bluuebunny/crossref_metadata_2025 huggingface dataset:
COL3A1 mutations in spontaneous coronary artery dissection
Authors: Mcgrath-Cadell L , Hessleson S , Thompson J L , Iismaa S E , Tarr I , Muller D W M , Kovacic J , Graham R M , Giannoulatou E
Published: November 2023

Background

Spontaneous coronary artery dissection (SCAD) affects mainly women with a mean age of 51 years.(1) Predicted damaging variants in connective tissue disease (CTD) genes have been found in a subset of patients with SCAD, however in some cases the typical phenotype associated with these conditions is lacking. Variants in the COL3A1 gene, on chromosome 2 encoding type III collagen, appear to be one of the most frequently reported in SCAD. Mutations in COL3A1 alter the production and structure of type III procollagen and weaken connective tissues, including blood vessel walls and cause vascular Ehlers-Danlos Syndrome (vEDS).(2)

Purpose

Systematically determine the known cases of SCAD with COL3A1 likely pathogenic/pathogenic (LP/P) variants to highlight COL3A1 as a SCAD-causative gene, in a subset of SCAD cases.

Methods

We searched PubMed using search terms "spontaneous coronary artery dissection" AND COL3A1, "spontaneous coronary artery dissection" AND "vascular Ehlers-Danlos syndrome", "spontaneous coronary artery dissection" AND genetics. We also searched the ClinVar database using COL3A1 [gene] and the following stipulations: clinical significance limited to pathogenic or likely

Pathogenic; molecular consequence limited to frameshift, missense or nonsense, and review status limited to multiple submitters or at least one star. The COL3A1 variants identified were reclassified using American College of Medical Genetics (ACMG) criteria. Fisher's exact test was used for statistical comparisons.

Results

There were 42 published cases of SCAD with a LP/P mutation in COL3A1. Of the 42 published cases, there were two cases published twice. Using updated ACMG criteria, three cases were reclassified to variant of uncertain significance (VUS), from LP/P. This resulted in 37 unique cases of SCAD with LP/P variants using ACMG criteria. Of the cases with LP/P mutations where sex was known, 11/33 cases (35%) were male, higher than that reported in a large, published cohort where 86/750 SCAD cases (11.5%) were male (1) (p = 0.001129, 95% CI 0.115876 0.614725). Most SCAD cases with a COL3A1 LP/P mutation in whom age was reported, were under age 40 years (23/31, 74%), proportionally more cases when compared to a cohort of SCAD cases where 82/460 SCAD cases were under age 40 years (18%) (p value = 8.782e-11, 95% CI 0.02837315 0.18361793).

Of the variant types reported (16/37), the majority were single nucleotide variants with one copy number variation (duplication).

Conclusion

While no one gene carries damaging variants in a large proportion of SCAD cases, COL3A1 variants have been found in a number of people with SCAD. Patients presenting with SCAD under 40 years and particularly males should be screened for pathogenic variants in aortopathy and connective tissue genes, such as COL3A1.Table:SCAD with COL3A1 LP/P variants 1TableSCAD with COL3A1 LP/P variants 2
Association between epicardial adipose tissue volume and follow-up echocardiographic outcomes in patients with acute coronary syndrome
Authors: Harada K , Terashima S , Takeda S , Kataoka T , Harada K , Nagao T , Shinoda N , Kato M , Marui N , Amano T , Murohara T
Published: November 2023

Background

The epicardial adipose tissue (EAT) plays important physiological and pathological roles in the regulation of myocardial function. Among obese patients, the development of inflammatory EAT precipitates myocardial dysfunction and heart failure. Recent studies highlighted the possible divergent role of EAT in the pathophysiology of heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, the effect of EAT on left ventricular remodelling among patients with acute coronary syndrome (ACS) remains unclear.

Purpose

According to the previous our study, patients with ACS had a higher EAT volume. This study evaluated the association of the EAT volume with left ventricular ejection fraction (LVEF) changes over time among patients with ACS.

Method

This prospective single-centre study selected 197 consecutive Japanese patients, who were hospitalised for ACS between June 2011 and November 2014. Among them, 143 (120 males, 23 females, mean age 64±12 years) patients underwent follow-up with serial echocardiograms. The EAT volume was measured using a multi-slice computed tomography in the hospital. Echocardiography was performed during their hospitalization and follow-up examinations for the next 3 (mean 3.2±1.8) years. They were divided into three groups according to the LVEF: HFrEF, heart failure with mildly reduced ejection fraction (HFmrEF), and HFpEF.

Results

No correlation existed between the EAT volume at the onset of ACS and LVEF during the follow-up (r=0.033, p=0.695). The peak creatine phosphokinase at ACS onset exhibited the strongest correlation with chronic ejection fraction (r=-0.512, p<0.01).

In the chronic phase, the patients with HFrEF had the highest EAT volume (HFrEF, 134±38 ml; HFmrEF, 102±35 ml; and HFpEF, 120±51 ml; p=0.042). However, there was no correlation between the EAT volume and LVEF changes during the follow-up (r=-0.058, p=0.518) (Figure 1). The change in LVEF was not statistically significant among the three groups (HFrEF -4.8±11 %, HFmrEF -1.2±10 % and HFpEF 0.1±9 %, p=0.156).

Among patients with chronic HFmrEF and HFpEF, the EAT volume was positively correlated with the body mass index (r=0.373, p=0.029 and r=0.453, p<0.01, respectively). This correlation was not found in patients with chronic HFrEF (Figure 2).

Conclusion

There was no association between the EAT volume and improvements in LVEF after a follow-up period of 3 years among patients with ACS. Patients with chronic HFrEF had a significantly higher EAT volume despite having a non-obese body mass index.

