bluuebunny/crossref_metadata_2025 huggingface dataset:
Triple therapy in the elderly patients and women – results from the MUNICH triple cohort in patients with AF undergoing PCI
Authors: Riesinger L , Strobl C.S , Mehr M , Kellnar A , Opitz K , Siebermair J , Rassaf T , Massberg S , Wakili R
Published: November 2020

Introduction

Approximately 20% of patients with atrial fibrillation (AF) are suffering from coronary artery disease (CAD), requiring percutaneous coronary intervention (PCI) and stenting over time. These patients are in need of a so-called “triple therapy” (TT) for prevention of stent thrombosis and stroke. Prospective and randomized trials examined risk for bleeding in TT and compared it to a dual regimen, but in majority excluded elderly patients. Moreover, in all to date presented triple therapy trials women represent a minority of included patients (mostly <30%). This raises the question, why female and elderly patients are underrepresented and these groups have a different outcome then younger and male patients, when treated with a guideline recommended TT.

Methods

The objective of our retrospective cohort study was to determine the number of women and elderly patients with the indication for TT and to evaluate the differences in medical treatment. Furthermore, we evaluated safety, represented by bleeding (BARC ≥2 bleedings) and efficacy endpoints (composite clinical endpoint: all-cause-death, myocardial infarction, stent thrombosis, stroke and other systemic thromboembolism) in women vs. men, and elderly vs. younger patients. Moreover, we investigated the influence of NOAC (new oral anticoagulant) vs. VKA (vitamin K antagonist) treatment. Follow-ups were performed via phone-calls or in-hospital visits.

Results

In total, we included 928 patients with AF, that underwent PCI and stenting. Mean follow-up was 464 days. 627 patients were <80 years old (mean age: 72±7 years), 301 were ≥80 years old (mean age: 84±4 years). Only 27.9% of all patients were female. The number of men and women receiving TT was comparable (83.0% vs. 82.2%, p=0.78), while in the younger group significantly more patients received TT (537 (85.6%) vs. 228 (74.7%) (p<0.001). The incidence of BARC ≥2 bleedings in patients with TT was not significantly different in younger vs. older patients and in men vs. women. Also, the incidence of the composite clinical endpoint did not differ significantly in both comparisons.

Conclusion

In our real-life cohort female sex represents around a quarter of TT patients in line with large RCTs. But, unlike the large RCTs, 1/3 of our included patients were older then 80 years and seem to be underrepresented in randomized TT trials.

TT seems to be safe in elderly as well as in female patients. As they both represent an important group, future trials should focus more on including a well balanced patient cohort to improve the applicability of the results.

Funding Acknowledgement

Type of funding source: None
Choice of P2Y12 inhibitor and clinical outcomes in the AUGUSTUS study: support for an individualised approach
Authors: Storey R , Alexander J.H , Wojdyla D.M , Mehran R , Vora A.N , Goodman S.G , Aronson R , Windecker S , Granger C.B , Lopes R.D
Published: November 2020

Background

AUGUSTUS randomized patients with atrial fibrillation and ACS and/or PCI to apixaban or VKA and aspirin or placebo for 6 months on background P2Y12 inhibitor.

Purpose

To characterise the clinical outcomes in patients receiving clopidogrel or ticagrelor.

Methods

Patients enrolled in AUGUSTUS (n=4614) were grouped by P2Y12 inhibitor at randomization. Baseline characteristics were compared among groups. Rates of ISTH major or CRNM bleeding, definite/probable stent thrombosis (ST), stroke, MI, and death or ischaemic event were quantified and treatment groups were compared according to treatment with clopidogrel or ticagrelor.

Results

At randomization, patients were treated with clopidogrel (n=4165), ticagrelor (n=280), prasugrel (n=51) or no P2Y12 inhibitor (n=118). Median ages were 71, 69, 66 and 72 years (P<0.001). Ticagrelor and prasugrel were more commonly used in PCI-managed ACS (53% and 55%) whilst clopidogrel or no P2Y12 inhibitor was more common in medically-managed ACS (25% and 36%); elective PCI was the index event in 37–41% for each group. Irrespective of P2Y12 inhibitor used, bleeding risk was lower with apixaban vs. VKA and higher with aspirin vs. placebo (Table). ST rate was lowest but major/CRNM bleeding rate highest with ticagrelor + aspirin vs ticagrelor without aspirin or clopidogrel with or without aspirin.

Conclusions

Apixaban is safer than VKA regardless of P2Y12 inhibitor used. Dropping aspirin reduces bleeding but is associated with numerically higher ST rates regardless of P2Y12 inhibitor used. These data support current recommendations for preferential use of NOAC vs. VKA and individualised choice of P2Y12 inhibitor and timing of aspirin cessation after PCI according to the patient's risks of bleeding and stent thrombosis.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Bristol-Myers Squibb/Pfizer
Retrospective comparison of Resting Full-cycle Ratio (RFR) and Fractional Flow Reserve (FFR) in a coronary artery disease cohort
Authors: Wienemann H , Mauri V , Baldus S , Halbach M
Published: November 2020

Background

The fractional flow reserve (FFR) is the gold standard for the assessment of the physiological severity of coronary artery disease. Measurement of FFR requires administration of a vasodilator (commonly adenosine) to achieve maximum hyperemia. The development of resting indices that do not require the administration of adenosine is of great importance. A novel hyperemia-free resting index is the “resting full cycle ratio” (RFR), which corresponds to the lowest pressure distal to the stenosis in relation to the aortic pressure during the entire cardiac cycle. The aim of the present study was to examine the diagnostic accuracy of RFR compared to FFR.

