bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of pulmonary-systemic pressure ratio and fibrosis-4 index in patients admitted for acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Kawahira M , Fukunami M 
Published: November 2020

Abstract

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. An increased mean pulmonary artery pressure to mean systemic arterial pressure ratio (MPS ratio), a marker of interventricular coupling and efficiency, is reported to be associated with worse clinical outcomes in patients with advanced HF. On the other hand, cardiohepatic interactions have been a focus of attention in HF, and liver dysfunction in HF patients is caused by liver congestion, which is related to liver stiffness. It has been recently shown that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4 (FIB4) index predicts the mortality in HF patients. However, there is no information available on the prognostic value of the combination of MPS ratio and FIB4 index in patients with acute decompensated heart failure (ADHF).

Methods and results
We studied 238 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. MPS ratio was obtained at the admission. FIB4 index was calculated by the formula: age (yrs) × AST [U/L] / (platelets [103/μL] × √(ALT[U/L])). FIB4 index &gt;2.67 was defined as abnormal, as previously reported. During a follow up period of 5.2±4.4 yrs, 93 patients died. At multivariate Cox analysis, MPS ratio (p=0.01) and FIB4 index (p=0.01) were significantly associated with the total mortality, independently of creatinine level and prior heart failure hospitalization, after the adjustment with hemoglobin, albumin levels and body mass index. The patients with both MPS ratio ≥0.388 (determined by ROC analysis; AUC 0.613 [0.541–0.687]) and abnormal FIB4 index had a significantly increased risk of the total mortality than those with either greater MPS or abnormal FIB4 index and none of them (52% vs 40% vs 28%, p=0.0068, respectively).

Conclusion
The combination of MPS ratio and FIB4 index might be useful for stratifying ADHF patients at higher risk for the total mortality.

Funding Acknowledgement
Type of funding source: None
The clinical impact of delirium in the patients with acute decompensated heart failure
Authors: Aikawa Y.A , Noguchi T.N , Morii I.M 
Published: November 2020

Abstract

Background
Delirium is frequent in-hospital complication in patients with illness. However, the clinical impact of delirium on cardiovascular mortality has not been fully addressed in patients with acute decompensated heart failure (ADHF).

Methods
Between April 2016 and May 2019, 474 consecutive patients with ADHF admitted to our institution were enrolled and followed for 6 months after discharge. Delirium was defined according to the Intensive Care Delirium Checklist. To compare the clinical outcome, we divided study patients into 3 groups according to the presence or absence of delirium: non-delirium (ND) (n=349), improved-delirium during hospitalization (ID) (n=68), and prolonged delirium (PD) (n=57).

Results
One hundred twenty-five (26.4%) patients developed delirium. During hospitalization, PD had higher incidence of all-cause death, cardiovascular death, and worsening heart failure compared with ND and ID (20.0% vs. 3.7% and 2.9%, 10.9% vs. 2.5% and 1.4%, 21.8% vs. 2.5% and 4.3%, p&lt;0.001, respectively). Multivariable analysis identified the presence of frailty (OR: 8.56, 95% CI: 3.46–23.7) and dementia (OR: 7.34, 95% CI: 3.52–15.9), use of H2-blocker (OR: 3.41, 95% CI: 1.08–10.9) and plasma level of CRP (OR: 1.30, 95% CI: 1.06–1.61) as significant independent determinants of delirium. Also, in multivariable analysis, the development of frailty (OR: 5.51, 95% CI: 2.80–11.5), delirium (OR: 4.59, 95% CI: 2.23–9.66) and age (OR: 1.06, 95% CI: 1.03–1.11) were the independent determinants of composite endpoint with in-hospital death and discharge to other than home. Early treatment of delirium performed significantly higher in ID than PD (55.7% vs. 29.1%, p=0.003).

