to elucidate. This arises from difficulties in objectively quantifying stress levels using conventional research methods, like questionnaires.

Purpose

The purpose of our study was to measure stress levels at the days preceding an acute myocardial infarction using a solid biomarker, Hair Cortisol Concentration (HCC).

Methods

102 consecutive patients with AMI (71 patients with ST-elevation Myocardial Infarction [STEMI] and 31 with Non ST-elevation Myocardial Infarction) from our institution were recruited for this study. We took hair samples from them to precisely measure HCC, which reflects cumulative cortisol levels for the time period preceding the acute event. We also did full clinical, biochemical and psychological evaluation. HCC levels were then compared with 50 age-matched healthy controls.

Results

To assess the temporal trend of HCC in hair segments, corresponding to specific time periods, we fitted linear mixed models. The mixed effects linear model including the main effects of time and group (AMI versus controls) and their interaction showed that cortisol concentration in hair increased over time with higher rate of increase in AMI patients versus controls (beta of interaction = 3.57; 95%CI: 1.74, 5.40; p < 0.001) The model explained a high percentage of the variance (conditional R2=0.940). No other baseline variable had a significant effect when added to the basic model. There was no significant difference between STEMI and NSTEMI (beta of interaction = 1.15; 95%CI: -1.330, 3.59; p = 0.358)

Conclusions

Hair cortisol levels, presumably reflecting stress levels, were gradually increasing before an acute myocardial infarction with higher rate of increase in patients compared to healthy controls. There was no significant difference between STEMI and NSTEMI patients.

Picture 1. Predicted hair concentrations of cortisol over time prior to the event, based on linear mixed models.
Octogenarians, nonagenarians and centenarians with myocardial infarction over time in Sweden
Authors: Venetsanos D , Desta L , Ekerstad N , Melbin L , Ravn-Fischer A , Pagonis C , Traff E , Persson J , Jernberg T , Alfredsson J
Published: October 2024

Background

The aim of this study was to evaluate temporal changes in baseline characteristics, in-hospital management and medication at discharge in very elderly with myocardial infarction (MI).

Methods

Between 2003 and 2016, we included all consecutive patients 80 years or-older, with a MI, included in the nationwide SWEDEHEART registry. The study period was divided into seven equal admission periods. Outcomes included major adverse cardiac and cerebrovascular events (MACCE, including death, MI or stroke) and net adverse cardiac and cerebrovascular events (NACCE, including MACCE and bleeding). All patients had complete 1-year follow up. To evaluate any potential associations between in-hospital management/medications at discharge and clinical outcomes, we adjusted for baseline characteristics and clinical presentation using multivariable Cox regression models.

Results

We included 85,054 patients. Over time, the proportion of patients with comorbidities such as hypertension, diabetes mellitus, prior percutaneous coronary intervention and a previous bleeding significantly increased but patients were less likely to have a prior MI and previous heart failure (HF). On arrival, the proportion of patients with acute HF declined. Invasive management significantly increased over time as well as prescription of evidence-based medication at discharge.

At 1 year, the cumulative rate of MACCE and NACCE significantly decreased. We found a significantly lower risk for death, MI and stroke and a higher risk for bleeding. The observed differences remained significant after adjustment. We found no significant interaction between infarct type and outcomes.

Conclusion

During the study period, the prognosis in very elderly patients with MI substantially improved. In a population that has been excluded from randomised control trials, implementation of evidence-based management for patients with a MI, seemed to be associated with the lower risk for MACCE and NACCE over time.Cumulative rate of MACCE
Alterations of gut microbiome profiles as potential markers in patients developing acute coronary syndrome
Authors: Piriyakunthorn C , Sripusanapan A , Suntornlekha N , Suparan K , Kunasol C , Leemasawat K , Suwannasom P , Chattipakorn N , Chattipakorn S
Published: October 2024

Background

Imbalanced gut microbiota or gut dysbiosis leads to systemic inflammation, one of key contributors to the development and progression of atherosclerosis. A recent study revealed the association of the gut microbiota and the severity of coronary artery lesions in patients with acute coronary syndrome (ACS). However, the gut microbiota profile in ACS patients in comparison with patients with high-risk cardiovascular disease (CVD) has not been thoroughly investigated.

Purpose

We aimed to compare the profiles of gut microbiome between patients with ACS and patients with high-risk CVD, as well as to determine the association between gut microbiota and CVD risk factors.

Methods

This cross-sectional study enrolled 24 stabilized ACS patients within 24 hrs of hospitalization and 59 outpatients in CVD clinics, as a control group. Echocardiography was done in those patients. Blood was collected for biochemical analysis, and fecal samples were collected for gut microbiome analysis via 16S RNA sequencing.

