bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking for ischemia in patients with stable atypical chest pain: useful or useless?
Authors: Cosmi D , Mariottoni B , Cosmi F
Published: November 2020

Introduction

Patients with stable atypical chest pain (SACP) represent more than half of those with chest pain who require an outpatient evaluation. It's not clear if in these patients the prognosis is linked more to the optimal control of risk factors and to the research and treatment of any unfavorable anatomical alterations (common trunk obstruction, proximal involvement of VAT, multivessel disease with systolic dysfunction of the left ventricle) rather than to ischemia assessment with functional tests.

Methods

In the past 20 years we have evaluated the lifestyles of 40,422 outpatient patients. 9% (3,638) had a history of stable chest pain with no history of previous cardiovascular events. In the 1,322 patients (36%) with non-anginal chest pain, no diagnostic examination was performed after the electrocardiogram (ECG) and the echocardiogram. 462 patients (13%) had typical chest pain, and 422 of them performed a coronary angiography.

The other 1,854 (51%) patients with SACP underwent functional testing for ischemia (exercise ECG, ecostress, nuclear stress testing). They were also stratified according to the presence of 4 main modifiable lifestyles (cigarette smoking, diet, physical activity, obesity) and the 3 main cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes).

Results

In the SACP group, the search for ischemia was positive in 192 patients (10.4%); 178 of them underwent coronary angiography, which demonstrated the presence of lesions with indication to revascularization to improve the prognosis, according to the ESC 2018 guidelines (Class IA), in 21 patients (11.7%). In the remaining 1,662 patients functional tests were negative.

We performed one-year follow-up. Major coronary events (fatal and non-fatal infarction, sudden death) occurred in 22 patients (1.3%) with negative stress tests and at least 3 risk factors or bad lifestyles (especially smoking, diabetes, high LDL). In patients with positive stress tests, there were 3 events, (1.5%), that occurred among patients with at least 3 risk factors, too. No events occurred in patients with fewer than 3 risk factors or lifestyles in either group.

Conclusions

In patients with SACP and negative functional test the risk of major coronary events remains 1.3% at 1 year of follow-up; the events occurr in patients with 3 or more factors or lifestyle at risk (especially smoking, diabetes, elevated LDL). The prognosis is similar to those with positive ischemia research.

The improvement of the outcomes should be entrusted more to a close control of the risk factors, to an optimal improvement of the lifestyles and to an anatomical evaluation (coronary CT) for the evaluation of those lesions that improve the prognosis rather than the search for ischemia which appears futile from a diagnostic and prognostic point of view as well as a source of economic waste.

Funding Acknowledgement

Type of funding source: None
Prognostic value of hybrid cardiac perfusion SPECT/CT for patients with coronary artery disease after coronary artery bypass grafting
Authors: Fukushima Y , Ishii Y , Kiriyama T , Nitta T , Kumita S
Published: November 2020

Introduction

Patients with coronary artery disease (CAD) undergoing coronary artery bypass grafting (CABG) occasionally experience recurrent myocardial ischemia. Because of their severe CAD and its complicated hemodynamics, conventional cardiac perfusion SPECT often cannot reveal the severity and prognosis solely. Hybrid cardiac SPECT/CT imaging simultaneously shows myocardial ischemia distribution, coronary artery lesion distribution, and their relationship, and this modality may enable detailed interpretation and risk stratification for such patients.

Aim

This study aimed to assess the prognostic value of hybrid cardiac SPECT/CT for patients with CAD and suspected myocardial ischemia after CABG.

Methods

A total of 201 consecutive patients, registered between April 2016 and September 2018, with suspected recurrent angina pectoris after CABG requiring examinations for myocardial ischemia were included in this study. Among these, 135 patients who underwent cardiac perfusion SPECT, cardiac CT, and hybrid cardiac SPECT/CT imaging were analyzed. In the SPECT-only analysis, SDS was calculated, and the patients were divided into none-to-mild (SDS <4) and moderate-to-severe ischemia (SDS ≥4) groups. In the SPECT/CT analysis, the patients were divided into a matched group (SPECT reversible accumulation defects [SDS ≥2] along coronary arteries with significant lesions) and an unmatched group (accumulation defects not coincided with coronary artery territories or no significant stenoses in the corresponding coronary arteries). All patients were observed from the time of these tests for the occurrence of major adverse cardiac events (MACE), and the prognostic performances of these analyses were compared.

Results

In the SPECT-only analysis, 62 were in the none-to-mild group and 73 were in the moderate-to-severe group. In the SPECT/CT analysis, 61 were in the matched group and 74 were in the unmatched group. Within the follow-up period of 29±8 months, 15 patients experienced MACE. The patients' prognoses were clearly stratified by hybrid SPECT/CT analysis (matched: 13/61, 21.3% vs. unmatched: 2/74, 2.7%) compared with SPECT-only analysis (moderate-to-severe: 11/73, 15.0% vs. none-to-mild: 4/62, 6.5%). The hybrid cardiac SPECT/CT analysis was more strongly associated with the occurrence of MACE compared with SPECT-only analysis (p=0.008 vs. p=0.04, respectively).

Conclusions

Hybrid cardiac SPECT/CT imaging can have higher prognostic value compared with stand-alone cardiac perfusion SPECT for patients with CAD after CABG.

