bluuebunny/crossref_metadata_2025 huggingface dataset:
P1467Long-term prognostic value of simultaneous assessment of atherosclerosis and ischemia in patients with suspected angina: implications for routine use of carotid ultrasound during stress echocardiograp
Authors: Ahmadvazir S , Pradhan J , Khattar R S , Senior R
Published: October 2019

Background

The long-term clinical impact of carotid plaque burden (CPB) in patients with new onset suspected stable angina beyond stress echocardiography (SE) with no history of coronary artery disease (CAD) is not known.

Methods

Consecutive patients referred for SE, underwent simultaneous carotid ultrasonography to assess CPB. Patients were prospectively followed up for major adverse events (MAE).

Results

Of the 592 patients, 573 (age 59±11, 45% male) had follow-up data. During a mean of 7±1.2 years, 85 patients had first MAE (all-cause mortality and acute myocardial infarction: 67 (hard events) and 18 unplanned revascularisation). On multivariate Cox regression analysis, pre-test probability of CAD, peak wall thickness scoring index and CPB predicted MAE (p<0.0001 for all); however, only CPB retained significance for both hard events and hard cardiac events (p=0.008 and 0.001, respectively). MAE and hard events were least in patients with normal SE and absent carotid plaque (annualised event rate: 1.1% and 1.01%respectively) with significant increase in normal SE with plaque disease (2.4% and 2.05%, p=0.004 and 0.01 respectively). Presence of plaque did not impact on these outcomes in abnormal SE.

Conclusions

In patients with suspected stable angina, carotid atherosclerosis and myocardial ischemia in combination provided synergistic MAE information long term but atherosclerosis predicted hard events particularly in patients with normal SE but not in ischemic patients. This implies routine use of simultaneous carotid ultrasound following a normal SE for optimum prognostication
P1501Can we measure the stiffening of hypertensive hearts non-invasively? A shear wave imaging study using ultra-high frame rate echocardiography
Authors: Cvijic M , Santos P , Petrescu A M , Bezy S , Orlowska M , Chakraborty B , Duchenne J , Vanassche T , Dhooge J , Voigt J U
Published: October 2019

Background

Cardiac shear wave (SW) elastography is a novel technique based on high-frame-rate (HFR) echocardiography which has been shown to be related to myocardial stiffness. In this study we explore the relation between myocardial SW velocity and myocardial remodelling in remodelled hearts of patients with arterial hypertension (AH).

Methods

We prospectively included 33 treated AH patients with hypertrophic left ventricular (LV) remodelling (59±14 years, 55% male) and 26 aged matched healthy controls (55±15 years, 77% male). AH patients were further divided according to their LV geometric pattern into a concentric remodelling (CR) group (13 patients) and a concentric hypertrophy (CH) group (20 patients). LV parasternal long axis views were acquired with an experimental HFR ultrasound scanner (HD-PULSE) at 1266±317 frames per seconds. Myocardial acceleration maps were created from the HFR-datasets and an anatomical M-mode line was drawn along the midline of the interventricular septum (IVS). The propagation velocity of natural SWs occurring at mitral valve closure (MVC) was measured on these M-modes (Figure A) in order to assess passive myocardial stiffness. Standard echocardiography using a commercial scanner was performed to evaluate LV remodelling.

Results

SW velocities at MVC differed significantly between AH patients and controls (5.83±1.20 m/s vs. 4.04±0.96 m/s; p<0.001). Within the patient group, patients with CH had highest SW velocities at MVC (p<0.001), whereas values between controls and patients with CR were comparable (p=0.075) (Figure B). In AH patients, significant positive correlations were found between SW velocity at MVC and parameters of LV remodelling (IVS thickness: r=0.728, p<0.001; LV mass index: r=0.780, p<0.001, LV end-diastolic volume: r=0.604, p=0.008) (Figure C) and also parameters of diastolic function (E/e': r=0.495, p=0.005, left atrium diameter: r=0.866, p<0.001, left atrium volume index: r=0.661, p<0.001).

Figure A, B, C

Conclusions

SW velocity – and therefore myocardial stiffness – is higher in AH patients compared to healthy controls and increases with increasing severity of hypertensive heart disease. Patients with concentric remodelling have still close-to-normal passive myocardial properties while patients with concentric hypertrophy show significant stiffening. Echocardiographic shear wave elastography is a promising new technique for the non-invasive assessment of myocardial stiffness and might provide valuable new insights into myocardial function and the pathophysiology of myocardial disease.
P1503Decrement of vortex formation time during dobutamine stress echo
Authors: Dimitroglou Y , Aggeli C , Maragiannis D , Patsourakos D , Gountas I , Polytarchou K , Verveniotis A , Angelis A , Savvalas D , Zisimos K , Raftopoulos L , Tousoulis D
Published: October 2019

Background

Vortex Formation Time (VFT) is a novel index of systolic and diastolic function which may be also affected by left ventricular geometry, but has never been evaluated during dobutamine stress echocardiography (DSE) protocols. We sought to investigate the changes in VFT during DSE protocol.

Methods

DSE was performed in 50 consecutive patients. Patients with poor acoustic window, atrial fibrillation, cardiac valve disease or pacemaker were excluded. Apical four and apical two chamber views were acquired and the following parameters were calculated off- line without knowledge of DSE result both at rest and at peak: left ventricular end-diastolic and end-systolic volume, stroke volume, ejection fraction, stroke work, e and a wave peak velocity and VTI, TDI-derived mitral annular early diastolic velocity at the lateral wall and mitral valve diameter. VFT calculated according to the following equation: VFT = [4 *(1 − β) * α3 * EF]/π, where α = (LVEDV/α3)(1/3) and is affected by ventricular geometry and β = VTIa-wave/(VTIe wave + VTIa-wave) reflecting the atrial filling fraction.