Results

The demographic data showed no significant differences between groups in CVD risk factors (age, levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides). However, patients with ACS had greater cigarette use and alcohol consumption than the control group. For gut microbiome, both alpha and beta diversity levels of ACS group were significantly higher than those in a control group (Figure 1A-B). Differential abundance analysis by ANCOM-BC revealed significantly increased level of bacteria in the Atopobiaceae family in ACS patients, compared to controls (Figure 1C). Since Atopobiaceae was reported to be positively associated with percent atheroma volume (PAV), a marker of plaque deposit in the arteries, we found an increased number of Atopobiaceae which was positively associated with serum Troponin T level (Figure 1D), systemic inflammation (Figure 1E), and a trend to negatively correlated with LV ejection fraction.

Conclusion

Our findings suggested that alterations of gut microbiota occurred in ACS patients, and an increase in gut Atopobiaceae level could potentially be the predictive marker of the development of ACS in CVD patients.Figure 1
Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with acute or chronic coronary syndrome undergoing percutaneous coronary intervention
Authors: Oliva A , Vogel B , Sartori S , Bay B , Smith K , Cao D , Gitto M , Dangas G , Pocock S , Bhatt D , Ridker P , Kini A , Sharma S , Mehran R
Published: October 2024

Background

Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as an inflammatory biomarker associated with atherosclerosis and cardiovascular events. However, its role in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear.

Purpose

We aimed to evaluate the clinical impact of baseline NLR in patients undergoing PCI for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).

Methods

We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US hospital. We excluded patients for whom NLR was not available and those who were deemed to have active hematological or infective diseases, including patients presenting with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to clinical presentation. Within each group, we estimated the risk of 12-month adverse events using the lowest NLR quartile as reference. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACE individual components and any periprocedural or post-discharge clinically relevant bleeding.

Results

A total of 7,201 patients were included in the analysis; of these 3,975 (55.2%) had ACS and 3,226 (44.8%) CCS. Patients in the 4th quartile (NLR > 5.0) were more frequently male, older, and presented more often with chronic kidney disease and complex coronary artery disease. Smoking, diabetes and history of CAD, as well as triglycerides, LDL, non-HDL and total cholesterol levels were lower in the 4th NLR quartile. In patients presenting with CCS, the risk of MACE, all-cause death, MI was similar across NLR quartiles, while the risk of bleeding increased stepwise (Figure 1). In patients presenting with ACS, the 4th NLR quartile had the highest adjusted risk of MACE (HRadj 1.82, 95% CI 1.25-2.67; P=0.002), all cause death (HRadj 2.56, 95% CI 1.41-4.66; P<0.001), and bleeding (HRadj 1.82 95% CI 1.25-2.63, P<0.001) at 1 year, as compared to the lowest quartile (Table 1).

Conclusions

Among patients undergoing PCI, elevated NLR is strongly associated with risk of MACE and all-cause mortality in patients presenting with ACS but not in those with CCS. Conversely, the risk of bleeding was augmented with higher NLR in both ACS and CCS patients undergoing PCI. In this setting, NLR may inform risk stratification at the time of PCI.
Association of polarimetric signatures with coronary plaque composition in patients with acute and chronic coronary syndrome: an intravascular polarization-sensitive optical coherence tomography study
Authors: Sugioka K , Otsuka K , Fujisawa N , Johns G , Yamaura H , Okamoto A , Yamaguchi T , Kagawa S , Shimada T , Yamazaki T , Kawarabayashi T , Villiger M , Bouma B E , Fukuda D
Published: October 2024

Background

Intravascular polarimetry with polarization-sensitive (PS-) optical coherence tomography (OCT) measures polarization properties, birefringence and depolarization, in parallel with structural features available with conventional OCT (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, which imparts mechanical integrity to fibrous caps. Depolarization is elevated in the presence of macrophages and lipid/necrotic core.

Purpose

This study aimed to investigate polarimetric signatures of coronary lesions in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions.

Methods

This was the first-in-human study of intracoronary PS-OCT in Japan, consisting of 17 patients with ACS (n = 5) or CCS (n = 12) who underwent intravascular PS-OCT. ACS culprit lesions (ACS-lesions) and CCS target lesions (CCS-lesions) were included in the analysis, resulting in a total of 862 cross-sections. In the cross-sectional images, lumen segmentation and guidewire artifact were automatically segmented. The median value of birefringence and depolarization were automatically analyzed using depolarization cut-off value (cross-sectional level). Birefringence and depolarization of ACS- and CCS-lesions were compared by using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate diagnostic performance of polarimetric signatures for the identification of ACS-lesions.