Funding Acknowledgement

Type of funding source: None
Percutaneous coronary intervention in spontaneous coronary artery dissection: a case-control study
Authors: Kotecha D , Premawardhana A.D.P.E , Garcia-Guimaraes M , Pellegrini D , Wood A.D , Maas A , Van Geuns R , Alfonso F , Adlam D
Published: November 2020

Background

Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndrome particularly in young-middle aged women. Revascularisation is challenging due to an underlying disrupted and friable coronary vessel wall leading to widely reported worse outcomes than for atherosclerotic coronary disease. Therefore, a conservative approach where possible is favoured however in some cases haemodynamic instability, ongoing ischaemia and reduced distal flow mandates consideration of revascularisation.

Purpose

To compare SCAD survivors managed with PCI or conservatively in terms of presentation characteristics, complications and long-term outcomes.

Methodology and results

226 angiographically confirmed SCAD survivors (95% female,47±9.7yrs) who underwent PCI were compared in a case control study with two hundred and twenty-five angiographically confirmed SCAD survivors (92% female, 49±9.9yrs) who were conservatively managed. Patients were recruited from UK, Spanish and Dutch SCAD registries and both groups were well matched in terms of baseline demographics.

Those treated with PCI were more likely to present with proximal SCAD (30.8% vs 7.6% P<0.01) and ST elevation myocardial infarction (STEMI) or cardiac arrest with reduced flow (32.3% vs 6.3% P<0.01). Intervention was performed with stents in 72.4%, plain old balloon angioplasty in 21.1% and wiring in 6.4% of cases and more often for multi-segment disease (40.8% vs 26.3% P<0.01). In cases with initial reduced flow undergoing PCI an improvement in flow was seen in 83%.

Analysis of UK PCI cases (n=144) reveal complications in 56 (38.8%). However, when assessed for significance defined by a reduction in flow in a proximal/mid vessel, stent extension into left main stem, iatrogenic dissection requiring PCI and CABG as a consequence of PCI only 13 cases (9%) met criteria. Iatrogenic dissection accounts for the majority (76.9%). SCAD lesion length was associated with presence of complications (P=0.025). There was a non-significant trend towards major adverse cardiovascular events (MACE) occurring more frequently in those undergoing PCI (18% vs 11% P=0.067) driven by revascularisation (5% vs 1% P=0.036). Median follow up was 2.7 years.

Conclusions

PCI in SCAD is often performed in higher risk patients; in those presenting with reduced flow, the majority demonstrate improvement. Importantly whilst overall complication rates were similar to those widely reported, clinically significant complications were low. Multivariate modelling will reveal factors associated with complications to aid future decision making in this challenging patient group.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation
Association between hypercoagulability and microvascular dysfunction in patients with acute myocardial infarction
Authors: Kang M.G , Kim K.H , Bae J.S , Ahn J.H , Park H.W , Park Y.W , Hwang S.J , Hwang J.Y , Koh J.S , Jeong Y.H
Published: November 2020

Background

Microvascular dysfunction (MVD) following percutaneous coronary intervention (PCI) can increase the risk of adverse clinical outcomes, which partly may be related with thromboembolic microvascular obstruction. This study was sought to determine whether hypercoagulability is linked with MVD post-PCI in patients with acute myocardial infarction (AMI).

Methods

Hypercoagulability was determined with thrombin-induced platelet-fibrin clot strength (maximal amplitude [MAthrombin] ≥68 mm evaluated by thromboelastography). Microvascular function was assessed by invasive physiological index after PCI (MVD: index of microcirculatory resistance [IMR] ≥40 U). Major adverse cardiovascular events (MACE) was defined as the incidence of death or rehospitalization for heart failure post-PCI.

Results

Among AMI patients (n=116), 46 patients (39.7%) met the criteria of hypercoagulability and 27 patients (23.3%) had a MVD. Level of IMR showed a significant correlation with MAthrombin value (r=0.313; p=0.001). Prevalence of MVD was increased proportionally according to the quartile scale of MAthrombin (3.6% vs. 21.9% vs. 25.9% vs. 41.4%; p for trend = 0.009). Hypercoagulability significantly increased the predictive value for MVD occurrence (odds ratio: 4.35; 95% confidence interval: 1.74 to 10.89; p=0.001). During the follow-up post-PCI of 40.9 months (IQR: 19.8 to 59.4 months), MVD and hypercoagulability were both associated with MACE (hazard ratio: 5.86 and 2.28 respectively). Patients with both MVD and hypercoagulability showed an increased risk for MACE compared with the others (18.2% vs. 5.3%; adjusted hazard ratio: 4.50; 95% confidence interval: 1.26 to 16.12; Log rank p=0.011) (Figure).

Conclusion

This is the first analysis to demonstrate that baseline hypercoagulability is an independent determinant of post-PCI MVD in AMI patients. Combining the measurements of hypercoagulability and MVD may enhance risk stratification and deserves further study.

Long-term outcomes

Funding Acknowledgement

Type of funding source: None
Clinical predictors and angiographic features of acute coronary syndromes caused by systemic embolism
Authors: Jeronimo Baza A , Salazar C , Perez Vyzcaino M.J , Nombela L , Jimenez Quevedo P , Nunez I , Salinas P , Mejia H , Escaned J , Fernandez Ortiz A , Ferrandez Escarabajal M , Martinez Gomez E , Ramos Lopez N , Gonzalo N
Published: November 2020

Introduction

Systemic embolism to coronary arteries is one of the mechanisms of acute myocardial infarction (AMI) of non-atherosclerotic cause. However, its clinical profile has not been properly established yet.

