bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular outcome in patients treated with SGLT2 inhibitors for heart failure: a meta-analysis
Authors: Gager G M , Gelbenegger G , Jilma B , Von Lewinski D , Sourij H , Eyileten C , Filipiak K , Postula M , Hengstenberg C , Siller-Matula J
Published: October 2021

Objective

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging class of glucose lowering drugs, which become increasingly relevant for treatment and prevention of heart failure (HF). Therefore we aimed to investigate various SGLT2 inhibitors in patients with established HF at baseline.

Design

Extensive search of PubMed and Web of Science until January 2021. Two reviewers independently and in duplicate applied the selection criteria. This meta-analysis was conducted according to the PRISMA guidelines. Data was pooled using a random-effects model.

Participants

Randomized clinical trials of SGLT2 inhibitors vs comparator in patients with HF reporting clinical outcomes.

Main outcomes and Measures: The primary efficacy outcome was the composite of hospitalization for HF (HHF) or cardiovascular (CV) mortality. All-cause mortality, CV mortality and HHF were considered as secondary endpoints. Subgroup analyses involving status of diabetes, type of HF, administered type of SGLT2 inhibitor, sex, age, BMI, eGFR, cause of HF and concomitant medication were performed.

Results

Seventeen RCTs, comprising a total of 20749 participants, were included (n=10848 treated with SGLT2 inhibitors and n=9901 treated with a comparator). Treatment with SGLT2 inhibitors was associated with a 27% relative risk reduction (RRR) of HHF or CV-mortality (RR=0.73, 95% CI: 0.68–0.78); 32% RRR of HHF (RR=0.68, 95% CI: 0.62–074); 18% RRR of CV mortality (RR=0.82, 95% CI: 0.73–0.91) and 17% RRR of all-cause mortality (RR=0.83, 95% CI: 0.75–0.91). The magnitude of the effect of SGLT2 inhibitors on the primary endpoint was comparable in patients with diabetes vs those without diabetes (RR=0.72, 95% CI: 0.67–0.78 vs RR=0.76, 95% CI: 0.66–0.87, respectively). Patients with HFmrEF (heart failure with mid-range ejection fraction) seemed to have the greatest benefit of SGLT2 inhibition (RR=0.58, 95% CI: 0.40–0.83), whereas patients with an ejection fraction over 45% profited the least (RR=0.79, 95% CI: 0.55–1.12). The direction of the effects was similar for all SGLT2 inhibitors for each outcome. Therapy with SGLT2 inhibitors was beneficial independently of patients' baseline data, except the concomitant use of ARNIs (angiotensin receptor neprilysin inhibitors).

Conclusions

In patients with HF, SGLT2 inhibitors are associated with improved CV outcome.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF-Austrian Science Fund Figure 1Figure 2
Enhancing sweat rate using a novel device for the treatment of congestion in heart failure
Authors: Aronson D , Nitzan Y , Petcherski S , Bravo E , Habib M , Burkhoff D , Abraham W T
Published: October 2021

Background

Current treatment of fluid retention in heart failure (HF) relies primarily on diuretics. However, adequate decongestion is not achieved in many patients.

Purpose

To study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate.

Methods

We used a device designed to enhance fluid and salt loss via the eccrine sweat glands. Skin temperature in the lower body was increased to 35–38°, where the slope of the relationship between temperature and sweat production is linear. With this wearable device, the sweat evaporates instantaneously, thus avoiding the awareness of perspiration. The primary efficacy endpoint was the ability to increase skin temperature to the desired range without elevating the core temperature above normal range. A secondary efficacy endpoint was a clinically meaningful hourly sweat output, defined as ≥150 mL/h. The primary safety endpoint was any procedure-related adverse events.

Results

We studied 6 normal subjects and 10 HF patients with clinical evidence of congestion and median NT-proBNP of 602 pg/mL [interquartile range 427 to 1719 pg/mL]. Participants underwent 3 treatment sessions of up to 4h. Skin temperature increased to a median of 37.5°C (interquartile range 37.1–37.9°C) with the core temperature remaining unchanged. The median total weight loss during treatment was 219±67 g/h (Figure) with a range of 100–338 g/h. In 77% of cases, the average sweat rate was ≥150 mL/h. Systolic (P=0.25) and diastolic (P=0.48) blood pressure and heart rate (P=0.11) remained unchanged during the procedure. There were no significant changes in renal function and no procedure-related adverse events.

Conclusion

Enhancing sweat rate was safe and resulted in a clinically meaningful fluid removal and weight loss. Further evaluation of this concept is warranted.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AquaPass Inc Weight loss due to sweat
Echocardiographic recovery changes in patients supported with veno-arterial extracorporeal membrane oxygenator and weaning success
Authors: Gonzalez Martin J , Alonso-Fernandez-Gatta M , Merchan Gomez S , Gonzalez Cebrian M , Diego-Nieto A , Martin-Herrero F , Toranzo-Nieto I , Barrio-Rodriguez A , Rodriguez-Estevez L , Sanchez-Fernandez P L
Published: October 2021

Introduction

The weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decision involves a meticulous evaluation of different factors, among which echocardiography is a decisive factor.

Purpose

Evaluate echocardiographic changes from the beginning of the support to the weaning test.

