bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronary artery disease is a stronger predictor of mortality than left ventricular ejection fraction among newly diagnosed patients with heart failure
Authors: Pryds K , Nielsen R R , Olesen K K W , Mortensen M B , Nielsen J C , Maeng M 
Published: October 2022

Abstract

Background
Heart failure (HF) prevalence remains high and prognosis is poor despite improvements in both medical treatment and implantation of primary prophylactic implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT) devices. At present, classification of HF and treatment algorithms are determined by the left ventricular ejection fraction (LVEF). However, in patients with LVEF &lt;50% and newly diagnosed HF, evidence remains sparse as to whether LVEF per se or presence of CAD provide independent prognostic information on mortality.

Methods
Using the Western Denmark Heart Registry, we identified newly diagnosed patients with HF and LVEF 10–49% undergoing first-time coronary angiography (CAG) from 2003 to 2016 referred due to HF. Patients were stratified by LVEF (10–35% vs. 36–49%, according as to whether primary prophylactic ICD and CRT treatment should be considered) and presence of coronary artery disease (CAD). Maximum follow-up was 10 years. We estimated 10-year cumulative incidence of death and calculated hazard ratios (HR) adjusted for relevant comorbidities and risk factors.

Results
Of 154,186 Western Danish residents undergoing CAG, 3,620 patients had HF and LVEF 10–49%. Among these, 2,780 (77%) patients had LVEF 10–35% and 840 (23%) patients had LVEF 36–49%. CAD was present in 1,592 (44%) patients.
There was a potential association in 10-year mortality when comparing patients with HF and LVEF 36–49% to those with LVEF 10–35% (37.3% vs. 42.1%, HR 1.15; 95% CI 0.99–1.34) (Figure 1A), with point estimates of mortality ranging from being 1% reduced to 24% increased. This result was not strongly influenced by the presence of CAD (HR 1.11; 95% CI 0.91–1.35) or absence of CAD (HR 1.24; 95% CI 0.97–1.57) (Figure 1B). There was no trend between LVEF categorized by 5-percentiles and mortality (p for trend = 0.24) (Table 1). In contrast, CAD was more strongly associated with increased 10-year mortality (55.0% vs. 31.5%, HR 1.43; 95% CI 1.25–1.64) irrespective of LVEF (Figure 1B).

Conclusion
Among newly diagnosed patients with HF and LVEF 10–49%, presence of CAD impacts mortality substantially more than LVEF per se. These results emphasize that assessment of CAD is pivotal for prognostication of newly diagnosed patients with HF and LVEF 10–49%.

Funding Acknowledgement
Type of funding sources: None.
Infarction of the papillary muscle is an independent predictor of heart failure, ventricular tachycardia, and consequent mortality
Authors: Beijnink C , Raessens S , Ortiz-Perez J T , Bodi V , Rodwell L , Valente F , Alamar M , Marcos-Garces V , Lorenzatti D , Rios-Navarro C , Gavara J , Ferreira I , Barrabes J A , Rodriguez Palomares J , Nijveldt R 
Published: October 2022

Abstract

Background
Previous studies have assessed the effect of papillary muscle infarction (papMI) as seen with Late Gadolinium Enhancement (LGE) Cardiac Magnetic Resonance imaging (CMR) after ST-segment elevation myocardial infarction (STEMI) on patient prognosis. As these studies delivered inconclusive results due to limited sample size and follow-up, we set out to assess whether STEMI patients with papMI are at an increased risk of cardiovascular mortality, heart failure, and arrhythmic events.

Methods
This is a 3-center observational study in n=1,055 consecutive STEMI patients who underwent CMR at a median of 6 (4–9) days, with a mean follow-up of 6.0 years (IQR 3.1–9.1 years). Any presence of papMI, be it supero-lateral, infero-medial, or double, was evaluated visually on the LGE images and checked on the matched cine images. The primary outcomes are time to cardiovascular mortality, heart-failure events defined as heart failure death and hospital admission for heart failure, and arrhythmic events, defined as arrhythmic death and ventricular tachycardia (VT).

Results
PapMI was diagnosed in 351 patients (33%). PapMI is an independent predictor of cardiovascular mortality after correction for clinically relevant parameters such as infarct size and left ventricular ejection fraction (Multivariate Cox Regression Hazard Ratio (HR)=2.46, 95% confidence interval (CI) 1.23–4.92). Secondly, papMI independently predicts the combined endpoints of heart failure death/heart failure (HR=1.72, 95% CI 1.12–2.63) and arrhythmic death/ VT (HR=4.52, 95% CI 2.18–9.36).

