bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term effects of low-dose tolvaptan in acute decompensated heart failure patients with severe aortic stenosis: the LOHAS registry
Authors: Watanabe Y , Nara Y , Hioki H , Kawashima H , Kataoka A , Nakashima M , Nishihata Y , Hayashida K , Yamamoto M , Tanaka J , Mizutani K , Jujo K , Nakazawa G , Izumo M , Kozuma K
Published: November 2020

Background

Tolvaptan exerts potent diuretic effects in heart failure patients without hemodynamic instability. Nonetheless, its clinical efficacy for acute decompensated heart failure (ADHF) due to severe aortic stenosis (AS) remains unclear. This study aimed to evaluate the short-term effects of tolvaptan in ADHF patients with severe AS.

Methods

The LOw-Dose Tolvaptan (7.5 mg) in Decompensated Heart Failure Patients with Severe Aortic Stenosis (LOHAS) registry is a multicenter (7 centers) prospective registry that assessed the short-term effects of tolvaptan in subjects hospitalized for ADHF with severe AS. A total of 59 subjects were enrolled between September 2014 and December 2017. The primary endpoints were changes in body weight and fluid balance measured daily from baseline up to 4 days.

Results

The median [interquartile range] patient age and aortic valve area were 85.0 [81.0–89.0] years and 0.58 [0.42–0.74] cm2, respectively. Body weight continuously decreased, and fluid balance was maintained from baseline to day 4 (p<0.001, p=0.194, respectively). Median serum B-type natriuretic peptide concentration significantly decreased from 910.5 to 740.0 pg/mL by day 4 (p=0.002). However, systolic blood pressure and heart rate were non-significantly changed (p=0.250, p=0.656, respectively). Hypernatremia (>150 mEq/L) and worsening renal function occurred in 2 (3.4%) and 4 (6.8%) patients, respectively.

Conclusions

Short-term treatment with low-dose tolvaptan is safe and effective, providing stable hemodynamic parameters in patients with ADHF and severe AS.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): This research was supported by Otsuka Pharmaceutical Co., Ltd.
Pericardial Left Ventricular Assist Device (PALVAD) development via large animal and cadaveric models
Authors: Premawardhana A.D.P.E , Lodge A.D , Sachdev S , Karamanavi E , Kotecha D , Rothman A.D , Samara-Ratna P , Adlam D
Published: November 2020

Background

Cardiogenic shock complicates around 8% of acute myocardial infarctions with a significant short term mortality of 35–50%. Traditional mechanical circulatory support can improve cardiac output (CO) however they have significant adverse event profiles related to their position within the circulation, including but not limited to infection, stroke and embolism.

PALVAD is an extra circulatory left ventricular assist device, designed to be implanted percutaneously., It provides cardiac support whilst sitting outside the circulatory system in the space between the pericardium and left ventricular (LV) free wall. The dual balloon system connects to an external pumping system via a drive line. The actuator balloon augments CO through ECG gated LV systolic compression and the positioning balloon sits against the pericardial surface dissipating this force across a large surface.

Purpose

Assess device efficacy in a low CO state in a non-recovery porcine model.

Understand device interactions with the left ventricle and pericardium in a cadaveric model.

Methodology

Non-recovery porcine model experiments were conducted in three 40k-50g pigs at a large animal catheterisation facility. An Esmolol infusion was titrated to create a low output state. A Millar catheter was placed in the LV for simultaneous pressure and volume measurements and a Transonic flow probe was placed around the internal carotid for flow measurements. The device was inserted percutaneously and operated for a total of 4.7 hrs.

For cadaveric experiments the device was inserted into a Thiel embalmed saline perfused cadaver following which detailed CT and MRI imaging was undertaken.

Results

When target reduction in cardiac output was met PALVAD increased systolic pressure by 34%, stroke volume by 54%, CO by 53% and flow by 53%. There was no macroscopic evidence of epicardial or pericardial damage. Cadaveric imaging further informed optimal positioning of the device in relation to the LV free wall.

Conclusions

PALVAD performance during low CO state in non-recovery porcine experiments is promising. Further recovery experiments, including histology assessment, are planed to evaluate safety and efficacy with longer term use to guide optimisation towards the eventual aim of a first-in-man trial.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Translational Research Grant
The occurrence and impact of blood transfusion in cardiogenic shock patients supported by an Impella device: a retrospective study
Authors: Bogerd M , Karami M , Raasveld S.J , Ouweneel D.M , Lagrand W.K , Vlaar A.P.J , Henriques J.P.S
Published: November 2020

Background

Cardiogenic shock (CS) patients are frequently supported by mechanical devices, such as the Impella. The use of these devices is associated with device-related complications, such as hemolysis and bleeding, which may necessitate blood transfusion. Blood transfusion has been associated with worse clinical outcome. Information on the occurrence and impact of blood transfusion in these patients is scarce.

Purpose

To assess the incidences of hemolysis, bleeding and red blood cell (RBC) transfusion in CS patients receiving Impella support, to identify patients at risk for RBC transfusion and to assess mortality in transfused and non-transfused patients.

Methods

We performed a single center retrospective cohort study between August 2006 and April 2019, collecting data on all patients supported by an Impella device (type 2.5, CP or 5.0) for more than 24 hours. Patient baseline characteristics, clinical course and outcomes were compared between patients transfused with RBCs and non-transfused patients. Multivariate logistic regression analysis was used to identify factors associated with RBC transfusion. Correlations between patient characteristics and the number of units of RBCs administered were tested using the Spearman's Rank correlation coefficient.

