bluuebunny/crossref_metadata_2025 huggingface dataset:
P5359Pulmonary artery pressure is elevated three month after delivery in patients with preeclampsia and antiphospholipid syndrome
Authors: Buffle E , Neagoe A , Raio L , Rimoldi S F , Messerli F H , Scherrer U , Rexhaj E
Published: October 2019

Introduction

Preeclampsia (PE) is a multisystem disease affecting 2–8% of all pregnancies. Recently we found that the prevalence of antiphospholipid syndrome (APS) in PE patients at 13.9%. APS can be the cause of thromboembolic pulmonary hypertension. However, data on heart function and pulmonary pressure in PE and in PE with APS are sparse.

Purpose

We sought to investigate cardiac hemodynamics in this population.

Method

Between July 2016 and December 2018, we performed echocardiography in patients who had suffered from PE alone (n=102, age=32.6±4.8 y) or PE with APS (n=21, age=32.1±4.2 y) 3 months after delivery. APS was diagnosed according to the Sapporo criteria.

Results

The overall prevalence of APS was 17%. Right ventricular to right atrial pressure (RV/RA) gradient was significantly higher in PE + APS patients than in patients who had PE only (21.1±3.8 vs. 17.9±4.6mmHg, p=0.04, PE+APS vs. PE). The indexed volume of the left atrium (LA: 20.3±4.4 vs 23.5±5.5ml/m2, p=0.01, PE+APS vs. PE) and the birthweight of the newborn (1379.8±759.1 vs 1848.1±879.6.1g, p=0.02, PE+APS vs. PE) were lower in APS patients.

Conclusion

In patients with preeclampsia and APS, three month after delivery, pulmonary artery pressure was higher and the left atrium size smaller than in patients who had PE only. Conceivably this may reflects multiple subclinical clots in the pulmonary vessels in APS patients and may put these patients at an elevated risk of pulmonary hypertension later in life.
P5366Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging
Authors: Konishi T
Published: October 2019

Background

The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described.

Hypothesis

EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI.

Methods

Data on coronary artery plaques from 121 patients presenting with acute coronary syndrome or stable angina who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no-EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI.

Results

We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low-density lipoprotein cholesterol concentration, triglyceride concentration, and high-density lipoprotein cholesterol concentration). The EPA group had significantly lower mean lipid index (818±806 vs. 1,574±891) and macrophage grade (13.5±5.9 vs. 19.3±7.4) but higher mean minimum fibrous cap thickness (109.2±55.7 vs. 81.6±36.4 μm) than the no-EPA group (P=0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P=0.043 and 0.024, respectively).

Conclusion

This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI.

Acknowledgement/Funding

None
P5370Pulmonary pressure overload stimulates cardiac stem or progenitor cell-derived cardiac regeneration in the right ventricular area
Authors: Kanda M , Nagai T , Kondou N , Tateno K , Hirose M , Akazawa H , Komuro I , Kobayashi Y
Published: October 2019

Introduction and purpose

The number of patients with right heart failure due to pulmonary hypertension has been increasing. Although several drugs have reportedly improved pulmonary hypertension, no treatments have been established for decompensated right heart failure. The heart has an innate ability to regenerate, and cardiac stem or progenitor cells (e.g., side population [SP] cells) have been reported to contribute to the regeneration process. However, their contribution to right ventricular pressure overload has not been clarified. Here, this regeneration process was evaluated using a genetic fate-mapping model.

Methods and results

We used Cre-LacZ mice, in which more than 99.9% of the cardiomyocytes in the left ventricular field were positive for 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) staining immediately after tamoxifen injection. Then, we performed either a pulmonary binding (PAB) or sham operation on the main pulmonary tract. In the PAB-treated mice, the right ventricular cavity was significantly enlarged (right-to-left ventricular [RV/LV] ratio, 0.24±0.04 in the sham group and 0.68±0.04 in the PAB group). Increased peak flow velocity in the PAB group (1021±80 vs 1351±62 mm/sec) was confirmed by echocardiography. One month after the PAB, the PAB-treated mice had more X-gal-negative (newly generated) cells than the sham mice (94.8±34.2 cells/mm2 vs 23.1±10.5 cells/mm2; p<0.01). The regeneration was biased in the RV free wall (RV free wall, 225.5±198.7 cells/mm2; septal area, 88.9±56.5/mm2; LV lateral area, 46.8±22.0/mm2; p<0.05). To examine the direct effects of PAB on the cardiac progenitor cells, bromodeoxyuridine was administered to the mice daily until 1 week after the PAB operation. Then, the hearts were isolated and SP cells were harvested. The SP cell population increased from 0.65±0.23% in the sham mice to 1.87% ± 1.18% in the PAB-treated mice. Immunostaining analysis revealed a significant increase in the number of BrdU-positive SP cells, from 11.6±2.0% to 44.0±18%, therefore showing SP cell proliferation.

Conclusions

Pulmonary pressure overload stimulated cardiac stem or progenitor cell-derived regeneration with a RV bias, and SP cell proliferation may partially contribute to this process.

Acknowledgement/Funding

JSPS KAKENHI Grant Number JP 17K17636, GSK Japan Research Grant 2016
P5396CRISPR/Cas9 mediated miR-29b editing restores muscle atrophy and exercise capacity in mice
Authors: Li J , Wang L J , Wang F , Tang H F , Chen R , Yang T T , Das S , Xiao J J
Published: October 2019

Background

Muscle atrophy is the loss of skeletal muscle mass and strength in response to diversity catabolic stimuli, such as heart failure. At present, no effective treatment except exercise is validated on reducing multiple muscle atrophy clinically. We have recently reported that microRNA-29b (miR-29b) promotes multiple types of muscle atrophy.