Conclusion
This study suggested that PD contributed to increasing in-hospital events in the patients with ADHF and significance of early screening and treatment for delirium.
Figure 1. Outcomes during hospitalization

Funding Acknowledgement
Type of funding source: None
Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease
Authors: Benincasa G , Schiano C , Infante T , Franzese M , Casale R , Della Mura N , Fiorito C , Mansueto G , Soricelli A , Nicoletti G.F , Salvatore M , Napoli C 
Published: November 2020

Abstract

Aims
Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features.

Methods
Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software.

Results
For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p&lt;0.05) between two groups.

Conclusions
Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health
Hemodialysis patients with better coronary flow reserve and nutrition status have surprising prognosis
Authors: Imaoka T , Umemoto N , Oshima S 
Published: November 2020

Abstract

Background
In clinical setting, ischemic heart disease is a challenging problem in hemodialysis (HD) population. Coronary flow reserve (CFR) measured by 13 ammonia positron emitting tomography (13NH3PET) is an established and reliable modality for detecting coronary artery disease. Furthermore, some prior studies show CFR is an important and independent predictor for cardiovascular event and mortality. On the other hand, HD patients with malnutrition status have poor prognosis. We have reported about the relationship between cardiovascular events and geriatric nutrition risk index (GNRI). Now, we wonder the predictability of combination of CFR and GNRI.

Methods and result
We collected 438 consecutive HD patients who received 13NH3PET in our hospital suspected for ischemic heart disease. 29 patients were excluded due to undergoing coronary revascularization within 60 days, 103 patients were excluded due to incomplete database. In total, 306 HD patients were classified into 4 group according the median value of CFR (1.99) and GNRI (97.73); Low CFR Low GNRI group (n=77), High CFR and Low GNRI group (n=76), Low CFR High GNRI group (n=78) and High CFR High GNRI group (n=75). We collected their follow up data up to 1544 days (median 833 days) about all-cause mortality and cardiovascular (CV) mortality. Surprisingly, there is no mortality event in High CFR High GNRI group. We analyzed about all-cause mortality, CV mortality. Kaplan-Meyer analysis shows there are statistically intergroup differences in each (all-cause mortality; log rank p&lt;0.01, CV mortality; log rank p=0.02). Furthermore, we calculated area under the curve (AUC) analysis, net reclassification improvement (NRI) and integrated discrimination improvement (IDI)m adding GNRI and CFR on conventional risk factors. There are intergroup differences for all-cause mortality in AUC [conventional risk factors, +GNRI, +GNRI+CFR; 0.70, 0.72 (p=0.29), 0.79 (p&lt;0.01)], NRI [+GNRI; 0.32 (p=0.04), +GNRI+CFR 0.82 (p&lt;0.01)] and IDI [+GNRI; 0.01 (p=0.05), +GNRI+CFR 0.09 (p&lt;0.01)].

Conclusion
HD patients with low CFR and malnutrition status has statistically significant poorer prognosis comparing HD patients with high CFR and without malnutrition status. Adding combination of GNRI and CFR on conventional risk factors improves the predictability of HD population's prognosis.

Funding Acknowledgement
Type of funding source: None
The detection of multivessel coronary artery disease: the value of quantitative myocardial blood flow and coronary flow reserve assessment
Authors: Zavadovskiy K , Mochula A , Maltseva A , Boshchenko A , Baev A , Andreev S , Liga R , Gimelli A 
Published: November 2020

Abstract

Background/Introduction
The recent Cadmium-Zinc-Telluride (CZT) camera for MPS allows evaluating absolute MBF and CFR, possibly increasing the accuracy in detecting of multivessel CAD.

Purpose
To evaluate the accuracy of myocardial blood flow (MBF) and coronary flow reserve (CFR) quantitation performed by myocardial perfusion scintigraphy (MPS) for the detection of multivessel coronary artery disease (CAD).