Methods

Analysis of VA-ECMO cases in a referral hospital which completed a weaning test. We evaluated the changes of echocardiographic parameters during the VA-ECMO support (initial and during weaning test) and successful weaning (survival >24h after explant and no mortality from cardiogenic shock/heart failure or cardiac arrest during admission).

Results

85 out of 134 VA-ECMO patients were included from 2013 to Oct-2020 (table 1.1). Successful weaning was achieved in 61.2% and final survival at discharge 49.4%.

We observed a significant increase in left ventricular ejection fraction (LVEF), left ventricular outflow tract time–velocity integral (LVOT VTI), tricuspid annular plane systolic excursion (TAPSE) and the percentage of patients with normal qualitative right ventricular function and 1:1 aortic valve opening from the initial to the weaning echocardiography (table 1.2), without significant changes in ventricular diameters. Among these changes, the increase in LVOT VTI was the only parameter that was related to weaning success (p=0.037, table 1.2). A higher LVEF increase from the initial value showed a trend to greater successful VA-ECMO disconnection (p=0.053 table 1.2).

Conclusion

Left and right ventricular function parameters improved significantly from baseline to weaning test echocardiography in VA-ECMO supported patients. Of these changes, the increase in LVOT VTI was related to successful disconnection from VA-ECMO and the LVEF improvement showed a trend to weaning success.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III in Spain (Co-funded by European Social Fund “Investing in your future”). Characteristics ECMO-VA patients
Left atrial venous arterial extracorporeal membrane oxygenation for biventricular failure in cardiogenic shock
Authors: Eng M , Al-Darzi W , Basir M , Singh-Kucukarslan G , Villablanca P , Koenig G , Alaswad K , Cowger J , Oneill W
Published: October 2021

Background

Cardiogenic shock complicated by biventricular (BIV) heart failure is associated with high mortality. Venous-arterial extra-corporeal membrane oxygenation is limited by the increase of left ventricular (LV) afterload. Complex configurations of paired circulatory support devices have been used with mixed results due to vascular access complications. One way to simply vascular access is to place a transseptal cannula under echocardiographic guidance with a long fenestrated segment enabling simultaneous left and right sided unloading known as left-atrial venous arterial (LAVA) ECMO.

Purpose

We aimed to review the safety and outcomes of LAVA ECMO utilized for shock at our institution.

Methods

Retrospective analysis of our Hospital Cath Lab Database yielded 6 patients undergoing LAVA-ECMO for shock from 7/2020–3/2021. Patient characteristics, procedural data and outcomes were analyzed. Variables are either expressed as proportions or medians (Interquartile range; IQR).

Results

Median age was 55.5 years (IQR, 51–61) and most patients were men (83.3%). Median baseline LV ejection fraction was 38% (IQR, 23–56%) and all had right ventricular dysfunction. 4/6 (66.7%) had severe valvular dysfunction including aortic regurgitation (2/6), mitral regurgitation (2/6) and mitral stenosis (1/6). One patient had a LV thrombus and hemodynamics necessitated LV unloading. Intracardiac echocardiography was used to guide the transseptal puncture in 5/6 (83%). Transesophageal echocardiography was used in one case. Procedural outcomes and hemodynamic variables are outlined in Tables 1 and 2 consecutively. One case of limb ischemia resulted from an embolus in the contralateral limb. LAVA-ECMO bridged 83% of patients to valve replacement, durable ventricular support or heart transplant (Table 1).

Conclusions

LAVA-ECMO provides BIV support with a single circuit and successfully bridged patients without direct complications. Given the safety, efficacy and simplified configuration of LAVA-ECMO, prospective studies are indicated.

Funding Acknowledgement

Type of funding sources: None.
Plasma PCSK9 levels increase following percutaneous coronary interventions
Authors: Azar R R , Sarkis A , Azar Y , Luscher T , Kadri Z , Abdelmassih T , Germanos M , Caligiuri G , Varret M , Boileau C , El Khoury P , Abifadel M
Published: October 2021

Background

Beside its role in cholesterol homeostasis, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has been associated with the processes of vascular inflammation and atherosclerosis. The protein is expressed in endothelial cells, smooth muscle cells and macrophages and it is detected inside the human atherosclerotic plaque.

Purpose

We aimed to investigate the effect of acute inflammation associated with plaque rupture and vascular injury during elective percutaneous coronary intervention (PCI) on plasma levels of PCSK9 in patients with coronary artery disease (CAD).

Methods

We measured PCSK9, C-reactive protein (CRP), Interleukin-6 (IL-6) and high-sensitivity cardiac Troponin T (hs-cTnT) plasma levels immediately before and 18–24 hours after PCI via the radial approach, in 68 consecutive patients with stable CAD referred for elective PCI of a de novo lesion in a native coronary artery. Patients with unstable coronary syndrome <3 months old, baseline inflammatory condition, malignancy, auto-immune disease or intervention via the femoral access, were excluded.

Results

All patients were treated with balloon angioplasty and implantation of a second-generation drug eluting stent (DES). Baseline plasma levels of PCSK9 were higher in women and in patients treated with statins. At 18–24 hours after the procedure, plasma levels of PCSK9, CRP, IL-6 and hs-cTnT increased significantly compared to baseline (table). The change (elevation) in CRP plasma levels was statistically correlated with that of IL-6 (r=0.33; p=0.006) and with that of hs-cTnT (r=0.28; p=0.023). However, there was no correlation between the change (elevation) in plasma PCSK9 levels and those of IL-6 (r=−0.09; p=0.47), CRP (r=0.01; p=0.9), and hs-cTnT (r=0.1; p=0.41).