Purpose

The goal of this study was to assess whether genome editing using a clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system can efficiently introduce loss-of-function mutations into the endogenous miR-29b in vivo and as a potential therapy by treating muscle atrophy.

Methods

We used lentivirus to express CRISPR-associated 9 and a CRISPR guide RNA targeting miR-29b. Mutagenesis rate of miR-29b and off-target mutagenesis were detected by T7 Endonuclease I (T7EI) Assay. The expression level of miR-29b were measured in vitro and vivo after administration of the virus by using qRT-PCR. After intramuscular administration of the virus, the angiotensin II (AngII), immobilization and denervation-induced muscle atrophy were performed. Then muscle function was assessed in exercise capacity, the appearance and weight of muscle, the size of the muscle fibers, molecular and cellular detection.

Results

Here, we report that CRISPR/Cas9 mediated genome editing through intramuscular administration efficiently targeting the biogenesis processing sites in pre-miR-29b. No off-target mutagenesis was detected in 10 selected sites. This CRISPR-based treatment resulted in decreased miR-29b levels specifically. In vivo, this CRISPR-based treatment could ameliorate the muscle atrophy induced by angiotensin II (AngII), immobilization and denervation via activation of PI3K-AKT-mTOR signaling pathway and protect against AngII-induced apoptosis in mice. Moreover, the exercise capacity is also significantly enhanced.

Conclusion

Our work establishes CRISPR/Cas9 based gene targeting on miRNA as a potential durable therapy for treatment of muscle atrophy and expands the strategies available interrogating miRNA function in vivo.

Acknowledgement/Funding

The grants from National Natural Science Foundation of China (81722008, 91639101 and 81570362 to JJ Xiao)
P5403Platelet lncRNA and mRNA: unravelling the role of epigenetic modulation in acute coronary syndrome
Authors: Grimaldi M C , Fabiani I , Aretini P , Mazzanti C M , Mandolini C , Larosa G , Liuzzo G , Volpe M , Crea F , Biasucci L M
Published: October 2019

Background

Platelets (PLT) play a pivotal role in thrombosis that represents the key event of acute coronary syndrome (ACS). Long noncoding RNA (lncRNA) are transcripts of more than 200 nucleotides not encoding for proteins and they are a challenging class of epigenetic regulators. As PLT are anucleated cellular fragments, they represent an ideal scenario to unlock ncRNAs undiscovered functions. In diabetic metabolic setting, PLT switch to a hyper-reactive phenotype, enhancing thrombotic risk of these subjects. As diabetes leads to macro and microvascular complications, lncRNA profile may unlock mechanism leading to pro-thrombotic milieu.

Purpose

Although PLT transcriptome and proteome have been widely investigated, only little is known about PLT lncRNA asset. Our pilot study aimed to assess how diabetes influences PLT coding and noncoding RNA in ACS.

Methods

Microarray analysis was performed on PLT RNA from three groups of patients (pts): 3 non-diabetic pts with not ST elevation (NSTE) ACS (ND-NSTE); 3 diabetic pts with NSTE (T2DM-NSTE) and 3 healthy controls (CTRL). We considered as significant RNA transcripts, those with a threshold of fold change >2 and p<0.05.

Results

Global transcriptomic analyses detected 20.642 lncRNAs and 18.949 mRNAs. We found significant dysregulation between T2DM-NSTE and ND-NSTE vs CTRL according to mRNA and lncRNA transcripts. Among the top ranked coding transcripts, mitochondrial-derived mRNAs, (ALAS, AHSP), were differentially expressed compared to CTRL. In addition, mRNAs linked to oxygen transport (HBG, HBA), PLT activation (SLC4A1), microparticles machinery (CORO6), calcium-homeostasis (CISD2), immune-thrombosis, apoptosis (APOPT1, EIF2AK2, IFI-6), cellular commitment (NOTCH3) related pathways were differently modulated. We identified a huge number of lncRNAs in PLT. Among them Linc ENSTehz746.03620452053 is a long intergenic noncoding RNA that could be involved in modulation of PI3K/AKT pathway, a central node for PLT activities

Different expressed mRNA Volcano Plot

Conclusion

Our platelet-derived RNA template pilot study confirms the central role of PLT in ACS and shows a potential role of lncRNAs, as master of the epigenetic control. As we found the main difference of expression between ND-NSTE vs T2DM-NSTE groups, our data show the critical role of diabetes in the transcriptional setting of ACS.
P5409Plasma volume status provides the additional prognostic information to the Get With the Guidelines-Heart Failure risk score in acute decompensated heart failure patients
Authors: Yamada T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Abe M , Yamamoto K , Kayama K , Kawahira M , Tanabe K , Fukunami M
Published: October 2019

Background

The Get with The Guidelines (GWTG) heart failure (HF) risk score was developed in the GWTG inpatient HF registry to predict in-hospital mortality and also reported to be associated with post-discharge long-term outcomes. Plasma volume (PV) expansion plays an essential role in HF. Recently, it has been reported that PV is estimated by a simple formula based on hematocrit and body weight, not using radioisotope assays, and PV status provides prognostic information in patients (pts) with acute decompensated heart failure (ADHF). However, there is no information available on the long-term prognostic value of the combination of PV status and GWTG-HF risk score in pts admitted for ADHF.

