bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between body mass index and 1-year outcome after acute myocardial infarction
Authors: Kim D.W
Published: November 2020

Background

Beneficial effects of overweight and obesity on mortality after acute myocardial infarction (AMI) have been described as “Body Mass Index (BMI) paradox”. However, the effects of BMI is still on debate. We analyzed the association between BMI and 1-year major cardiocerebrovascular events (MACCE) after AMI.

Methods and findings

Among 13,104 AMI patients registered in an Institute of Health in Korea between November 2011 and December 2015, 10,568 patients who eligible for this study were classified into 3 groups according to BMI (Group I; <22 kg/m2, 22 ≤ Group II <26 kg/m2, Group III; ≥26 kg/m2). The primary end point was a composite of cardiac death (CD), myocardial infarction (MI), target vessel revascularization (TVR), and cerebrovascular events at 1 year. Over the median follow-up of 12 months, the composite of primary end point occurred more frequently in the Group I patients than in the Group III patients (primary endpoint: adjusted hazard ratio [aHR], 1.290; 95% confidence interval [CI] 1.024 to 1.625, p=0.031). Especially, cardiac death in MACCE components played a major role in this effect (aHR, 1.548; 95% confidence interval [CI] 1.128 to 2.124, p=0.007).

Conclusions Higher BMI appeared to be good prognostic factor on 1-year MACCE after AMI. This result suggests that higher BMI or obesity might confer a protective advantage over the life-quality after AMI.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research of Korea Centers for Disease Control and Prevention and the Korea Health Technology R&D Project, Ministry of Health & Welfare (HI13C1527), Republic of Korea.
Comparison of prasugrel and ticagrelor for patient with acute coronary syndrome: a systematic review and meta-analysis
Authors: Fong L.C.W , Lee N , Yan A.T , Ng M.Y
Published: November 2020

Background

Prasugrel and ticagrelor are both effective anti-platelet drugs for patients with acute coronary syndrome. However, there has been limited data on the direct comparison of prasugrel and ticagrelor until the recent ISAR-REACT 5 trial.

Purpose

To compare the efficacy of prasugrel and ticagrelor in patients with acute coronary syndrome with respect to the primary composite endpoint of myocardial infarction (MI), stroke or cardiac cardiovascular death, and secondary endpoints including MI, stroke, cardiovascular death, major bleeding (Bleeding Academic Research Consortium (BARC) type 2 or above), and stent thrombosis within 1 year.

Methods

Meta-analysis was performed on randomised controlled trials (RCT) up to December 2019 that randomised patients with acute coronary syndrome to either prasugrel or ticagrelor. RCTs were identified from Medline, Embase and ClinicalTrials.gov using Cochrane library CENTRAL by 2 independent reviewers with “prasugrel” and “ticagrelor” as search terms. Effect estimates with confidence intervals were generated using the random effects model by extracting outcome data from the RCTs to compare the primary and secondary clinical outcomes. Cochrane risk-of-bias tool for randomised trials (Ver 2.0) was used for assessment of all eligible RCTs.

Results

411 reports were screened, and we identified 11 eligible RCTs with 6098 patients randomised to prasugrel (n=3050) or ticagrelor (n=3048). The included trials had a follow up period ranging from 1 day to 1 year. 330 events on the prasugrel arm and 408 events on the ticagrelor arm were recorded. There were some concerns over the integrity of allocation concealment over 7 trials otherwise risk of other bias was minimal. Patients had a mean age of 61±4 (76% male; 50% with ST elevation MI; 35% with non-ST elevation MI; 15% with unstable angina; 25% with diabetes mellitus; 64% with hypertension; 51% with hyperlipidaemia; 42% smokers). There was no significant difference in risk between the prasugrel group and the ticagrelor group on the primary composite endpoint (Figure 1) (Risk Ratio (RR)=1.17; 95% CI=0.97–1.41; p=0.10, I2=0%). There was no significant difference between the use of prasugrel and ticagrelor with respect to MI (RR=1.24; 95% CI=0.81–1.90; p=0.31); stroke (RR=1.05; 95% CI=0.66–1.67; p=0.84); cardiovascular death (RR=1.01; 95% CI=0.75–1.36; p=0.95); BARC type 2 or above bleeding (RR=1.17; 95% CI =0.90–1.54; p=0.24); stent thrombosis (RR=1.58; 95% CI =0.90–2.76; p=0.11).

Conclusion

Compared with ticagrelor, prasugrel did not reduce the primary composite endpoint of MI, stroke and cardiovascular death within 1 year. There was also no significant difference in the risk of MI, stroke, cardiovascular death, major bleeding and stent thrombosis respectively.

Figure 1. Primary Objective

Funding Acknowledgement

Type of funding source: None
Long-term adherence to low-dose aspirin therapy for cardiovascular prevention in routine clinical practice in United Kingdom and Germany
Authors: Vora P , Soriano-Gabarro M , Russel B , Morgan Stewart H
Published: November 2020

Background

Low-dose aspirin is effective in the prevention of ischemic vascular events and studies have shown a preventative effect on colorectal cancer (CRC). However, adherence to therapy is likely an important factor for these benefits to be seen and non-adherence is associated with sub-optimal outcomes.

