bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of changes in weight and haematocrit on the reduction in systolic office and ambulatory blood pressure with empagliflozin in patients with type 2 diabetes
Authors: Sharma A , Wanner C , Ofstad A P , Mattheus M , Kraus B J , Zinman B , Ferreira J P
Published: October 2021

Background

There is uncertainty on how empagliflozin (EMPA) reduces blood pressure (BP), and in particular the potential role for changes in weight and haematocrit in mediating these effects.

Purpose

To assess the contributions of changes in weight and haematocrit on EMPA induced changes in BP in patients with type 2 diabetes mellitus (T2DM) in the EMPA-BP and EMPA-REG OUTCOME trials.

Methods

Patients received placebo (PBO), EMPA 10 mg or EMPA 25 mg. In EMPA-BP (12-week study), 823 patients with T2DM and hypertension (mean [SD] age 60.2 [9.0] years, HbA1c 7.90 [0.74] %, BMI 32.6 [5.1] kg/m2) were studied. In EMPA-REG OUTCOME, of the 7,020 treated patients with T2DM and cardiovascular disease (mean [SD] age 63.1 [8.6] years, HbA1c 8.07 [0.85] %, BMI 30.6 [5.3] kg/m2), 95.0% were on anti-hypertensive treatment at baseline. ANCOVA/MMRM models were applied to assess changes in systolic BP (SBP) at week 12 associated with, and independent of, changes in weight and haematocrit (Hct). SBP measurements are based on mean 24-h measurements from an ambulatory blood pressure monitoring (ABPM) device in EMPA-BP and seated office measurements in EMPA-REG OUTCOME.

Results

Mean (SD) baseline SBP was 131.7 (11.8), 131.3 (13.0) and 131.2 (12.1) mmHg in the PBO, EMPA 10 mg and EMPA 25 mg groups, respectively in EMPA-BP (mean 24-h SBP) and 135.8 (17.2), 134.9 (16.8) and 135.6 (17.0) mmHg (office SBP), respectively in EMPA-REG OUTCOME. In these relatively young patients with T2DM and mildly elevated mean SBP, EMPA reduced mean SBP by 3.4–4.2 mmHg compared with PBO (table) at week 12. Mean (SE) weight was reduced with EMPA (10 and 25mg) vs PBO treatment by −1.5 (0.2) kg and −2.0 (0.2) kg in EMPA-BP and by −1.2 (0.1) kg and −1.5 (0.1) kg in EMPA-REG OUTCOME at week 12. Mean (SE) haematocrit was increased by 2.1 (0.2) % and 1.8 (0.2) % versus placebo in EMPA-BP and by 2.2 (0.1) % and 2.5 (0.1) % in EMPA-REG OUTCOME with EMPA 10 mg and EMPA 25 mg, respectively. Weight loss accounted for 21–24% of the SBP reduction with EMPA treatment in EMPA-BP and 9–11% in EMPA-REG OUTCOME. Changes in Hct accounted for negligible (between −10% to 1%) SBP reduction with EMPA.

Conclusion

The reduction in SBP is modestly mediated through a reduction in weight. There was no meaningful effect of EMPA induced changes in Hct on SBP. Results were consistent using ABPM or office SBP. These findings suggest that EMPA's effects on SBP are likely mediated through other mechanisms such as natriuresis or reduction in arterial stiffness.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company. Table 1
Clinical outcomes and death associated with cardiorenal syndromes. A comprehensive nationwide cohort study
Authors: Fauchier L , Gatault P , Bisson A , Gueguen J , Gouin N , Sautenet B , Herbert J , Angoulvant D , Halimi J M
Published: October 2021

Background

Cardiorenal syndromes (CRS) are associated with increased risks of all-cause and cardiovascular death, end-stage kidney disease (ESKD), myocardial infarction (MI), heart failure (HF) and ischemic stroke. Whether subtypes of CRS are more prone to develop specific complications is unclear.

Methods

This longitudinal cohort study was based on the national hospitalisation database covering hospital care from the entire French population. The analysis focused on those with at least 5 years of complete follow-up (or dead earlier) as described by others. We identified 385,687 consecutive patients hospitalized in France in 2012 who had heart failure (HF), chronic kidney disease (CKD) and/or CRS. We estimated incidence of cardiovascular and all-cause death, MI, hospitalization for HF, ischemic stroke, ESKD (chronic dialysis or transplantation). Analysis were adjusted for 1) age and sex and 2) all baseline characteristics except cardiac and renal comorbidities.

Results

Overall, 57.7% were male, 67.3% had hypertension, 31.1% had diabetes mellitus and their mean age was 75.3±13.2; 34,217 had isolated CKD, 324,141 had HF, 11,162 had acute concomitant CRS (which could be type 1, 3 or 5 CRS), 12,198 had type 2 CRS and 3,969 had type 4 CRS.

Type 2 CRS was associated with the highest 5-year incidence of all-cause (30.3/100 patient-years [29.7–30.9]) and cardiovascular (10.7 [10.4–11.1]) death and HF (46.9 [45.9–47.9]), type 4 CRS with the highest incidence of MI (2.50 [2.21–2.83]) and patients with acute CRS with the highest incidence of ischemic stroke (2.05 [1.89–2.21]). The incidence of ESKD was 7.43/100 patient-years [6.92–7.99] for type 4 and 6.31 [6.03–6.61] for type 2 CRS, 6.16 [5.88–6.45] for aCRS, 6.00 [5.87–6.14] for CKD and 1.17 [1.15–1.19] for HF.

