bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of visceral and general obesity on vascular and left ventricular function and geometry: a cross-sectional magnetic resonance imaging study of the UK Biobank
Authors: van Hout Max J P , Dekkers Ilona A , Westenberg Jos J M , Schalij Martin J , Scholte Arthur J H A , Lamb Hildo J
Published: October 2019

Aims 

We aimed to evaluate the associations of body fat distribution with cardiovascular function and geometry in the middle-aged general population.

Methods and results 

Four thousand five hundred and ninety participants of the UK Biobank (54% female, mean age 61.1 ± 7.2 years) underwent cardiac magnetic resonance for assessment of left ventricular (LV) parameters [end-diastolic volume (EDV), ejection fraction (EF), cardiac output (CO), and index (CI)] and magnetic resonance imaging for body composition analysis [subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)]. Body fat percentage (BF%) was assessed by bioelectrical impedance. Linear regressions were performed to assess the impact of visceral (VAT) and general (SAT and BF%) obesity on cardiac function and geometry. Visceral obesity was associated with a smaller EDV [VAT: β −1.74 (−1.15 to −2.33)], lower EF [VAT: β −0.24 (−0.12 to −0.35), SAT: β 0.02 (−0.04 to 0.08), and BF%: β 0.02 (−0.02 to 0.06)] and the strongest negative association with CI [VAT: β −0.05 (−0.06 to −0.04), SAT: β −0.02 (−0.03 to −0.01), and BF% β −0.01 (−0.013 to −0.007)]. In contrast, general obesity was associated with a larger EDV [SAT: β 1.01 (0.72–1.30), BF%: β 0.37 (0.23–0.51)] and a higher CO [SAT: β 0.06 (0.05–0.07), BF%: β 0.02 (0.01–0.03)]. In the gender-specific analysis, only men had a significant association between VAT and EF [β −0.35 (−0.19 to −0.51)].

Conclusion 

Visceral obesity was associated with a smaller LV EDV and subclinical lower LV systolic function in men, suggesting that visceral obesity might play a more important role compared to general obesity in LV remodelling.
3037The prognostic significance of grade of ischemia in patients with STEMI: a substudy of the randomized trial of primary PCI with or without routine manual thrombectomy (TOTAL trial)
Authors: Leivo J , Anttonen E , Jolly S S , Dzavik V , Koivumaki J , Tahvanainen M , Koivula K , Nikus K , Wang J , Cairns J A , Niemela K , Eskola M
Published: October 2019

Background

The importance of grade of ischemia (GI) classification in the risk assessment of patients with ST-elevation myocardial infarction has been shown previously. Grade 3 ischemia (G3I) is defined by the Sclarovsky-Birnbaum grading system as ECG with ST-elevation and distortion of the terminal portion of the QRS complex in two or more adjacent leads, while grade 2 ischemia (G2I) is defined as ECG with ST-elevation without QRS distortion.

Methods

In a substudy of the international, multicenter, prospective, randomized Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI (TOTAL), we studied the prognostic impact of the grade of ischemia classification on the outcome in patients with STEMI (n=7,211). The primary outcome was a composite of death from cardiovascular causes, recurrent MI, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within one year.

Results

The primary outcome occurred in 153 of 1,563 patients (9.8%) in the G3I group vs. 364 of 5,648 patients (6.4%) in the G2I group (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.29 to 1.88; p<0.001). The rates of cardiovascular death (4.8% with G3I vs. 2.5% with G2I; HR, 1.92; 95% CI, 1.45 to 2.54; p<0.001) and all-cause mortality (5.2% with G3I vs. 3.3% with G2I; HR, 1.62; 95% CI, 1.25 to 2.10; p<0.001) were also higher in patients with G3I. The rate of stroke or TIA were similar within the two groups (1.1% with G3I vs. 1.0% with G2I; HR, 1.13; 95% CI, 0.66 to 1.95; p=0.650). The grade of ischemia (G3I vs G2I) was shown to be an independent predictor of primary outcome in adjusted multivariable analysis (adjusted HR, 1.43; 95% CI, 1.18 to 1.74; p<0.001).

Conclusions

STEMI patients with G3I in the presenting ECG proved to have an increased rate of cardiovascular death, recurrent MI, cardiogenic shock, or NYHA class IV heart failure within one year compared to patients with G2I.

Acknowledgement/Funding

Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, The unit of Heart Center Co. [Z60064]
3150Predictors as exercise intolerance and myocardial fibrosis of clinical outcomes in patients with hypertrophic cardiomyopathy
Authors: Hwang J W , Kim S.U.N.G.M , Park S.U.N.G.-J , Kim E U N K , Chang S.U.N.G.-A , Lee S.A.N.G.-C , Choe Y.E.O.N.H , Park S W O O , Kim D.A.R.A.E , Choi J.I.N.-O.H , Kim H A J , Ok S.E.O.N.H
Published: October 2019

Reduced exercise capacity is common in patients with hypertrophic cardiomyopathy (HCMP), affecting patients along a broad spectrum of clinical severity. Replacement fibrosis is associated with worse outcomes in patients with HCMP. The aim of study was to evaluate cardiopulmonary exercise test (CPET) and cardiac magnetic resonance (CMR) to predict clinical outcomes in HCMP patients.

We enrolled 371 patients with HCMP and normal left ventricular (LV) systolic function (ejection fraction >50%), who underwent both CPET and CMR. CMR at 1.5 T, including late gadolinium delayed enhancement (LGE), was carried out to define the amount of myocardial fibrosis. The primary outcome was hard events including cardiac death, myocardial infarction, cardiac transplantation, sustained ventricular tachycardia, cerebral stroke, and heart failure requiring hospitalization.

