bluuebunny/crossref_metadata_2025 huggingface dataset:
P4450Atherosclerosis in women with systemic lupus erythematosus with and without nephritis
Authors: Panafidina T , Popkova T V , Novikova D S
Published: October 2019

Background

Nephritis in systemic lupus erythematosus (SLE) is a factor contributing to early development of atherosclerosis (AS).

Objectives

The aim of the study is to determine differences in cardiovascular risk factors and AS in SLE pts with and without lupus nephritis (LN).

Methods

The study included 162 females, age 35 [26–43] years (median [interquartile range 25–75%])) with SLE (ACR,1997). We divided SLE pts on two groups, comparable in age: the 1st group is the pts with LN (n=84, 52%), the 2nd - without LN (n=78, 48%). We considered traditional factors of cardiovascular disease (CVD): (smoking, family history of CVD, blood pressure, cholesterol (total, HDL, LDL) and triglyceride (TG) levels, body mass index, diabetes mellitus) and SLE-related factors (age at onset, duration, clinical features, SLE Disease Activity Index (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics damage index (SLICC/DI), treatment with steroids); intima-media thickness (IMT) and the 10-year risk for coronary events. Carotid intima-media wall thickness of common carotid arteries was measured by high resolution B-mode ultrasound. The 10-year risk for coronary events was estimated by the Framingham risk equation.

Results

Median SLE duration was 8,0 [2,3–17,0] years, SLEDAI 2K – 8 [3–16], SLICC/DI score – 2 [0–3], duration of prednisone treatment – 72 [26–141] months. SLE pts from the 1st group had higher prevalence of hypertension (61% vs 36%, p<0,01), systolic blood pressure (130 [110–150] vs 120 [110–130]mm Hg, p<0,01), diastolic blood pressure (80 [70–95] vs 70 [70–80] mm Hg, p<0,05), TG concentration (136 [98–184] vs 100 [61–162] mg/dl, p<0,01), Framingham Risk Score (5 [1–30] vs 1 [1–27]%, p<0,05), SLEDAI-2K (12 [5–19] vs 4 [2–10], p<0,ehz745.08501), SLICC/DI score (2 [0–4] vs 0 [0–2], p<0,01), prednisone therapy duration (95 [26–192] vs 44 [14–98] months, p<0,05), prednisone cumulative dose (34,4 [13,6–82,5] vs 15,7 [6,2–35,2] g, p<0,001), mean IMT (0,73 [0,65–0,83] vs 0,67 [0,61–0,75] mm, p<0,01), than the pts from the 2nd group. There is no difference in CVD frequency in these groups (17% vs 8%, p=0,084).

Conclusions

SLE patients with and without LN had no difference in frequency of clinical manifestations of AS (CVD), but had a greater value of mean IMT, Framingham Risk Score and a higher incidence of both traditional (hypertension, TG concentration) and SLE-related (disease activity, prednisone therapy) risk factors for AS.
P4492Peripheral blood mononuclear cell expression of the stabilizing RNA-binding protein HuR is associated with incidence and extent of human atherosclerotic cardiovascular disease
Authors: Sachse M , Mareti A , Georgiopoulos G , Sopova K , Vlachogiannis N , Tual-Chalot S , Kritsioti C , Laina A , Kontogiannis C , Zaman A , Spyridopoulos I , Gatsiou A , Stamatelopoulos K , Stellos K
Published: October 2019

Background

Human Antigen R (HuR) is a stabilizing RNA-binding protein that regulates the expression of several pro-inflammatory molecules. However, its regulation in human atherosclerotic cardiovascular disease remains unknown.

Purpose

To determine the association of peripheral blood mononuclear cell HuR expression with established markers of increased cardiovascular risk and atherosclerosis burden in patients with subclinical or clinically overt coronary artery disease (CAD).

Methods

HuR mRNA expression was measured in peripheral blood mononuclear cells derived from 289 patients with stable CAD or acute myocardial infarction (AMI) and 373 individuals without clinically overt cardiovascular disease (CVD). Structural and functional vascular measurements including intima-media thickness (IMT) and number of atheromatous plaques by carotid and femoral artery ultrasonophaphy, markers of arterial wave reflections by pulse wave analysis and pulse wave velocity were used as surrogate markers of subclinical CVD. The number of angiographically confirmed diseased coronary arteries (>50% stenosis) was used to assess the extent of CAD.

Results

HuR mRNA expression was significantly increased in patients with CAD (both stable and AMI) compared to controls (p=0.039). Subgroup analysis revealed that STEMI patients (n=107) had increased levels of HuR expression compared to NSTEMI (n=49, p=0.03). Among patients with stable CAD (n=133), high HuR expression was independently associated with the number of diseased coronary arteries (OR=1.35 for 1-SD increase in HuR, 95% CI 1.07–1.72, p=0.012), as well as with reduced ejection fraction (EF<45%, OR=1.32 per 1-SD increase, 95% CI 1.05–1.85, p=0.024). Among individuals without CVD, high HuR was associated with lower HDL levels (adjusted beta=-5.2 mg/dl for highest versus lowest quartile, p=0.03) and higher diastolic blood pressure (adjusted beta=3.6 mmHg, p=0.007), while, after adjustment for traditional cardiovascular risk factors, HuR levels in individuals without CVD were independently associated with increased IMT in the common carotid artery (mean increase 6.2% for highest versus lowest quartile, p=0.019).