Results

We included 122 CS patients who received Impella support for longer than 24 hours. Seventy-eight percent was male and the median age was 60.0 years. Transfused patients had a longer support duration compared with non-transfused patients (respectively; 97 (52–173) hours versus 51 (39–76) hours, p<0.001). Of all included patients, 68% received RBC transfusion. Transfused patients received a median of 1.5 (0.6–2.8) units of RBCs per day. The incidence of hemolysis was 10% in transfused patients and 11% in non-transfused patients (p=NS). Bleeding occurred in 61% of the transfused patients and 11% of the non-transfused patients (p<0.001). Higher age, lower hemoglobin level prior to Impella implant and longer support duration increased the odds of receiving RBC transfusion. The 30-day mortality was similar in transfused and non-transfused patients, respectively 58% and 42% (p=NS) (Figure 1. Kaplan-Meier Curve showing 30-day mortality of transfused and non-transfused patients).

Conclusion

RBC transfusion was required in more than two-third of the CS patients who received Impella support for longer than 24 hours. Higher age, lower hemoglobin level prior to implant and longer support duration were independent risk factors for RBC transfusion. In contrast to previous studies, transfusion was not associated with 30-day mortality. Future research should focus on the effects of RBC transfusion on morbidity and mortality and investigate the optimal transfusion criteria and aims.

Funding Acknowledgement

Type of funding source: None
Impact of the angle between aortic and mitral annulus on the occurrence of hemolysis during Impella support
Authors: Nakamura M , Imamura T , Ueno H , Kinugawa K
Published: November 2020

Background

Hemolysis of Impella is known as a major comorbidity and adequate device positioning and optimization of volume status are recommended. However, we have sometimes experienced hemolysis refractory to these adjustments and anatomical feature appears to be crucial in such cases.

Methods

We enrolled 26 patients (median 71 y; BSA 1.6 m2; LVEF 27%) with cardiogenic shock who received Impella insertion from March 2018 to November 2019. The angle of the aortic and mitral annulus which was drawn at the apical 3-chamber view on echocardiography, just before or after Impella insertion was measured (Figure). Hemolytic event was defined as follows; (1) Gross dark red urine and elevation of serum LDH level after initiation of Impella support were seen and subsequently required to lower the support level of Impella under P6. (2) Blood sample data indicating hemolysis (i.e. elevation of LDH level over 1.5 fold of normal range, anemia complicated with decreased haptoglobin, the elevation of total bilirubin level accompanied indirect bilirubin elevation) was found and subsequently required to initiate continuous hemodiafiltration.

Results

The freedom from hemolytic event was significantly lower in the narrow angle group (<126.5 degrees, Figure A) compared with the wide angle group (≥126.5 degrees, Figure B) (18% vs 83%, p<0.0001). The narrow angle was a significant risk factor of hemolytic event with an unadjusted hazard ratio 13.9 (95% confidence interval 2.88–67.2, p=0.0499) and a hazard ratio 15.5 (95% confidence interval 3.15–76.3, p=0.0008) adjusted for lower pulmonary artery pulsatility index, which was another risk factor significant in the univariate analyses. Furthermore, 30-day survival rate was significantly lower in the narrow angle group compared with the wide angle group (63% vs 100%, p=0.0116).

Conclusions

The narrow angle (<126.5 degrees) was an independent risk factor of hemolytic event and 30-day survival was lower compared with the wide angle group.

Figure 1

Funding Acknowledgement

Type of funding source: None
Impact of acute kidney injury on in-hospital outcomes among patients hospitalized with acute heart failure: a propensity score matched analysis
Authors: Shetty S , Malik H , Abbas A , Ying Y , Aronow W , Briasoulis A
Published: November 2020

Background

Acute kidney injury (AKI) is frequently present in patients admitted for acute heart failure (AHF). Several studies have evaluated the mortality risk and have concluded poor prognosis in any patient with AKI admitted for AHF. For the most part, the additional morbidity and mortality burden in AHF patients with AKI has been attributed to the concomitant comorbidities, and/or interventions.

Purpose

We sought to determine the impact of acute kidney injury (AKI) on in-hospital outcomes in patients presenting with acute heart failure (AHF). We identified isolated AKI patients after excluding other concomitant diagnoses and procedures, which may contribute to an increased risk of mortality and morbidity.

Methods

Data from the National Inpatient Sample (2012- 14) were used to identify patients with the principal diagnosis of AHF and the concomitant secondary diagnosis of AKI. Propensity score matching was performed on 30 baseline variables to identify a matched cohort. The outcome of interest was in-hospital mortality. We further evaluated in-hospital procedures and complications.

Results

Of 1,470,450 patients admitted with AHF, 24.3% had AKI. After propensity matching a matched cohort of 356,940 patients was identified. In this matched group, the AKI group had significantly higher in-hospital mortality (3.8% vs 1.7%, p<0.001). Complications such as sepsis and cardiac arrest were higher in the AKI group. Similarly, in-hospital procedures including CABG, mechanical ventilation and IABP were performed more in the AKI group. AHF patients with AKI had longer in-hospital stay of ∼1.7 days.

Conclusions

In a propensity score-matched cohort of AHF with and without AKI, the risk of in-hospital mortality was >2-fold in the AKI group. Healthcare utilization and burden of complications were higher in the AKI group.

