bluuebunny/crossref_metadata_2025 huggingface dataset:
P5981Impact of radiotherapy on myocardial function and paravalvular leaks after transcatheter aortic valve implantation (TAVI)
Authors: Cicenia M , Marchetta S , Dulgheru R , Ilardi F , Bouziane M , Cimino S , Mancone M , Fedele F , Lancellotti P
Published: October 2019

Introduction

Thanks to the anticancer therapies, the life expectancy of the oncologic patients has noticeably increased, but several cardiac diseases can be observed in these patients as the result of the cardiotoxic effects.

Purpose

To investigate the impact of radiotherapy on the clinical and echocardiographic outcomes, in patients with severe aortic stenosis (AS) and preserved left ventricle ejection fraction (LVEF) treated with transcatheter aortic valve implantation (TAVI).

Methods

We recruited patients with severe AS and left ventricular ejection fraction (LVEF) ≥50‰ treated with TAVI and who received prior radiotheraphy. Patients with LVEF <50‰, treated with valve in valve, with inadequate acoustic windows or the absence of echocardiographic images pre-TAVI and after 3–6 months were excluded. Demographic, clinical and echocardiographic data were recorded.

Results

102 patients were included in the present analysis. They were divided in two groups: 19 (18‰) with an oncologic history treated with previous left thoracic/mediastinal radiotherapy and 83 (82‰) patients without an oncologic history. The two groups were homogeneous in terms of demographic and clinical data, brain natriuretic peptide (BNP), echocardiographic data pre-TAVI. They only differed for a greater prevalence of mitral stenosis and calcifications in the oncologic patients versus the non-oncologics (respectively 36‰ vs. 12‰ p=0,016; 73‰ vs. 29‰ p=0,001). No differences in terms of in-hospital clinical outcomes were observed. The echocardiographic evaluation in both groups showed a significant decrease of the peak velocities and of the transprosthetic gradients. There was a higher incidence of at least moderate degree paraprosthetic leaks in the oncologic group vs. the non-oncologic one: 6 (31‰ total leaks, 37‰ leaks >2+) vs. 7 (8‰ total leaks, 12‰ leaks >2+); p=0.029. After 3–6 months, there was not a statistically significant improvement of ejection fraction (EF) in neither of the two groups but there was a statistically significant improvement of transmural, subepicardial and subendocardial longitudinal strain values in the non-oncologic group compared to pre-TAVI values, respectively −19±4 vs. −17±4 (p<0.001); −17±3 vs. −15±3 (p<0.001); −22±4 vs. −19.8±4 (p<0.001). Any statistically significant improvement was detected in the group with history of anticancer treatments between the longitudinal strain values post and pre-TAVI (−18±3‰ vs. −16±3‰; −14±3‰ vs. −20±5‰; −20 ±± 5‰ vs. −19±4‰).

Conclusions

Patients affected by severe AS treated with TAVI and who received received prior radiotheraphy, showed the absence of statistically significant improvement of multilayer strain values, at 3–6 months after TAVI. Oncologic patients also had a higher incidence of haemodynamically relevant paravalvular leaks after the intervention, compared to the non-oncologic patients.
P5992Why aortic valve disease may persist after surgery? A joint basic science - Clinical effort
Authors: Petersen J , Kloth B , Grammatika-Pavlidou N , Eschenhagen T , Reichenspurner H , Nikolaev V O , Christ T , Molina C E , Girdauskas E
Published: October 2019

Background

Diseases of the aortic valve are a common reason for heart surgery. Aortic stenosis (AS) is associated with pressure and aortic regurgitation (AR) with a volume overload of the left ventricle (LV). Over time both pathologies lead to systolic and diastolic heart failure, while progressive downregulation of β-adrenoceptors occurs. While LV re-remodeling occurs in the majority of patients after aortic valve surgery, LV dysfunction persists in one fourth of such patients and leads to a terminal heart failure. We aimed to investigate whether differential remodeling in the protein kinase A (PKA) dependent inotropic response in myocytes and myocardial tissue obtained from patients undergoing aortic valve surgery is associated with the LV re-remodeling after surgery.

Methods

Preoperatively, pro BNP levels were measured and left ventricular strain analysis via echocardiography was performed. Interventricular septal biopsy was obtained intraoperatively in 10 patients who underwent aortic valve surgery. In-vitro contractility was analyzed in myocardial tissue paced with 4 Hz at 37 °C. Freshly isolated cells were transduced with an adenovirus expressing a cytosolic Förster resonance energy transfer (FRET) based cAMP biosensor (Epac1-camps). After 48 hours of culture, Föster-resonance energy transfer (FRET) was used for the first time to measure cAMP in 60 isolated human ventricular myocytes. Isoprenaline (10 nM – 10 μM) was used for β-adrenoceptor activation and forskolin (10 μmol) to activate adenylyl cyclase directly.

Results

We found a significantly downregulated β-adrenergic sensitivity in cardiomyocytes of patients with aortic valve disease, although contractile response to forskolin was maintained. Furthermore, we found a clear association between reduced sensitivity to isoprenaline (i.e., high EC50 values) and low maximum effect size to isoprenaline in myocardial tissue of patients with aortic valve disease, pointing out relevant β-adrenoceptor dysfunction. There were no significant differences in basal myocardial force between tissue samples of patients with AR and AS.

Conclusion

Collectively, our data show a profound remodelling in the cAMP/PKA pathway in patients with aortic valve disease. These disturbances may have an impact on the postoperative ventricular function and possibly on the long-term LV re-remodelling after aortic valve surgery.
P6001Inflammation, coronary microvascular function and diastolic function - Is there a link?
Authors: Suhrs H E , Schroder J , Bove K B , Mygind N D , Frestad D , Michelsen M M , Lange T , Gustafsson I , Kastrup J , Prescott E
Published: October 2019

Background

It has been proposed that multiple comorbidities including diabetes, hypertension and dyslipidemia contribute to a pro-inflammatory state that induces oxidative stress in the microvascular endothelium, leading to coronary microvascular dysfunction (CMD) and cardiac diastolic dysfunction.