Conclusion

HuR expression is associated with early subclinical arterial disease in individuals without clinically overt CVD and with the presence and severity of cardiac and vascular dysfunction in patients with clinically overt CAD. These findings imply a clinical role of the HuR pathway in cardiovascular disease and warrant further investigation.
P4494Renal insufficiency mitigates the protective effects of elevated anti endothelial cell antibodies on survival in patients undergoing coronary angiography
Authors: Teodorovich N , Gandelman G , Jonas M , Shimoni S , George J , Swissa M
Published: October 2019

Background

We previously demonstrated that elevated levels of antiendothelial cell antibodies are associated with improved survival of patients undergoing coronary angiography. However, renal insufficiency, which is associated with decreased survival, leads to increased level of the antiendothelial cell antibodies. The purpose of this study was to evaluate the correlation of the levels of these antibodies with survival in patients with normal versus reduced renal function.

Patients and methods

This was a single center prospective study. Eight hundred thirty eight consecutive patients undergoing coronary angiography with detectable antibody levels were enrolled. The levels of antiendothelial antibodies were determined by ELISA and measured in optical density units. Renal insufficiency was defined as adjusted GFR<60 ml/min. The mean follow up was 30 months.

Results

Of total 838 patients, 481 (57%) had normal and 357 (42.6%) had reduced renal function. Total mortality was 13.6%, being significantly higher in patients with reduced (23.2%) versus normal (6.4%) renal function (p<0.0001). Antiendothelial cell antibody levels were higher in patients with normal versus reduced renal function (4.76±7.05 versus 3.84±6.09 OD units, p=0.042). Antiendothelial cell antibody levels were significantly higher in survived versus deceased patients (4.56±6.82 versus 3.14±5.50 OD units, p=0.014). This association with survival was even more pronounced in patients with normal renal function (4.98±7.19 versus 11.69±3.29 OD units, p<0.0001). In patients with reduced renal function, there was no significant difference between survived and deceased patients (3.89±6.12 versus 3.68±6.05 OD units, p=0.788).

Conclusions

Renal insufficiency leads to mild decrease in the antiendothelial cell antibodies' levels. Higher levels of antiendothelial cell antibodies are associated with improved survival in patients undergoing coronary angiography. This association is significant in patients with normal but not reduced renal function. Thus, the effect of the higher levels of these antibodies on survival cannot be explained by its association with renal dysfunction.
P4510Impact of secondary tricuspid regurgitation on survival in heart failure - insights from COMMIT-HF registry
Authors: Nowak J , Pyka L , Kurdziel M , Siedlecki L , Niedziela J , Krajewski A , Skowron W , Danicic M , Kazik A , Gasior M
Published: October 2019

Background

Functional tricuspid regurgitation (fTR) is common in left sided heart disease, especially in patients with concomitant left-sided valvular diseases and can lead to functional impairment and reduced survival. However, the impact of fTR on survival in chronic heart failure with reduced left ventricular ejection fraction (HFrEF) without severe left valvular diseases (LVD) is not fully established. The aim of the present study was to observe if moderate to severe fTR may influence the survival in patients with HFrEF without severe LVD.

Methods

We have analyzed a large single-center registry (n=2731) of HFrEF patients treated in a large-volume cardiovascular center between 2009–2015. After exclusion of patients with severe aortic and mitral valve disease we have included 2435 patients with HFrEF (left ventricular ejection fraction (LVEF) ≤35%). Functional moderate to severe tricuspid regurgitation without severe left valvular diseases was present in 465 patients. Twelve -month vital status was available for the whole patient population. Univariate and multivariate Cox proportional hazard regression models were performed to evaluate the relationship between moderate to severe fTR and mortality in the study group.

Results

Comparison of clinical data of fTR and non-fTR in HFrEF patients revealed some significant differences (age 63.3±12.9 vs 61.3±12.4, p=0.002; female sex 25.8% vs 17,9%, p<0.001; chronic kidney disease stage III-V 45.3 vs 26.6%, p=0.001; atrial fibrillation 52.4% vs 28.5%, p<0.001). Twelve-month all-cause mortality was over 2-fold higher in the fTR group (21.2% vs 8.1%, p<0.001). There were no significant differences with regard to the medical treatment, implantable defibrillator or cardiac resynchronization therapy. The presence of fTR was identified as an independent echocardiographic factor impaired 12-month all-cause survival (HR 1.59, CI 1.2- 2.09, p<0.001, figure 1)

Conclusion

Apart from the LVEF, the presence of moderate to severe fTR may predict 12-month all-cause mortality in patients with HFrEF.

Acknowledgement/Funding

None
P4520APAP therapy does not improve impaired sleep quality and sympatho-vagal balance: a randomized trial in patients with obstructive sleep apnea and systolic heart failure
Authors: Spiesshoefer J , Aries J A , Giannoni A G , Fox H F , Boentert M B , Bitter T B , Oldenburg O O
Published: October 2019

Introduction and purpose

In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown.

Methods

In this randomized controlled trial, sleep quality and SVB in patients with HFrEF and OSA were monitored noninvasively across different breathing conditions (5-minute segments of OSA or normal breathing [NB]) during stable N2 sleep) at baseline (T0), during APAP initiation (T1) and after 6 months of successful APAP treatment (T2).

Results

75 patients (61 male, 65±12 years, LVEF 31±9%) were enrolled. OSA was associated with a 17% increase in the low frequency/high frequency component ratio of heart rate variability (LF/HF) versus baseline, suggesting an increase in sympathetic drive (SVB) with OSA compared with normal breathing at baseline. Respiratory indices and oxygen saturation all significantly improved at both T1 and T2, but 6 months' APAP had no clinically relevant effect on objective sleep quality versus control. In HFrEF patients -suitable for HRV analysis (n=23)-, there was a trend (p=0.097) towards an increase in LF/HF at T2 in the therapy group (+17%), suggesting increased SVB.