Funding Acknowledgement

Type of funding source: None
Plaque instability in acute coronary syndromes: a possible pathogenic role of gut microbial communities
Authors: Pisano E , Severino A , Bugli F , Pedicino D , Paroni Sterbini F , Martini C , Vinci R , Canonico F , Bonanni A , D'Aiello A , Ciampi P , Ponzo M , Sanguinetti M , Crea F , Liuzzo G
Published: November 2020

Background

The imbalance between protective and harmful bacteria in the microbial communities leads to a non-physiological condition, known as “dysbiosis”. In the last decade, several studies have suggested that gut microbiota can contribute to the development and progression of various disease including cardiovascular disease through metabolism-mediated pathways. The production and the release of bacterial metabolites, including Trimethylamine N-oxide (TMAO), can affect host health acting to distant organs.

Purpose

The aim of the present study was to explore the gut microbiota and the levels of TMAO in patients with stable angina (SA) and acute coronary syndrome (ACS) with or without elevation of the ST segment, respectively STEMI and NSTEMI, and in control subjects.

Methods

Feces were obtained from ACS (n=31) and SA (n=23) patients and controls (n=24). Genomic DNA was isolated using the QIamp DNA Stool Mini Kit. Samples were subjected to 16S rRNA gene V3–V4 region sequencing by an Illumina MiSeq TM platform. A combination of software packages QIIME and VSEARCH was used to generate a biological observation matrix (BIOM) at different taxonomic levels (from phylum to genus). The BIOM was analysed using the Web-based program MicrobiomeAnalyst. β-diversity between groups was obtained by weighted UniFrac distance metric analysis. Serum TMAO levels were measured with a UPLC-MS/MS mass spectrometry in SA and ACS patients.

Results

β-diversity analysis showed a different bacterial composition in SA and ACS patients and controls ([PERMANOVA] F-value: 1.9706; R-squared: 0.050567; p-value <0.018) (Figure 1A). In particular, analysis between the three groups revealed a significant enrichment of Streptococcus genus in ACS patients (Kruskas Wallis test; p=0.0085) (Figure 1B). Controls and ACS revealed a similar gut microbial composition ([PERMANOVA] F-value: 0.7591; R-squared: 0.014388; p-value <0.61) (Figure 2A); in contrast, controls and SA showed separate clusters according to relative differences in taxonomic composition ([PERMANOVA] F-value: 3.0498; R-squared: 0.064821 p-value <0.006) (Figure 2B). Finally, β-diversity analysis in SA and ACS revealed different microbial communities in the two groups [PERMANOVA] F-value: 2.5103; R-squared: 0.046051; p-value <0.025) (Figure 2C) that could partially explain the severity progression of cardiovascular disease. Serum TMAO levels were higher in STEMI (n=14) as compared to SA and to NSTEMI (n=16) (respectively p=0.016 and p=0.028) (Figure 3).

Conclusion

These results, taken together, suggest that gut microbiota and its derived metabolites might play an essential role in the progression of atherosclerosis and in coronary plaque instability.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Linea D1 Università Cattolica del Sacro Cuore
Artificial intelligence-enabled detection of paroxysmal atrial fibrillation from normal sinus ECGs in patients with coronary microvascular dysfunction
Authors: Ahmad A , Corban M , Toya T , Attia Z.I , Noseworthy P , Shelly Cohen M , Lopez-Jimenez F , Kapa S , Friedman P.A , Lerman A
Published: November 2020

Background

Artificial Intelligence (AI) algorithms enabled the detection of patients with paroxysmal atrial fibrillation (PAF) from a single normal sinus rhythm (NSR) ECG. Coronary microvascular dysfunction (CMD) is a precursor for coronary artery disease, which is a known risk factor for AF.

Purpose

The aim of this study is to examine the probability of PAF, according to AI-enabled algorithm estimation, in patients with CMD.

Methods

1858 patients without persistent atrial fibrillation with signs and/or symptoms of ischemia and with non-obstructive CAD (<40% stenosis) who underwent invasive coronary microvascular functional assessment and the ECG closest to the functional assessment were included in this analysis. Patients with coronary flow velocity reserve (CFR) <2 in response to adenosine were labelled as endothelial-independent CMD; % increase in coronary blood flow (%ΔCBF) <50% in response to acetylcholine were labelled as endothelial-dependent CMD. Patients were categorized into 4 groups. G1: Normal (NL) CFR/NL %ΔCBF; G2: Abnormal (ABN) %ΔCBF only; G3: ABN CFR only; G4: ABL CFR & %ΔCBF. The probability of having PAF (%probAF) was calculated by a previously-trained and validated AI algorithm. AF Flag = %probAF >9%; which is a pre-set cut-off found to have the highest accuracy of identifying patients with PAF (Area Under the Curve = 0.87).

Results

Mean age for patients was 51.2±12.4 and 66.3% were females. 835 (45%) were in G1, 39 (2%) in G2, 911 (49%) in G3, and 73 (4%) in G4. Compared to G1 and G2, G3 and G4 were older, had more diabetes and higher smoking rates (p<0.05 for all). Furthermore, G4 had a significantly higher %probAF compared to other groups (Fig. 1). G4 were also more likely to be flagged by the algorithm as having PAF, even after adjusting for cardiovascular risk factors, with an odds ratio of 1.9 [CI 95% 1.1–3.3; p=0.03]) (Fig. 2).

Conclusion

Patients with combined CMD have a significantly higher probability of having PAF based on an AI-enabled algorithm. Further research is warranted to know if patients with CMD would benefit from formal AF screening at the time of diagnosis.

Funding Acknowledgement

Type of funding source: None
Intracoronary nitroglycerin injection through a homemade side-hole ballon for coronary slow/no-reflow phenomenon prevention
Authors: Gu C , Qiao R.U.I
Published: November 2020

Objective

The evaluate nitroglycerin-injection during the homemade side-hole ballon into the proximal segment of the target lesion by TIMI blood flow and the corrected TIMI frame count (CTFC) during primary PCI for patients with ST-segment elevation myocardial infarction (STEMI).