Results

Median age of the study population was 61 [53–72], 38 men (76%) and 13 (26%) had an old myocardial infarction. Fifteen patients (30%) were positive for myocardial ischemia during DSE. At rest, median LVEDV was 121.5ml (101.8–148.0), median EF (%): 59.9 [54.4–64.1], median atrial filling fraction: 0.43 [0.40–0.48], median mitral valve diameter (cm): 2.8 [2.6–3.0] and median VFT: 2.44 [1.74–3.10]. At peak, median LVEDV was 102.0ml [86.4–122.3] median EF (%) 65.7 [58.8–69.8], median atrial filling fraction: 0.67 [0.59–0.73], median mitral valve diameter (cm): 2.7 [2.5–2.9] and median VFT: 1.45 [1.05–1.88]. VFT decreased in the whole population (Wilcoxon rank test, p<0.001) (figure 1A) and when patients were stratified according to test result. Median VFT decrease was significantly higher in patients with a positive DSE (50%) than in patients with negative DSE (39%) (Mann- Whitney U test, p=0.048) (figure 1B).

Figure 1

Conclusion

The VFT decreased significantly during DSE and most prominently in patients with ischemic response. This may indicate the deterioration of left ventricular diastolic or systolic function as well as change in left ventricular geometry during DSE protocol.
P1511Promising prognostic value of negative stress echocardiography in patients with incomplete revascularization after successful primary PCI
Authors: Boskovic N , Markovic F , Petrovic M T , Giga V , Jovanovic I , Dedic S , Banovic M , Aleksandric S , Tesic M , Dobric M , Nedeljkovic I , Beleslin B , Djordjevic-Dikic A
Published: October 2019

Background

The specific role of non-invasive functional testing in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) still needs to be evaluated. The aim of our study was to assess negative prognostic value of stress echocardiography (SECHO) after successful pPCI and incomplete revascularization of non-culprit lesions.

Methods

Our study consisted of 202 patients (mean age 59±10 years, male 142) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were interrogated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow-up of the patients was 70 months (IQR 55–83 months) for the occurrence of cardiovascular death and non-fatal myocardial infarction. We also assessed the independent predictors for the occurrence of the adverse events.

Results

Out of 202 patients, 42 (20.8%) had positive SECHO test, 4 patients (1.98%) had died due to non-cardiac causes and 7 patients (3.5%) were lost to follow-up. From the remaining 149 patients with negative SECHO, 13 (8.7%) had an adverse event (7 cardiovascular deaths and 6 non-fatal MI). Negative predictive value of SECHO test was 91.3%. Univariate predictors of adverse events were slow HRR (HR 4.343 [95% CI 1.473–14.011], p=0.008), and not achieved THR (HR 0.322 [95% CI 0.105–0.985], p=0.047). By multivariate analysis, only slow HRR remained independent predictor of adverse events (HR 3.324 [95% CI 1.013–10.906], p=0.048).

Conclusion

SECHO test has excellent negative prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI. Still, particular care should be taken to the patients with slow HRR and negative SECHO due to increased risk for the occurrence of adverse events.

Acknowledgement/Funding

Ministry of Education and Science of the Republic of Serbia (Grant No III41022)
P1513Exercise-induced cardiac troponin I release and incident cardiovascular morbidity and mortality
Authors: Aengevaeren V , Hopman M T E , Thompson P D , Bakker E A , George K P , Thijssen D H J , Eijsvogels T M H
Published: October 2019

Background

Blood concentrations of cardiac troponin I (cTnI) above the 99th percentile (upper reference limit, URL) are a key criterion for the diagnosis of acute myocardial injury and infarction. cTnI concentrations, even below the URL, also predict adverse outcomes in general and patient populations. cTnI increases after exercise, but the clinical significance of this exercise-induced cTnI increase is unknown. We examined the association between exercise-induced cTnI elevations and clinical outcomes in long-distance walkers.

Methods

cTnI was measured in 726 participants (median 61 [54–69] yrs) before and immediately after 30–55 km of walking. The primary endpoint was a composite of all-cause mortality and major adverse cardiovascular events (MACE, i.e. myocardial infarction, stroke, heart failure, revascularization or sudden cardiac arrest).

Results

Participants walked 498 [440–555] min at 68±10% of their maximum heart rate. Baseline cTnI concentrations were 2 [0–8] ng/L, with 9 participants (1%) demonstrating a baseline cTnI value above the URL (>40 ng/L). cTnI increased after walking (8 [1–18] ng/L, p<0.001) and 63 participants (9%) had a post-exercise cTnI value >URL. During 43 [23–77] months of follow-up, 62 participants (9%) experienced a primary endpoint; 29 died and 33 had MACE. 27% of participants with post-exercise cTnI >URL experienced a primary endpoint compared to only 7% with cTnI below the URL (log-rank p<0.001). The hazard ratio was 2.35 (95% CI: 1.21–4.53) after adjusting for age, sex, cardiovascular risk factors (hypertension, hypercholesterolemia or diabetes mellitus), cardiovascular diseases (myocardial infarction, stroke or heart failure) and baseline cTnI.

Kaplan-Meier of Mortality and MACE

Conclusion

Post-exercise cTnI concentrations >URL were associated with higher all-cause mortality and MACE, independent of age, sex, presence of cardiovascular risk factors or cardiovascular diseases and baseline cTnI concentrations in a large cohort of older long-distance walkers. Exercise-induced increases in cTnI may not be a benign physiological response to exercise in all, but an early marker of future mortality and cardiovascular events.