As compared to CKD, the adjusted risk of ESKD was higher in type 4 (HR: 1.18 [1.10–1.28]) and aCRS (1.07 [1.02–1.13]) and similar for type 2 (HR: 0.99 [0.94–1.04]) CRS. The adjusted risk of all-cause and cardiovascular death and HF was higher in patients with type 2 CRS vs all other groups, and higher in aCRS and 4 CRS than isolated CKD.

Conclusion

The long-term prognosis of CRS subtypes is poor but varies widely, some CRS subtypes being more closely associated with specific complications than others.

Funding Acknowledgement

Type of funding sources: None. All-cause deathCardiovascular death
Prognostic value of the combination of pulmonary-systemic pressure ratio and a new systemic inflammation-nutrition index in patients admitted for acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Fukunami M
Published: October 2021

Background

Concomitant presence of pulmonary hypertension in heart failure (HF) is associated with increased adverse events and may be related to interventricular uncoupling and impaired cardiac efficiency. It has recently been shown that an increased mean pulmonary artery pressure to mean systemic arterial pressure ratio (MPS ratio), a marker of interventricular coupling and efficiency, is associated with worse clinical outcomes in patients with advanced HF. On the other hand, systemic inflammation plays a critical role in the outcomes of heart failure, and malnutrition is also associated with poor outcome in heart failure patients It has been recently reported that advanced lung cancer inflammation index (ALI), which is calculated as body mass index × serum albumin / neutrophil to lymphocyte ratio (NLR), is an independent prognostic marker in several types of cancer. However, there is no information available on the prognostic value of the combination of MPS ratio and ALI in patients with acute decompensated HF (ADHF).

Methods and results

We studied 219 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. During a follow up period of 5.1±4.2 yrs, 57 had cardiovascular death (CVD). MPS ratio was significantly greater (0.401±0.107 vs 0.346±0.105, p=0.0009) and ALI was significantly smaller (34.2±18.7 vs 52.0±27.1, p<0.0001) in patients with than without CVD At multivariate Cox analysis, MPS ratio and ALIwere significantly associated with CVD, independently of eGFR and prior heart failure hospitalization, after the adjustment with left ventricular end-diastolic dimension and serum sodium level. The patients with both greater MPS ratio>0.350 (AUC 0.652 [0.569–0.735]) and smaller ALI <35.767 (AUC 0.714 [0.636–0.792]) had a significantly increased risk of CVD than those with either greater MPS or smaller ALI and none of them (67% vs 22% vs 11%, p<0.0001, respectively).

Conclusion

The combination of MPS ratio and ALI might be useful for stratifying ADHF patients at higher risk for CVD.

Funding Acknowledgement

Type of funding sources: None.
A human arterial transcriptomic signature predicts major adverse cardiac events and identifies novel, redox-related therapeutic targets within the vascular wall
Authors: Kotanidis C P , Lockstone H , Polkinghorne M , Badi I , Akoumianakis I , Siddique M , Antonopoulos A , Evans T , Farid S , Srivastava V , Krasopoulos G , Sayeed R , Channon K M , Antoniades C
Published: October 2021

Background

The transcriptomic profile of the human vascular wall is implicated in a range of pathologies. RNA sequencing technologies allow for interrogation of gene expression patterns that are associated with clinical outcomes and can guide future research and drug development.

Purpose

To apply discovery network transcriptomics to internal mammary arteries (IMAs) obtained from patients undergoing cardiac surgery, in order to identify redox-related molecular pathways within the vascular wall that can be treated therapeutically.

Methods

Arm 1 included 377 patients in whom segments of IMA were used for ex-vivo quantification of NADPH-stimulated superoxide production by lucigenin-enhanced chemiluminescence. Arm 2 included 205 patients in whom bulk RNA sequencing was performed in RNA isolated from IMA, and the WGCNA package used for the analyses. The association with future incidence of major adverse cardiac events (MACE: cardiovascular death, non-fatal myocardial infarction, and stroke) was assessed using Cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, body mass index, smoking, and plasma TNFa).

Results

Over a median follow-up of 4.84 years [IQR: 2.03–7.14], 38 (11.2%) MACE occurred in Arm 1. High arterial NADPH-stimulated superoxide was independently associated with MACE risk (Adj. HR [95% CI]: 2.62 [1.13–6.07] high group, p=0.02). Unsupervised transcriptomic analysis in Arm 2 allowed identification of 10 coexpressed gene “modules”. Eigengenes summarising modular coexpression signatures were then correlated with NADPH-stimulated superoxide revealing the red module (a) as the most significant (rho=0.19, p=0.01). In survival analysis the red module showed significant correlation with MACE (Adj. HR [95% CI]: 1.40 [1.00–1.95] per SD, p=0.04). For an optimal cut-off, patients with high eigengene values for the red module showed a 4-fold higher risk of MACE (b), and significantly higher arterial oxidative stress (c). Enrichment analysis (performed with Enrichr) of genes in the red module revealed “Electron Transport Chain”, “Oxidative phosphorylation”, “Striated Muscle Contraction Pathway”, and “Glycolysis and Gluconeogenesis” amongst the top enriched pathways (d).