Purpose

To identify clinical predictors and angiographic characteristics of acute coronary syndromes caused by systemic embolism to a principal coronary artery (ACS-E), as well as to describe in-hospital mortality of these patients.

Methods

40 patients with ACS-E, admitted between 2003 and 2018 in a tertiary hospital. Epidemiological, clinical and angiographic characteristics of these cases were compared with those from 4989 patients, attended for acute coronary syndrome of atherosclerotic cause (ACS-A) in the same hospital during the same period.

Results

Patients with ACS-E were younger (28% vs 10% were <45 years old, p<0.001) and had a higher proportion of women (43% vs 22%, p 0.003), atrial fibrillation (40% vs 5%, p<0.001) and neoplasia (18% vs 7%, p 0.009). They had also undergone previous valvular surgery more frequently than patients with ACS-A (13% vs 0.5%, p<0.001) and a higher proportion of them were under treatment with warfarin (15% vs 3%, p<0.001). Variables identified as independent predictors of ACS-E in the multivariate analysis are shown in the table. Regarding clinical presentation, ST elevation AMI was more frequent in ACS-E cases (83% vs 67%, p 0.04). Patients with ACS-E did not present any significative stenosis in other vessels apart from the culprit one (number of other vessels with at least 1 severe stenosis was 0 in the ACS-E group vs 1.33 + 1 in the ACS-A arm, p<0.001). PCI was attempted in 75% of the patients with ACS-E, resulting successful in 80% of the cases. On the other hand, 100% of SCA-A underwent PCI, with a success proportion of 99% (p<0.001). In-hospital mortality in ACS-E group was 15% and 4% in the control group (p<0.001).

Conclusions

ACS-E and ACS-A have different clinical and angiographic features. Atrial fibrillation, chronic warfarin treatment, previous valvular surgery, presence of any neoplasia and female sex are independent predictors for ACS-E.

Funding Acknowledgement

Type of funding source: None
Morphological characteristics of plaque erosion with noncritical coronary stenosis: an optical coherence tomography study
Authors: Fang C , Dai J , Zhang S , Wang J , Wang Y , Li L , Xing L , Hou J , Yu B
Published: November 2020

Background

Plaque erosion is a frequent and important mechanism of acute coronary thrombosis only secondary to plaque rupture. Recent studies suggested plaque erosion with noncritical stenosis could be treated conservatively that distinct from those with critical stenosis. However, characteristics of plaque erosions with different coronary stenosis remain unknown.

Purpose

The present study aimed to investigate morphological features of plaque erosions with different coronary stenosis using optical coherence tomography (OCT).

Methods

Consecutive ST-segment elevated myocardial infarction (STEMI) patients with OCT images of culprit lesion between August 2014 and December 2017 were enrolled and 348 cases presented with plaque erosion identified by OCT. Based on the severity of lumen area stenosis [calculated by (1-minimal lumen area/reference lumen area) * 100%], all culprit plaque erosions were divided into three groups: Group A (area stenosis<50%, n=50, 14.4%); Group B (50%≤area stenosis<75%, n=146, 42.0%); Group C (area stenosis≥75%, n=152, 43.7%). Clinical characteristics, lesion features detected by coronary angiography and OCT were compared among three groups.

Results

Of all 348 STEMI patients with plaque erosions, patients in Group A were youngest (p=0.008) and had the lowest frequency of hypertension (p=0.029) as compared with those in Group B and C. Angiographic analysis showed 72.0% of plaque erosions in Group A located in LAD, while 67.8% in Group B and 53.9% in Group C (p=0.039). OCT findings (Figure 1-A) showed the prevalence of fibrous plaque was significantly highest in Group A than those in Group B and C (82.0% vs. 54.8% vs. 34.9%, p<0.001), whereas lipid rich plaque was most frequent in Group C (16.0% vs. 43.8% vs. 62.5%, p<0.001). The prevalence of macrophage (p<0.001), microvessel (p=0.009) and cholesterol crystals (p<0.001) increased gradually from plaque erosion with lumen area stenosis <50% to 50–75% to ≥75%. Notably, compared with Group B and C, nearby bifurcation was most common in Group A (72.0% vs. 67.1% vs. 55.3%, p=0.036). Multivariable regression analyses (Figure 1-B) showed fibrous plaque and nearby bifurcation were independently associated with plaque erosion with noncritical stenosis (area stenosis<75%).

Conclusion

56.3% plaque erosion in STEMI patients presented with noncritical stenosis, having distinct morphological features from erosion with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with the presence of noncritically stenotic plaque erosion, remaining a desire to tailor treatment therapy to individual patients.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National Key R&D Program of China
Metformin exerts cardioprotection via attenuating mitochondrial fission in cardiac ischaemia-reperfusion injury in rats
Authors: Palee S , Higgins L , Leech T , Chattipakorn S.C , Chattipakorn N
Published: November 2020

Background

Cardiac ischemia/reperfusion (I/R) injury following myocardial infarction reperfusion therapy is a phenomenon that results in further cardiomyocytes death and impaired cardiac contractility. Although metformin has been shown to exert cardioprotection in addition to glycemic control, its effect on cardiac I/R injury are still controversy, and the comparative doses of metformin in cardiac I/R injury have never been investigated.

Purpose

We hypothesized that metformin given acutely prior to cardiac ischaemia exerts cardioprotection in rats with cardiac I/R injury via attenuating cardiac mitochondrial dysfunction, leading to improved left ventricular (LV) function.