Conclusions

Plasma levels of PCSK9 increased by 26% following PCI with DES. That elevation was however, not correlated with the degree of myocardial injury (hs-cTnT) or of inflammation (IL-6 and CRP). The mechanism underlying PCK9 elevation post PCI requires further investigation.

Funding Acknowledgement

Type of funding sources: None.
Infectious agents, protein electrophoresis and immunoglobulin levels in patients with coronary artery ectasia
Authors: Yetkin G , Tascioglu D , Ozturk S , Cuglan B , Zorkun C S , Yalta K , Yetkin E
Published: October 2021

Background

Even the mechanism of coronary artery ectasia (CAE) shares the common pathophysiologic steps and risk factors with atherosclerosis which led to assume that CAE is a variant of atherosclerosis, there are certain discrepancies or aspects incompatible of atherosclerosis.

Purpose

We hypothesized that pathophysiology of CAE might differ from that of atherosclerosis in terms of inflammatory parameters, infectious agents. Therefore, we assessed and compared the levels of IgG antibody against Chlamydia pneumonia, and Helicobacter Pylori, components of serum protein electrophoresis and plasma levels of total Ig G and Ig E.

Materials and methods

Seventy patients with coronary artery disease (CAD) and 30 patients with CAD coexisted with CAE comprised the study populations. Blood samples were allowed to clot at room temperature then centrifuged at 1500 rpm for 5 minutes then serum kept at deep freeze (−20°C) to be used for the measurement of IgG antibodies against C. pneumoniae and H. Pylori, total IgE, IgG levels and protein electrophoresis.

Results

There were not statistically significant differences between patients with and without CAE regarding the clinical and laboratory parameters except hemoglobin levels (Figure I). IgE, Alpha 2 macroglobulin, Beta-1 globulin levels were found to be higher in patients with CAE+CAD than those of CAD alone (Figure IIa). There was no statistically significant correlation between the Gensini score, and IgG antibody against H. Pylori (r=0.048, p=0.66) and C. Pneumoniae (r=−0.12, p=0.27) regarding the whole study population. Additionally, logistic regression analysis by including variables IgE, hemoglobin, Alpha 2 macroglobulin, beta-1 globulin, and gender, revealed that Ig E and alpha 2 macroglobulin were independently and positively associated with the presence of CAE (Figure IIb).

Conclusion

Independent association of serum IgE levels and alpha2 globulins with the presence of CAE underlines the divergent features of pathophysiology of CAE compared with atherosclerosis or CAD alone.

Funding Acknowledgement

Type of funding sources: None. Figure IFigure II
Sex-specific differences in first event of st- elevation myocardial infarction; new insights on age-related mortality
Authors: Fischer A J , Feld J , Kuehnemund L , Makowski L , Engelbertz C M , Guenster C , Gerss J , Droege P , Ruhnke T , Lange S A , Reinecke H , Freisinger E , Koeppe J
Published: October 2021

Background

For patients with ST-elevation myocardial infarction (STEMI) as the primary manifestation of coronary artery disease (CAD), data on predictors and outcome are limited. We hypothesized that specifically age and sex influence short- and long-term outcome in patients after first event of STEMI.

Methods and results

Based on claims data of the Federal Association of the Local Health Insurance Funds (Allgemeine Ortskrankenkasse) (≈26 million insurance holders in Germany with ≈83 million inhabitants), adults with STEMI between 01/2014 to 12/2015 and no history of CAD were selected for further analysis. Patient demographics, details on in-hospital treatment as well as age- and sex-related differences in 30-day mortality, re-infarction/ death, major adverse cardiovascular events (MACE), overall and long-term survival were assessed.

Overall, 17,444 patients presented with STEMI as the primary manifestation of CAD throughout the study period, thereof 33% were women. At index, women were older compared to men (median age 74 years vs. 60 years) and suffered from more cardiovascular comorbidities such as diabetes (35.8% vs. 25.2% in men), chronic kidney disease (26.0% vs. 14.9% in men), and arterial hypertension (84.6% vs. 72.6%; all p<0.001). Women with STEMI underwent endovascular reperfusion (78.5% vs. 88.1%) or coronary artery bypass grafting (4.2% vs. 5.5%; both p<0.001) less frequently. In-hospital complications such as shock (19.2% vs. 16.0%) and resuscitation (15.1% vs. 12.9%; both p<0.001) were observed more often in women.

Female sex was independently associated with adjusted 30-day mortality (Odds Ratio 1.17; p=0.01). Long-term outcomes revealed women to be at increased risk of the combined end-point of re-infarction and/or death (Hazard ratio (HR) 1.09; p=0.01), MACE (HR 1.09; p=0.01) and all-cause mortality (HR 1.10; p=0.01). Particularly in patients younger than 60 years, female sex was a strong predictor of adverse outcomes. Surprisingly, among patients that survived at least 90 days after STEMI, no differences between the sexes were noted regarding long-term survival (HR 0.99; p=0.91) (see Figure for adjusted odds/hazard ratios presenting the association of sex with different endpoints depending on age after first event of STEMI).