Conclusion

We present for the first time a novel human arterial transcriptomic signature reflecting changes in redox state, which identifies long-term cardiovascular risk. Targeting pathways in the vasculature related with the mitochondrial electron transport chain, the contractile mechanism, or glucose metabolism may lead to the development of novel therapeutics in cardiovascular disease.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): EPSRC-EP/N509711/1-2119518British Heart Foundation Figure 1
Degree of peripheral Thyroxin Deiodination and recurrent cardiovascular events in euthyroid patients undergoing PCI: five-year findings from a large single-center cohort study
Authors: Yuan D S , Jia S D , Zhang C , Liu Y , Zhao X Y , Yang Y J , Gao R L , Xu B , Gao Z , Yuan J Q
Published: October 2021

Background

In euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether thyroxin deiodination level can predict the recurrence of cardiovascular events (CVEs). Using free triiodothyronine to free thyroxine (FT3/FT4) ratio, a marker of peripheral thyroxin deiodination, we aim to investigate its association with recurrent long-term adverse events in this population.

Methods

3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T1<2.41, n=1170; 2.41≤T2<2.75, n=1198; T3>2.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death.

Results

The median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P<0.05). After adjustment of confounding factors, decreased FT3/FT4 ratio was independently associated with an increased risk of all-cause death (HR 1.82, 95% CI 1.13–2.93, P=0.014), cardiac death (HR 1.90, 95% CI 1.04–3.46, P=0.036) and MACCE (HR 1.33, 95% CI 1.10–1.60, P=0.003).

Conclusions

In euthyroid patients undergoing PCI, FT3/FT4 ratio, a surrogate marker of peripheral thyroxin deiodination, demonstrates a strong association with long-term recurrent cardiovascular events. Routine assessment of FT3/FT4 ratio might be a simple and effective tool for risk stratification in this specific patient population.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China (No. 2016YFC1301300, 2016YFC1301301); National Natural Science Foundation of China (No. 81770365)
Association between distance to tertiary hospital and cardiovascular outcomes in coronary artery disease patients
Authors: Gonzalez-Manzanares R , Carmona-Artime L , Ruiz-Moreno M , Perea-Armijo J , Piserra A , Rodriguez-Nieto J , Flores G , Pericet-Rodriguez C , Ojeda S , Hidalgo F J , Suarez De Lezo J , Mazuelos F , Segura J M , Romero M , Pan M
Published: October 2021

Background

The impact of distance from residence to Tertiary Referral Hospital and cardiovascular (CV) outcomes in patients with coronary artery disease (CAD) is unknow. Despite longer travel distances hinder access to healthcare and may worsen CV outcomes, we hypothesize that Mediterranean lifestyle and behaviors in distant rural areas may be associated with a reduced risk of CV death and events.

Purpose

To investigate the association between travel distance to Tertiary Hospital and mid-term cardiovascular outcomes in a population of CAD patients in Southern Spain.

Methods

Retrospective study including all patients discharged after percutaneous coronary intervention (PCI) at a high-volume center in Southern Spain during 2018. Those belonging to another healthcare area were excluded. One-way driving distances from residence to hospital were computed using Google Maps Distance Matrix API with R package “gmapsdistance”. Patients were stratified into tertiles according to travel distance (short, STD; intermediate, ITD; and long, LTD). Kaplan-Meier (KM) and Multivariable Cox regression (adjusted for age, sex, atrial fibrillation, cancer history, prior revascularization and clinical presentation) were used to assess the impact of travel distance on CV death and a composite outcome of MACE (Myocardial Infarction, unplanned PCI and CV death).

Results

Of 1005 patients discharged after PCI during the study period, 966 met the selection criteria. Flowchart and baseline characteristics by distance groups are presented in Figure 1. Median travel distance tertiles were 6.1 (STD), 41.7 (ITD) and 78.4 (LTD). During a median follow-up of 31 (IQR 28–35) months, 50 cardiovascular deaths [STD 27 (8.4%), ITD 13 (4%), LTD 10 (3.1%), p=0.006)] and 63 MACE occurred [STD 45 (13.9%), ITD 37 (11.5%), LTD 26 (8.1%), p=0.060)]. KM curves for the three distance groups are shown in Figure 2. In univariable and multivariable Cox models, longer travel distances were associated with better outcomes, as for every 10 Km increase, there was a 11% and 7% decrease in the hazards of CV death (HR adj: 0.89, CI 0.82–0.98, p=0.029) and of MACE (HR adj: 0.93, CI 0.87–0.99, p=0.025), respectively.

Conclusion

Travel distance was inversely associated with CV events in a population of CAD patients in Southern Spain. Patients in the first tertile of distance had a higher rate of CV death. Multicenter studies involving other Mediterranean regions are needed to confirm these findings and to look for explanations.

Funding Acknowledgement

Type of funding sources: None. Flowchart and baseline characteristicsSurvival curves by distance groups
Trends in all-cause and cardiovascular mortality in patients with acute myocardial infarction: a nationwide analysis over 10 years
Authors: Angoulvant D , Bouteau J , Semaan C , Genet T , Darwiche W , Bisson A , Ivanes F , Fauchier L
Published: October 2021

Background

The decline in mortality reported during last decades in patients with acute myocardial infarction (AMI) has been attributed mainly to improved use of reperfusion therapy. We sought to determine the trends in all-cause and cardiovascular mortality for patients with AMI seen at a nationwide level in recent years.

Methods

Based on the administrative hospital-discharge database, we collected information for all patients treated with AMI between 2010 and 2019 in France. Adverse outcomes including all-cause death and cardiovascular (CV) death were investigated during follow-up.