Purpose

To assess the long-term adherence to low-dose aspirin therapy in the primary and secondary cardiovascular (CVD) prevention population

Methods

This retrospective cohort study used data from United Kingdom (UK) – The Health Improvement Network Database and Germany (DE) – IQVIA Disease Analyzer and analyzed using an adaptation of Observational Health Data Sciences and Informatics (OHDSI) ATLAS Tool. Patients 18 years or older, with at least two prescriptions of low-dose aspirin (75–100mg) within the first year of index date during the study period between 2007 and 2018, and with at least 12 months of observation before and after the index date were included in the study. The patients with a CVD diagnosis or a CABG/PCI procedure before the index date or a prescription of dual antiplatelet at index date were classified as secondary CVD prevention. The remaining patients were classified as potential primary CVD prevention. The index date was first prescription of low-dose aspirin. Adherence was calculated using medication possession ratio (MPR) which is number of days of medication supplied within the refill interval divided by number of days in the refill interval. Long term adherence was divided in three categories namely patients with ≤2 years, 2-≤5 years, and 5-≤10 years of follow-up.

Results

The total number of patients receiving low-dose aspirin was 327,806 (183,089 in UK and 144,717 in DE with up to 10 years of follow-up). A total of 112,887 and 101,704 received low-dose aspirin for secondary CVD prevention; 70,202 and 43,013 potentially for primary CVD prevention in UK and DE, respectively. Median adherence to low-dose aspirin in UK and DE for patients with ≤2 years of follow-up was 88% and 80% for secondary CVD prevention, respectively; 84% and 74% for 2-≤5 years; and 75% and 59% for 5-≤10 years, respectively. Median adherence to low-dose aspirin in UK and DE for patients with ≤2 years was 76% and 75% for potential primary CVD prevention; 65% and 66% for 2-≤5 years; 49% and 49% for 5-≤10 years, respectively (Figure).

Conclusion

The long-term adherence to low dose aspirin was quite high with more than half the patients being adherent to their treatment. Overall, the adherence was higher in secondary compared to primary CVD prevention. The estimates for adherence might be underestimated due to potential over the counter use of low-dose aspirin.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Bayer AG
Prevalence of myocardial viability and ischemic burden in chronic total occluded coronary artery disease
Authors: Yang X , Tian J.F , Zhang L.J , Dong W , Li J.N , Li J.H , Han Y , Zuo H.J , He Y , Mi H.Z , Song X.T
Published: November 2020

Aims

We assessed the viable myocardium status and investigated the relationship between collaterals with the ischemia burden and myocardial viability utilizing cardiac magnetic resonance imaging (CMR) and adenosine stress single-photon emission computed tomography (SPECT).

Methods and results

150 consecutive patients with at least one native CTO artery, as confirmed by coronary arteriography or coronary CT angiography, were prospectively recruited. SPECT examination was accepted by only 50 patients while declined by the other 100 patients for reasons such as financial problems. Of all segments in the 173 CTO artery territories, only 10.4% exhibited transmural myocardial infarction and 60.2% showed no late gadolinium enhancement. Among 50 patients who completed SPECT examination, 36 patients showed inducible perfusion defect in CTO territory, and the proportion of the ischemic area of 42% patients was over 10%.

Conclusion

Most patients with CTO had different degrees of myocardial infarction detected by CMR, but only a minority of them showed transmural infarction and cardiac function in patients with transmural infarction declined compared to those without transmural infarction. Approximately half of CTO patients exhibited inducible ischemia in CTO territory. Based on this, a large proportion of patients potentially benefit from CTO-PCI.

Figure 1. Relationship between WMSI, LVE

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Beijing Municipal Education Commission Science and Technology Plan for 2020, Capital Health Development Research Project (no. 2018-2-2063)
Impact of hinge motion on stent edge restenosis after new generation drug-eluting-stent implantation in RCA
Authors: Jimba T , Ikutomi M , Nishijyo D , Yamasaki M , Shindou A , Mochida K , Yanagisawa T , Sato T , Matsushita M , Onishi S , Yamasaki M
Published: November 2020

Background

Edge restenosis still occurs after stent implantation, even by using new generation drug-eluting stents (DES) considered to have favorable biomechanical properties. Mechanical stress imposed on the stent edge are thought to be aggravated by hinge motion at a point between the stented and unstented segments, inducing chronic local inflammation and neointimal overgrowth.

Purpose

The aim of this study was to investigate the association between the development of edge restenosis and hinge motion in right coronary artery (RCA) where the excessive vessel movement is commonly observed.

Methods

Among consecutive 650 lesions in RCA where new generation DESs were implanted between 2009 and 2019, 427 serial lesions with sets of angiographies at baseline and follow-up (6–18 month) were included. In addition to conventional quantitative angiography analysis, hinge angle at stent edges was measured (Fig. 1). All the appropriate data for intravascular imaging were analyzed for both stent edges and reference segments.

