bluuebunny/crossref_metadata_2025 huggingface dataset:
P5748Impact of specific crossing techniques in chronic total occlusion percutaneous coronary intervention on recovery of absolute myocardial perfusion
Authors: Schumacher S P , Stuijfzand W J , Driessen R S , Van Diemen P A , Bom M J , Everaars H , Kockx M , Raijmakers P G , Boellaard R , Van De Ven P M , Van Rossum A C , Opolski M P , Nap A , Knaapen P
Published: October 2019

Background

Multiple techniques in chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) have been developed to cross CTOs.

Purpose

To compare recovery of quantitative myocardial blood flow (MBF) after different CTO PCI techniques.

Methods

Consecutive patients with [15O]H2O positron emission tomography perfusion imaging before and three months after successful CTO PCI were included. Change in quantitative hyperemic MBF, coronary flow reserve (CFR) and perfusion defect size were compared between antegrade wire escalation (AWE), retrograde wire escalation (RWE), antegrade dissection and reentry (ADR) and retrograde dissection and reentry (RDR), and further between specific subintimal crossing and reentry techniques.

Results

193 patients were treated with AWE (N=90), RWE (N=24), ADR (N=35) and RDR (N=44). Significant improvements (all p<0.01) in hyperemic MBF (1.19±0.77, 0.94±0.65, 1.09±0.63, and 1.02±0.75 mL min–1 g–1, respectively), CFR (1.34±1.08, 1.14±1.09, 1.31±0.96, and 1.24±0.99, respectively), and perfusion defect size (3.17±2.13, 3.00±2.21, 2.74±2.09, and 2.93±1.92 segments, respectively) were comparable between the four approaches (p=0.40, p=0.84, and p=0.77, respectively). Recovery of hyperemic MBF was less pronounced after subintimal crossing with a knuckle-wire-technique compared to the use of CrossBoss in controlled ADR and RDR (p=0.02), and less after reentry with subintimal tracking and reentry (STAR) in ADR compared with controlled ADR (Stingray) or limited antegrade subintimal tracking (LAST) (p=0.02 and p<0.01).

Conclusions

Recovery of hyperemic MBF, CFR, and perfusion defect size was significant after CTO PCI and comparable between different crossing techniques. Improvement of hyperemic MBF was inferior after using the knuckle-wire subintimal crossing technique and STAR compared to other subintimal crossing and reentry techniques.

Acknowledgement/Funding

None
P5974Prognostic value of global tangential strain by three-dimensional echocardiography heart failure patients with intermediate ECG criteria for cardiac resynchronization therapy
Authors: Sugahara M , Ashida K , Fukuhara E , Kishima H , Goda A , Mine T , Ishihara M , Masuyama T
Published: October 2019

Background

In the current clinical guidelines, cardiac resynchronization therapy (CRT) is recommended in heart failure (HF) patients with left bundle branch block (LBBB) with QRS width ≥150ms as Class I indication. In terms of HF patients with intermediate ECG criteria, prediction for benefit of CRT is still controversial in routine echocardiography.

Purpose

The aim was to assess whether three-dimensional (3D) echocardiographic indexes of global LV function at baseline has a prognostic value following CRT implantation in patients who fulfilled with intermediate ECG criteria.

Methods

We studied 62 HF patients who fulfilled with the indication criteria of CRT implantation according to current the clinical guidelines. In addition to routine two-dimensional echo, 3D echo dataset was acquired for determination of 3D global tangential strain (GTS) and 3D global longitudinal strain (GLS). We tracked predefined unfavorable outcomes for 3 years after CRT implantation: death, hospitalization due to worsening HF.

Results

LBBB with QRS width ≥150ms was evident in 26 of 62 patients (aged 68±11 years with 160±26 ms of QRS duration and 29±7% of LV ejection fraction), and the other 36 patients only fulfilled intermediate ECG criteria (QRS width 120–149ms or non-LBBB). Unfavorable events occurred in 21 patients (34%). The median GTS was −15.4%. Although GLS was not predictive, GTS greater than −15.4% had high probability of unfavorable outcomes over 3 years (Log-rank, p<0.05). There is no difference in the probability of unfavorable outcomes between LBBB and intermediate ECG criteria. Baseline GTS in patients with intermediate ECG criteria was associated with unfavorable outcomes: −12.6±2.6% vs. −17.3±3.8% (p<0.05). Outcome was better in the intermediate ECG criteria patients with GTS ≤−15.4% than in those with LBBB and in those with intermediate ECG criteria patients with GTS >−15.4% (Log-rank: p<0.05, p<0.0001, respectively).

Conclusions

Baseline GTS by 3D echocardiography is useful for predicting outcome over 3 years after CRT implantation regardless of the ECG criteria for CRT indication.
P5979Impact of disease stage on performance of strain markers for prediction of atrial fibrillation
Authors: Ramkumar S , Pathan F , Kawakami H , Ochi A , Yang H , Potter E , Marwick T H
Published: October 2019

Background

Efforts to predict incident atrial fibrillation (AF) may be associated with complications, and there is interest in AF prediction in primary prevention (PP; pts with risk factors) and secondary prevention (SP; pts with possible AF complications). These pts have different risk levels, we sought whether that influenced the predictive value of LV dysfunction (measured as global longitudinal strain, GLS) or LA dysfunction (LA reservoir strain).

Methods

The PP cohort comprised 351 community-based pts ≥65 years with ≥1 risk factor for AF (age 70±4y,43% male, median follow-up 22 months) and the SP cohort comprised 532 pts after transient ischaemic attack or stroke (age 68±12y, 51% male, median follow-up 36 months). GLS and LA strain were measured offline (Image Arena-Tomtec, Germany). AF was diagnosed by 12 lead ECG, Holter or by single lead monitor. The clinical and echocardiographic characteristics of those with AF were compared to those in sinus rhythm. Nested Cox-regression models were used to assess for independent and incremental predictive value of LA strain/GLS in both cohorts.