Results

Compared to CCS-lesions, ACS-lesions featured higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05) (Figure 2). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025).

Conclusions

Intravascular PS-OCT provides quantitative compositional assessment of coronary lesions. Decreased birefringence and pronounced depolarization within the ACS-lesions indicate increased collagenolytic activity and the presence of macrophage infiltration, respectively. These results suggest that polarization properties may serve as quantitative imaging markers for assessing natural history of coronary atherosclerosis.
The paradox of CAC score and plaque vulnerability
Authors: Chapman I N , Viruel M L , Furmento J F , Kuschnir P , Sciancalepore A , Ricapito M P , Conde D , Costabel J P
Published: October 2024

Introduction

The effect of coronary artery calcification on plaque vulnerability remains unclear. The coronary artery calcium (CAC) score, quantified using coronary computed tomography, has a strong correlation with total atherosclerotic burden and risk of adverse cardiac events. Nevertheless, different patterns in the distribution of coronary artery calcium have been reported to convey different effects on plaque stability.

Some biomechanical models suggest that microcalcifications can intensify stress in the fibrous cap, promoting plaque rupture. On the other hand, large calcium deposits are hypothesized to promote plaque stability, as statin therapy has been shown to promote the calcification of atherosclerotic lesions.

The purpose of this study is to investigate the relationship between CAC score and vulnerable plaque using coronary computed tomographic angiography (CCTA) in patients with an acute coronary syndrome (ACS).

Methods

CCTA was performed in 444 patients; these patients were divided into two groups (those with vulnerable plaque and those without). CAC score of each patient was obtained. We calculated median value of CAC score of both groups and compared them using Two Sample Mann-Whitney U Test. All tests were 2-sided, p values below a threshold of 0.05 were considered to be significant. All statistical analyses were performed using IBM SPSS Statistics 29.0 (SPSS Inc, Chicago, IL).

Results

Out of 444 patients with an ACS and evaluated with CCTA, vulnerable plaques were found in 57 patients (13%). The median value of CAC score in patients with vulnerable plaques was significantly higher compared with patients without vulnerable plaques (mean CAC score 1065,07 AU (95% Confidence Intervals 526,26-2656,40 AU) vs 444,03 AU (95% CI 120,18-766,88 AU, p < 0.001). Using Mann–Whitney U test, we found a statistically significant difference between CAC score of patients with vulnerable plaques and those that did not have such plaques.

Conclusion

Although CAC score is a reliable marker of atherosclerosis it is still uncertain whether CAC score is an indicator of plaque vulnerability.

In our study, CAC score was higher in patients with vulnerable plaque compared to those without such plaques. A highly statistically significant difference was found between the median value of CAC score between these two groups of patients.Boxplot
Association between lipoprotein-associated phospholipase A2 gene Val279Phe homozygous genotypes and variant angina in Japanese women
Authors: Iwasaki T , Shibutani S , Soma T , Saito K , Washima S , Kato K , Konno Y , Umezaki H , Hirosawa S , Hanada K , Yokoyama H , Tomita H
Published: October 2024

Background

The role of the lipoprotein-associated phospholipase A2 gene (PLA2G7) in the pathogenesis of cardiovascular diseases remains controversial. The PLA2G7 gene normally produces a protein called "plasma platelet activating factor-acetylhydrolase"(PAF-AH). Homozygotes of rs76863441, which is PLA2G7 Val279Phe polymorphism, produce none of PAF-AH, and heterozygotes produce less than half of the normal levels. This polymorphism is rare outside of Asia and is particularly common in Japan, where homozygous mutations account for 4% of the population. The association between rs76863441 and risk of myocardial infarction was significant in ethnicity for Japanese population, but not in other countries. Variant angina is a severe case of coronary artery spasm (CSA) and causes an acute myocardial infarction. It is widely accepted that variant angina is more common in Japanese than in other races.

Purpose

The aim of this study was to examine the possible association between rs76863441 and variant angina.

Methods

rs76863441 was analyzed by direct sequencing in 62 patients with variant angina (43 men and 19 women with a mean age of 60.0±11.6 years). In all patients, ST segment elevation was recorded on ECG and coronary angiography was performed. Acetylcholine provocation test was performed in 31 patients. We compared genotypes of rs76863441 between variant angina patients and 872 healthy volunteers without a history of heart diseases living in the same area, who participated in the Iwaki Health Promotion Project, which has been conducted by the Hirosaki University School of Medicine since 2005. These volunteers had undergone Japonica Arrays, which is the SNP array for the Japanese population.