Non obese ACS patients with increased EAT may be prone to HFrEF in the chronic phase.Figure 1Figure 2
Impact of chronic kidney disease staging by estimated glomerular filtration rate on clinical outcome of acute myocardial infarction
Authors: Mori H
Published: November 2023

Background

Although chronic kidney disease (CKD) has been known to have poor clinical outcome in patients with acute myocardial infarction (AMI), CKD staging by estimated glomerular filtration rate (eGFR) is not widely utilized in daily practice.

Purpose

This study was aimed to assess the impact of CKD staging by eGFR on clinical outcome in patients with AMI.

Methods

We analyzed the Japanese observational prospective multi-center registry of AMI which included a total of 10870 patients between October 2016 and December 2021. Based on eGFR, patients were divided into stage 1(≧90), 2 (60-89), 3a (45-59), 3b (30-44), 4 (15-29) and 5 (<15) and clinical outcomes were followed for 30 days. A major adverse cardiac event (MACE) was defined as cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke. Bleeding Academic Research Consortium (BARC) type 3 or 5 was used to assess bleeding events. Composite events included both MACE and bleeding events.

Results

Almost half of patient were grouped in CKD stage 2 (n=4895, 45%) which was followed by stage 3a (n=2686, 24.7%), stage 3b (n=1359, 12.5%), stage 1 (n=1045, 9.6%), stage 4 (n=471, 4.3%) and stage 5 (n=414, 3.8%). As shown in Table 1 (Patient characteristics), CKD staging had positive correlation with age, hypertension, diabetes, atrial fibrillation, and previous MI but had negative correlation with dyslipidemia and smoking. As shown in Table 2 (AMI characteristics), proportion of non-ST elevation MI was greater in CKD stage 4 and 5 which leaded to lower peak CK level and longer door to device time. Percentage of Killip 4 increased from stage 3a (12.2%) and exceeded 20% from stage 3b resulting in greater demand for mechanical devices. Each CKD staging had quite distinct and significant impact on MACE, bleeding, and composite events as shown in Kaplan-Meier curve of figure 1A∼C. After adjustment with multiple confounding factors, composite events still significantly differ from stage 3B (Adjusted risk ratio: stage1, 1.1[0.4-2.6]; stage2; 1.1[0.6-2.0], stage 3a, 1[reference]; stage 3b, 1.8 [1.0-3.2]; stage 4, 2.4 [1.3-4.5]; stage 5, 4.1 [1.6-10.7]).

Conclusion

Each CKD staging had distinct clinical feature with significant impact on clinical outcome.
Incidence of coronary anomalies in patients with D-transposition of great arteries (D-TGA) after arterial switch operation (ASO)
Authors: Calvao J , Costa C , Amador A F , Proenca T , Cabrita A , Marques C , Pinho A , Oliveira C , Santos L , Carvalho A , Rebelo J , Vasconcelos M , Moreira J , Cruz C , Macedo F
Published: November 2023

Background and purpose

D-transposition of great arteries (D-TGA) is a congenital cardiac defect defined by atrioventricular concordance and ventriculo-arterial discordance. Arterial switch operation (ASO) is currently the surgical repair and implies reimplantation of the coronary arteries from the aorta into the neo-aortic root. As such, long-term coronary anomalies and complications are possible and potentially dangerous. Recently, coronary computed tomography angiography (CCTA) has gained a prominent role for characterization of the coronary anatomy in these patients (pts) and its relationship with adjacent structures. However, routine coronary evaluation among asymptomatic pts after ASO remains controverse, as the reported incidence of coronary-related complications is low. The purpose of this study is to perform a descriptive analysis of CCTA findings in pts with D-TGA after ASO.

Methods

We performed a retrospective single center study that included patients with D-TGA submitted to ASO who underwent CCTA. Demographic, clinical and imaging data were collected.

Results

We identified 57 pts with D-TGA submitted to ASO. Of these, 39 (68%) performed a CCTA. Mean age of pts was 20.4 (± 3.8) years; 54% were male; 32% had complex D-TGA. In 35 patients (90%), CCTA was performed as part of a routine screening. In 4 (10%) pts CCTA was done due to symptoms or an abnormal non-invasive test suggestive of myocardial ischemia. Eighteen (46%) pts had coronary anomalies: 5 (13%) had an acute angulation at the coronary origin; 13 (33%) pts had anomalous origin of the coronary arteries, ranging from presence of a single coronary artery in 3 (8%) pts, common independent origin from a single sinus of Valsalva in 6 (15%) cases and anomalous origin of the circumflex artery from the right coronary artery (RCA) in 4 (10%) pts. An interarterial course was described in 2 (5%) pts and a retroaortic course was reported in 8 (21%) cases. One patient had anomalous course of the LAD into the right ventricle, a mild calcified ostial stenosis of the left main coronary artery and a chronic total occlusion of the RCA.

Conclusions

D-TGA patients submitted to ASO have a high incidence of coronary anomalies. Routine screening with CCTA may be justified to identify patients who may be at higher risk of coronary events.
Stress hyperglycemia ratio and long-term clinical outcome in patients with acute coronary syndrome
Authors: Minopoli T C , Toso A , Leoncini M , Villani S , Maioli M , Grimaldi E , Di Mario C , Bellandi F
Published: November 2023

Background

Stress hyperglycemia is strongly associated with adverse prognosis in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR- relationship between acute/chronic glycemic values) has been proposed as a better measurement of stress hyperglycemia. Studies on SHR and long-term clinical outcome in ACS are limited. This study aimed to clarify the association between SHR and 3-year adverse clinical events in patients with ACS.