Methods
Fifty-two patients with suspected or known CAD were enrolled in the study. All patients underwent CZT MPS, with the evaluation of MBF and CFR, followed by invasive coronary angiography. According to MPS and coronary angiography results, patients were divided into three groups. 1) non-obstructive CAD and normal MPS scan (control group) (n=7), 2) one vessel disease (1VD) (n=16), with significant coronary stenosis (≥70%) in one major epicardial coronary artery, 3) multivessel disease (MVD) group (n=29), with two or more major epicardial coronary arteries with (≥70%) stenoses or with ≥50% LMA stenosis.

Results
Absolute MBF and CFR were significantly reduced in patients with MVD as compared to those with 1VD [0.93 (IQR 0.76; 1.39) vs 1.94 (1.37; 2.21) ml/min/g, p=0.00012] and [1.4 (IQR 1.02; 1.85) vs 2.3 (1.8; 2.67), p=0.0004], respectively. The Syntax score correlated with global stress MBF (ρ=−0.64; p&lt;0.0001) and CFR (ρ=−0.53; p=0.0003). ROC analysis showed higher sensitivity and specificity for stress MBF (85.2% and 81%), and CFR (88.9% and 80%) compared with semiquantitative MPS stress evaluation (69% and 69%). Multivariate regression analysis showed that only stress MBF [OR (95% CI) 0.59 (0.42–0.82); p&lt;0.0003] was an independent predictor of MVD.

Conclusion
The use of absolute myocardial blood flow analysis with the CZT camera may identify high risk patients, such as those with multivessel disease. This approach could be used in clinical practice, increasing the accuracy in the evaluation of patients with known or suspected coronary artery disease.

Funding Acknowledgement
Type of funding source: None
Artificial intelligence-derived physiological aging is associated with coronary endothelial dysfunction
Authors: Ahmad A , Toya T , Corban M , Attia Z.I , Lopez-Jimenez F , Shelly Cohen M , Noseworthy P.A , Kapa S , Friedman P.A , Lerman A 
Published: November 2020

Abstract

Background
An Artificial intelligence (AI)-enabled algorithm can provide an age estimate from a single standard resting ECG. The gap between AI-estimated age (ECG age) and chronological age (Age-Gap) has been associated with total and cardiovascular mortality. We hypothesized that coronary endothelial dysfunction (CED), an early feature of coronary atherosclerosis, is associated with physiological aging, as measured by ECG age.

Purpose
The aim of this study is to investigate the association of CED, a potential index of cardiac aging, and AI-estimated physiological aging.

Methods
1902 patients with signs and/or symptoms of ischemia and with non-obstructive coronary artery disease (&lt;40% angiographic stenosis) who underwent functional coronary angiography with intracoronary (IC) acetylcholine (Ach) infusions and a resting ECG within one year were included in this analysis. CED was defined as coronary artery constriction [%ΔCoronary artery diameter (CAD) &lt;0] in response to IC Ach. Patients were categorized as CED+ or CED−. The ECG age were calculated by a previously-trained AI algorithm that was built using the Keras framework with Tensorflow backend and Python. The association between ECG-age and Age-Gap, with CED was investigated.

Results
Average chronological age was 50.9±12.5, ECG age was 54.1±11.6, 1261 (66%) were females. Compared to CED−, the CED+ group had more males and hyperlipidaemia (p&lt;0.05 for both). Age-gap was significantly higher in patients with CED+ (Fig. A). Multiple regression analysis showed that CED+ was associated with Age-gap (standardized β [sβ] coefficient = 0.08, P=0.001) even after adjustment for chronological age (sβ coefficient = 0.07, P=0.001), and even after adjusting for other cardiovascular risk factors like gender and obesity (sβ coefficient = 0.07, P&lt;0.0001). Furthermore, there is a significant gradual increase in vasoconstriction, in response to IC Ach, with increasing Age-gap (Fig. B).

Conclusion
Abnormal coronary endothelial function is associated with an increased AI-estimated age which could indicate a higher physiological age.