Results

Binary restenosis occurred in 43 lesions, and 39 of them were referred to re-intervention. Fifty five percent of them were related to stent edges (15 at proximal and 9 at distal edges). Classical risk factors including diabetes and hemodialysis were more prevalent in the restenosis group (p<0.05). Hinge angle was statistically larger in edge restenosis group than body restenosis or no restenosis group (17.3° vs 11.6° vs 10.6°, p<0.001, Fig. 2). In per-edge analysis, hinge angle, dissection and residual plaque ratio were the independent predictors for binary restenosis (Table 1) with the optimal cut-off value of hinge angle 11.5°. The coexistence of excessive hinge angle and residual plaque burden had an amplified effect on the angiographic stenotic progression at stent edge (p for interaction <0.001) and the incidents of binary restenosis (16.7% vs 1.7% p<0.01, Figs. 3,4).

Conclusion

Substantial stress determined by angulation at the stent edge and its interaction with residual plaque can be considered as one of the plausible mechanisms for edge restenosis. For tortuous RCA lesions, it would be important to decide the stent-landing zone for minimizing hinge motion and optimize the future stent design.

Funding Acknowledgement

Type of funding source: None
Hybrid coronary revascularization with endoscopic closed-chest arterial coronary bypass technique (endo-CABG)
Authors: Claessens J , Van Genechten S , Kaya A , Yilmaz A
Published: November 2020

Introduction

Treatment of three-vessel coronary disease in minimally invasive manner could be complex in some cases. Percutaneous coronary intervention (PCI) with drug-eluting stents (DES) gives good patency rates which outlive vein grafts. The hybrid approach, combination of PCI with minimally invasive endoscopic coronary artery bypass graft (endo-CABG), might be a valuable option for treatment of multivessel coronary disease. Hereby we describe our series of patients undergoing arterial revascularization of the anterior and/or lateral wall combined with PCI of the right coronary artery or a marginal branch.

Methods

From March 2013 until December 2019, 208 patients (82.2% males, mean age: 66.69±10.44 years) underwent hybrid coronary revascularization for multivessel disease. Patients with multivessel disease suitable for hybrid approach were accepted at the heart team. All patients received total arterial revascularisation by endo-CABG. The PCI was prior or after the endo-CABG. There was no discontinuation of dual platelet therapy. Uni or bilateral internal mammary artery (IMA) harvesting was performed through three 5mm endoscopic ports in the 2nd, 3rd and 4th intercostal space. Cardiopulmonary bypass was established using a minimally invasive extracorporeal circulation (MiECC) with groin cannulation. Transthoracic aortic cross-clamping was followed by antegrade administration of a single shot cold mixed blood cardioplegia. A utility port of three centimeter was used for direct vision anastomosis.

Results

The procedure was successful in all patients, requiring no conversion to full sternotomy. Mean cross-clamping and cardiopulmonary bypass times were 44.38±28.33 and 91.75±37.97 minutes, respectively, with a mean of 2.1±0.91 bypasses for each patient. All patients received total arterial revascularization. The mean ICU and hospital length of stay were 62.5±39.74 hours and 8.80±4.64 days, respectively. Average postoperative blood loss over 24 hours was 555.20±859.19 mL. There were 8 re-interventions on the target vessels (3.8%) and 2 patients suffered from a stroke (1%). The 30-day mortality rate was 0.5%.

Conclusion

Minimally invasive hybrid arterial coronary revascularization is a safe and valuable alternative to coronary artery bypass grafting in many patients with multivessel coronary artery disease. The endo-CABG is a safe and feasible technique without compromising operative morbidity and providing good postoperative results.

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Jessa Hospital
Immediate versus staged revascularisation in multivessel coronary disease: an updated meta-analysis
Authors: Von Renteln F , Hassan S , Szummer K , Edfors R , Venetsanos D , Kober L , Braunschweig F , Lewinter C
Published: November 2020

Background

Percutaneous coronary interventions (PCIs) are often aimed at the culprit vessel in acute coronary syndromes (ACSs) followed by revascularisation of other stenoses later in the index hospitalisation or shortly after discharge. PCI delay of non-culprit coronary vessels stenoses is supported by lower contrast fluid use and thrombocyte aggregation. Distinct coronary interventions increase the risk of both non- and coronary artery complications, e.g. acute abdominal and periphery artery bleeding, suggesting undertaking all PCIs at the same time.

Purpose

To assess the effect on mortality and re-myocardial infarction (MI) of immediate versus staged revascularisation in multivessel coronary disease, with the latter constrained to initial PCI of the culprit coronary vessel.

Methods

The syntax of “randomised controlled trial (RCT) & acute coronary syndrome & complete revascularisation” was undertaken in PubMed.

Clinical characteristics were gathered at the index hospitalisation. The intervention scenario was acute coronary syndrome or not.

Meta-analyses calculated relative risk (RR) reductions on outcomes of 1) mortality and 2) re-MI. Meta-regression assessed linear difference between interventional treatment benefits and baseline characteristics.

Results

A total of 148 studies was found. Of those, 8 was found eligible for further analyses and their baseline characteristics are shown in Table 1.

Comparison of immediate versus staged revascularisation on mortality was nonsignificant (RR, 1.19; 95% CI: 0.78–1.81, p=0.43) (Figure 1). The impact of Immediate vs staged revascularisation on re-MI was also nonsignificant (RR, 0.83; 95% CI: 0.44–1.55, p=0.56). Meta-regression found no associations between the outcomes and study characteristics (not shown).

Conclusion

The intervention of immediate compared to staged revascularisation assessed on outcomes of all-cause mortality and re-MI were nonsignificant.