Methods

All patients were diagnosed with STEMI. A dual antiplatelet therapy was given; patients were able to receive pPCI. The basic TIMI blood flow and CTFC were recorded after angiography and randomized according to the random number table by group A (n=61, early nitroglycerin injection via side-hole ballon) andgroup B (n=59, Traditional protocol PCI). Side-hole ballon was made by the ballon that passed the target lesion and puncture it with holes with needle. The TIMI blood flow and CTFC status immediately after the pPCI and the related events during the hospitalization and 6 months discharged.

Results

There were no significant differences between the baseline and laboratory parameters of the two groups (P>0.05). Also no differences in TIMI blood flow and CTFC frame before the target vessel was opened (P>0.05), Further no difference in number of implanted stents, stent length and diameter. The immediate effect after pPCI showed, the early nitroglycerin injection via side-hole ballon have effect on the TIMI blood flow (P=0.027), the CTFC (P=0.007) and the proportion of slow/no-reflow (6.56% vs. 22.03%, P=0.015). There was no difference in the incidence of MACE between two groups during hospitalization and 30 days follow-up. The incidence of MACE at 6 months follow-up was significantly lower in group A (1.63% vs. 10.17%, P=0.046).

Conclusion

In pPCI process, the early upstream nitroglycerin injection via homemade side-hole ballon can significantly reduce the incidence of slow/no-reflow after pPCI while the guidewire/balloon passes through the lesion. After pretreatment by this manner, the patient's 6-month MACE rate can be significantly improved.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The basic research project of Anhui Medical University
Fractional flow reserve and instantaneous wave-free ratio discordance in patients with severe aortic valve stenosis
Authors: Yamanaka F , Shishido K , Yokota S , Moriyama N , Mashimo Y , Hayashi T , Miyashita H , Yokoyama H , Tobita K , Mizuno S , Tanaka Y , Murakami M , Takahashi S , Tsujita K , Saito S
Published: November 2020

Background

It has been reported that discordance between fractional flow reserve (FFR) and Instantaneous Wave-Free Ratio (iFR) could occur in up to 20% of cases. However, there are no reports regarding discordance between FFR and iFR in patients with severe aortic valve stenosis (AS).

Purpose

We aimed to investigate the discordance between FFR and iFR in patients with severe AS.

Methods

Severe AS was defined as an aortic-valve area of ≤1.0 cm2, a mean aortic-valve gradient of 40mmHg or more, or a peak aortic-jet velocity of 4.0 m/s or more. Intermediate coronary artery stenosis was defined as 30% to 70% stenosis (visual estimation). FFR and iFR were calculated in 4 quadrants based on values of FFR ≤0.8 and iFR ≤0.89 (positive discordance; low FFR and high iFR, negative discordance; high FFR and low iFR).

Results

We examined consecutive 140 patients (164 intermediate coronary artery stenosis vessels). Mean FFR and iFR ± standard deviation was 0.82±0.09 and 0.82±0.14, respectively. The discordance was observed in 48 vessels (29.3%). In the discordant group, most of cases were negative discordance (45 cases, 93.6%). Binary logistic regression analysis showed that left anterior descending artery (Hazard Ratio 3.80; 1.55 to 9.31, p=0.0036) was independently associated with negative discordance.

Conclusions

In patients with severe AS, the discordance between FFR and iFR could be observed in 29.3% of the vessels, mostly negative discordance. The left anterior descending artery is an independent predictor for negative discordance.

Funding Acknowledgement

Type of funding source: None
The Gly82Ser polymorphism in the receptor for advanced glycation end products is associated with increased risk for coronary events in the general population
Authors: Grauen Larsen H , Sjogren M , Engstrom G , Nilsson P.M , Orho-Melander M , Nilsson J , Melander O , Schiopu A
Published: November 2020

Background/Introduction

Activation of the receptor for advanced glycation end products (RAGE) by AGEs and various immune mediators has pro-inflammatory and pro-atherogenic effects. RAGE also exists in a soluble form, sRAGE, that acts as a decoy receptor for RAGE ligands. Low plasma sRAGE has previously been found to be associated with a higher risk for major adverse coronary events (MACE) in the population.

Purpose

The purpose of our study was to examine the causality of the association, by exploring whether genetic variants that influence sRAGE are associated with atherosclerosis progression and incident MACE and mortality in the population.

Methods

We performed a genome-wide association study (GWAS) in 4192 individuals from a randomly selected subgroup of a population-based cohort. Subsequently, we explored the associations between the identified single nucleotide polymorphims (SNPs) associated with plasma sRAGE levels, baseline intima media thickness (IMT) and IMT progression in the common carotid artery during a median follow-up of 16.5 years. Further, we analyzed the prospective relationships between the sRAGE-associated SNPs, incident MACE and mortality in the entire population-based cohort of 29245 individuals. The median follow-up time from baseline was 21.2 years for MACE and 21.6 years for total mortality (time to event or end of follow-up).

Results

We found the minor alleles of two single nucleotide polymorphisms (SNPs), rs2070600 and rs204993, to be independently associated with lower plasma sRAGE. While rs204993 is a silent intronic mutation, rs2070600 is known to cause a Gly82Ser polymorphism in the ligand binding domain, enhancing RAGE propensity for activation. In Cox regression analyses, we found an association between the minor T (vs. C) allele of rs2070600 and increased risk for first-time MACE [HR 1.12 (1.02–1.23); P=0.023]. The association was independent of traditional cardiovascular risk factors, blood pressure-lowering medication and lipid-lowering medication at baseline. rs204993 was not associated with MACE. Neither SNP was associated with carotid IMT at baseline or with IMT progression. We did not identify any relationships with total mortality.