Conclusion

On non-selective data, two-thirds of patients with STEMI as the primary manifestation of CAD were male. Women were observed to receive endovascular reperfusion less frequently than men and suffered from more in-hospital complications. Being female and younger than 60 years was associated with an increased risk of adverse outcomes specifically early after STEMI.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The study is part of the GenderVasc project funded by the joint federal committee, Germany.
Comparison of the GRACE score, TIMI score and a New Laboratorial Score to predict adverse outcomes in acute coronary syndrome
Authors: Correia J , Pires I , Santos J , Neto V , Ferreira G , Goncalves L , Cabral J , Costa A
Published: October 2021

Introduction

Acute coronary syndrome (ACS) is a clinical entity which includes a heterogeneous group of patients with different outcomes. Risk scores are in this setting a resourceful tool to identify the subset of patients with a worse prognosis, in order to plan therapeutic and surveillance strategies.

Aim

To create a risk score – Laboratory Risk Score (LRS) – which exclusively includes analytical and echocardiographic parameters, as a predictor of adverse outcomes (in-hospital mortality and 1-year mortality), and compare it with other well-known scores: GRACE Score (GS) and TIMI-score (TS).

Methods

A retrospective cohort study was conducted, which included patients admitted in the Cardiology Department with the diagnosis of ACS. In order to calculate the new LRS, the authors attributed the value of 1 to each of the satisfied condition from the following: leucocytes >11,7g/L, hemoglobin <13.3g/dL, red cell distribution width >14%, prothrombinemia <90%, glycaemia at admission >143mg/dL, urea >53.5mg/dL, creatinine >1.16mg/dL, reactive C-protein >1.0mg/dL, maximum troponin >35.0ng/dL, natriuretic brain peptide >416 pg/dL and left ventricular ejection fraction <40%. LRS resulted from the sum of the satisfied conditions.

ROC curves for LRS, GS and TS to predict in-hospital mortality and to predict 1-year mortality were constructed. The statistical analysis was performed in SPSS and Medcalc. p value <0.05 was considered statistically significant.

Results

1714 patients (70.4% male, average age 69±13 years-old) were included in this study. Intra-hospital mortality rate was 6.8% and 1-year mortality rate after de discharge was 4.8%.

The areas under the ROC curves for predicting in-hospital mortality were the following: 0,790 (LRS, p<0,001), 0,793 (GS, p<0.01), 0.817 (TS, p<0.001). For predicting 1-year mortality, the areas under the ROC curves were: 0,715 (LRS, p<0,001), 0,761 (GS, p<0,001), 0.742 (TS, p<0.001). Pairwise comparison of ROC curves showed no significant differences between the scores.

Conclusion

The above-mentioned risk scores, including the new LRS, are obtained with non-invasive and widely available parameters and displayed a good performance in predicting in-hospital and 1-year mortality. Pairwise comparison of ROC curves demonstrated that the new laboratorial score was not inferior predicting adverse outcomes. The SRL is an easily obtained score, that shows a statistical significance in predicting mortality, especially the prediction of in-hospital mortality.

Funding Acknowledgement

Type of funding sources: None.
Diagnostic value of coronary flow reserve assessment by dynamic 99mTc-MIBI SPECT-CZT gamma camera for the detection of coronary artery disease
Authors: Cygulska K M , Blaszczyk M , Kasprzak J D , Wejner-Mik P , Frynas-Jonczyk K , Plachcinska A , Kusmierek J , Cichocki P , Lipiec P
Published: October 2021

Background

Coronary flow reserve (CFR) obtained by dynamic acquisition of myocardial blood flow using 99mTc-MIBI SPECT-CZT gamma camera may be useful to diagnose myocardial perfusion defects in patients with coronary artery disease (CAD).

Purpose

To assess the feasibility and diagnostic value of SPECT-derived CFR in patients with suspected of confirmed CAD.

Methods

The study group comprised 55 patients (pts) (43.6% females, mean age 64.6±8.4 years) with suspected CAD who were referred for scheduled coronary angiography. All pts underwent myocardial perfusion study with solid-state CZT nuclear camera (dipyridamole stress protocol) to calculate myocardial blood flow reserve. We measured total CFR, as well as CFR in three coronary territories: left anterior descending artery (LAD CFR), right coronary artery (RCA CFR) and left circumflex artery (LCx CFR).

Results

On coronary angiography 27 pts were found to have significant CAD (at least one major coronary artery ≥70% narrowed). Mean total CFR in pts with CAD was lower than in pts without CAD (1.73±0.59 vs 2.09±0.56, respectively, p=0.02). Similar differences were noted in LAD territory (1.47±0.57 vs 2.00±0.57; respectively, p=0.004) and RCA territory (1.55±0.54 vs 2.01±0.62; respectively, p=0.03). However, the differences in LCx CFR between CAD and no-CAD group did not reach statistical significance. Modest, but significant correlations were detected between LAD CFR and the percentage of LAD stenosis (r=−0.3; p=0.02). Total CFR has acceptable diagnostic value for detecting significant CAD (AUC=0.672; p=0.03). The criterion with the highest diagnostic accuracy was CFR <1.8 – its sensitivity was 63%, specificity 71.4%, and overall accuracy 67%. In analysis of coronary territories the highest diagnostic value was achieved for CFR LAD (AUC=0.744; p=0.007).

Conclusions

SPECT-derived CFR provides acceptable diagnostic accuracy for the detection of significant CAD.