Conclusions
PapMI predicts cardiovascular mortality, arrhythmic death and heart failure. PapMI should be taken into account, especially when conducting new prognosis studies after STEMI and as a stratification factor in studies for secondary prevention of VT and arrhythmic death.

Funding Acknowledgement
Type of funding sources: Other.
Noninvasive evaluation of coronary velocity reserve: need for correction of the sympathetic tone
Authors: Armenis I , Hatzigeorgiou G , Marinou M , Kyrzopoulos S , Tsiapras D , Athanassopoulos G 
Published: October 2022

Abstract

Introduction
Noninvasively Doppler estimated coronary velocity (as a surrogate of flow) reserve (CVR) by adenosine is a useful parameter for risk stratification in chronic coronary syndromes (CAD). However, baseline velocity fluctuation due to sympathetic drive, as in mental stress, may affect the evaluation of the actual CVR.

Aim
Aim of the study was to assess the effect of b blocker administration following adenosine infusion in the coronary velocity and thus the consequences in the estimated CVR.

Patients and methods
Sixty (females 8) patients (pts) with stable CAD (mean/SD: age 64/10, ejection fraction % 55/8) were studied before the performance of a dobutamine stress echo. Distal left anterior descending (LAD) velocity was estimated at rest (CVrest), at maximal adenosine infusion (140γ/kg/min: CVaden) and following esmolol infusion 3–5 min later (CVbbl). CVR was estimated using as baseline velocity either CVrest (CVRrest) or CVbbl (CVRbbl). Respective changes of heart rate (HR) and systolic blood pressure (SBP) were also estimated.

Results
CVbbl was smaller than CVrest (23/7 vs 29/13, p&lt;0.0.01). Thus, CVRbbl was greater than CVRrest (3/0.9 vs 2.7/0.6, p&lt;0.001) with an absolute difference (dCVR) of 0.46/0.84, a % difference (%dCVR) of 23/34%, with a modest linear relationship (R2=0.08, p=0.02 figure). The %dCVR was also linearly related to CVRrest (R2=0.13, p=0.003 figure) and it was independent from age, HR/BP changes and the dobutamine stress echo outcome.
Differences between CVRbbl and CVRrest were greater in females (females/males: dCVR 1.2/0.9 vs 0.36/0.8, %dCVR 0.67/0.56 vs 0.36/0.26, both p&lt;0.001).

Conclusions
Noninvasively estimated CVR is affected by the baseline sympathetic tone, irrespectively from the age in stable CAD. A gender effect is evident, reiterating the microvascular susceptibility in females. Thus, potential mental stress background must be considered, and b-blockade subsequently might be applied during CVR evaluation to overcome any sympathetic effect.

Funding Acknowledgement
Type of funding sources: None.
Cardiovascular risk factors and underlying pathology and prevalence of lipid plaques in women with acute coronary syndromes in different age groups
Authors: Seegers L M , Araki M , Nakajima A , Yuki H , Yonetsu T , Soeda T , Kurihara O , Higuma T , Minami Y , Adriaenssens T , Nef H , Lee H , Sugiyama T , Kakuta T , Jang I K 
Published: October 2022

Abstract

Background
An incidence of cardiovascular events increases with age in women. The relationship between cardiovascular risk factors, and the underlying pathology and the prevalence of lipid plaques has not been systematically studied in different age groups in women presented with acute coronary syndromes (ACS).

Purpose
We investigated the underlying pathology and the prevalence of lipid plaques in culprit lesions by optical coherence tomography (OCT) in women with different risk factors.

Methods
A total of 382 women who underwent pre-intervention OCT imaging were included. The underlying pathology and the prevalence of lipid plaques in the culprit lesion was compared between women with and without cardiovascular risk factors (i.e. hypertension, smoking, hyperlipidemia, diabetes mellitus, family history and chronic kidney disease) in three different age groups (&lt;60 yr, 60–70 yr, &gt;70 yr).

Results
The relative prevalence of plaque erosion was higher in younger women (&lt;60 yr) and decreased with age (from 51% to 28%, p&lt;0.001). There was no significant difference in the prevalence of lipid plaques between women with and without risk factors, except a higher prevalence of lipid plaques in current smokers compared to non-smokers (79% vs. 63%, p=0.003). In women with hyperlipidemia, the prevalence of lipid plaques was modest in young ages (&lt;60 yr), but increased steeply with age (p&lt;0.001). The increasing age trend for lipid plaque was also observed in women with hypertension (p=0.03) and current smokers (p=0.01). In women with diabetes mellitus and family history, the prevalence of lipid plaques was high even in young ages (&lt;60 yr) and did not increase with age.

