bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donepezil as a novel therapy for suppressing the progression of cardiovascular remodeling in obesity-induced hypertensive rats with reperfused myocardial infarction
Authors: Li M , Zheng C , Kawada T , Inagaki M , Uemura K , Sugimachi M 
Published: November 2020

Abstract

Introduction
Acetylcholinesterase inhibition by donepezil has been shown to improve long-term survival in permanent myocardial infarction (MI)-induced chronic heart failure rats. This study examined whether donepezil is applicable to the treatment of obesity-induced hypertension with reperfused MI (RMI).

Methods
Four-week-old SD rats were fed a high-fat diet (57% kcal as fat) for 15 weeks. We implanted a blood pressure (BP) telemetry into the animals (8-week-old) for monitoring artery pressure. After a 1-week recovery, RMI was created by occluding the left coronary artery (30min) followed by reperfusion. Surviving animals were randomly assigned to untreated (UT, n=16) or donepezil treated (DT, n=16, 3 mg/kg/day) group. After a 10-week treatment, the effects of donepezil were evaluated by hemodynamics, blood biomarkers, immunohistochemistry, and morphology.

Results
The high-fat diet caused obesity and hypertension (9-week-old: systolic BP = 134±4 mmHg; diastolic BP = 92±2 mmHg) in the normal rats. Compared with UT, DT significantly decreased the heart rate (296±5 vs. 318±8 bpm, P&lt;0.05). DT significantly prevented the progression of cardiac remodeling and dysfunction [cardiac index: 91±4 vs. 73±9 ml/min/kg, P&lt;0.01; left ventricular (LV) end-diastolic pressure: 11±1 vs. 20±2 mmHg, P&lt;0.01; LV dp/dt max: 5347±206 vs. 3637±433 mmHg/sec, P&lt;0.01], through increasing capillary density (+120%/field, P&lt;0.001), reducing cardiac fibrosis (−50%, P&lt;0.01) and myocardial infarcted area (17±2 vs. 24±2%, P&lt;0.05), suppressing cardiac hypertrophy (2.35±0.04 vs. 2.70±0.14 g/kg, P&lt;0.01) and coronary artery remodeling (wall thickness: 30±1 vs. 37±2 mm, P&lt;0.01; media-to-lumen ratio: 2.3±0.2 vs. 6.2±1.6, P&lt;0.001). Additionally, DT not only decreased plasma levels of insulin, norepinephrine, BNP, angiotensin II, but also improved the systemic inflammation.

Conclusions
Donepezil treatment significantly suppressed the progression of cardiovascular remodeling and dysfunction following RMI in obesity-induced hypertensive rats, suggesting that donepezil may be used as a potential candidate for post-RMI therapy in obesity-induced hypertensive patients.

Funding Acknowledgement
Type of funding source: None
Predictors of mortality in patients with VA-extracorporeal membrane oxygenation
Authors: Kang J , Lee H.S , Han S.M , Cho H.J 
Published: November 2020

Abstract

Background
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is a lifesaving tool used in the treatment of cardiogenic shock, acute heart failure, or extracorporeal cardiopulmonary resuscitation (CPR). We report on a single center experience with ECMO and aim to identify the prognostic markers for in-hospital mortality and death at 72 hours after ECMO.

Methods
Between 2011 and 2019 we evaluated 131 patients, who received ECMO. Collected data was analyzed to identify baseline characteristic, outcomes including clinical variables predictive of poor outcome.

Results
The mean age was 62.5 years, 67.2% were male patients, with prior CPR in 61.8%. The annual number of VA-ECMO procedures steadily increased, whereas in-hospital mortality is decreasing. Within the total cohort, the indication for VA-ECMO was cardiac arrest in 19.1%, acute coronary syndrome in 41.2%, acute heart failure in 23.7%, and myocarditis in 10.7%.
Overall in-hospital mortality was 58.8%. Multivariate logistic regression model revealed presence of malignancy, history of revascularization, duration of cardiac arrest, and low BMI as independent predictors for mortality in 72 hours after ECMO (table). On the other hand, predictors of in-hospital mortality were prior congestive heart failure, male, and history of malignancy. The C-statistic for discriminating mortality in 72 hours after ECMO with the duration of cardiac arrest was 0.67 (figure).