Methods

Forty Male Wistar rats were subjected to cardiac I/R injury. Four treatment groups were investigated. The first group received saline as a control group. The second to the fourth groups received metformin at 100, 200, and 400 mg/kg intravenously, respectively. During the I/R protocols, the LV function, arrhythmia score, and mortality rate were determined. At the end, the hearts were rapidly removed to determine infarct size, cardiac mitochondrial function, cardiac mitochondrial dynamics, and cardiac apoptosis.

Results

Metformin 200 mg/kg exerted the highest level of cardioprotection through the attenuated incidence of arrhythmia, decreased infarct size (Fig. 1), improved cardiac mitochondrial function, and decreased mitochondrial fission (Fig. 1) and cardiac apoptotic markers, leading to improved cardiac function during I/R injury. Although Metformin at all doses effectively decreased infarct size, improved cardiac mitochondrial function and LV function, Metformin at 200 mg/kg exerted the best efficacy (Fig. 1).

Conclusions

Metformin exerts cardioprotection by attenuating mitochondrial dysfunction and decreased mitochondrial fission, leading to decreased infarct size and ultimately improved LV function after acute cardiac I/R injury in rats. These findings also indicate the potential biphasic effects of metformin on infarct size which are dose-dependent.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science and Technology Development Agency Thailand (NC), and Thailand Research Fund (SCC)
Characterization of thromboembolic and bleeding risks in cancer patients with acute myocardial infarction under the use of guideline-recommended dual-antiplatelet therapy
Authors: Hayashi H , Kataoka Y , Hosoda H , Nakashima T , Honda S , Fujino M , Nakao K , Yoneda S , Otsuka F , Asaumi Y , Noguchi T , Izumiya Y , Yoshiyama M , Yasuda S
Published: November 2020

Background

Atherosclerotic cardiovascular disease including acute myocardial infarction (AMI) has become one of major co-existing diseases in cancer patients due to their improved survival rate. Current guideline recommends dual-antiplatelet therapy (DAPT) in patients with AMI. Given that the presence of cancer elevates not only coagulability but bleeding risks, these substrate may further worsen cardiovascular outcomes and bleeding risks in cancer subjects with AMI receiving DAPT.

Methods

We retrospectively analyzed 712 AMI patients treated by primary PCI with drug-eluting stent and DAPT between 2007 and 2017. The diagnosis of cancer was determined through medical record review. Clinical characteristics, thromboembolic (=all-cause death+non-fatal MI+stroke) and bleeding events were compared in AMI subjects with vs. without cancer.

Results

Cancer was identified in 11.1% (=79/712) of study subjects. Of these, around 40% of them had gastrointestinal cancer (=35/79), followed by lung cancer (=5/79) and breast cancer (=8/79). Cancer patients were more likely to be older (77±7 v. 69±13 years, p<0.001) with a history of Af (25 v. 10%, p<0.001), CKD (eGFR<60: 60 v. 42%, p=0.002), anemia (hemoglobin: 12.8±1.8 v. 13.9±1.8 g/dl, p<0.001). Under anti-thrombotic (DAPT=86%, triple-antiplatelet therapy=14%) and optimal medical therapies (ACE-I=90%, beta-blocker=76%, statin=96%), more frequent occurrence of thromboembolic events was observed in patients with cancer (34.2 v. 12.6%, p=0.004, Picture). Furthermore, the presence of cancer was associated with more than four times greater risk of bleeding events compared to non-cancer subjects (18.9 v. 4.3%, p<0.001, Picture). In particular, the frequency of both major (10.1 vs. 3.3%, p=0.003) and minor (8.9 vs. 0.9%, p<0.001) bleeding events was significantly higher in patients with cancer. In multivariate analysis, cancer independently predicted bleeding events (Table).

Conclusions

Under the use of guideline recommended DAPT, the concomitance of cancer in AMI subjects was a predictor for thromboembolic as well as bleeding events. In particular, the relationship between cancer and bleeding was significant. These observations underscore the appropriate selection and duration of anti-thrombotic agents in AMI subjects with cancer.

Cardiac/Bleeding Events in AMI Subjects

Funding Acknowledgement

Type of funding source: None
Ischemic and bleeding risk stratification in diabetic patients after acute coronary syndrome based on insulin requirement
Authors: Cavallari I , Sagazio E , Antonucci E , Calabro' P , Gragnano F , Cirillo P , Gresele P , Palareti G , Pengo V , Pignatelli P , Marcucci R , Patti G
Published: November 2020

Background

Diabetes is a known risk factor for a first or recurrent cardiovascular event, however, its association with an increased risk of bleeding is controversial. To date, no study has explored the prognostic weight of insulin therapy in the setting of ACS.

Purpose

To investigate the differential role of insulin versus no insulin therapy on ischemic and bleeding risks in patients with diabetes and ACS.

Methods

START-ANTIPLATELET is a prospective, real-world multicenter registry including consecutive patients admitted for ACS. For the purpose of this analysis, patients were stratified according to diabetes status and insulin therapy. We compared 1-year rates of major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction and stroke, and of any bleeding, according to diabetes status (no diabetes, diabetes not on insulin therapy, diabetes on insulin therapy). In addition, we evaluated the net clinical benefit of dual antiplatelet therapy with the newer P2Y12 inhibitors (ticagrelor or prasugrel) vs dual antiplatelet therapy with clopidogrel according to diabetes status.