Methods

We analyzed data of 795 patients admitted to our center for ACS who were enrolled in the PRATO-ACS Registry (ClinicalTrials.gov ID: NCT04087200) and underwent laboratory analyses 1 month after the index event. All patients had undergone early invasive strategy and received high intensity statins during hospitalization and at discharge. Patients were stratified in baseline SHR tertiles: < 0.95, ≥ 0.95 to < 1.17 and ≥ 1.17. The primary end point was 3-year all cause death; secondary end points were major adverse clinical events (MACE) including all-cause death, myocardial infarction or congestive heart failure. The association between SHR and outcome measures was evaluated with Cox proportional analysis expressed by hazard ratio (HR) and 95% confidence intervals (CI).

Results

With increasing SHR, there was a significant progressive increase in mortality (4.2, 8.3, and 11.7% in the 1st, 2nd, and 3rd tertile, respectively, p= 0.006) and MACE (10.6, 14, and 20.8% in the 1st, 2nd, and 3rd tertile, respectively, p=0.004). Multivariable analysis shows that SHR was an independent predictor of 3-year all-cause death (HR 1.65, 95% CI 1.12-2.4; p= 0.012). Subgroup analysis evidenced that the relationship between SHR and mortality was statistically significant only for patients with poor glycemic control at 1 month follow up (HR 3.4, 95% CI 1.14-10.9, p= 0.02 in the 2nd tertile and HR 3.9, 95% CI 1.3-11.8, p= 0.015 in the 3rd tertile).

Conclusion

Baseline SHR is significantly associated with 3-year all-cause death and MACE in patients with ACS. However, its prognostic impact is much stronger in patients who do not achieve desired glycemic targets at 1 month after the index event. Therefore, insistent attention to glycemic values is mandatory in ACS patients even after discharge.
Association of lipoprotein(a) with severity of coronary artery atherosclerosis in patients with acute coronary syndromes
Authors: Koziel-Siolkowska M , Kalarus Z , Mitrega K , Lazar M , Olma A , Streb W
Published: November 2023

Background

Elevated level of lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. However, the association of Lp(a) with acute coronary syndromes (ACS) has not been sufficiently studied.

Purpose

To evaluate the relationship between high serum levels of Lp(a) and (i) factors that play a role in the long-term development of the severity of coronary artery disease (CAD), (ii) extent of CAD amongst patients with ACS.

Methods

In this study we enrolled 74 consecutive patients hospitalized for ACS in tertiary cardiology center form December 2022 to January 2023. Patients characteristics were compared for patients with Lp(a) <75 nmol/L (53 patients) and ≥75 nmol/L (21 patients). Logistic regression analyses were performed to evaluate the relationship of Lp(a) with severity of CAD.

Results

In the studied population, the mean age of patients with high Lp(a) levels was 65 years. They were more likely to have arterial hypertension and hypercholesterolemia than those with normal Lp(a) levels (p <0.05). There were no significant differences in distribution of ACS subtype between groups. On univariate analysis, triple vessel CAD [odds ratio (OR) 4.22, 95% confidence interval (CI) 1.34-13.27, p = 0.014), and multivessel CAD (OR 3.05, 95% CI 1.06-8.81, p = 0.040) were significantly associated with abnormal Lp(a) levels. Multivariable determinants of of high Lp(a) levels were also triple vessel CAD (OR 4.19, 95% CI 1.33-13.26, p = 0.013), and multivessel CAD (OR 3.04, 95% CI 1.05-8.80, p = 0.042).

Conclusions

Lp(a) ≥75 nmol/L was closely associated with the extent and severity of CAD in patients with ACS.
Negative coronary artery remodeling in young properly controlled diabetic patients is associated with diabetes duration
Authors: Farrag A A M , Sheikh M , El Amragy A A , Shehata A
Published: November 2023

Introduction

Coronary artery remodeling is a focal compensatory change in the vessel wall in response to atherosclerotic plaque. Computed tomography coronary angiography (CTCA) is very useful in assessing remodeling pattern of atherosclerotic lesions. Patients with type 2 diabetes mellitus (T2DM) has extensive atherosclerotic burden with inadequate compensatory remodeling. Diabetes duration is independently associated with macro-and microvascular events. The goal of this study was to characterize the pattern of coronary artery remodeling and its relation with diabetes duration in a group of properly controlled diabetic patients.

Methods

We prospectively studied 263 patients below age of 60 years (mean age 54 ± 6 years) who were scheduled for CTCA. CTCA was performed using 256-MDCT scanner with dedicated software for calcium measurement. Positive coronary remodeling (PR) was defined as remodeling index (RI) >1.05, and negative coronary remodeling (NR) as RI <0.95.Atherosclerotic burden was assessed using Gensini score and coronary calcium score (CCS).

Results

Patients with NR had longer diabetes duration (8.8 ± 5.7 vs. 5.5 ± 4.4 years, p<0.001) higher prevalence of insulin (31% vs. 20%, p= 0.041) and statin therapy (70.8% vs. 58.7%, p= 0.043) higher Gensini (24.9 ±26.9 vs.18.2 ± 21.9, p= 0.039) and calcium scores (295.8 ± 301.8 vs. 170.2 ± 201.2, p<0.001). NR was correlated with CACS (r= -0.138, p= 0.025) and diabetes duration (r= -0.313, p<0.001)

Conclusion

Longer diabetes mellitus duration was associated with higher prevalence of NR in young patients with controlled T2DM.
Growth differentiation factor-15 is associated with myocardial infarction and death at 30 and 90 days in ED patients with suspected acute coronary syndrome
Authors: Allen B , Mumma B , Tran N , Christenson R , Wilkerson R G , Madsen T , Weaver M , Mahler S
Published: November 2023

Background

Growth differentiation factor (GDF)-15 is a novel biomarker of cardiac stress that may be an accurate predictor of mortality and acute myocardial infarction (AMI) in patients with acute chest pain. However, data from US populations are lacking.