Conclusions
Although the use of ECMO as a last line in the treatment of critical patients measures constitutes an important improvement in their care; with 41.2% overall survival; patient selection and timing of ECMO initiation remains challenging. The importance of consideration for ECMO use earlier in course of illness rather than later.

Funding Acknowledgement
Type of funding source: None
Long-term prognostic value of the combination of malnutrition and pulmonary-systemic pressure ratio in patients admitted with 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 , Fukunami M 
Published: November 2020

Abstract

Background
Malnutrition is associated with increased mortality risk in patients (pts) with acute decompensated heart failure (ADHF). On the other hand, concomitant presence of pulmonary hypertension in heart failure 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 heart failure. However, there is no information available on the long-term prognostic value of the combination of malnutrition and MPS ratio in pts admitted for ADHF.

Methods and results
We studied 248 pts admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. Malnutrition was assessed by geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). During a mean follow-up period of 5.2±4.4 yrs, 62 pts had cardiovascular death (CVD). MPS ratio was significantly greater in pts with than without CVD (0.408±0.114 vs 0.347±0.102, p=0.0001). GNRI and PNI were significantly lower, CONUT was significantly greater in pts with than without CVD. At multivariate Cox regression analysis, GNRI and MPS ratio were significantly associated with CVD, independently of prior heart failure hospitalization, eGFR, and serum sodium level and anemia, although PNI and CONUT showed the association with CVD at unvariate analysis. Pts with malnutrition (GNRI≤median value=96.5) and greater MPS ratio (≥median value=0.346) had a significantly higher CVD risk than those with either and none of them (51% vs 20% vs 12%, p&lt;0.0001, respectively).

Conclusions
The combination of malnutrition and MPS ratio might be useful for stratifying pts at risk for CVD in patients with ADHF.

Funding Acknowledgement
Type of funding source: None
Chronic coronary syndromes lead to reduced strain parameters compared to patients without myocardial ischemia in a propensity score-matched cohort assessed by cardiac magnetic resonance imaging
Authors: Vietheer J , Unbehaun C.U , Weferling M , Fischer-Rasokat U , Wolter J.S , Von Jeinsen B , Zipse L , Keller T , Hamm C.W , Rolf A 
Published: November 2020

Abstract

Background
Vasodilator perfusion cardiac magnetic resonance (CMR) has evolved as gold standard in detecting myocardial perfusion deficits (MPD). Even reversible chronic MPD in chronic coronary syndromes can lead to impaired myocardial contractility similar to hibernating myocardium. Feature tracking strain analysis (FTS) provides the opportunity to detect these subclinical alterations of myocardial function before ejection fraction (EF) is impaired. It was therefore the aim of this study to investigate, if subtle changes in myocardial mechanics can be detected by FT strain analysis in patients with MPD.

Methods
Between April 2017 and October 2019 we identified 226 patients with MPD by vasodilator stress CMR out of 1500 patients included in our tertiary care center registry. Propensity score matching was used to identify patients without MPD with similar myocardial characteristics defined by EF, enddiastolic volume indexed by body surface area (EDVi) and native T1-mapping. Steady state free precession cine CMR sequences were analyzed by FTS retrospectively generating three global strain parameters: global longitudinal, circumferential and radial strain (GLS, GCS, GRS).

Results
Propensity score matching yielded 104 patients in each group (MPD mean age 63.6±12.8 years, 25 females; no MPD mean age 67.7±10.6 years, 26 females; LV-EF 51.3±16.0% vs. 52.6±15.2%, p=0.2307; EDVi 88.3±32.7 ml/m2 vs. 82.6±29.3 ml/m2, p=0.1533; native T1 values 1139±60 ms vs. 1125±63 ms, p=0.118). All global strain parameters were significantly reduced in MPD patients compared to patients with no MPD (global longitudinal strain −15.5±4.9 vs. −17.1±4.9, p=0.0046, global circumferential strain −18.0±5.4 vs. −19.4±5.6, p=0.0298; global radial strain 35.4±14.8 vs. 39.4±15.6, p=0.0127).

Conclusion
Chronic Coronary Syndromes cause subtle changes of myocardial mechanics, which are not reflected by EF but can be detected with FTS.