Methods and results

We studied 301 ADHF pts discharged with survival. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, serum levels of blood urea nitrogen and sodium, and the presence of chronic obstructive pulmonary disease. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). During a follow-up period of 4.3±3.2 yrs, 95 pts had all-cause death (ACD). At multivariate Cox analysis, GWTG-HF risk score and PV status were significantly associated with the total mortality, independently of eGFR and the prior history of heart failure hospitalization, after the adjustment with serum albumin level and anemia. Pts with both high GWTG-HF risk score (≥39 by ROC analysis; AUC 0.655 [0.586–0.724]) and greater PV status (≥8.1% by ROC analysis; AUC 0.624 [0.566–0.692]) had a significantly higher risk of ACD than those with either or none of them (58% vs 30% vs 21%, p<0.0001, respectively).

Conclusion

PV status would provide the additional long-term prognostic information to GWTG-HF risk score in ADHF pts.
P5422Long-term performance of vagus nerve stimulation lead: low rate of complications and failures
Authors: Libbus I , Stubbs S , Mindrebo S , Kenknight B , Dicarlo L
Published: October 2019

Background

Autonomic Regulation Therapy (ART) is a novel therapy for heart failure (HF) that has been shown in a pilot study to be associated with improvement in left ventricular function, 6-minute walk distance, NYHA class, and quality of life. ART is provided using chronic stimulation through a self-sizing lead that is placed on the cervical vagus nerve without any need for response-mapping. The lead is functionally identical in its design and manufacture to a commercially available lead that has been implanted since February 2009 for the treatment of refractory epilepsy and treatment-resistant depression.

Purpose

A survival analysis was performed to evaluate long-term lead performance.

Methods

Lead survival was calculated for those patients whose survival status was obtainable from public records. All devices registered as implanted in the United States for any indication were included for the analysis. All available data on device explants, device replacements, returned product analyses, and customer complaints were collected and used to identify failures and out-of-specification conditions. Device survival probability was defined as the likelihood of the implanted device remaining implanted and performing as intended.

Results

As of the time of this analysis, there have been 26467 registered system implantations and a total of 53200 device-years of lead use. Survival status was obtainable for 9700 patients from public records. After 1 year, 99.5% of implanted leads have remained implanted and performing as intended. At 7 years, 95.8% of leads have remained implanted and performing as intended. The most common causes of lead failure have been infection (0.87%), vocal cord dysfunction (0.68%), lead protrusion (0.36%), and lead extrusion (0.27%).

At implant 1 year 2 year 3 year 5 year 7 year Cumulative Survival Probability (%) 100 99.5 (99.4–99.6) 99.1 (98.8–99.2) 98.6 (98.4–98.9) 97.4 (96.9–97.7) 95.8 (94.9–96.5) Number of Patients 9700 8500 7200 6000 3300 700

Conclusions

Lead performance during chronic vagus nerve stimulation has included over 5ehz746.0379 device-years of use in over 25000 patients. A low rate of long term complications and failures have been reported, and the cumulative survival probability of the lead appears to be high.

Acknowledgement/Funding

LivaNova PLC
P5424Anxiety and all-cause mortality in patients with congestive heart failure and implanted cardiac devices
Authors: Pushkarev G S , Kuznetsov V A , Fisher Y A , Enina T N
Published: October 2019

Background

Several studies suggest that psychological factors including anxiety are associated with negative outcomes and in particular higher mortality rates among congestive heart failure (CHF) patients. However, the impact of anxiety on mortality in patients with implanted cardiac devices has not been fully appreciated.

Purpose

To estimate the influence of anxiety on all-cause mortality in patients with CHF after implantation of cardiac electronic devices.

Methods

The study enrolled 268 patients (mean age 57.1±10.1 years, 218 men and 50 women) with CHF and implanted cardiac devices (170 patients with implanted cardiac devices for resynchronization therapy, 98 patients - with implantable cardioverter defibrillators). We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale. Cox proportional hazards regression model was used to estimate hazard ratios (HR) with 95% confidence interval (95% CI) for impact of anxiety symptoms on all-cause mortality. HR was calculated after adjustment for the following confounders: age, gender, smoking status, hypertension, diabetes mellitus, body mass index, hypercholesterolemia, atrial fibrillation, left ventricular ejection fraction, number of hemodynamically significant lesions of the coronary arteries and the type of the implanted cardiac devices.

Results

According to State-A scale 119 (44.4%) patients had light symptoms of state anxiety (SA), 115 (42.9%) – mild SA symptoms and 34 (12.7%) – expressed SA symptoms. According to Trait-A scale 10 (3.7%) patients had light trait anxiety (TA) symptoms, 99 (40.0%) – mild TA symptoms and 159 (59.3%) – expressed TA symptoms. During prospective observation period, 46 (17.2%) patients died of all-causes. Multivariant analysis in patients with the expressed SA symptoms resulted in mortality HR which complied 5.26, 95% CI 1.99–13.90; patients with the expressed TA symptoms – 3.5, 95% CI 1.48–6.29.

Conclusion

SA and TA have significant and independent influence on all-cause mortality in patients with CHF after implantation of cardiac electronic devices.
P5442The non-steroidal mineralocorticoid receptor antagonist finerenone prevents structural cardiac remodeling
Authors: Lavall D , Jacobs N , Mahfoud F , Kolkhof P , Boehm M , Laufs U
Published: October 2019

Background

Mineralocorticoid receptor (MR) signaling mediates cardiac fibrosis. We studied the ability of the non-steroidal MR antagonist finerenone to prevent fibrotic remodeling.