Results

Compared to SP, PP had higher clinical AF risk (CHARGE-AF 5.6±5.5% vs 4.7±12.1%, p=0.02) but a lower thromboembolic risk (CHA2DS2-VASC 3±2 vs. 4±2, p<0.001). AF developed in 42 PP pts (12%) and 61 SP (12%). AF patients were older, with higher CHARGE-AF score, LA volume and LV mass. Pts developing AF had reduced GLS (17±4% vs. 20±3%, p<0.001), reservoir (28±11% vs. 35±8%, p<0.001) and pump strain (13±7% vs. 17±5%, p<0.001). GLS and LA strain had greater AUC in SP (0.84 vs 0.58 for GLS and 0.85 vs 0.57 for reservoir strain, both p<0.001). Nested cox-regression models showed that LA reservoir strain was independently associated with AF in both cohorts (p<0.05). GLS was only independently associated with incident AF in SP (Figure).

Conclusion

LA reservoir strain is independently associated with AF in different risk cohorts and its effect is incremental to clinical parameters and LA volume. GLS may be more useful in AF risk assessment in those in SP.

Acknowledgement/Funding

This study was partially supported by the Tasmanian Community Fund and Siemens Healthcare Australia.
P5984Clinical results and predictors of long-term mortality after Transcatheter Aortic Valve Replacement in according to gender
Authors: Munoz-Garcia E , Munoz-Garcia M , Munoz Garcia A J , Dominguez-Franco A J , Carrasco-Chinchilla F , Alonso-Briales J H , Hernandez-Garcia J M , Jimenez-Navarro M F , Gomez-Doblas J J
Published: October 2019

Although it is well known, the differences between both sexes in cardiovascular disease, however, there is a lack of data in aortic valve, treated with Transcatheter Aortic Valve Replacement (TAVR). The purpose of our study was to analyze the long-term clinical results of patients treated with TAVR in the female and male population.

Material

Between April 2008 and December 2017, 647 patients with aortic stenosis and 20 patients with aortic prosthesis dysfunction, were treated with TAVR consecutively in our center. The primary objective was to analyze, by Cox regression, the predictors of long-term mortality in both sexes.

Results

59.1% were women. Males had a higher number of comorbidities and after a mean follow-up of 2.87±2.2 years (range between 0 and 9 years), mortality was higher for male patients 40.7% vs. 32% (HR = 1.447 [95% CI 1.057–2.009], p=0.022) and there were no differences for the presence of threatening bleeding (HR = 1.654 [IC95% 0.719–3.808], p=0.237), myocardial infarction (HR = 1,768 [IC95% 0.753–4.132], p=0.191), stroke (HR = 0.992 [IC95% 0.564–1.743], p=0.976) and hospitalizations for heart failure (HR = 1.388 [IC95% 0.811–2.376], p=0.231). Among the predictors of long-term mortality, common to both sexes were: threatening bleeding, heart failure, Charlson index, Karnofsky, and STS score.

Conclusion

In our series, there was clinical differences between both sexes, which has an impact on survival, being worse for men due to comorbidities, however, in the population of patients with aortic stenosis treated with TAVI, we found predictors of late mortality similarities between in female and male.
P6019His-Purkinje system pacing in single centre experience after 324 cases
Authors: Jastrzebski M , Moskal P J , Bednarek A , Kielbasa G , Czarnecka D
Published: October 2019

Introduction

His-Purkinje system pacing preserves or restores physiologic depolarization of the left ventricle during permanent pacing. It consists of two complementary techniques: His bundle pacing (HB-P) and the recently introduced left bundle branch pacing (LBB-P). There is limited data on HB-P outcomes and only a few reports of LBB-P results.

Purpose

Our aim was to investigate success rate, complications, acute and early pacing parameters in patients undergoing HB-P and LBB-P in the setting of a cardiology tertiary centre that routinely implants HB-P and LBB-P pacemakers.

Methods

On the basis of a prospective database we performed a longitudinal cohort study of all consecutive patients with His-Purkinje system devices implanted in the years 2014–2019. In all cases, model 3830 lumen-less 4.1 Fr pacing lead was used. HB-P was achieved via HB mapping or pace mapping, LBB-P was achieved via deep septal lead deployment under electrophysiological and 12-lead ECG guidance.

Results

Since 2014 there were 324 implantations of His-Purkinje system pacemakers. Baseline patients' characteristics are presented in Table. The overall success rate was 81.5%. Selective HB-P, non-selective HB-P and LBB-P were achieved in 53%, 19% and 28% of successful cases. The mean fluoroscopy time was 11±9 min. The lead delivery was performed using single sheath (C315His) in 83% cases, while in 17% extra steerable sheath was necessary (C304XL). The acute mean LBB-P capture threshold @0.5 ms was significantly lower than in HB-P (0.65±0.43V vs. 1.47±0.8V). The mean chronic LBB-P capture threshold @1.0 ms was also lower than in HB-P (0.45±0.3V vs. 0.95±0.7V, p<0.001). The acute sensing amplitude was significantly higher in LBB-P vs HB-P (10±5mV vs 4±3mV). The mean paced QRS duration was significantly shorter for selective HB-P (113±22 ms) and LBB-P (108±12 ms) vs. non-selective HB-P (132±22 ms). The complications included: 4 cases of threshold increase that required lead revision; 3 early lead dislodgments; 1 loss of LBB capture, 3 pocket hematomas, 2 system infections and 1 pneumothorax.

Baseline characteristics Age; sex 73±12 years (19–95 years); 64% males Mean EF; mean QRS duration; Presence of heart failuire or ischemic heart disease 47±15%; 128±32 ms; 48%; 37.5% Pacing indication AV block 31%; sinus node disease 12%; atrial fibrillation with bradycardia 37%; CRT 20% QRS morphology narrow QRS 61%; LBBB 20%; other 14%; IVCD 6% CRT, Cardiac Resynchronization Therapy; IVCD, Interventricular Conduction Delay.