During follow-up (6.1±2.6 years), there were 74 hard events. The patients were older (56.11±10.37 vs. 52.19±11.17, p=0.006) in the group with hard events. Exercise intolerance as peak oxygen consumption (peak VO2) showed in the group with hard events (25.60±6.01 vs. 30.18±6.81, p<0.001). In addition, the amount of myocardial fibrosis as LGE was larger (27.67±23.07 vs. 18.09±15.80, p=0.001). Larger left atrium size as volume index (LAVI) (50.01±18.14 vs. 41.55±16.48, p<0.001), increased LV filling pressure as E/e' (13.80±5.43 vs. 11.50±4.48, p=0.001) and higher level of NT-proBNP in laboratory finding (941.01±895.22 vs. 575.68±910.76, p=0.003) were showed in the group with hard events. Multivariable Cox-proportional analysis with adjustment as age and gender showed that peak VO2 [hazard ratio (HR) = 0.926, 95% confidence interval (CI) 0.872–0.984, p=0.013], LGE (HR=1.022, 95% CI 1.000–1.055, p=0.05) and LAVI (HR=1.03, 95% CI 1.007–1.053, p=0.009) could predict the clinical outcome as hard events. The incremental prognostic value for the prediction of hard events of peak VO2, LGE and LAVI over clinical variables was from 0.759 to 0.772 as the value of area under the curves (AUC).

This study demonstrated that the exercise intolerance, progression of myocardial fibrosis, and abnormal diastolic parameters could be significant predictors of clinical outcome in the patients with HCMP. CPET and CMR may help us to monitor and manage cardiac events in these patients.

Acknowledgement/Funding

None
4098Reduced skeletal muscle mass is associated to worsened long-term clinical outcomes in patients with coronary artery disease: a quantitative analysis by computed tomography
Authors: Kang D O , Park S Y , Park Y , Jang W Y , Kim W , Choi B G , Na J O , Choi C U , Kim E J , Rha S.-W , Park C G , Hong S.-J , Seo H S
Published: October 2019

Background

Sarcopenia is closely associated to poor clinical outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear whether the skeletal muscle mass at baseline has quantitative effect on future cardiovascular outcomes.

Purpose

We investigated the quantitative effect of skeletal muscle mass on future cardiovascular outcomes in patients with coronary artery disease (CAD).

Methods

Total 475 patients those who underwent successful percutaneous coronary intervention (PCI) for CAD and performed computed tomography (CT) scan within 30 days of PCI were enrolled. The cross-sectional area of skeletal muscle at the first lumbar vertebra (L1) level was measured. Whole study population was divided into 4 groups according to the sex-specific quartiles of skeletal muscle index (SMI). Primary outcome was all-cause mortality and secondary outcome was major adverse cardiovascular event (MACE) within 3 years of follow-up.

Results

Mean follow-up duration was 4.11±3.02 years and average time period from the date of PCI to CT scan was −3.33±11.72 days. The incidence of 3-year all-cause mortality (23.2% vs. 9.9% vs. 6.6% vs. 4.4%, p<0.001) and MACE (42.9% vs. 24.0% vs. 14.3% vs. 6.2%, p<0.001) was significantly higher in the group of lower quartiles of L1-SMI. In the fully adjusted multivariable analysis, lower quartiles of L1-SMI was an independent predictor of higher risk of all-cause mortality and MACE (lowest vs. highest quartile; OR: 4.90, 95% CI: 1.54 to 15.5, p=0.007; and OR: 12.3, 95% CI: 4.99 to 30.4, p<0.001, respectively).

Results of 3-year clinical outcomes SMI Q1 (n=124) SMI Q2 (n=116) SMI Q3 (n=112) SMI Q4 (n=123) Log-rank p-value All-cause mortality 27 (23.2) 11 (9.9) 7 (6.6) 5 (4.4) <0.001 Non-fatal MI 9 (8.7) 3 (3.0) 2 (2.0) 3 (2.6) 0.038 Repeat revascularization 20 (24.9) 15 (15.2) 7 (7.1) 4 (3.8) <0.001 Total MACEs 47 (42.9) 26 (24.0) 15 (14.3) 7 (6.2) <0.001 Data are expressed as n (%). MACE = major adverse cardiovascular event; MI = myocardial infarction; SMI = skeletal muscle index; Q = quartile.

Impact of reduced skeletal muscle on CAD

Conclusion

Skeletal muscle mass at baseline is a powerful predictor of future adverse clinical outcomes in patients with CAD undergoing successful PCI. Quantitative assessment of skeletal muscle mass at L1 level by CT scan provides prognostic implication for future cardiovascular risk stratification.

Acknowledgement/Funding

National Research Foundation of Korea (NRF-2016R1A2B3013825), Ministry of Future Creation and Science of Korea (2018K000255)
4250Sports-related sudden cardiac arrest in Germany
Authors: Bohm P , Scharhag J , Schmied C , Meyer T
Published: October 2019

Background

Knowledge about causes of sports-related sudden cardiac arrest (SrSCA) may influence national strategies to prevent such events.

Purpose

We established a prospective registry on SrSCA to estimate the incidence and in particular describe the etiologies of SrSCA in the general population in Germany.

Methods

The registration of SrSCA based upon 4 pillars: a) a web-based platform to record SrSCA cases in competitive and recreational athletes, b) media-monitoring and c) a cooperation with the German Resuscitation Registry as well as d) 15 institutes of forensic medicine.

Results

After an observation period of 6 years, a total of 349 cases was recorded (mean age 48.0±12.7 years) of which 109 subjects survived. Most of the cases occurred during non-elite competitive or recreational sports. Bystander cardiopulmonary resuscitation (CPR) was initiated in 262 cases (75%), however rhythm analysis and defibrillation (if indicated) was mainly performed by medical service. In subjects ≤35 years, premature coronary artery disease (CAD) and sudden arrhythmic death syndrome (SADS) prevailed, followed by myocarditis. In athletes ≥35 years, CAD predominated.