Methods

The study included consecutive patients undergoing pressure wire studies for standard indications at our university hospital from March 9, 2015 to February 15, 2019. Lesions with FFR ≤0.80 were classified as functionally significant. The RFR values were calculated retrospectively from the curves of the FFR measurements, using a point in time before adenosine administration, so that non-hyperemic resting conditions were present.

Results

A total of 635 patients with 733 coronary lesions were investigated using FFR. The average age of the subjects was 68.1±10.7 years. 459 (72.3%) were male. The distribution of the lesions was as follows: LAD: 444 (60.5%), RCA: 140 (19.1%), RCX: 127 (17.3%), RIM: 12 (1.6), LM: 6 (0.9%) and bypasses: 4 (0.5). Overall, the FFR and RFR values were 0.841±0.08 and 0.91±0.06. The RFR showed a significant correlation with the FFR (Table 1). Diagnostic accuracy of the RFR compared to the FFR was highest at a cut-off value of 0.89. This could be demonstrated using the receiver operating characteristic curve (Picture 1).

In 408 measurements, coronary stenoses that were not hemodynamically relevant were found (FFR>0.8 and RFR>0.89). 164 measurements showed hemodynamically relevant coronary stenoses (FFR ≤0.8 and RFR ≤0.89). In 66 lesions, the FFR measurement showed hemodynamic relevance and the RFR measurement did not, whereas in 95 patients the RFR measurement showed hemodynamic relevance and the FFR values were normal.

Conclusions

The RFR as a new resting index has a significant correlation with the FFR after adenosine administration. In 22% of the measurements, a different therapeutic decision would have been made based on the RFR vs. the FFR. A randomized study should therefore investigate whether a RFR-guided approach is non-inferior to a FFR-guided approach in terms of avoiding cardiovascular complications.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Abbott Laboratories
The effect of preloading statins prior to primary reperfusion on in-hospital mortality risk in a contemporary large-scale cohort of patients with ST-elevation myocardial infarction
Authors: Fu R , Song C.X , Li X.D , Yang Y.J
Published: November 2020

Background

The benefit of statins in secondary prevention of patients stabilized after acute coronary syndrome (ACS) has been well established. However, the benefit of preloading statins, i.e. high-intensity statins prior to reperfusion therapy remains unclear. Most previous studies included all types of ACS patients, and subgroup analysis indicated the benefit of preloading statins was only seen in ST-elevation myocardial infarction (STEMI) patients who underwent percutaneous coronary intervention (PCI). However, the sample size of subgroup population was relatively small and such benefit requires further validation.

Objective

To investigate the effect of loading dose of statins before primary reperfusion on 30-mortality in patients with STEMI.

Methods

We enrolled patients in China Acute Myocardial Infarction (CAMI) registry from January 2013 to September 2014. CAMI registry was a prospective multicenter registry of patients with acute acute myocardial infarction in China. Patients were divided into two groups according to statins usage: preloading group and control group. Patients in preloading group received loading does of statins before primary reperfusion and during hospitalization. Patients in control group did not receive statins during hospitalization or at discharge. Primary outcome was in-hospital mortality. Baseline characteristics, angiographic characteristics and outcome were compared between groups. Propensity score (PS) matching was used to mitigate baseline differences between groups and examine the association between preloading statins on in-hospital mortality risk. The following variables were used to establish PS matching score: age, sex, classification of hospitals, clinical presentation (heart failure at presentation, cardiac shock, cardiac arrest, Killip classification), hypertension, diabetes, prior angina, prior myocardial infarction history, prior stroke, initial treatment.

Results

A total of 1169 patients were enrolled in control group and 6795 in preloading group. A total of 833 patients (334 in control group and 499 in preloading group) died during hospitalization. Compared with control group, preloading group were younger, more likely to be male and present with Killip I classification. The proportion of hypertension and diabetes were higher in preloading group. After PS matching, all the variables used to generate PS score were well balanced. In the PS-matched cohort, 30-day mortality risk was 26.3% (292/1112) in the control group and 11.9% (132/1112) in the preloading group (p<0.0001).

Conclusions

The current study found preloading statins treatment prior to reperfusion therapy reduced in-hospital mortality risk in a large-scale contemporary cohort of patients with STEMI.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Chinese Academy of Medical Sciences
Twenty-year trends in clinical outcome of randomized controlled trial for coronary intervention: systematic review and meta-regression analysis of 46 randomized controlled trials
Authors: Asano T , Ono M , Saito A , Kanie T , Takaoka T , Komiyama N
Published: November 2020

Aim

The technology of percutaneous coronary intervention (PCI) has been developed after the advent of coronary stent. However, the impact of the technological development on clinical outcomes is still unclear, whereas a remarkable improvement of clinical outcomes after PCI has not been observed in the trials comparing to medical therapy or coronary bypass graft. The current analysis aims to investigate trends in clinical outcomes after PCI after the emargence of coronary stent, using the randomized controlled trials (RCTs) comparing coronary stents.