Conclusion

His-Purkinje system pacing in routine practice has an acceptable success rate, pacing parameters and complication rate; the LBB-P provides better pacing parameters than HB-P. We believe that such single-centre experience paves the way for a large randomized trial of physiologic pacing.
P6020His bundle pacing in patients with abnormal versus intact atrioventricular conduction: from the IMAGE-HBP Study
Authors: Koneru J A Y , Dandamudi G O P I , Subzposh F A I Z , Shepard R K S , Kalahasty G K , Strobel J S , Ellenbogen K A E , Bergemann T B , Zhou X Z , Hughes L H , Vijayraman P V
Published: October 2019

Background

Frequent right ventricular pacing causes ventricular dyssynchrony and adverse outcomes. His bundle pacing (HBP) offers a physiological alternative. HBP electrical performance characteristics with cardiac conduction system abnormalities are not well established.

Purpose

To compare HBP implant procedure related parameters in patients with abnormal atrioventricular (AV) conduction versus those with intact AV conduction.

Methods

Patients prospectively enrolled in the IMAGE-HBP study undergoing implant attempt with a SelectSecure 3830 lead placed at the putative His-bundle location were included in the analysis. Patients were divided into groups based on AV conduction status. Implant characteristics and electrical performance of the pacemaker were tabulated and compared between the two groups with formal statistical tests.

Results

Among 60 patients (age 74.7 years old and 60% male), 29 patients (48%) had abnormal AV conduction at or below the AV node (18 with AV block of which 5 also had bundle branch block (BBB), 6 with SND and BBB, and 5 with AV node ablation). The remaining 31 patients (52%) had intact AV conduction. Procedure times were not significantly different between the groups (P=0.26). Selective HBP was achieved in 20.7% of abnormal AV conduction patients and 45.2% of intact AV conduction patients (P=0.06); the remaining patients had non-selective HBP. There were no differences detected in pacing characteristics at implant and paced QRS durations by AV conduction status.

Patient with intact AV conduction (N=31) Patients with abnormal AV conduction at or below AV node (N=29) Procedure time in minutes (mean ± SD, Median, IQR) 99±38; 87 [43, 180] 108±32; 108 [65, 182] Fluoroscopy time in minutes (mean ± SD, Median, IQR) 15±12; 11 [3, 50] 16±9; 13 [4, 36] Number of fixation attempts 3.0±2.2 2.2±2.0 sHBP PCT N=14 N=6 V at 0.5ms 1.8±0.9 1.7±1.2 V at 1.0ms 1.6±1.2 1.2±0.8 nsHBP PCT N=17 N=22 V at 0.5ms 2.2±1.9 1.7±1.3 V at 1.0ms 1.5±1.1 1.3±1.1 His signal recorded, number 30 (96.8%) 28 (96.6%) H-QRS interval, ms 46±7 48±13 His Injury of Current, N (%) 23 (74.2%) 18 (62.1%) Baseline Intrinsic QRS, ms 96±16 107±22 Paced QRS duration, ms (from HBP at 1.0ms) 119±23 121±19

Conclusions

Selective and non-selective HBP are achievable in bradycardic patients with abnormal and intact AV conduction, including those with BBB. There were no major differences in HBP implant parameters between patients with abnormal AV conduction and those with intact AV conduction.
P6143Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective cohort study of 146,665 participants
Authors: Lacey B W H , Armas N , Burrett J A , Peto R , Duenas A , Lewington S
Published: October 2019

Background

Cardiovascular disease (CVD) is a leading cause of premature death in Cuba, accounting for about one third of all deaths under age 70 years. Substantial uncertainty remains, however, about the relevance of major metabolic risk factors to CVD mortality in this population.

Purpose

To relate body-mass index (BMI), systolic blood pressure (SBP), and diabetes to risk of CVD death in Cuba.

Methods

In a prospective cohort study, 146,665 adults were recruited from the general population in five areas of Cuba between 1996 and 2002. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to Cuban national death registries to Jan 1 2017; 24,345 participants were resurveyed between 2006 and 2008. After excluding all with missing data or chronic disease at recruitment or, to further limit reverse causality, those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate mortality rate ratios (RRs) at ages 35–79 years to BMI, SBP and diabetes. Correlations of baseline and resurvey values were used to corrected RRs for regression dilution, and thereby estimate associations with long-term average (“usual”) levels of SBP and BMI.

Results

After exclusions, there were 117,008 participants age 35–79 (mean age 52 [SD 12]; 55% women). At recruitment, mean SBP was 124 mm Hg (SD 15), mean BMI was 24.2 kg/m2 (SD 3.6) and 5% had diabetes; mean SBP and diabetes prevalence were both strongly related to BMI. Correlations of resurvey and baseline measurements were 0.48 for SBP and 0.60 for BMI. At ages 35–79 years, there were 3780 CVD deaths (1871 ischaemic heart disease [IHD], 766 stroke, and 1143 other). CVD mortality was positively associated with BMI (down to about 22–23 kg/m2; figure), SBP and diabetes: 10 kg/m2 higher usual BMI approximately doubled CVD mortality (RR 1.90, 95% CI 1.61–2.24), as did 20 mmHg higher usual SBP (2.03, 1.88–2.20), and a prior diagnosis of diabetes (2.18, 1.97–2.42). The associations were similar in men and women. Given these associations, about one quarter (27%) of CVD deaths in this study were attributable to these metabolic risk factors combined.

Conclusion

These associations differ to those reported from other parts of Latin America, and are more consistent with studies in Europe and North America, highlighting the need for many more large-scale prospective studies in low and middle income countries. This study provides direct evidence for the expected benefit on CVD mortality of addressing major metabolic risk factors in Cuba. As the levels of these metabolic risk factors are increasing in Cuba, so too is their importance as determinants of premature CVD death.