Results

Homozygotes genotype for rs76863441, heterozygotes genotype, and wild genotype were present in 4 (6.5%), 22 (35.5%), and 36 (58.1%) of the variant angina group, respectively, and in 30 (3.4%), 246 (28.2%), and 596 (68.3%) of the control group, respectively. Statistically, there were no significant differences in genotypes between the variant angina group and the control group. Next, males and females were analyzed separately. In males, there were no significant differences in homozygous mutations (1 out of 43 patients (2.3%) in the variant angina group vs. 11 out of 327 patients (3.4%) in the control group, P=1.00). However, in females, there was a significant difference in homozygous mutations (3 out of 19 (15.8%) in the variant angina group vs. 19 out of 545 (3.4%) in the control group, P=0.033).

Conclusions

These findings indicate that homozygotes of rs76863441, which has PAF-AH deficiency, may be associated with the pathogenesis of variant angina in Japanese women. Further functional analyses of this mutation are of great interest.Genotypes of rs76863441Gender disparities of rs76863441
Diagnostic potential of relative changes in high-sensitivity troponin levels during intracoronary acetylcholine provocation testing
Authors: Yaginuma H , Saito Y , Kitahara H , Kobayashi Y
Published: October 2024

Background

Intracoronary acetylcholine (ACh) provocation testing is useful for the diagnosis of vasospastic angina (VSA). However, the positive or negative diagnosis of ACh testing is often challenging when lacking typical anginal symptoms and electrocardiographic changes during provocation tests. We hypothesized that relative changes in cardiac troponin levels during ACh provocation testing may be suggestive of myocardial ischemia and would be helpful for the VSA diagnosis.

Purpose

To evaluate the diagnostic potential of relative changes in high sensitivity troponin I (hs-TnI) levels during intracoronary ACh provocation test.

Methods

This preliminary study included a total of 29 patients undergoing invasive coronary angiography with or without ACh provocation tests. Patients were divided into three groups; no ACh provocation tests (i.e. angiography alone), negative ACh tests, and positive ACh tests. Blood samples were obtained twice, before and after angiography, through the arterial sheath to evaluate hs-TnI. The primary measure was relative changes in hs-TnI (i.e. Δhs-TnI). Positive ACh provocation test was defined as total or subtotal coronary occlusion accompanied by chest pain and/or ischemic electrocardiographic changes.

Results

Of the 29 patients, 10 (34.5%) underwent coronary angiography alone, while ACh provocation testing was performed in 19 (65.5%) patients, of whom 7 (36.8%) and 12 (63.2%) had negative and positive ACh test results. Overall, the mean time interval between the blood sample collections was 76 minutes. Levels of hs-TnI before angiography did not differ significantly in the no, negative, and positive ACh test groups (5.3 [2.8, 8.6] vs. 2.9 [1.3, 8.8] vs. 3.3 [1.6, 8.5] pg/ml, p=0.76), while Δhs-TnI was highest in the positive ACh test group, followed by the negative and no ACh test groups (4.2 [0.5, 8.1] vs. 0.8 [0.4, 4.6] vs. −0.3 [−0.6, 0.3], p=0.002) (Figure).

Conclusions

In patients undergoing intracoronary ACh testing for the VSA diagnosis, a relative increase in Δhs-TnI during angiography was observed than in those who did not undergo the provocation tests, particularly when the ACh test diagnosis was positive. Our findings suggest that Δhs-TnI has the potential to aid in the positive or negative diagnosis of ACh provocation testing.
Demographic, clinical characteristics, managements strategies and in-hospital outcomes of patients enrolled in prospective nationwide SCAD registry
Authors: Mehmedbegovic Z , Krljanac G , Ilic I , Petrovic M , Kovacevic M , Djokovic A , Mitov V , Zdravkovic V , Majstorovic M , Iveljic I , Radocic D , Stankovic S , Maricic B , Bojovic D , Apostolovic S
Published: October 2024

Spontaneous coronary artery dissection (SCAD) is an uncommon yet increasingly recognized cause of acute coronary syndrome (ACS), particularly in young to middle-aged women. This multicentric, prospective nation-wide registry aimed to elucidate the demographic characteristics, clinical presentation, management strategies, and outcomes of patients with SCAD.