Results

We used the French administrative hospital-discharge database, including all patients admitted for AMI between 2010 and 2019 (n=797,212, mean age 69 years, 66% male). Among them, 520,258 patients (65%) had ST-segment elevation myocardial infarction (STEMI) and 276,954 (35%) had non-STEMI (NSTEMI). Reperfusion therapy with primary percutaneous coronary intervention increased from 40% in 2010 to 58% in 2019 for patients with STEMI. Revascularization between day 0 and day 8 increased from 38% in 2010 to 49% in 2019 for patients with NSTEMI. At day 30, all-cause death was recorded in 78,826 patients (9.9%), among whom 56,582 (72%) had CV death. The rate of all-cause death and CV death in patients with STEMI and NSTEMI are in the table. Our data showed higher reduction rates in NSTEMI vs STEMI patients regarding both all cause death (−18,4% vs −14,1%) and CV death (−24.21% vs −9.2%).

Conclusion

In a large and systematic nationwide analysis of patients with AMI, the rate of all-cause death and CV death at day 30 decreased from 2010 to 2019, both for those with STEMI and those with NSTEMI. Both death rate reductions were more important in NSTEMI patients despite a lower increase of reperfusion therapy compared to STEMI patients. Earlier diagnosis and management as well as improvement of pharmacological intervention and revascularization strategy may explain this difference.

Funding Acknowledgement

Type of funding sources: None.
Deep learning algorithm predicts angiographic coronary artery disease in stable patients using only a standard 12-lead electrocardiogram
Authors: Leasure M , Jain U , Butchy A , Otten J , Covalesky V , McCormick D , Mintz G
Published: October 2021

Background

Current standard electrocardiogram analysis algorithms cannot predict the presence and extent of coronary artery disease (CAD), especially in stable patients.

Objectives

This study assessed the ability of a novel artificial intelligence algorithm (ECGio) to predict the presence, location, and severity of coronary artery lesions in an unselected stable patient population.

Methods

A cohort of 1659 stable outpatients were randomly divided into training (86%) and validation (14%) subsets, maintaining population characteristics. ECGio was trained and then validated using electrocardiograms paired with angiograms collected from electronic medical records. Coronary artery lesions were classified in two analyses. The primary classification was no/mild (≤30% diameter stenosis [DS]) vs moderate (30–70% DS) vs severe (≥70% DS) CAD; and the secondary classification was yes/no based on ≥50% DS in any vessel.

Results

In the primary analysis of the validation cohort, 22 had no angiographic CAD and were grouped with 56 patients with mild CAD (DS ≤30%), 31 had moderate CAD (DS 30–70%), and 113 had severe CAD (DS ≥70%). The weighted average sensitivity was 93.6%, and the weighted average specificity was 96.5%. In the secondary analysis of the validation cohort, 93 had significant CAD; and 128 did not have significant CAD. There was a sensitivity of 93.1% and specificity of 85.6% in determining the presence of clinically significant disease (≥50% DS) in at least one vessel. On a vessel level ECGio was able to predict stenosis severity with average error in the LAD of 18%, the LCX of 19%, the RCA of 18%, and the LM of 8%.

Conclusion

This validation study strongly suggests that it is possible to utilize an artificial intelligence algorithm to determine the presence and severity of CAD in stable patients using data from a standard 12-lead electrocardiogram.

Funding Acknowledgement

Type of funding sources: None. Confusion MatrixROC Curve
Artificial intelligence approach improves ischaemia prediction beyond the known pretest probability scores
Authors: Bakula A , Haaf P , Caobelli F , Thommen K , Tsirkin A , Failer M , Ruff P , Zellweger M J
Published: October 2021

Background

Pre-test probability (PTP) assessment is crucial in the assessment of patients with suspected ischaemia/coronary artery disease. Presently there is no established role for artificial intelligence in estimating PTP.

Purpose

Comparison of a recently developed memetic pattern based algorithm (MPA) with the diagnostic power of established scores in predicting ischaemia on positron emission tomography myocardial perfusion imaging (PET MPI).

Methods

Consecutive patients undergoing Rubidium PET MPI for routine clinical evaluation of ischaemia were included. The PTP for each patient was estimated by MPA, the Diamond and Forrester scores (DFS), the PTP models from the European Society of Cardiology Guidelines from 2013 (ESC 2013) and 2019 (ESC 2019) and the Framingham scores (FRS). The PET MPI studies were assessed for the presence of ischaemia. Ischaemia was defined as a summed difference score (SDS) ≥2.

Results

The mean age of the 531 patients was 66±11 years, 34% were female, and 50% had known prior coronary artery disease; 208 patients had evidence of ischaemia. No ischaemia was found in 323 patients. The areas under the curve (AUC) are shown in the figure. The artificial intelligence based MPA provided an AUC of 0.76, PTP (ESC 2013) AUC of 0.67, PTP (ESC 2019) AUC 0.67, DFS AUC 0.56, FRS 0.68.

Conclusion

The MPA outperforms the established scores for PTP assessment of the ESC, DFS and FRS in prediction of ischaemia on PET MPI. It has the potential to improve the accuracy of the established diagnostic algorithm for CAD and ischaemia.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was in part funded by the Swiss Heart Foundation.
Percutaneous coronary interventions in patients with left main coronary artery pseudobifurcation lesions: 5-years follow-up
Authors: Maximkin D , Shugushev Z , Faybushevich A , Chepurnoy A , Volkov S , Gitelzon E , Korobkov A , Bagin S , Veretnik G , Bolivougui J M
Published: October 2021

Aims

To increase the effectiveness of percutaneous coronary interventions (PCI) in patients with ostium coronary artery lesions: left arterial descending (LAD) or left circumflex (LCx) – pseudobifurcations.