Methods and results

We performed a systematic review of RCTs investigating coronary stents in non-specific population (excluding the trials particularly enrolling diabetic or myocardial infarction etc.) conducted between 1996 and 2015 (publication between 1997 and 2019) with independent clinical event adjudication. The random-effect meta-regression analysis including 90 arms with 94,831 patients in 46 RCTs was performed investigating the 20-year trends in clinical outcomes such as death, cardiac death, myocardial infarction, target lesion revascularization (TLR) and stent thrombosis at one and five years after the index procedure. The sensitivity analysis was performed by limiting to 20 all comer trials. In the meta-regression analysis, we did not observe significant change in the incidences of cardiac death and myocardial infarction after PCI over 20 years (P values for cardiac death: 0.666 at one year, 0.256 at five years and P values for myocardial infarction: 0.121 at one year, 0.376 at five years; R2 for cardiac death: <0.01 at one year and five years and R2 for myocardial infarction: <0.01 at one year and five years), whereas the incidences of clinically indicated TLR (P value <0.001, R2 = 0.40 at one year, P value = 0.002, R2 = 0.22 at five years) and stent thrombosis were decreased steeply in the first decade and slightly in the second decade (P value = 0.040, R2 = 0.09 at one year; P value = 0.017, R2 = 0.17 at five year). The sencitivity analysis limiting all-comer population revealed the consistent results.

Conclusion

The development of PCI had an impact on the 20-year trends in TLR and ST, despite there were no trends in the cardiac death and myocardial infarction.

Trends in the incidence of the outcomes

Funding Acknowledgement

Type of funding source: None
Aggressive therapy to prevent contrast-induced kidney damage during percutaneous coronary interventions
Authors: Safyanova O.E , Repin A.N
Published: November 2020

Introduction

In the era of the development of medical technology percutaneous coronary intervention (PCI) has become the most common method of surgical treatment of coronary arteries in patients with coronary heart disease (CHD). Contrast-induced nephropathy (CIN) is a harbinger of chronic renal failure. The recommendations for myocardial revascularization for the prevention of CIN recommend the use of statin treatment. The choice of the optimal statin, the duration of its administration and the effectiveness of loading doses of statins in preventing CIN still remain unresolved topical issues.

The purpose of research work: 1) to evaluate the effectiveness of the prevention of contrast-induced kidney damage when using a loading dose of statins; 2) to study the possibility of early diagnosis of renal damage by examining serum creatinine levels, calculating the glomerular filtration rate (GFR) and the index of a new biomarker of cystatin C.

Material and methods

All patients with CHD, hemodynamically significant stenosis of the coronary arteries were sent to elective endovascular myocardial revascularization. All patients underwent: general clinical examination, a serial study of biochemical blood analysis parameters: creatinine, c-reactive protein (CRP), cystatin C level, GFR. Using the envelope method, the patients were divided into two groups. Patients of the first group were prescribed atorvastatin at a dose of 80 mg for 7 days: 3 days before PCI and 4 days after it. The second group included patients who were treated with rosuvastatin at a dose of 40 mg for 7 days: 3 days before PCI and 4 days after PCI.

Conclusion

The incidence of CI AKI in patients with planned PCI during the administration of high doses of rosuvastatin was less frequent compared with loading therapy with atorvastatin, respectively 3.33% and 12.12%. On average, an increase in the concentration of serum creatinine to the maximum level in patients receiving atorvastatin was higher than in the second group with loading therapy of rosuvastatin (14.3% versus 8.1%, p=0.024).

The decrease in GFR calculated by the formula CKD-Epi was detected 48 and 72 hours after PCI. At the same time, a study of plasma cystatin C showed a decrease in renal function 12 and 24 hours after surgery with the introduction of a contrast agent. This biomarker is an effective marker for early detection of renal failure, even with normal creatinine levels. The anti-inflammatory effect was evaluated by a highly sensitive CRP. In patients with CHD after PCI during therapy with rosuvastatin it was significantly stronger compared with the group of patients using atorvastatin. Thus, the use of rosuvastatin in order to prevent CI of AKI during CPI in patients with CHD seems to be preferable in comparison with atorvastatin due to a more pronounced nephroprotective and anti-inflammatory effect.

Aggressive statin therapy

Funding Acknowledgement

Type of funding source: None
Elevated TG/HDL-C ratio is an independent predictor of outcome and it is associated with CAD progression in patients with stable coronary artery disease
Authors: Caselli C , Rocchiccioli S , Smit J.M , Ragusa R , Rosendael R , Buechel R , Teresinska A , Pizzi M.N , Magnacca M , Campolo J , Knuuti J , Parodi O , Pelosi G , Scholte A.J , Neglia D
Published: November 2020

Background

Elevated TG/HDL-C ratio is associated with CVD outcomes in high-risk populations presenting for coronary angiography, but studies were limited in gender-specific populations or in pts with ACS.

Purpose

Aim of this study was to evaluate the prognostic role of TG/HDL-C levels and their association with CAD progression in pts with suspected stable CAD.

Methods

TG/HDL-C ratio was calculated in 545 pts (60±9yrs,330males) with symptoms of stable CAD enrolled in the EVINCI study. 490 pts underwent coronary CTA to assess the presence of CAD (>50%stenosis) and entered a clinical follow up (4.5±0.9yrs). The CVD outcome measure included all cause mortality, non fatal MI, hospitalization for unstable angina or HF. After 6±1yrs, during the SMARTool study, a second CTA was obtained in 171 EVINCI pts and a CTA risk score (based on plaque extent, severity, composition, and location) was calculated at enrolment and at follow up to assess CAD progression (ΔCTA score).