Purpose

We tested the hypothesis that subclinical inflammation is an underlying cause of both CMD and diastolic dysfunction and that the effect of inflammation on diastolic function is partly mediated by CMD.

Methods

In a cross-sectional study design, we included women with angina but no flow limiting coronary artery stenosis (180 with diabetes, 156 without diabetes) and 95 asymptomatic controls. Blood samples were analysed for 91 mainly inflammatory cardiovascular biomarkers. Coronary microvascular function was assessed as coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography. Correlation of each biomarker with CFVR and E/e' as a marker of diastolic function, was examined by age adjusted linear regression and mediation analysis was conducted to assess if any effect of inflammation on E/e' was mediated by impaired CFVR.

Results

CFVR was lowest in patients with diabetes and highest in controls and, conversely, E/e' was highest in patients with diabetes (both test for trend p<0.001). Of the 91 biomarkers, 29 had a significant negative correlation with CFVR, 26 had a significant positive correlation with E/e' and 14 were associated with both CFVR and E/e'. CFVR and E/e' were correlated in a subgroup of patients with more pronounced CMD and higher E/e' (p=0.012) but not in the total population (p=0.818). A mediation analysis did not indicate that any effect of inflammation on E/e' was mediated by impaired CFVR.

Population charachteristics compared across groups with trend test (unadjusted linear regression) Diabetes (n=180) No diabetes (n=156) Control (n=95) p for trend Age, mean (min, max) 64 (36,80) 62 (32,80) 61 (32,81)* 0.003 BMI, mean (min, max) 30.7 (15.2, 45.5) 26.1 (18.6,40.0)* 24.7 (18.6,38.4)* <0.001 Hypertension, n (%) 133 (75%) 85 (55%)* 15 (18%)* <0.001 CFVR, median (IQR) 2.22 (1.90, 2.56) 2.35 (1.96, 2.74) 2.63 (2.22, 3.08)* <0.001 E/e' ratio, median (IQR) 9.79 (8.14, 12.21) 8.07 (6.85, 9.95)* 7.86 (6.89, 9.58)* <0.001 *p<0.005 compared with the diabetes group. BMI: body mass index; CFVR: coronary flow velocity reserve.

Generic directed acyclic graph

Conclusion

This is the first study to link a large number of mainly inflammatory biomarkers to CMD and diastolic dysfunction in patients suspected of microvascular angina. Direct association between CMD and diastolic function was only seen in those with impaired CFVR and poorest diastolic function.

Acknowledgement/Funding

The Danish Council for Independent Research and the Danish Heart Foundation
P6002Impaired peripheral endothelial function is associated with microvascular injury assessed by cardiac magnetic resonance imaging and decreased coronary flow in patients with STEMI
Authors: Van Der Hoeven N W , Janssens G N , Nap A , Everaars H , Van De Ven P M , Van Rossum A C , Escaned J , Van Leeuwen M A H , Van Royen N
Published: October 2019

Background

Microvascular injury (MVI) occurs in about 50% of successfully revascularized ST-elevation myocardial infarction (STEMI) patients and is associated with a decreased clinical outcome. MVI results from myocardial reperfusion injury, subsequent inflammation and coronary endothelial dysfunction. A correlation between peripheral and coronary endothelial function has been suggested and peripheral endothelial dysfunction is associated with the occurrence of cardiovascular events. Therefore we hypothesize a relation between peripheral and coronary endothelial function.

Purpose

The primary aim of our study was to assess the relationship between peripheral endothelial function and microvascular injury in successfully resvascularized STEMI patients.

Methods

Peripheral endothelial function and laboratory values were measured in the acute and stable setting (at 1 year follow-up). Reactive hyperemia-pulse amplitude tomography on the index finger was used to assess peripheral endothelial function by means of the reactive hyperemia index (LnRHI). After revascularization of the culprit vessel, we measured intracoronary coronary flow reserve (CFR). Cardiac magnetic resonance imaging (CMR) at day 5 evaluated the occurrence of MVI defined as microvascular obstruction (MVO) or intramyocardial hemorrhage. Myocardial salvage index (MSI) was calculated as (area at risk − final infarct size) / area at risk.

Results

We included 110 STEMI patients with the age of 60.1±9.5 years. Acute LnRHI was 0.56±0.33 and stable LnRHI was 0.64±0.27 (p=0.070). In the acute setting, LnRHI was impaired in patients with MVI compared to patients without MVI (0.44±0.37 vs. 0.61±0.34, p=0.045). The quantity of MVO (in grams) correlated with acute LnRHI (rho=-0.24, p=0.028). Acute LnRHI correlated to CFR in the revascularized culprit vessel (rho=0.25, p=0.015). In patients with decreased coronary blood flow after successful revascularization (TIMI-flow≤2), stable LnRHI was decreased (0.51±0.36 vs. 0.67±0.24, p=0.019). Stable LnRHI correlated to MSI (rho=0.28, p=0.020). Acute LnRHI correlated to leukocyte count (rho=-0.21, p=0.028) and LDH (rho=-0.25, p=0.018). LnRHI was impaired in patients who were hospitalized during 1 year follow-up (0.45±0.35 vs. 0.66±0.25, p=0.024).