Funding Acknowledgement

Type of funding sources: None.
Coronary angiography in patients with native or prosthetic aortic-valve endocarditis: outcomes and implications for myocardial revascularisation
Authors: Berger T , Siepe M , Dees D , Fagu A , Pingpoh C , Kondov S , Zeh W , Beyersdorf F.-J , Rylski B , Schroefel H , Czerny M , Neumann F.-J , Hochholzer W , Kreibich M
Published: October 2021

Background

Coronary angiography (CA) remains the cornerstone of the preoperative assessments before open-heart surgery to detect or rule out coronary artery disease (CAD). Preoperative CA is currently not recommended in patients with active infective aortic valve endocarditis, but may help to reduce the risk of perioperative myocardial infarction.

Purpose

This study aimed to evaluate the risks and benefits of preoperative CA in selected patients before aortic valve replacement to treat active infective endocarditis of the aortic valve and to assess the incidence and relevance of CAD.

Methods

Sixty-five patients with native or prosthetic aortic-valve endocarditis underwent preoperative diagnostic CA between 03/2008 and 09/2020. We collected their baseline characteristics, including the neurological status, previous cardiac surgical procedures, and reviewed the preoperative echocardiograms and the CA data. We evaluated the intraoperative data, and clinical outcomes after CA and after surgery. Patients were selected according to the site, size and mobility of vegetations of the underlying active infective process.

Results

CA revealed CAD in the majority of patients (n=34; 52%): one-vessel disease n=17 (26%), two-vessel disease n=6 (9%), and three-vessel disease n=11 (17%). Coronary sclerosis without hemodynamic significance were detected in 23 patients (35%). Sixteen patients had a previous history of CAD. We observed no adverse events following preoperative diagnostic CA, particularly no thromboembolic complications, including stroke, visceral, or lower body ischaemia. Surgery was performed 3 [IQR 1; 5] days after CA. During surgical aortic-valve replacement, concomitant coronary artery bypass grafting was performed in 19 patients (29%). Postoperative in-hospital mortality was 12% (n=8) and the new-onset disabling-stroke incidence was 2% (n=1). Neither stroke nor visceral or lower body ischemia due to embolism were observed in any patient after surgery.

Conclusions

By weighing risks and benefits of CA together as a team, no adverse clinical outcomes but significant clinical implications could be identified in patients with active infective aortic valve endocarditis. Concomitant surgical myocardial revascularization was frequent and may well have contributed to favorable clinical outcome. Therefore, active infective endocarditis of the aortic valve per se should not be regarded as an absolute contraindication for CA.

Funding Acknowledgement

Type of funding sources: None.
Comparing loading strategies of P2Y12 inhibitors in patients undergoing elective PCI: a network meta-analysis
Authors: Gupta R , Malik A , Vadhar S , Briasoulis A , Vyas A , Patel N
Published: October 2021

Introduction

Effective platelet inhibition prior to elective percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. Newer P2Y12 inhibitors are preferred agents over clopidogrel for patients presenting with acute coronary syndrome. However, the comparative efficacy and safety of them over clopidogrel in elective PCI is unclear. Our objective was to perform a network meta-analysis and assess that from randomized controlled trials (RCT).

Methods

We conducted a systematic review of RCTs up to and including November 2020. The endpoints of interest were overall mortality, rates of myocardial infarction (MI), stroke, revascularization and major bleeding. Random effects model using frequentist approach was used to perform a network meta-analysis using R software.

Results

5 trials with total of 5,194 patients were included in our analysis. For ischemic outcomes including MI, Stroke and revascularization, prasugrel had the most favorable trend. However, clopidogrel had the highest probability of being most effective for major bleeding and all-cause mortality. None of these trends were statistically significant due to lack of power for each individual outcome (Figure 1).

Conclusion

Prasugrel and ticagrelor seem to show better efficacy in preventing MI and stroke. However, their effects are marginal and do not translate into improved overall mortality and bleeding. Therefore, in this lower risk population presenting for elective PCI, clopidogrel remains a reasonable P2Y12 inhibitor choice in lower risk population.

Funding Acknowledgement

Type of funding sources: None. Results
A meta-analysis of randomised controlled trials investigating the impact of colchicine on major adverse cardiovascular events in acute coronary syndrome
Authors: Blake N , Alonso A , Rai H , Colleran R , Giacoppo D , Byrne R A ,   Cardiovascular Research Institute (CVRI), Dublin
Published: October 2021

Background/Introduction

Colchicine has been shown to reduce inflammation and has a potential to stabilise atherosclerotic plaques. Prior meta-analyses on the topic suggest its role in reducing components of major adverse cardiovascular events (MACE).

Purpose

The aim of the present meta-analysis was to delineate the effect of colchicine on post-PCI (percutaneous intervention) MACE among acute coronary syndrome (ACS) patients.

Methods

We included randomised controlled trials (RCTs) comparing colchicine to placebo in ACS patients undergoing PCI. To identify potentially relevant trials a PUBMED search was undertaken using the MESH terms “colchicine” and “cardiovascular system”. Eligible RCTs published up to November 2020 were included. Our search strategy also included presentations from the proceedings of international meetings. The primary endpoint was MACE. However, definitions of MACE varied between included studies. Study level odds ratios (ORs) and 95% confidence intervals (CI) of MACE were pooled using the Mantel-Haenszel method and random effects model. Forest plots were generated using Review Manager (RevMan) 5.4 software.