Figure 1

Funding Acknowledgement

Type of funding source: None
Is there value in prescribing colchicine in coronary artery disease for secondary prevention: a meta-analysis of over 5,000 patients
Authors: Sunjaya A.F , Sunjaya A.P
Published: November 2020

Introduction

Coronary Artery Disease (CAD) is the single greatest cause of mortality and loss of disability adjusted life years (DALYs) worldwide. Inflammation plays a central role in the pathogenesis of atherosclerosis, with numerous evidence from prospective studies indicating that increasing C-reactive protein levels (hs-CRP) are independently associated with increasing risk of cardiovascular events. Colchicine, is an inexpensive, potent anti-inflammatory drug considered as a staple therapy for gout. Recent studies have shown that colchicine use may prove to be useful in the prevention of cardiovascular events.

Purpose

In patients with coronary artery disease (CAD) does administration of low dose colchicine lead to reduced all-cause mortality, cardiovascular risk and morbidity.

Methods

A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include all-cause mortality, cardiovascular events, CRP levels and prevalence of CRP levels less than 2.0 mg/L. Data synthesis and analysis was done using RevMan 5.3 using a random effects model.

Results

A total of 5 randomized controlled trials, representing 5,430 patients were included in this meta-analysis. Three trials administered colchicine 1 mg/day while the rest were assigned colchicine. 5 mg/day. Administration of colchicine in CAD patients was found to reduce all-cause mortality (RR=0.66, 95% CI: 0.30 to 1.46, p=0.31) and major adverse cardiovascular events (MACE) (RR=0.61, 95% CI: 0.25 to 1.47, p=0.27), although results were non-significant. Reduced CRP levels (Mean difference = −0.88, 95% CI: −1.76 to 0.01, p=0.05) compared to control group as well as a higher prevalence of patients with CRP levels <2.0 mg/L were found (RR=2.27, 95% CI: 0.45 to 11.33, p=0.32), although results were non-significant.

Discussion

Few studies are available evaluating the benefits of low dose colchicine in CAD patients. The beneficial effects of colchicine has been proposed due to its ability to inhibit neutrophil chemotaxis which may reduce the risk of plaque instability. The use of colchicine for secondary prevention of CAD will require long-term use, which will require the need for preparations that address its intolerance (mostly gastrointestinal) to prevent early discontinuation of the medication.

Conclusion

There's limited evidence on the benefit of low dose colchicine in CAD patients. Further large scale randomized-controlled trials are needed, and its dose-response relationship ascertained before consideration of its use could be given in CAD patients.

Funding Acknowledgement

Type of funding source: None
Association of circulating proprotein convertase subtilisin/kexin type 9 concentration with prothrombin time in patients with chest pain
Authors: Peng J , Li J.J
Published: November 2020

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has multiple roles in the development and progression of atherosclerosis. Recent studies have indicated an association of PCSK9 with thrombotic process.

Purpose

We aimed to examine whether there exists a relationship between plasma PCSK9 concentration and the most commonly coagulation parameters including prothrombin time (PT) and activated partial thromboplastin time (APTT).

Methods

A total of 2293 consecutive patients with angina-like chest pain who had no treatment of lipid-lowering drugs were enrolled in this study. The baseline clinical and laboratory data were collected. PT and APTT tests were performed. Circulating PCSK9 concentrations were determined by ELISA and classified into three subgroups according to their levels of PCSK9 tertiles. The relation of PCSK9 concentration to PT or APTT were analyzed.

Results

Firstly, we found that the patients with high PCSK9 levels trended to have lower PT and APTT (p<0.0001, p=0.003) according to results of PCSK9 tertiles. Then, pearson correlation analysis showed that log-transformed PCSK9 concentration was negatively correlated with PT (r=−0.194, p<0.0001) and was significantly but weakly related with APTT (r=−0.075, p<0.0001). The stepwise multivariable regression analysis revealed that PCSK9 was independently related with PT after adjusting traditional atherosclerotic risk factors and coagulation parameters (β=−0.137, p<0.0001; β=−0.121, p<0.0001, respectively).

Conclusion

Circulating PCSK9 concentration was independently negative associated with PT, suggesting a potential link between PCSK9 and PT that may be involved in atherogenesis and atherothrombosis.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences
Intracoronary acetylcholine spasm testing: differences in epicardial coronary artery response between smooth and atherosclerotic coronary arteries
Authors: Gollwitzer R , Martinez Pereyra V , Seitz A , Bekeredjian R , Sechtem U , Ong P
Published: November 2020

Background

Coronary artery spasm is an established cause for angina pectoris. Epicardial coronary spasm may occur in patients with obstructed as well as unobstructed coronary arteries. Previous studies have suggested that epicardial plaque/atherosclerosis is a prerequisite for the development of epicardial spasm. The aim of the present study was to compare the results of intracoronary acetylcholine (ACh) testing in patients with signs and symptoms of myocardial ischemia with completely smooth versus atherosclerotic yet unobstructed epicardial arteries.