Results

In an overall population of 907 patients, 198 had diabetes, 10.6% of whom were on insulin. From non-diabetic patients to diabetic patients not on insulin and diabetic patients on insulin there was a stepwise decrease of MACE-free survival (log-rank p 0.039) with incidence of events at 1 year being 3.8%, 6.8% (adjusted p vs no diabetes 0.49) and 12.5% (adjusted p vs no diabetes 0.047), respectively (Figure, panel A). The rates of any bleeding were higher in patients on insulin (20.8% vs 8.8% in those without diabetes and 5.8% in diabetic patients not receiving insulin; log-rank p 0.028; Figure, panel B). Multivariable analysis demonstrated an almost 5-fold increase of any bleeding in diabetic patients with vs without insulin (OR 4.98, 95% CI 1.46–16.92; p=0.010). In the overall population, the incidence of the net composite endpoint including MACE or major bleeding with the use of ticagrelor/prasugrel on top of aspirin was significantly lower compared to use of clopidogrel (4.7% vs 8.4%; OR 0.54, 95% CI 0.30–0.94, p=0.031). This net clinical benefit in patients receiving a newer P2Y12 inhibitor was regardless of the diabetes status (p for interaction 0.48).

Conclusions

In this cohort of ACS patients, the presence of diabetes stratified by insulin therapy was associated with a graded increase in the 1-year rates of MACE. Conversely, insulin therapy significantly contributed to the overall increase of bleeding risk in diabetes.

Funding Acknowledgement

Type of funding source: None
Short and medium chain acylcarnitines as markers of outcome in diabetic and non-diabetic subjects with acute coronary syndromes
Authors: Davies A , Li X , Obeid S , Roffi M , Klingenberg R , Mach F , Raber L , Windecker S , Templin C , Muller O , Nanchen D , Matter C , Wang Z , Hazen S , Luescher T
Published: November 2020

Background

Dietary carnitine that is not absorbed can serve as a precursor for gut microbiota-dependent generation of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombosis promoting metabolite. Gut microbiome-derived metabolites of dietary carnitine, including TMAO and g-butyrobetaine, may accelerate atherosclerosis, increase platelet reactivity and in vivo thrombosis. Carnitine metabolism also produces numerous molecular species of short, medium and long chain acylcarnitines, which play important roles in energy metabolism and intracellular fatty acid transport.

Purpose

We sought to evaluate the differences between diabetics and non-diabetics presenting with ACS with respect to acylcarnitines, and to explore their relationship with incident cardiovascular outcomes.

Methods

Using a large, prospectively recruited cohort of patients presenting to the cardiac cath lab with suspected acute coronary syndromes, we measured levels of plasma acylcarnitines, carnitine and its gut microbial-derived metabolites to assess their relationship with independently adjudicated major adverse cardiac events (MACE = myocardial infarction, stroke or TIA, need for revascularization or all-cause mortality) amongst diabetics and non-diabetics.

Results

We analysed 1683 patients who presented with ACS, were treated according to current guidelines and had undergone acylcarnitine analysis. There were 294 diabetics and 1389 non-diabetics. Diabetics had significantly higher plasma levels of all acyl carnitine metabolites than non-diabetics (P<0.001), but not of carnitine itself. Baseline plasma levels of all gut microbiome derived carnitine metabolites (TMAO, g-butyrobetaine and crotonobetaine) were also significantly higher in those who subsequently experienced a MACE. All carnitine metabolites, apart from octenoylcarnitine, were significantly associated with MACE on univariate analysis, while acetylcarnitine and crotonobetaine were independently associated with MACE after multivariate adjustment.

Conclusion

Serum short- and medium- chain acylcarnitine levels are significantly higher in diabetic patients presenting with ACS and predict MACE. After multivariate adjustment, acetylcarnitine and crotonobetaine remained an independent predictor of MACE.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Zurich Heart House - Foundation for Cardiovascular Research
C-reactive protein increases myocardial damage after STEMI
Authors: Garlichs C.D , Ries W , Torzewski J , Pfluecke C , Heigl F , Darius H , Ince H , Mitzner S , Nordbeck P , Butter C , Sheriff A
Published: November 2020

Background

The CAMI-1 study dealt with the depletion of CRP by apheresis in patients with acute myocardial infarction (AMI). CRP, the prototype human acute phase protein, has been known as a marker of poor prognosis in AMI and independently predicts 30-day mortality.

Methods

66 STEMI patients were enrolled in the study following complete coronary revascularization (2–12 h after the onset of symptoms). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. A specific CRP adsorber removed up to 79% of the original CRP. In each apheresis session, 6000 ml of plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 2–9 days after STEMI.

Results

Aphereses sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 9 to 279 mg/l. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the CRP concentration is significantly associated with the damage (infarct size, LVEF, circumferential strain) in the controls. This association was lost in the aphereses patients: they performed significantly better at all endpoints (infarct size, LVEF, circumferential strain) than the controls. The CRP apheresis significantly reduced myocardial damage. To our surprise, two apheresis patients had an infarct size of 0%.

Conclusions

For the first time we find an unequivocal association between myocardial infarct size and the CRP concentration. This is in some respects a surprise, since the basic assumption in AMI is that the vascular occlusion leads to primary damage and the reperfusion to secondary damage, which would not have led one to expect such a clear dose-response relationship as that observed here. In addition, our results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry).

