bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6596S100A8/A9 and sRAGE peripheral blood levels in patients with heart failure and an implanted cardioverter/defibrillator: relation with sustained, fast ventricular arrhythmias
Authors: Flevari P , Leftheriotis D , Kroupis C , Kitsinelis V , Stasinos V , Varlamos C , Dima K , Deftereos S , Iliodromitis E 
Published: October 2019

Abstract

Background
Prediction of sudden cardiac death in heart failure (HF) remains suboptimal. Blood levels of the S100A8/A9 heterodimer protein complex and the soluble receptor of advanced glucation end product (sRAGE) are promising biomarkers in HF, reflecting inflammatory/fibrotic and apoptotic pathways, possibly involved in ventricular arrhythmogenesis. The relation of S100A8/A9 and sRAGE with ventricular arrhythmias and sudden cardiac death risk has not been previously assessed.

Purpose
Purpose of the study was to investigate whether S100A8/A9 and sRAGE serum blood levels of patients (pts) with systolic heart failure are related to the occurrence of life-threatening ventricular tachyarrhythmias.

Patients and methods
We studied 60 pts with clinically stable heart failure due to coronary artery disease (n=37) and dilated cardiomyopathy (n=23), all with a chronically implanted ICD for primary (n=43) or secondary (n=16) sudden death prevention, all in sinus rhythm. Their mean age (±1 SE) was 62±2 years, NYHA class I-II, mean LVEF 28±1%, Nt-pro-BNP 893±85 pg/dl. Blood was drawn at study initiation for S100A8/A9 and sRAGE assessment (ELISA, R&D Systems). They all were systematically followed-up for 4 years regarding the occurrence of fast ventricular tachyarrhythmias (>180 bpm) necessitating antiarrhythmic intervention through the ICD.

Results
S100A8/A9 and sRAGE levels were 16±1.6 ng/ml and 1076±99 pg/ml respectively. S100A8/A9 levels were lower than in normal controls, while sRAGE levels were within normal limits. During the 4-year follow-up period, 39 pts had an uneventful course (Group I), while 16 pts exhibited fast ventricular tachyarrhythmic episodes necessitating ICD activation (anti-tachycardia pacing or shock, Group II). Three pts died of pump failure and 2 pts of non-cardiac causes. No differences were observed between Group I and Group II pts regarding mean NYHA class, Nt-pro-BNP levels. Group II patients had significantly lower LVEF as well as S100A8/A9 serum levels relative to pts without ventricular arrhythmias (LVEF: 30±1.2 vs, 25±1.3%, p<0.05, S1OOA8/A9: 18.9±2.2 vs 11.8±1.5 ng/ml, p<0.05), while no difference was observed between Groups regarding sRAGE levels 1097±101 1105±239 pg/ml, p:NS). S100A8/A9 levels were not related significantly to LVEF (r:-21, p=0.13).

Conclusion
S100A8/A9 protein levels are reduced in pts with stable HF and an implanted ICD. They are even lower among pts with rapid ventricular tachyarrhythmias occurring during follow-up. This finding implies that S100A8/A9 may constitute a biomarker of increased sudden cardiac death risk in HF, in addition to reduced LVEF.
29Prognostic safety of automatic cancellation of rest myocardial perfusion scan by machine learning: a report from multicenter REFINE SPECT registry of new generation SPECT
Authors: Hu L , Sharir T , Fish M B , Ruddy T D , Di Carli M , Dorbala S , Einstein A J , Betancur J , Eisenberg E , Commandeur F , Germano G , Damini D , Berman D , Slomka P J 
Published: October 2019

Abstract

Background
We aimed to develop a machine learning (ML) computer score derived from stress imaging and clinical data, which indicates if the rest scan could be automatically and safely canceled in the routine stress/rest myocardial perfusion SPECT (MPS).