Conclusions

We demonstrate for the first time an independent link between a genetic RAGE determinant and the risk for MACE in the population. Despite both identified SNPs being associated with lower sRAGE levels, only the functional rs2070600 mutation was associated with MACE, suggesting that the link is probably due to the enhancement of RAGE function rather than to the sRAGE lowering effect.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): This study was supported by grants from the Swedish Research Council and the Swedish Heart and Lung foundation.
Indoleamine 2,3 dioxygenase (IDO) as a new predictor for advance coronary artery diseases
Authors: Wongpraparut N , Pengchata P , Piyophirapong S , Pongakasira R , Maneechotesuwan K
Published: November 2020

Background

Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in in the kynurenine (Kyn) pathway of tryptophan (Trp) degradation, is modulated by inflammation and regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. This response accelerates the resolution of inflamed tissues to protect them against collateral damage and facilitate tissue healing. A growing body of evidence indicates that IDO-mediated Trp metabolism is involved directly or indirectly in atherogenesis. Little is known about IDO activity in patients with active coronary artery disease (CAD).

Purpose

We hypothesized that IDO activity as reflected by Kyn/Trp ratio and Kyn levels correlated with coronary artery disease (CAD) severity and predicted 1-year major adverse cardiac events (MACE).

Method

We prospectively enrolled the patients whom underwent coronary angiography in our institute. We excluded the patients whom might have other non-cardiac causes of elevated inflammatory biomarkers such as rheumatoid arthritis, allergic asthma, and so on. Measurements of IDO, hs-troponin and hs-CRP levels were performed at baseline and IDO activity was monitored every 6 month at interval. Baseline demographic, coronary angiogram/interventions data were recorded. Significant CAD defined as >70% stenosis in major epicardial vessel. Patients were followed up for 1-year. MACE were pre-specified.

Results

Three-hundred and five patients were enrolled. Ninety-eight patients (32%) presented with acute coronary syndrome. There was a significant difference in IDO, kynurenine, and hs-troponin between patients with and without significant CAD (Table 1). In addition, baseline IDO activity, kynurenine and hs-troponin levels were significantly higher in significant CAD patients with 3-vessel, 2-vessel and 1-vessel involvements than those with insignificant CAD; (0.17 vs 0.14 vs 0.14 vs 0.04, p<0.01), (5.8 vs 4.5 vs 5.1 vs 2.9 μM/g, p<0.01) and (18.2 vs 12.4 vs 12.7 vs 11.1 mg/dL, p<0.001), respectively. Preliminary data in 287 patients with completion of 1-year follow up showed that 1-year mortality was 2.9%. In comparison between patients who survived and death, it demonstrated markedly higher baseline kynurenine (5.12 vs 0.54 μM/g, p<0.03) and IDO (0.15 vs 0.01, p<0.02) in the patients without 1-year mortality.

Conclusion

Immunometabolic response mediated through IDO function were enhanced in patients with CAD and correlated with the severity and extent of the disease. Patient with inadequate IDO response had a higher 1-year mortality.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): The Siriraj grant for research development and medical education of the Faculty of Medicine Siriraj Hospital
Acute coronary syndrome patients with two minor high-bleeding risk criteria have the same bleeding rate that patients with one major criteria
Authors: Cordero A , Garcia-Acuna J.M , Rodriguez-Manero M , Cid B , Alvarez Alvarez B , Agra-Bermejo R , Escribano D , Bertomeu-Gonzalez V , Moreno-Arribas J , Zuazola P , Gonzalez-Juanatey J.R
Published: November 2020

Background

In 2019 the Academic Research Consortium of high-bleeding risk (ARC-HBR) proposed a new and binary definition of high-bleeding risk (HBR) patients based on the presence of 1 major or 2 minor criteria.

Methods

Prospective study of all consecutive patients admitted for ACS in two different centers. We analyzed bleeding incidence in patients with 1 major criteria (1MC) vs. 2 minor criteria (2mC) using the 2019 ARC-HBR consensus. Bleeding events were collected according those fitting definitions 3 or 5 of the BARC consortium.

Results

We included 8,724 patients included and 40.9% we classified as HBR; 20.9% for 1MC and 20.0% for 2mC. In-hospital mayor bleeding rate was 8.6%; no-HBR patients had 0.3%, 2mC 15.1% and 1MC 29.7% (p<0.001 for the comparison). In contrast, the statistically highest in-hospital mortality was observed in patients with 2mC (11.4%), followed by patients with 1MC (8.0%) and no-HBR patients (2.0%).

During follow-up (median time 57.8 months) all-cause mortality rate was 21.0% and cardiovascular dead 14.2%. The incidence of post-discharge major bleeding was 10.5%. No-HBR patients had the lowest bleeding rate (7.4%) and no difference was observed in patients with 1MC (14.6%) or 2mC (15.8%) (figure). The multivariate analysis, adjusted by age, gender, medical treatment, atrial fibrillation and revascularization and considering all-cause mortality as competing risk, showed independent association of 1MC (sHR: 1.46, 95% 1.22–1.75) and 2mC (sHR: 1.31, 95% CI 1.05–1.63) with post-discharge major bleeding.