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Pentracor GmbH
Extend of coronary lesion, in-hospital complications in patients with STEMI, treated with PCI and high levels of CD14++CD16+ monocytes subpopulation
Authors: Dovhan O.V , Parkhomenko A.N , Talayeva T.V , Tretyak I.V , Shumakov O , Gurjeva O.S
Published: November 2020

Aims

Acute myocardial infarction with the ST elevation (STEMI) is accompanied by the development of an inflammatory reaction, in particular, activation of monocytes. To date, the relationship between the levels and dynamics of monocyte populations in patients with STEMI and the prevalence of coronary atherosclerosis on the one hand (and with the clinical course of the disease, on the other hand) is not well understood.

Methods and results

The 50 STEMI patients (pts) were studied prospectively. All the pts underwent the PCI (alone, or followed by angioplasty/stenting) and have the monocytes (Mc) population analysis data obtained at 1st and 7th–10th days. According to the angiography data, pts were divided into three groups: “single-vessel lesion” (group 1, n=13), “two-vessel lesion” (group 2, n=14) and “three-vessel lesion” (group 3, n=23). There was an in-hospital increase in CD14++CD16-, CD14++CD16+ and CD14+CD16++ populations of Mc in 3rd group (+5%, +43% and +44%, respectively, p<0.05 for all), whereas in subgroups 1 and 2 there was an increase in CD14+CD16++ population (+70% in group 1, p<0.05 and +90% in group 2, p<0.001), without significant dynamics of CD14++CD16− and CD14++CD16+ populations. In addition, there was an increase in the CD14+CD16++ population only in pts with 1–3 coronary lesions (+72%, p<0.001 versus −12% of decrease in pts with more than 3 lesions, p>0.1). The number of CD14++CD16+ Mc on day 1 of STEMI correlated positively with levels of C-reactive protein (C-RP, r=0.34, p<0.05), erythrocyte sedimentation rate (ESR, r=0.39, p<0.01), and with left ventricle (LV) end-systolic volume (r=0.33, p<0.05) and negatively – with LV ejection fraction (r=−0.22, p<0.1), while there were only slight correlations of CD14++CD16- Mc levels with left ventricle (LV) end-systolic volume (r=0.28, p<0.05) and with LV ejection fraction (r=−0.23, p<0.1). According to the hospital follow-up, the 1st day count of CD14++CD16+ Mc was higher in patients with in-hospital complications (mean 42.9±6.9x106/L vs 26.6±5.3x106/L in uncomplicated cases, p<0.05), and was correlated with number of in-hospital complications per patient (r=0.25, p=0.05).

Conclusion

Higher baseline number of CD14++CD16+ Mc correlates with other “pro-inflammatory” indices (C-RP, ESR) and indicates the worse baseline cardio-hemodynamic and unfavorable course of in-hospital period in pts with STEMI, treated with PCI. Incremental in-hospital dynamic of all Mc populations was observed in multi-vessel lesion cases.

Funding Acknowledgement

Type of funding source: None
Coronary plaque natural history displays significant longitudinal heterogeneity along the length of individual coronary plaques
Authors: Wentzel J.J , Papafaklis M , Antoniadis A , Takahashi S , Cefalo N.V , Cormier M , Saito S , Coskun A , Stone P.H
Published: November 2020

Background

The natural history of plaque growth is, among other systemic risk factors, related to the blood flow induced local shear stress. Especially at regions of low shear stress plaques are initiated. Upon plaque encroachment into the lumen, plaques will be exposed to high shear stress. Interestingly, it has been observed that individual plaques are very heterogeneous regarding the local shear stress exposure and remodeling patterns along the plaque length. However no information is available on the spatial heterogeneity of temporal changes in plaques burden. We studied the longitudinal spatial heterogeneity of plaque burden progression, regression, quiescence in human coronary plaques.

Methods

591 coronary arteries from 302 patients with coronary artery disease who presented with an acute coronary syndrome from the PREDICTION study were investigated for local plaque progression, regression, quiescence patterns after 6–10 months follow up. Arterial geometry was derived from angiography/IVUS-based vascular profiling and reported in 3 mm segments. Plaques were defined as >3 consecutive segments with maximal wall thickness>0.5 mm. Plaque progression was defined as >5% increase, regression as <−5% decrease, and quiescence as no change in plaque burden (plaque area/ total vessel area * 100%). Logistic mixed model regression analysis was performed with plaque progression features as outcome and plaque length as independent variable with vessel as random factor to account for clustering of the data.

Results

5658 3mm-segments of 661 plaques were analyzed. Plaque burden changes over time ranged from −22% to +20%, with an average of −0.4%±4% which was not significant different from 0. Among all plaques, 56% showed segments with plaque progression of more than 5%, 60% with plaque regression (<−5%) and 96% of the plaques had segments that did not change over time (quiescence). On average, 17% of the plaque length displayed plaque progression, 20% regression and 63% was quiescent. The presence and number of features (progression, regression, quiescence) within the plaque were significantly related to the plaque length (figure).

Conclusion

Plaques are very heterogeneous in plaque progression patterns. Most of the plaques show within the plaque length simultaneously more than one plaque progression feature (segments that do not change in plaque burden, segments that regress or progress). The number of observed plaque progression features was related to the plaque length.