Results

Pts were divided according to TG/HDL-C quartiles: IQ (<1.32), IIQ (1.32–2.03), IIIQ (2.04–3.33), and IVQ (>3.33). As reported in Table, the frequency of male, diabetes, metabolic syndrome and obesity increased among quartiles. Glucidic biomarkers progressively increased from quartile I to IV, while LDL-C decreased. The prevalence of obstructive CAD at CTA did not differ among groups. The CVD endpoint occurred in 7% of pts. At multivariable analyses, high TG/HDL-C ratio (IVQ) was associated with the outcome endpoint independently from presence of obstructive CAD and treatment (HR 3.477, 95% CI 1.181–10.239, P=0.0237). CTA score was significantly higher in pts in IVQ compared to IQ at both SMARTool enrolment and follow up (Figure1). A significantly higher ΔCTA score was observed in pts in III-IVQ compared with those in I-IIQ (Figure2).

Conclusion

Elevated TG/HDL-C ratio is an independent predictor of outcome and it is associated with CAD progression in patients with stable CAD.

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): “EValuation of INtegrated Cardiac Imaging” - EVINCI [GA number: 222915]; “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support - SMARTool” [GA number: 689068]
Non-alcoholic fatty liver disease fibrosis score predicts cardiovascular mortality in post percutaneous coronary intervention patients: a 5-years results from observational registry
Authors: Lee D , Kim J
Published: November 2020

Background and aims

The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of metabolic risk indicators that may accurately predict residual cardiovascular risk in patients with CAD.

Method

This is a nested case control study of the post PCI registry from single tertiary hospital. Among 5589 patients who underwent PCI from 2010 through 2014, previously diagnosed 1510 NAFLD patients and 296 consecutive NAFLD patients who had undergone both PCI and ultrasonography of abdomen within 1 year between the tests were enrolled. (median age, 64y (IQR 55–73)). We applied the NFS to the patients at baseline, using validated NFS cut-offs and 201 patients with higher NFS, defined as NFS >0.67 at PCI, were 1:1 matched with controls, based on propensity scores for higher NFS >0.67.

Results

Higher NFS (NFS >0.67) was more prevalent in patients with left ventricle (LV) dysfuction (LVEF at PCI <40%) than in those without (81.0% vs 33.6%, p<0.001). Baseline higher NFS was significantly associated with LV dysfunction (adjusted OR 1.86, 95% CI 1.36 to 2.55, p<0.001), and baseline higher NFS and persistent higher NFS at 1 year after PCI were independent predictor of a 5-years CV death, after adjustment for LVEF (adjusted HR 1.42, 95% CI 1.03 to 1.95, p=0.023; adjusted HR 1.52, 95% CI 1.08 to 2.64, p=0.033).

Conclusion

With a longitudinal assessment of the association between NAFLD status by NFS and the risk of CV death, we found post-PCI patients with persistent higher NFS were at higher risk of CV death compared with those without.

KM rates of CV death according to NFS

Funding Acknowledgement

Type of funding source: None
Coronary artery fistulas: a single-center case series
Authors: Cardoso Torres S , Vasconcelos M , Resende C.X , Diogo P , Pinto R , Proenca T , Carvalho J.M , Calvao J , Amador F , Costa C , Cruz C , Moreira J , Pinho P , Silva J.C , Maciel M.J
Published: November 2020

Introduction

Coronary artery fistulas (CAFs) are rare anomalous connections between a coronary artery and a major vessel or cardiac chamber. Currently they are being increasingly encountered due to the more widespread use of various imaging modalities and coronary angiography. Although the vast majority of CAFs are incidentally diagnosed and have no clinical relevance, they can cause significant morbidity such as myocardial infarction, congestive heart failure and endocarditis.

Methods

A consecutive series of 55867 coronary arteriograms performed in our Cardiology Department from 2007 to 2019 was retrospectively investigated for the presence of coronary artery fistulas. Patients clinical, angiographic and therapeutic data up to november 2019 were analyzed. Data were obtained from medical records of hospital stay and subsequent consultations.

Results

We identified 50 patients who were diagnosed with one or more CAFs, with ages between 5 and 85 years (mean 59 years). 62% (n=31) were males.

The great majority of patients had a single fistula (n=34, 68%), 11 patients had two fistulas (22%), 1 patient had 3 fistulas (2%) and 4 patients had multiple fistulas (8%).

CAFs arose more frequently from the left anterior descending artery (n=27), followed by the right coronary (n=18), left circumflex (n=15), left main (n=5) and intermediate artery (n=2). The most frequent drainage site was the pulmonary artery (n=38).

The majority of CAFs were incidentally found (n=32; 64%) and thought to have no significance for the patients' clinical status. As for the rest of the patients, CAFs were diagnosed during evaluation of: a heart murmur (n=7); exertional chest pain with no associated significant atherosclerotic coronary artery disease (n=7); exertional dyspnea (n=2); positive exercise stress test (n=1); NSTEMI and cardiac arrest (n=1).

Regarding treatment, watchful waiting was the main approach (n=40; 80%). 3 patients had their CAFs closed during surgery for another heart condition (CABG/aortic valve replacement). In 1 patient, heart surgery was specifically conducted for fistula closure. 6 patients (12%) underwent fistula transcatheter closure.