Acknowledgement/Funding

V.L.A was supported by a grant from the Radboud Institute for Health Sciences, T.M.H.E by a Horizon 2020 grant from the European Commission
P1527The applicability of the dual pathway approach criteria after coronary angiography
Authors: Olesen K K W , Wurtz M , Gyldenkerne C , Thrane P G , Thim T , Kristensen S D , Botker H E , Eikelboom J W , Maeng M
Published: October 2019

Background

The combination of aspirin and low-dose rivaroxaban (dual pathway approach, DPA) has been approved for high-risk patients with stable coronary artery disease (CAD) in the COMPASS trial. Patients with CAD combined with ≥1 DPA criteria, defined as peripheral artery disease, renal failure, heart failure, or diabetes, have been proposed as high-risk patients eligible for DPA.

Purpose

To determine the prevalence of patients meeting the DPA criteria and the association with major adverse cardiovascular events (MACE) in patients with stable CAD after coronary angiography (CAG). Further, to evaluate use of the DPA criteria in CAD patients meeting the inclusion criteria in the COMPASS trial.

Methods

We studied patients included in the Western Denmark Heart Registry after examination by CAD 2004–11. Patients without CAD or myocardial infarction (MI) <1 year before or 30 days after CAG were excluded. Patients were stratified according to 0 or ≥1 DPA criteria and being eligible/ineligible for the COMPASS trial. Event rates and incidence rate ratios (IRRs) of MACE (cardiac death, ischemic stroke, and MI) were estimated.

Results

Of 80,071 patients undergoing CAG, 18,689 (23%) patients had stable CAD. According to the DPA criteria, 7,730 patients (10%) were DPA eligible. Rates of MACE were 1.98 (95% CI 1.86–2.34) events per 100 person-years among DPA ineligible patients and 4.26 (95% CI 4.04–4.50) events per 100 person-years among DPA eligible patients (IRR 2.15, 95% CI 1.98–2.34). When stratifying patients according to eligibility in the COMPASS inclusion criteria, COMPASS eligible patients with 0 DPA criteria and COMPASS ineligible patients with ≥1 DPA criteria were at intermediate risk compared to patients meeting both (high risk) or none (low risk) of these criteria (Figure 1).

Figure 1

Conclusion

In a cohort of consecutive patients undergoing CAG, 1 in 10 patients would be eligible for DPA according to the DPA criteria. Patients with stable CAD and ≥1 DPA criteria had >2-fold higher rate of MACE than CAD patients without any DPA criteria.
P1531The association between plasma choline and acute myocardial infarction is modified by potential markers of endogenous PPAR activation
Authors: Svingen G F T , Lysne V , Ueland P M , Zeisel S , Pedersen E R , Dhar I , Bjornestad E O , Schartum-Hansen H , Tell G S , Nilsen D W , Karaji I , Nygaard O K
Published: October 2019

Background

Choline is related to lipid handling and higher plasma concentrations have been associated with an adverse cardiovascular risk profile. However, previous studies have suggested that the relationship between plasma free choline and later cardiovascular events may differ according to patient phenotypes.

Purpose

To explore the risk association between plasma choline and later acute myocardial infarction (AMI) according to plasma methylmalonic acid (MMA) or dimethylglycine (DMG). The latter two metabolites are suggested markers of endogenous activation of perixosome proliferator-activated receptors (PPARs), which are nuclear receptor proteins involved in lipid metabolism.

Methods

Risk relationships were explored by Cox regression among 2232 patients evaluated for suspected stable angina pectoris in the overall population and according to median plasma MMA and DMG.

Results

Baseline plasma choline was related to several cardiovascular risk factors (Table 1). After median follow-up of 7.3 years, 338 patients were reported with at least one incident AMI. In the overall population, the age and gender adjusted HR (95% CI) for each increment of 1 SD log-transformed plasma choline and AMI was 1.21 (1.08–1.35), P=0.001, and the association persisted in multivariate analyses.

In patients with plasma MMA or DMG≥median, the HRs (95% CIs) were 1.33 (1.16–1.54) and 1.38 (1.20–1.58), respectively, both P<0.0001; however no significant relationships were observed between plasma choline and later AMI among patients with either plasma MMA or DMG < median (P interaction <0.008) (Figure 1).

Table 1. Baseline characteristics according to plasma choline quartiles Quartile 1 Quartile 4 P for trend Age, years 58 (52–66) 66 (58–73) <0.0001 Smoking, n (%) 212 (37.9) 153 (27.9) <0.0001 Diabetes, n (%) 61 (10.9) 85 (15.5) 0.12 Previous acute myocardial infarction, n (%) 200 (35.7) 238 (43.4) <0.0001 Estimated glomerular filtration rate, mL/min/1.73m2 96 (87–104) 79 (63–92) <0.0001 Serum hs-troponin T, ng/L 4 (3–8) 9 (4–17) 0.0002 Serum triglycerides, mmol/L 1.35 (1.00–2.03) 1.60 (1.16–2.25) <0.0001 Serum apolipoprotein A1, mg/L 1.29 (1.12–1.51) 1.32 (1.17–1.53) 0.01 Statin therapy, n (%) 384 (68.6) 435 (79.4) 0.01

Figure 1

Conclusion

Among patients with stable angina, plasma choline was related to increased long-term AMI risk among patients with higher plasma MMA or DMG only. This finding potentially reflects increased risk conferred by choline during concomitant endogenous PPAR activation.

Acknowledgement/Funding

None
P1545Predictve factor for major adverse cardiovascular events in health check-up participants
Authors: Takase H , Machii M , Nonaka D , Ohno K , Sugiura T , Ohte N , Dohi Y
Published: October 2019

Background/Introduction

Health check-up has been carried out for individual health management. One of its main objectives is the early detection and prevention of major adverse cardiovascular event (MACE).

Purpose

We investigated predictive factors for MACE among clinical test items in health check-up program.