Conclusion(s)

In patients with successfully revascularized STEMI, impaired peripheral endothelial function is associated with microvascular injury, decreased coronary flow and an increased inflammatory status. Furthermore, impaired peripheral endothelial function was associated with the occurrence of clinical events.
P6010Deficiency in milk fat globule-epidermal growth factor 8 delays thrombus resolution
Authors: Hofbauer T M , Alimohammadi A , Altmann J , Sharma S , Ondracek A S , Sadushi-Kolici R , Seidl V , Mangold A , Lang I M
Published: October 2019

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the obstruction of pulmonary vessels by organized thrombotic and fibrotic lesions. Efferocytosis refers to the engulfment of apoptotic cells (ACs) by phagocytes, a process that is facilitated by bridging proteins. Milk fat globule-epidermal growth factor 8 (MFG-E8) connects phosphatidylserine on ACs with integrin alpha-v beta-III on phagocytes. MFG-E8-deficient mice develop auto-immune disease closely resembling systemic lupus erythematosus. In humans, decreased MFG-E8 levels were observed in patients with coronary heart disease and chronic obstructive pulmonary disease. Whether defective efferocytosis is involved in failure to resolve thrombi in CTEPH remains unknown.

Purpose

We aimed to assess whether deficiency in MFG-E8 is responsible for of chronic non-resolving thrombosis in CTEPH.

Methods

We employed a murine model of chronic thrombosis by inferior vena cava ligation, in MFG-E8 knockout (KO) or wild-type (WT) mice to assess thrombus formation and resolution. Thrombus size at days 3, 7, 14 and 28 after ligation was assessed using either histologic trichrome stainings (n=4–13 per group and time point) or in vivo high-frequency ultrasound (n=10 per group and time point). We furthermore recruited CTEPH patients (n=60, 53% female, mean age 56±11 years) and sex- and age-matched healthy controls for measurement of MFG-E8 plasma levels using ELISA. In CTEPH patients, hemodynamic measurements were performed. Human lung specimens harvested during surgery for CTEPH or from healthy controls, and isolated monocytes from whole blood of CTEPH patients or controls were analyzed using RT-qPCR.

Results

We observed substantially increased thrombus volume in MFG-E8 KO mice compared to WT, which persisted until day 14 after ligation. In human CTEPH patients, MFG-E8 in plasma was increased compared to healthy controls. Similarly, CTEPH monocytes displayed higher concentrations of MFG-E8 mRNA. Conversely, MFG-E8 expression of CTEPH pulmonary artery specimens was downregulated. No correlations between MFG-E8 levels and hemodynamic parameters were observed.

Conclusion

MFG-E8 plays an important role in thrombus resolution. In CTEPH, dysregulation of efferocytosis via impaired MFG-E8 expression in the pulmonary arteries, might drive persistence of thrombus in pulmonary arteries. The absence of a correlation between MFG-E8 and hemodynamic measures argues against pressure as a confounder of the observation.
P6012Active selexipag metabolite MRE-269 increases endothelin receptors in pulmonary artery smooth muscle cells
Authors: Maruyama H , Sakai S , Ieda M
Published: October 2019

Background

The pathology of pulmonary arterial hypertension (PAH) indicates the abnormal outgrowth of pulmonary artery smooth muscle cells (PASMCs) of the media. Abundant expression of endothelin 1 (ET-1) is observed in vessels of PAH, and has been considered to play a pathogenic role. There are several endothelin receptors including ETA, ETB. Compared to ETA, ETB mRNA is less expressed in PASMCs from control individuals, and is reported to be increased in those from PAH patients. However, how ETB is involved in PAH remains unclear. Selexipag, a non-prostanoid IP receptor agonist, was recently authorized for treating PAH. Compared to selexipag, the active metabolite MRE-269 has a higher affinity for the IP receptor. Initial combination therapy come to be accepted as a standard strategy for this disease, although the interaction of each drug has not been discussed enough.

Purpose

To assess the effect of selexipag on ET-1 receptors in PASMCs.

Methods

We stimulated purchased human PASMCs and endothelial cells by MRE-269 (300 nM), ET-1 (100 nM) or combination of them in vitro. Quantitative PCR was performed to quantify mRNA expressions. Cell proliferation was assessed by CCK8 cell proliferation assay kit. BQ123, A192621, bosentan was used as blocker against ETA, ETB, or both, respectively.

Results

In PASMCs, MRE-269 increased ETA and ETB expressions 2- and 7-fold, respectively. On the other hand, it increased ETB 1.2-fold in pulmonary artery endothelial cells; ETA was not detected in those cells. After pretreatment by MRE-269, ET-1 accelerated the proliferation of PASMCs. A192621 and bosentan abrogated this proliferation. In contrast, BQ123 did not abrogate it.

Conclusions

In PASMCs, active selexipag metabolite MRE-269 increases ETB more strongly than ETA, resulting in accelerated cell proliferation by ET-1 predominantly via ETB. These data call for further study focused on the choice of ET-1 receptor antagonists in the case of combination therapy with selexipag.
P6015Histological pattern of penetrating His bundle division: implications for atrioventricular conduction damage during and following transcatheter aortic valve implantation
Authors: Cabrera J A , Porta-Sanchez A , Nunez Pernas D , Rubio J M , Navarro F , Salvador-Montanes O , Macias Y , Nevado-Medina J , Sanchez-Quintana D
Published: October 2019

Background

Severe damage to the atrioventricular conduction system is one of the most common complications of transcatheter aortic valve implantation (TAVI) and can be linked to important comorbidity, increased healthcare expense, need for long-term monitoring and pacemaker implantation.

Purpose

To provide a detailed description of the His bundle (HB) arrangement within the left ventricular outflow tract.