Acknowledgement/Funding

Medical Research Council, British Heart Foundation, Cancer Research UK
P6149Coronary computed tomographic angiography (CTA) for risk stratification in the diagnostic triage of patients undergoing liver transplantation (LT): A long-term outcome study
Authors: Strobl S , Senoner T , Finkenstedt A , Widmann G , Plank F , Zoller H , Steinkohl F , Friedrich G , Feuchtner G M
Published: October 2019

Background

Cardiovascular (CV) risk stratification in patients with end-stage liver disease (ESLD) prior to liver transplantation (LT) is crucial: CV-disease poses a major threat for posttransplant survival.

Therefore, our purpose was to assess safety of coronary computed tomographic angiography (CTA) in patients prior to orthotopic LT over a long-term follow up period, and its value for CV risk stratification.

Methods

In this single center, retrospective observational study 458 patients underwent coronary calcium score (CCS) and coronary CTA for pre-LT risk stratification between 2005 and 2016. CTA was evaluated for 1) stenosis severity (CADRADS: 4-severe>70%/3-intermediate50–70%/2-mild<50%/1-minimal<25%/0=no CAD) 2) plaque burden (SIS, G-score), 3) high–risk plaque features (Napkin Ring Sign, low attenuation plaque, positive remodelling) and 4) Coronary Calcium Score. Primary endpoint was mortality (all-cause and cardiovascular), secondary endpoint major cardiovascular events (MACE).

Results

Finally 270 patients (79.3% males, age 61±8.5 years) who underwent orthotopic LT were included (mean follow-up 7.5 years±3.1, range 2–13). 87 (32.2%) had CCS zero and 60 (22.2%) CCS >300 Agatston Units (CCS 335.6 AU± 868.9). 248 patients underwent CTA after CCS. The majority had CAD (n=173, 72.3%) by CTA while only 75 (27.7%) had no CAD. 102 patients (38.8%) had minimal-or-mild stenosis<50% (CADRADS 1–2), 34 (12.9%) intermediate and 17 (6.5%) severe stenosis.Out of CCS 0 patients, 13 had non-calcified plaque.

All-cause mortality rate was 46 (17.0%), with the majority of patients (43 (93.5%) experiencing non-cardiac death and 3 (6.5%) cardiovascular death due to 1 myocardial infarction and 2 cardiopulmonary failure. CADRADS predicted mortality (Kaplan Meir, p<0.001). On multivariate Cox Regression modell, SIS and G-score predicted all-cause mortality (HR 1.1:p=0.034; 95% CI: 0.649–0.983 and HR 1.1, p=0.029; 95% CI: 1.0–1.6), while Calcium Score did not. There were 6 MACE (3 STEMI, 3 NSTEMI). MACE rate was 0% in CADRADS 0 or 1, 1 in CADRADS-2 and increasing to 5 in CADRADS 3 and 4 groups.

Coronary CTA for LT risk stratification

Conclusion

Cardiac CT is a reliable non-invasive modality for pre-LT assessment of CV-risk over a long-term period, with 0% MACE in patients with no CAD or minimal CAD. CTA allows for an improved CV-risk stratification by stenosis severity (CADRADS) and plaque burden as compared to calcium scoring.
P6156Coronary atherosclerosis characteristics in long-term antiretroviral therapy and HIV infection: insights from coronary CTA
Authors: Senoner T , Barbieri F , Adukauskaite A , Sarcletti M , Plank F , Beyer C , Dichtl W , Feuchtner G M
Published: October 2019

Purpose

To assess coronary artery disease (CAD) characteristics by coronary CT-angiography (CTA) in individuals with HIV-infection on long-term ART in a retrospective matched case-controlled cohort study.

Methods

69 HIV positive patients who underwent 128-slice dual source coronary CTA (mean age 54.9 years, 26.1% females) with mean 17.8±9.4 years of HIV-infection and a mean duration on ART of 13±7.3 years were propensity score matched with 69 HIV negative controls.

CTA was evaluated for: Stenosis severity (CAD-RADS), total plaque burden, mixed-non-calcified plaque burden (G-score), high-risk-plaque (HRP) features (Napkin-Ring-Sign, low-attenuation-plaque, spotty calcification, positive remodeling), perivascular fat attenuation index (FAI) and ectatic coronary segments.

Results

CAD-RADS was higher in HIV-positive participants as compared to controls (2.21±1.4 vs 1.69±1.5, p=0.031). A higher prevalence of CAD and G-score (p=0.043 and p=0.003) were found.

HRP prevalence (23 (34.3%) vs 8 (12.1%); p=0.002) and the number of HRP (36 vs 10, p<0.001) were higher in HIV-positive individuals. A positive perivascular FAI >-70 HU was present in 27.8% of HRP. Ectatic coronary arteries were found in 10 (14.5%) individuals with HIV-infection vs 0% in controls (p=0.003).

Conclusion(s)

HIV positive individuals on long-term ART display higher CAD burden and more HRP indicating vulnerable, potentially inflamed plaques.

CT- Angiography results HIV+ (N=67) HIV− (N=67) P-value CAD prevalence (any plaque), n (%) 56 (83.6) 46 (68.7) 0.043 SSS, mean ±SD 1.16±1.6 0.95±2.1 0.038 CAD RADS   0 11 22   1 11 7   2 10 21 <0.001   3 23 4   4 12 13   Total >50%, n (%) 35 (52.2) 17 (25.4) 0.001 CAD RADS, mean ±SD 2.21±1.4 1.69±1.5 0.031 SIS, mean ±SD 3.93±3.0 3.06±3.1 0.067 G-score, mean ±SD 10.04±8.5 5.76±5.9 0.003 Calcium score, mean ±SD 149.4±287.1 133.2±329.3 0.015 HRP, n (%) 23 (34.3) 8 (12.1) 0.002 HRP, n 36 10 <0.001 Non-calcifying plaque component, n (%) 44 (65.7) 34 (51.5) 0.097 Ectatic coronary segments, n (%) 10 (14.5) 0 (0) 0.003 CAD RADS: coronary artery disease reporting and data system; CCS: coronary calcium score; HRP: high-risk plaque; SIS: segment involvement score; SSS: stenosis severity score.