Methods

A total of 13522 subjects (male=8140, 52.8±12.3 year-old at baseline), who visited our hospital for a health check-up between 2008 and 2015, were enrolled. After the baseline examination, they were followed up until December 2016 (median 1827 days) with the endpoint being the incident of MACE. The outcome was confirmed using a questionnaire at health check-up, medical record, telephone, or letter. Possible association between MACE and clinical test items including gender, age, waist circumference, blood pressure, kidney function, fasting plasma glucose, lipid profile, hemoglobin, electrocardiogram (ECG), smoking habit and alcohol consumption was investigated.

Results

During the follow-up period, MACE occurred in 196 subjects (3.03 per 1000 person-year), with the incidence being more frequent in male than female subjects (4.07 vs. 1.42 per 1000 person-year). Multivariate Cox-hazard analysis demonstrated that male gender (hazard ratio [HR] = 2.457, 95% confidence intervals [CI] = 1.498–4.028), age (HR = 1.056, 95% CI = 1.040–1.071), waist circumference (HR = 1.023, 95% CI = 1.004–1.042), systolic blood pressure (HR = 1.015, 95% CI = 1.005–1.024), hemoglobin (HR = 0.868, 95% CI = 0.758–0.994) and Sokolow–Lyon voltage in the ECG (HR = 1.227, 95% CI = 1.033–1.458) were significant predictors for MACE. However, in a model where B-type natriuretic peptide (BNP) was also added as an independent variable, BNP (HR = 2.593, 95% CI = 1.602–4.196) was the strongest predictor for MACE.

Conclusions

In participants underwent health check-up, systolic blood pressure and hemoglobin as well as age and gender were the risk factors of MACE. Appropriate control of blood pressure and treatment of anemia may be useful for the prevention of MACE. Measurement of BNP may give us additional important information associated with future MACE.
P1553Differential association between vascular and chronological age with cardiovascular outcomes
Authors: Bruno R M , Nilsson P , Engstrom G , Wadstrom B , Empana J P , Boutouyrie P , Laurent S
Published: October 2019

Background/Introduction

Increased pulse wave velocity (PWV), is a reliable marker of early vascular aging (EVA). However, the identification of individuals whose arteries are abnormally healthy in comparison to their age and cardiovascular (CV) risk profile might be of interest, to discover novel pathways of cardioprotection and provide preventive strategies for successful vascular aging.

Purpose

1) to provide a novel calculation for vascular age and examine his determinants; 2) to test the hypothesis that individuals with the largest difference between chronological and vascular age (C-V age) show a lower rate of CV events than their counterparts, and may thus be defined as the supernormal vascular aging group (SUPERNOVA).

Methods

Vascular age was defined as predicted age based on classical CV risk factors and PWV. The best fitting model for vascular age was investigated in the multicenter, European, cross-sectional Reference Values for Arterial stiffness Collaboration Database (n=11406). Continuous variables were modelled as smoothing splines. Thereafter, the risk of fatal and non-fatal CV events associated with C-V age was examined in the longitudinal cohort of the Malmo Diet and Cancer Study (n=2663) using Cox proprotional hazard regression models. C-V age was examined as a continuous variable (natural splines) and as a 3 levels categorical variables based on the best grouping of the deciles of C-V age and corresponding to the EVA (<3.0 years), normal vascular aging (3.0 to 8.8 years) and SUPERNOVA (>8.8 years) respectively.

Results

In the Reference Values Cohort (age range 17–85 years, 52.4% men, 38.1% hypertensives, 3.9% diabetics, average PWV 7.8 m/s), the most significant predictor of vascular age (full model r2 0.598) was PWV. In the Malmo Diet and Cancer Study Cohort (age 61–89 years, 63.6% men, 64.0% hypertensives, 12.9% diabetics, PWV 11.5 m/s), during follow-up (6.6 years on average), 286 individuals developed a first cardiovascular event. In the Cox survival analysis, C-V age was significantly and inversely associated with CV events. Compare to normal vascular aging, participants with SUPERNOVA had lower risk for CV events [HR 0.51 (0.34–0.76)] whereas those with EVA had a higher risk [HR 2.71 (1.80–4.09)]. Instead, there was no significant association with all-cause mortality.

Conclusions

The use of PWV and CV risk factors may be useful to define early and supernormal vascular aging in particular, and to assess its clinical relevance towards the risk of cardiovascular disease and death.
P1560Prognostic predictors of mortality in very elderly patients presenting with NSTEMI
Authors: Cacho C , Cordero Fort A , Gonzalez Ferrero T , Perez Dominguez M , Torrelles Fortuny A , Antunez Muinos P J , Cid Menendez A , Agra Bermejo R M , Rigueiro Veloso P , Iglesias Alvarez D , Alvarez Alvarez B , Gonzalez Juanatey J R , Garcia Acuna J M
Published: October 2019

Background

Elderly patients are usually under-represented in randomized controlled trials, therefore there is less data providing prognostic information for this particular group. NSTEMI clinical practice guidelines indicate that older patients should receive the same therapeutic strategy than younger patients.

Methods

Observational retrospective study including 8771 patients admitted for acute coronary syndrome in two tertiary referral hospitals between 2003 and 2017: 5673 NSTEMI (64.3%) and 3098 STEMI (35.7%). 999 patients presenting with NSTEMI and aged over 75 years were selected and divided into 3 groups: aged 75–80, aged 80–89 and aged over 90. Cox proportional hazard regression analysis was performed in order to determine independent predictors of mortality. Mortality and survival were represented by Kaplan-Meier curves and log rank test was conducted to assess significant differences in survival between groups. Median follow-up period was 48 months.