Conclusion

The prevalence of cardiac pathologies in young athletes seems to vary across different countries. CAD represents the most common cause of SrSCA in the general population of Germany, highlighting the need for a targeted cardiovascular risk evaluation including young athletes. Public education on basic life support including the appropriate use of an automated external defibrillator (AED) may further decrease the burden of sudden cardiac death.

Acknowledgement/Funding

Funding from the German Heart Foundation
4259Discovery of the first genome-wide significant risk loci for syncope and collapse
Authors: Ahlberg G , Hadji-Turdeghal K , Andreasen L , Hagen C M , Ghouse J , Baekvad-Hansen M , Bybjerg-Grauholm J , Hougaard D M , Hedley P , Haunsoe S , Svendsen J H , Jepps T A , Skov M W , Christiansen M , Olesen M S
Published: October 2019

Background

Syncope is a common condition in the general population causing frequent hospitalisation and visits to the emergency department. Family aggregation and twin studies have previously indicated that syncope and collapse has a heritable component.

Purpose

We investigated whether common genetic variants predispose to syncope and collapse.

Methods

We used genome-wide association data on syncope and collapse for 408,961 individuals with European ancestry from the UK Biobank study. In a replication study, the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n=86,189) was used to investigate the risk of incident syncope stratified by genotype carrier status.

Results

We report on a genome-wide significant locus on chromosome 2q32.1 with the lead SNP rs12465214 (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.10–1.17, P=5.8x10–15; Figure 1a). This association was replicated in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (HR=1.30, CI: 1.15–1.46, P=1.68x10–5; Figure 1b). LD score regression demonstrated a significant genetic correlation (rg) with coronary artery disease (rg=0.41, P=6.99x10–15) and related phenotypes such as angina and hypertension (Figure 1c). Analyses of eQTL (P=4x10–8) and epigenetic chromatin states revealed that variation in this locus likely affects expression of the gene ZNF804A, which resides in its proximity (Figure 1d). A qPCR analysis showed that ZNF804A was mostly expressed in the brain. A lower level of ZNF804A expression was also detected in the cerebral arteries. ZNF804A was not expressed in heart tissue.

Figure 1

Conclusion

rs12465214 is associated with syncope and collapse. Variation in this locus likely modulates the expression of the nearby gene ZNF804A through eQTLs and chromatin interactions. ZNF804A is mainly expressed in the brain and cerebral arteries. However, the precise function of ZNF804A is unknown. Furthermore, syncope and collapse is a polygenetic trait and share a significant genetic overlap with coronary artery disease, angina and hypertension.

Acknowledgement/Funding

This work was supported by grants from The John and Birthe Meyer Foundation, The Research Foundation of the Heart Centre, Rigshospitalet, The Research
4305The interrelation of left ventricular geometry with myocardial work
Authors: Sahiti F , Morbach C , Tiffe T , Cejka V , Breunig M , Eichner F , Gelbrich G , Heuschmann P U , Stoerk S
Published: October 2019

Introduction

A novel echocardiographic method to non-invasively determine myocardial work based on speckle-tracking derived longitudinal strain and blood pressure has recently been validated and offers new opportunities to study mechanistic associations. Left ventricular (LV) dilation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately heart failure, but the mechanisms are still not well understood. We aimed to assess the association of LV geometry and myocardial work in a non-diseased population.

Methods

The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of a medium-sized town in Germany, aged 30–79 years. By off-line analysis of the standardized, quality-controlled transthoracic echocardiograms the following parameters describing myocardial work can be derived. Global constructive work (GCW): work performed during shortening in systole and adding negative work during lengthening in isovolumic relaxation; global wasted work (GWW): negative work performed during lengthening in systole adding work performed during shortening in isovolumic relaxation; global work efficiency (GWE): GCW/(GCW+GWW). Further, LV volumes and mass were measured and indexed to body surface area.

Results

Myocardial work analysis was performed in 1568 individuals, who were in sinus rhythm, had preserved LV ejection fraction (EF), and were free from significant valvular disease (50.3% female, aged 53±12 years). In linear regression, we included age, sex, LVEF, low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1c), heart rate, body mass index, hypertension as well as LV mass index (LVMi) and LV end-diastolic volume index (LVEDVi) as parameters of LV geometry. We found increasing LVEDVi (52±10 mL/m2), associated with higher GWW (+0.35, p<0.001) and lower GWE (–0.01, p<0.05), while increasing LVMi (73±17 g/m2) was associated with both, higher GWW (+0.23, p<0.01) and GCW (+1.6, p<0.05) resulting in a lower GWE (–0.09, p<0.01).

Conclusion

The new echocardiography-based method to non-invasively assess myocardial work offers new insights into the relationship of LV geometry and myocardial work in a non-diseased population. While larger LV volumes were associated with more wasted work, higher LV mass was associated with an increase in both constructive and wasted work. Both alterations of LV geometry adversely affected myocardial work efficiency. This new echocardiographic method is change-sensitive and thus holds promise to further explore the relationship of LV geometry with myocardial work in different disease entities.

Acknowledgement/Funding

Funding of the STAAB cohort study in the frame of the Comprehensive Heart Failure Center, BMBF 01EO1004 and 01EO1504
P3138Age based outcomes after implantable cardioverter-defibrillator extraction
Authors: Sharedalal P , Shah N S , Cubberley A C , Saltzman H S , Kutalek S K
Published: October 2019

Background

There are growing numbers of defibrillator implantations for prevention of sudden cardiac death. As such, there has been a concomitant need for lead extraction. This procedure is often indicated in the setting of device or systemic infection, device upgrade, lead malfunction or elective extraction in cases of abandoned leads. Lead Extraction is associated with increased morbidity and mortality. The comparative safety and effectiveness of lead extraction in various age groups has not been well evaluated.