Methods

Between 2008 and 2016 a total number of 617 patients with signs and symptoms of myocardial ischemia yet unobstructed epicardial arteries (<50% epicardial stenosis) was included in the present study (mean age 61±11, 61% female). All patients underwent invasive diagnostic coronary angiography followed by intracoronary ACh testing according to a standardized protocol. The ACh-test was considered “positive” in the presence of (a) angina, ischemic ECG shifts during the test and ≥75% focal or diffuse coronary diameter reduction (“epicardial coronary artery spasm”) or (b) ischemic ST-shifts and angina in the absence of epicardial spasm (“microvascular spasm”). All angiograms were assessed regarding any visible epicardial plaque/atherosclerosis in a blinded fashion and patients were categorized into those with completely smooth versus those with atherosclerotic coronary arteries. The analysis included 179 patients (29%) with epicardial spasm and 172 patients with microvascular spasm (28%). The remaining 266 patients (43%) had an uneventful or an inconclusive ACh-test result.

Results

There were 389 patients (63%) with completely smooth epicardial arteries. The remaining 228 patients (37%) had non-obstructive epicardial plaques <50%. Patients with smooth arteries developed epicardial spasm in 24%, microvascular spasm in 32% and a negative/inconclusive test result in 44% of cases. Patients with atherosclerotic arteries developed epicardial spasm in 38%, microvascular spasm in 21% and an inconclusive/negative test result in 41% of cases. On univariate analysis the presence of epicardial atherosclerosis was associated with epicardial spasm (p=0.006) whereas this was not the case for microvascular spasm (p=0.094). Multivariate analysis revealed the presence of epicardial atherosclerosis (OR 1.921, CI 1.285–2.871, p=0.001) as well as female sex (OR 1.526, CI 1.024–2.274, p=0.038) as independent predictors for epicardial spasm.

Conclusion

In patients with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries the presence of epicardial atherosclerosis is an independent predictor for the occurrence of epicardial spasm but not microvascular spasm on acetylcholine testing.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Robert-Bosch-Stiftung, Berthold-Leibinger-Stiftung
Prognostic impact of right ventricular overload in patients with acute coronary syndrome
Authors: Sato T , Ogihara Y , Kurita T , Mizutani H , Takasaki A , Moriwaki K , Tanimura M , Sawai T , Ito M , Dohi K
Published: November 2020

Background

Right ventricular (RV) overload is associated with adverse outcome in patients with chronic heart failure. However, its prognostic value in acute coronary syndrome (ACS) patients remains unknown.

Purpose

The purpose of this study was to investigate the prevalence and prognostic impact of right ventricular overload in ACS patients.

Methods

We studied 2797 ACS patients from Mie ACS registry, a prospective and multicenter registry in Japan. They were divided into 4 subgroups according to the severity of RV overload and the extent of Left Ventricle Ejection Fraction (LVEF) assessed by echocardiography before hospital discharge. High RV overload was defined as trans-tricuspid pressure gradient (TRPG) ≥40mmHg and preserved LVEF was defined as ≥50%. The primary outcome was defined as 2-year all-cause mortality. Median follow up duration was 730 days (1–2215 days).

Results

High RV overload was detected in 76 patients (2.7%). In basic patients characteristics, high RV overload patients were significantly older and higher killip classification than low RV overload patients (P<0.01, respectively). Laboratory data in high RV overload patients showed lower hemoglobin level and higher serum creatinine level than those in low RV overload patients (P<0.01, respectively).

Echocardiographic findings in high RV overload represented lower LVEF, higher rate of moderate or severe mitral regurgitation and left atrial enlargement than those in low RV overload patients (P<0.01, respectively).

During the follow-up periods (median 730 days), 260 (9.3%) patients experienced all-cause death. Multivariate cox hazard regression analysis for all-cause mortality demonstrated that high RV overload was an independent poor prognostic factor in the entire study population. Among patients with preserved LVEF, high RV overload resulted in an increased risk of all-cause mortality compared to low RV overload (P<0.0001).

Conclusion

In ACS patients, high RV overload strongly contributes to worsening of prognosis regardless of the extent of LVEF.

Kaplan-Meier survival curve

Funding Acknowledgement

Type of funding source: None
Platelets reactivity as a predictor of the extent of myocardial infarct damage and poor outcomes in STEMI patients undergoing primary PCI
Authors: Massalha E , Goitein O , Fardman A , Grupper A , Mazin I , Natanzon S , Beigel R , Matetsky S
Published: November 2020

Background

Despite optimized management of STEMI patients including primary PCI (PPCI) and use of novel anti-platelet agents, a substantial proportion still display a large infarct size and microvascular damage. The extent of MI and presence of microvascular damage as determined by cardiac MRI (CMR) are considered as powerful prognostic factors in predicting both early and long-term prognosis in those patients. Platelets reactivity has been implicated in pathogenesis of microvascular and subsequent myocardial damage including distal embolization, microvascular platelets plugging and inflammation.

Methods

We prospectively evaluated 105 consecutive STEMI patients, with no prior MI, who underwent PPCI. Patients underwent 2D-echocardiography within 48 hours of admission and cardiac MRI (CMR) 5±1 day post admission. All Patients were treated with dual antiplatelet agents and blood sample were analyzed for platelets reactivity (PA) at 72 hours post admission, using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists. Aspirin hypo-responsiveness was defined as AA-PA≥30%, and P2Y12 non-responsiveness as ADP-PA ≥50%. CMR was evaluated for late gadolinium enhancement (LGE) and microvascular obstruction (MVO), which reflects MI size and microvascular damage respectively. Both parameters were quantified as % of the LV mass. Major adverse cardiac events (MACE) were defined as the composite of death, MI, stroke, urgent revascularization and hospitalization due to either heart failure or bleeding during the first year post AMI.