A total of 95 patients with SCAD were enrolled in 10 centers, with females constituting 81% of the cohort, and with an average age of 49.7±11.9 years. Among the traditional risk factors, prior hypertension was observed in 49%, followed by hyperlipidemia in 43%, diabetes mellitus in 9% and prior or current smoking in 47% of patients. The presentation of SCAD as ST-elevation myocardial infarction (STEMI) was predominant, occurring in 61% of cases, with the left anterior descending artery (LAD) being the most involved vessel (68%). Regarding the classification of SCAD, type 2 SCAD was the most frequent (53%), followed by type 1 (24%) and type 4 (16%). Notably, involvement of the distal segment of the culprit artery was observed in 68% of cases, while baseline TIMI 3 flow was noted in 52% of patients. Percutaneous coronary intervention (PCI) was performed in 52% of cases, with pre-interventional TIMI 0-2 flow (62% Vs. 28%; p<0.05) and proximal artery involvement (41% Vs. 13%; p<0.05) being more prevalent compared to conservatively managed patients. Final stent implantation was performed in 67% of PCI cases, with TIMI 3 flow restoration in 76% of patients undergoing PCI. The average left ventricular ejection fraction prior to discharge was 51±9.9%. In-hospital mortality was reported in three female patients, undergoing attempted PCI with left main and LAD involvement. The use of antiplatelet therapy was widespread, with aspirin administered to 98% and P2Y12 inhibitors to 75% of patients at discharge.

Data from this prospective nationwide multicentric SCAD registry show that SCAD occurs predominantly in relatively young female patients, with moderately prevalent traditional cardiovascular risk factors, usually presents as STEMI, with good overall survival rates despite half of the patients managed conservatively. PCI was often attempted in SCAD lesion with compromised arterial flow and located proximally, with lower rates of stent implantation and procedure success compared to traditionally observed rates in primary PCI. This underscores the importance of heightened awareness and tailored management approaches for this unique subset of ACS patients in order to refine risk stratification, optimize treatment strategies, and improve outcomes in this population.
TLR7 deficiency alleviated myocardial ischemia reperfusion injury via regulating macrophage-neutrophil interaction
Authors: Lai Y , Zharkova O , Chong S Y , Wang X Y , Vaarsha N , Chan M Y , Richards A M , Wang J W
Published: October 2024

Background

Toll-like receptor 7 (TLR7) is an intracellular innate immune receptor activated by single-stranded RNA. We previously reported that TLR7 could recognize RNA from dying cardiac cells and thereby deteriorating post myocardial infarction left ventricular remodeling. However, its effect on myocardial ischemia reperfusion (IR) injury is still unknown.

Purpose

In this study, we aimed to investigate the role of TLR7 in myocardial IR injury and the underlying mechanisms.

Methods

C57BL/6J wild type (WT) and TLR7 deficient (TLR7-/-) mice underwent left anterior descending artery occlusion for 30min followed by reperfusion. Myocardial infarct size was measured by Evan’s blue and TTC staining. mRNA expression levels of cytokines and phagocytosis-related receptors were detected by qPCR. TUNEL assay was conducted to determine apoptosis in the heart. Influx of neutrophils and macrophages in ischemic myocardium was analyzed by flow cytometry and Histone Cit3 was imaged to examine formation of neutrophils extracellular traps (NETs), cardiac function was evaluated by echocardiography during post-IR injury follow-up.

Results

TLR7 expression was up-regulated after IR injury in ischemic myocardium of WT mice. Compared to WT mice, fewer apoptotic cells and smaller infarct size (34±2% vs. 23±3% of area at risk, p<0.01) were observed in TLR7-/- mice at 24 hours post-IR, which was accompanied by reduced inflammatory cytokines (IL-1β: 110.5±14.1 vs. 54.8±13.7, p<0.05; TNF-α: 4.6±1.0 vs. 2.0±0.4, p<0.05) and increased anti-inflammatory factors (TNF-β: 2.9±0.3 vs. 8.6±2.6, p<0.05; IL-10: 14.2±2.1 vs. 32.3±8.8, p<0.05). Surprisingly, although the influx of neutrophils and macrophages increased to a similar extent in WT and TLR7-/- mice, the latter exhibited remarkably less NETs formation and enhanced macrophage phagocytosis in the infarct region. Moreover, TLR7 deficiency improved cardiac function, as indicated by increased left ventricular ejection fraction (LVEF) and fraction shortening (FS) at 56d post-IR.

Conclusions

TLR7 deficiency alleviates myocardial IR injury and improves cardiac function probably via enhancing macrophage clearance of NETs in the injured myocardium.TLR7 deficiency in cardiac functionTLR7 deficiency decreased NETs formation