60 yo HIV-infected (31 yrs) male patient

These features strongly support the predominant inflammatory theory of cardiovascular events in HIV-infected individuals.

Acknowledgement/Funding

None
P6163Promotion of coronary plaque progression associated with different anticoagulation agents - a longitudinal CTA analysis
Authors: Beyer C , Wildauer M , Feuchtner G , Friedrich G , Hintringer F , Stuehlinger M , Plank F
Published: October 2019

Objective

Possible antithrombotic effect of anticoagulants in coronary artery disease have been proposed but mechanism are poorly understood. Experimental and clinical data indicate a key role of coagulation factors in the progression of atherosclerosis. We sought to evaluate the effect of different oral anticoagulation agents on the progression of atherosclerosis.

Methods

This retrospective matched case controlled study included patients with atrial fibrillation (AF) who underwent repeated CT angiography for ablation planning. Patients with known structural cardiac pathologies or significant comorbidities were excluded.

Patients were stratified according to their anticoagulation into 3 groups: vitamin K antagonist (VKA), direct oral anticoagulation (DOAC) and control (CR; aspirin or no therapy) with equal distribution of age and cardiovascular risk factors. Baseline and follow-up CT exams for repeated AF ablations were evaluated for the CAD profile and (semi)automated quantitative plaque analysis.

Results

One-hundred sixty-one patients were included (mean CT time interval: 31 months). The three cohorts did not differ in patient characteristics or CT findings at baseline. Absolute plaque volume progression was significantly higher in patients using VKA (66.5±136.7 mm3) compared to both CR (27.2±73.6 mm3) and DOAC (−7.1±42.1 mm3, p<0.001), translating into an annual change of 23.2±47.0 mm3 for VKA, 12.3±4.3 mm3 for CR and −4.6±22.9 mm3 for DOAC (p=0.003). The number of affected segments (SIS) increased by 1.2±1.3 compared to 0.6±1.3 in the control group and 0.2±0.7 in the DOAC group (p<0.0001).

Baseline CTA findings Control (n=61) DOAC (n=50) VKA (n=50) p Vessel Volume (mm3) 26.9±42.9 23.1±43.3 27.9±40.7 0.85 Lumen Volume (mm3) 15.7±24.8 13.3±25.1 16.6±27.0 0.82 Coronary Calcium Score (AU) 63.4±187.2 42.0±114.6 53.8±118.6 0.75 Segment Involvement Score 1.8±2.1 1.8±2.3 1.9±2.2 0.96 Stenosis Average Area (%) 19.0±21.7 0.5±0.7 0.5±0.7 0.71 Maximal Plaque Thickness (mm3) 0.5±0.7 0.5±0.7 0.5±0.7 0.69 Total Plaque Volume (mm3) 33.6±60.0 30.0±55.6 34.2±48.0 0.92 AU, Agatston units; DOAC, direct oral anticoagulation; SIS, segment involvement score; VKA, vitamin K antagonist.

Changes between baseline and follow-up

Conclusion

In serial coronary CTs, patients using vitamin K antagonists showed the highest plaque volume progression while patients using a direct oral anticoagulant showed a regression of total plaque volume. Therefore, direct anticoagulation may have a beneficial effect on atherosclerosis.
P6164High level of EPA is associated with lower perivascular coronary attenuation as measured by coronary CTA
Authors: Bittner D O , Goeller M , Zopf Y , Achenbach S , Marwan M
Published: October 2019

Introduction

Pericoronary adipose tissue (PCAT) composition has been recently shown to be a potential novel marker of coronary inflammation with higher PCAT attenuation shown to indicate increased cardiac mortality. Polyunsaturated fatty acids (PUFAs), especially Omega-3 fatty acids (n3), are thought to alter inflammatory response and intake of high dose Eicosapentaenoic acid (EPA, C20_5 n3) was shown to decrease mortality, however exact pathophysiological mechanisms are unclear. Therefore, we sought to determine whether blood levels of PUFAs are associated with differences in pericoronary fat attenuation.

Methods

In 64 symptomatic patients with intermediate pretest-likelihood for coronary artery disease presenting with atypical angina, coronary CTA was performed. PCAT attenuation was measured in Hounsfield Units (HU) around the proximal 40mm of the right coronary artery (RCA) using semi-automated software. Erythrocyte membrane fatty acid composition (in percentage) was analyzed with a standardized analytical methodology, displaying a variety of fatty acids including n-3 fatty acids using gas chromatography.

Results

Patients were divided into two groups (each n=32) using the median PCAT attenuation of −78.1 Hounsfield units (HU), resulting in one group with low (−95.58 to −78.17 HU) and one with high (−78.06 to −62.92 HU) PCAT attenuation. Among both groups, no differences were seen in age, sex, BMI, traditional cardiovascular risk factors or the number of cardiovascular risk factors (all p>0.05). In univariate analysis, significantly higher values of EPA (1.00% [0.78; 1.26] vs. 0.78% [0.63; 0.99]; p=0.02) were seen in patients with lower PCAT attenuation. All other fatty acids showed no significant differences (all p>0.05). Moreover, a significant negative correlation was seen between PCAT attenuation and EPA (Pearson correlation coefficient −0.38; p=0.002), but not for age, sex, BMI or number of cardiovascular risk factors (all p>0.1). Multivariable linear regression analysis confirmed this association and showed a significant inverse association of EPA to PCAT attenuation (β=−0.31, p=0.017), independent of age, gender, BMI and number of CV risk factors (all p>0.1).