Conclusions

HBR patients according to the 2019 ARC-HBR containing 2mC or 1MC are at similar and higher risk of in-hospital or post-discharge bleeding events

Funding Acknowledgement

Type of funding source: None
Characteristics and outcome in foreign-born vs Sweden-born patients with myocardial infarction
Authors: Zwackman S , Karlsson J.-E , Sederholm Lawesson S , Jernberg T , Leosdottir M , Eriksson M , Alfredsson J
Published: November 2020

Introduction

Immigration is increasing in most European countries. Little is known about differences in baseline characteristics and outcome between foreign-born and native patients with myocardial infarction (MI).

Purpose

To investigate differences in baseline characteristics and one-year mortality after an MI, based on region of birth.

Methods

We included 194 498 MI patients (36% women) between 2005 and 2016 from the SWEDEHEART registry and compared them according to region of birth: Sweden (Sw, n=166020), Other Nordic countries (No, n=10856), EU countries except Nordic (EU, (n=6301), Non-EU Europe (non EU, n=4779), Asia (n=4927), Africa (n=669), S America (n=567) and N America (n=379). One-year mortality was assessed using a Cox regression model (pairwise with Swedish-born as reference) and in a second model adjusting for age and sex. Data are presented as hazard ratios (HR) with 95% confidence intervals (CI).

Results

There was an increased proportion of foreign-born patients over time (12.8 to 16.7%).

We observed substantial differences in risk factors and comorbidity according to region of birth (lowest vs highest value) in age (mean) (58 vs 72 year, African vs Sw. born), smoking (19 vs 39%, Sw. vs Asian born), history of diabetes (20 vs 36%, African vs Sw. born), hypertension (40 vs 59%, born in African vs No.), MI (17 vs 23%, S America vs EU born) stroke (9 vs 20%, born in S American vs No.), low income (28% vs 56%, Sw. vs Asian born) and low level of education (27 vs 49%, born in Africa vs No.). One-year mortality according to region of birth was 15.4% for patients born in Sweden, 14.0% for patients born in other Nordic countries, 12.8% in EU, 9.6% for non-EU Europe, 6.3% for Asia, 8.4% for Africa, 6.7% for S America and 15.0% for N America. After adjustment for age and sex, the only significant differences were higher mortality in patients born in other Nordic countries (HR 1.1, 95% CI: 1.01–1.12), non-EU Europe (HR=1.12, 95% CI: 1.02–1.23) and Africa (HR=1.68, 95% CI: 1.29–2.19) compared to patients born in Sweden.

Conclusions

We observed increased rate of foreign-born MI patients, with differences in risk profile, comorbidity, education and financial resources according to region of birth, which may impact on observed differences in outcome. Equal access to care pose a challenge which may merit a more comprehensive and individualised approach to cardiac care. Future analyses should explore differences in treatment based on region of birth and potential association with outcome.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Kamprad Family for Entrepeneurship, Research and Charity; The County Council of Östergötland, Sweden; Medical Research Council of Southeast Sweden
Clinical characteristics and prognosis in patients with premature coronary artery disease of different genders after intervention
Authors: Tang X.F , Yao Y , Jia S.D , Liu Y , Xu B , Yuan J.Q
Published: November 2020

Objective

To investigate the clinical characteristics and long-term prognosis of coronary intervention in patients with premature coronary artery disease (PCAD) between different genders.

Methods

From January 2013 to December 2013, 4 744 patients diagnosed as PCAD with percutaneous coronary intervention (PCI) in our hospital were enrolled. The general clinical data, laboratory results and interventional treatment data of all patients were collected, and the occurrence of major adverse cardio-cerebrovascular events (MACCE) within 2 years after PCI was followed up.

Results

Of the 4 744 patients undergoing PCI, 3 390 (71.5%) were males and 1 354 (28.5%) were females. The 2-year follow-up results showed that the incidence of BARC grade 1 hemorrhage in female patients was significantly higher than that in male patients (6.9% vs. 3.7%; P<0.001); however, there was no significant difference in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), all-cause death, cardiac death, recurrent myocardial infarction, revascularization (target vessel revascularization and target lesion revascularization), stent thrombosis, stroke and BARC grade 2–5 hemorrhage between the two groups (P>0.05). Multivariate COX regression analysis showed that gender was an independent risk factor for BARC grade 1 bleeding events in PCAD patients (HR=2.180, 95% CI: 1.392–3.416, P<0.001), but it was not an independent risk factor for MACCE and BARC grade 2–5 bleeding. Hyperlipidemia, preoperative SYNTAX score, multivessel lesions and NSTE-ACS were the independent risk factors for MACCE in PCAD patients with PCI (HR=1.289, 95% CI: 1.052–1.580, P=0.014; HR=1.030, 95% CI: 1.019–1.042, P<0.001; HR=1.758, 95% CI: 1.365–2.264, P<0.001; HR=1.264, 95% CI: 1.040–1.537, P=0.019); gender, hyperlipidemia, anticoagulant drugs like low molecular weight heparin or sulfonate were the independent risk factors for bleeding events (HR=1.579,95% CI 1.085–2. 297, P=0.017; HR=1.305, 95% CI 1.005–1.695, P=0.046; HR=1.321, 95% CI 1.002–1.741, P=0.048; HR=1.659, 95% CI 1.198–2.298, P=0.002).