Methods and results

In neonatal rat cardiac fibroblasts, finerenone prevented aldosterone-induced nuclear MR translocation. Treatment with finerenone decreased the expression of connective tissue growth factor (CTGF) (74±15% of control, p=0.005) and prevented aldosterone-induced upregulation of CTGF and lysyl oxidase (LOX) completely. Transforming growth factor β (TGF-β) upregulation induced through the Rac1 GTPase activator L-buthionine sulfoximine was attenuated by finerenone.

Transgenic mice with cardiac-specific overexpression of Rac1 (RacET) showed increased left ventricular (LV) end-diastolic (63.7±8.0 vs. 93.8±25.6μl, p=0.027) and end-systolic (28.0±4.0 vs. 49.5±16.7μl, p=0.014) volumes compared to wild-type FVBN control mice. Treatment of RacET mice with 100ppm finerenone over 5 months prevented LV dilatation. Systolic and diastolic LV function was similarly preserved in the three groups. RacET mice exhibited overactivation of MR and 11β hydroxysteroid dehydrogenase type 2. Both effects were reduced by finerenone (reduction about 36%, p=0.030, and 40%, p=0.032, respectively). RacET mice demonstrated overexpression of TGF-β, CTGF, LOX as well as collagen and myocardial fibrosis in the left ventricle. In contrast, expression of these parameters did not differ between finerenone-treated RacET and control mice. Finerenone prevented left atrial dilatation (6.4±1.5 vs. 4.7±1.4mg, p=0.004) and left atrial fibrosis (17.8±3.1 vs. 12.8±3.1%, p=0.046) compared to vehicle-treated RacET mice. The prevalence of atrial arrhythmias at 5 months did not differ between finerenone- and vehicle-treated RacET mice.

Conclusion

Finerenone prevented from MR-mediated structural remodeling in cardiac fibroblasts and in RacET mice. These data demonstrate anti-fibrotic myocardial properties of finerenone.
P5454PCSK9 as a predictor of cardiovascular events in atrial fibrillation: role of platelet activation
Authors: Carnevale R , Cammisotto V , Nocella C , Bartimoccia S , Pastori D , Violi F , Pignatelli P
Published: October 2019

Background

High circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) were shown to be predictive of cardiovascular events (CVEs) in patients with atrial fibrillation (AF). Because high PCSK9 plasma levels were significantly correlated with 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation, it is conceivable to hypothesize a direct effect of PCSK9 on platelet activation but the mechanism is still unclear.

Purpose

We evaluated the association between PCSK9 and platelet activation in FA patients and investigate the possible molecular mechanism involved.

Methods

According to our previous prospective study, we conducted a post-hoc analysis including 50 patients with baseline PCSK9 below and 50 above the median value of 1200pg/ml. The two groups were balanced for age and sex. In vivo platelet activation was assessed by aggregation (PA), recruitment, plasma thromboxane B2 (TxB2) formation and sPselectin levels. As markers of oxidative stress we used sNox2-dp, H2O2 production, urinary isoprostanes and oxLDL. To asses the role of PCSK9 in platelet activation, we performed an in vitro study with platelets from healthy subjects (n=5) added with PCSK9 concentrations achievable in human circulation (1000pg/ml and 2000pg/ml) measuring PA, TxB2, isoprostanes production, Nox2 activation, H2O2 production, oxLDL, p38, p47 and PLA2 phosphorylation.

Results

We observed an increased of platelet activation and oxidative stress in patients with PCSK9 levels above median (1200pg/ml) compared to those below (p<0.05). A significant correlation between plasma levels of PCSK9 and markers of platelet activation and markers of oxidative stress were found. In vitro study demonstrated that PCSK9, at the concentration similar to that of patients with CVEs, was able to increase platelet activation act by binding oxLDL receptor. PCSK9 dependent platelet activation is mediated by p47 phosphorylation, a key step in Nox2 activation and is mediated by the PLA2 phosporylation.

Conclusions

PCSK9, at concentration achievable in patients with CVEs, increased platelet aggregation via oxLDL receptor with a pathway involving Nox2 activation.
P5457Assessment of carotid cross sectional area in hypertensive patients: phenotyping and prognostic validation in the campania salute network
Authors: Mancusi C , Izzo R , Losi M A , Barbato E , Trimarco V , Morisco C , Canciello G , Manzi M V , Rozza F , De Luca N , De Simone G , Trimarco B
Published: October 2019

Background

Increased intima media thickness (IMT) of common carotid artery (CA) is considered the hallmark of vascular hypertension-mediated target organ damage, even though vessel remodeling due to mechanical stress can be accompanied also by changes in diameter.

Purpose

We developed a method computing both diameter and IMT of CA, and assessed correlates and prognostic impact of carotid cross sectional area (CCSA) in a large registry of treated hypertensive patients.

Methods

We selected 7049 hypertensive patients of the Campania Salute Network registry free of overt cardiovascular (CV) disease and with available CA ultrasound (54±11 yrs; 57% male). CCSA was computed as:

π × [((CA diameter + 2 × (mean IMT)) / 2)]2 − π × [((CA diameter) / 2)]2.