Methods

We examined by dissection techniques and histological sections the course of the AV conduction axis (penetrating, non-branching and branching HB) in relation with the membranous and muscular interventricular septum in 57 structurally normal human heart specimens (48 males, 77±7 years)

Results

The AV conduction axis is located along the inferior edge of the membranous septum (MS). The MS is divided into AV and interventricular components and is located at the base of the interleaflet triangle between the right and non-coronary leaflets of the aortic valve. The conduction axis enters the AV component of the MS and is encircled by the fibrous tissue of the central fibrous body to reach the left ventricular outflow tract. The MS showed in cadaveric hearts variable dimensions in length (4.6±1.5 mm) with a range bewteen 1 to 9mm. In 17.5% of specimens the MS length was ≤2 mm. After penetrating the AV membranous septum it has a non-branching component that in 85.5% of cases runs only for a short distance (1–3 mm) along the septal crest before giving rise to the fascicles of the left bundle (LB) on the septal surface (Type A). The most anterior fibers of the LB originate at the end of the branching portion located underneath the inferior edge of the MS. In 5 hearts (9%) the HB division was found before it reached the interventricular MS (Type B) and in 3 cases (5.5%)2–3.5 mm distal to the crest (Type C). 22 hearts (49%) were shown to have a relatively left-sided deviation of the AV bundle with the anterior part of the bundle closely related to the nadir of attachment of the right coronary leaflet of the aortic valve. In the remaining 51% of hearts, the bundle coursed centrally or with a right-sided deviation. The HB measures were (mm, mean±SD (range)): length: 3±0.6 (2–4.5), width: 3.7±1.4 (2.5–5.6), thickness: 1.4±0.5 (0.5–2.2), HB to endocardium: 0.7±0.3 (0.2–1.5).

His bundle position types

Conclusions

A shorter membranous septum length, the variable HB dimensions and the left-sided deviation of the AV conduction axis are extremely relevant anatomic features that are linked to the frequent injury to the HB branch or complete AV block following TAVI.
P6135Improving detection of AF: insights from real world screening programme
Authors: Khan S , Butt H , Khokhar A , Orlowski A , Porter B , Unger-Graeber B , Khan S
Published: October 2019

Background

AF related stroke places a significant burden on individuals, carers and health and social care systems. The observed prevalence of AF in populations is often lower than expected and this results in high rates of AF diagnosis at the time of the stroke event. Opportunistic screening for AF in at risk populations is recommended by ESC, however, is often missed due to time constraints and lack of expertise. Technological advancements such as m-health ECG monitors can aid in the diagnosis of AF with improvements in timely risk assessment and initiation of protective anticoagulation.

Purpose

The purpose of this study was to determine whether introduction of a suite of m-health tools including electronic patient record based tools and smart phone based ECG recording could improve the rates of AF detection and subsequently reduce the rate of AF related strokes.

Methods

The study was conducted in a city region with a population of around 300 000, served by 48 primary care practices. The project involved a three staged approach; education and support for primary care staff, creating an “at-risk” register on primary care electronic patient record for those over 60 or with relevant co-morbidities associated with electronic prompts for screening and a standardized assessment template and the roll-out of smart phone based single-lead ECG monitors to facilitate rhythm checks. The population was followed over a 4 year period to monitor rates of AF diagnosis, anticoagulation and stroke rates.

Results

The study population were male (53%), aged between 30–39 (22.4%) and were of white ethnicity (40%). At baseline, in 2014, the prevalence of AF was 0.89% (2492 individuals). By 2018, this had increased to 1.1% (3328 individuals) with on average 40 new diagnoses of AF compared to 26 in the baseline period (see figure).Anticoagulation prescription within 30 days of diagnosis increased from 29.80% to 50.00% whilst prescription of antiplatelet monotherapy within same time period decreased from 12.73% to 6.4%. This was also associated with a reduction in the proportion of strokes seen in the population secondary to AF with 35% (n=143) of strokes secondary to AF in 2014 and 25% (n=127) secondary to AF in 2017.

Conclusion

The study found that implementation of a screening programme across a wide range of primary care practices led to an improvement in AF diagnosis, management and timeliness of care. This highlights the benefit of using simple methods such as GP educations in conjunction with new technology device to detect AF more effectively and subsequently treat in an appropriate and time-effective fashion. In our population this appears to be associated with real reductions in AF related strokes

Acknowledgement/Funding

CLAHRC NWL, NHS Hounslow CCG, Pfizer
P6140Health education program at the “happy life, healthy heart” school: a randomized clinical trial
Authors: Alievi Mari M , Santin Dal Ri C , Portal Teixeira P , Campos Pellanda L
Published: October 2019

Background

School interventions based on playful activities are good strategies to provide health knowledge to children, impacting on healthy habits and potentiating the prevention of cardiovascular diseases.

Purpose

To verify whether classroom intervention for cardiovascular health prevention increases the health knowledge of schoolchildren and makes behavioral changes in the lifestyle of teachers and students.

Methods

The study was placed in ten public schools of Frederico Westphalen, a city in the south of Brazil, where students from the 1st to 5th grade of elementary school aged 6 to 12 years and 32 teachers were recruited. Randomized clinical trial which examined the effects of an intervention with teachers and students on their health knowledge. Subjects such as cardiovascular health, nutrition and physical activity (PA) were broached with the teachers undergoing training and with students in classroom by the teachers themselves. Nutritional status of schoolchildren was evaluated by weight, height and z-score, level of PA and food consumption by DAFA questionnaire and health knowledge by CARDIOKIDS. Socio-demographic, nutrition and physical activity data of the teachers were evaluated by semi-structured questionnaire.

Results

A total of 473 students were evaluated, 211 (44.6%) in the Control Group (8.8±1.5 years, 57.3% girls) and 262 (55.4%) in the Intervention Group (8.5±1.6 years, 51.1% boys). 32 teachers were also divided into CG (CGt), 43.8% (n=14, Age 39.2±7.7) and IG (GIt), 56.3% (n=18, Age 43.4±9.6). CARDIOKIDS demonstrated that there was no interaction effect of time and group on the level of children's knowledge (effect size = 2.293, p=0.131), indicating an improvement in both groups. In relation to food consumption, IG increased 15.2% and 19.8% the number of students who followed the recommendations of pizza/hamburger (p<0.001) and soft drinks (p<0.001) respectively. In IGt there was an increase of 27.9% in the number of teachers who started practicing PA after the intervention.