Methods
A total of 20414 stress/rest cases from the REFINE SPECT registry collected from 5 sites in 3 countries with Tc-99m-based MPS images, clinical data, and clinical follow-up were included in the study. All images were automatically processed at our Medical Center. The automatically generated myocardial contours were checked by experienced technologists. In total, 93 variables (26 clinical, 17 stress-test, and 50 stress-imaging variables) were used to build a LogitBoost model for prediction of adverse events (AE), including coronary revascularization, death, myocardial infarction, and unstable angina. 10-fold cross-validation was performed to separate test from validation data for the assessment of ML. The overall ML predictive performance was compared to quantitative (stress total perfusion deficit [TPD]) by the area under the receiver operating characteristic curves (AUC). ML cut-off (ML1) to simulate the decision of cancellation of the rest scan was set to result in the same % of normal scans as these determined by the normal clinical reader diagnosis on a 4-point scale in the whole population, or the same % of scans with visual summed stress scores (SSS) = 0 in the subpopulation with available SSS. A second ML cutoff (ML2) was established to achieve a 1% annual risk of AE. The annual risk of AE of the normal ML score was compared with normal clinical diagnosis and with the finding of SSS = 0.

Results
The mean follow-up interval was 4.7±1.5 years. Overall, 3542 AE were observed (3.7% annual risk). The AUC for AE was higher for ML (0.780±0.005) than for stress TPD (0.698±0.006) (p<0.001). Normal clinical diagnosis was reported in 60% cases. In 70% (14242 scans) with available segmental scores, 53% had SSS=0. ML1 and ML2 thresholds were compared with normal visual diagnosis and with SSS = 0 for AE (Figure). ML1 achieved a lower annual risk (1.5%) than normal clinical diagnosis (2.1%) or SSS = 0 (1.6% versus 2.3%) (p<0.001). The more conservative ML2 threshold with a 1% annual risk of AE resulted in a 40% canceling rate.
Figure 1

Conclusion
ML could be used to automatically cancel the rest MPS scan with the same proportion as using normal visual MPS reading, but with significantly lower AE rate in stress-only scans.

Acknowledgement/Funding
R01HL089765 from the National Heart, Lung, and Blood Institute/National Institutes of Health (NHLBI/NIH)
56The SGLT2 inhibitor empagliflozin reduces mortality in experimental pulmonary hypertension
Authors: Chowdhury B , Luu V Z , Luu A Z , Kabir M G , Pan Y , Teoh H , Quan A , Mazer C D , Verma S 
Published: October 2019

Abstract

Introduction
Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion and profoundly reduces hospitalisation for heart failure and cardiovascular mortality in individuals with type 2 diabetes. While empagliflozin has been reported to reduce blood pressure, its effect on pulmonary arterial hypertension (PAH) is unknown. PAH is a serious and progressive disease that is characterised by pulmonary artery vasoconstriction, vascular remodelling, right ventricular hypertrophy, and ultimately heart failure.

Purpose
To investigate the impact of empagliflozin on PAH-associated mortality and the progression as well as reversal of PAH in monocrotaline (MCT)-treated Sprague-Dawley rats.

Methods
A total of 66 male rats (220–250 g) were randomly assigned to one of three studies. PAH was induced with a single intraperitoneal injection of MCT on day 0 and empagliflozin (10 mg/kg) was administered daily by oral gavage. Survival study: PAH was induced with 60 mg/kg MCT. Starting on day 1, rats were treated with empagliflozin (n=8) or vehicle (n=8) for 28 days and monitored for up to 45 days post-MCT injection. Prevention study: Rats were administered 60 mg/kg MCT and treated with empagliflozin (n=12) or vehicle (n=12) for 20 days from day 1 onwards. Reversal study: 21 days after being injected with 40 mg/kg MCT, rats were given empagliflozin (n=8) or vehicle (n=8) for 14 days. At the end of the treatment window, rats in the latter two studies underwent haemodynamic assessments before their tissues were harvested for histological review.