Funding Acknowledgement
Type of funding source: None
Thermodilution-derived resting coronary flow measurement: “a reverse dose finding study”
Authors: Gallinoro E , Colaiori I , Di Gioia G , Fournier S , Kodeboina M , Candreva A , Sonck J , Pijls N.H.J , Collet C , De Bruyne B 
Published: November 2020

Abstract

Background
Hyperemic absolute coronary blood flow (in mL/min) can be safely and reproducibly measured with intracoronary continuous thermodilution of saline at room temperature at an infusion rate of 20 mL/min. This study aims at assessing the best infusion rate to measure resting flow by thermodilution, i.e. low enough to avoid microvascular dilation but high enough to allow reliable thermodilution tracings

Methods and results
In 26 coronary arteries (24 patients) with angiographic non-significant stenoses, absolute flow was assessed by continuous saline thermodilution at infusion rates of 10 mL/min and 20 mL/min using a pressure/temperature sensored guide wire, a dedicated infusion catheter and a dedicated software. Average peak velocity (APV) was measured simultaneously using an intracoronary Doppler-wire. In addition, in a subgroup of 10 arteries, absolute flow and APV were also measured during saline infusion at 6 ml/min and 8 ml/min.
In 26 coronary arteries there was no significance difference in the Pd/Pa and in the APV at baseline and during the infusion of saline at 10 ml/min (Pd/Pa: 0.94±0.057 vs 0.94±0.059, p=0.82; APV: 22.2±8.40 vs 23.2±8.39 cm/s, p=0.63). In contrast, at an infusion rate of 20 mL/min, we observed a significant decrease in Pd/Pa compared to baseline (0.85±0.089 vs 0.95±0.053 vs, respectively, p&lt;0.001) and a significant increase in APV (22.2±8.4 cm/s to 57.8±25.5 cm/s, respectively, p&lt;0.001). The coronary flow reserve (CFR) evaluated by Doppler and intracoronary continuous thermodilution correlated well (r=0.87, 95% CI = 0.72–0.94, p&lt;0.001) and Bland-Altman analysis documented a mean bias of −0.003 (limit of agreement −1.05 to 1.04) thus indicating the presence of resting coronary blood flow during the infusion of 10 mL/min of saline. In 10 coronary arteries saline infusions at 6 and 8 ml/min did not produce any significant changes in the Pd/Pa and in the APV compared to baseline and both Doppler and Thermodilution derived CFR correlated well at each infusion rate (6 ml/min: r=0.71, 95% CI 0.14–0.92, p=0.02; 8ml/min: r=0.78, 95% CI=0.31–0.95, p=0.007). However, with an infusion rate of 6 mL/min, an unstable thermodilution tracing was observed. Accordingly, Bland-Altman analysis showed a significantly larger dispersion of the CFR values when 6 ml/min was used to measure resting coronary flow (as compared with 8 m/min): mean bias at 6 ml/min: −0.53, limits of agreement: −2.25 to 1.20: mean bias at 8 ml/min: 0.004, limits of agreement: −0.72 to 0.73.

Conclusion
Absolute resting coronary flow can be measured by intracoronary continuous thermodilution of saline at infusion rate of 8–10 ml/min.

Funding Acknowledgement
Type of funding source: None
Role of peroxisome proliferators-activated receptor-gamma in advanced glycation end product-mediated functional loss of voltage-gated potassium channel in rat coronary arteries
Authors: Li W , Gao S.D , Hua B , Liu Q.B , Liu H.R , Li H.W 
Published: November 2020

Abstract

Background
Voltage-gated K+ (Kv) channels in coronary artery smooth muscle cells (CSMCs), especially the major specific Kv1 subfamily, contribute to coronary artery vasodilation. Advanced glycation end products (AGEs) have been strongly implicated in diabetes-related cardiovascular complications. Our previous study showed AGEs can impair Kv channel-mediated coronary vasodilation by reducing Kv channel activity. However, its underlying mechanism remains unclear.