Conclusions

Both groups of students increased the level of knowledge, but only the IG changed food behavior. This change was observed by greater adherence to the Brazilian Food Guide recommendations of not consuming pizza/hamburger and soft drinks. Teachers of the IGt started to practice more physical activity.

Acknowledgement/Funding

This work will be funded by Capes and Fappic
P6151Fully automated epicardial adipose tissue volume and density measured from non-contrast CT predict major adverse cardiovascular events in asymptomatic subjects
Authors: McElhinney P , Eisenberg E , Commandeur F , Chen X , Cadet S , Goeller M , Cantu S , Miller R , Slomka P , Wong N , Rozanski A , Achenbach S , Tamarappoo B K , Berman D , Dey D
Published: October 2019

Background

Epicardial adipose tissue (EAT) volume and density has shown to correlate with standard markers of coronary artery disease (CAD) and may predict major adverse cardiovascular events (MACE).

Purpose

We aimed to evaluate the prognostic value of EAT volume and density measured by fully automated deep-learning software from non-contrast cardiac computed tomography (CT).

Methods

We assessed 2071 consecutive asymptomatic subjects (age 56±9 years, 59% male) from the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) trial with long-term follow-up after coronary artery calcium (CAC) measurement. EAT volume and mean density were quantified using automated deep-learning software from non-contrast cardiac CT. MACE was defined as myocardial infarction (MI), cardiac death, late (>90 days) revascularization and acute coronary syndrome (ACS). EAT volume and density were systematically compared to CAC score and atherosclerotic cardiovascular disease (ASCVD) risk score using Cox proportional hazards regression for MACE prediction.

Results

At 14±3 years, 217 subjects suffered MACE. In age-and-gender-adjusted multivariate analysis, ASCVD risk score, CAC (two-fold increase) and EAT volume (two-fold increase) were associated with increased risk of suffering MACE [Hazard Ratio (HR) (95% CI): 1.03 (1.01–1.04); 1.25 (1.19–1.30); and 1.36 (1.08–1.70) respectively, p<0.01 for all] (Figure); the corresponding Harrell's C-statistic was 0.76. The area-under-the curve from receiver-operator characteristic analysis for MACE prediction increased significantly from 0.69 to 0.77 (p<0.0001) when EAT volume and CAC were added to the current clinical standard (ASCVD, family history and obesity measures BMI and BSA). Both in men and women, increase in EAT volume was associated with increased risk of MACE, with HR 1.14 (1.06–1.22), p<0.001 in men vs. 1.15 (1.01–1.31), p=0.03 in women, for each 20 cubic centimeter increase in volume. EAT density (HU) was independently inversely associated with MACE [HR: 0.96 (0.93–0.99), p=0.01].

MACE Prediction

Conclusions

EAT volume and density measurements improve prediction of MACE in asymptomatic populations over the current clinical standard. Fully automated EAT volume and density quantification by deep-learning from non-contrast cardiac CT can provide additional prognostic value for the asymptomatic patient.

Acknowledgement/Funding

1R01HL133616, Forschungsstiftung Medizin Universitätsklinikum Erlangen, grant from Dr Miriam and Sheldon G. Adelson Medical Research Foundation
P6196Lipoprotein (a) and cardiovascular risk: are women at increased risk?
Authors: Santos M R , Pereira A , Mendonca F , Sousa J , Neto M , Monteiro J , Sousa A C , Freitas S , Henriques E , Ornelas I , Drumond A , Palma Dos Reis R , Mendonca M
Published: October 2019

Introduction

Coronary artery disease (CAD) is the leading cause of death worldwide, placing a major economic and resource burden on health and public health systems, so efforts are being made to accurately predict risk for major adverse cardiac events (MACE). The field of risk prediction and CAD prevention continues to evolve with the identification of novel risk factors and biomarkers, such as lipoprotein a [Lp)a]. Almost 20% of the population has elevated circulating levels of Lp(a), which is recognized as an independent risk factor for CAD, stroke, peripheral arterial disease, and aortic stenosis. Importantly, studies showed that this was particularly true for women.

Objective

To evaluate if the elevation of Lp(a) is associated with MACE in female, male or both.

Materials and methods

Case control study of 3050 subjects from the GENEMACOR study population. In female population (n=676): cases were 341 patients with at least one >75% coronary stenosis (median age 55.7±7.2) and 335 normal controls (median age 55.8±6) adjusted by age with cases. In male population (n=2374): 1278 patients with at least one >75% coronary stenosis (median age 52.7±8) and 1096 controls (median age 51.9±8) also adjusted by age. χ2 and T student tests were used to analyze the demographic, laboratorial, angiographic and anthropometric characteristics of the population. Lipoprotein (a) was determined by immunoturbidimetry. High Lp(a) level was considered if superior to 30 mg/dl. Logistic regression was used to evaluate Lp(a) as a risk factor for CAD in total, female and male populations.

Results

In female population 44.0% patients vs 21.2% controls (p<0.000) had Lp(a)>30mg/dl. In male population 39.4% patients vs 23.8% controls (p<0.000) had Lp(a)>30mg/dl. In total population Lp(a)>30mg/dl was a predictor for CAD (OR 2.24, 95% CI: 1.91–2.62, p<0.0001). Analyzing by gender, Lp(a)>30mg/dl was also a predictor for CAD either in male (OR 2.08, 95% CI: 1.74–2.5, p<0.0001) or female population (OR 2.92, 95% CI: 2.08–4.09, p<0.0001).