Purpose

Our objective was to determine whether GDF-15 is an independent predictor of index, 30-day, and 90-day day AMI and death in a U.S cohort of ED patients with possible acute coronary syndrome.

Methods

This study was a secondary analysis of the STOP-CP (High Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification) trial, which prospectively enrolled adults (≥ 21 years) presenting to eight emergency departments in the US with suspected AMI (1/25/2017-9/6/2018). Blood sampling was performed at baseline and 3 hours later, and hs-TnT, NT-pro-BNP, and GDF-15 assays were performed at a central laboratory. The primary outcome was the composite of AMI and all-cause death at index visit, 30 days, and 90 days and secondary outcomes were AMI and death separately. Multivariable logistic regression models were fitted for the outcomes at each timepoint with the following independent variables: age, sex, number of cardiac risk factors, ECG findings, hs-TnT, and NT-pro-BNP. Odds ratios (ORs) are reported per 100 ng/L increase in GDF-15 levels.

Results

In 1,428 patients the median age was 58 (IQR: 49, 66) years and 25% (353/1,428) had a history of coronary artery disease. The median GDF-15 level was 1,233 pg/mL (IQR: 754, 2206) at baseline and 1,363 pg/mL (IQR: 851, 2434) at 3 hours. The composite outcome of AMI or death occurred in 12% (169) at index visit, an additional 2% (34) at 30 days, and an additional 3% (37) at 90 days. In multivariable regression models, GDF-15 was independently associated with the composite outcome of AMI or death at 30 days (OR ng/L 1.01, 95% CI 1.00-1.02) and 90 days (OR 1.01, 95% CI 1.01-1.02), but not during the index visit (OR 1.00, 95% CI 1.00-1.00). It was also associated with both AMI (OR 1.01, 95% CI 1.00-1.02) and death (OR 1.01, 95% CI 1.01-1.02) separately at 90 days, but was only associated with death (OR 1.01, 95% CI 1.01-1.02) at 30 days.

Conclusion

Among adult ED patients with suspected AMI, GDF-15 was independently associated with subsequent 30-day and 90-day AMI or death. These data suggest a potential role for GDF-15 in risk stratifying ED patients with regard to future cardiac events.
Derivation and validation of a novel 3hour-pathway for the observe-zone of the ESC 0/1h-hs-cTnI algorithm
Authors: Lopez Ayala P , Boeddinghaus J , Nestelberger T , Strebel I , Koechlin L , Rubini Gimenez M , Miro O , Martin-Sanchez F J , Keller D , Mueller C
Published: November 2023

Background

The latest non-ST elevation myocardial infarction (NSTEMI) guidelines from the European Society of Cardiology (ESC) recommend a 3-hour cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-hs-cTnI algorithm; however, no specific cut-off for further triage is endorsed.

Purpose

To derive and internally validate a novel 3h-pathway for the observe-zone of the ESC 0/1h-hs-cTnI (Architect) algorithm.

Methods

In an multicentre international diagnostic study, we prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of MI. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI, based on complete cardiac work-up including cardiac imaging, serial hs-cTnI sampling and 90-day follow-up information. High sensitivity-cTnI (Architect) concentrations were measured at presentation and after 1 and 3 hours. The primary outcome was safety, quantified by the sensitivity and NPV for early rule out of NSTEMI. Internal validation was assessed with a bootstrapping procedure.

Results

Among 2481 eligible patients, application of the ESC 0/1h-algorithm triaged 1725 patients (69.5%) to either rule-out or rule-in of NSTEMI, remaining 756 patients (30.5%) in the observe-zone (adjudicated NSTEMI prevalence 65/756 patients, 13.7%). A novel derived 3h-pathway for the observe-zone patients ruled-out NSTEMI with a 3h hs-cTnI concentration <8 ng/L and a 0/3h-hs-cTnI absolute change <3 ng/L, triaging 241 patients (32%) towards rule-out, resulting in a sensitivity of 100% (95%CI 94.4-100) and a NPV of 100% (95%CI 98.4-100). A 0/3h-hs-cTnI absolute change ≥8 ng/L ruled-in 69 patients (9.1%), resulting in a specificity of 95.8% (95%CI 94.0-97.1) and a PPV of 58.0% (95%CI 46.2-68.9), Figure. The novel 3h-pathway reduced the number of patients remaining in the observe zone from 756 (30.5%) to 446 (18%), resulting in a relative reduction of 41%, while the number of NSTEMI was reduced from 65 to 25, resulting in a relative reduction of 62%. Findings were confirmed in the optimism-corrected bootstrap internal validation.

Conclusions

A novel derived pathway combining a 3h hs-cTnI concentration <8 ng/L and a 0/3h absolute change <3 ng/L allowed to safely rule-out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnI (Architect) algorithm.Performance of the novel derived cutoffs
Derivation and external validation of machine-learning- models for risk stratification in chest pain with normal troponin
Authors: Fernandez Cisnal A , Lopez-Ayala P , Minana G , Valero E , Koechlin L , Catarrala A , Boeddinghaus J , Noceda J , Nestelberger T , Miro Andreu O , Nunez J , Mueller C , Sanchis J
Published: November 2023

Importance

Risk stratification of patients with chest pain and a high-sensitivity cardiac troponin T (hs-cTnT) concentration 180 minutes). Probability thresholds for safe discharge were derived in the derivation cohort.