Funding Acknowledgement
Type of funding source: None
Effect of myocardial ischemia in diabetic and non-diabetic patients: long-term follow-up of MASS registry
Authors: Camara De Carvalho F , Hueb W , Lima E.G , Linhares Filho J.P.P , Ribeiro M.O.L , Martins E.B , Batista D.V , Garzillo C.L , Ribas F.F , Boros G.A.B , Rezende P.C , Serrano Junior C.V , Ramires J.A.F , Kalil Filho R 
Published: November 2020

Abstract

Background
Prognostic role of ischemia has been debated. The association with diabetes mellitus (DM) seems to add risks of cardiovascular events. We aimed to assess whether ischemia confers additional risks in diabetic population.

Methods
A single-center, prospective study including subjects with multivessel coronary artery disease who underwent surgery, percutaneous intervention or medical therapy. They were stratified according to presence of ischemia and DM. Primary endpoint was defined as death or myocardial infarction (MI). Secondary endpoint was death.

Results
We enrolled 1001 patients with conclusive stress tests: 790 (79%) with ischemia and 211 (21%) without ischemia. Mean follow-up was 8.7 years (IQR 4.04–10.07). The primary outcome occurred in 228 (28.9%) patients with ischemia and 64 (30.3%) without ischemia (p=0.60). Event rate among those with negative stress test, with or without DM, was similar (p=0.96 and p=0.60 respectively). Among those with ischemia, 145 (35.6%) with DM presented the combined event compared to 83 (21.7%) without DM (HR: 1.39; 95% CI 1.06–1.83, p=0.01). Death occurred in 117 diabetic and 65 (17%) in non-diabetic subjects (HR: 1.49, 95% CI: 2.03, p=0.01).

Conclusion
Overall, the presence or absence of ischemia was not related to death or MI. However, subset of patients with DM and ischemia revealed increased risk of death and cardiovascular events irrespective of treatment strategy.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Zerbini Foundation
Diagnostic accuracy of two-dimensional coronary angiographic derived fractional flow reserve
Authors: Sadeghipour P , Babakhani H , Abdi S , Ghasemi M , Moosavi J , Sadeghian M , Shafe O , Mohebbi B 
Published: November 2020

Abstract

Background
Non-invasive fractional flow reserve (NiFFR) is an emerging method for evaluating the functional significance of a coronary lesion during diagnostic coronary angiography (CAG). The method relies on the computational flow dynamics and the 3D reconstruction of the vessel extracted from CAG. In the present study, we sought to evaluate the diagnostic performance and applicability of 2D-based NiFFR.

Methods
In this prospective observational study, we evaluated 2D-based NiFFR in 279 candidates for invasive CAG and invasive FFR. NiFFR was calculated via 2 methods: variable NiFFR, in which the contrast transport time was extracted from the angiographic view, and fixed NiFFR, in which a prespecified frame count was applied.

Results
The final analysis was performed on 245 patients (250 lesions). Variable NiFFR had an area under the receiver operating characteristic curve of 81.5%, an accuracy of 80.0%, a sensitivity of 82.2%, a specificity of 82.2%, a negative predictive value of 91.4%, and a positive predictive value of 63.6%. The mean difference between FFR and NiFFR was −0.0244 ±0.0616 (P≤0.0001). A pressure wire-free hybrid strategy was possible in 68.8% of our population with variable NiFFR.

Conclusions
Our 2D-based NiFFR yielded results comparable to those derived from 3D-based software. Our findings should, however, be confirmed in larger trials.
Pressure wire-free hybrid strategy

Funding Acknowledgement
Type of funding source: None
Prognostic value of pre-revascularization fractional flow reserve mediated by the post-revascularization level: a causal mediation analysis
Authors: Hamaya R , Mittleman M , Hoshino M , Kanaji Y , Lee J , Hwang D , Zhang J , Chen S , Koo B , Kakuta T 
Published: November 2020

Abstract

Background
The prognostic value of pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) can depend on that of the post-PCI FFR and their interaction. To correctly interpret the prognostic value of pre-PCI FFR, it is essential to understand to what extent the relationship between pre-PCI FFR and clinical outcome is explained by pre-PCI FFR-related post-PCI FFR.

Purpose
The aim of this study is to investigate the extent to which post-PCI FFR mediates the relationship between pre-PCI FFR and vessel-related outcomes using a global, multicenter collaboration registry.