Results

Our initial search identified 1,049 articles for potential inclusion. Of them, 4 RCTs were found to be eligible: COPS, COLCHICINE-PCI, COLCOT time-to-Initiation (TTI) 0–3 days and PODCAST-PCI.

A pool of 2,709 patients were randomly allocated to treatment with either colchicine (n=1,367) or placebo (n=1,342). Patients received colchicine either prior to angiography or within 3 days post-procedure. Follow up duration ranged from 30 days to 3 years during which MACE were recorded. Mean age of the whole analysed cohort was 60.3±10.5 years. 73% were male. 51% had history of hypertension, 26% had diabetes mellitus, 38% were current smokers. There were 89 events in the colchicine group as opposed to 133 events in the placebo group. The risk of post-PCI MACE was lower in patients treated with colchicine as compared with placebo (OR 0.63, 95% CI 0.48–0.84, p=0.001) (see figure 1). Heterogeneity was not detectable (I2=0).

Conclusions

Our results indicate lower risk of MACE in patients treated with colchicine. This indicates a potential use of colchicine in patients undergoing PCI in an ACS setting. Further investigations in larger cohorts are warranted to test this effect.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Platelet reactivity and bleeding outcomes in female patients presenting with ST-segment elevation myocardial infarction: a COMPARE CRUSH substudy
Authors: Vogel R F , Vlachojannis G J , Wilschut J M , Lemmert M E , Diletti R , Nuis R J , Paradies V , Alexopoulos D , Zijlstra F , Montalescot G , Angiolillo D J , Krucoff M W , Van Mieghem N M , Smits P C , Delewi R
Published: October 2021

Background/Introduction

Females presenting with ST-segment elevation myocardial infarction (STEMI) are characterized by an increased risk of bleeding after primary percutaneous coronary intervention (pPCI) compared with males. The reason for increased bleeding rates is multifactorial, including age, comorbidities, vessel anatomy and possible differences in platelet biology. Data about platelet reactivity levels in females versus males presenting with STEMI is scarce.

Purpose

Investigation of gender-driven variances in platelet reactivity and bleeding outcomes in STEMI patients planned to undergo pPCI.

Methods

The COMPARE CRUSH trial was a randomized multicenter ambulance trial assessing the effect of prehospital administration of P2Y12 inhibitor loading dose with crushed versus integral prasugrel tablets in STEMI patients. We assessed the occurrence of high platelet reactivity (HPR), predictors of HPR at baseline and bleeding outcomes between females and males. Blood samples were analyzed at four prespecified time points using VerifyNow.

Results

The COMPARE CRUSH trial included 633 STEMI patients in the period between November 2017 and March 2020. Females more frequently exhibited HPR at baseline than males (76% vs. 41%, odds ratio (OR), 4.58 [95% CI, 2.52 to 8.32], p<0.01). Moreover, female sex was a strong, independent predictor for HPR at baseline (OR, 4.93 [95% CI, 2.30 to 10.57], p<0.01). HPR rates at other time points were not significantly different between females and males. The risk of bleeding within the first 48 hours was significantly increased in females (OR, 6.02 [95% CI, 2.58 to 14.08], p<0.01), but after adjustment for baseline characteristics this increased risk was no longer statistically significant (OR, 2.61 [95% CI, 0.73 to 9.32], p=0.14).

Conclusion

Female sex is an independent predictor for occurrence of HPR at baseline in STEMI patients. However, females exhibit a stronger platelet inhibition effect by oral P2Y12 inhibitors than males, which may contribute to an increased bleeding risk. A more tailored antiplatelet therapy approach should be considered for female STEMI patients to reduce bleeding risk.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Unrestricted grants from Daiichi-Sankyo and Shanghai MicroPort Medical.
The age-specific prognostic impact of the platelet-to-lymphocyte ratio on long-term outcome after acute coronary syndrome
Authors: Kazem N , Hofer F , Koller L , Hammer A , Hofbauer T , Hengstenberg C , Niessner A , Sulzgruber P
Published: October 2021

Background

Personalized risk stratification within the ageing society after ACS remains scarce. With increasing general life expectancy, easily applicable age-specific strategies for the prediction of fatal adverse events are in urgent need. Increased platelet activity together with inflammatory activation play a key role during ACS.

Objective

We aimed to evaluate the age-specific prognostic potential of the platelet to lymphocyte ratio (PLR) on long-term cardiovascular mortality after ACS.

Methods

Patients presenting with ACS admitted to a tertiary care centre with a high-volume cardiac catheterization unit between December 1996 and January 2010 were recruited within a clinical registry including assessment of peripheral blood samples. The impact of the PLR on survival was assessed by Cox-regression hazard analysis.

Results

We included a total of 681 patients with a median age of 64 years (IQR:45–84). 200 (29.4%) individuals died during the median follow-up time of 8.5 years. A strong and independent association of the PLR with cardiovascular mortality was found in the total study population (adjusted [adj.] hazard ratio [HR] per one standard deviation [1-SD] of 1.52 [95% CI: 1.18–1.96; p<0.001). After stratification in individuals <65 years (n=339) and ≥65 years (n=342), a prognostic effect of the PLR on cardiovascular mortality was solely observed in elderly patients ≥65 years (adj. HR per 1-SD of 1.32 [95% CI: 1.01–1.74]; p=0.045), but not in their younger counterparts <65 years (adj. HR per 1-SD of 1.08 [95% CI: 0.60–1.93]; p=0.804).