Purpose

The average age of patients undergoing lead extraction in our single center database is (65.5±15.9). There are lack of studies on age associated outcomes with lead extraction. We intend to evaluate differences in major in minor adverse outcomes in patients undergoing lead extraction stratified by age.

Methods

We identified 1,297 patients who underwent lead extraction between January 2003 and April 2016 at a major metropolitan center and evaluated procedural outcomes stratified by age. Age groups were stratified as <55, 55–64, 65–74, 75–84, and >85 years old. Baseline characteristics including history of coronary artery bypass graft (CABG), hypertension (HTN), congestive heart failure (CHF), hyperlipidemia (HLD), diabetes mellitus (DM) and coronary artery disease (CAD) were evaluated using chi-squared analysis. Adverse events were identified as major complications (death, cardiac arrest, cardiac perforation, coronary venous dissection, pericardial tamponade, or urgent cardiac surgery), and minor complications (coronary sinus dissection, pneumothorax, pocket bleeding requiring drainage, worsening tricuspid valve function, vegetation embolization, venous thrombosis, requirement of blood transfusion or lead migration). Subgroups for age were also analyzed using chi squared analysis to prevent type 1 error.

Results

There was no statistically significant difference in overall major and minor complications amongst different age groups (P>0.05). An overall statistically significant difference was noted in baseline characteristics of CABG, HTN, HLD, DM, and CAD (P<0.05). Within each age subgroup, no statistically significant difference was noted for major or minor complications post lead extraction (P>0.05).

Conclusion

This study shows lead extraction can be performed safely in patients of all age groups without significant overall risk of major or minor complications.

Acknowledgement/Funding

None
P3393Comparison of intermediate-term vascular response to new-generation biodegradable polymer and durable polymer-based drug-eluting stents: optical coherence tomographic study
Authors: Kawamura A , Nishino M , Matsuhiro Y , Nakamura Z , Yasumura K , Yasumoto K , Tanaka A , Matsunaga Y , Nakamura D , Yano M , Yamato M , Egami Y , Syutta R , Tanouchi Z
Published: October 2019

Background

Over the last decade, drug-eluting stents (DES) have undergone substantial modifications with thinner struts and more biocompatible durable polymer (DP) or biodegradable polymer (BP). In DP-based DES, after drug elusion has been completed, DP remnants may trigger of local inflammatory vascular reactions and promote delayed healing, leading to accelerated neoatherosclerosis (NA). Thus, BPs have been developed to reduce the above-mentioned risks. Recently, poor strut coverage and in-stent NA are increasingly recognized the cause of late stent failure, but it is unclear whether BPs can reduce the incidence of NA and the poor stent coverage as compared to DPs.

Objectives

The purpose of this study was to compare the incidence of NA and the stent coverage using optical coherence tomography (OCT) between the DPs and the BPs.

Methods

Between July 2016 and April 2018, 127 consecutive patients with new-generation DES who underwent 8-month follow up OCT imaging were enrolled. Patients were divided into the two groups: DP group who had the new-generation durable polymer everolimus-eluting and zotarolimus-eluting stents and BP group who had the new-generation biodegradable polymer sirolimus-eluting and everolimus-eluting stents. We compared patient characteristics including hypertension, dyslipidemia and diabetes mellitus and 8-month follow up OCT findings including NA, uncovered struts and malapposed struts between the two groups.

Results

The DP group comprised 64 patients (50.4%. The incidence of NA, uncovered struts and malapposed struts were similar between the two groups (DPs vs BPs, 1.56% vs 7.94%, P=0.11; 7.80% vs 5.88%, P=0.16 and 2.76% vs 2.01%, P=0.43, respectively) (table). The other parameters were also similar between the two groups.

Table 1 DP group (n=64) BP group (n=63) P value Hypertension 44 (68.8%) 50 (79.4%) 0.2251 Dyslipidemia 39 (60.9%) 37 (58.7%) 0.8573 Diabetes mellitus 25 (39.1%) 30 (47.6%) 0.3731 8 month OCT follow up findings   Neoatherosclerosis 1 (1.6%) 5 (7.9%) 0.1147   Uncovered struts 7.8% (2.8–20.4) 5.9% (0.7–16.7) 0.1616   Malapposed struts 0.2% (0–2.8) 0% (0–2.8) 0.4392

Conclusions

The new-generation DP based-DES may have similar effects on vascular response compared to the new-generation BP-based DES during 8-month follow-up period.
P3449Revealing the burden of acute cardiac and arterial complications in 715 patients diagnosed with Lemierre syndrome
Authors: Valerio L , Sacco C , Zane F , Granziera S , Russo M , Konstantinides S , Pecci A , Barco S
Published: October 2019

Background

Lemierre syndrome is a potentially life-threatening condition occurring in otherwise healthy children and adolescents with head/neck bacterial infections (usually tonsillitis due to anaerobe bacteria). Peculiar complications are neck vein thromboses contiguous to the site of infection and multiple septic embolization. Arterial thrombosis and cardiac complications have been described as possible clinical manifestations of Lemierre syndrome: however, in light of the rarity of this condition (one case/1,000,000 person-years), no comprehensive analysis has ever been conducted.

Purpose

To describe the frequency and the patterns of acute cardiac and arterial complications in patients with Lemierre syndrome.

Methods

We identified 715 cases of Lemierre syndrome (years 2000–2016) and retrieved complete individual patient-level data. Study outcomes assessed on admission or during hospitalization were: i) objectively diagnosed ischemia or arterial infarction/thrombosis, arterial stenosis due to inflammatory process, and septic aneurysms; ii) new objectively diagnosed cardiac complications; iii) all-cause death.