Results

A significant association between female sex and elder age was observed, also a higher prevalence of hyperlipemia and diabetes. In acute phase, no significant differences were found in between congestive heart failure onset, myocardial re-infarction, acute renal failure, stroke or in-hospital mortality amongst the 3 groups. However, at follow-up period, higher mortality in elder groups was documented. After performing a multivariate analysis, age was identified as an independent predictor of mortality at follow-up (<90 years: HR 1.50 CI 95% 1.23–1.83, p=0.0001, >90 years: HR 1.93 CI 95% 1.27–2.93, p=0.002) as well as GRACE score (HR 1.06, CI 95% 1.02–1.09, p=0.002), CRUSADE score (HR 1.01 CI 95% 1.01–1.02, p=0.0001) and treatment with digoxine (HR 1.38 CI 95% 0.95–2.0, p=0.08). On the other side, beta-blockers (HR 0.71 CI 95% 0.59–0.86, p=0.0001) and complete coronary revascularization (HR 0.48 CI 95% 0.37–0.64, p=0.0001) were found to be protective factors.

Conclusions

In very elderly patients presenting with NSTEMI, prognostic predictors of mild-term mortality are similar to those present in younger patients. Recommendations of clinical practice guidelines, such as beta-blockers' treatment and coronary revascularization, should also be applied in elderly patients.
P1561An elevated risk of heart failure and stroke events in octogenarian Japanese patients with acute myocardial infarction who received percutaneous coronary intervention
Authors: Tsuda K , Kataoka Y , Nishikawa R , Doi T , Nakashima T , Hosoda H , Honda S , Fujino M , Yoneda S , Otsuka F , Nakao K , Tahara Y , Asaumi Y , Noguchi T , Yasuda S
Published: October 2019

Background

The proportion of the octogenarian population is expanding especially in Eastern society. Due to the clustering of risk factors, acute myocardial infarction (AMI) represents a major cardiovascular complication in octogenarian subjects. This suggests the need to further optimize their therapeutic management to prevent future cardiac events after AMI. However, analysis of clinical characteristics and cardiovascular outcomes in octogenarian subjects with AMI who received the current established medical therapies is limited.

Purpose

To investigate clinical features and prognosis in octogenarian AMI subjects treated with percutaneous coronary intervention (PCI).

Methods

We analyzed 1547 AMI subjects underwent PCI between 2007 and 2017. Baseline characteristics and the occurrence of composite major adverse cardiovascular events (cardiac death, non-fatal MI, revascularization, heart failure and stroke) were compared in octogenarian and non-octogenarian subjects.

Results

22.0% (340/1547) of study subjects was octogenarian. They were more likely to have chronic kidney disease (CKD) and a lower level of LDL-C on admission (Table). Moreover, a higher prevalence of severer Killip class and LVEF <30% were observed in octogenarians (Table). However, they were not optimally treated with the established medical therapies at discharge (Table). During the observational period (median=3.1 years), the composite of cardiovascular events more frequently occurred in octogenarian subjects. Of note, they exhibited a 2.15-fold and 3.01-fold increased risk for heart failure and stroke events, respectively (Figure).

Table 1 Non-Octogenarian (n=1207) Octogenarian (n=340) P-value CKD* (%) 33.8 63.2 <0.0001 LVEF <30% (%) 5.7 10.3 0.02 Killip class 1.33±0.03 1.55±0.05 <0.0001 LDL-C (mmol/L) 3.20±0.03 2.80±0.05 <0.0001 Statin (%) 86.3 78.2 0.0006 Beta-blocker (%) 74.0 65.8 0.005 ACE-I/ARB (%) 87.3 76.6 <0.0001 DAPT (%) 86.0 88.6 0.42 *CKD is defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.

Figure 1

Conclusions

Octogenarian subjects with AMI were high-risk group associated with heart failure and stroke events. Their distinct clinical backgrounds may affect the adoption of optimal medical therapies, potentially resulting in worse cardiovascular outcomes. Further intensified management should be applied to octogenarian subjects with AMI.
P1570Cardiac strain detects subclinical decline of cardiac function after hematopoietic stem cell transplantation in patients with hematologic malignancies
Authors: Oboshi M , Oka T , Yasui T , Shioyama W , Tada Y , Ishikawa J , Fujita M
Published: October 2019

Background

Hematopoietic stem cell transplantation (HSCT) has been established as a treatment of various hematologic malignancies and improved their prognoses. HSCT includes intensive chemotherapy and systemic radiation, which occasionally induces cardiac dysfunction. However, early predictor of cardiac dysfunction associated with HSCT is still elusive. Recently, left ventricular (LV) global longitudinal strain (GLS) has been recognized as an early detector of cardiotoxicity. In this study, we retrospectively analyzed GLS and cardiac parameters in patients with hematologic malignancies before and after HSCT to explore HSCT-induced cardiac dysfunction.

Methods

Thirty-one consecutive patients undergone HSCT were enrolled and reviewed their cardiac comorbidities, medications, chemotherapy, and radiotherapy before HSCT. Transthoracic echocardiographic variables including GLS, cardiac troponin-I, and B-type natriuretic peptide were analyzed prior to and 1 month after HSCT.

Results

The patients were 49.7±13.5 years of age, 61% were male, and 52% had cardiovascular risk factors. Cardiac troponin-I was significantly increased following HSCT from 0.010±0.002 ng/ml to 0.016±0.014 ng/ml (P=0.02), indicating that HSCT should have certain impact on cardiac myocytes. Echocardiographic analyses revealed that LV GLS was significantly decreased after HSCT from −19.4±0.8% to −18.8±0.8% (P<0.001), whereas there was no significant difference in LV ejection fraction between these time points of HSCT (63.6±5.5% vs. 64.7±4.6%; P=0.13). Although there was no correlation between the decline of GLS and the increase of troponin-I in this cohort, these results clearly indicated that GLS, but not LVEF, predicted HSCT-induced early and subclinical cardiac dysfunction at 1 month after the HSCT.