Results

AA and ADP inhibition were 22±17, and 34±16 respectively. Aspirin hypo-responsiveness was associated with significantly higher extent of LGE (p=0.04) and MVO (p=0.003). A multivariate logistic regression analysis revealed that AA-PA hypo-responsiveness is an independent predictor of both MI size as reflected in LGE (OR 3.87; 95% CI: 1.47–10.5, p=0.031), and higher extent of microvascular damage as reflected by MVO% of LV mass (OR 3.6; 95% CI: 1.15–10.3, p=0.027). Patients with aspirin hypo-responsiveness were significantly more likely to sustain MACE (36% vs 12%, HR 4.13, 95% CI: 1.52–10.2, p=0.003). As opposed to AA related platelets reactivity, no significant correlation was demonstrated between ADP induced platelets reactivity and either measures of MVO or LGE.

Conclusions

In patients undergoing PPCI for STEMI, platelets reactivity in response to AA is an independent predictor of the extent of both myocardial and microvascular damage. Aspirin hypo-responsiveness is associated with higher rate of adverse events during 1-year follow-up.

Funding Acknowledgement

Type of funding source: None
Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome-dependent pyroptosis
Authors: Chen A , Chen Z.W , Qian J.Y , Ge J.B
Published: November 2020

Background

Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI) after coronary interventions, bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified.

Purpose

To determine whether NLRP3 inflammasome contributes to CME-induced cardiac injury and to investigate the effect of statin therapy on CME.

Methods

In vivo study, CME models were established in C57BL/6J mice by injecting 500,000 polyethylene microspheres (diameter 9 μm) into the left ventricle chamber with the occlusion of the ascending aorta. Mice with CME were treated with 40 mg/kg/d rosuvastatin orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Cardiac function was evaluated by echocardiography. Cardiac histological analysis was performed. The NLRP3 inflammasome and pyroptosis-related genes and proteins were detected. Cardiac injury was evaluated by Heidenhain's iron hematoxylin stain and serum lactate dehydrogenase (LDH) measurement. Cardiac reactive oxygen species (ROS) production and mitochondrial morphology were also determined. In vitro study, H9c2 myoblasts, stimulated with the classic NLRP3 inflammasome activators lipopolysaccharide (LPS) plus nigericin (Nig), were used to reveal underlying mechanisms of the rosuvastatin's effects.

Results

The expression of NLRP3, caspase-1 and interleukin-1β (IL-1β) were all increased and peaking at 3 days after CME. Mice treated with MCC950 and rosuvastatin showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum LDH level. Mechanistically, rosuvastatin decreased the expression of NLRP3, caspase-1, IL-1β and the pyroptosis executor Gasdermin D. Furthermore, reduced ROS level and alleviated mitochondrial damage were observed in rosuvastatin-treated mice. In vitro study, rosuvastatin effectively inhibited the activation of NLRP3 inflammasome induced by LPS and Nig in H9c2 cells, as evidenced by decreased expression of NLRP3, caspase-1, IL-1β and Gasdermin D. Flow cytometry revealed that rosuvastatin rescued LPS and Nig-induced caspase-1 activation from 22.2±1.6% to 4.09±0.85%. Meanwhile, the pyroptosis was also suppressed by rosuvastatin, indicated by the increased cell viability, decreased LDH and propidium iodide uptake. Similarly, rosuvastatin also reduced the level of ROS generation in vitro.

Conclusions

NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of rosuvastatin in CME, which is associated with regulating mitochondrial ROS.

Funding Acknowledgement

Type of funding source: None
Investigating sodium-glucose co-transporters 1 (SGLT1) in myocardium and its role in hyperglycaemia ischaemia-reperfusion injury
Authors: Almalki A , Harding I , Jasem H , Arjun S , Yellon D , Bell R
Published: November 2020

Background

Hyperglycaemia is a common finding in diabetic and non-diabetic patients presenting with ACS, and is a powerful predictor of prognosis and mortality. The role of hyperglycaemia in ischemia-reperfusion injury (IRI) is not fully understood, and whether the Sodium Glucose co-Transporter 1 (SGLT1) plays a role in infarct augmentation, before and/or after reperfusion, remains to be elucidated. However, diabetes clinical trials have shown SGLT inhibition improves cardiovascular outcomes, yet the mechanism is not fully understood.

Purpose

(1) Characterise the expression of SGLT1 in the myocardium, (2) determine the role of high glucose during IRI, (3) whether SGLT1 is involved in a glucotoxicity injury during IRI, and (4) whether inhibiting SGLT1 with an SGLT inhibitor may reduce infarct size.