Results
Mortality rates between the two groups were significantly different (median survival 24 vs 33 days for vehicle vs empagliflozin; p<0.05). Compared to the MCT-vehicle-treated rats, the MCT-empagliflozin group had significantly lower mean pulmonary artery pressure (77.4±8.6 vs 51.0±4.9 mmHg [Prevention study]; 56.0±4.3 vs 43.0±3.4 mmHg [Reversal study]); higher pulmonary acceleration time (21.0±0.8 vs 27.4±1.4 ms [Prevention study] and 27.1±1.0 vs 33.4±1.3 ms [Reversal study]); and less right ventricular hypertrophy (0.52±0.01 vs 0.41±0.04 [Prevention study]). Histological assessments revealed significantly less medial wall thickening (50.8±2.2 vs 44.7±1.1 mm) and muscularisation (53.2±1.3 vs 43.6±2.1 mm) in pulmonary arterioles from the empagliflozin- vs vehicle-treated rats (p<0.001 for both).

Conclusion
This is the first study demonstrating that SGLT2 inhibition with empagliflozin lowers mortality in experimental pulmonary hypertension in part via reduced pulmonary vascular remodelling.

Acknowledgement/Funding
This study was supported by grants from the Canadian Institutes of Health Research.
66Clinical outcomes after catheter ablation for atrial fibrillation in elderly patients: a French nationwide cohort study
Authors: Bisson A , Mondout F , Bodin A , Clementy N , Pierre B , Gaborit C , Herbert J , Guillon Grammatico L , Babuty D , Fauchier L 
Published: October 2019

Abstract

Catheter ablation for atrial fibrillation (AF) is a validated therapy for patients with symptomatic AF to prevent recurrences. The CASTLE AF trial indicated that ablation for AF in patients with heart failure was associated with a lower rate of death from any cause or hospitalization for worsening heart failure than was medical therapy. However, the benefit of AF ablation was not significant in older patients (>65 yo). The purpose of our study was to compare the incidence of these events in patients after AF catheter ablation versus patients not treated with AF ablation at a nationwide level and to analyse whether the possible benefit with AF ablation may differ among patients younger or older than 75 yo.

Methods
This French longitudinal cohort study was based on the national hospitalization PMSI (Programme de Médicalisation des Systèmes d'Information) database covering hospital care from the entire population. We included all patients, over 18 years old, with AF from January 2010 to December 2015.

Results
Among the 1,663,284 patients identified with AF, 28,018 patients were treated with AF ablation (28% female, mean age 60±10 yo) and 1,635,266 did not have AF ablation (48% female, mean age 78±11 yo). Among those treated with AF ablation, 1,605/28,018 patients (5.7%) were aged >75 yo.
During follow-up (456±546 days), hospitalization with a primary diagnosis of HF and death were recorded. Incidences of hospitalization for HF and death were significantly lower in AF ablation group (respectively 6.09% vs 13.29% person per year, p<0.0001, and 1.49% vs 17.11% person per year, p<0.0001). These associations were confirmed in a multivariable analysis after adjustment on age and other comorbidities (HR 0.66, 95% CI 0.63–0.69, p<0.0001 for HF and HR 0.21, 95% CI 0.19–0.23, p<0.0001 for all-cause death). Results were significant and relatively similar whether patients were aged below or above 75 yo: HR 0.63, 95% CI 0.60–0.66, p<0.0001 when age <75 yo and HR 0.60, 95% CI 0.51–0.70, p<0.0001 when age >75 yo for hospitalization for HF; HR 0.21, 95% CI 0.19–0.24, p<0.0001 when age <75 yo and HR 0.36, 95% CI 0.29–0.45, p<0.0001 when age >75 yo for all-cause death.