Results

Of the 715 patients with Lemierre syndrome, 56 (7.6%, 95% confidence interval [CI]: 6.1%–10.0%) experienced cardiac or arterial complications. Median age was 19 (interquartile range [IQR]: 16–25) years and 35 (62.5%) were men. Intracranial ischemia or infarction was found in 23 patients, corresponding to 3.2% of the whole study population. Carotid artery thrombosis, stenosis, or septic aneurysm occurred in 28 (3.9% of total), pericardial disease in 11 (1.5% of total), and infective endocarditis in 5 (0.7% of total) (Figure). A total of 32 (57.1%) patients developed these complications during the course of hospitalization after a median of 6 (IQR: 3–12 days) days from admission. A total of 37 (66.1%) patients received anticoagulation. Fatality rate was 10.7% (95% CI: 5.0%–21.4%; n=6).

Cardiac and arterial complications.

Conclusions

An unexpectedly high proportion of patients with Lemierre syndrome developed acute cardiac or arterial complications. In this group, the fatality rate was substantial. Our observation that most of the cardiovascular events occurred during the course of hospitalization may have implications for the development of diagnostic and management strategies. It remains unclear whether antithrombotic therapies may influence prognosis.
P3456'Heart, arteries and women', an innovative healthcare pathway based on collaboration between gynecologists and cardiologists for women at cardiovascular risk: design and evaluation at five years
Authors: Madika A , Nasserdine P , Langlet S , Letombe B , Devos P , Mounier Vehier C
Published: October 2019

Introduction

In women, cardiovascular diseases are the leading cause of death worldwide. Prevention and diagnosis typically occur at late stages and less frequently than is men and treatments are not optimal in women. Preventive measures must be implemented, and management approaches improved. To this end, an innovative coordinated healthcare pathway was initiated at the our University Hospital for women at risk of cardiovascular diseases.

Purpose

The objective of this study was to describe the design of the healthcare pathway and to assess its relevance to improve prevention, diagnosis and treatment in women at cardiovascular risk.

Methods

The healthcare pathway “Heart, arteries and women” implemented at our University Hospital since January 1st, 2013 is based on collaboration between gynecologists and cardiologists. Women after an adverse pregnancy outcome and women at menopause with increased cardiovascular risk were referred by the gynecologist to the cardiologist for complete cardiovascular evaluation if eligible (Figure 1). Screening for both traditional and nontraditional cardiovascular risk factor and cardiovascular diseases if indicated, lifestyle counseling and adjustment of medical treatment were performed for each woman. The present study focused on post-menopausal women at risk or high cardiovascular risk according to American Heart Association (AHA) classification who had a complete cardiovascular evaluation through the healthcare pathway between January 1st, 2013 and December 31st, 2017.

Results

We included 690 post-menopausal women with a mean age of 58±8 years. According to AHA classification, 339 women (50,8%) were at high risk and 351 (49,2%) at risk. Cardiovascular risk control was poor with 146 current smokers (21,2%) and 264 obese women (38,3%). Only 320 women (46,4%) reached the targeted blood pressure of <140/90 mmHg and 169 (24.5%) attained their low-density lipoprotein (LDL)-cholesterol target. Among the 212 women treated for diabetes, 45,3% achieved the glycated haemoglobin (HbA1c) target of <7.0%. Lower extremity artery disease was newly diagnosed in 46 women, renal artery disease in 51 women and ischemic heart disease in 62 women. Statins, renin-angiotensin system inhibitors and antiplatelet agents were significantly more prescribed according to guidelines after the cardiovascular evaluation (p<0.001).

Conclusion

Our coordinated healthcare pathway based on partnership between gynecologists and cardiologists allowed to improve assessment of specific cardiovascular risk, screening, prevention and treatment of cardiovascular diseases in women. Enhanced collaboration between gynecologists and cardiologists offers a real opportunity to improve cardiovascular heath in women.
P3480Tissue-specific regulation of the mitochondrial proteome by adiponectin receptor 1
Authors: Gollmer J , Koentges C , Pepin M , Pfeil K , Wende A R , Bode C , Zirlik A , Bugger H
Published: October 2019

Lack of the adiponectin target receptor adiponectin receptor 1 (AdipoR1) impairs gene expression of mitochondrial OXPHOS proteins due to impaired AMPK-SIRT1-PGC-1α signaling. Since decreased adiponectin serum levels in diabetes mellitus should thus compromise AdipoR1 signaling, we hypothesized that impaired AdipoR1 signaling may causally contribute to typically observed mitochondrial defects in diabetes complications. Thus, we performed comparative proteomics in cardiac, renal and hepatic tissue of AdipoR1−/− mice using LC-MS/MS. Using principal component analysis, heatmapping and hierarchical clustering, a significant separation of genotypes was observed across tissues. Enrichment analysis of differentially expressed proteins revealed disproportionate representation of proteins involved in oxidative phosphorylation, TCA cycle and fatty acid oxidation in all tissues. While 121 or 98 or 78 proteins were differentially regulated in cardiac or renal or hepatic tissue, respectively, only 15 proteins were regulated in the same direction across all tissues. Pathway analysis identified HNF4, NRF1, LONP, RICTOR, SURF1, insulin receptor and PGC-1α as most likely upstream regulators. Importantly, we found a dramatic downregulation of AdipoR1 expression in heart (−70%), liver (−90%) and kidney (−80%; all p<0.05) of high fat-fed and prediabetic non-transgenic mice compared to low fat-fed mice. In addition and beyond diabetes, AdipoR1 expression was also decreased in endstage failing hearts of non-diabetic human subjects compared to non-failing donor hearts. Thus, we conclude that AdipoR1 signaling regulates mitochondrial protein composition across all tissues in a functionally conserved, yet molecularly distinct, manner. Impaired AdipoR1 signaling may causally contribute to mitochondrial defects in diabetic complications and even human heart failure.
P3482Leptin, receptor to leptin and expression in adipocytes isolated from different adipose depots in patients with ischemic heart disease
Authors: Dyleva Y A , Gruzdeva O , Uchasova E , Belik E , Brel N , Kokov A , Sinitsky M , Kozyrin K , Barbarash O
Published: October 2019

Purpose

To study the peculiarities of the content of leptin and the leptin receptor in adipocyte culture of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue and the expression of their genes.