Results

CCSA was considered high if >90th percentile of the sex-specific distribution (>48 mm2 in men and >41 mm2 in women). Higher CCSA correlated with older age, male sex, higher pulse pressure (PP), higher total and LDL cholesterol and presence of diabetes (p<0.01 for all). During a median follow-up of 45 months (IQR 19–92), 324 incident composite major and minor CV events occurred. In Cox regression analysis high CCSA was associated with more than 100% increased risk of incident CV events (p<0.0001, figure), independently of the effect of older age, male sex, PP>60mmHg, presence of left ventricular hypertrophy (LVH), carotid plaque (CP), and less anti-RAS therapy (p<0.05 for all).

Conclusions

In treated hypertensive patients, increased CCSA is associated with worse metabolic and lipid profile and predict incident CV events, independently of high PP, presence of LVH and CP.
P5480Impact of Silent Myocardial Ischemia on One Year Mortality after Successful Coronary Intervention: Data from Japanese Multicenter (KICS) Registry
Authors: Motozato K , Sakamoto K , Nakao K , Fujimoto K , Miyao Y , Shimomura H , Tsunoda R , Sato R , Nagamatsu S , Yamashita T , Kaikita K , Tsujita K
Published: October 2019

Introduction

Under the awareness of appropriate use criteria, the significance of PCI for the patients with silent myocardial ischemia (SMI) decreases. On the other hand, the prognoses of SMI patients have been reported to be equivalent to those of symptomatic effort angina pectoris (EAP) patients. We aimed to clarify the prognosis of SMI after PCI and elucidate the factors influencing the mortality.

Methods

The Kumamoto Intervention Conference Study is multicenter registry enrolling consecutive patients undergoing PCI in 16 centers in Japan. Overall, 17,688 consecutive patients were enrolled during April 2008 to March 2017. To compare the clinical events between SMI and EAP, 8,278 subjects, excluding acute coronary syndrome, post successful PCI were enrolled with 1-year follow-up data.

Results

In this study, 2,071 patients were classified as SMI and 6,207 patients were EAP. Male, lower body mass index (BMI), diabetes, chronic kidney disease (CKD), smoking habits, prior myocardial infarction (MI), composite of cerebrovascular disease and composite of peripheral arterial disease were all significantly higher in the SMI group. Although nonfatal MI and stent thrombosisduring 12-monthswere comparable between the 2 groups, all-cause mortality and cardiac death during 12-months were significantly higher in the SMI group than in the EAP group (3.9% vs 1.8%, p<0.001, 1.4% vs 0.5%, p<0.001, respectively). On the other hand, Repeat Revascularization rate during 12-months was significantly lower in the SMI group than in the EAP group (15.7% vs 19.5%, p<0.001).Kaplan-Meier analysis for cardiac death showed a significant difference between the 2 groups (Figure). In a multiple logistic regression analysis, in addition to lower BMI and CKD, SMI was an independent predictor for cardiac death. Even after adjustment by propensity-score matching with predictive factors for cardiac event, SMI showed a higher cardiac death rate compared with EAP (1.4% vs 0.5%, p=0.004), and it remained as a significant predictor.

Conclusion

In this study, SMI itself was associated with higher mortality after PCI. Strict follow-up and assessment of residual ischemia should be necessary for SMI patients.
P5499Coronary angioplasty for octogenarian acute coronary syndrome patients? Is it worth it?
Authors: Vila Cha Vaz Saleiro C , Campos D , Teixeira R , Lopes J , Sousa J P , Puga L , Ribeiro J M , Lourenco C , Costa M , Goncalves L
Published: October 2019

Background

As the population ages, doctors are being challenged by the decision to offer intervention treatment in increasingly older and fragile patients. The comorbidity burden and performance status should be considered when making the decision.

Purpose

To assess the impact of optimal medical therapy (OMT) versus percutaneous coronary intervention (PCI) in non-ST elevation acute coronary syndrome (ACS) patients older than 80 years.

Methods

182 patients older than 80 years old admitted to a single coronary care unit with a diagnosis of non-ST elevation ACS, who survived hospital stay were included. Clinical, laboratorial and echocardiographic data were evaluated. Two groups were created: Group A (OMT group) N=83; Group B (PCI group) N=99. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer curves and Cox regression were conducted to evaluate the impact of OMT versus PCI on the primary endpoint. The mean time of follow-up was 37±29 months.

Results

Groups were homogenous regarding gender, cardiovascular risk factors, heart failure diagnosis, left ventricular (LV) systolic function and peak troponin I. OMT group patients were older (85.1±3.7 vs 82.7±3.2 years old, P<0.01), had a higher prevalence of chronic kidney disease (CKD) (61.4% vs 46.5%, P<0.05), a lower haemoglobin (Hb) level (12.0±1.9 vs 12.6±1.7 g/dL, P<0.05) and were less likely to receive double antiplatelet therapy at discharge (80.8% vs 100%, P<0.001). 84 patients met the primary outcome. Kaplan-Meyer curves showed increased survival in the PCI group (36.5% vs 59.3%, Log Rank P<0.001 – Figure 1). Nevertheless, PCI was not associated with long-term mortality (HR 1.05, 95% CI 0.98–1.12) in a model adjusted for age, CKD, peak troponin, LV systolic function and Hb level. Only Hb (HR 0.81, 95% CI 0.73–0.93), peak troponin (HR 1.01, 95% CI 1.00–1.01) and LV function (slightly impaired [HR 1.89, 95% CI 1.03–3,48] and moderate/severely impaired [HR 1.96, 95% CI 1.14–3.36]) remained associated with the outcome.