Methods
Patient data from 4 global FFR registries were pooled and 1488 patients with pre-PCI FFR ≤0.80 were analyzed. The primary outcome was target vessel failure (TVF) during 2-years of follow-up. We evaluated the extent to which post-PCI FFR &lt;0.90 mediated the association between pre-PCI FFR &lt;0.75 and TVF employing a causal mediation analysis in a counterfactual framework.

Results
Among 1488 patients, the mean (standard deviation) age was 63.5 (9.9) years and 78% (1161 patients) were male. The median (IQR) pre-PCI and post-PCI FFR were 0.71 (0.62–0.76) and 0.88 (0.83–0.92), respectively. The direct effect of low pre-PCI FFR (&lt;0.75) on TVF was significantly elevated (OR: 1.81, 95% CI: 1.03–3.18, p=0.038), and was not mediated by post-PCI FFR&lt;0.90 (indirect effect, OR: 1.01, 95% CI: 0.98–1.05, p=0.39). In the model, post-PCI FFR explained only 2.2% of the association between pre-PCI FFR and TVF. The subgroup analysis implicated that the prognostic information of pre-PCI FFR was mainly for diffuse lesions.

Conclusions
The prognostic information of pre-PCI FFR did not greatly depend on the results of PCI assessed by post-PCI FFR. Pre-PCI FFR, as a prognostic marker, may mainly reflect the global atherosclerotic burden of the artery, not the extent of the modifiable epicardial stenosis, thus providing independent information from post-PCI FFR.
Interpretation

Funding Acknowledgement
Type of funding source: None
Regulation and role of arginine vasopressin in myocardial infarction/reperfusion
Authors: Andre N , Spyridopoulos I 
Published: November 2020

Abstract

Background
Little attention is paid to the coronary microvasculature when treating acute myocardial infarction (MI). Microvascular obstruction contributes to ischaemia-reperfusion (I-R) injury. One proposed mechanism is a persistent vasoconstrictor tone during MI/reperfusion. Arginine vasopressin (AVP) has a vasoactive effect on the coronary microvessels. Moreover, cardiac AVP synthesis was found in an animal model. To exert vasoconstriction, AVP binds to its receptor 1a (AVPR1a).

Aims
(i) To analyse the AVP levels during MI/reperfusion (ii) To assess cardiac AVP and AVPR1a expressions in MI/reperfusion mouse models.

Methods
We took arterial blood samples from ST elevation MI (STEMI) patients admitted to our hospital over the course of MI/reperfusion for AVP levels quantification. We also measured AVP through its more stable surrogate biomarker, copeptin. Cardiac MRI was done to evaluate coronary microvasculature, infarct size, and left ventricular ejection fraction (LVEF) 1 week post-admission. Cardiac AVP and AVPR1a expressions were assessed by polymerase chain reaction (PCR) in mouse models.

Results
STEMI patients displayed bothAVPand copeptinlevels elevation at baseline (130.8±20.5 pmol/l, n=23) until 90 min post-reperfusion (55.7±6.2 pmol/l, n=23). Their concentrations began to approach normal levels at 24h. Patients with poorer reperfusion outcomes had copeptin concentrations that remained above normal level after 24h following reperfusion. Copeptin levels at 24h post-reperfusion were significantly higher in patients who developed larger infarct size (p=0.004) and lower LVEF (p=0.009). Patients with microvascular obstruction tended to have higher copeptin levels from admission until 24h post-reperfusion. Mouse models showed no cardiac AVP expression but significantly high AVPR1a expression at 2h post-reperfusion.

Conclusion
In STEMI patients, circulating AVP level is elevated over the course of MI/reperfusion. In MI/reperfusion mouse models, cardiac AVP synthesis is absent but cardiac AVPR1a is upregulated. The combination of delayed decline in AVP concentrations and AVPR1a upregulation may increase the possibility for AVP to mediate I-R injury through microvascular disturbance. Increased AVP levels at 24h post-reperfusion are significantly associated with poor reperfusion outcome. These results warrant further studies concerning the use of AVP receptor antagonist in STEMI patients undergoing reperfusion therapy
Copeptin levels and reperfusion outcomes

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Newcastle University MRes Programme
Genetic factors and the presence of coronary collaterals in patients with stable coronary artery disease
Authors: Kozlova E , Starostin I , Balatskyi A , Bulkina O , Lopukhova V , Karpov U 
Published: November 2020

Abstract

Background
The coronary collateral circulation (CCC) varies in patients with coronary artery disease (CAD). Although many studies were provided to detect factors associated with collateral development, genetic factors are still studied insufficiently. The goal of this study was to assess the association of single nucleotide polymorphisms (SNP) in genes involved in vascular growth with CCC in patients with stable CAD.