Methods

This prognosis study used a single centre cohort (July 2016-Decembre 2019) to develop and internally validate the models and a international prospective APACE cohort to perform the external validation. All Patients presenting to the ED with a complaint of chest pain and a first hs-cTnT concentration <99th percentile (14 ng/L).Candidate predictors included demographics, tradicional cardiovascular risks factors, electrocardiogram and blood tests (haemoglobin, creatinine and hs-cTnT). The endpoint was90-days death or myocardial infarction Four machine learning-based models and one logistic regression (LR) model were trained on 4075 patients and externally validated on 3609 patients. Models were compared with GRACE and HEART scores and a single undetectable hs-cTnT-based strategy (u-cTn; hs-cTnT<5ng/L and time from symptoms onset>180 minutes). Probability thresholds for safe discharge were derived in the derivation cohort.

Results

A 99.1% (4074) of the patients completed the follow-up in the derivation cohort and a 99.4% (3609) in the validation cohort.The endpoint occurred in 105 (2.6%) patients in the training set and 98 (2.7%) in the external validation set. Gradient boosting full (GBf) showed the best discrimination (AUC=0.808). Calibration was good for the reduced NNET and LR models. GBf identified the highest proportion of patients for safe discharge (36.7% vs 23.4% vs 27.2%; GBf vs LR vs u-cTn, respectively) with similar safety (missed endpoint per 1000 patients: 2.2 vs. 3.5 vs. 3.1, respectively). All derived models were superior to the HEART and GRACE scores (p<0.001).

Conclusions and relevance

Machine learning and logistic regression prediction models were superior to the HEART, GRACE and u-cTn for risk stratification of patients with chest pain and a baseline hs-cTnT.
Diagnostic performance of the 0/2 hours ESC algorithm with high-sensitivity cardiac troponin T in an unselected community United States cohort
Authors: De Michieli L , Ola O , Akula A , Knott J D , Mehta R A , Hodge D O , Tak T , Cagin C , Gulati R , Jaffe A S , Sandoval Y
Published: November 2023

Background

There are no robust data addressing the United States (US) experience with the 0/2 hours (h) European Society of Cardiology (ESC) algorithm using high-sensitivity cardiac troponin T (hs-cTnT).

Purpose

To evaluate the diagnostic performance of the 0/2h ESC-recommended absolute deltas in a US population.

Methods

Observational US cohort study of ED patients undergoing 0 and 2 h hs-cTnT measurements. The 99th percentiles upper reference limits (URL) used were 10 ng/L for women and 15 ng/L for men. Diagnostic outcomes were the adjudicated diagnoses of acute myocardial infarction (MI, type 1 or 2).

Results

A total of 1084 patients met inclusion criteria, amongst which 49% were women. Chest discomfort was reported in 521 (48%) patients. Among patients with a baseline hs-cTnT≤99th URL (n=434), 4 MIs occurred. To rule-out MI, an absolute 0-2h delta change <4 ng/L resulted in a sensitivity of 100% (95% CI: 39.8, 100) and a negative predictive value (NPV) of 100% (95% CI: 99.1, 100). To rule-in MI, an absolute 0-2h delta ≥10 ng/L had a specificity of 99.8 % (95% CI: 98.7, 99.9) and positive predictive value (PPV) of 75% (95% CI: 19.4, 99.4). Among patients with a baseline hs-cTnT >99th URL (n=650), 110 MIs occurred. In these patients, both rule-out (sensitivity 65%, NPV 91%) and rule-in (specificity 7.2%, PPV 11%) were poor using the ESC-recommended absolute deltas. Among patients with modest hs-cTnT increases (99th URL to 100 ng/L) neither the ESC-recommended absolute nor the Fourth Universal Definition of MI (UDMI)-recommended relative deltas provided acceptable performance. Among patients with marked hs-cTnT increases at presentation (>100 ng/L), a relative delta change >20% as recommended by the UDMI resulted in a superior rule-in performance, with a specificity of 92.0% (95% CI 74.0, 99.0) and PPV of 84.6% (57.4, 95.7).

Conclusions

In our unselected US-cohort of patients undergoing hs-cTnT, the 0/2h ESC algorithm had a good diagnostic performance in patients without myocardial injury at presentation. Conversely, in patients with myocardial injury at baseline, the ESC-recommended absolute deltas performed poorly to determine who had MI. In patients with marked hs-cTnT increases >100 ng/L at presentation, the UDMI recommended 20% relative change showed good rule-in performance.
Invasive coronary function testing in patients with INOCA - a single center experience
Authors: Ferreira A , Teixeira R , Ferreira V , Mendonca T , Silva T P , Rodrigues H , Silva F , Marques F , Oliveira E , Ferreira R C , Ramos R
Published: November 2023

Background

Coronary vasomotion disorders (CVDs) represent a frequent cause of angina in patients with ischemia with non-obstructed coronary arteries (INOCA). Invasive coronary angiography (ICA) often fails to identify patients with vasospastic angina and/or microvascular dysfunction.

Purpose

Our aim was to describe and characterize CVDs in INOCA patients, using a multi-parametric, invasive, coronary function testing protocol.

Methods

Patients with INOCA that underwent our protocol for coronary function testing (CFT), between July 2021 and October 2022 were included in this single-center prospective study. The protocol consisted of an invasive assessment of coronary circulation vasorelaxation at rest and during hyperemia, as well as the propensity for coronary vasospasm using increasing doses of intra-coronary acetylcholine. Fractional flow reserve, coronary flow reserve (CFR), and index of microvascular resistance (IMR) were recorded. CVDs were diagnosed based on the criteria proposed by the Coronary Vasomotor Disorders International Study Group.