Methods

29 patients with coronary heart disease were examined. Adipocytes were isolated from SAT, EAT and PVAT samples obtained during coronary artery bypass grafting, followed by evaluation (after 24 hours) of the leptin concentration (Human resistin ELISA, R&D Systems, USA) and leptin gene expression in cell culture. Magnetic resonance imaging (MRI) was used to determine the area of the visceral (VAT) and subcutaneous adipose tissue (SAT) of the abdominal region, the thickness of epicardial adipose tissue (EAT). The calculation of the free leptin index (FLI) was determined by the formula: leptin/SOB-R * 100. Leptin resistance was defined as an FLI >0.25. All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 10.0.

Results

In adipocytes of EAT, leptin secretion was 1.2 times higher than in adipocytes of PVAT, which is consistent with the expression of the leptin gene. The content of leptin soluble receptor was opposite in the adipocytes of PVAT higher than in EAT and SAT 2.3 and 3.1 times, respectively. At the same time, the index of free leptin was higher in SAT adipocytes 1.3 and 3.2 times in comparison with EAT and PVAT. The correlation analysis confirmed the relationship between EAT thickness and the serum concentrations of leptin. Thus, in patients with VO, the leptin concentration had a negative dependence on the thickness of the left and right ventricle (r=−0.28, p=0.02; r=−0.33, p=0.02, respectively). A negative dependence on the EAT thickness was also established for the FLI (r=−0.28; p=0.03). PVAT of the abdominal aorta is similar to the properties of visceral AT. An analysis of the possible relationship between perivascular adipocytes and adipokine exchange rates showed a direct relationship between the volume PVAT of the abdominal aortic ventricle and leptin (r=0.44, p=0.01), as well as the FLI (r=0.56; p=0.03).

Conclusion

Adipocytes SAT, EAT and PVAT differed in the level of secretion of leptin. In epicardial and, to a greater extent, in perivascular adipocytes, a protective mechanism against a high concentration of leptin was observed due to increased secretion of the soluble receptor to leptin. The high content of leptin and the low soluble receptor for leptin led to the development of leptin resistance, which was more pronounced in the culture of adipocytes SAT. Meanwhile, the EAT thickness was inversely related to the concentration of leptin and the FLI index (one of the main leptin-resistance markers).
P3512Sex differences in rats with heart failure with preserved ejection fraction and the effect of autonomic modulation
Authors: Stavrakis S , Elkholey K , Morris L , Li Y , Po S S
Published: October 2019

Background

Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF and sudden death is the leading cause of mortality. There are considerable sex differences in cardiac structure and function, which may be related to outcomes in HFpEF. Transcutaneous vagus nerve stimulation (tVNS) is antiarrhythmic.

Purpose

To describe sex differences in mortality, autonomic tone and ECG parameters in rats with HFpEF and examine the effect of tVNS on these outcomes.

Methods

Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of LS or HS diets, HS rats were randomized to receive active or sham tVNS, 30min daily (20Hz, 3mA) for 4 weeks. The rats were monitored daily for 4 weeks for the development of HFpEF. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint). Heart rate variability (HRV) was calculated at the respective time points. ECG and HRV parameters were analyzed in a blinded fashion. Logistic regression analysis was performed to identify independent predictors of mortality.

Results

A total of 58 rats were included (5 male LS, 6 female LS, 22 male HS and 25 female HS). HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There were 4 sudden cardiac deaths in males (with ventricular tachycardia documented in 1 rat), whereas all the females died of HF or stroke. Corrected QT (QTc) at baseline significantly prolonged in HS compared to LS rats (250.5±14.4ms vs. 226.8±13.9ms, respectively, p=0.0007), while all other ECG parameters did not differ significantly between groups. In HS rats, QTc prolongation was significantly more pronounced in males compared to females (259.4±20.6ms vs. 243.8±14.5ms, respectively, P=0.002). In univariate analysis, prolonged baseline QTc (OR=1.04; 95% CI 1.01–1.06, p=0.003) and male sex (OR=3.21, 95% CI 1.19–8.66, p=0.016) predicted mortality. However, in multivariate analysis, QTc was the only significant predictor of mortality (OR=1.04; 95% CI 1.01–1.06, p=0.003). After 4 weeks of treatment, active tVNS significantly decreased QTc compared to sham (244.6±13.8ms vs. 255.8±14.0ms, respectively, p=0.017) in both male and female rats in a similar manner. The low frequency to high frequency ratio (LF/HF) of HRV, which reflects sympathovagal balance, was significantly decreased in active tVNS rats compared to sham (0.21±0.13 vs. 0.54±0.14, respectively; p=0.001) in both male and female rats in a similar manner.

Conclusions

Male rats with HFpEF exhibit worse survival compared to females and are at higher risk for sudden death. QTc prolongation accounts for the increased risk of sudden death in males compared to females. Autonomic modulation with tVNS attenuates the unfavorable changes in QTc and HRV induced by HS diet and may be used to prevent ventricular arrhythmias in patients with HFpEF.
P3535Prognostic value of congestion status by bioelectrical impedance analysis and natriuretic peptide levels in acute heart failure with preserved versus reduced left ventricular ejection fraction
Authors: Yazaki Y , Iijima R , Hara H , Moroi M , Nakamura M
Published: October 2019

Background

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-known predictor of acute heart failure (HF). Congestion volume status estimated by bioelectrical impedance analysis (BIA) is also associated with adverse cardiovascular events in HF patients. However, it is unclear whether these biomarkers reflecting pathophysiological pathways are different between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF).