Conclusions

As opposed to other studies, in our population elevated Lp(a) levels (>30mg/dl) were associated with elevated CAD risk, in both men and women. We conclude that Lp(a) can be considered an independent risk factor for CAD disease in our population, and further strategies for Lp(a) reduction may indeed translate in improved outcomes in CAD disease.
P6198Lipoprotein(a) as a potential residual risk associated with coronary lipid-rich atheroma in type2 diabetic subjects with coronary artery disease who achieved lowdense lipoprotein cholesterol<1.7mmol/l
Authors: Nakamura H , Kataoka Y K , Hosoda H H , Nakashima T N , Honda S H , Fujino M F , Nakao K N , Yoneda S Y , Otsuka F O , Nishihira K N , Kanaya T K , Asaumi Y A , Noguchi T N , Yasuda S Y
Published: October 2019

Background

Type 2 diabetic patients with coronary artery disease (CAD) is a high-risk subjects who require intensive secondary preventive management. The current guideline recommends lowering LDL-C with a statin as a first-line therapy in diabetic patients with CAD. However, its anti-atherosclerotic efficacy is diminished compared to non-diabetic subjects. These suggest the need to further identify additional therapeutic target associated with diabetic atherosclerosis. Lipoprotein (a) [Lp (a)] is a plasma lipoprotein which consists of an LDL-like particle with apolipoprotein (a). While Lp (a) has been shown to associate with ASCVD, whether this lipoprotein promotes diabetic coronary atherosclerosis under LDL-C control with a statin remains to be fully elucidated.

Purpose

To investigate the relationship between Lp (a) and coronary lipidic atheroma by near-infrared spectroscopy (NIRS), which quantitatively measures lipidic burden in vivo.

Methods

Culprit lesions in 127 type 2 diabetic patients with CAD who already received a statin were evaluated by NIRS imaging. Maximum 4-mm lipid core burden index at culprit lesion (MaxLCBI4mm) was measured.

Results

High-intensity statin and ezetimibe were used in 13 and 14% of study subjects, respectively. Their on-treatment LDL-C level and Lp (a) were 2.0±0.7 mmol/l and 22.1±26.7 mg/dl. Despite these lipid lowering therapy, average MaxLCBI4mm was 419.6±248.2 and MaxLCBI4mm≥400 was observed in 49% of study subjects. Multivariate linear regression analysis demonstrated LDL-C and Lp (a) as independent determinants associated with MaxLCBI4mm (Table). Of note, in subjects who achieved LDL-C<1.8 mmol/l, an elevated Lp (a) level but not LDL-C predicts MaxLCBI4mmat culprit lesions (Table).

Multivariate linear regression analysis t p-value Entire subjects (n=127)   LDL-C 2.04 0.04   Lp (a) 2.88 <0.01 LDL-C <1.8 mmol/l (n=47)   LDL-C 0.45 0.66   Lp (a) 2.74 0.01

Conclusions

The association of Lp (a) with coronary lipid-rich atheroma even under guideline-recommended LDL-C control indictaes Lp (a) as an additional therapeutic target to further stabilize diabetic atherosclerosis.
P6211Efficacy of comprehensive Managed Care after Acute Myocardial Infarction (MC-AMI) in a long-term follow-up - preliminary experience of a single high-volume center
Authors: Wita K , Wilkosz K , Wita M , Kulach A , Wybraniec M , Polak M , Matla M , Maciejewski L , Skowerski T , Fluder J , Kalanska-Lukasik B , Gomulka S , Turski M , Szydlo K
Published: October 2019

Introduction

Despite substantial progress in the medical and interventional treatment of acute myocardial infarction (AMI), a long-term prognosis in MI survivors remains unsatisfactory. The Managed Care in Acute Myocardial Infarction (MC-AMI, KOS-zawal) is the first program of a comprehensive, supervised care for patients with AMI to improve long-term prognosis. It includes acute intervention, complex revascularization, cardiac rehabilitation (CR), outpatient follow-up, and prevention of SCD.

Purpose

To assess the effect of MC-AMI on major adverse cardiovascular and cerebrovascular events (MACCE) in 12 months follow-up.

Methods

In this single-center, retrospective observational study we enrolled 1211 patients, out of which 719 consented for participation in MC-AMI and compared them to 1130 subjects in the control group. After propensity score matching two groups of 529 subjects each were compared. Cox regression was performed to assess the effect of MC-AMI on clinical endpoints.

Results

Primarily, MC-AMI has been proved to reduce MACCE rate by 40% in a 12-month observation. Participants of MC-AMI had a higher adherence to cardiac rehabilitation (98 vs. 14%) higher rate of scheduled revascularisation (coronary artery bypass grafting: 9.8% vs. 4.9%, p<0.001; elective percutaneous coronary intervention: 3.0% vs 2.1%, p<0.05) and ICD implantation (2.8% vs. 0.6%, p<0.05) compared to control.

Multivariable Cox regression analysis revealed MC-AMI participation to be inversely associated with the occurrence MACCE at 12 months (HR=0.500, 95%Cl 0.349–0.718, p<0.001). Besides, older age, diabetes mellitus, hyperlipidemia, prior PAD, previous UA, and lower LVEF were significantly associated with the primary endpoint.

12-month FU - freedom from MACCE

Conclusions

MC-AMI is the first program of a comprehensive in-hospital and post-discharge care for AMI patients. MC-AMI improves prognosis by increasing the rate of patients undergoing CR, complete revascularization and ICD implantation, thus reducing MACCE rate by 40% in 12 months. Participation in MC-AMI is inversely related to mortality rate, recurrent MI and heart failure related hospitalization during 12 months.
P6219Can too much exercise “burn” your endothelium?
Authors: Terentes-Printzios D , Vlachopoulos C , Kardara D , Anastasakis A , Vogiatzi G , Xaplanteris P , Georgakopoulos C , Lazaros G , Tousoulis D
Published: October 2019

Background/Introduction

Regular aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is an aerobic and extremely vigorous exercise. Endothelial function and carotid subclinical atherosclerosis are independent predictors of cardiovascular risk.