Results

A total of 56 patients were included, mean age was 64±12 years and 57.1% were female. At baseline, all patients had either typical angina (82.1%, n=46) or a positive ischemia test (67.9%, n=38). Twenty patients (35.7%) had a history of a previous ICA or computed tomography due to anginal symptoms, while only 8.9% of patients had known structural ischemic heart disease and were subjected to percutaneous coronary intervention. Our CFT protocol was completed in all patients without any serious complications. Isolated epicardial vasospasm was found in 16 (28.6%) patients, isolated coronary microvascular dysfunction (CMD) in 9 (16.1%), and a combination of CMD and coronary vasospasm in 9 (16.1%). Only 1 patient (1.8%) had isolated microvascular spasm.

We were able to further identify two distinct endotypes of CMD, using a combined assessment of CFR and IMR, termed structural and functional CMD: Functional CMD - 7 patients (12.5%) had CFR < 2.0 and IMR < 25; Structural CMD - 6 patients (10.7%) had CFR < 2.0 and IMR > 25.

Conclusion

Coronary vasomotion disorders are a common cause of INOCA. A CFT protocol is safe, can be used in clinical practice, and can provide a definite diagnosis for the underlying cause of angina.
CAD-RADS score, vascular inflammation, and plaque vulnerability
Authors: Kinoshita D , Suzuki K , Minami Y , Yuki H , Niida T , Dey D , Lee H , Mcnulty I , Ako J , Ferencik M , Kakuta T , Jang I K
Published: November 2023

Background

Coronary artery disease reporting and data system (CAD-RADS), which is widely used to report the severity of coronary artery disease on coronary computed tomography angiography (CTA), predicts the risk of future cardiovascular events. However, the relationship between the CAD-RADS score and vascular inflammation and plaque vulnerability has not been investigated.

Objective

The aim of this study was to correlate the CAD-RADS score with vascular inflammation and plaque vulnerability.

Methods

This is an observational, single-center cohort study with prospective clinical follow-up. Patients who underwent both coronary CTA and optical coherence tomography (OCT) before coronary intervention were enrolled. All OCT and CTA images were analyzed at the core laboratory. Patients were categorized into two groups according to the CAD-RADS score (≤4a or 4b/5). All coronary arteries were analyzed for high-risk plaque features (positive remodeling, low-attenuation plaque, napkin-ring sign, and spotty calcification) and peri-coronary adipose tissue (PCAT) attenuation. PCAT attenuation was measured around the culprit lesion and in the proximal segment of all 3 coronary arteries. OCT features of plaque vulnerability were evaluated in culprit vessels. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as composite endpoints of unplanned target vessel revascularization, unplanned non-target vessel revascularization, nonfatal acute coronary syndrome, stroke, and cardiac death.

Results

Among 369 patients with 902 lesions, 104 (28.2%) were categorized in CAD-RADS 4b/5 and 265 (61.8%) in CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had higher PCAT attenuation than those with CAD-RADS ≤4a at all three levels (mean of 3 coronary vessels: -67.9 ± 6.9 HU vs. -70.2 ± 6.5, P=0.004; culprit vessel: -67.4 ± 7.9 vs. -70.2 ± 7.6, P=0.004; culprit plaque: -67.0 ± 9.3 vs. -69.9 ± 10.5, P=0.009; respectively) (Figure 1 A). Lipid-rich plaque and macrophage, as detected by OCT, were more prevalent in the culprit vessel in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (89.0% vs. 78.5%, P=0.001; 76.6% vs. 64.9%, P=0.001; respectively) (Figure 1B). All HRP features, as detected by CTA, were more frequently observed in patients with CAD-RADS 4b/5 than those with CAD-RADS ≤4a (P for all <0.001) (Figure 2). The cumulative incidence of MACCE was higher in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (15.0% vs. 5.8%, P=0.045).

Conclusions

Higher CAD-RADS score was associated with a higher level of pan-coronary vascular inflammation and plaque vulnerability.Figure 1Figure 2
SGLT2 inhibitor for secondary prevention in acute myocardial infarction patients with diabetes mellitus
Authors: Kim D B , Kim H Y
Published: November 2023

Background

SGLT2i is effectively used for heart failure (HF), but secondary prevention after acute myocardial infarction (AMI) is unknown.

Methods

Among the National Health Insurance Service data, AMI patients hospitalized with first-use diabetes drugs were enrolled. Primary endpoints는 composite of all death and rehospitalization of HG. Secondary endpoints는 all death, rehospitalization of HF, recurrent AMI, and Ischemic stroke.

Results

We enrolled 4,831 patients (SGLT2 inhibitor: 1,739, other glucose-lowering medication: 3,092). After inverse probability of treatment weighting, primary endpoint showed a significantly good clinical outcome in SGLT inhibitor groups compared to other glucose-lowering medications. (HR, 95% CI: 0.663(0.54-0.82)). All death and HF also showed good results in SGLT2i group (0.79(0.71-0.0.91); 0.77 (0.62-0.95), respectively). There were no differences in recurrent AMI and stroke in both groups.

Conclusion

In AMI patients with diabetes, SGLT2i use is associated with a lower rate of overall death and HF, but the incidence of recurrent AMI and ischemic stroke showed no difference. These studies need to be verified as large-scale random studies in the future.
Real-world assessment of antiplatelet treatment therapies for acute coronary syndrome (ACS) patients in the United States in a nationwide Electronic Health Record in 2018-2020
Authors: Kang A , Jiang J , Li X , Horrow J , Garcia Sanchez R , O-Brien E , Abdul Sultan A , Krishnamurthy S P , Cannon C P
Published: November 2023

Background

Acute coronary syndrome (ACS) is one of the leading causes of cardiovascular related deaths for adults in US. The clinical presentation of ACS is broad, which includes ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation MI (NSTEMI), and unstable angina (UA). There are limited data around contemporary real-world treatment landscape, therefore it is critical to understand the treatment pattern of the US ACS patients in the real-world setting.