Conclusion

Treatment of OSA in systolic HF patients improves respiratory indices but has no favorable effect on sleep quality. While OSA per se was associated with an increase in sympathetic drive, APAP treatment was not associated with a desired reduction in sympathetic drive. There was even a trend towards additional increases in sympathetic drive during the entire night and N2 sleep in particular.

Acknowledgement/Funding

This research (conductance of the APAP trial) has been supported by Resmed Germany (Martinsried, Germany).
P4542Revisiting the obesity paradox in heart failure: percent body fat as predictor of biomarkers and outcome
Authors: Aimo A , Januzzi J , Vergaro G , Latini R , Anand I S , Cohn J N , Gravning J , Brunner-La Rocca H P , Bayes-Genis A , De Boer R A , Egstrup M , Takeishi Y , Huber K , Passino C , Emdin M
Published: October 2019

Background

Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF). We assessed whether another anthropometric measure, percent body fat (PBF), reveals different associations with outcome and HF biomarkers (NT-proBNP, high-sensitivity troponin T [hs-TnT], soluble suppression of tumorigenesis-2 [sST2]).

Methods

In an individual patient dataset, BMI was calculated as weight (kg)/height (m)2, and PBF through the Jackson-Pollock and Gallagher equations.

Results

Out of 6468 patients (median 68 years, 78% men, 76% ischaemic HF, 90% reduced EF), 24% died over 2.2 years (1.5–2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4–33.0%) with the Jackson-Pollock equation, and 28.0% (23.8–33.5%) with the Gallagher equation, with an extremely strong correlation (r=0.996, p<0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥30 kg/m2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome.

Conclusion

Patient prognosis improves with either BMI or PBF. Obesity, assessed with BMI or PBF, is associated with lower NT-proBNP but not hs-TnT or sST2. hs-TnT or sST2 are stronger prognostic predictors than NT-proBNP among obese patients.
P4544Impact of hyponatremia improvement on one-year outcomes in patients with acute decompensated heart failure
Authors: Tamaki Y , Yaku H , Yamamoto E , Ozasa N , Inuzuka Y , Kondo H , Tamura T , Morimoto T , Nakagawa Y , Kimura T , Kato T
Published: October 2019

Background

Impact of hyponatremia improvement on prognosis in patients with acute decompensated heart failure (ADHF) remains unclear.

Methods

Patients hospitalized for ADHF at 19 hospitals in Japan were enrolled between October 2014 and March 2016. Hyponatremia was defined as serum sodium concentration less than 135 mmol/l. Primary endpoint was composite of all-cause death and heart failure rehospitalization one year after discharge.

Results

Among 3805 patients enrolled, 486 patients with hyponatremia at admission showed higher in-hospital mortality (13.3% vs. 5.4%, p<0.001). Of 486 hyponatremic patients, 396 patients were discharged alive. One hundred forty-three patients showed persistent hyponatremia at discharge (group P), whereas 253 patients showed improvement of hyponatremia (group I). Baseline characteristics are shown in the table. Patients in group I showed higher sodium concentration at admission (132±3 mmol/l vs. 130±4 mmol/l, p<0.001) and more increase in serum sodium concentration at discharge (7±4 mmol/l vs. 1±5 mmol/l, p<0.001). One-year survival rate free from primary endpoint was not different between the groups (56.4% in group P vs. 58.5% in group I, p=0.79). After adjusting for confounders, improvement of hyponatremia was not associated with better prognosis (hazard ratio 1.00; 95% confidence interval 0.70–1.45, p=0.99). Hyponatremia improvement showed significant interaction with left ventricular ejection fraction (LVEF) less than 40% (p=0.01). In patients with LVEF<40%, improvement of hyponatremia was associated with better prognosis (hazard ratio 0.48, 95% confidence interval 0.28–0.85, p=0.01) whereas not in patients LVEF≥40%.

Patient characteristics Group P (n=143) Group I (n=253) p value Age (years) 81 (72–86) 81 (72–87) 0.73 Female 71 (49.7) 110 (43.5) 0.24 Ischemic etiology 42 (29.4) 81 (32.0) 0.58 Prior hospitalization 62 (43.7) 98 (39.5) 0.42 SBP at admission (mmHg) 140±36 144±38 0.40 HR at admission (bpm) 92±23 95±29 0.27 Atrial Fibrillation 47 (32.9) 103 (40.7) 0.12 NYHA class IV 60 (42.2) 138 (54.8) 0.02 Intravenous inotropic use 35 (24.5) 59 (23.3) 0.80 LVEF <40% 54 (37.8) 95 (37.6) 0.97 Values are median (interquartile range), mean ± standard deviation or number (%).

Conclusion

Improvement of hyponatremia at discharge was not associated with better prognosis in patients hospitalized for ADHF.
P4553Clinical and prognostic value of right ventricular dysfunction in patients with chagas heart disease during acute decompensated heart failure
Authors: Siqueira S R R , Ayub-Ferreira S M , Chizzola P R , Salemi V M C , Lage S H G , Oliveira M T , Soares P R , Bocchi E A , Issa V S
Published: October 2019

Introduction

The occurrence of right ventricular disfunction (RVD) is common in heart failure (HF) patients due to Chagas' disease (ChD). However, its clinical and prognostic value has not been studied during episodes of acute decompensated heart failure (ADHF).

Purpose

Evaluate the prognostic value of RVD in ADHF patients with ChD during hospitalization and after 180 days of discharge compared to other etiologies.

Methods

We analysed a prospective cohort of consecutive 768 patients admitted for ADHF between March 2013 and October 2018; 490 (63.7%) patients were male and the median age was 58 (48.3–66.8) years and left ventricular ejection fraction was 26% (median) (IQR 22–35%). We compared the clinical characteristics and the prognosis of ChD patients according to the presence of RVD in the echocardiogram to other etiologies.