Conclusion
The prevalence of plaque erosion was higher in younger women (&lt;60 yr) and decreased with age. Current smokers had significantly higher prevalence of lipid plaque. Patients with diabetes and positive family history had a higher prevalence of lipid plaque at young age. The prevalence of lipid plaques increased with age particularly in women with hyperlipidemia and hypertension.

Funding Acknowledgement
Type of funding sources: Foundation.
Heterogeneous plaque geometry is associated with major adverse cardiovascular events
Authors: Gu Z S , Huang Y , Costopoulos C , Jessney B , Bourantas C , Teng Z , Maehara A , Raber L , Stone G , Bennett M R 
Published: October 2022

Abstract

Objectives
To determine whether coronary artery plaque-lumen geometry predicts major adverse cardiovascular events (MACE), and incorporating geometric measures enhances risk stratification from intravascular imaging.

Background
Prospective studies show that only a minority of plaques with higher-risk features result in future MACE, indicating the need for more predictive markers of plaque vulnerability. Plaques show heterogeneous structures and plaque-lumen geometry, both of which can promote high plaque structural stress (PSS); however, the relationships between geometric heterogeneity and MACE or PSS are unknown.

Methods
We examined plaque-lumen curvature, irregularity, lumen aspect ratio (LAR), roughness, PSS and their longitudinal heterogeneity (Figure 1A) in 35 non-culprit lesions (NCL) associated with MACE and 66 propensity-matched no-MACE NCL from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Causes of heterogeneous geometry and PSS were examined using a separate group of co-registered virtual histology-intravascular ultrasound (VH-IVUS) and optical coherence tomography (OCT) images (n=53 plaques).

Results
Plaque geometry heterogeneity indices (HI) were increased in NCL MACE vs. no-MACE lesions across the whole plaque and peri-minimal luminal area (MLA) segments (HI curvature: p=0.002; HI irregularity: p&lt;0.001; HI LAR: p=0.001; HI roughness: p=0.002). Peri-MLA HI roughness was an independent predictor of future MACE (hazard ratio: 3.69, p&lt;0.001) (Figure 1B). Inclusion of HI roughness improved identification of NCLs leading to MACE in VH-defined thin-cap fibroatheromas (VH-TCFA, p=0.005), MLA ≤4mm2 (p=0.001), and plaque burden (PB) ≥70% (p&lt;0.001) (Figure 1C–E), and further improved the ability of PSS to identify MACE NCLs in VH-TCFA (p=0.041), MLA ≤4mm2 (p=0.033), and PB ≥70% (p&lt;0.001). HI roughness generally corresponded with HI PSS, but was also increased at sites of local calcification and multilayering.

Conclusions
Plaque-lumen geometric heterogeneity is increased across whole plaque and peri-MLA segments of NCLs causing MACE. Inclusion of geometric heterogeneity may improve the ability of intravascular imaging to predict MACE.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): British Heart Foundation
The effects of smoking on cardiac structure and function in a general population
Authors: Holt E , Skaarup K G , Lassen M C H , Johansen N D , Joergensen P G , Hauser R , Lind J N , Jensen G , Schnor P , Prescott E , Soegaard P , Moegelvang R , Biering-Soerensen T 
Published: October 2022

Abstract

Background
Cigarette smoking is the leading preventable cause of death worldwide. Smoking is known to cause coronary artery disease, but studies have also shown that smoking independently is associated with higher risk of heart failure. However, the link between smoking and cardiac structure and function is not yet fully examined.

Purpose
The aim of the study was to investigate the independent effect of cigarette smoking on cardiac structure and function in a general population using echocardiographic measures.

Methods
A prospective cohort of 3,874 participants from a general population free of prevalent heart disease underwent an echocardiographic examination including two-dimensional speckle-tracking analysis. Smoking history was obtained through a self-administered questionnaire, that generated three groups; current smokers (18.6%), former smokers (40.9%) and never smokers (40.5%). Pack-years were estimated from the questionnaire.