Purpose

This study evaluated antiplatelet therapy (APT) treatment patterns among US patients without atrial fibrillation or oral anticoagulants (OACs) who experienced their first hospitalized ACS event during observation period.

Methods

The Optum® de-identified Electronic Health Record dataset from January 2018 through December 2020 was used for this study. Adult patients with an inpatient primary diagnosis of ACS during the index period were identified by ICD10 codes. The date of admission for the first ACS hospitalization was the index date. Patients with atrial fibrillation diagnosis or a record for OAC use before index date and during hospitalization were excluded. ACS subgroups and percutaneous coronary intervention (PCI) status were assessed during index hospitalization; patient characteristics and in-hospital antiplatelet treatment type were also evaluated.

Results

Among 63,767 patients included in this study, the mean age was 64.1 and 40.5% were female; 89.2% were treated with APT. For those patients not treated with APT, majority were treated with parental anticoagulants. Among 89.2% APT treated patients, 52.7% were initiated on dual antiplatelet therapy (DAPT), 27.4% were initiated on single antiplatelet therapy (SAPT), and 9.1% switched between different DAPT regimens. The top three used DAPT were aspirin+clopidogrel (30.5%), aspirin+ticagrelor (18.9%) and aspirin+prasugrel (2.6%); the most used SAPT were aspirin (22.6%), clopidogrel (2.6%), and ticagrelor (2.0%). For ACS subtypes, 26.3% were diagnosed as STEMI, 62.9% were NSTEMI, and 10.8% were UA; of them, 45.0% had PCI procedure within 30-days before or after the index date. ACS patients with PCI procedure had the highest APT treatment rate (95.2%) and highest DAPT treatment rate (70.6%). Across ACS subtypes, patients hospitalized for STEMI had the highest usage of aspirin+ticagrelor (34.5%), whereas patients hospitalized for NSTEMI had the highest usage of aspirin+clopidogrel (34.7%).

Conclusion

We observed wide variability in APT treatment across STEMI vs. NSTEMI and +/-PCI. Only 38.1% of non-PCI treated ACS patients received DAPT despite current guidelines. Further analyses are planned to explore the varying APT (and/or anticoagulant) regimens.Figure 1Figure 2
Early initiation of PCSK9 inhibitor therapy versus placebo in patients with acute coronary syndrome: a systematic review and meta-analysis
Authors: Justino G B , Justino L B , Muller M E , Rocha A V , Mazetto A , Cardoso R , Leucker T M
Published: November 2023

Background

In patients with stable atherosclerotic cardiovascular disease (ASCVD) and prior atherosclerotic events, PCSK9 inhibitors (PCSK9i) have shown a 50-60% reduction in LDL-C from baseline, on a background of high-intensity or maximally tolerated statin therapy, leading to a 15% relative reduction in the incidence of major adverse cardiovascular events. However, less is known about the impact of PCSK9i initiation acutely in the setting of an acute coronary syndrome (ACS).

Purpose

To assess the efficacy of early initiation of PCSK9i therapy in lipid parameters among patients presenting with ACS.

Methods

We performed a systematic review and meta-analysis comparing PCSK9i with placebo in the setting of ACS, added to guideline directed high-intensity or maximally tolerated statin therapy. Inclusion was restricted to randomized controlled trials (RCTs) with initiation of PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. The systematic review and meta-analysis followed Cochrane and PRISMA recommendations.

Results

Six RCTs with a total of 996 patients were included, of whom 503 (50.5%) received PCSK9i. Mean follow-up ranged from 4 to 52 weeks. Mean time from presentation to administration of first dose ranged from 3.6 hours to 6.5 days. LDL-C levels were significantly lower at follow-up in the PCSK9i group (mean difference [MD] -44 mg/dL; 95% CI -54.3 to -33.8 mg/dL; p<0.001; Figure 1A). Lp(a) was also significantly decreased with PCSK9i therapy (MD -24.0 nmol/L; 95% CI -43.0 to -4.9 nmol/L; p=0.01; Figure 1B). Similarly, total cholesterol (MD -49.2 mg/dL; 95% CI -59 to -39.3 mg/dL; p<0.001) and triglycerides (MD -19 mg/dL; 95% CI -29.9 to -8.2 mg/dL; p<0.001) were significantly reduced with PCSK9i therapy, respectively. HDL-C was marginally increased in this same group (MD 2.5 mg/dL; 95% CI 0.9 to 4.2 mg/dL; p=0.003).

Conclusions

In patients with ACS, early initiation of PCSK9i, in addition to statin therapy, leads to a significant reduction in LDL-C and Lp(a) as compared with placebo. Whether the differences in these lipoproteins translate into a reduction in clinical endpoints is yet to be determined.
SGLT-2 inhibitors are associated with lower rates of mortality following myocardial infarction in patients with type 2 diabetes - A SWEDEHEART observational study
Authors: Rosen H C , Mohammad M A , Jernberg T , Erlinge D
Published: November 2023

Introduction

Secondary prevention following myocardial infarctions is critical in patients with type 2 diabetes due to the substantial risk of adverse events. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisation and cardiovascular death in patients with type 2 diabetes in several randomised studies. We hypothesised that the cardiovascular benefits associated with SGLT2 inhibitors could be observed in patients with diabetes treated with SGLT2 inhibitors following myocardial infarction in a real-world setting.

Methods

We included all patients with type 2 diabetes with an eGFR >30 ml/min/1.73m2 discharged from the cardiac care unit following a type 1 acute myocardial infarction between 1 January 2018 to 15 February 2022 from the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registries and cross-referenced the registry to the National Prescribed Drug Register. We identified all patients with a redeemed SGLT2 inhibitor 365 days prior to admission or within 10 days after discharge from the cardiac care unit. The primary outcome measure was a composite of all-cause death and hospitalisation for heart failure within 1 year from hospital discharge. Follow-up started at discharge.