Conclusion

The incidence of minor bleeding in women with PCAD is significantly higher than that in men; After adjusting for various risk factors, gender is an independent risk factor for minor bleeding events, but not an independent risk factor for MACCE in patients with PCAD.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Science and Technology Support Program of China
Quality and clinical outcomes of primary percutaneous coronary intervention after ST-segment elevation myocardial infarction: a population density analysis of a Japanese nationwide registry
Authors: Yamaji K , Kohsaka S , Inohara T , Numasawa Y , Ishii H , Amano T , Ikari Y
Published: November 2020

Background

Despite progress in acute myocardial infarction (MI) treatment, data on geographical disparities in its care remain limited.

Purpose

We aimed to assess the discrepancy by population density (PD) on the quality and clinical outcomes of patients with primary percutaneous coronary intervention (PCI) after ST-segment elevation MI (STEMI).

Methods

The J-PCI registry is a prospective procedural registry conducted by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) to assure the quality of delivered care. Between January 2014 and December 2018, 209,521 patients underwent PCI for STEMI in 1,126 institutes. Population of administrative municipal-level districts was determined through the complete population census. The patients were divided into tertiles according to the PD of the PCI institution location (low: <951.7/km2, n=69,797; middle: 951.7–4,729.7/km2, n=69,750; high: ≥4,729.7/km2, n=69,974).

Results

Patients treated in high PD administrative districts were younger (low: 69.1±12.9, middle: 68.7±12.9, high: 68.0±13.1) and likely to be male (low: 75.6%, middle: 76.0%, high: 76.6%). No significant correlation was observed between PD and door-to-balloon time (DTB: regression coefficients: 0.036 per 1000 people/km2, 95% CI: −0.232 to 0.304, P=0.79). Patients treated in low PD areas had higher crude in-hospital mortality rates than those treated in high PD areas (low: 2.89%, middle: 2.60%, high: 2.38%; P<0.001). Moreover, PD and in-hospital mortality had a significantly inverse association, before and after adjusting for baseline characteristics (crude odds ratio [OR]: 0.983 per 1,000/km2, 95% confidence interval [CI]: 0.973–0.992, P<0001; adjusted OR: 0.980 per 1,000/km2, 95% CI: 0.964–0.996, P=0.01, respectively). Higher PD districts had more operators per institute (low: 6, interquartile range [IQR] 3–10; middle: 7, IQR 3–13; high: 8, IQR 5–13, P<0.001), suggesting an inverse association with in-hospital mortality (OR: 0.992, 95% CI: 0.986–0.999, P=0.03).

Conclusions

Marked geographical inequality was observed in immediate case fatality; patients treated in population-dense areas had a lower in-hospital mortality than those treated in less dense areas. Variation in the number of operators per institute, rather than traditional quality indicators (e.g. DTB) may explain the difference in in-hospital mortality.

Funding Acknowledgement

Type of funding source: None
Impact of age on the obesity paradox in acute coronary syndrome: a nationwide analysis
Authors: Narasimhan B , Ho K , Wu L , Amreia M , Isath A , Bhatia K , Shah A , Kantharia B
Published: November 2020

Background

The obesity paradox – indicating improved short term mortality in obese individuals has been widely explored in a number of cardiovascular conditions. However, its validity in an elderly population and the possible physiological impact of aging on this phenomenon in Acute Coronary syndrome (ACS) remain unclear. In this study, we aim to determine the relationship between obesity and in-hospital mortality, morbidity, and health care resource utilization in this cohort of patients.

Methods

A retrospective study was conducted using the AHRQ-HCUP National Inpatient Sample for the year 2014. Elderly adults (≥65 years) with a principal diagnosis of ACS and a secondary diagnosis of obesity were identified using ICD-9 diagnosis codes as described in the literature. The primary outcome of in-hospital mortality and secondary outcomes like length of hospital stay (LOS), and total hospitalization costs were analyzed. Propensity score (PS) using the next neighbor method without replacement with 1:1 matching was utilized to adjust for confounders. Independent risk factors for mortality were identified using a multivariate logistic regression model.

Results

In total, 1,137,108 hospital admissions with a primary diagnosis of ACS were identified, of which 7.46% were obese. In-hospital morality during the index admission was lower among obese patients with ACS compared to non-obese patients (4.62 vs 6.87%, p<0.001) with significantly lower 30-day readmission rates as well (p<0.001). However, in-hospital mortality rates during readmission were statistically equivalent between the obese and non-obese groups (5.6 vs 8.3%, p=0.72). LOS during the index admission was longer for obese patients (6.39 vs 5.36 days, p=0.65) but equivalent to non-obese patients during subsequent readmissions (p=0.12). The total cost of these admissions was significantly more in the obese cohort as well (p<0.001).

Conclusion

In this study, obese elderly patients admitted with ACS were found to have significantly reduced in-hospital mortality and 30-day readmission rates when compared to non-obese patients - reinforcing the obesity paradox independent of patient age.

Funding Acknowledgement

Type of funding source: None
The efficacy of a PCSK9 inhibitor for the plaque stabilization in the non-culprit lesion of ACS patients by using near-infrared intravascular ultrasonography
Authors: Wakana N , Zen K , Yanishi K , Nakanishi N , Nakamura T , Yamada H , Matoba S
Published: November 2020

Background and purpose

In acute coronary syndrome (ACS) patients, major cardiovascular events during follow-up were equally attributable to recurrence at the site of culprit lesions and to non-culprit lesions, and mostly occurred within one year. Recent studies showed that Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor significantly reduces the risk of cardiovascular events. However, the rigorous effects of PCSK9 inhibitor in patients with ACS, especially for the stabilization of plaque in the non-culprit lesions has not been identified. The purpose of this study was to evaluate the efficacy of a PCSK9 inhibitor for the plaque stabilization in the non-culprit lesion of ACS patients.