Conclusion

CAFs are rare coronary anomalies and the majority has no clinical relevance, so watchful waiting is the commonest approach. When they are hemodynamically significant or symptoms/complications arise, surgical or transcatheter closure should be considered. This study describes the angiographic, clinical and therapeutic data of CAFs detected along the last 12 years in a single tertiary care center catheterization laboratory.

Funding Acknowledgement

Type of funding source: None
Impact of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome
Authors: Centola M , Maloberti A , Persampieri S , Castini D , Morici N , Sabatelli L , Oliva F , Giannattasio C , Carugo S
Published: November 2020

Background

Hyperuricemia has been associated with high mortality rates in patients with acute myocardial infarction. The role and the prognostic relevance of increased serum uric acid (SUA) in patients with acute coronary syndrome (ACS) are still under debate

Aim

We sought to assess the association between elevated admission levels of SUA and in-hospital adverse outcomes in a real-world patient population with ACS and to investigate the potential incremental prognostic value of SUA added to GRACE score

Methods

1088 consecutive patients admitted with a diagnosis of ACS to the Coronary Care Unit of two Hospitals were enrolled. Medical history, clinical characteristic, biochemical and electrocardiographic findings, angiographic data, treatments administered during hospitalization were all collected on an electronic database. All patients' data were entered prospectively in the database of the two hospitals and retrospectively analysed.

Results

The mean age was 68 years (IQR 60–78). Less than one-third of the total population was female (24%). Diabetes mellitus was present in 308 (28%) patients. The proportion of patients with STEMI and NSTEMI/UA was quite similar: 504 (46%) patients had a diagnosis of STEMI and 584 (54%) patients had a diagnosis of NSTEMI/UA. The GRACE score was 133 (IQR 112–156). In-hospital mortality rate was 2.3% in the overall population. Two variables were associated with a significantly increased risk of in-hospital death at the multivariate analysis: SUA (OR 1.72 95% CI 1.33–2.22, p<0.0001) and GRACE score (OR 1.04 95% CI 1.02–1.06, p<0.0001). To investigate the potential incremental prognostic value of SUA added to GRACE score for in-hospital death, we analyzed the results of adding hyperuricemia as categorical variable to the original GRACE risk model (GRACE-SUA score). The areas under the ROC curve (AUC) for GRACE score and for SUA were 0.91 (95% CI 0.89–0.93, p<0.0001) and 0.79 (95% CI 0.76–0.81, p<0.0001) respectively. The AUC was larger for predicting in-hospital mortality with the GRACE-SUA score (0.94; 95% CI 0.93–0.95; p<0.0001). The addition of hyperuricemia to the GRACE score led to reclassifying 18 of 211 (8.5%) patients without in-hospital deaths from high to low risk. No patients with o without events were incorrectly reclassified. The net-reclassification index (NRI) of the GRACE-SUA score was 1.7% (z value of 4.3; p<0.001).

Conclusions

High admission levels of SUA are positively and independently associated with in-hospital adverse outcomes and mortality in a contemporary and unselected population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality and to improve risk classification in this study population.

Funding Acknowledgement

Type of funding source: None
Myocardial infarction coincides with increased expression of NO2X2 and the advanced glycation end product N-e-(carboxymethyl) lysine in the microvasculature of the brain
Authors: Korn A , Baylan U , Schalkwijk C.G , Niessen H.W.M , Krijnen P.A.J
Published: November 2020

Background

Acute Myocardial Infarction (AMI) is associated with mental health disorders such as cognitive impairment and depression. Neuroinflammation and cerebral microvascular dysfunction may play an important role herein. We previously showed an increased presence of the pro-inflammatory factors N-ε-Carboxymethyllysine (CML) and NADPH oxidase 2 (NOX2) in the microvasculature of the human infarcted heart and diabetic brain. In this study we have quantified the presence of CML and NOX2 in the cerebral microvasculature of patients in time after AMI.

Methods

Brain tissue was obtained at autopsy from 24 AMI patients and 9 control patients. According to their infarct age, the AMI patients were divided into three groups: 3–6 hours old (phase 1), 6 hours–5 days old (phase 2) and 5–14 days old (phase 3). The presence of CML and NOX2 in the microvasculature was quantified through immunohistochemical analysis.

Results

We observed a significant approximately 2.5 fold increase in microvascular CML in phase 2 and phase 3 AMI patients in comparison with control patients (p=0.015). NOX2 was present in significantly more microvessels in phase 2 AMI patients compared to control patients (p=0.042). However, no correlation was found between CML and NOX2 (r=0.06, p=0.74).

Conclusion

AMI coincides with an increased presence of CML and NOX2 in the microvasculature of the brain. These data point to pro-inflammatory alterations in the brain microvasculature that may underlie the mental health disorders associated with AMI.

CML and NOX2 in the brain microvessels

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Novo Nordisk BV, European Foundation for the Study of Diabetes
Fluid-dynamics and biological features of unstable plaques: different shear stress for different plaques
Authors: Russo G , Pedicino D , Burzotta F , Lodi Rizzini M , Genuardi L , Vinci R , Bologna M , D'Aiello A , Gallo D , Chiastra C , Aurigemma C , Bonanni A , Trani C , Liuzzo G , Crea F
Published: November 2020

Background

The use of Optical Coherence Tomography (OCT) in acute coronary syndromes (ACS) allows recognizing ruptured fibrous cap (RFC) and intact fibrous cap (IFC) culprit lesions. The biological differences between them, as recently pointed out in translation studies, highlight different mechanisms for a similar clinical manifestation that might deserve different therapeutic approaches. The relationship between endothelial wall shear stress (WSS) and ACS has been demonstrated, however the differences in WSS features between RFC and IFC have not been elucidated.