Funding Acknowledgement

Type of funding source: None
Elevated serum carboxy-terminal telopeptide of type I collagen predicts clinical outcome in patients with acute coronary syndrome who underwent percutaneous coronary intervention
Authors: Aono T , Watanabe T , Toshima T , Takahashi T , Otaki Y , Wanezaki M , Kutsuzawa D , Kato S , Tamura H , Nishiyama S , Takahashi H , Arimoto T , Shishido T , Watanabe M
Published: November 2020

Introduction

Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is a collagen degradation product of type I collagen in the extracellular matrix of the heart, blood vessels, and bone. The serum levels of I-CTP were reportedly a predictive marker for cardiac remodeling after acute myocardial infarction. However, it remains unclear whether I-CTP can predict poor clinical outcome in patient with acute coronary syndrome (ACS).

Purpose

The aim of this study was to investigate the association between serum levels of I-CTP and clinical outcome in patients with ACS.

Methods

Serum levels of I-CTP were measured in 200 patients with ACS who underwent percutaneous coronary intervention (PCI). All patients were prospectively followed during the median follow-up period of 1312 days with the end point of major adverse cardiovascular events (MACE). We divided the patients into tertiles according to serum I-CTP level: low I-CTP group (≤4.4 ng/ml, n=72), middle I-CTP group (4.4–6.4 ng/ml, n=65), and high I-CTP group (≥6.5 ng/ml, n=63).

Results

There were 44 MACE, including 24 all-cause death and 9 rehospitalization due to heart failure. I-CTP was significantly higher in patients with MACE than those without (4.90 [interquartile range (IQR): 3.80–6.38] ng/ml vs. 6.65 [IQR: 5.00–10.08] ng/ml, p<0.001). Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP had the greatest risk of MACE. In a univariate analysis, age, Albumin, estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (LDL-C), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP) and I-CTP were significant predictors of MACE. A multivariate Cox proportional hazard analysis showed that the high I-CTP group had a higher risk for MACE (Hazard ratio [HR] 2.6, p=0.049) compared with the low I-CTP group after adjusting for confounding factors.

Conclusions

I-CTP was significantly associated with MACE, suggesting that I-CTP could be a reliable marker for clinical outcome in patients with ACS who underwent PCI.

Figure 1

Funding Acknowledgement

Type of funding source: None
Sex differences in health-related quality of life among acute myocardial infarction survivors: an inverse weighted propensity score analysis
Authors: Dondo T , Munyombwe T , Hall M , Hurdus B , Oliver G , Gale C.P
Published: November 2020

Background

Over 800,000 women in the UK are living with coronary heart disease, which is the main cause of acute myocardial infarction (AMI). Marked improvements have been noted in clinical outcomes following AMI due to improved use of evidence-based treatments. However, sex differences in outcomes following AMI persist, with limited evidence in the literature concerning patient reported outcomes such as health related quality of life (HRQoL).

Purpose

To investigate sex differences in HRQoL following AMI.

Methods

Data on HRQoL among 9,566 survivors of AMI were collected from 77 National Health Service hospitals in England between 1 November 2011 and 24 June 2015. HRQoL at time of hospitalisation with an AMI as well as at 1, 6 and 12 months post discharge were collected using the self-reported EuroQol five dimension questionnaire which contains a descriptive system (EQ-5D ranging from −0.5 “worse than death” to 1 “full health”) and a visual analogue scale (EQ-VAS ranging from 0 “worst imaginable health state” to 100 “best imaginable health state”). Multilevel regression modelling coupled with inverse probability weighting propensity score analysis was used to investigate longitudinal trajectories of sex differences in perceived HRQoL following AMI.

Results

Overall, there were 2,397 (25%) women in the study. HRQoL improved over time, however, women had a lower baseline HRQoL compared with men (EQ-VAS mean (SD) 59.8 (20.4) vs. 64.5 (20.9), and EQ-5D median (IQR) 0.73 (0.52 to 0.88) vs. 0.81 (0.62 to 1.00). Sex differences in HRQoL over time persisted, with women having a reduced HRQoL (EQ-VAS coefficient: −4.41, 95% CI: −5.16 to −3.66 and EQ-5D coefficient: −0.07, −0.08 to −0.06) and across the individual EQ-5D dimensions women were more likely to report problems with anxiety (odds ratio 2.03, 95% CI: 1.80 to 2.29), mobility (1.82, 1.58 to 2.09), self-care (1.75, 1.47 to 2.08), usual activities (1.70, 1.52 to 1.89) and pain (1.59, 1.45 to 1.75).

Conclusion

Although quality of life improves for AMI survivors, women have a lower baseline and worse recovery compared with men.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): British Heart Foundation, Wellcome Trust, Sir Henry Wellcome Postdoctoral Fellowship
Endothelial dysfunction and cardiovascular mortality in patients with acute coronary syndrome
Authors: Yoshii T , Matsuzawa T , Nakahashi H , Satou R , Akiyama E , Kimura Y , Okada K , Maejima N , Iwahashi N , Hibi K , Kosuge M , Ebina T , Kimura K , Tamura K
Published: November 2020

Background

Although the prognostic value of non-invasive endothelial function test has been reported in several populations including heart failure patients and angina pectoris patients, it is unknown in patients with acute coronary syndrome (ACS). Furthermore, the role of endothelial dysfunction in increased risk for specific causes of death has not been investigated.

Purpose

To study the relation between endothelial dysfunction and the risk of death in ACS patients, both overall and with regard to the main causes of death.

Method

Six hundred and ninety-two patients who were hospitalized for ACS from 2010 to 2014 were enrolled. Reactive hyoeremia index (RHI) was measured to assess endothelial function non-invasively in all patients using the peripheral arterial tonometry. RHI values below 1.67 were interpreted as signs of endothelial dysfunction in accordance with the manufacturer. Patients were followed up for a median of 6.5 years.