Results

RVD was presented in 289 (37.6%) patients. Among patients with non-chagasic etiologies, those with RVD were younger [53 (41–62) vs 61 (52–70) years, p<0.0001], had high levels of BNP in the moment of hospitalization [1195 (606–2209) vs 886 (366– 555) pg/mL], p<0,0001], received more inotropes (79.2% vs 57.9%, p<0,0001), had longer hospitalization [35 (17–51) vs 21 (10–37) days, p<0.001] and more clinical signs of congestion as hepatomegaly (49% vs 28.6%, p<0.0001); jugular venous distension (68.3% vs 41.2%, p<0.0001) and leg edema (65.4% vs 49.2%, p=0.001). Among patients with ChD, those with RVD were older [61 (48- 66) vs 58 (48 - 67) years, p=0.017], and had more frequently signs of hypoperfusion (56.8% vs 36.5%, p=0.029), jugular venous distension (72.8% vs 52.8%, p=0.01) and hepatomegaly (56.8% vs 31.1%, p=0.011), higher BNP levels [1288 (567–2180) vs 1066 (472–2007) pg/mL, p=0.006] and more frequent use of intravenous inotropes (88.9% vs 67.1%, p=0.003); additionally ChD patients with RVD had a higher rate of death and transplant during hospitalization (51.2% vs 38.3%, p=0.001). When all groups were compared together, ChD patients with RVD had the highest rate of death, transplant and readmissions at 180-days of follow-up (Figure).

Figure 1

Conclusion

Patients with RVD demonstrated a distinct clinical presentation, biomarkers and worse prognosis in all etiologies. ChD patients with RVD in ADHF had the worst prognosis with the highest rate of death, heart transplant e rehospitalization in follow-up.
P4564Sympathetic renal denervation in patients with refractory arterial hypertension: 2-years follow-up
Authors: Shugushev Z , Maximkin D A , Chepurnoy A , Safonova O , Faibushevich A
Published: October 2019

Aim

To evaluate the efficacy of the sympathetic renal denervation procedure in patients with refractory arterial hypertension and heart failure.

Methods

The study included 72 patients with refractory arterial hypertension. We used randomization in 2 main groups: the Group I (n=36) included patients, who underwent denervation procedure of the main trunk of the renal artery and the Group 2 (n=36) - included patients who underwent denervation procedure in main trunk and also in second-order renal arteries. Additionally, patients were divided into 2 subgroups: the subgroup A (n=30) included patients, who underwent denervation procedure with a SYMPLICITY catheter, and the subgroup B (n=42) - included patients who underwent denervation procedure with a VESSIX catheter. Also, the renal denervation procedure efficacy, in patients with chronic heart failure (CHF) was analyzed. In all groups, 24-hour blood pressure monitoring, echocardiography and a 6-minute walk test were monitored. Inclusion criteria: refractory hypertension, age of patients 18–85 years, systolic blood pressure (SBP) ≥140/90 mmHg and ≥130/90 mmHg in patients with diabetes mellitus, functioning kidneys, renal arteries ≥40 mm in diameter and the length of the site up to the first bifurcation of at least 20 mm, absence of stenoses in the renal arteries, GFR≥40 ml/min/1.73m2, suitable anatomy of the renal arteries for endovascular procedure.

Results

24 months result after the denervation procedure was demonstrated significantly decreased SBP in patients of both groups. In group I, it was, compared with pre-operative data (174.9±1.6 vs. 151.7±2.3 mmHg, respectively; p<0.05), and in group II - 181.9±2.1 vs. 140.4±3.8 mmHg, respectively; p<0.05). However, when comparing SBP values between groups, SBP in group I was significantly higher, than in group II (151.7±2.3 vs. 140.4±3.8 mmHg, respectively; p<0.05). In addition, the average number of drugs in group I was decreased to 2.1±0.8 after 24th month, and in group II - to 1.4±0.6 (p<0.05). When comparing SBP value in subgroup A and subgroup B, the average daily SBP also significantly difference and amounted to 147.8±1.8 vs. 138.4±3.2 mmHg, respectively; p<0.05). Among the all patients included in the study, 38 patients were with CHF. The 6-minute walk test results, compared with pre-operative data, showed a significant improvement and amounted to 321.24±83.22 vs. 212.42±54.72m, respectively; p<0.05.

Conclusions

The sympathetic renal denervation may be regarded as an effective method of treatment of patients with resistant hypertension, as well as patients with concomitant chronic heart failure. Performing denervation in the arteries of the second order, significantly improves the prognosis of patients, and in patients with concomitant heart failure significantly increases the quality of life and exercise tolerance.

Acknowledgement/Funding

Russian Academic Excellence Project 5-100
P4566Comparison of standard renal denervation procedure versus novel distal and branch vessel ablation with brachial arterial access
Authors: Petrov I , Tasheva I , Garvanski I , Stankov Z , Simova I
Published: October 2019

Objectives

We assessed a novel approach to percutaneous renal denervation for uncontrolled hypertension consisting of ablation beyond the proximal main renal artery (Y-pattern), including the primary branches, and compared it to the standard procedure applied only within the main vessel. We also assessed the safety and practicality of a brachial access approach.

Methods and results

Renal denervation was performed on 119 consecutive patients (60±13 years). In 68 of the patients, femoral arterial vascular approach was used and in 51 brachial. In 80 patients treated with the standard ablation, 12.0±3.0 total ablations (both sides) were applied while 20.4±3.9 total ablations were delivered for the group of 39 patients with Y-pattern denervation (P<0.001). Technically successful renal denervation was achieved in all patients. Office blood-pressure levels at baseline were 170±17/93±10 mm Hg for the standard group and 169±13/96±9 mm Hg for the Y-pattern group. No major adverse events occurred during the procedure or in the postprocedural in-hospital period. Renal denervation was associated with significant decreases in both office and ambulatory systolic and diastolic blood pressure in both groups. The reduction in 24-hour mean ambulatory systolic blood pressure at 6 months was significantly greater (P=0.002) for the Y-Pattern group (−22.1±15.4 mm Hg) compared to the Standard group (−11.8±16.2 mm Hg). Changes in diastolic office and ambulatory pressure were also significantly greater at 6 months in the Y-pattern ablation group. Indices of blood pressure variability improved in both groups.