Purpose

The aim of this study is to provide a fluid-dynamic and biological description of unstable and stable (SA) plaques, according to OCT analysis.

Methods

We enrolled 10 SA and 20 Non-ST Elevation Myocardial Infarction (NSTEMI)-ACS patients, with IFC (n=10) and RFC (n=10) culprit lesions according to OCT analysis. We performed Real-time PCR primer array on pooled Peripheral Blood Mononuclear Cell (PBMC) for 30 different molecules whose expression is strictly dependent on WSS. High-fidelity 3D-coronary artery models were created for 3 patients per group, applying previously validated methodologies.

Results

Among the groups we found a broad difference in molecular expression (Fig. 1A), with RFC displaying higher levels of molecules involved in vasoconstriction/dilatation (EDN1, NOS3), cellular adhesion (ICAM1), and peptidase inhibition (PI16). A significantly higher WSS was observed in RFC group (p<0.001, Fig 1B and C), with larger variability and larger areas exposed to both low and high WSS (Fig. 1D). Interestingly, the molecules overexpressed in RFC are known to be upregulated by high WSS.

Conclusions

Our data demonstrated that IFC and RFC unstable plaques are associated with different WSS conditions, alongside with the expression of different molecular patterns specifically related to altered WSS. In the era of precision medicine these findings may have relevant therapeutical implications.

Funding Acknowledgement

Type of funding source: None
Cardioprotective strategy in ST-elevation acute myocardial infarction patients after reperfusion with percutaneous coronary intervention
Authors: Kozhukhov S , Parkhomenko A , Lutay Y.A , Yershova Y
Published: November 2020

Objectives

Reperfusion may cause no-reflow phenomenon. Both microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) have been recognized as poor prognostic factors in myocardial infarction (MI) patients. The aim of the study was to evaluate hypothesis whether cardioprotective strategy prevent IMH in MI patients after primary percutaneous coronary intervention (PCI).

Methods

This multicenter open-label randomized clinical trial enrolled 143 patients with first acute anterior ST-elevation MI (STEMI) reperfused within 6 h after symptoms onset. Cardiac magnetic resonance (CMR) was performed to assess left ventricular (LV) function and microvascular injury in 23 patients within the first week (3.5±1.2 days) after STEMI. Nine patients were randomized into soluble intravenous form of quercetin (Q) group and 14 - to the control group. Q infusions were started before PCI and used during the next 5 days. MVO was visualized using early gadolinium enhancement (EGE) and IMH was detected by using T2-WI.

Results

The study groups did not differ in terms of demographic characteristics, time to admission and main clinical data. Initially, the number of LV myocardial segments with edema was similar - 7.8±1.7 in patients of Q subgroup versus 6.8±1.8 in patients of the control subgroup (p=0.245). However, patients of the Q subgroup tended to have greater number of segments with gadolinium accumulation and higher value of the transmural index (7.7±1.2 compared to 6.2±1.5; p<0.05) according to the late gadolinium enhancement (Area at Risk, gray zone of AMI). According to gadolinium enhancement MVO was detected in more than 90% patients of both groups, but IMH rate was higher in the control group (53.3 vs 11.1%; p=0.03). Additionally, Q limited final infarct size assessed by CK-MB AUC 18% compare to control group (p<0.021).

Conclusion

Detection of MVO and IMH by CMR can accurately demonstrate the severity of myocardial injury. Intravenous Q can decrease the rate of IMH additionally to infarct size limitation. Further investigations are needed to confirm our results and to determine whether prevention of IMH can impact on better prognosis.

Funding Acknowledgement

Type of funding source: None
Role of diuretics on long-term mortality may differ in volume status in patients with acute myocardial infarction
Authors: Kawai T , Nakatani D , Yamada T , Watanabe T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Seo M , Nakamura J , Hikoso S , Fukunami M , Sakata Y
Published: November 2020

Background

Diuretics has been reported to have a potential for an activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, leading to a possibility of poor clinical outcome in patients with cardiovascular disease. However, few data are available on clinical impact of diuretics on long-term outcome in patients with acute myocardial infarction (AMI) based on plasma volume status.

Methods

To address the issue, a total of 3,416 survived patients with AMI who were registered to a large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed with the estimated plasma volume status (ePVS) that was calculated at discharge as follows: actual PV = (1 − hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females), and ePVS = [(actual PV − ideal PV)/ideal PV] × 100 (%). Multivariable Cox regression analysis and propensity score matching were performed to account for imbalances in covariates. The endpoint was all-cause of death (ACD) within 5 years.

Results

During a median follow-up period of 855±656 days, 193 patients had ACD. In whole population, there was no significant difference in long-term mortality risk between patients with and without diuretics in both multivariate cox regression model and propensity score matching population. When patients were divided into 2 groups according to ePVS with a median value of 4.2%, 46 and 147 patients had ACD in groups with low ePVS and high ePVS, respectively. Multivariate Cox analysis showed that use of diuretics was independently associated with an increased risk of ACD in low ePVS group, (HR: 2.63, 95% confidence interval [CI]: 1.22–5.63, p=0.01), but not in high ePVS group (HR: 0.70, 95% CI: 0.44–1.10, p=0.12). These observations were consistent in the propensity-score matched cohorts; the 5-year mortality rate was significantly higher in patients with diuretics than those without among low ePVS group (4.7% vs 1.7%, p=0.041), but not among high ePVS group (8.0% vs 10.3%, p=0.247).