Purpose

The aim of this study was to investigate whether the prognostic value of NT-proBNP and extracellular water/free fat mass (ECW%) assessed by BIA is different between HFrEF and HFpEF in acute HF patients.

Methods and results

One hundred-and-forty-three patients admitted for acute HF between November 2013 and January 2015 were estimated for NT-proBNP levels and ECW% by BIA on admission. A total of 49 HFrEF (LVEF<40%) and 75 HFpEF (LVEF≥50%) patients were included in this study (mean age: 76±14 years, male: 63%). The median of NT-proBNP levels in HFrEF patients was higher than in HFpEF (6022 [IQR: 2531–9163] pg/mL and 3179 [1076–6054] pg/mL, respectively, p=0.012). Conversely, ECW% was similar between HFrEF and HFpEF (29.0 [25.7–33.7] % and 31.7 [27.3–38.8] %, respectively, p=0.088). The primary endpoint was the composite of all-cause mortality and/or hospitalisation due to HF. During a median follow-up of 5.9 months, 16 (35.6%) and 35 (50.7%) patients were observed to have composite events in HFrEF and HFpEF, respectively, (p=0.111). Elevated NT-proBNP levels in HFrEF patients were associated with an increased risk of composite events after adjustment for traditional risk factors (hazard ratio [HR]: 2.39; 95% Confidence interval [CI]; 1.04–5.47; p=0.040), but not in HFpEF (p=0.063). Meanwhile, a high ECW% in HFrEF patients was associated with increasing composite events risk (HR: 3.30; 95% CI; 1.32–8.25; p=0.011), as well as in HFpEF patients (HR: 1.62; 95% CI; 1.03–2.55; p=0.037). Furthermore, the ECW% in addition to NT-proBNP in HFpEF patients resulted in a significant improvement in prediction for composite events (net reclassification improvement 0.67 [95% CI 0.24–1.11]; p=0.002 and integrated discrimination improvement 0.12 [0.004–0.20]; p=0.004).

Conclusion

Elevated levels of NT-proBNP in acute HF were predictive for mortality and hospitalisation due to HF in HFrEF but may not be for HFpEF patients, and ECW% had a better predictive value than NT-proBNP in HFpEF patients.
P3545Association between diastolic dysfunction and two-year survival in heart failure patients with mid-range or reduced left ventricular ejection fraction
Authors: Nordbeck P , Liu D , Hu K , Lau K , Kiwitz T , Robitzkat K , Hammel C , Ertl G , Frantz S
Published: October 2019

Background

Extensive studies have demonstrated prognostic impact of echocardiographic defined diastolic dysfunction (DD) in patients with preserved as well as reduced left ventricular ejection fraction (LVEF). Nevertheless, it remains controversial whether evaluation of DD could provide additional prognostic information in heart failure (HF) patients with impaired systolic function. The purpose of present study, therefore, is to investigate the prognostic impact of echocardiography-defined DD on survival in HF patients hospitalized in our centre from 2009 to 2017 with mid-range LVEF (HFmrEF, LVEF 41–49%) and reduced LVEF (HFrEF, LVEF<40%).

Methods

A total of 2018 patients with echocardiography-evidenced LVEF<50% and hospitalized in our centre between July 2009 to December 2017 were included. Baseline demographic and clinical data were obtained by reviewing the medical records. All patients subsequently completed a median clinical follow-up of 24 (IQR 13–36) months by medical record review or telephone interview. The primary endpoint was all-cause mortality or heart transplantation (HTx). Patients were divided into mild, moderate and severe DD according to recent guidelines.

Results

The mean age was 69±13 years in the HFmrEF group and 68±13 years in the HFrEF group. All-cause mortality/HTx rate was significantly higher in the HFrEF (all-cause death n=318 and HTx n=11, 30.9%) group than in patients with HFmrEF (all-cause death n=235 and HTx n=2, 24.9%, P=0.003). All-cause mortality/HTx rate increased in proportion to DD severity in HFmrEF patients: 17.1% (54/315) in the mild DD group, 25.4% (115/452) in the moderate DD group, and 37.0% (68/184) in the severe DD group (P<0.001) and in HFrEF patients: 18.9% (43/228) in the mild DD group, 30.3% (146/482) in the moderate DD group, and 39.2% (140/357) in the severe DD group (P<0.001). Multivariable Cox regression analysis showed that Doppler parameter early-diastolic mitral inflow velocity to septal mitral annular velocity ratio (E/E') >14 (HR 1.41, 95% CI 1.06–1.89, P=0.020) and peak tricuspid regurgitation velocity (TRVmax) >2.8m/s (HR 1.75, 95% CI 1.33–2.29, P<0.001) were independent determinants of all-cause mortality/HTx in patients with HFmrEF; while E/E'>14 (HR 1.48, 95% CI 1.08–2.04, P=0.015) remained as an independent determinant of all-cause mortality/HTx in patients with HFrEF after adjustment for clinical and other echocardiographic confounders. Besides DD-related parameters, after adjustment with age and sex, lower tricuspid and mitral annular plane systolic excursions (TAPSE and MAPSE) were also closely related to higher mortality/HTx rate in both HFmrEF and HFrEF patients.