Conclusion

High levels of EPA are associated with lower PCAT attenuation on coronary CTA indicating different composition of pericoronary adipose tissue potentially caused by a lesser degree of coronary inflammation.
P6168Low PCSK9 plasma level is an independent predictor of coronary atherosclerotic burden in patients with stable coronary artery disease
Authors: Caselli C , Ragusa R , Del Turco S , De Graaf M , Basta G , Scholte A , De Caterina R , Neglia D
Published: October 2019

Background

Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL cholesterol levels and has emerged as a new therapeutic target in coronary artery disease (CAD). Plasma PCSK9 levels have also been related to other components of the lipid profile associated with atherosclerotic risk.

Purpose

Aim of the present study was to evaluate the relationship of plasma PCSK9 levels with lipid profile and measures of coronary atherosclerotic burden and risk in patients with stable CAD enrolled in the European EValuation of INtegrated Cardiac Imaging (EVINCI) study.

Methods

PCSK9 was measured in 412 patients (60.3±8.6 years, 256 males) with symptoms of stable CAD fully characterized by clinical risk factors, bio-humoral profiles, and treatment. All patients underwent coronary computed tomography (CT) angiography to assess the presence and characteristics of coronary atherosclerosis. We calculated an individual CT risk score, expressing the coronary atherosclerotic burden, combining extent, severity, composition, and location of plaques.

Results

Patients were divided in groups according to PCSK9 quartiles: I (<136 ng/mL), II-III (136–266 ng/mL), and IV quartile (>266 ng/mL). LDL and HDL-cholesterol levels were significantly lower while total/HDL-cholesterol ratio was significantly higher in patients in the quartile I than in those in quartile IV (Figure A). CT angiography documented normal vessels in 30 and obstructive CAD in 35% of cases. Compared with patients with the highest levels (quartile IV), patients with the lowest PCSK9 levels (quartile I) had a higher CT risk score, a higher number of mixed plaque and higher hs-cTnI plasma levels (Figure B). PCSK9 itself was not associated with obstructive CAD. At multivariable analysis including clinical variables, medications and lipid variables PCSK9 was an independent predictor of the CT risk score (Coefficient - 0.129 (SE 0.03), p<0.0001), together with age, male gender and statin treatment.

Figure 1

Conclusion

PCSK9 levels are independently and inversely associated with the coronary atherosclerotic burden in patients with stable CAD.

Acknowledgement/Funding

AMGEN grant, EU FP7-CP-FP506 2007 project (grant agreement no. 222915)
P6171Role of myocardial mass for identifying FFR-verified ischemia and determining therapeutic strategy
Authors: Kawai H , Motoyama S , Miyajima K , Hoshino M , Ohta M , Takahashi H , Ishii J , Muramatsu T , Sarai M , Ozaki Y
Published: October 2019

Background

Conventional noninvasive approach using coronary CT angiography (CTA) focusing on only coronary artery lesions remains mismatch in identifying functional ischemia and determining indication for coronary revascularization.

Purpose

We aimed to assess the usefulness of CT-verified myocardial mass for identifying FFR-verified myocardial ischemia and determining the indication of coronary revascularization after FFR examination.

Methods

We examined 244 vessels with intermediate stenoses (50 to 90% stenosis visually on CTA) in 216 patients (mean age 69.2±9.2, 166 men) who underwent both coronary CTA and invasive FFR. In addition to coronary stenosis severity and plaque characteristics on visual, minimal lumen diameter (MLD), minimal lumen area (MLA), plaque volume, the entire myocardial volume of the target vessel (MTV) and that exposed to ischemia (FFR ≤0.80) (myocardial volume of ischemia: MVI) were evaluated. Additionally, therapeutic strategy after FFR was recorded.

Results

Of 244 vessels, myocardial ischemia (FFR ≤0.80) was shown in 99 (40.6%). MTV was larger in the patients with FFR-verified ischemia than those without (53.3±19.2 vs. 41.5±21.6, P<0.001); MLA, plaque burden (PB) and percentage of aggregated plaque volume (%APV) were also associated with ischemia. The area under the curves (AUCs) of MLA, PB, %APV, and MTV were 0.69, 0.67, 0.64, and 0.71, respectively. Addition of MTV to a model with coronary stenosis on visual, MLA, PB, and %APV improved C-index (from 0.72 to 0.79, P<0.01), net reclassification improvement (NRI) (0.71, P<0.01), and integrated discrimination improvement (IDI) (0.10, P<0.01). Of 99 vessels with FFR ≤0.80, MVI was larger in the vessels with early revascularization after FFR than those without (38.8 vs. 29.1, P=0.01).

Conclusions

The measurement of myocardial mass improves the diagnostic performance of coronary CTA for the identification of coronary arteries with FFR-verified ischemia. Furthermore, it is associated with therapeutic strategy for the diseased vessels after FFR examination.
P6174On-site CT-derived FFR predicts the need for revascularization
Authors: Bos Real L , Vilades D , Jimenez M , Altisent O , Rodriguez O , Alomar X , Ferrero A , Schuijf J , Carreras F , Leta R
Published: October 2019

Background and purpose

Coronary computed tomography angiography (CTA) in combination with CT-derived fractional flow reserve (CT-FFR) is a solid tool for assessing both the anatomical and functional impact of coronary atherosclerotic disease (CAD) in a single study. The development of new software for on-site CT-FFR quantification may reduce costs and increase availability. The aim of this study was to analyze the incremental value of CT-FFR over CTA alone and its ability to predict the need for revascularization.

Methods

Patients referred for invasive coronary angiography (ICA) who accepted to undergo a CTA/CT-FFR study were prospectively included. Patients with any contraindication for CT, atrial fibrillation, chronic total occlusions, severe ventricular hypertrophy or previous coronary revascularization were excluded. On-site CT-FFR was calculated for each coronary vessel. Invasive FFR was quantified during ICA, considering ≤0.8 as a surrogate for the need for revascularization.