Between group comparison of blood pressure and other parameters at follow up Standard Y-Pattern P (Standard vs Y) Change in Office Diastolic Blood Pressure (mmHg)   1 Month −8.0±13.2* −9.8±8.5* 0.49   3 Months −6.3±6.9* −6.4±9.0* 0.96   6 Months −5.0±9.0* −9.9±10.8* 0.01 Change in Ambulatory Diastolic Pressure (mmHg)   24-Hour −5.2±8.4* −6.2±10.0* 0.61   Daytime −3.2±9.4* −5.6±10.0* 0.24   Night Time −7.6±8.4* −6.5±11.5* 0.56 Antihypertensive Medication Classes 4.9±1.1* 5.3±0.8* 0.07 otal Number of Lesions† 12.0±3.0 20.4±3.9 <0.001

Conclusion

Renal denervation using a Y-pattern ablation strategy combined with a greater number of lesions is safe and resulted in significant greater decreases in mean 24-hour ambulatory systolic and diastolic blood pressure compared to the conventional
P4568Effect of intravitreal anti-vascular endothelial growth factor therapy on aortic stiffness and serum interleukin-6 levels in hypertensive patients with age-related macular degeneration
Authors: Gourgouli I , Vlachopoulos C , Ioakeimidis N , Pietri P , Spai S , Mouhtouris T , Abdelrasoul M , Terentes-Printzios D , Miliou A , Tousoulis D
Published: October 2019

Purpose

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults over 65 years old and it is associated with moderate to severe arterial hypertension and increased aortic stiffness. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, can reverse the symptoms of neovascular (wet) AMD. We sought to investigate whether intravitreal anti-VEGF therapy may influence aortic elastic properties of hypertensive patients with AMD.

Methods

54 hypertensive patients with exudative (“wet”) AMD received intravitreal ranibizumab (0.5mg) and blood pressure (BP) and carotid-femoral pulse wave velocity (PWV) were measured at baseline (approximately 2 days before the first injection), 24 h after the first and second injection (time interval between the injections: 1 month) and 1 month after the second injection. Serum levels of high sensitivity interleukin-6 (hsIL-6) were measured at three time points (baseline, first injection, 1 month after the second injection).

Results

Systolic BP decreased by 3.2 mmHg and by 3.0 mmHg after the first and second injection respectively and remained decreased (by 2.6 mmHg) 1 month after the second injection (overall p=0.07, by ANOVA). The changes in diastolic BP were minimal (overall p=0.74). Ranibizumab injection caused a significant decrease of PWV after the first (by 0.34 m/s) and the second injection (by 0.31 m/s). Furthermore, as upper figure shows, PWV remained decreased 1 month after the second injection. Among the treated naïve eyes, 45 (83%) had a good response to ranibizumab while 9 (17%) were poor responders. Interestingly, PWV decreased significantly in good responders to AMD therapy (overall p=0.004) whereas, it increased in poor responders (overall p=0.21) over the study period. In responders to therapy serum hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 pg/ml, overall p=0.02, lower figure). The levels of hsIL-6 increased in poor responders (overall p=0.54).

Ranibizumab, PWV and serum hsIL-6 levels

Conclusions

This is the first study showing that intravitreal administration of ranibizumab, a anti-VEGF used for improvement of wet AMD was associated with a beneficial acute and mid-term systematic effect on aortic elastic properties. Changes in systemic inflammatory activation may be involved. The findings have important implications for assessing the effect of anti-VEGF interventions on cardiovascular performance in hypertensive patients with exudative AMD.
P4571PFA-100, a test of platelet adhesion/aggregation, predicts cardiovascular events after an acute coronary syndrome and can help in the decision-making for dual antiplatelet extension
Authors: Chiappino S , Della Pina F , Paradossi U , De Caterina A R , Parri M S , Emdin M , Berti S , Maffei S , Benedetti G , Pizzino F , Scattina R , Gianetti J
Published: October 2019

Background

The dual antiplatelet therapy (DAPT) duration is a matter of great interest among cardiologists. Because of the conflicting evidences and the necessity to balance the reduction in major cardiac events (MACE) occurrence and the risk of major bleedings after an acute coronary syndrome (ACS), there is a general consensus on prolonging DAPT on an individual basis. There is less consensus on which parameters are to be evaluated. Nowadays tests of platelet reactivity are not included in the decision-making. Few data are available on the prognostic value of aspirin response tests that are sensitive to other mediators of platelet adhesion and aggregation in vivo under flow conditions.

Purpose

To demonstrate the role of the Platelet Function Analyzer (PFA-100) Collagen/Epinephrine (CEPI) cartridge, which is very sensitive to von Willebrand factor (VWF) levels, an emerging vascular risk factor, in risk stratification in ACS patients undergoing percutaneous coronary intervention (PCI).

Methods

We measured platelet reactivity by PFA-100 CEPI cartridges in a prospective cohort of 928 patients admitted for ACS between January 2006 to December 2009 and urgently treated by PCI at day 6±1 after admission. All the patients were treated with aspirin and clopidogrel according to current standard of that time.