Methods

We retrospectively analyzed the 10 ACS patients (STEMI:5 cases, NSTEMI:1 case, and UAP:4 cases) who had non-culprit lesions and were injected with a PCSK9 inhibitor. We analyzed 11 non-culprit lesions before and after PSCK9 injections by using a near-infrared intravascular ultrasonography (NIRS-IVUS).

Results

The follow up intervals were 229.4±82.9 days. Major cardiovascular events did not occur in all patients. The serum low-density lipoprotein (LDL) cholesterol levels were significantly decreased form 128±36.7 mg/dl to 26.7±7.4 mg/dl (P<0.01; Figure 1A). There were no significant changes in percent atheroma volume before and after PCSK9 injections. However, the max lipid core burden index (LCBI) were significantly improved from 392.5±155.8 to 209.4±116 (P<0.01; Figure 1B). Although the lesion characteristics did not change in the images, by IVUS, the LCBI of the lesion was significantly decreased after PCSK9 injections. This study suggested that NIRS-IVUS had the possibility of detection for the slight changes in the plaque characteristics, which could not be detected by only an IVUS.

Conclusion

This study suggested that the plaque morphology can be altered by the aggressive lipid lowering therapy by using a PCSK9 inhibitor, and NIRS-IVUS can detect these plaque stabilizations of non-culprit lesion in ACS patients.

The authors have no financial conflicts of interest to disclose concerning the presentation.

Figure 1

Funding Acknowledgement

Type of funding source: None
The effect of unguided de-escalation of P2Y12 receptor inhibitor therapy after acute myocardial infarction in patients undergoing percutaneous coronary intervention: a nationwide cohort study
Authors: Yeh J.S , Hsu C.Y , Huang C.Y , Chen W.T , Hsieh Y.C , Chien L.N
Published: November 2020

Aims

To examine the effect of de-escalation of P2Y12 inhibitor in dual antiplatelet therapy (DAPT) on major adverse cardiovascular events (MACE) and bleeding complications after acute myocardial infarction (AMI) in Taiwanese patients undergoing percutaneous coronary intervention (PCI).

Methods and results

We retrospectively evaluated patients who had received PCI during AMI hospitalisation and were initially on aspirin and ticagrelor and without adverse events at 3 months between 2013 and 2016. In total, 1,901 and 8,199 patients were identified as switched DAPT (switched to aspirin and clopidogrel) and unswitched DAPT (continued on aspirin and ticagrelor) cohorts, respectively. With a mean follow-up of 8 months, the incidence rates (per 100 person-year) of death, AMI readmission and MACE were 2.89, 3.68 and 4.91 in the switched cohort and 2.42, 3.28 and 4.72 in the unswitched cohort, respectively based on an inverse probability of treatment weighted method. (Table) After adjustment for patients' clinical variables, two groups were no significant difference in death (A), AMI admission (B) and MACE (C). Additionally, there was no difference in the risk of major (D) or non-major clinically relevant bleeding (E) (Figure 1).

Conclusions

Unguided de-escalation of P2Y12 inhibitor in DAPT was not associated with higher risk of death, MACE, AMI readmission in Taiwanese patients with AMI undergoing PCI.

Figure 1

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Taipei Medical University
The effect of SGLT2 inhibitors on silent myocardial ischemia
Authors: Kadro W , Al Turkmani M , Kadro K , Kadro M.Y , Rigali D , Pietro G , Hamid M , Mathew S
Published: November 2020

Background

In large cardiovascular (CV) outcome trials, sodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the development of heart failure (HF) in patients with type 2 diabetes (T2DM). Also it reduced CV death and worsening HF events in HFrEF patients. It is unknown whether SGLT2 inhibitors work through glucose-dependent mechanism or it could have other effects not related to glucose on cardiovascular morbidity and mortality in diabetic patients. Its effect on silent ambulatory myocardial ischemia (SAMI) has not been reported yet. In this study we report the effect of SGLT2 inhibitors on (SAMI). Treating silent myocardial ischemia has a prognostic effect and may improve long term mortality of chronic ischemic heart disease (CIHD).

Methods

We enrolled 44 type 2 diabetic patients with proven stable coronary artery disease (CAD) and at least one episode of on silent ambulatory myocardial ischemia (SAMI) on ambulatory ECG monitoring. All of them were receiving optimal therapy for CIHD and type 2 DM. 22 patients were randomized to receive Dapagliflozin 5mg qd and the other 22 patients received placebo. Ambulatory monitoring was repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, HgbA1c level, and baseline serum cholesterol levels. Holters were read by a blinded cardiologist.

Results

The Dapagliflozin group experienced a significant reduction in the number of episodes of ST-segment depression compared with the placebo group. ST-segment depression completely resolved in 8 of 22 patients (36%) in the Dapagliflozin group versus 3 of 22 (13%) in the placebo group and the Dapagliflozin group exhibited a highly significant reduction in (SAMI) (P<0.001). By logistic regression, treatment with Dapagliflozin was an independent predictor of (SAMI) resolution.

Conclusions

Therapy with SGLT2 inhibitors in type2 DM patients results in reduction or resolution of (SAMI) recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG. A larger study is required to confirm this theory and to see the effect of SAMI reduction on long term mortality of CIHD in diabetics. Possible mechanisms for this beneficial effects of SGLT2i includes: Reduction in oxygen supply-demand mismatch, improvement in cardiac microvascular function, modulation of cardiac energy metabolism, reduction in glucotoxicity, reduction in sympathetic nervous system activation and reduction in blood pressure.

Funding Acknowledgement

Type of funding source: None