Conclusion

Increased survival in older patients receiving PCI after a non-ST elevation ACS may be ascribed to the selection of patients with less comorbidities. This reinforces the idea it may be applied in well-fit patients regardless of age. In our elderly population, lower Hb level, peak troponin and impaired LV systolic function appear to be the main contributors to decreased survival, irrespective of intervention.
P5510High plasma sRAGE is associated with slower carotid intima media thickness progression and lower risk for first-time coronary events and mortality
Authors: Grauen Larsen H , Nilsson P M , Nilsson J , Engstrom G , Melander O , Orho-Melander M , Schiopu A
Published: October 2019

Background/Introduction

The receptor for advanced glycation end products (RAGE) and the extracellular matrix metalloproteinase inducer (EMMPRIN) are immune receptors for pro-inflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, by acting as a decoy receptor for its ligands. Whether sEMMPRIN has similar roles is unknown.

Purpose

The purpose of our study was to investigate the associations between sRAGE and sEMMPRIN in plasma and the progression of vascular disease, incident coronary events and mortality in the general population.

Methods

We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free middle aged individuals from a population-based cohort. Measurements of intima media thickness (IMT) in the common carotid artery were performed at inclusion and after a median of 16.5 years. Incident major adverse coronary events (MACE) and mortality were recorded during a follow-up period of 21 years.

Results

sRAGE was negatively correlated with the progression of carotid IMT, independently of traditional cardiovascular risk factors, kidney function and hsCRP. Additionally, sRAGE was associated with decreased risk for MACE [HR=0.91 (0.83–0.99); p=0.031] and total mortality [HR=0.92 (0.87–0.99); p=0.017] in multivariate Cox regression analyses. We found no correlations between EMMPRIN, IMT progression or prognosis.

Conclusion

We show that individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression, and a lower risk for coronary events and mortality. These findings support further research into the potential atheroprotective properties of sRAGE.

Acknowledgement/Funding

This study was supported by grants from the Swedish Research Council, Marianne and Marcus Wallenberg Foundation, Swedish Heart and Lung Foundation
P5530The low expression of circulating microRNA-19a represents an additional mortality risk in stable patients with vascular disease
Authors: Mayer O , Seidlerova J , Bruthans J , Cerna V , Pesta M
Published: October 2019

Background

Secondary prevention of atherosclerotic vascular diseases represents a cascade of procedures to reduce the risk of future fatal and non-fatal cardiovascular events. We sought to determine whether the expression of selected microRNAs influenced mortality of stable chronic cardiovascular patients.

Methods

The plasma concentrations of five selected microRNAs (miR-1, miR-19, miR-126, miR-133 and miR-223) were quantified in 826 patients (mean age 65.2 years) with stable vascular disease (6–36 months after acute coronary syndrome, coronary revascularization or first-ever ischemic stroke). All-cause and cardiovascular mortality rates were followed during our prospective study.

Results

Low expression (bottom quartile) of all five miRNAs was associated with a significant increase in five-year all-cause death, even when adjusted for conventional risk factors, treatment, raised troponin I and brain natriuretic protein levels [hazard risk ratios (HRRs) were as follows: miR-1, 1.65 (95% CI: 1.16–2.35); miR-19a, 2.27 (95% CI: 1.59–3.23); miR-126, 1.64 (95% CI: 1.15–2.33); miR-133a, 1.46 (95% CI: 1.01–2.12) and miR-223, 2.05 (95% CI: 1.45–2.91)]. Nearly similar results were found if using five-year cardiovascular mortality as the outcome. However, if entering all five miRNAs (along with other covariates) into a single regression model, only low miR-19a remained a significant mortality predictor; and only in patients with coronary artery disease [3.00 (95% CI: 1.77–5.08)], but not in post-stroke patients [1.63 (95% CI: 0.94–2.86)].

Conclusions

In stable chronic coronary artery disease patients, low miR-19a expression was associated with a substantial increase in mortality risk independently of other conventional cardiovascular risk factors.

Acknowledgement/Funding

Health Development Agency of the Czech Ministry of Health [project 17-29520A], Charles University Research Fund (PROGRES, project Q39)
P5534Causes and predictors of short, intermediate and long-term mortality in patients after PCI
Authors: Zeitouni M , Procopi N , Kerneis M , Hammoudi N , Berman E , Barthelemy O , Choussat R , Guedeney P , Braik N , Silvain J , Le Feuvre C , Helft G
Published: October 2019

Background

Causes of death after percutaneous coronary intervention (PCI) along multiple time-periods are poorly described.

Objective

To describe causes and predictors of short-term, intermediate-term, and long-term mortality after PCI.

Methods

Consecutive men and women admitted for PCI from 2008 to 2011 were prospectively included and followed-up in this cohort study. A dedicated follow-up by independent reviewers was performed to collect the outcomes and adjudicate the causes of death. A log-rank analysis was used to compare the occurrence of cardiovascular and non-cardiovascular death at 30 days, one year and up to 8 years. Last detailed cardiovascular and vital status were collected in January 2019.