Results

High platelet reactivity (HPR) defined as PFA-100 values <190”was found in 307 (33%) patients. No significant differences were found in demographic, angiographic and biochemical characteristics of both populations (PFA-100 <190” and PFA-100>190”). At a mean follow up of 5±1 years patients with HPR had a significant increase in cardiac death: 12.3% vs 2.6% (hazard ratio 6.05; 95% confidence interval: 3.34–10.95; p<0.0001) and recurrence of myocardial infarction (MI): 49% vs 17% (hazard ratio 4,29; 95% confidence interval: 3,27–5,64; p<0.0001). The trend in events incidence in our cohort of patients, in line with recent evidences, was maintained beyond the first year of follow-up

Conclusions

Using a multivariable Cox-proportional hazard model, HPR was found to be an independent predictor of MACE. These results indicate that PFA-100 CEPI cartridge, which correlates well with VWF levels, may be a useful point-of-care test to stratify the cardiovascular risk after an ACS. This also underlines the additional value of this test in the decision-making about the correct extension of DAPT.
P4582The role of TDI diastolic measurements for prognostic prediction early and late after surgical ventricular reconstruction
Authors: Iliuta L
Published: October 2019

Aim

1. To evaluate the impact of preoperative left ventricular (LV) diastolic performance on early and late outcomes in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) and surgical ventricular reconstruction (SVR).

2. To investigate LV diastolic function dynamics according to the results of tissue Doppler imaging (TDI) in these patients.

3. To assess the echographic predictors for persistence of the restrictive LV diastolic filling pattern (LVDFP) late after CABG and SVR.

Material and method

Prospective study on 157 pts with LV systolic dysfunction (LVEF <30%) who underwent CABG and SVR, evaluated including TDI preoperatively, early (<1 month), medium (3 and 12 months) and late postoperatively (mean 4,8 years). Statistical analysis used SYSTAT and SPSS. The primary outcome was the time to death from any cause or hospitalization for cardiac causes.

Results

1. The preoperative restrictive LVDFP was an independent and predominant predictor for increasing the early and late postoperative risk of cardiovascular events (p=0.001). At 5 years postoperatively, cardiovascular event-free survival was significantly higher in pts with nonrestrictive LVDFP (75%) compared with restrictive LVDFP (55,74%) (p<0.0001).

2. Conventional transmitral diastolic Doppler indices before and after CABG +SVR remained unchanged. TDI showed significant improvement before and in 3 and 12months postoperatively of both LV systolic (S: 6.1±0.9, 7.5±1.1 and 7.3±1.2 cm/sec, p<0.01) and diastolic function (e': 7.2±1.8, 8.3±1.4 and 8.8±1.5 cm/sec; E/e' ratio: 17.8±2.1, 13.1±1.7 and 11.3±1.8; Vp 3.2±0.55, 2.4±0.28 and 1.9±0.26, p<0.01).

3. The evolution of LVEF, LV end-diastolic volume (LVEDV) and mitral regurgitation (MR) severity was different in nonrestrictive group (early and late postoperatively these variables improved) compared with restrictive group (late after surgery the variables deteriorated: LVEF from 27±8% to 22±6%, LVEDV from 181±49 to 234±63 cm3 and MR degree from 0.9±0.6 to 1.8±0.7; p<0.005).

4. Regression analysis identified as predictors for persistence of a restrictive LVDFP late after surgery: E/E' ratio >14 (RR=19.3), LA dimension index >30 mm/m2 (RR=9.2), LVEDV >200 cm3 (RR=9.6), severe PHT (RR=11.4), 2 degree MR (RR=14.8).

Conclusions

1. TDI evaluation demonstrate significant improvement of LV systolic diastolic function in CABG + SVR pts, regardless of transmitral flow pattern. TDI is more sensitive and preload independent method of LV function evaluation.

2. The preoperative LVDFP has an independent and incremental prognostic value in CABG+SVR pts, strongly related to higher mortality with aggravation of LV systolic function, MR severity or LV remodeling. This might be attributable to deterioration of diastolic function induced by SVR.

3. Late after CABG+SVR the restrictive LVDFP persistence was predicted by: E/E' ratio >14, LA dimension index >30 mm/m2, LVEDV >200 cm3, severe PHT and 2 degree MR.
P4592Total arterial revascularization in severe coronary artery disease: a 25-years single-center experience
Authors: Nader J , Marzouk M , Dagenais F , Baillot R , Mohammadi S , Kalavrouziotis D , Laflamme M , Jacques F , Perron J , Dumont E , Charbonneau E , Doyle D , Voisine P
Published: October 2019

Objective

To evaluate very long-term survival of Total Arterial Revascularization (TAR) in patients with severe coronary artery disease (CAD) undergoing Coronary Artery Bypass Grafting (CABG).

Methods

Between January 1992 and December 2017, 13798 patients aged 70 years or less underwent primary isolated CABG with at least two grafts in our department. Patients receiving TAR were matched by propensity-score analysis to the rest of the population. All pre- and peri-operative data were collected prospectively in our institutional database. Long-term survival was assessed using provincial vital statistics data. The primary outcome was very-long time survival, secondary outcomes were operative mortality and early complications.

Results

Propensity-score matching identified 602 pairs with similar preoperative characteristics. In the matched control group, 65.4% and 30.9% of patients received 1 and 2 arterial grafts, respectively, whereas 3 or more arterial grafts were used in 3.6%. Less distal anastomoses (2.57±0.77 vs 3.39±0.97, p<0.0001) were performed in TAR patients, who therefore had a shorter cross-clamping time (44.2±14.7 vs 52.9±19.6, p<0.0001). Operative mortality was similar (0.5% vs 1.0%, p=0.51) and there was no difference in the rate of mediastinitis (2.5% vs 0.8%, p=0.28)for the TAR and matched control groups, respectively. TAR patients were less likely to receive blood transfusions (34.9% vs 40.7%, p=0.04). The average follow-up was 13.4±6.7 years. Cox-adjusted survival was significantly better in patients receiving TAR compared to the matched population, up to 25 years postoperatively (HR 0.87 [0.86–0.88], p<0.0001, Figure 1).