Results
After multivariable adjustment for age, sex, body mass index, hypertension, hypercholesterolemia, diabetes and lung function, current smokers had significantly alterations in septal thickness (1.1±0.2 cm, P=0.018) and relative wall thickness (0.4±0.1 cm, P=0.016) compared to never smokers. Furthermore, left ventricular mass index (LVMi) was increased in current smokers compared to never smokers (85.8±19.3 g/cm2, P=0.048). Reduced left ventricle systolic function as assessed by global longitudinal strain (GLS) was evident in current smokers compared to never smokers (19.1±2.3%, P&lt;0.001). Additionally, after multivariable adjustment increasing pack-years was associated with decreases in left ventricular ejection fraction (LVEF) (β=−0.04, P=0.031), E/A ratio (β=−0.06, P&lt;0.001) and GLS (β=−0.04, P=0.008). Comparing cardiac structure and function in never smokers, continuous smokers and former smokers after 10 years, showed that continuous smokers developed increased LVMi (Δ=3.97±17.48 g/cm2, P&lt;0.001) and decreased GLS (Δ=−0.77±3.84%, P=0.04) and LVEF (Δ=−4.23±5.7, P&lt;0.001) compared to never and former smokers.

Conclusion
In a large general population study without known heart disease, current smoking and accumulated pack-years were independently associated with alterations in cardiac structure and reduced systolic function. Furthermore, we found that continuous smokers over a 10-year period developed relatively worse systolic function and increased LV structure alterations compared to never smokers and to participants that stopped smoking during that period.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Copenhagen City Heart Study is funded by The Danish Heart Foundation andThe Metropolitan Region of Denmark.
Prognostic implications of fractional flow reserve and coronary flow reserve after newer-generation drug-eluting stent implantation
Authors: Ueno H , Hoshino M , Sugiyama T , Kanaji Y , Hada M , Misawa T , Nagamine T , Nogami K , Sayama K , Matsuda K , Yonetsu T , Sasano T , Kakuta T 
Published: October 2022

Abstract

Background
FFR after percutaneous coronary intervention (PCI) has been reported to provide prognostic information. However, limited data are available regarding the prognostication by CFR in patients treated with elective PCI using newer generation DES.

Purpose
This study aimed to assess the prognostic value of post-procedural fractional flow reserve (FFR) and coronary flow reserve (CFR) after newer-generation drug-eluting stent implantation (DES).

Methods
A total of 466 stenoses in 466 patients underwent FFR-guided PCI. FFR and CFR measurements before and after PCI by a pressure-temperature sensor-tipped wire were performed. Follow-up data were studied to determine the predictors of target vessel failure (TVF), defined as death, target vessel-related nonfatal myocardial infarction, and unplanned clinically driven target vessel late revascularization. Prognostic value of post-PCI CFR was compared with that of FFR or FFR/CFR combination.

Results
After PCI completion, 13.7% showed post-PCI FFR ≤0.80 and 44.2% exhibited post-PCI CFR &lt;2.5. Discordant results were observed in 42.5% (198/466). During 2.7 (1.8–3.3) years follow-up, 57 (12.2%) TVF were documented. The multivariable Cox proportional hazard regression analysis revealed that post-PCI FFR and post-PCI CFR were independent prognostic factors. ROC analysis revealed that the optimal cut-off values of post-PCI FFR and CFR values were 0.85 and 2.26, respectively. Significant differences in TVF were detected according to post-PCI FFR (≤0.85 vs &gt;0.85: 17.8% vs 8.9%, P&lt;0.05) and post-PCI CFR (≤2.26 vs &gt;2.26: 20.5% vs 7.2%, P&lt;0.01), although the reclassification ability for TVF was improved only with post-PCI CFR (net reclassification index 0.598; P&lt;0.01; integrated discrimination index 0.038; P&lt;0.01), but not with post-PCI FFR, in comparison with the clinical model. Compared with patients with FFR &gt;0.85, those with post-PCI FFR ≤0.85 and CFR ≤2.26 showed significantly higher risk of TVF (8.9% vs 28.9%, P&lt;0.01, HR 4.24, 95% CI 2.40–7.50, P&lt;0.01), whereas those with post-PCI FFR &lt;0.85 and CFR &gt;2.26 had similar TVF risk (8.9% vs 9.2%, P=1.00, HR 1.01, 95% CI 0.47–2.16, P=0.97).

Conclusions
After PCI completion with newer-generation DES, discordant results between FFR and CFR were observed in 42.5%. Compared with post-PCI CFR, post-PCI FFR provided limited reclassification ability for TVF. Among patients with lower post-PCI FFR, only patients with lower post-PCI CFR showed significantly higher risk of TVF than those with higher post-PCI FFR.