Conclusion

Prescription of diuretics at discharge was associated with increased risk of 5-year mortality in patients with AMI without PV expansion, but not with PV expansion. The role of diuretics on long-term mortality may differ in plasma volume status. Therefore, prescription of diuretics after AMI may be considered based on plasma volume status.

Funding Acknowledgement

Type of funding source: None
Impact of percutaneous coronary intervention on short and long-term prognosis of elderly patients with acute myocardial infarction from 2010 to 2017 in Japanese population
Authors: Goto J , Watanabe T , Kobayashi Y , Toshima T , Wanezaki M , Nishiyama S , Otaki Y , Kutsuzawa D , Kato S , Tamura H , Arimoto T , Takahashi H , Shishido T , Kubota I , Watanabe M
Published: November 2020

Background

Advances in therapies have successfully decreased short-term mortality in patients with acute myocardial infarction (AMI). Although aging population is recently increasing in developed countries, there are few reports about the association between prevalence of percutaneous coronary intervention (PCI) and long-term prognosis in elderly patients with AMI in Japan.

Purpose

The aim of this study was to clarify the prevalence of PCI and the impact of PCI on short and long-term prognosis of elderly patients with AMI.

Methods and results

We investigated the prevalence of PCI and short-term mortality in 4,109 patients with AMI who were registered in Yamagata AMI Registry from 2010 to 2017. Long-term mortality was investigated using data from death certification in July 2019. We divided patients with AMI into three age groups (group 1, <65 years old; group 2, 65–79 years old; and group 3, ≥80 years old). Short-term mortality within 30 days was 6.5%, 12.1%, and 28.6%, respectively. Also, prevalence of PCI was 88.0%, 84.7%, and 62.7%, respectively. Multivariate analysis revealed that age, PCI, and severity of Killip classification were significantly associated with short-term mortality after adjustment for confound factors in group 3. Since the prevalence of PCI in group 3 was the lowest among three groups, the cause of PCI not being executed was investigated in 1,429 patients aged ≥80 years old. Elderly patients who didn't undergo PCI was older, more women, and had higher prevalence of chronic kidney disease, previous stroke, and severe Killip classification. Multivariate analysis revealed that age and Killip III/IV were significantly associated with non-executed PCI after adjustment for confound factors. Next, we investigated impact of PCI on long-term mortality in elderly patients who escaped acute death. Multivariate Cox hazard analysis revealed that PCI was associated with lower mortality after adjustment for confound factors (adjusted hazard ratio 2.47, 95% CI: 1.47–4.06; p=0.0008).

Conclusion

Lower prevalence of PCI and higher short-term mortality were observed in elderly patients with AMI aged ≥80 years old. PCI ameliorated long-term mortality as well as short-term mortality in elderly patients with AMI.

Funding Acknowledgement

Type of funding source: None
Premature acute coronary syndrome patients do not have a better prognosis for their age than mature ACS patients by propensity score match analysis
Authors: Mizutani H , Kurita T , Takasaki A , Nakata T , Konishi K , Izumi D , Omura T , Masuda J , Ito M , Dohi K
Published: November 2020

Background

Acute coronary syndrome (ACS) is the most important cardiovascular (CV) disease with a prevalence that increases with age. There is no data which compared the prognosis with premature ACS and mature ACS using propensity score matched analysis

Purpose

The purpose of this study was to compare the prognosis of premature ACS patients and mature ACS patients using propensity score matched analysis.

Methods

We analyzed of 4249 ACS patients (69.1±12.6, male 77%) including 773 premature ACS patients (50.1±6.8, male 78%) and 3476 mature ACS (73.3±9.3, male 77%) from January 2013 to December 2018, using data from Mie ACS Registry, a prospective and multicenter registry in Japan.

Premature onset of ACS was defined as younger than 65 years old in male and 55 years old in female.

Primary end point was as major adverse cardiac event (MACE) including cardiovascular death, non-fetal myocardial infarction, heart failure requiring admission and unstable angina.

Results

During median follow duration of 742 days ranging from409 to 828 days, 502 MACE were occurred. Premature ACS patients were younger and showed higher body mass index compared to mature ACS patients (50.1±6.8 vs 73.3±9.3 y.o., 25.5 vs 23.0, P<0.001, respectively). However, premature ACS patients were more likely to be associated with ST elevation myocardial infarction, dyslipidemia, family history of coronary artery disease (CAD) and lower Killip classification compared to mature ACS patients (P<0.01, respectively). Common CAD risk factors such as hypertension, diabetes mellitus and past history of CAD were less associated with premature ACS patients compared to mature ACS patients (P<0.01, respectively). Unadjusted Kaplan-Meier survival curves demonstrated the favorable prognosis in premature ACS patients compared to mature ACS patients with hazard ratio of 0.57 (95% CI 0.45–0.71, P<0.001, see Figure 1A). We compared a 1:1 propensity score-matched cohort of 1208 patients with or without premature onset of ACS adjusting the several factors mentioned above (n=604, respectively). Age could not be introduced as a factor of propensity score match when comparing premature and mature ACS patients. After propensity score-match, premature ACS patients is about 18 years younger than mature ACS patients (50.7±6.5 vs 68.5±8.2 y.o., P<0.001). The average age of premature ACS was younger than that of mature ACS, but MACE by Kaplan-Meier survival analysis for premature ACS patients was equivalent to mature ACS patients (P=0.77, see Figure 1B).