Purpose
To assess if genetic variations in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (gene PLAU) are associated with the presence of coronary collaterals in patients with stable CAD.

Methods
A single-centered study was performed between March 2012 and December 2017. In 579 patients with stable CAD who underwent coronary angiography and had at least 50% stenosis in at least one major coronary artery collaterals were assessed by the use of the Rentrop score (0–3) during coronary angiography. SNPs PLAU rs4065, VEGF rs1570360, rs2010963 and rs699947, HGF rs5745752 were genotyped, multivariate logistic regression was carried out to determine the association of genotypes with CCC.

Results
337 patients had visible coronary collaterals (Rentrop grade 1, 2 and 3) and 236 patients didn't have visible collaterals (Rentrop grade 0). Beside traditional risk factors of poor CCC - diabetes, smoking and arterial hypertension – patients without visible coronary collaterals (Rentrop 0) showed a higher frequency of the HGF rs5745752 CC genotype than those with visible coronary collaterals (Rentrop 1–3; p=0.001). (Fig. 1) The odds ratio of having CCC Rentrop 0 in patients with genotype CC was statistically significant (odds ratio = 1.94 [95% confidence interval: 1.38–2.76]; p=0.001). Statistical analysis showed that the PLAU rs4065 and VEGF rs1570360, rs2010963 and rs699947 polymorphisms were not associated with CCC (p&lt;0.05).

Conclusion
An association was found between the HGF rs5745752 polymorphism and the CCC in patients with stable CAD. Patients with the CC genotype are at greater risk of developing poor coronary collaterals.
Figure 1

Funding Acknowledgement
Type of funding source: None
Myocardial energetic efficiency is depressed in ischemia with non-obstructive coronary arteries
Authors: Eskerud I , Mancusi C , Khan I , Berge C.A , Larsen T , Lonnebakken M.T 
Published: November 2020

Abstract

Background
Ischemia with non-obstructive coronary arteries (INOCA) is incompletely understood. Depressed myocardial energetic efficiency index (MEEi), the ratio between external work and myocardial oxygen consumption, has been shown in heart failure. However, MEEi in INOCA has not been explored.

Purpose
To test whether MEEi is associated with INOCA.

Methods
We included 125 patients (56% women, age 62±9 years) with exercise-induced chest pain and non-obstructive coronary arteries (stenosis &lt;50%) by coronary computed tomography angiography (CCTA). Stroke volume (SV) and left ventricular (LV) mass were assessed by echocardiography. MEEi was calculated as (systolic blood pressure (SBP) x SV) / (SBP x heart rate) and normalized for LV mass. LV hypertrophy was defined as LV mass index &gt;46.7 g/m2.7 in women and &gt;49.2 g/m2.7 in men. Myocardial ischemia was detected by myocardial contrast stress echocardiography. Coronary artery plaque burden was measured as plaque volume by CCTA.

Results
In univariable regression analysis, stress-induced ischemia, male sex, diabetes, hypertension, LV hypertrophy, lower LV ejection fraction and higher SBP were associated with MEEi (all p&lt;0.05). There were no associations with age, obesity or coronary artery plaque burden. MEEi was lower in patients with stress-induced ischemia (n=66) compared to patients without ischemia (0.47±0.16 vs. 0.54±0.21 ml/sec x g–1, p=0.026). In multivariable linear regression analysis, MEEi remained associated with stress-induced myocardial ischemia after adjustment for cardiovascular risk factors, SBP, LV hypertrophy, LV ejection fraction and coronary artery plaque burden (R2 0.26, p&lt;0.001, Table).

Conclusion
MEEi is depressed in patients with INOCA. Our results suggest that myocardial ischemia negatively influences MEEi in patients with non-obstructive coronary arteries.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority, University of Bergen