Result

A mean age (standard deviation) was 66 (12) years, and 542 patients (78%) were male. The patients in this study consist of 377 ST-elevation myocardial infarction (54%), and 263 non ST-elevation myocardial infarction (38%), and 52 unstable angina (8%). Endothelial dysfunction was detected in 276 patients (40%). During the follow-up period, 84 patients (12%) died (48 from cardiovascular disease, 36 from other causes). Patients with endothelial dysfunction had an increased risk of death (hazard ratio (HR) 1.83, 95% confidence interval (95% CI): 1.19–2.83, p=0.006) compared with those without endothelial dysfunction. Analyses for specific causes of death showed that patients with endothelial dysfunction had a 2.4-fold higher increased risk of cardiovascular death (HR: 2.44, 95% CI: 1.35 ro 4.59, p=0.003) after multivariate adjustment. However there was no significant relation between endothelial dysfunction and non-cardiovascular mortality (HR: 0.69, 95% CI: 0.34 to 1.36, p=0.29).

Conclusion

Endothelial dysfunction is strongly associated with an increased risk of cardiovascular mortality in ACS patients.

Figure 1

Funding Acknowledgement

Type of funding source: None
Haemorrhagic risk of oncology patients with myocardial infarction
Authors: Branco Mano T , Timoteo A.T , Aguiar Rosa S , Cruz Ferreira R
Published: November 2020

The approach of acute coronary syndrome (ACS) in oncology patients (pts) is challenging due to higher haemorrhagic risk.

Objectives and methods

Retrospective analysis of pts included in an ACS registry between October 2010 and September 2019 with cancer (active or diagnosed in <5 years). Aim: evaluate safety and efficacy of single vs dual antiplatelet therapy (DAPT), anticoagulation and revascularization strategy. Primary safety endpoint: major haemorrhagic events (MHE). Secondary efficacy endpoints: ischemic events, intra-hospital (IH) mortality; combined efficacy endpoint of IH mortality, reinfarction and ischemic stroke.

Results

934 pts (5%) of a total of 18845 pts with ACS had diagnosis of cancer. Compare to pts without malignancy, oncology pts were older, had more atrial fibrillation (AF), lower left ventricle ejection fraction (LVEF), underwent invasive coronary angiography (ICA) and angioplasty less often. Oncology pts had more events: MHE (2.9% vs 1.5%, p<0.001), mortality (5.8% vs 3.4%, p<0.001) and combined endpoint (7.4% vs 4.9%, p<0.001). Oncology population: pts with MHE (N=27) had more previous haemorrhagic events, AF, higher creatinine level, ST-Elevation Myocardial Infarction (STEMI), more use of anticoagulation, less use of DAPT or acetylsalicylic acid (ASA) and higher IHmortality. In multivariate analysis, previous haemorrhagic events, AF, STEMI and no ASA were independent predictors of MHE. Pts who reached combined endpoint (N=69) were older, had more renal impairment, thrombocytopenia, STEMI, Killip class > I, lower LVEF, less prescribe with antiplatelet therapy and neurohormonal therapy, less submitted to ICA and a trend to less angioplasty. In multivariate analysis, STEMI, Killip >I, creatinine >2mg/dL, thrombocytopenia, LVEF<40%, no ACEi therapy and no ICA were independent predictors of the combined endpoint (Table 1).

Conclusion

Oncology pts had worse prognosis than general population with ACS. MHE were mainly related to previous haemorrhagic event and AF, associated with anticoagulation strategy. On the other hand, IH mortality, reinfarction and ischaemic stroke were associated with lower use of antiplatelet and neurohormonal therapy and ICA.

Funding Acknowledgement

Type of funding source: None
Has the proportion of patients diagnosed with myocardial infarction that receives a 12 ECG in the prehospital setting in the UK changed over time?
Authors: Quinn T , Watkins A , Hampton C , Halter M , Weston C , Gale C.P , Gavalova L , Driscoll T , Davies G , Snooks H.A
Published: November 2020

Background

Two thirds of patients with Acute Myocardial Infarction (AMI) arrive at hospital in the UK by ambulance, usually staffed by paramedics who routinely carry out 12 lead ECGs for patients with suspected heart attack. However, recent research found that prehospital ECGs were missing for 40% of these patients, with better survival prospects in those who had received one.

Purpose

We are investigating reasons for non-administration of 12 lead ECG for patients diagnosed with AMI, in order to develop an intervention to improve practice. Firstly we explored whether the proportion of patients with AMI that receive a prehospital ECG has changed over time.

Methods

Interrogation of national UK national heart attack register (MINAP) database, extraction of data related to patients brought by ambulance by year.

Results

The cohort of patients diagnosed with AMI and taken to hospital by ambulance ranged from 32410 in 2005 to 60265 in 2017; the proportion with a prehospital ECG increased steadily across this period, from 51% to 78%, an average increase of 1.9% per annum.

Conclusions

Evidence based guidelines supporting the use of 12 lead ECG by ambulance paramedics may have contributed to improvements in care. However, 1 in 5 patients brought to hospital by ambulance still does not receive an ECG prior to arrival, which we know compromises their survival prospects. In order to optimise care we need to establish whether non-administration is a question of misdiagnosis, patient refusal or lack of availability of trained crews/equipment.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): British Heart Foundation