Conclusion

GLS detected early decline of cardiac function after HSCT in the patients with hematologic malignancies. Further follow-up investigations will reveal relationship between GLS, troponin-I and prognosis of cardiac function after HSCT in patients with hematologic malignancies.
P1576Association of colorectal cancer with genetic and epigenetic variation in PEAR1 - a population-based cohort study
Authors: Yang W.-Y , Izzi B , Zhang Z.-Y , Thijs L , Citterio L , Wei F.-F , Salvi E , Delli Carpini S , Manuta P , Kuznetsova T , Cusi D , Hoylaerts M F , Luttun A , Verhamme P , Staessen J A
Published: October 2019

Background

Platelet Endothelial Aggregation Receptor 1 (PEAR1) modulates angiogenesis and platelet contact-induced activation, which play a role in the pathogenesis of colorectal cancer.

Purpose

To study the association of colorectal cancer with genetic and epigenetic variation in PEAR1.

Methods

Among 2532 randomly recruited participants enrolled in the family-based Flemish Study on Environment, Genes and Health Outcomes (51.2% women; mean age 44.8 years), we recorded the incidence of colorectal cancer and genotyped SNP rs12566888 located in intron 1 of the PEAR1 gene. In 929 participants, we also measured the methylation at 16 CpG sites in the PEAR1 promoter. In multivariable-adjusted analyses, we contrasted the risk of colorectal cancer in minor-allele (T) carriers vs. major allele (GG) homozygotes. We applied partial least square discriminant analysis (PLS-DA) to identify methylation sites associated with colorectal cancer.

Results

Over a median follow-up of 18.1 years, 49 patients developed colorectal cancer. While accounting for clustering within families and adjusting for sex, age, body mass index, the total-to-HDL cholesterol ratio, serum creatinine, plasma glucose, smoking and drinking, use of antiplatelet and nonsteroidal anti-inflammatory drug, the hazard ratio contrasting minor allele carriers vs. major allele homozygotes was 2.17 (95% confidence interval, 1.18–3.99; P=0.013). Bootstrapped analyses, from which we randomly excluded from two to nine cancer cases, provided confirmatory results. PLS-DA identified two methylation sites in the PEAR1 promoter associated with higher colorectal cancer risk and two with lower risk. In-silico analysis suggested that methylation of the PEAR1 promoter at these four sites affects binding of the transcription factors p53, PAX5, and E2F-1, thereby modulating gene expression.

Potential pathways

Conclusions

Our findings suggest that genetic and epigenetic variation in PEAR1 modulates the risk of colorectal cancer in white Flemish.

Acknowledgement/Funding

The European Union, the European Research Council, the European Research Area Net for Cardiovascular Diseases, and the Research Foundation Flanders.
P1582Prognostic value of C-reactive protein/albumin ratio for cardiovascular morbidity and mortality in end-stage renal disease patients with incident haemodialysis therapy
Authors: Takahashi H , Ishii H , Kumada Y , Oshima T , Sakakibara T , Ito R , Murohara T , Ozaki Y
Published: October 2019

Background

Hypoalbuminemia, a manifestation of protein-energy wasting or malnutrition, is commonly observed in patients with end-stage renal disease (ESRD), and is associated with chronic inflammation and increasing cardiovascular (CV) risk. Recently, C-reactive protein (CRP)/albumin ratio at discharge is reportedly a well-predictor of mortality in severe sepsis or cancer patients.

We investigated prognostic value of the CRP/albumin ratio at just starting haemodialysis (HD) therapy for CV morbidity and mortality in patients with ESRD.

Methods

A total of 1,548 ESRD patients were enrolled and were divided into quartiles according to CRP/albumin levels at initiation of HD; quartile 1 (Q1): <0.22, Q2: 0.23–0.54, Q3: 0.55–1.83 and Q4: >1.84. They were followed up for 10-year after starting HD therapy. Primary endpoint was CV events defined as hospitalization due to CV events such as cardiac disease, stroke and peripheral artery disease and CV death. We also evaluated the incremental value with C-index when CRP alone, albumin alone and the CRP/albumin ratio were added into a model with established risk factors.

Results

During follow-up period (median: 59 months), 512 cases experienced CV events (33.1%) including 165 cases of CV deaths (10.7%). Kaplan-Meier analysis shows that CV event-free survival rates for 10 years were 63.5%, 53.8%, 47.5% and 31.9% in Q1, Q2, Q3 and Q4, and that CV survival rates were 90.4%, 83.9%, 77.2% and 64.6% in Q1, Q2, Q3 and Q4, respectively (p<0.0001 in both). After adjustment for all baseline variables, elevated CRP/albumin ratio was identified as an independent predictor for CV events [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11–2.07, p=0.0093 for Q2 vs. Q1, HR 1.79, 95% CI 1.33–2.42, p<0.0001 for Q3 vs. Q1and HR 2.27, 95% CI 1.70–3.07, p<0.0001 for Q4 vs. Q1, respectively]. As to CV mortality, similar results were obtained (HR 1.80, 95% CI 0.98–3.44, p=0.056 for Q2 vs. Q1, HR 2.56, 95% CI 1.45–4.71, p=0.0009 for Q3 vs. Q1 and HR 2.66, 95% CI 1.53–4.86, p=0.0004 for Q4 vs. Q1, respectively). Furthermore, adding the CRP/albumin ratio to a baseline model with established risk factors improved the C-index greater than that of CRP alone or albumin alone, respectively (0.715 from 0.692, p=0.0095 and from 0.683, p=0.0019)

Conclusion

The CRP/albumin ratio, which easily available from daily practice, could strongly stratify the risk of future CV morbidity and mortality in ESRD patients who need HD therapy.
P1583The association of carotid atherosclerosis, protein-energy wasting and inflammation status with mortality in patients on haemodialysis
Authors: Ito R , Oshima S , Ishii H , Sakakibara T , Yamabe S , Umemoto N , Murohara T
Published: October 2019

Background

Carotid atherosclerosis such as increased intima-media thickness (IMT) is associated with poor cardiovascular outcome. On the other hand, protein-energy wasting (PEW) or malnutrition, currently considered to be due to inflammatory process rather than poor nutritional intake, is highly prevalent in in chronic kidney disease (CKD) patients, particularly those on haemodialysis (HD). We investigated the association of carotid atherosclerosis, PEW and inflammation, and their joint role with prediction of mortality in chronic HD patients.