Conclusion
In the nationwide analysis of unselected AF patients seen in hospitals, AF ablation was independently associated with a lower risk of hospitalization for HF and death whether patients were aged below or above 75 yo.
101Characterization of the calcium component of vulnerable coronary plaque in patients with NSTEMI: prospective comparison between coronary CT and optical coherence tomography
Authors: Pezel T , Sideris G , Dillinger J G , Logeart D , Manzo-Silberman S , Cohen-Solal A , Beauvais F , Laissy J P , Henry P 
Published: October 2019

Abstract

Background
Acute Coronary Syndrome (ACS) remains a leading cause of mortality worldwide with a high risk of recurrence. Apart culprit plaques, the presence of vulnerable plaques could be associated with the occurrence of future cardiac events and need to adapt treatments. Several studies have demonstrated a role for Coronary Computed Tomographic Angiography (CCTA) to predict the vulnerability of the plaque but with limited analysis of its calcium component. Recent works suggest a role for calcification in this vulnerability.
To our knowledge, no studies have been performed to assess if the study of the calcium component of plaques with CCTA can help to predict vulnerability in non-ST elevation myocardial infarction (NSTEMI).

Purpose
To assess if the CCTA study of the calcium component of plaques can help to predict plaque vulnerability defined by intracoronary OCT analysis in patients with non-ST elevation myocardial infarction (NSTEMI).

Methods
Monocentric prospective study of consecutive patients referred for NSTEMI with elevated high-sensitivity cardiac troponin I level (hs-TnI>50 ng/ml) from January to October 2018. CCTA was systematically performed before coronary angiography to assess the presence of CAD. When CCTA demonstrated significant lesions, coronary angiography was performed within 24 hours associated with systematic OCT study of three coronary arteries. Apart culprit plaques, vulnerable plaques were defined in OCT by a fibrous screed thickness <65 microns. Calcified plaques were analysed with CT and then classified into 3 groups: vulnerable culprit plaque (VCP), vulnerable non-culprit plaque (VNCP) and stable plaque (SP).

Results
Of 1478 patients with chest pain, 257 (17%) had NSTEMI with high level of hs-TnI. From this 257 NSTEMI patients, 44 (17%) were without known CAD and among these, 33 (75%) had received coronary angiography with 29 (66% - mean age 59±13 years, 73% men) having coronary anatomy compatible with OCT assessment. A total of 123 calcified plaques were identified. Among them, OCT allowed to identify 77 (63%) SP and 47 calcified vulnerable plaques; 28 (23%) VNCP and 19 (15%) VCP. After CCTA analysis of the calcium component, predictive factors of plaque vulnerability were identified: longer calcification length (p<0.001), larger calcification volume (p<0.001), lower calcium mass (p=0.003), higher single plaque Agatston score (p<0.001), lower sphericity index (p=0.001), more spotty calcifications (p=0.001), as well as more intimal position in the wall (p<0.001). No significant differences were observed comparing VNCP and VCP (Figure).
OCT and “Virtual Histology” CT

Conclusion
CCTA study of the calcium component of plaque allows to identify predictors of plaque vulnerability defined by OCT in patients with NSTEMI.
105Calcified nodule in coronary artery: clinical features and prognosis with optical coherence tomography-guided percutaneous coronary intervention
Authors: Shibata H , Kijima Y , Nagoshi R , Kozuki A , Fujiwara R , Suzuki A , Kakizaki S , Fujimoto D , Kyo S , Masuko E , Miyata T , Shite J 
Published: October 2019

Abstract

Background
Calcified nodule (CN) in coronary artery is known to be a significant factor for stent underexpansion, however, its baseline characteristics and long-term prognosis is unclear.

Method
421 consecutive severe calcified lesions (Defined as maximum calcium arc >180 degrees) which underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) were analyzed between January 2013 and December 2017. We investigated baseline characteristics and OCT parameter (maximum arc of calcium, maximum thickness of calcium, and length of calcium) and long-term clinical outcome (Major adverse cardiac event (MACE), any cause of death, acute myocardial infarction (AMI) and target vessel failure (TVF)). Median follow up period was 33.7 months.