Purpose

We investigated the chronic alterations of these indices in marathon runners.

Methods

We studied 30 marathon runners and 20 age- and sex-matched recreationally active control subjects. Endothelial function was evaluated with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid intima-media thickness (cIMT). All subjects completed analytical questionnaires about their medical history and training.

Results

Marathon runners had significantly higher systolic and pulse pressure compared to controls. They also had reduced body-mass index, waist to hip ratio and heart rate compared to controls (p<0.05, for all). Common cIMT was significantly lower in athletes than controls (0.56±0.11 vs. 0.63±0.07, p=0.029), while there was no difference in carotid bulb IMT between groups. FMD was higher in marathon runners compared to controls and nitrate-mediated dilatation (NMD) was similar in the two groups (9.0±3.7 vs. 6.4±1.7 and 12.6±5.7 vs. 12.3±3.4; p=0.002 and p=0.821, respectively). We also observed a reverse U-shaped curve between endothelial function and amount of exercise. (Figure)

Effect of amount of exercise on FMD

Conclusions

Our study shows, that marathon runners have higher FMD compared to controls, indicating better vascular endothelial function, and also have lower cIMT compared to controls. Increased amount of exercise training seems to abolish the beneficial effect of exercise on endothelial function. These findings provide further insights in the effects of marathon running on endothelial function and carotid atherosclerosis.
P6231Iron status and risk of cardio-metabolic diseases in European adults: a Mendelian randomization study
Authors: Gan W , Bennett D , Mahajan A , Du H , Chen Z , McCarthy M , Clarke R
Published: October 2019

Background

Observational studies have reported conflicting results about the associations of iron status with risk of cardio-metabolic diseases but such studies are constrained by confounding and reverse causality.

Purpose

To assess the causal relevance of iron status biomarkers (transferrin, serum iron, and ferritin) for risk of coronary artery diseases (CAD), ischaemic stroke (IS), and type 2 diabetes (T2D), using Mendelian randomization (MR).

Methods

Effect size estimates for genetic variants associated with iron status biomarkers were obtained from the Genetics of Iron Status consortium (transferrin saturation, serum iron, and ferritin: n=48,972). The corresponding effects of these variants on the risk of CAD, IS and T2D were obtained from a meta-analysis of unrelated participants of European ancestry in the UK Biobank (UKB), together with previously recruited participants in CARDIOGRAMplusC4D (total n=90,377 CAD cases), MEGASTROKE (total n=43,381 IS cases) and DIAGRAM (total n=74,124 T2D cases), respectively. The main analysis used a two-sample inverse-variance weighted MR, while the sensitivity analyses used weighted-median, weighted-mode, MR-PRESSO, and MR-Egger approaches.

Results

MR analysis demonstrated significant inverse association of each of the three genetically-instrumented iron status biomarker with risk of CAD (transferrin saturation OR=0.96 [95% CI: 0.92–0.99], p=0.02; serum iron OR=0.93 [0.89–0.97], p=0.001; and ferritin OR=0.86 (0.79–0.94), p=0.001, per 1 SD higher level). In contrast, these iron status biomarkers showed positive associations with risk of T2D (transferrin saturation OR=1.06 [1.01–1.11], p=0.01; serum iron OR=1.06 [0.99–1.13], p=0.07; and ferritin OR=1.12 [0.99–1.26], p=0.06, per 1 SD higher level). There was positive, but non-significant, association of IS with each of the iron status biomarker analysed. Sensitivity analyses using several different MR approaches yielded concordant results.

Conclusions

Among European adults, iron status appeared to have causal associations, but in opposite directions, with the risk of CHD and T2D. Our findings highlight the need for caution about strategies for advocating iron supplementation in individuals with normal haemoglobin levels for prevention of CAD.

Acknowledgement/Funding

British Heart Found, Medical Research Council, Wellcome Trust, NIHR Biomedical Research Centre, Oxford
P6253Electrocardiographic characteristics for prediction of irreversible fulminant hepatitis in patients with acute hepatic failure
Authors: Im S I , Park H S
Published: October 2019

Background

There was limited data about the association between the electrocardiographic characteristics and irreversible fulminant hepatitis (IFH) in patients with acute hepatic failure (AHF) in the long-term follow up.

Purpose

The aim of this study was to analysis the electrocardiographic characteristics for prediction of IFH in patients with AHF.

Methods

Our University echocardiography, electrocardiogram (ECG) and viral hepatitis database were reviewed from 2008 to 2017 to identify patients with AHF. Patients were followed for a mean 32.0±0.8 months and were analyzed to find out the predictors for IFH.

Results

Among 202 patients with AHF, 23 (11.4%) patients had IFH. In our study, there are 118 (58.7%) viral hepatitis patients (hepatitis A, 83 patients, 41.3%; hepatitis B, 19 patients, 9.5%; hepatitis C, 15 patients, 7.5%) and alcoholic hepatitis patients (83 patients, 41.3%). Based on the ROC curve, we set the corrected QT interval (QTc) cutoff value of 425 msec for prediction of IFH, which gave a sensitivity of 66.7% and a specificity of 66.0% (P=0.002). In univariate analysis, age, QTc, diabetes mellitus (DM), heavy alcoholics, labile INR, hemoglobin, albumin, total bilirubin, sodium, and c-reactive protein were significantly associated with IFH. In multivariate analysis, age, QTc, DM, heavy alcoholics, and total bilirubin were independent risk factors for IFH at the long-term follow-up.

Conclusion

Longer QTc (>425msec) in patients with AHF was associated with higher IFH, suggesting close clinical and electrocardiographic follow-up will be required.