Methods

Carotid ultra-sound was performed in a total of 774 CKD patients stably undergoing HD therapy. Carotid atherosclerosis is defined as IMT>0.8mm as median value with hyperechoic plaque. Geriatric nutritional risk index (GNRI) which calculated from serum albumin levels, body weight and height as a surrogate marker of the PEW, and C-reactive protein (CRP) were measured at the same point. Patients were followed-up for 7 years.

Results

Declined GNRI and elevated CRP levels were independently associated with carotid atherosclerosis [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93–0.98, p=0.0082 and OR 1.30, 95% CI 1.04–1.64, p=0.019, respectively] accompanied with age (OR 1.03, 95% CI 1.01–1.05, p=0.0024) and hypertension (OR 1.78, 95% CI 1.12–2.91, p=0.013). During follow-up period (median of 67 months), 180 patients (23.3%) died. Carotid atherosclerosis [62.7% vs. 79.3% for 7-year survival rate, hazard ratio (HR) 1.57, 95% CI 1.12–2.16, p=0.0078], GNRI<91.2 as an established cut-off value (58.8% vs. 83.7%, HR 1.87, 95% CI 1.35–2.59, p=0.0002) and CRP>1.1 mg/l as a median value (65.8% vs. 88.6%, HR 2.87, 95% CI 2.00–4.22, p<0.0001) were identified as independent predictors of mortality after adjustment for other confounders. When patients were divided into groups according to number of these three risk factors, 7-year Kaplan-Meier survival rate was 92.7%, 91.1%, 56.8% and 37.2% among groups with no risk factor, any 1 risk factor, any 2 risk factors and all risk factors, respectively (p<0.0001 for trend). After adjustment for other confounders, patients with any 1, any 2 and all risk factors had 2.21-fold (95% CI 1.26–4.14), 5.44-fold (95% CI 3.13–10.1) and 7.19-fold (95% CI 3.67–14.6) higher risk for mortality compared to those without any risk factor, respectively (p<0.0001 for trend).

Conclusions

Presence of carotid atherosclerosis was closely associated with both declined GNRI and elevated CRP levels in CKD patients on HD. Combination of these predictors was also additively associated with an increasing risk of mortality. These results clearly manifested the so-called malnutrition, inflammation and atherosclerosis (MIA) syndrome in this high-risk population.
P1584The prognostic significance of the blood pressure-pulse wave velocity association for cardiovascular outcomes and mortality in hemodialysis patients
Authors: Loutradis C , Sarafidis P , Mayer C , Karpetas A , Bikos A , Papadopoulos C E , Pagourelias E , Wassertheurer S , Vassilikos V , Schmaderer C , Papagianni A , London G
Published: October 2019

Introduction and purpose

Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies showed that when BP decrease is accompanied by PWV decrease the survival is improved. The aim of this study is to examine the prognostic significance of BP sensitivity of PWV for major cardiovascular outcomes and all-cause mortality in hemodialysis patients.

Methods

This is a prospective cohort study including 242 hemodialysis patients [age, 62.6±14.2 years; female, 91 (37.6%); hemodialysis vintage, 41.53±43.46]. All subjects underwent 48-hour-ABPM with Mobil-O-Graph-NG and followed-up for 33.17±19.68 months. The within-individual MBP-PWV association (MBP, dependent and PWV independent variable) was evaluated using the beta-coefficient value from simple linear regression analysis for each patient. The primary end-point was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary end-points were: (i) all-cause mortality; (ii) cardiovascular mortality; (iii) a combination of cardiovascular events.

Results

Patients who experienced the primary end-point during follow-up had significantly lower beta-coefficient levels (primary end-point: 19.877±3.975 vs 18.483±3.550, p=0.008). Higher quartiles of beta-coefficients (indicating dependency of PWV on MBP) were associated with higher cumulative freedom from the primary end-point (50.8%, 60.0%, 70.0% and 80.3% for quartiles 1 to 4 respectively; logrank-p=0.001), higher overall survival (60.7%, 61.7%, 73.3%, 86.9%; logrank-p=0.002) and higher cardiovascular survival (78.7%, 75.0%, 81.7%, 91.8% for quartiles 1 to 4; logrank-p=0.044). The future risk for the primary end-point, all-cause and cardiovascular mortality and the combined outcome was progressively increasing for lower quartiles of beta-coefficients (HR for all-cause mortality 3.395; 95% CI: 1.524–7.563, p=0.003 for quartile 1 vs quartile 4). Age (OR: 1.046, 95% CI: 1.016–1.077 per year increase, p=0.003) and 48h heart rate (OR: 0.949, 95% CI: 0.916–0.982 per bpm increase, p=0.003) were independently associated with weaker relationship between 48h-MBP and 48h-PWV.

Conclusions

Lower within-individual MBP-PWV association, based on AMBP recordings, is associated with higher risk of death and cardiovascular events in hemodialysis. These findings support that BP-independent arterial stiffness may be the underlying factor for adverse outcomes in these individuals.
P1591Cardiovascular toxicity of ibrutinib: a pharmacovigilance study
Authors: Salem J E , Manouchehri A , arie Bretagne M , Lebrun Vignes B , Groarke J D , Johnson D B , Yang T , Reddy N M , Funck-Brentano C , Brown J R , Roden D M , Moslehi J J
Published: October 2019

Importance

Ibrutinib, a first in class Bruton tyrosine kinase inhibitor, has revolutionized treatment for several B-cell malignancies. However, early data suggested that ibrutinib was associated with supra-ventricular arrhythmias (SVA) and bleeding. Other types of cardiovascular adverse drug reactions (CV-ADR) induced by ibrutinib have been sporadically reported.