Methods

220 patients were included in the study. Inclusion criteria: ostium atheroslerotic lesions of left arterial descending (LAD) or left circumflex (LCx) >70% according to angiography and optical coherence tomography (OCT); myocardial ischemia according the FFR measurement. According OCT data, all patients were devoiced into 2 groups. In I group (n=110) according to OCT, atherosclerotic plaque spread from the ostium of LAD and/or LCx to the left main coronary artery (LMCA), and in group II (n=110) - the plaque did not spread into the LMCA. In Group I all patients were initially treated with “Provisional T” stenting of the LMCA, and in Group II – precision stenting of the ostium LAD or LCx. Primary endpoints: frequency of MACE (death, MI, revascularizations).

Results

The long-term results after 5-years were observe in 98 patients from group I and 92 patients from group II. The survival rate of patients from group I and II, free from cardiac events, were 94.9±4.03 and 81.5±3.23, respectively (p<0.001). Cardiac death were observed in 2 (2.04%) patients from group I and 2 (2.17%) patients from group II (p>0.05). Myocardial infarction were observed in 2 (2.04%) patients from group I and 5 (5.43%) patients from group II (p>0.05). The target lesion revascularization (TLR) was performed in 3 patients (3.06%) in group I, and in 12 patients (13.04%) in group II (p<0.001). The total incidence of MACE were 5.2% in group I and 18.5% in group II (χ2=7.825; p=0.023).

Conclusions

OCT-guiding analysis of ostium LAD or LCx could be help in choosing the optimal stenting technique, as well as reliably improve long-term PCI results. However, despite the use of intravascular imaging techniques during PCI, precision stenting of the ostium LAD or LCx, differs worst long-term prognosis of patients.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Russian academic excellence project 5-100
Feasibility, safety and long term outcomes of complex left main bifurcation treatment using the nano inverted t stenting: a multicentre registry
Authors: Rigatelli G , Zuin M , Vassilev D , Huy D , Nguyen V T , Nguyen N , Ronco F , Roncon L
Published: October 2021

Background

The role of double stenting techniques in distal bifurcation left main (LM) disease has gaining interest over the latest years.

Purpose

We present the 3-year multicentre registry outcomes of dual stenting using ultra-thin strut stents and the Nano Inverted-T (NIT) technique in complex unprotected true LM bifurcation disease.

Methods

We analysed the procedural and medical data of consecutive patients enrolled between 1st January 2014 and 1st December 2019 in a multicentre registry for complex LM bifurcation disease treated with the double stenting technique called NIT due contraindications and/or refusal to surgical treatment. Target lesion failure (TLF) was defined as the composite of cardiovascular death, target-vessel MI (TVMI) and clinically driven target lesion revascularization (TLR).

Results

Among two hundred-ninety-five patients (138 males, mean age 70.3±12.8 years), post-operative success was achieved in 100% of cases. Contrast volume, procedural time, and radiation exposure were 139.2±23.4 ml, 15.3±4.9 min, and 1080±1034 cGy/m2 (Figure), respectively. At a mean follow-up of 39.5±0.6 months TLF rate was 6.1% (n=18) while TLR and cardiovascular mortality rates were 3.0 (n=9) and 2.6% (n=8), respectively. Clinically driven angiographic follow-up was available in 26.4% of patients at a mean time from the procedure of 7.5±0.4 months. Clinically restenosis rate was 3.3%.

Conclusions

Revascularization of complex LM bifurcation disease using the NIT double stenting technique resulted feasible and safe with a low incidence of TLF, excellent survival rate and no stent thrombosis. Figure 1.The NIT technique is based on the use of ultra-thin strut (≤80 micron) stents and double stenting starting with side branch stenting frst. The side branch stent is precisely positioned with one possibly only strut protruding into the main vessel which is balloon crushed before the implantation of the main branch stenting. The Proximal optimization technique (POT)–snuggle kissing–POT sequence is mandatory to ensure the coverage of the side branch ostium by both side branch and main branch stents. Snuggle kissing was performed placing the LCX balloon with the proximal marker at the middle rather than at the proximal marker of the LM-LAD balloon, in order to minimize the elliptical deformation of the LM stent.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Mortality after bleeding versus myocardial infarction in coronary artery disease: a systematic review and meta-analysis
Authors: Oliva A , Avvedimento M , Franzone A , Windecker S , Valgimigli M , Esposito G , Juni P , Piccolo R
Published: October 2021

Background

Bleeding is the principal safety concern of antithrombotic therapy and occurs frequently among patients with coronary artery disease (CAD).

Aims

We aim to evaluate the prognostic impact of bleeding on mortality compared with that of myocardial infarction (MI) in patients with CAD.

Methods

We searched Medline and Embase for studies that included patients with CAD and that reported both, the association between the occurrence of bleeding and mortality, and between the occurrence of MI and mortality within the same population. Adjusted hazard ratios (HRs) for mortality associated with bleeding and MI were extracted and ratio of hazard ratios (rHRs) were pooled by using inverse variance weighted random effects meta-analyses. Early events included periprocedural or within 30-day events after revascularization or acute coronary syndrome (ACS). Late events included spontaneous or beyond 30-day events after revascularization or ACS.