Results

33 patients (90 vessels) were included. Mean age was 65±10 years, 88% were males, 60% had hypertension, 77% dyslipidaemia and 40% diabetes. The average analysis time of CT-FFR was 16±4 minutes. There was a good correlation between CT-FFR and FFR in all three main epicardial vessels as well as in proximal segments or in moderate to severe stenosis (see Table). 83% of vessels with FFR≤0.8 were predicted by CT-FFR study (89% of LAD lesions, 86% of LCX and 66% of RCA). CT-FFR added incremental diagnostic value over CTA alone to predict FFR≤0.8 (ΔAUC 0.0336 with a net reclassification index 1.4±0.23; p<0.001) (see Image).

n Mean difference from Bland-Altman Pearson's r coefficient p value All-vessels 90 0.037±0.1 0.8 <0.001 Lesions in LAD 40 0.005±0.11 0.81 <0.001 Lesions in LCX 32 0.061±0.094 0.85 <0.001 Lesions in RCA 18 0.06±0.11 0.83 <0.001 Moderate lesions (50–69% QCA stenosis) 24 0.02±0.06 0.88 <0.001 Severe lesions (70–99% QCA stenosis) 25 0.034±0.18 0.4 <0.001 Proximal lesions 42 0.012±0.11 0.84 <0.001 Non-proximal lesions 48 0.061±0.1 0.78 <0.001

Conclusions

On-site CT-FFR is a good predictor of the need for revascularization in all three main coronary vessels and adds incremental diagnostic value over CTA alone. There is higher dispersion of the values in severe stenosis, lesions in LCX or RCA although this do not result in misclassification.
P6185Impact of coronary atherosclerotic plaque metrics on the correlation between on-site CT-FFR and invasive FFR
Authors: Bos Real L , Vilades D , Jimenez M , Altisent O , Rodriguez O , Alomar X , Ferrero A , Schuijf J , Carreras F , Leta R
Published: October 2019

Background

Developed in the last years, coronary computed tomography-derived fractional flow reserve (CT-FFR) has shown good correlation with invasive fractional flow reserve (FFR). However, little is known about the interaction of coronary atherosclerotic plaque characteristics in the correlation between CT-FFR and FFR.

Purpose

This study sought to determine the effect of main coronary atherosclerotic plaque metrics (APM) on the correlation between on-site CT-FFR and invasive FFR.

Methods

Patients referred for invasive coronary angiography (ICA) who accepted to undergo a CT-FFR study were prospectively included. We excluded patients with atrial fibrillation, chronic total occlusions, severe ventricular hypertrophy or previous coronary revascularization, and those with any contraindication for CT. On-site CT-FFR and APM were calculated for each coronary vessel. Continuous variables of APM were dichotomized as above and below the median and their interaction on the correlation between on-site CT-FFR and invasive FFR was assessed by multiple linear regression model.

Results

33 patients (90 vessels) were included. Mean age was 65±10 years, 88% were males, 60% had hypertension, 77% dyslipidaemia and 40% diabetes. The mean delay time between CTA and ICA of 21 days. The average analysis time of CT-FFR was 16±4 minutes. Overall, correlation between FFR and CT-FFR showed a Pearson's r coefficient of 0.77±0.06 and a standardized beta coefficient of 0.8 (p<0.001). The beta coefficients between CT-FFR and FFR did not change significantly after the interaction with different APM (p>0.05 for all) (see Table).

Standardized Beta coefficients for on-site CT-FFR with invasive FFR as a gold standard Below the median Above the median p value for interaction Total atheroma volume (TAV) (mm3) 0.66 0.93 0.071 Percent atheroma volume (PAV) (%) 1.00 0.69 0.063 Calcified atheroma plaque volume (%) 0.89 0.68 0.175 Remodeling index 0.94 0.71 0.129 Lesion length (LL) (mm) 0.67 0.89 0.158 Minimal lumen area (mm2) 0.73 0.71 0.955

Conclusions

There is a good correlation between on-site CT-FFR and invasive FFR, which is not affected by main atherosclerotic plaque characteristics.
P6194Therapeutic effect of nanoliposomal anti-PCSK9 vaccine on hypercholesterolemia and atherosclerosis in C57BL/6 mice
Authors: Momtazi-Borojeni A A , Jaafari M R , Banach M , Sahebkar A
Published: October 2019

Background

Proprotein convertase subtilisin/kexin 9 (PCSK9) promotes hypercholesterolemia through reducing protein level of liver low-density lipoprotein (LDL) receptor (LDLR). Currently, PCSK9 inhibition is known as an efficient lipid-lowering approach.

Purpose

Here, we constructed a liposomal anti-PCSK9 vaccine, and evaluated its therapeutic effects on dyslipidemia and atherosclerosis in atherosclerotic mice.

Methods

Liposomal anti-PCSK9 vaccine was prepared viaattaching immunogenic peptide, termed Immunogenic Fused PCSK9-Tetanus (IFPT), on the surface of nanoliposome carriers by using DSPE-PEG-Maleimide lipid (L-IFPT). The L-IFPT formulation was adsorbed to Alum adjuvant (L-IFPTA+) and administrated subcutaneously four times with a bi-weekly interval in hypercholesterolemic C57BL/6 mice. Plasma levels of anti-PCSK9 antibody, plasma concentration of PCSK9 protein, effect of anti-PCSK9 antibody on PCSK9-LDLR interaction, protein levels of liver LDLR, lipid profile, as well as atherosclerotic lesion size and severity were measured in the vaccinated hypercholesterolemic mice. To determine immune safety, Inflammatory response was measured by evaluating IFN-γ and IL-10 producing splenic cells using ELISpot assay.