Objective

To determine the full spectrum of CV-ADR associated with ibrutinib and provide data concerning their clinical characteristics.

Design

An observational, retrospective, pharmacovigilance study

Setting

VigiBase, the World Health Organization's pharmacovigilance database.

Main outcomes and measures

A disproportionality analysis using reporting odds-ratios (ROR) and information component (IC). IC compares observed and expected values to find associations between drugs and ADR using disproportionate Bayesian reporting; IC025 (lower end of the IC 95% credibility interval) >0 is considered statistically significant.

Exposures

Exposure to ibrutinib versus entire database.

Results

Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVA; ROR: 23.1 [21.6–24.7]; IC025:3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7 [3.4–4.1]; IC025:1.63), heart failure (HF; ROR: 3.5 [3.1–3.8]; IC025:1.46), ventricular arrhythmias (VA; ROR: 4.7 [3.7–5.9]; IC025:0.96), conduction disorders (CD; ROR: 3.5 [2.7–4.6]; IC025:0.76), CNS ischemic events (ROR: 2.2 [2.0–2.5]; IC025:0.73) and hypertension (ROR: 1.7 [1.5–1.9]; IC025:0.4). CV-ADR occurred early after ibrutinib administration, as soon as after the first dose, with a shorter median time to onset of 27.5 days (IQR: 1–138.5 days) for CD (p<0.01, Kruskal-Wallis), as compared to CNS ischemic events (51 days; IQR: 17.5–160 days, p: 0.05 vs. CD), CNS hemorrhagic events (53.5 days; IQR: 20.3–183.3 days, p: 0.03 vs. CD), HF (54 days; IQR: 20–142.8 days, p: 0.05 vs. CD), VA (70 days; IQR: 28.5–152.5 days, p: 0.03 vs. CD), SVA (74 days; (IQR: 29.5–196.5 days, p: 0.0004 vs. CD) and hypertension (164 days; IQR: 20–274 days, p: 0.04 vs. CD). CV-ADR were associated with fatalities, with rates ranging from ∼10% (SVA and VA) to ∼20% (CNS events, HF and CD). More deaths occurred when SVA cases were associated with CNS hemorrhagic and/or ischemic events compared to their absence (15/52, 28.8% vs. 88/907, 9.7%, p<0.0001, respectively).

Conclusions

Severe and occasionally fatal cardiac events related to cardiac SVA, VA, CD, HF, hypertension, CNS hemorrhagic and ischemic events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs.
P1592A cardioprotective effect of dietary nitrate mediated by red blood cells
Authors: Jiao T , Yang J N , Sundqvist M , Tratsiakovich Y , Hellenius M L , Weitzberg E , Lundberg J , Pernow J
Published: October 2019

Background

Reduced bioavailability of nitric oxide (NO) is a key factor behind coronary artery disease and ischemic heart disease. Besides being produced from L-arginine by NO synthase, reduction of nitrate/nitrite to NO is also an important pathway for NO generation, especially during hypoxic/ischemic conditions. Existing evidences suggest that dietary nitrate improves endothelial function and ischemic tolerance via a NO-dependent mechanism. Recent data indicate that red blood cells (RBCs) are an important source of NO bioactivity that protects the heart from ischemia-reperfusion injury. It is unknown whether dietary nitrate exerts cardioprotection by increasing export of RBC NO bioactivity.

Purpose

To investigate whether dietary nitrate protects the heart against ischemia-reperfusion injury via a mechanism mediated by RBCs.

Methods

Patients with mild hypertension (systolic blood pressure >130, ≤159 mmHg) were randomly assigned to three groups after a 2-week run-in period on a diet low in nitrate: group 1 received nitrate-rich vegetables (green leafy, ∼150 g/day) plus capsules with placebo salt (KCl), group 2 received low nitrate vegetables (cherry tomato, sweet corn, capsicum, carrot, ∼150 g/day) and capsules with nitrate salt (KNO3, 300mg) and group 3 received low nitrate vegetables and placebo capsules for 5 weeks. The nitrate content of the pills and nitrate-rich vegetables were precisely matched. As a pre-specified substudy, RBCs were collected blindly from 48 subjects before (baseline) and after the 5-week treatment (follow-up). The RBCs were given to isolated Langendorff-perfused rat hearts at the onset of ischemia with and without the soluble guanylyl cyclase (sGC) inhibitor (1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ). The hearts were subjected to 25 min global ischemia following 60 min reperfusion. Left ventricular developed pressure (LVDP) was recorded as an indicator of cardiac function.

Results

The recovery in LVDP during reperfusion following global ischemia in hearts given RBCs collected at baseline was similar in the three groups (Fig. A). Of note, post-ischemic recovery of LVDP was significantly improved by administration of RBCs from patients randomized to high nitrate vegetables or nitrate capsule compared to the group randomized to low nitrate and placebo (Fig. B). There was no difference in LVDP recovery between the groups receiving high nitrate vegetables or nitrate capsule (Fig. B). The nitrate-induced improvement in post-ischemic cardiac recovery was totally abolished by the sGC inhibitor ODQ (Fig. C), indicating that the protective effect induced by RBCs from subjects given nitrate is NO-sGC dependent.

Conclusion

Dietary nitrate in the form of leafy vegetables induces protection against myocardial ischemia-reperfusion injury via a mechanism involving the NO-sGC signaling pathway in RBCs.