Figure 1

Conclusion

Total arterial revascularization is not associated with increased perioperative risk of complications and provides long-term survival benefits up to 25 years postoperatively.
P4604Insights into left ventricular remodelling and clinical outcomes after Wharton's jelly multipotent stem cells transcoronary administration in a pilot cohort of CIRCULATE-AMI Trial (NCT03404063)
Authors: Kwiecien E , Drabik L , Mazurek A , Urbanczyk M , Szot W , Kostkiewicz M , Banys R P , Brzyszczyk-Marzec M , Czyz L , Kozynacka A , Plazak W , Olszowska M , Majka M , Podolec P , Musialek P
Published: October 2019

Introduction

CIRCULATE-Acute Myocardial Infarction Trial (NCT03404063) is a double-blind controlled trial (RCT) that is randomizing consecutive patients with their first, large AMI (LVEF ≤45% and/or cMRI -infarct size ≥10% of LV) successfully treated by infarct-related artery (IRA) primary percutaneous coronary intervention reperfusion (TIMI ≥2) to transcoronary administration of Wharton Jelly Multipotent Stem Cells (WJMSCs) vs. placebo (2:1), preceded by evaluation of safety, WJMSCs myocardial uptake, and echocardiographic, cMRI and SPECT left ventricular remodelling and hemodynamic changes in pilot study cohort (PSC).

Purpose

To evaluate LV remodelling and hemodynamic features following WJMSCs transplantation in CIRCULATE-AMI PSC.

Methods

Ten consecutive patients (age 32–65 years) were administered 30 000 000 WJMSCs via the infarct-related artery at ≈5–7 days after AMI using transradial approach and a coronary-non-occlusive catheter dedicated to cell delivery. Within 3 years of follow up SPECT was performed at baseline and 1 year, echo and cMRI were performed at baseline, 1 year and 3 years.

Results

3-year observation (cMRI) shows a significant decrease of median left ventricular mass (LVM) between WJMSCs administration and 1 year 140 g (IQR 128–150) vs. 97 g (95–128), that is sustained at 3 years 93 g (80–119), p<0,001. There were no significant changes of left ventriular end-diastolic volume (LVEDV) in all diagnostic methods: SPECT baseline vs. 1 year (157.1±27.1 ml vs. 174±24 ml); cMRI baseline vs. 1 year vs. 3 years (171.6±17.7 ml vs. 198.2±23.4 ml vs. 181.9±17.6 ml) and Echo (137±13.3 ml vs. 135±2.9 ml vs. 148±21.8 ml), p value >0,05 for all. Furthermore, there was a significant increase in stroke volume measured by SPECT baseline vs. 1 year (53.3±7.6 ml vs. 68.2±5.2ml); cMRI baseline vs. 1 year vs. 3 years (72.7±5.2 ml vs. 96.9±8.1 ml vs. 93.2±7.8 ml) and Echo (64.3±2.9 ml vs. 68.8±4.1 ml vs. 81.9±7.1 ml), p<0,05 for all. By 3 years there was one non-index territory AMI. There were no other adverse events in the study cohort.

cMRI Left Ventricular Mass evolution

Conclusions

Long-term follow up in CIRCULATE-AMI PSC suggests that transcoronary administration of WJMSCs in a recent large AMI in humans might be associated with an inhibition of LV adverse remodelling and a significant hemodynamic improvement. Our currently running randomized double-blind controlled trial will verify LV remodelling evolution in WJMSCs-treated patients.

Acknowledgement/Funding

K/ZDS/00564 Jagiellonian University Medical College; STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland
P4613Long-term impact of postnatal nutritional programming on cardiac sensitivity to ischemia-reperfusion injury in vivo and on cardio-protective pathways in mice
Authors: Rigal E , Greco C , Porcherot I , Meloux A , Rochette L , Vergely C
Published: October 2019

Introduction

Nutritional disturbances during the postnatal period may be responsible for a predisposition, or “programming”, to increased cardio-metabolic risk and to a progressive alteration of left ventricular contractility in adulthood. This nutritional perinatal programming may also lead to an alteration of cellular pathways involved in cardiac protection, such as the specific RISK and SAFE pathways, highlighted during pre- and post-ischemic conditioning or those of sirtuins (SIRT), histone deacetylases involved in the regulation of essential biological process.

Purpose

Our aim was to evaluate in mice the impact of postnatal overfeeding (PNOF) on cardiac sensitivity to ischemia-reperfusion (I-R) injury in vivo and on the myocardial expression of genes involved in heart protection against ischemia.

Methods

PNOF was induced by the reduction of litter size of C57/BL6 mice immediately after birth: normally-fed group (NF) was composed of 9 male pups/mother and overfed group (OF) of 3 pups/mother. In vivo ischemia-reperfusion injury was induced by the ligation of the anterior interventricular artery for 45 minutes followed by 24 h of reperfusion in hearts from 6-months aged mice. The gene expressions of proteins of interest composing the cardioprotective pathways (RISK pathway: Akt, ERK; SAFE pathway: JAK/STAT3; Sirtuins: SIRT1) were measured by RT-qPCR in mice aged 4 and 6 months.

Results

PNOF induced in OF group an early and permanent increase in body weight (+23%, p<0.01, n=11) and a significant increase of infarct size (+32%, p<0.05, n=11) at 6 months. Hearts OF mice aged 4 months showed a decreased expression of cardioprotective pathways, represented by a reduction in the gene expression of ERK1, Akt, PI3K, STAT3 and SIRT1. At 6 months, the expression of cardioprotective pathways was also reduced in OF group, with the diminution of the gene expression of STAT3, Akt and Erk1.