Results

L-IFPTA+vaccine promoted the high IgG antibody response against PCSK9 peptide in the hypercholesterolemic mice. L-IFPTA+-induced antibodies targeted plasma PCSK9 and thereby decreased plasma consecration of PCSK9, which was associated with the reduced PCSK9-LDLR interaction and the increased liver levels of LDLR protein. Inhibitory effect of L-IFPTA+vaccine was accompanied with a significant reduction of plasma levels of total cholesterol (TC), LDL-C, and VLDL-C. Interestingly, L-IFPTA+vaccine could considerably reduce atherosclerotic lesion size and intima to media thicknessin hypercholesterolemic mice. Long-term evaluation of hypercholesterolemic vaccinated mice showed that L-IFPTA+vaccine was able to promote a long-lasting anti-PCSK9 antibody titration, which was paralleled by a significant reduction of LDL-C over 16 weeks post prime immunization (Figure). Splenocytes isolated from vaccinated mice indicated the reduced IFN-γ producing cells and the elevated IL-10 producing cells, suggesting immune safety of liposomal anti-PCSK9 vaccine.

Figure 1

Conclusions

L-IFPTA+vaccine induced efficient anti-PCSK9 antibodies which could exert long-term therapeutic effect on hypercholesterolemia and atherosclerosis in mice, revealing a feasible vaccine-based approach for managing hypercholesterolemia and cardiovascular disease.
P6195Nanoliposomal anti-PCSK9 vaccine induces long-term and safe protection against atherosclerosis in C57BL/6 mouse
Authors: Momtazi-Borojeni A A , Jaafari M R , Badiee A A , Banach M , Sahebkar A A
Published: October 2019

Background

Proprotein convertase subtilisin/kexin 9 (PCSK9) can increase plasma levels of low-density lipoprotein (LDL) cholesterol (LDL-C) through reducing protein levels of liver LDL receptor (LDLR). PCSK9 inhibition has been found to efficiently alleviate hypercholesterolemia.

Purpose

In the present study, we prepared nanoliposomal anti-PCSK9 vaccine and evaluated its protective effects against hypercholesterolemia and atherosclerotic plaque formation in C57BL/6 mice fed on atherogenic diet.

Methods

Nanoliposome formulation containing 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC), 1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) and cholesterol (Chol) were prepared using the lipid-film hydration method, and used as the vaccine delivery system. Immunogenic peptide called Immunogenic Fused PCSK9-Tetanus (IFPT) was exhibited on the surface of nanoliposome carriers by using DSPE-PEG-Maleimide lipid (L-IFPT) and adsorbed to Alum adjuvant (L-IFPTA+). The prepared vaccine formulations IFPT, L-IFPTA+, IFPTA+, IFPT, and empty liposome as the negative control were subcutaneously administrated four times with a bi-weekly interval in C57BL/6 mice fed on atherogenic diet. Protein levels of liver LDLR, lipid profile, plasma levels of anti-PCSK9 antibody, plasma concentration of PCSK9 protein, and effect of anti-PCSK9 antibody on PCSK9-LDLR interaction were measured in the vaccinated mice. Aortic arch atherosclerotic lesions were studied using hematoxylin and eosin staining. To determine inflammatory response, splenic CD4+producing IL-4 and IFN-γ were evaluated using flow cytometry analysis.

Results

Among formulated vaccines, the L-IFPTA+vaccine could generate the highest IgG anti-PCSK9 antibody in the vaccinated hypercholesterolemic mice. The generated anti-PCSK9 antibodies inhibited interaction of PCSK9 with LDLR through targeting plasma PCSK9, whereby protein levels of liver LDLR was elevated in the vaccinated mice. As reveled by lipid profile analysis, liposomal vaccines, with more extent the L-IFPTA+vaccine, could significantly decrease plasma TC and LDL-C in hypercholesterolemic mice. Of note, L-IFPTA+ vaccine could reduce size and severity of atherosclerotic lesion in the aorta arch. Importantly, long-term (48 weeks) follow-up of hypercholesterolemic vaccinated mice revealed that L-IFPTA+vaccine could induce a long-lasting humoral immune response against plasma PCSK9, which was accompanied with a significant decrease of TC and LDL-C (Figure). Additionally, Anti-inflammatory Th2 cells and IL-4 cytokine were significantly elevated in splenic cells isolated from hypercholesterolemic vaccinated mice.

Figure 1

Conclusions

L-IFPTA+vaccine can promote long-lasting, functional and safe anti-PCSK9 antibodies in hypercholesterolemic C57BL/6 mice, revealing long-term protective effect against hypercholesterolemia and atherosclerosis.
P6204Oral vaccination of Lactococcus lactis expressing Ling Zhi 8 protein prevents nonalcoholic fatty liver and early atherogenesis in cholesterol-fed rabbits
Authors: Lin W W , Lee M F , Lin S J , Wu T J
Published: October 2019

Background

Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis. Epidemiology studies have indicated that NAFLD may be an independent risk factor for atherosclerosis. Anti-inflammation therapy by inhibiting IL-1β led to a significantly lower cardiovascular event rate in recent clinical trial (CANTOS trial). Ling Zhi 8 (LZ8) is an immunomodulatory protein that possesses a broad range of pharmacological properties, including anti-inflammatory activities.

Methods and findings

In this study, we developed an oral vaccination of Lactococcus lactis expressing LZ8 protein in a nisin-controlled gene expression system and investigated its anti-inflammation properties. Experimental rabbits received commercial rabbit chow supplemented with 2% cholesterol for 5 weeks and recombinant LZ8 L. lactis vaccine once a day on weekdays. The expression of IL-1β in the aorta (Figure A) was significantly suppressed after LZ8 vaccination. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the sub-endothelial space (Figure C). LZ8 also inhibited the expression of IL-1β in the liver (Figure B), decreased fat droplet deposits and infiltration of inflammatory cells (Figure D), and improved liver function by decreasing liver enzymes.

Figure 1

Conclusions

Our results suggest that LZ8 could be used as a therapeutic tool to improve both atherosclerosis and NAFLD due to its anti-inflammatory effect.

Acknowledgement/Funding

TCVGH-1067317C, TCVGH-1063108C