Results

141,059 patients were included across 16 studies and 128,660 (91%) underwent percutaneous coronary intervention. Major bleeding increased the risk of mortality to the same extent of MI (ratioHR bleedingvsMI 1.10, 95% CI, 0.71–1.71, P=0.668). Early bleeding was associated with a higher risk of mortality than early MI (ratioHR bleedingvsMI 1.46, 95% CI, 1.13–1.89, P=0.004), although this finding was not present when only randomized trials were included. Late bleeding was prognostically comparable to late MI (ratioHR bleedingvsMI 1.14, 95% CI, 0.87–1.49, P=0.358).

Conclusions

Compared with MI, major and late bleeding is associated with a similar increase in mortality, whereas early bleeding might have a stronger association with mortality.

Impact on daily practice. Major and late bleeding should be considered prognostically equivalent to MI, given the similar association with mortality. Early bleeding has even a stronger association with mortality than early MI, emphasizing the importance of bleeding avoidance strategies among patients undergoing PCI.

Funding Acknowledgement

Type of funding sources: None. Visual AbstractBleeding vs MI risk of mortality
Pharmacodynamic evaluation of the platelet antiaggregant effect of swallowed Ticagrelor versus chewed Ticagrelor in patients with acute coronary syndrome
Authors: Barrera-Ramirez C F , Pineda-Pineda L R , Ilarraza-Lomeli H , Pacheco-Rios M R , Martinez-Gallegos J C , Cordova-Alvelais L T , Tellez-Reynoso O
Published: October 2021

Introduction

Dual antiplatelet therapy represents the standard of care for the treatment of patients with acute coronary syndrome (ACS). Ticagrelor is a direct-acting P2Y12 inhibitor and does not require metabolic activation.

Objective

To assess whether the chewed 180 mg of ticagrelor loading dose (LD), compared to conventional oral administration, increases platelet inhibition and reduces high on-treatment platelet reactivity (HTPR) in patients with ACS.

Method

Single-center randomized clinical trial in patients with ACS. We measured platelet reactivity and % platelet aggregation (%IPA) using VerifyNow P2Y12 (Accumetrics) at baseline, 30 minutes, 1, 4 and 24 hours after LD. HTPR was defined as ≥208 PRU and/or % platelet inhibition ≤15%.

Results

We studied 40 consecutive patients (Pts.), 21 Pts. in the swallowed ticagrelor group and 19 Pts. in the chewed ticagrelor group. At 30 minutes, platelet reactivity was 180.81±64.16 PRU vs. 117±58.62 PRU p<0.01 (95% CI 24.3 to 103.3); At one hour 154.29±84.55 PRU vs 54.84±59.6 PRU p<0.001 (95% CI 52.1 to 146.7) respectively. The baseline results, at 4 and 24 hours, had no differences (p=NS). %IPA was 11.19±22.42 vs 42.26±27.3 <0.0001, (95% CI 15.3, 47); 25.33±34.03 vs 75.47±26.27 p<0.0001, 95% CI (27.5, 66.7) Platelet reactivity in the chewed ticagrelor group was significantly reduced by 52.65% at 30 minutes after LD, compared to 16.79% in the swallowed group (95% CI −0.63 to −0.083; p<0.01). The frequency of HTPR at one hour was 57.14% in the swallowed group vs. 5.26% in the chewed group; p<0.001. After 4 hours, HTPR was not observed in any group.

Conclusions

Chewed ticagrelor allowed a significant reduction in platelet reactivity and HTPR from the first 30 minutes and the first hour.

Funding Acknowledgement

Type of funding sources: None.
Low ALT levels are associated with poor outcomes in acute coronary syndrome patients admitted to the intensive cardiac care unit
Authors: Segev A , Itelmad E , Beigel R , Segal G , Chernomordik F , Matezky S , Grupper A
Published: October 2021

Background

Frailty is an under recognized and important entity that bears worse prognosis.

Purpose

Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients.

Methods

A retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU) between 1/5/2011 and 1/12/2020 at a single tertiary medical center.

Results

The study included 3956 patients after excluding patients with ALT >40 IU/L, cirrhosis and missing data, followed for a median duration of 47 months (IQR 20–77). Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT >10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 vs. 65, P<0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, P<0.001), had higher rates of comorbidities at baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (P<0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, P=0.99), long-term mortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, P<0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46–3).

Conclusion

Lower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU.

Funding Acknowledgement

Type of funding sources: None. 5-year survival according to baseline ALForest plot of variables associated with
Prognostic value of growth differentiation factor-15 in patients with acute myocardial infarction
Authors: Sabirzyanova A , Galyavich A
Published: October 2021

Introduction

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily. Its expression was found in various tissues under the circumstances of hypoxia, inflammation, acute injury. GDF-15 is considered as a biomarker of the risk of cardiovascular events, however, most of the studies on GDF-15 have been carried out in patients with chronic heart failure and comorbid pathology. Our study assessed the clinical value of GDF-15 in the acute stage of myocardial infarction (MI) in patients without concomitant inflammatory diseases, cardiac arrhythmias and with an ejection fraction above 40% according to echocardiography.

Purpose

To evaluate the prognostic value of GDF-15 in patients with acute MI.