Result
CN was seen in 22.3% (94 lesions) of all severe calcified lesions. Baseline characteristics and OCT parameters were significantly different in CN and non-CN groups (Hemodialysis; 23.6% vs. 14.1%, p=0.03, Multivessel Disease; 57.4% vs. 44.6, p=0.03, maximum arc of calcium; 305.4 vs. 286.1, p=0.02, maximum thickness of calcium (μm); 1206.2 vs 1123.8, p=0.01, length of calcium (mm); 24.6 vs. 19.0, p=0.01). CN lesions was strongly associated poor long-term clinical outcome (MACE; 50.5% vs. 25.7%, p<0.01), any cause of death; 18.1% vs. 9.5%, p=0.02, AMI; 7.4% vs. 2.4%, p=0.02, TVF; 38.3% vs. 19.2%, p<0.01).

Conclusion
Hemodialysis, multivessel disease and abundant calcium component may have accompanied with CN which may result in poor long-term prognosis.
108Biologic significance of healed culprit plaques in stable angina versus acute coronary syndromes
Authors: Fracassi F , Sugiyama T , Yamamoto E , Kurihara O , Kim H O , Thondapu V , Lee H , Fujimoto J G , Fuster V , Jang I K 
Published: October 2019

Abstract

Background
Healed plaques, the signature of prior subclinical plaque destabilization, are frequently found in autopsy studies and have recently been described in patients with acute coronary syndromes (ACS).

Objectives
To compare the prevalence and features of plaque vulnerability of healed culprit lesions in stable angina pectoris (SAP) versus ACS patients by using Optical Coherence Tomography (OCT).

Methods
A total of 752 patients were included: 376 patients with SAP were selected using propensity score matching, comparable to 376 patients with ACS. Healed plaques were identified using established criteria, defined as layers of different optical density on OCT. Healed plaque prevalence along with angiographic and OCT findings were compared between the two groups.

Results
Healed plaques were more frequent in SAP than in ACS patients (42.0% vs 28.7%, p<0.001). LDL-cholesterol and high sensitive C-reactive protein (hs-CRP) levels were significantly lower in SAP patients with layered plaque as compared to ACS patients with layered plaque [97.9±36.9 mg/dL vs 116.7±39.2 mg/dL, p<0.001; 0.20 (0.10–0.83) mg/L vs 4.98 (1.00–11.32) mg/L, p<0.001, respectively]. Thin-cap fibroatheroma, macrophage accumulation and microvessels were significantly less frequent in layered plaques in SAP patients as compared to those in ACS patients (12.7% vs 56.5%, p<0.001, 7.0% vs 79.6%, p<0.001, and 20.3% vs 43.5%, p<0.001, respectively). Calcifications were found more frequently among layered plaques in SAP patients than in ACS patients (51.3% vs 33.6%, p=0.006).

Conclusions
Healed plaques, detected more frequently in SAP than in ACS patients, portend different atherosclerotic backgrounds. In SAP patients, plaque destabilization frequently does not lead to occlusive thrombosis, possibly due to low level of local vulnerability and systemic inflammation. In ACS patients, the presence of high level of local vulnerability and systemic inflammation may play an important role in occlusive thrombus formation, resulting in terminating the cycles of subclinical thrombosis and healing.
130The effect of parity on exercise physiology in women with heart failure with preserved ejection fraction
Authors: Beale A L , Cosentino C , Segan L , Mariani J , Vizi D , Evans S , Nanayakkara S , Kaye D M 
Published: October 2019

Abstract

Introduction
Women are overrepresented amongst patients with HFpEF, however the underpinning mechanism for this asymmetric distribution is unclear. Pregnancy has been demonstrated to contribute to cardiovascular risk, and represents a potential gender specific risk factor for HFpEF.

Purpose
To investigate the relationship between parity and severity of HFpEF on invasive haemodynamic and echocardiographic studies.

Methods
Patients referred for investigation of dyspnoea with exercise right heart catheterisation from 2008–19 were included and classified as HFpEF with an ejection fraction (EF) ≥50% and a resting PCWP ≥15mmHg or exercise PCWP ≥25mmHg. All patients underwent detailed haemodynamic and echocardiographic assessment, and an obstetric history including socioeconomic data were obtained using a questionnaire.