Purpose
Here, we used isolated rat small coronary arteries (RSCAs) and primary CSMCs to investigate the effect of AGEs on Kv channel-mediated coronary vasodilation and the possible involvement of peroxisome proliferators-activated receptor (PPAR)-γ pathway.

Methods
RSCAs and primary CSMCs were isolated, cultured and treated with bovine serum albumin (BSA), AGE-BSA, alagrebrium (ALA, AGE cross-linking breaker), pioglitazone (PIO) and/or GW9662, and then divided into the following groups: DMEM, BSA, AGE, AGE+ALA, AGE+PIO, and AGE+PIO+GW9662. Kv channel-mediated coronary vasodilation was analyzed using wire myograph. Histology and immunohistochemistry of RSCAs were performed. Western blot was used to detect the protein expression of RAGE, the major Kv1 channel subunits expressed in CSMCs (Kv1.2/1.5), PPAR-γ, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2).

Results
AGEs markedly reduced forskolin-induced Kv channel-mediated vasodilation of RSCAs by interacting with the receptor for AGEs (RAGE), and ALA or PIO significantly reversed this effect. In both RSCAs and primary CSMCs, AGEs decreased Kv1.2 and Kv1.5 channel protein expression, inhibited PPAR-γ expression, increased RAGE and NOX-2 expression. Treatment with ALA or PIO partially reversed the effects of AGEs on Kv1.2/Kv1.5 expression, accompanied by elevation of PPAR-γ level and diminished oxidative stress.

Conclusion
AGE/RAGE axis-induced inhibition of PPAR-γ pathway and enhancement of oxidative stress may contribute to AGEs-mediated Kv channel dysfunction and coronary vasodilation in RSCAs. Our results may provide new insights into developing therapeutic strategies to manage diabetic vasculature.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China; Natural Science Foundation of Beijing (7172059)
Proteoglycan remodeling is accelerated in women with angina pectoris and diffuse myocardial fibrosis: the iPOWER Study
Authors: Mygind N.D , Holm Nielsen S , Mide Michelsen M , Pena A , Bechsgaard Frestad D , Suhrs E , Bove K.B , Genovese F , Nielsen H.B , Karsdal M , Vejlstrup N , Prescott E , Kastrup J 
Published: November 2020

Abstract

Background
Women with angina and no obstructive coronary artery disease (CAD) have an unfavourable prognosis, possibly due to coronary microvascular disease and diffuse myocardial fibrosis (DMF). In DMF myocardial extracellular matrix (ECM) proteins are actively remodeled by matrix metalloproteinase (MMP).

Purpose
We investigated MMP-mediated degradation of the protegoglycans biglycan and versican in women with angina pectoris and possible DMF assessed by cardiac magnetic resonance T1 mapping.

Methods
Seventy-one women with angina pectoris and no obstructive CAD were included. Asymptomatic age-matched women served as controls (n=32). Versican and biglycan were measured in serum by specific competitive enzyme-linked immunosorbent assays. T1 mapping was performed by cardiac magnetic resonance with gadolinium measuring T1 and extracellular volume (ECV).

Results
Both biglycan and versican levels were higher in symptomatic women compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p&lt;0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p&lt;0.001), respectively (Figure 1) and were moderately correlated to global ECV (r2=0.38, p&lt;0.001 and r2=0.26, p=0.015 respectively).

Conclusion
Turnover of biglycan and versican was increased in symptomatic compared to asymptomatic women and associated to ECV, supporting a link between angina with no obstructive CAD and fibrotic cardiac remodeling. The examined biomarkers may prove to be suitable for monitoring active ECM remodeling.
Figure 1. Levels of BGM and VCANM

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): This work was supported by The Danish Heart Foundation, the Danish Research Fund (Den Danske Forskningsfond) and by University of Copenhagen.