Methods

RT-PCR and in-situ hybridization (RNAScope) techniques were used to detect SGLT1 mRNA expression in Sprague-Dawley whole myocardium and isolated primary cardiomyocytes. An Ex-vivo Langendorff ischemia-reperfusion perfusion model was used to study the effect of high glucose (22mmol) on the myocardium at reperfusion compared to normoglycaemia (11mmol). The mixed SGLT1&2 inhibitor, Phlorizin was introduced following ischaemia, at reperfusion and its effect on infarct size measured using triphenyltetrazolium chloride (TTC) staining.

Results

RT-PCR found SGLT1 mRNA is expressed in whole myocardium and in individual cardiac chambers. SGLT1 expression was not detected in isolated cardiomyocyte but it is detected in the non-cardiomyocyte population. Cardiomyocytes were found to express mRNA SGLT1 if incubated overnight. RNAscope detected SGLT1 mRNA within intact myocardium: not in the cardiomyocyte, but rather in a perivascular distribution. Importantly, hyperglycaemia (22mmol) at reperfusion increased infarct size (51.80±3.52% vs. 40.80±2.89%; p-value: 0.026) compared to normoglycaemia, and the mixed SGLT inhibitor, Phlorizin, significantly attenuated infarct size (from 64.7±4.2%to 36.6±5.8%; p-value<0.01) when given at reperfusion.

Conclusion

We have shown that SGLT1 is present in the myocardium, but not expressed in cardiomyocytes. The cell type is yet to be determined, but the distribution of SGLT1 is perivascular. Hyperglycaemia appears augment myocardial infarction and inhibition of SGLT1&2 attenuates this increase. We suspect SGLT1 may plays a role in exacerbating the injurious effect of glucotoxicity during ischemia-reperfusion.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): British Heart Foundation
Left atrial strain is associated with left ventricular remodeling in patients with ST-elevation myocardial infarction
Authors: Legallois D , Hodzic A , Milliez P , Manrique A , Saloux E , Beygui F
Published: November 2020

Background/Introduction

Left ventricular remodeling (LVR) remains common and is associated with outcomes in patients with ST-elevation myocardial infarction (STEMI). Left atrial (LA) volume has been described as a predictor of outcomes in the latter population.

Purpose

To investigate the association between LA mechanical function using speckle tracking imaging and LVR at follow-up in STEMI patients.

Methods

Baseline 3D transthoracic echocardiograms were performed in 121 STEMI patients. LA global longitudinal strain was reported separately for the reservoir (LASr), conduit (LAScd), and contraction (LASct) phases. Follow-up echocardiograms were performed at 6 months.

Results

Mean age was 58.3±12.5 years and 98 (81%) were men. Baseline left ventricular ejection fraction (LVEF) was 46.8% [41.0, 52.9] and significantly improved to 52.1% [45.8, 57.0] at follow-up, (p<0.001). A lower LASct was associated with a significant dilation of left ventricle at follow-up (%end-diastolic volume increase: −1.9% [−11.0, 15.2] in the two higher LASct tertiles group vs. 19.2% [5.0, 34.3] in the lower LASct tertile group, p=0.001). A higher %end-systolic volume increase at follow-up was associated with lower LASct as well: 12.6% [−16.2, 39.8] in the lower LASct group vs. −6.8% [−23.6, 14.4] in the two higher LASct tertiles group (p=0.004). Regarding LVEF, a low LVEF at follow-up was associated with the worst tertile of all LA strains (LASr, p=0.002; LAScd, p=0.01 and LASct, p=0.01).

Conclusion(s)

The three components of baseline LA strain were associated with LVEF at follow-up in patients with STEMI. Some of these components were also significantly associated with lower LVEF at baseline or predictive of a significant increase in left ventricular volumes during follow-up, indicating LVR.

Funding Acknowledgement

Type of funding source: None
T1 mapping of the remote non-infarct myocardium for predicting adverse left ventricular remodeling following STEMI
Authors: Lorenzatti D , Vega J , Perea R.J , Prat S , Doltra A , De Caralt T , Lopez T , De Diego O , Ortiz Perez J.T
Published: November 2020

Background

Adverse Left Ventricular (LV) remodeling (ALVR) following ST-segment Elevation Myocardial Infarction (STEMI) is the result of numerous mechanical, neurohormonal, micro and macrovascular factors, and remains a major clinical problem. Cardiac Magnetic Resonance (CMR) is a multimodality technique that provides comprehensive functional and tissue characterization of infarcted and non-infarcted myocardium. Whether changes in the extracellular matrix in the remote myocardium in patients following a STEMI are associated with adverse LV remodeling has been a topic of debate.

Aim

We explored the additive value of native T1 variation (ΔnT1) and derived-extracellular volume (ECV) fraction in the remote non-infarcted myocardium as predictors of adverse LV remodeling following STEMI.

Methods

A total of 99 subjects (83% male) with their first mechanically reperfused STEMI underwent CMR within 2 weeks and at 6 months, including T1 mapping prior and 15 to 20 minutes following a bolus of gadolinium (0.2 mmol/kg), with a MOLLI sequence. ECV and nT1 values were computed by averaging co-registered ROIs in three distinct segments in the remote non-infarcted myocardium.

Results

Baseline nT1 but not ECV correlated with infarct size (r=0.349, P<0.001 and r=0.162, P=0.096 respectively). In addition, ΔnT1 but not ΔECV correlated with an increase in LV end-diastolic volume index (LVEDVi) (r=0.268, P<0.01 and r=0.113, P=0.285).