Materials and methods

Our study included 118 patients under the age of 70 years with MI with and without elevation of the ST-segment on the electrocardiogram. We determined the levels of GDF-15 by enzyme-linked immunosorbent assay in the first 48 hours from the clinical onset of MI. The clinical dynamics was assessed by questioning patients at 1, 3, 6 and 12 months after discharge from the hospital. The statistical significance of differences in quantitative indicators was assessed by the Student's t-test for a normal distribution and by the Mann-Whitney U test for a non-normal distribution; in qualitative indicators – according to the Pearson's χ2 criterion. Pearson's and Spearman's correlation coefficients were used to assess the tightness of the relationship between quantitative indicators.

Results

The average GDF-15 level in patients with acute MI was 2.25±1.0 ng/ml. 29 cardiovascular events occurred during 12 months of observation, including 2 deaths and 8 recurrent MI. According to autopsy data both deaths occurred due to large-focal transmural MI. 22.8% of patients were re-admitted to hospitals for unstable angina pectoris or recurrent MI. Moreover, in 89.6% of that cases GDF-15 was in the third or fourth quartiles and was ≥2.07 ng/ml. Absolutely all patients with recurrent MI and in the case of death had GDF-15 level in the upper quartile (>2.73 ng/ml). Patients with GDF-15 in the upper quartile had a significantly higher risk of recurrent cardiovascular events including cardiovascular mortality and hospitalizations for unstable angina and MI (RR 4.3 [95% CI 2.4–7.9], p<0.05) in comparison with patients with GDF-15 in the three lower quartiles. We assessed the possibility of combined use of GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and it was revealed that patients who simultaneously had GDF-15 and NT-pro-BNP in the upper quartiles (GDF-15 >2.73 ng/ml, NT-proBNP >1418 pg/ml) had a 5.4 times higher risk of recurrent cardiovascular events (RR 5.4 [95% CI 3.4–8.5] p<0.05).

Conclusion

The increased level of GDF-15 in the acute stage of MI has predictive value and may serve as an additional cardiovascular risk marker.

Funding Acknowledgement

Type of funding sources: None.
Assessment of the ESC quality indicators in patients with acute myocardial infarction: a systematic review
Authors: Masso Van Roessel A , Perello Bordoy A , Mas Llado C , Ramis Barcelo M , Vives Borras M , Pons J , Peral V , Rossello X
Published: October 2021

Background

Quality indicators (QIs) provide a mechanism for measuring opportunities to improve cardiovascular care and outcomes. To help improving quality of care in patients with acute myocardial infarction (AMI), the European Society of Cardiology (ESC) set (in 2017) 20 QIs to evaluate several dimensions of care. These 20 QIs are organized in 3 areas and 7 domains defined in structural, performance measures including patient's feedback and outcomes. Several registries have reported their performance using real-world data, and some of them have reported that higher compliance is associated with lower mortality. There is a need to compile and summarize QI availability, feasibility and global compliance in real-world registries.

Methods

A systematic review of PubMed and Web of Science was conducted including all original articles reporting the use of the ESC QIs in AMI patients. Methods and reporting follow the guidelines of the PRISMA Statement and the protocol was registered in PROSPERO (CRD42020190541). Inclusion criteria were studies providing original data, and studies evaluating the 2017 ESC ACVC set of QIs in patients with AMI (STEMI or NSTEMI). The main exclusion criterion was for non-original articles and studies evaluating a different set of QIs.

Results

Among de 220 screened citations, 9 studies met the inclusion criteria after full-text review. Among these 9 studies, there were 11 different cohorts. Patients were recruited from 3 different continents (31 countries) between 2003 and 2018. The number of QIs assessed ranged from 6 to 20, with 5 studies (56%) reporting data for at least 75% of the 20 QIs. There was variability in the percentage of data availability with 4 QIs from 3 different cohort with limited data (2.4, 3.1, 3.2 and 6.1) and 13 QIs reported in 64% of the cohorts. We found that some publications were unable to provide the exact definition determined by the ESC ACVC working group, with 6 QIs with suboptimal definition (QIs 2.2, 5.1, 6.1, and the 3 QIs from domain 7). The rate of attainment had a great variation. In performance measures we found a higher level of compliance in the QIs 2.1, 4.3 and 5.2, and lower in 2.2 and 4.2.

Conclusions

Our systematic review has shown that it is possible to measure most QIs in existing registries, and that there is room for improvement in terms of data availability, feasibility and levels of attainment to QIs. Our findings may influence the design of future registries to capture this information and help in QIs definition updates. In light of the experience accumulated from existing registries, there is a need to design registries and surveys specifically assessing QIs to have a more accurate picture.

Funding Acknowledgement

Type of funding sources: None.
Systemic immune-inflammation index predicts major adverse cardiovascular events in patients with ST-elevation myocardial infarction
Authors: Denegri A , Obeid S , Raeber L , Windecker S , Gencer B , Mach F , Rodondi N , Heg D , Nanchen D , Matter C M , Klingenberg R , Luescher T F
Published: October 2021

Background

ST-elevation myocardial infarction (STEMI) represents the life-threatening manifestation of atherosclerosis, a chronic inflammatory disease of arterial wall, and is associated with high rate of morbidity and mortality. Thus, inflammatory biomarkers may be useful in identifying high inflammatory burden patients who may benefit from tailored high-intensity secondary prevention therapy.

Purpose

We therefore assessed the relationship between the systemic immune-inflammation index (SII) and CV outcomesamong 1144 all-comers patients admitted to four Swiss University Hospital for STEMI and enrolled in the prospective multicenter SPUM registry cohort I (NCT 01000701).