Conclusion

Nutritional programming through short-term PNOF induced a long-lasting decrease in the expression of signaling pathways involved in cardiac cellular protection, which could explain why 6-months old mice show increased susceptibility to myocardial I-R injury in vivo. The mechanism of these alterations needs further exploration, but could involve alterations in cardiomyocyte's balance between apoptotic and regenerative pathways, and epigenetic modifications.

Acknowledgement/Funding

French Fundation
P4617Early electrocardiographic changes as markers of coronary microvascular obstruction in acute myocardial infarction with ST segment elevation
Authors: Garcia Talavera C S , Camblor Blasco A , Rivero Monteagudo A L , Arroyo Rivera M B , Cortes Garcia M , Franco Pelaez J A , Navarro Del Amo F , Tunon Fernandez J
Published: October 2019

Background

Coronary microvascular obstruction (CMVO), occurs frequently even after a quickly epicardial revascularization of the infarct-related artery (IRA), and has been associated with an increased risk of adverse cardiovascular events and poor prognosis in patients with ST-segment myocardial infarction (STEMI). After primary coronary intervention (PCI), incomplete ST-segment elevation (STE) resolution in the ECG has been related to CMVO and worse clinical outcome. However, there is lack of information regarding other ECG changes. The aim of this study is to describe the initial ECG changes in STEMI and evaluate their association with CMVO.

Methods

From January 2007 to December 2017, all patients with the diagnosis of STEMI that underwent urgent coronary angiography were retrospectively included. Clinical, echocardiographic, and electrocardiographic data were taken from medical records. A univariate and multivariate analysis was performed to evaluate the relationship between initial ECG changes (before PCI) and CMVO defined as final TIMI <3 in the IRA.

Results

1022 patients were included; the mean age was 67.8 years (±14), 73.7% were male and 14.4% had previous coronary artery disease. The most frequent IRA was the anterior descending artery in 43.2% of the cases and CMVO was found in 18.3% of the patients. The mean value of STE sum (defined as the sum of STE in V1-V6, I and aVL in anterior STEMI and the sum of II, III, aVF, V5 and V6 in non-anterior STEMI), maximum STE in one lead and number of leads with STE was 11.36mm (± 8.2), 3.65mm (± 2.3) and 4.14mm (± 1.4), respectively. After a univariate analysis, STE sum, maximum STE in one lead and number of leads with STE were associated with CMVO, while only STE sum remained significantly associated with the presence of CMVO after a multivariate analysis (Table). The resolution of STE in the first 2 hours after PCI was a protector factor for CMVO.

Univariate and Multivariate Analysis Univariate Multivariate Variables OR 95% CI p OR IC 95% p Sum of STE 1.03 1.01–1.04 0.013 1.03 1.01–1.05 0.005 Number of leads with STE 1.13 1.02–1.26 0.021 1.04 0.87–1.23 0.67 Maximum STE 1.09 1.02–1.16 0.016 1.04 0.92–1.17 0.49 Resolution of STE 0.35 0.25–0.49 <0.001 0.36 0.25–1.18 <0.001 STE, ST-segment elevation.

Conclusion

Initial ECG changes such as STE sum, number of leads with STE and maximum STE in one lead can be used as early predictors of CMVO and poor prognosis. STE resolution in the first 2 hour was associated with a lower incidence of CMVO as reported in previous studies.

Acknowledgement/Funding

None
P4619Comparison of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding risk scores for predicting in-hospital bleeding in acute myocardial infarction patients undergoing primary PCI
Authors: Mehmedbegovic Z , Milasinovic D , Jelic D , Zobenica V , Matic D , Dedovic V , Radomirovic M , Pavlovic A , Veljic I , Zaharijev S , Asanin M , Vukcevic V , Stankovic G
Published: October 2019

Background

Considering clinical importance of bleeding complications in patients with acute myocardial infarction (AMI), bleeding risk stratification is a key part of the management of these patients. CRUSADE, ACTION and ACUITY-HORIZONS bleeding risk scores are available for predicting in-hospital major bleeding events in patients with acute myocardial infarction.

Purpose

We aimed to evaluate performance of the three above mentioned risk scores for predicting in-hospital bleeding events defined according to The Bleeding Academic Research Consortium (BARC) criteria.

Methods

From a prospective electronic registry of a high-volume catheterization laboratory in a period from January 2009 to December 2017, a total of 6505 consecutive patients with acute myocardial infarction who underwent pPCI were included in analysis. Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow (H-L) goodness-of-fit test and C-statistic, respectively.

Results

Overall there were 372 (5.7%) bleeding events out of which 117 (1.8%) fulfilled stage BARC 3 or higher bleeding criteria. All three scores showed good model calibration as assessed by the H-Ls test and very good discriminative power for BARC 3 of higher bleeding events detection as assessed by C-statistics (Table 1 & Figure 1):

Bleeding events stage BARC 3 or higher were statistically highly related with higher in-hospital mortality (13.7% vs. 3.5%; p<0.000).

Table 1 Risk score H-L H-L p AUC 95% CI p CRUSADE 11.46 0.177 0.761 0.750–0.771 vs. ACUITY = ns vs. ACTION <0.000 ACUITY-HORIZONS 10.47 0.236 0735 0.724–0.745 vs. ACTION = ns ACTION 5.74 0.677 0.701 0.698–0.712

Figure 1

Conclusions

All three evaluated scores showed very good discriminative capacity for predicting BARC 3 or higher bleeding events in patients undergoing pPCI for AMI.