Funding Acknowledgement
Type of funding sources: None.
Direct cost analysis of genetic testing for CYP2C19*2 and *3 loss of function variants in percutaneous coronary intervention patients
Authors: Huxley S , Pereira N , Borah B , Lennon R , Moriarty J 
Published: October 2022

Abstract

Background/Introduction
Patients with CYP2C19*2 or *3 loss of function (LOF) variants who undergo percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel.

Purpose
A subgroup of patients who were included in the TAILOR-PCI trial were also enrolled in this study to determine if a genotype-guided (GG) approach based on CYP2C19*2 or *3 LOF variants is cost-effective.

Methods
Patients were randomized to the conventional therapy group with clopidogrel and to the GG group who underwent point of care genotype testing for CYP2C19*2 or *3 LOF variants. In the GG group, therapy was based on genotype results. Those identified as LOF carriers were prescribed ticagrelor while non-carriers were prescribed clopidogrel.

Results
There were no significant differences in direct medical costs between the conventional therapy group and GG group (mean $19,747 versus $20,682, p=0.11), however total costs were significantly greater in the GG group which was primarily driven by the outpatient cost of ticagrelor. Furthermore, there was no significant cost difference between ticagrelor treated LOF carriers and clopidogrel treated non-carriers.

Conclusion
These findings suggest that a GG approach with point of care testing for CYP2C19*2 or *3 LOF variants in patients undergoing PCI may be a cost-effective practice.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): NIH grants
Effects of CYP3A4*22 carrier and CYP3A5 expressor status on clinical outcome in patients treated with ticagrelor for acute coronary syndrome
Authors: Azzahhafi J , Bergmeijer T O , Van Den Broek W W A , Chan Pin Yin D R P P , Rayhi S , Peper J , Bor W L , Van Schaik R H N , Ten Berg J M 
Published: October 2022

Abstract

Background
Current guidelines recommend using ticagrelor in patients with acute coronary syndrome. Ticagrelor is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5. CYP3A4*22 allele and the CYP3A5 expressor status influence the metabolization of ticagrelor, increasing plasma concentration and platelet inhibition. Nevertheless, little is known about the impact of the CYP3A4*22 allele or CYP3A5 expressor status on clinical outcomes in ticagrelor treated patients.

Purpose
Our study aims to assess the effects of the CYP3A4*22 allele and CYP3A5 expressor status in patients with STEMI and treated with ticagrelor, with regards to clinical outcomes and the clinical side-effect dyspnea.

Methods
Patients from the POPular Genetics trial treated with ticagrelor were genotyped for the CYP3A4*22 and CYP3A5*3 alleles. Patients were divided into two groups based on their CYP3A4 (*22 carriers vs. *22 non carriers) and CYP3A5 status (expressor vs. non-expressors). The primary thrombotic endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis and stroke. The primary bleeding outcome consisted of PLATO major and minor bleeding. The key secondary endpoint was clinically relevant dyspnea. The follow-up duration was one year.

Results
A total of 1,281 patients with ST-elevation myocardial infarction (STEMI) were used for the analyses. In the first analysis, CYP3A4*22 carriers (n=152) versus CYP3A4*22 non-carriers (n=1,129) were not found to have a significant correlation with the primary thrombotic outcome (1.3% vs. 2.5% adjusted hazard ratio 1.81 [0.43–7.62]) or the primary bleeding outcome (13.2% vs. 11.3% adjusted hazard ratio 0.93 [0.58–1.50]) (See Figure 1 and 2). CYP3A5 expressors (n=196) versus non-expressors (n=926) did not show a significant difference for the primary thrombotic outcome (2.6% versus 2.5% adjusted hazard ratio 1.03 [0.39–2.71] or the primary bleeding outcome (12.8% versus 10.9% adjusted hazard ratio 1.13 [0.73–1.76]). With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers 44.0% vs. 45.0%, risk ratio 1.04 [0.45–2.42] or CYP3A5 expressors versus CYP3A5 non-expressors 35.3% versus 47.8% risk ratio 0.60 [0.27–1.30].

Conclusions
In STEMI patients treated with ticagrelor, CYP3A4*22 carriers and CYP3A5 expressors did not affect clinical outcomes with regards to thrombotic events, bleeding rate, or the side-effect dyspnea.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organization for Health Research and Development (ZonMW). The authors are solely responsible for designing and conducting this study, conducting all study analyses, and drafting and editing the manuscript and its final contents.