Conclusion

The present investigation highlights a strong and independent age-specific association of the PLR with cardiovascular mortality in patients with ACS. The PLR only allows to identify patients ≥65 years at high risk for fatal events after ACS – even from a long-term perspective.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Vienna Effect of PLR stratified by age
Systemic immune-inflammation index predicts in-hospital and long-term outcomes in patients with ST-segment elevation myocardial infarction
Authors: Ocal L , Keskin M , Cersit S , Eren H , Cakmak E O , Cakir H , Dogan S , Ozturk B , Kaya A , Turkmen M M
Published: October 2021

Background

Inflammatory markers are significantly associated with cardiovascular disease and many markers have been used as predictor in patients with STEMI. This study examines the predictive value of the novel systemic immune-inflammation index (SII) in patients with ST-segment elevation myocardial infarction (STEMI).

Method

A total of 1660 patients with STEMI who underwent primary percutaneous coronary intervention in a tertiary heart center were enrolled in the study. SII was calculated using the following formula: Platelet × Neutrophil/Lymphocyte ratio. The patients were stratified into four quartiles (Q) according to admission SII level. In-hospital and 3-year outcomes were compared between the four groups (Q1–4)

Results

In-hospital cardiogenic shock, acute respiratory failure, acute kidney injury, ventricular arrhythmia, stent thrombosis, recurrent myocardial infarction, major adverse cardiac events, and mortality were significantly higher in the high SII groups (Q3 and Q4). Logistic regression models demonstrated that Q3 and Q4 had independent risk of mortality and Q4 had an independent risk of cardiogenic shock compared to Q1. ROC analysis showed that the best cut-off value of the Systemic Immune-Inflammatory Index to predict the in-hospital mortality was 1781 with 66% sensitivity and 74% specificity (AUC: 0.75; 95% CI: 0.69–0.81; p<0.001). Kaplan Meier overall survivals for Q1, Q2, Q3 and Q4 were 97.6%, 96.9%, 91.6% and 81.0% respectively. Cox proportional analysis for 3-year mortality demonstrated that Q3 and Q4 had independent risk of death compared to Q1.

Conclusion

SII, a novel inflammatory index, had a better prediction of in-hospital and long-term outcomes than traditional risk factors in patients with STEMI.

Funding Acknowledgement

Type of funding sources: None.
The total amount of CRP within the first 72 h after STEMI is crucial for the outcome
Authors: Garlichs C , Ries W , Torzewski J , Pfluecke C D , Darius H , Heigl F , Ince H , Mitzner S , Nordbeck P , Butter C , Sheriff A ,   CAMI-1 Investigators
Published: October 2021

Background

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

Methods

66 STEMI patients were enrolled following complete coronary revascularization (2–12 h after AMI). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. A specific CRP adsorber removed ≤79% of the original CRP. 6000 ml of plasma was treated via peripheral venous access. Primary endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 3–9 days after STEMI.

Results

Aphereses sessions were well tolerated with no relevant side effects. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24h after the onset of symptoms (CRP gradient). The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP gradients. The mean CRP gradient does not differ between both groups, whereas the mean area under the curve (AUC) of CRP within the first 72 h after AMI does. Thus, there was no bias in CRP kinetics between the two groups. The AUC of CRP is a significant indicator for infarct size (p=0.002), LVEF (p<0.001), circumferential strain (p<0.001), longitudinal strain (p=0.021). Therefore, the aphereses patients performed significantly better at all endpoints than the controls. The CRP apheresis significantly reduced myocardial damage by a reduction of the AUC of CRP. To our surprise, two apheresis patients had an infarct size of 0%.

Conclusions

For the first time we find an unequivocal association between myocardial infarct size and the AUC of CRP. The results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry).

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Pentracor GmbH
Iron deficiency – a factor in left ventricular ejection fraction depression post-myocardial infarction
Authors: Dias Claudio F , Carias M , Rocha R , Picarra B , Neves D , Trinca M
Published: October 2021

Introduction

Iron deficiency was shown to affect functional capacity and ejection fraction in patients with heart failure and reduced ejection fraction. Myocardial infarction is an important cause of reduced left ventricular ejection fraction (LVEF). Moreover, there is some evidence of the iron deficiency as a factor to predict cardiovascular and non-cardiovascular mortality.

Purpose

Evaluate the presence of iron deficiency in patients with acute coronary syndromes (ACS) admitted to the intensive cardiac care unit and its eventual association with LVEF and mortality.

Population and methods

We performed a prospective study in which ACS patients were divided into groups according to the presence or absence of iron deficiency. We collected demographic data, comorbidities, as well as determination of troponin I, haemoglobin and criteria for absolute and functional iron deficiency (ID) and other data related to the use of mechanical ventilation, need for aminergic support, LVEF and death.

Results

From 148 patients we included 78 patients who met the criteria for being analysed. 49 patients had iron deficiency (51% had absolute iron deficiency and 49% had relative iron deficiency). There were no differences between groups in terms of myocardial infarction with or without ST segment elevation (p=0.609 and p=0.329, respectively), hypertension (p=0.926), diabetes (p=0.882), obesity (p=0.343), dyslipidaemia (p=0.482), smoking (p=0.876), valvular heart disease (p=0.888), acute and chronic renal failure (p=0.800 and p=0.888, respectively) and LVEF (p=0.886). There were no differences in need for aminergic support (p=0.984), ventilation (p=0.315) and death (p=0.704).