Results
58 women were included, and categorised as having either 0–2 births, or ≥3 births, dividing the cohort equally. Women with ≥3 births achieved a lower peak exercise workload than those with 0–2 births (46 [31–68] vs. 38 [24–51] W, p=0.04). Women with ≥3 births had a greater rise in pulmonary capillary wedge pressure indexed to workload with exercise (0.5 [0.3–0.8] vs. 0.3 [0.2–0.5] mmHg/W, p=0.03), paralleled by a greater rise in right atrial pressure (10 [8–12] vs. 7 [3–11] mmHg, p=0.01), pictured. Pulmonary vascular resistance was also higher in women with ≥3 births (1.9 [1.6–2.4] vs. 1.6 [1.4–1.9] mmHg/L/min rest, p=0.046, and 1.9 [2.4–2.4] vs. 1.4 [1–1.8] mmHg/L/min exercise, p=0.024). Left ventricular ejection fraction was lower at rest (60 [57–61] vs. 63 [60–66] %, p=0.008) and during exercise (65 [62–67] vs. 68 [66–70] %, p=0.038) in women with higher parity. Otherwise, echocardiographic parameters did not differ according to parity. There were no significant differences between parity groups in baseline characteristics, including age, body mass index, systemic blood pressure, natriuretic peptides or dyspnea class. Similarly, comorbidities and socioeconomic status did not differ.

Conclusion(s)
Higher parity is associated with impairments in multiple physiologic parameters of HFpEF severity in women, including diastolic reserve, pulmonary vascular resistance, and systolic function. This may indicate a role for pregnancy in the development of HFpEF, and suggests that multiparous women should be targeted for intensification of preventative measures for HFpEF.
171Intravascular polarimetry in patients with coronary artery disease: a first-in-human pilot study
Authors: Otsuka K , Villiger M , Karanasos A , Van Zandvoort L J C , Doradla P , Daemen J , Diletti R , Van Geuns R J , Zijlstra F , Van Soest G , Dijkstra J , Nadkarni S K , Regar E , Bouma B E 
Published: October 2019

Abstract

Background
Polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties of tissue together with conventional cross-sectional OFDI images of subsurface microstructure. PS-OFDI offers refined insight into plaque morphology and composition, which are implicated in the pathogenesis of acute coronary syndromes (ACS).

Purpose
This first-in-human pilot study of intravascular polarimetry aimed to investigate birefringence and depolarization features of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional OFDI and with clinical presentation.

Methods
30 patients undergoing PS-OFDI (acute coronary syndrome; ACS, n=12 and stable angina pectoris; SAP, n=18) participated in this study. 342 cross-sectional images evenly distributed along all imaged coronary arteries were classified into one of seven plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross-section were compared between plaque types and with structural parameters. Further, we assessed the polarization properties in the fibrous caps of ACS and SAP culprit lesions and compared them with structural features using a generalized linear model.

Results
The median birefringence and depolarization showed statistically significant differences among plaque types (both p<0.001, one-way ANOVA). Depolarization significantly differed between individual plaque types (p<0.05), except between fibro-fatty and fibro-calcified plaques. Caps of ACS lesions and ruptured caps exhibited lower birefringence than caps of SAP lesions (p<0.01). In addition to clinical presentation, cap birefringence also associated with macrophage accumulation as assessed by normalized standard deviation.
Intravascular polarimetry

Conclusions
Intravascular polarimetry provides quantitative metrics that help to characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients (Figure). Quantitative assessment of plaque polarization properties by intravascular polarimetry may open new avenues for studying plaque progression and detecting high-risk patients.

Acknowledgement/Funding
The JSPS Overseas Research Fellowship, the Uehara Memorial Foundation, and the Japan Heart Foundation and Bayer Yakuhin