Results

A total of 3524 patients including 2720 men (77.2%) and 804 women (22.8%) were followed-up for a median time of 7.0 years (IQ1: 5.4; IQ 3: 7.2). The rate of complete follow-up was 97.6%. All-cause death occurred for 30.3% (n=1070) of patients in the cohort, in a median time of 2.5 years after PCI, with a rate of 5.3 deaths per 100 patient-years. Overall, mortality was mostly related to cardiovascular causes than non-cardiovascular causes (17.7% versus 12.6%, log-rank <0.001) (Figure). This trend was strong within 30 days (4.7% vs. 0.3%, p<0.0001) and the first year after PCI (3.1% vs. 2.2 p=0.01), but became non-significant beyond one year (9.9% vs. 10.2%, P=0.67). Of note, cancer was the major cause of non-cardiovascular death (5.6%; 1 per 100 patient-years). Diabetes (adHR = 1.48 95% [1.29–1.71], p<0.001), active smoking (adHR = 1.37, 95% [1.16–1.62]) and chronic kidney disease (adHR = 1.97, 95% [2.55–3.45], p<0.001) were the strongest risk factors for all-cause death.

Survival after PCI

Conclusions

In this long-term cohort study, cardiovascular death was more frequent than non-cardiovascular death in patients treated with PCI in the short and intermediate-term but not beyond one year. Cancer accounted for one fifth of the overall mortality.
P5547First results of TranslatiOnal Registry for CardiomyopatHies (TORCH)
Authors: Sedaghat-Hamedani F , Trebing J , Tan K , Kayvnapour E , Sluka S , Gi W T , Amr A , Weitmann K , Hoffmann W , Katus H A , Meder B
Published: October 2019

Introduction

The cardiomyopathies (CMPs) are a diverse group of cardiac disorders and leading cause of heart failure (HF) and sudden cardiac death (SCD). Clinical courses of CMPs vary considerably even between patients with the same disease entity. The TranslatiOnal Registry for CardiomyopatHies (TORCH) is a comprehensive CMP registry that aims to provide a database and biomaterial bank for basic science and clinical research in this field. The long-term objective of this registry is to increase the understanding of disease pathomechanisms on the way to a better risk stratification as well as identification of new diagnostic and therapeutic approaches in CMP.

Methods

TORCH is a national, prospective, and multicentre registry within the German Centre for Cardiovascular Research (DZHK), which includes 2300 consecutive patients with non-ischemic (primary and secondary) CMP in 20 centres. The minimum follow up time is one year. The DZHK-wide harmonization of datasets and eCRFs (electronic case report form) were performed to ensure a high level of data quality across different study centres.

Results

Seventy percent of the enrolled patients are male. Idiopathic/familial dilated cardiomyopathy (DCM) holds the highest prevalence with 54%, followed by inflammatory DCM/myocarditis with a prevalence of 24%. Hypertrophic cardiomyopathy (HCM) is the third-most prevalent CMP in this registry (16%). Infrequent CMPs such as left ventricular non-compaction (LVNC), arrhythmogenic right ventricular cardiomyopathies (ARVC) are also represented in TORCH with a prevalence of 4% and 2% respectively. Major clinical findings are registered in TORCH. Atrial fibrillation was present with a high prevalence among all CMPs (22%-35%). The highest prevalence of stroke or TIA at baseline was reported in patients with LVNC (15.1%) and the lowest in those with amyloidosis (3.3%). Patients with ARVC had the highest number of ICD implantation and adequate ICD therapy (56.7%, p<0.05; 47.1%, p<0.05). Preliminary data analysis showed higher frequency of therapy refractory heart failure symptoms and worse outcome in patients with familial DCM in comparison to those with inflammatory or idiopathic DCM.

Conclusion and outlook

TORCH represents one of the largest cardiomyopathy registries in Europe. The patients are comprehensively phenotyped through clinical examinations, state-of-the-art imaging modalities, as well as molecular, genetic, and epigenetic investigations. This registry can help researchers design further studies investigating new diagnostic tools or therapeutic strategies in CMPs.
P5554Follow the light - The prognostic value of late gadolinium enhancement in hypertrophic cardiomyopathy
Authors: Fortuni F , Abete R , Raineri C , Ghio S , Angelini F , Scelsi L , Turco A , Crimi G , Leonardi S , Oltrona Visconti L , De Ferrari G M
Published: October 2019

Background and aim

Hypertrophic cardiomyopathy (HCM) is a genetic based cardiomyopathy with heterogeneous phenotypic expression. Since it is one of the most common cause of sudden cardiac death (SCD) in the young different risk score have been proposed to properly identify the patients that would benefit from a primary prevention with an implantable cardioverter-defibrillator (ICD). ESC guidelines on HCM suggest to estimate the risk of SCD considering clinical and echocardiographic parameters and mention the use of cardiac magnetic resonance (CMR) only in the case of poor echo windows. The aim of the present study-level meta-analysis was to explore the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for adverse fatal events.

Methods

We searched PubMed and EMBASE for studies that investigated the prognostic value of LGE in patients with HCM. The outcomes of interest were SCD or aborted SCD, all-cause mortality and cardiovascular (CV) mortality. Random-effects Odds Ratios (ORs) were estimated using a DerSimonian-Laird method with a person-year approach. Moreover, an univariate meta-regression was performed to assess the moderator effect of mean age, LGE % of left ventricle (LV) and gender (expressed as male percentage).

Results

A total of 7 studies (n=3351) were included in the analysis. Mean follow-up was 3±0.63 years. Mean age was 47.7±14.6 years and 56.9% were male. LGE was detected in 1845 (55%) patients with a mean LGE percentage of LV of 7%. The presence of LGE was associated with an increased incidence of SCD or aborted SCD (OR 3.44; 95% CI 2.02–5.86; p<0.001- Figure), all-cause mortality (OR 1.92; 95% CI 1.31–2.81; p<0.001) and CV mortality (OR 3.16; 95% CI 1.77–5.64; p<0.001) compared with the absence of LGE at CMR. The LGE percentage of LV, mean age and gender did not have any moderator effect on the outcomes of interest. However, LGE % of LV was reported only in 4 studies and the absence of any moderator effect of this parameter could be due to a type II error.