ALVR, defined as Δ>20% inLVEDVi, occurred in 21 cases, despite optimal medical therapy. Subjects with ALVR showed greater ΔnT1 (13.2±44.1 vs −5.2±30.2 ms, P<0.05) but no significant differences in ΔECV (1.27±2.77 vs 0.72±2.45%, P=0.401). Also, subjects with ALVR were more likely hypertensive (67 vs 33%, P<0.05), had more segments with microvascular obstruction (2.1±2.2 vs 0.8±1.7, P<0.01) and lower baseline EF (39.8±8.8 vs 44.6±9.6%, P<0.05). Infarct size was not significantly larger in ALVR subjects (20.7±13.4 vs 17.5±13.0% LV mass, P=0.322). A multivariate analysis including all these factors, showed the extent of microvascular obstruction (ExpoB: 1.35 [1.05–1.73], P=0.019) and remote ΔnT1 (ExpoB: 1.02 [1.00–1.03], P=0.026) to be the independent predictors of ALVR.

Conclusions

The nT1 variation in remote non-infarcted myocardium and the extent of microvascular obstruction are superior to ECV changes and infarct size in predicting ALVR following STEMI.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fundaciό La Maratό TV3 2015 30 31 32. Fondos FEDER
Long-year follow-up of acute myocardial infarction with preserved initial LVEF: prognostic impact of progressively reduced LVEF
Authors: Yoshioka G , Watanabe N , Shibata Y , Node K
Published: November 2020

Background

Severely reduced left ventricular ejection fraction (LVEF ≤35%) is commonly seen in approximately 5% of the myocardial infarction (MI) survivors in its acute-phase, which is recognized as a risk factor of post-MI cardiac death. However, clinical incidence and risk factor of the progressively reduced LVEF in the chronic-phase after MI has not been clarified.

Purpose

To evaluate clinical incidence and risk factor of the progressively reduced LVEF in the chronic-phase after MI by serial echocardiography.

Method

We evaluated 1144 consecutive patients with acute MI with preserved LVEF (≥50%) in acute-phase. Primary outcome was severely reduced LVEF (<35%) in the chronic-pahse. We analyzed the predictive factor using multivariate analysis.

Result

During follow-up (median:1097 days), severely reduced LVEF newly developed in 8.6% of AMI survivors. Kaplan-meier curve is shown in the Figure. Multivariate analysis showed that men, eGFR <30, AMI of LAD and absence of renin-angiotensin system blocking drugs was an independent predictor of severely reduced LVEF.

Conclusions

Progressively reduced LVEF during chronic-phase occurred 8.6% in acute MI survivors with preserved initial LVEF. Especially patients with these risk factors, careful long-term follow-up after MI should be needed to identify possible candidate for the implantable cardioverter-defibrillator.

Figure 1

Funding Acknowledgement

Type of funding source: None
The mechanism of supply-demand imbalance and clinical outcomes in patients with type 2 myocardial infarction
Authors: Bularga A , Anand A , Strachan F.E , Lee K.K , Stewart S , Ferry A.V , Marshall L , McAllister D , Shah A.S.V , Newby D.E , Mills N.L , Chapman A.R
Published: November 2020

Background

Type 2 myocardial infarction is common and associated with substantial risk of adverse clinical outcomes, worse than type 1 myocardial infarction, with as few as 30% of patients still alive at five years. However, this broad diagnostic term encompasses multiple mechanisms of supply-demand imbalance, which may be associated with different risks of adverse outcomes.

Purpose

We aimed to assess the prevalence and clinical outcomes of different mechanisms of supply-demand imbalance related to survival in the High-STEACS (High-Sensitivity Troponin in the Evaluation of patients with Acute Coronary Syndrome) randomised controlled trial.

Methods

The High-STEACS trial was a stepped wedge cluster randomised controlled trial in ten hospitals across Scotland, including 48,282 consecutive patients with suspected acute coronary syndrome. The diagnosis was adjudicated according to the Fourth Universal Definition of Myocardial Infarction. In patients with type 2 myocardial infarction, we prospectively adjudicated the cause for supply demand imbalance. Linkage of electronic healthcare records was used to track investigation, treatments and clinical outcomes. We used the Kaplan-Meier method, the log rank test and cox regression models adjusted for age, sex, renal function and co-morbidities to evaluate the risk of future all-cause mortality between categories.

Results

We identified 1,121 patients with type 2 myocardial infarction (age 74- ± 14, 55% female). At one year, death from any cause occurred in 23% (258/1,121) of patients. The most common reason for supply-demand imbalance was tachyarrhythmia in 55% (616/1,121), followed by hypoxaemia in 20% (219/1,121) of patients. Tachyarrhythmia was associated with reduced future risk of all-cause mortality (adjusted HR 0.69, 95% CI 0.43–1.09), similar to those with type 1 myocardial infarction. Comparatively, patients with hypoxaemia appeared at highest risk (adjusted HR 1.75, 95% CI 1.09–2.80).

Conclusion

The mechanism of myocardial oxygen supply-demand imbalance is associated with future prognosis, and should be considered when risk stratifying patients with type 2 myocardial infarction.

Supply-demand imbalance survival

Funding Acknowledgement

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