Acknowledgement/Funding

None
P6268Cardiovascular outcomes of new anti-diabetic agents - A meta-analysis of randomized controlled trials
Authors: Lin Y , Parco C , Brockmeyer M , Karathanos A , Schulze V , Krieger T , Heinen Y , Perings S , Kelm M , Wolff G
Published: October 2019

Background and purpose

The risk of major cardiovascular events (MACE) is increased in patients with diabetes mellitus. Recently published clinical trials of three different pharmacological classes (DPP4 inhibitors (DPP4i), SGLT2-inhibitors (SGLT2i), GLP-1-receptor-antagonists (GLP1RA)) of new anti-diabetic agents (ADA) showed potential benefits for cardiovascular (CV) outcomes. We thus aimed to perform a meta-analysis of randomized controlled trials (RCTs) of these ADA to elucidate benefits on CV outcomes in diabetic patients.

Methods

Following a systematic online database search, all RCTs reporting CV outcomes of DPP4i, SGLT2i or GLP1RA vs. Placebo in diabetic patients up until December 2018 were eligible for inclusion in the meta-analysis. Studies including patients with acute coronary syndrome (ACS) were excluded. Data were abstracted and analyzed with the inverse-variance method and a random-effects model, hazard ratios (HR) with 95% confidence intervals (CI) were used as summary statistics. CV outcomes of MACE, myocardial infarction (MI), stroke, heart failure (HF), CV death and all-cause mortality were analyzed.

Results

Eleven RCTs (DPP4i: SAVOR, TECOS, CARMELINA; GLP1RA: LEADER, SUSTAIN-6, EXSCEL, Harmony; SGLT2i: EMPA-REG OUTCOME, CANVAS Program, DECLARE) with 109,316 patients were selected for inclusion. ELIXA and EXAMINE were excluded due to their inclusion of patients with ACS, CAROLINA was excluded for lack of placebo-control. In the pooled meta-analysis of all trials, ADA significantly reduced the risk for MACE (Hazard ratio (HR) 0.91, CI 0.86–0.96, p=0.0004), MI (HR 0.91, CI 0.85–0.96, p=0.02), CV death (HR 0.9, CI 0.82–0.99, P=0.02) and all-cause mortality (HR 0.92, CI 0.85–0.99, p=0.03). There was no difference in the risk for stroke (HR 0.94, CI 0.87–1.02, p=0.16) and HF (HR 0.88, CI 0.76–1.02, p=0.08). In agent-specific subgroup analyses, GLP1RA and SGLT2i showed significant reductions in MACE (GLP1RA: HR 0.85, CI 0.78–0.92, p<0.0001; SGLT2i: HR 0.89, CI 0.83–0.96, p=0.001), MI (GLP1RA: HR 0.86, CI 0.76–0.98, p=0.02; SGLT2i: HR 0.88, CI 0.79–0.97, p=0.01) and all-cause mortality (GLP1RA: HR 0.88, CI 0.81–0.95; p=0.001; SGLT2i: HR 0.83, CI 0.70–0.99; p=0.03). GLP1RA significantly reduced risk for stroke (HR 0.85, CI 0.75–0.96, p=0.008) and CV death (HR 0.86, CI 0.78–0.95, p=0.002). SGLT2I were especially effective in the reduction of risk for HF (HR 0.69, CI 0.61–0.79; p<0.0001). DPP4i inhibitors however failed to show superiority in all analyzed outcomes.

Conclusions

This meta-analysis lends evidence to GLP1RA and SGLT2i benefits for MACE, MI and all-cause mortality, while DPP4i failed to show superiority in cardiovascular outcomes. Individualized medication for diabetic patients depending on CV disease status should be considered.
P6279Mitochondria targeted catalase overexpression protects against beta-adrenergic receptor mediated cardiac remodeling in mice
Authors: Uribe E , Andersson D
Published: October 2019

Background

Beta-adrenergic receptor signaling is widely recognized as a fundamental component in the pathogenesis of chronic heart failure. However, the mechanisms behind beta-adrenergic receptor-mediated remodeling in cardiomyocytes and the myocardium are not fully understood. Oxidative stress has been proposed as a central pathophysiological mediator in cardiovascular disease and heart failure. The triggers and sources of oxidative stress in heart failure remain unclear. In this study we use mice with mitochondria-targeted overexpression of the antioxidant enzyme catalase (mCAT) to link beta-adrenergic receptor-mediated stress to mitochondrial reactive oxidative species (ROS) and the progression of heart failure.

Hypothesis

Mitochondrial ROS, induced by beta-adrenergic receptor-activation, is a mediator in the progression of the heart failure phenotype.

Methods

mCAT and wild type mice (n=10) were administered the non-selective beta-adrenergic agonist Isoprotenerol (Iso; 50mg/kg/day) through subcutaneous osmotic pumps for 3 weeks. Hearts were taken for biochemistry (western blotting, qPCR). Cardiomyocytes were isolated and loaded with Fluo-3 AM to study intracellular Ca2+ transients and fractional shortening using confocal line scan microscopy. All experiments were performed in accordance with the Stockholm ethical committee for animal research.

Results and conclusions

The WT mice displayed an increased heart/body weight ratio following chronic Iso administration. In contrast, mCAT mice displayed resistance to Iso-induced cardiac hypertrophy (p<0.05). Furthermore, chronic Iso exposure in WT mice induced increased ROS-dependent post-translational protein modifications, impaired cardiomyocyte Ca2+ handling and reduced contractility in isolated cardiomyocytes (p<0.05). Cardiomyocytes from mCAT mice did not display the deleterious effects of chronic Iso exposure on cardiomyocyte Ca2+ and contractility.

Our study demonstrates that beta-adrenergic receptor stimulation-induced remodeling of the heart, which is similar to what is seen in heart failure, can be prevented by overexpressing catalase in the mitochondria. This indicates an important role of mitochondrial ROS in the link between adrenergic signaling and the development of cardiomyopathy and heart failure.

Acknowledgement/Funding

Hjärtlungfonden