Prognostic value of LGE for SCD

Conclusions

The presence of LGE at CMR in patients with HCM exhibited a substantial prognostic value in fatal events and, in particular, in the prediction of SCD. LGE assessment is an effective tool to stratify the arrhythmic risk in HCM. Therefore, it should be considered, especially in borderline cases, to improve the identification of HCM patients who could benefit from ICD implantation.
P5562Increased microRNA-21 gene expression levels as a biomarker of myocardial damage in acute myocarditis
Authors: Marketou M , Kontaraki J , Konstantinou J , Maragkoudakis S , Plevritaki A , Lempidakis D , Vougia D , Fragiadakis K , Kassotakis S , Theodosaki O , Vardas P , Parthenakis F
Published: October 2019

Purpose

MicroRNAs (miRs) are implicated in various cardiovascular pathologies and are promising diagnostic and therapeutic targets. miR-21 plays a critical role in the regulation of inflammation and cardiac fibrosis. In this study, we evaluated miR-21 expression levels in peripheral blood mononuclear cells from patients with acute myocarditis compared to healthy individuals and explored their diagnostic potential as predictor of myocardial damage.

Methods

We assessed the expression levels of miR-21 in 55 patients with acute myocarditis (40 men, mean age 30±12 years) and 20 healthy individuals (15 men, mean age 30±9 years). Blood samples were taken on admission and miR-21 expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Plasma high sensitive troponine (TnI) was measured by immunoassay and a value above the laboratory reference range (11.6 pg/ml) was considered elevated.

Results

Myocarditis patients showed significantly higher troponine levels compared to healthy individuals (256.59±94.9 versus 11.9±9.01, p<0.001). miR-21 expression levels in peripheral blood mononuclear cells were significantly elevated in the myocarditis group compared to the control group (47.01±18.3 versus 3.8±2.2, p=0.02). In addition, miR-21 expression levels in peripheral blood mononuclear cells revealed a significant correlation with troponine levels in those patients (r=0.55, p<0.001)

Conclusions

Our data reveal that miR-21 is upregulated in peripheral blood mononuclear cells from patients with acute myocarditis relative to healthy individuals and is significantly correlated with myocardial damage in those patients. Our findings indicate that miR-21 may be involved in the pathophysiology of myocarditis and represent promising biomarker in the disease.
P5580Stroke volume an echocardiographic prognostic marker in patients with high gradient aortic stenosis undergoing transcatheter aortic valve implantation (TAVI)
Authors: Alkhalil M , Brennan P B , McQuillan C M , Jeganathan R J , Manoharan G M , Owens C O , Spence M S
Published: October 2019

Background

TAVI is currently being evaluated in patients with low surgical risk. Better characterisation of aortic stenosis to reflect the disease process is needed to more precisely identify those who are at increased risk. Indexed stroke volume (SVi) is an echocardiographic measurement that is used for low gradient aortic stenosis.

Purpose

We studied whether (SVi) is a high-risk marker in high gradient aortic stenosis patients and whether SVi is related to other clinical factors contributing to this risk.

Methods

699 consecutive patients who underwent TAVI were screened, and only patients with high gradient aortic stenosis were included. A 35 ml/m2 cut-off for SVi was used to define patients with high versus low flow. The primary endpoint was defined as a combination of cardiovascular death and re-admission to hospital with heart failure at 30 days.

Results

Of the 390 patients with high gradient severe aortic stenosis, 168 (43%) had low flow. They had higher NTproBNP [2578 (1043–5480) vs. 1714 (821–3599) ng/L, P=0.005], and smaller indexed valve area [0.28 (0.23–0.36) vs. 0.35 (0.29–0.42) cm2/m2, P<0.001]. The primary endpoint was significantly more frequent in low flow compared to high flow patients [8.92% vs. 3.60%, HR 2.54 (95% CI 1.08 to 5.98), P=0.034] (Figure). This was driven mainly by a higher incidence of cardiovascular death [7 (4.2% vs. 0 (0%), P=0.003].

Previous myocardial infarction, CAD, AF, LV impairment, logistic Euroscore, in addition, to low flow were all predictors of 30 days clinical outcomes in an unadjusted model. When all these factors were included in the same adjusted model, only low flow appear to be a predictor of clinical outcomes (HR 2.43, 95% CI 0.86 to 6.64, P=0.08), although this did not reach statistical significance (Table).

Unadjusted and adjusted predictors of 30 HR (unadjusted) 95% CI P value HR (adjusted) 95% CI P value Low flow 2.54 1.08, 5.98 0.03 2.43 0.86, 6.64 0.08 Previous MI 2.55 1.08, 6.01 0.03 1.88 0.65, 5.45 0.24 AF 2.47 1.09, 5.60 0.03 2.11 0.81, 5.47 0.13 Severe LV impairment 4.68 1.10, 19.96 0.04 1.55 0.20, 12.23 0.68 CAD 2.69 1.16, 6.21 0.02 1.61 0.57, 4.51 0.37 Logistic Euro score 1.04 1.01, 1.07 0.02 1.01 0.98, 1.05 0.47

Conclusions

SVi can further characterise patients with high gradient aortic stenosis and may help to identify those who are at increased risk following TAVI.