Figure 1. Kaplan-Meier curves

Conclusion

Our results indicate that all-cause mortality/HTx rate increases in proportion to DD severity in both HFmrEF and HFrEF patients.
P3563The influence of circadian patterand obstructive sleep apnean of blood pressure in nocturnal arrhythmias in hypertensive patients
Authors: Marinheiro R , Parreira L , Amador P , Mesquita D , Farinha J , Fonseca M , Esteves A , Pinheiro A , Sousa S , Silva M , Lopes C , Fernandes A , Guerreiro A , Chambel D , Caria R
Published: October 2019

Introduction

There is growing evidence suggesting hypertension is related to the occurrence of arrhythmias. When occurring predominantly during the night, two potential entities commonly present in hypertensive patients could be related with increased arrhythmogenesis: (1) the lack of normal nocturnal dipping of blood pressure (BP) (non-dipping pattern of hypertension) or (2) obstructive sleep apnea (OSA). Thus, nocturnal arrhythmias (NAs) can identify hypertensive patients with OSA and/or non-dipping pattern, both related with adverse outcomes.

Aims

To determine if NAs are related with non-dipping hypertension, OSA or both.

Methods

We studied hypertensive patients who performed ambulatory blood pressure monitoring (ABPM) and also polysomnography and 24-hour Holter monitoring. Non-dipping pattern was considered when nocturnal BP reduction was inferior to 10%. Based on Holter monitoring, NAs were present when atrial fibrillation, frequent premature atrial contractions (PACs) (>30 PACs/hour), runs of >4 consecutive PACs, frequent premature ventricular contractions (PVCs) (>30PVCs/hour) or runs of >4 consecutive PVCs were present predominantly during sleeping hours. During polyssonography, apnoea/hypopnoea index (AHI) and oxygen saturation (SaO2) were analysed. Moderate to severe OSA was considered when AHI >15.

Results

We studied 104 patients [median age 62 (54–70) years, 65% male): 42 (40%) had moderate to severe OSA (median AHI=11 (6–26), mean SaO2=94% (92–95)] and 64 (61%) were non-dippers. NAs occurred in 18 patients (17%) and they were independently associated with AHI (Odds Ratio (OR) for a one unit increase 1.04, 95% confidence interval (CI) 1.01–1.07, p=0.03) but not with SaO2 (OR 0.96, CI 0.78–1.19, p=0.73) nor non-dipping pattern (OR 1.23, CI 0.38–3.98, p=0.72). No interaction was found between OSA and non-dipping hypertension (p=0.35). In patients with dipping pattern (n=40), AHI was higher in NAs patients comparing with no NAs patients (median AHI 29 versus 10, p=0.04), while in those with non-dipping pattern (n=64), AHI was not statistically different between patients with and without NAs (21 versus 11, p=0.12) (figure).

Figure 1

Conclusion

In this population of hypertensive patients, the presence of NAs was associated with OSA severity (i.e AHI), but not with the non-dipping pattern of hypertension. The importance of obstructive events in arrhythmogenesis seemed to be more pronounced in dipping patients, suggesting the abnormal high blood pressure during the night may also have some impact on NAs in non-dipping patients. Overall, our results suggest that OSA screening should be considered when nocturnal arrhythmias are detected in hypertensive patients, but ABPM should not be forgotten since multiple mechanisms can be involved in nocturnal arrhythmogenesis.
P3566Ambulatory blood pressure response to riboflavin supplementation in adults with the C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR)
Authors: Ward M , Hughes C F , Mc Mahon A , Rooney M , Strain J J , Plumb R , Troesch B , Bendik I , Mc Nulty H
Published: October 2019

Background

Epidemiological evidence suggests that the C677T polymorphism in the folate metabolising enzyme MTHFR is associated with a 24–87% increased risk of hypertension. Riboflavin (a cofactor for MTHFR) can modify this phenotype, as demonstrated in a series of RCTs, at this centre. ABPM measures BP over 24hrs and provides a more reliable assessment of an individual's BP compared to clinic BP.

Aim

To investigate the effect of riboflavin supplementation on BP (by ABPM) in adults with the MTHFR 677TT genotype.

Methods

Adults (n=3462) were recruited and screened for the MTHFRTT genotype and those eligible (n=81), were stratified by baseline SBP and randomised to receive riboflavin (10mg/day/16weeks) or placebo. Riboflavin status was measured using the erythrocyte glutathione reductase activation coefficient (EGRac) assay and clinic and ABPM were measured in accordance with clinical guidelines.

Results

Mean 24hr, daytime and night-time SBP was 6mmHg higher (p<0.05) in adults with the TT v CC genotype. BP response to riboflavin was strongly dependent on baseline BP. In participants with a baseline SBP≥125mmHg, riboflavin resulted in a significant BP lowering in daytime SBP (Table).

Day-time SBP response to riboflavin Treatment Placebo P-value Age 48.6 (11.3) 47.8 (12.0) 0.823 Male n (%) 17 (73.9) 12 (46.2) 0.093 BMI 28.8 (3.8) 27.2 (3.1) 0.131 Riboflavin status (EGRac)†   Pre 1.33 (1.28–1.38) 1.29 (1.24–1.34)   Post 1.20 (1.14–1.25) 1.31 (1.25–1.36) <0.001   Change −0.12 0.02 Daytime BP (mmHg)‡   Pre 137.1 (132.7–141.3) 134.7 (130.3–139.1)   Post 133.0 (128.9–138.1) 134.8 (130.6–139.1) 0.036   Change −3.8 −0.2 ANCOVA, adjusting for sex. †Higher EGRac values indicate lower riboflavin status; ‡mean of participant daytime/awake hrs personalised for each participant.

Conclusion

This is the first study to show, using ABPM, that riboflavin supplementation, targeted at adults with the MTHFR 677TT genotype, results in significant lowering of mean, day and night BP. Given the frequency of this genotype worldwide (approximately 10%, but as high as 30% in some populations) these findings could offer a personalised approach for BP management in at-risk sub-populations.

Acknowledgement/Funding

This work was supported by DSM Nutritional Products, Ltd and Wellcome Trust-Wolfston Northern Ireland Clinical Research Facility are acknowledged