Conclusion

Premature ACS patients are required very careful management because they might have factors with unfavorable prognosis, such as lifestyle habit and genetics, that may be beyond age.

Figure 1

Funding Acknowledgement

Type of funding source: None
Temporal trends in treatment and outcomes of patients with acute coronary syndrome and concomitant moderate to severe renal failure
Authors: Bossard M , Witassek F , Radovanovic D , Moccetti F , Erne P , Rickli H , Kobza R , Cuculi F
Published: November 2020

Introduction

Limited information about the management and outcomes of patients with acute coronary syndromes (ACS) and moderate to severe renal failure (RF) is available owing to underrepresentation of this population in most studies.

Methods

We evaluated the use of guideline-recommended therapies and in-hospital outcomes of totally 49'191 ACS patients with normal-mild renal failure (RF) (defined as eGFR >45ml/min/m2) versus moderate-severe RF (eGFR <45ml/min/m2) enrolled in the prospective Acute Myocardial Infarction in Switzerland (AMIS) cohort between 2002 and 2019 according to 2-year periods.

Results

Overall, 3'478 (7.1%) patients had moderate-severe RF. They were older (65.2+12.9 versus 77.2+10.6 years) and had significantly more comorbidities (including heart failure, cerebrovascular and peripheral vascular disease). Moderate-severe RF patients received less frequently guideline-recommended drugs, including P2Y12 inhibitors, ACEI/ARBs and statins (p<0.0001). Between the first and last 2-year periods, the number of patients with moderate-severe RF and number of performed percutaneous coronary interventions (PCI) increased in this cohort (p-for-trend=0.001). At the same time, in-hospital mortality significantly decreased among ACS patients with and without RF (17.5% to 10.5% and 6.0% to 3.9%, respectively, p-for-trend=0.001 for both, see Figure). Similar trends were observed for other complications, namely cardiogenic shock and reinfarction. However, major bleedings increased significantly over time in patients with and without RF (p-for-trend=0.038 and <0.001, respectively).

Conclusions

Outcomes of ACS patients with moderate to severe RF improved over the last two decades. Even though the rate of PCI increased in ACS patients with moderate-severe RF, they were less likely to receive guideline-recommended therapies and still suffer a high in-hospitality mortality (>10%). With respect to the increasing burden of ACS patients with RF, our study implicates that more efforts should be undertaken to further improve outcomes of those patients.

Funding Acknowledgement

Type of funding source: None
Real-world evidence on short- and long-term outcomes for acute coronary syndrome patients with a prior history of atrial fibrillation
Authors: Gouda P , Savu A , Bainey K , Welsh R , Sandhu R.K
Published: November 2020

Background

Acute coronary syndromes (ACS) are often complicated by new-onset atrial fibrillation (AF), which is associated with higher short-term mortality. It is unknown whether a prior history of AF affects outcomes beyond in-hospital mortality in a real-world setting.

Purpose

To assess (i) the prevalence of prior AF in patients with ACS, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI); (ii) clinical characteristics of ACS patients with and without AF; and (iii) in-hospital mortality and long-term outcomes in the presence of prior AF.

Methods

We used linked administrative health databases to identify patients hospitalized with a primary diagnosis of ACS and prior history of non-valvular AF (ICD-9 code 427.3 and ICD-10 code 148), which was defined as 1 hospitalization or 1 emergency department visit or 2 outpatient visits at least 30 days apart in 1 year in any position, between April 2002 and March 2016 in Alberta, Canada. Outcomes included in-hospital mortality, long-term mortality and a composite of all-cause mortality, hospitalisation for myocardial infarction (MI) or stroke over 3 years. Kaplan-Meier curves were constructed for mortality and the composite outcome according to presence of prior AF and ACS type.

Results

Of 31,056 presenting with an ACS, 4,173 (13.4%) had a prior history of AF. Compared to patients without prior AF, patients with AF were older (75.7 versus 64.7 years), female (35.5% versus 29.9%), with a higher comorbidity burden (Charlson Comorbidity Index 1.7 versus 1.1). Patient with AF more often presented with NSTEMI (57.7% versus 48.2%) and UA (17.1% versus 16.4%) compared to STEMI (25.2% versus 35.4%). In-hospital mortality was higher for ACS patients in the presence of prior AF (8.1% versus 3.3%; p<0.0001). Mortality and the composite endpoint were also significantly higher in patients with prior AF compared to those without AF (Panel A and B) over the 3-year period. A worse prognosis was observed for STEMI and NSTEMI patients with prior AF compared to any other group (panel C and D).

Conclusion

In this large, population-based study, we found that a history of AF is common in patients presenting with an ACS. In the presence of AF, short- and long-term prognosis is poor particularly for STEMI and NSTEMI patients. Aggressive modification of shared risk factors and use of evidence-based therapies to improve outcomes is needed in this high-risk population.

Outcomes by presence of AF and ACS type

Funding Acknowledgement

Type of funding source: None