Methods

SII was calculated as platelet counts x neutrophil counts / lymphocyte counts. Patients were subdivided into three groups according to SII tertiles. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE: stroke, myocardial infarction, CV death). Adjusted Cox proportional hazards regression models were implemented to determine the risk associated with SII and outcomes.

Results

Out of 1144 STEMI patients, 912 patients (79,7%) had available for SII. Patients within the highest tertile were slightly more frequently male (23.0 vs 22.0%, p=0.05), with higher plasma values of neutrophils (11.4±2.4 vs 6.5±3.7 G/l, p<0.001), platelets (275.3±97.5 vs 202.5±51.6 G/l, p<0.001) and lower levels of lymphocytes (1.0±0.6 vs 2.1±1.1 G/l, p<0.001) and LVEF (46.4±11.5% vs 50.4±10.3%, p<0.001) (Fig. 1A). At 1 year, these patients presented the highest rate of all-cause mortality (7.2% vs 2.6%, p=0.02) and MACCE (8.2% vs 3.3, p=0.03). This enhanced risk persisted for all-cause mortality and MACCE, after adjustment for age, sex, ace-inhibitors and statin therapy (Adj. HR 2.85, 95% CI 1.30–6.70, p=0.03 and Adj. HR 2.63, 95% CI 1.25–5.55, p=0.03, respectively, Fig. 1B).

Conclusions

Among a real-world cohort of STEMI-patients, SII highlights the highest inflammatory risk phenotype, being associated with significant increased rates of MACCE and all-cause of death. These observations might help clinicians to furtherly identify patients who may derive the greatest benefit from tailored more intense secondary prevention therapies including inflammatory modulation.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Different COVID19 pandemic phases & STEMI: experience from an Italian hub centre
Authors: Tumminello G , Barbieri L , Toriello F , Lucreziotti S , Carla' M , Conconi B , Salerno Uriarte D , Mafrici A , Carugo S
Published: October 2021

Introduction and methods

During Coronavirus disease 2019 (COVID-19) pandemic a reduction in ST-elevation acute myocardial infarction with an increase in in-hospital mortality has been observed. In our region the pandemic temporal trend was sinusoidal with peaks and valleys. A first outbreak (phase-peak 1 “P-P1”) was in March 2020 (248.12 cases for 100,000 inhabitants), a reduction (phase-valley 1 “P-V1”) in May 2020 (16.68 cases for 100,000 inhabitants) and a second outbreak (phase-peak 2 “P-P2”) in November 2020 (540.17 cases for 100,000 inhabitants; data from Italian Health Ministry). Our hospital was reorganized as one of the 13 Macro-Hubs identified in Lombardy for the treatment of STEMI. Here we describe our experience in the treatment of STEMI patients in the three different phases of COVID-19 pandemic.

Results

In the three different phases the groups were superimposable for mean characteristics, but they differ for COVID-19 infection incidence (table). At multivariate analysis for the entire population COVID-19 infection (OR 45.8 [95% CI] 1.39–1511.79; p=0.03) was the only independent predictor of in-hospital mortality. Focusing on COVID-19 patients (figure) they experienced a 5-time increased incidence of in-hospital mortality (COVID-19pos vs COVID-19neg, 50% vs 11.1%; p=0.02). Moreover, the compresence of COVID-19 infection induced an 8 times increased risk of death (OR 8; [95% CI] 1.85–34.60; p=0.005) determined by a higher incidence respiratory complications (COVID-19pos vs COVID-19neg, 33.3% vs 8.9%; p=0.03) with a similar incidence of cardiac death (COVID-19pos vs COVID-19neg, 16.7% vs 11.17%; p=0.60).

Conclusions

In conclusion our data suggest the crucial necessity of an early and precise diagnosis of COVID-19 infection in STEMI to establish a correct management of this very high risk patients.

Funding Acknowledgement

Type of funding sources: None. STEMI mortality in COVID+ vs COVID−
Clinical impact of CREDO-kyoto risk score on in-hospital bleeding in patients with acute coronary syndrome
Authors: Minematsu Y , Natsuaki M , Yoshioka G , Shinzato K , Nishimura Y , Nishikido T , Node K
Published: October 2021

Background/Introduction

CREDO-Kyoto bleeding risk score was developed to predict the post-discharge bleeding events in patients with percutaneous coronary intervention. However, there were limited reports of the effectiveness of this score to predict the in-hospital bleeding events in patients with acute coronary syndrome (ACS).

Methods

We evaluated 562 consecutive ACS patients in Saga university hospital between 2014 and 2019. Primary outcome was major bleeding during hospitalization. Major bleeding was defined as the GUSTO moderate/severe bleeding. Patients were classified into three groups according to the CREDO-Kyoto bleeding risk score (low, intermediate and high).

Results

Major bleeding events occurred in 12.1% of all patients during hospitalization. Patients in the high risk group (n=22) had significantly higher incidence of major bleeding than those in the intermediate (n=113) and the low risk groups (n=427) (22.7%, 18.6%, versus 9.8%, respectively, p=0.018, see figure). Multivariate analysis showed that intermediate and high risk groups were independent predictors for the in-hospital major bleeding.

Conclusions

CREDO-Kyoto risk score successfully identified high risk ACS patients for the major bleeding during hospitalization.

Funding Acknowledgement

Type of funding sources: None. Results