Results

The study included 12,502 patients, of whom 2,770 (22.2%) were treated with SGLT2 inhibitors. Patients who were prescribed SGLT2 inhibitors were younger but had more comorbidities. The primary endpoint occurred in 2,128 (17.0%) patients during the follow-up period. After adjustment for differences in baseline characteristics and medical therapy, the use of SGLT2 inhibitors was associated with a 15% lower rate of the primary outcome, with an adjusted hazard ratio (HR) of 0.85 (95% CI 0.75 – 0.97). This was primarily driven by a lower rate of all-cause mortality, with an adjusted HR of 0.63 (95% CI 0.51 – 0.79). However, no difference was observed in hospitalisations for heart failure, with an adjusted HR of 1.07 (95% CI 0.93 – 1.22).

Conclusion

Treatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower incidence of a composite outcome comprising of all-cause mortality or hospitalisation for heart failure. The lower observed rate appeared to be driven by a lower all-cause mortality rate in those treated with SGLT2 inhibitors.Baseline characteristicsCumulative incidence of the outcome
Changes of hospital-level variation in use of optimal medical treatment for long-term follow-up from a multi-level methodological approach
Authors: Lee J , Jeong M , Rhee E , Jung J , Chang E , Kwak H , Jung M , Park Y , Park B , Kim H , Kim N , Jang S , Bae M , Yang D , Park H
Published: November 2023

Background

Contemporary guidelines documented that optimal medical therapy (OMT) should be prescribed to improve clinical outcome in patients with acute myocardial infarction (AMI). However, the changes of hospital-level variations in prescription rates of OMT for long-term follow-up are unknown.

Purpose

We aimed to investigate (1) impact of hospital-level variation on the use of each medication and OMT and (2) changes of hospital-level variation in prescription rates of individual medical therapy and OMT during the follow-up.

Methods

We examined hospital medications of 13,516 AMI patients without documented contraindications to antiplatelet agents, β-blockers (BB), angiotensin-converting enzyme inhibitors (ACE) /angiotensin II receptor blockers (ARB), or statins from the Korean Acute Myocardial Infarction Registry (KAMIR) – National Institute of Health (NIH) database. OMT was deﬁned as use of all 4 indicated medications. Hierarchical generalized linear mixed models estimated hospital-level variation in prescription rates of OMT and each medication after adjustment for patient-level factors. Variation was explored with a median rate ratio (MRR), which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals.

Results

The prescription rates of OMT and each effective cardiac medications are presented in Figure. There were substantial decreases in the prescription rates for OMT (from 66.7% to 51.6%) and dual antiplatelet agents (from 99.1% to 50.4%) for 2 years follow-up. After adjustment for patient-level covariates, hospital-level MRR for OMT was 1.47 at discharge, indicating an 47% likelihood that 2 random hospitals would differ in treating identical AMI patients. As the prescription rates of OMT and each effective cardiac medications decreased, adjusted hospital-level MRR for OMT (from 1.47 to 1.22), BB therapy (from 1.35 to 1.15), ACE/ARB therapy (from 1.68 to 1.16), and statin therapy (from 1.19 to 1.06) decreased for 2-year follow-up, whereas MRR for dual antiplatelet therapy increased at 1 year (MRR; 1.61) and 2 years (MRR; 1.63) follow-up (Figure). Among patient-level factors, age >70 years, Killip class>2, obesity, hypertension, previous coronary artery disease, renal dysfunction, reduced ejection fraction, percutaneous coronary intervention was independently associated with the use of OMT.

Conclusion

Hospital-level variations in the use of OMT and each effective cardiac medications were observed at discharge, but weakened overtime, except for use of dual antiplatelet therapy.
Effect of statin therapy on long-term mortality among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA)
Authors: Nowak K , Stepien K , Kachnic N , Horosin G , Karcinska A , Walczak P , Nessler J , Zalewski J
Published: November 2023

Background

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is associated with the lack of visible atherosclerosis in coronary arteries. Current 2020 ESC Guidelines on the management of acute coronary syndromes state that statins may be beneficial to reducing all-cause mortality and major adverse cardiac events (MACE) among MINOCA patients. Although, the existing literature data remains conflicting, recent meta-analysis based on observational studies showed that statin therapy resulted in a reduction of MACE and mortality.

Purpose

We aimed to assess the effect of statin therapy on long-term mortality among MINOCA patients.

Methods

1011 patients were hospitalized between 2012 and 2017 with the diagnosis of MI based on clinical symptoms, electrocardiographic findings, and the evolution of myocardial necrotic biomarkers according to the universal criteria of MI. On admission, coronary angiography was performed in all patients to assess the existence of obstructive lesions in coronary arteries. 72 patients had lesions narrowing a coronary artery by less than 50% and were classified as MINOCA.

Results

Statins were used by 54 (75.0%) of MINOCA patients. Those treated with statins had a higher prevalence of hypertension (P=0.001), dyslipidemia (P<0.001), lower Killip class on admission (P=0.005) and a higher LVEF (P=0.019) than MINOCA not treated with a statin. At the time of the decision about statin therapy, LDL cholesterol level was higher in the MINOCA population with subsequently prescribed statins (P=0.008). Long-term mortality was significantly higher in MINOCA patients not treated with statins (17.7%/year versus 6.6%/year, P=0.009) compared with those treated with statins.

Conclusions

According to our results, statins should be routinely prescribed in the heterogeneous group of MINOCA patients. However, more research regarding that issue is needed.The long-term outcomes.