We found that in the sub-population of patients without anaemia (Hb>12g/dL), the proportion of patients with depressed LVEF (inferior to 50%) and relative iron deficiency was significantly higher than those with preserved LVEF (48.1 vs 13.8%, p=0.005). Furthermore, we also found that in this sub-population, patients with myocardial infarction without ST segment elevation had higher proportion of absolute iron deficiency (45.0 vs 19.4%, p=0.043).

Conclusion

Our study showed that the prevalence of iron deficiency in ACS patients is 62.9% (n=49). Moreover, in patients without anaemia, this results seems to point out that the presence of iron deficiency may be related with LVEF, at least during the acute event. Further studies with a higher sample size are warranted to either establish or discard this association. Furthermore, a follow-up of this patients can further enlighten us as to the role of iron deficiency in long term LVEF and mortality.

Funding Acknowledgement

Type of funding sources: None.
Impact of lipoprotein(a) as a residual risk on long-term cardiovascular outcomes in patients with acute coronary syndrome treated with statin
Authors: Takahashi D T , Wada H W , Ogita M O , Yasuda K Y , Nishio R N , Takeuchi M T , Takahashi N T , Yatsu S Y , Sonoda T S , Shitara J S , Suwa S S , Dohi T D , Miyauchi K M , Daida H D , Minamino T M
Published: October 2021

Background

It is still uncertain that lipoprotein(a) [Lp(a)] concentration could be a residual risk for cardiovascular events among patients with acute coronary syndrome (ACS).

Purpose

The aim of the present study is to evaluate the impact of Lp(a) on long-term cardiovascular outcomes in patients with ACS treated with statins.

Methods

We studied 1758 consecutive ACS patients who underwent emergency percutaneous coronary intervention (PCI). We finally enrolled 1131 patients who had data of Lp(a) and were treated with statin. They were divided into two groups according to Lp(a) levels (15.0mg/dL). Primary endpoint was major adverse cardiac events (MACE), composite of all-cause death and myocardial infarction.

Results

The cumulative incidence of MACE was significantly higher in the high Lp(a) group than in the low Lp(a) group. After adjustment for other risk factors, the high Lp(a) group had a significantly higher risk of MACE compared with the low Lp(a) group (HR 1.59, 95% CI 1.01–2.48, p=0.04). Multivariate Cox hazard analysis also showed that increasing Lp(a) was associated with worse clinical outcomes (HR 1.33 per log Lp(a) 1 increase, 95% CI 1.05–1.69, p=0.02).

Conclusions

Elevated levels of Lp(a) is significantly associated with long-term cardiovascular outcomes among ACS patients treated with statin.

Funding Acknowledgement

Type of funding sources: None.
Prevalence, clinical characteristics, and in-hospital mortality of patients with angiographic acute total thrombotic occlusion presenting as non-ST-segment elevation myocardial infarction
Authors: Toledo Aleman E , Gonzalez-Pacheco H , Sanchez-Nieto J , Gopar-Nieto R , Sierra-Lara D , Viana-Rojas A , Briseno-De La Cruz J L , Manzur-Sandoval D , Arias-Mendoza M A , Araiza-Garaygordobil D
Published: October 2021

Background

The current paradigm in the treatment of acute coronary syndromes classifies patients according to the presence of persistent ST-segment elevation as a potential marker of total coronary thrombosis, in whom immediate fibrinolysis or primary PCI is appropriate. However, patients with NSTEMI may present with a total acute thrombotic coronary occlusion and may not be detected by this approach, therefore precluding the benefits of early reperfusion strategies.

Purpose

To identify the prevalence of total thrombotic occlusion elicited by coronary angiography in patients with NSTEMI, and to analyze their baseline characteristics and in-hospital mortality.

Methods

Retrospective cohort study including consecutive patients admitted with NSTEMI in a single center over a 15-year period. Patients with coronary angiography were further classified in three groups: patients with a total angiographic coronary thrombotic occlusion (TIMI thrombus V), patients with subtotal coronary thrombus (TIMI thrombus I–IV) and patients without angiographic thrombus. Baseline characteristics and in-hospital outcomes were compared among the three groups.

Results

A total of 4216 of NSTEMI patients were admitted within the study period, of whom 3191 underwent coronary angiography and constituted in the final analytic sample. In 211 patients (6.6%) a TIMI thrombus V was found. Table 1 summarizes the main characteristics among the three groups. In the group of patients with total thrombotic occlussion, a higher proportion were male, were more prone to be current smokers, had a lower prevalence of major cardiovascular risk factors and had suffered less cardiovascular events at enrollment. During hospital follow-up, 15 (7.1%) patients within the total thrombus group, 14 (4.3%) patients within the subtotal thrombus group and 112 (4.2%) patients within the no-thrombus group died. No statistically significant differences in hospital mortality were noted when comparing total thrombotic occlusion vs. no thrombus (HR 1.69, 95% CI 0.94–3.01, p=0.07) (Figure 1).

Conclusions

In our study, 6.6% of the patients with NSTEMI presented an acute total thrombotic occlusion in coronary angiography. Patients with total thrombotic occlusion showed a different risk-factor profile and a similar in-hospital mortality when compared with non-total thrombus or no thrombus.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Ignacio Chavez National Heart Institute, Mexico City, Mexico Table 1. Baseline characteristicsFigure 1. In-hospital mortality