bluuebunny/crossref_metadata_2025 huggingface dataset:
P3379Diagnostic value of cardiac computed tomographic angiography in suspected prosthetic valve dysfunction
Authors: Youssef Hassan A , Kandil H , Heshmat H , Ali Salem M , Meshaal M , Shehata A
Published: October 2019

Background

Echocardiographic assessment of prosthetic mechanical valves is limited by shadows, artefacts and the need for cumbersome Doppler calculations. CT scan has the potential to overcome some of the limitations of echocardiography in assessment of prosthetic valves.

Objectives

Determine the incremental diagnostic value of cardiac computed tomographic angiography (CTA) over transesophageal echocardiography (TEE) in patients with suspected prosthetic valve dysfunction (PVD) and its impact on treatment decisions.

Methods

50 consecutive patients with suspected PVD underwent both 64-slice ECG-gated CT and TEE and the results were compared. Imaging was compared against surgical findings (Reference standard). Echocardiographic evaluation focused on the detection of signs of PVD: vegetations, new or increased paravalvular leakage (PVL), aortic root pseudoaneurysms or abscesses and occluder malfunction. The CT interpreter was blinded to the findings of TEE.

Results

ECG-gated CT showed findings that were not detected by TEE in fifteen patients (30%). Additional aortic root abscess in four patients (8%), additional aortic root pseudoaneurysm in four patients (8%), and sclero-degenerative change across one of occluder of aortic prosthesis as cause of PVL in another patient (2%) not detected by TEE. CT negated the presence of aortic root abscess in one patient (2%), negated the presence of PVL in another patient (2%) both were detected by TEE. CT diagnosed occluder malfunction in one patient (2%) and underlying cause in two patients (4%) both were not detected by TEE. CT diagnosed presence of aortic arch dissection in one patient (2%) with large aortic root pseudoaneurysm.

CT showed minor diagnostic change in six patients (12%). CT showed better delineation of site and periannular extension of aortic root abscess in four patients (8%). CT showed better assessment severity of PVL in one patient (2%) and cause of PVL across mechanical aortic prosthesis in another patient (2%).

CT resulted in change of treatment strategy in 14 patients (28%). This included surgical excision of additional aortic root abscess or aortic root pseudoaneurysm in four patients (8%), surgical removal of prosthesis for underlying pathology (vegetation, malfunction due to underlying thrombus or PVL) in four patients (8%), aortic arch replacement with tubular graft and reimplantation of coronaries in one patient (2%) and conservative treatment with antibiotic therapy for small aortic root abscess not detected by TEE in 2 patients (4%), proper anticoagulation therapy and close monitor of INR in one patient (2%).

Conclusion

ECG-gated CT and TEE are complementary in patients with prosthetic valve dysfunction. Therefore, CT imaging has to be considered after clinical routine workup and TEE in patients with a high suspicion on prosthetic valve dysfunction.
P3385Difference of vascular healing after percutaneous coronary intervention between 4 kinds of new generation drug-eluting stents: an optical coherence tomography analysis
Authors: Matsuhiro Y , Nishino M , Nakamura H , Yasumoto K , Tanaka A , Nakamura D , Matsunaga Y , Yano M , Yamato M , Egami Y , Shutta R , Tanouti J
Published: October 2019

Background

New generation drug eluting stents (DES) have improved target vessel failure as compared with early generation DES and bare metal stent. Contemporary several new generation DES are different each other regarding strut thickness and drug and polymer type. A little is known about which stent induces a more favorable vascular healing at follow up.

Purpose

In this study, we compared the vascular healing at 8-month follow up by optical coherence tomography (OCT) between 4 different kinds of new generation DES.

Methods

We enrolled 112 consecutive patients (121 lesions) who underwent PCI using 4 kinds of new generation DES including biodegradable-polymer everolimus-eluting stents (BP-EES), biodegradable-polymer sirolimus-eluting stents (BP-SES), durable-polymer everolimus-eluting stents (DP-EES) and durable-polymer zotarolimus-eluting stents (DP-ZES) and who underwent 8-month follow up angiogram and OCT between July 2016 and April 2018. We compared the OCT parameters including percentage of covered struts, uncovered struts, well-apposed and uncovered struts, malapposed strut and mean neointimal hyperplasia (NIH) thickness between them.

Results

BP-EES consisted of 29 lesions, BP-SES consisted of 25 lesions, DP-EES consisted of 38 lesions and DP-ZES consisted of 29 lesions. A total of 734 frames with 5163 struts in BP-EES, 481 frames with 4214 struts in BP-SES, 783 frames with 6119 struts in DP-EES and 583 frames with 4708 struts in DP-ZES were analyzed. As shown in a table, mean NIH thickness was significantly higher in BP-EES and BP-SES. Thus, we compared the OCT parameters between durable-polymer (DP) group including DP-ZES and DP-EES and biodegradable-polymer (BP) group including BP-EES and BP-SES. The percentage of uncovered struts was significantly lower and mean NIH thickness was significantly higher in BP group than DP group.

Results of OCT parameters BP-EES (n=29) BP-SES (n=25) DP-EES (n=38) DP-ZES (n=29) P value BP group (n=54) DP group (n=67) P value Covered struts (%) 89.5±13.6 92.4±8.6 85.5±17.5 85.0±17.7 0.29 90.9±11.6 85.3±17.4 0.08 Uncovered struts (%) 8.8±10.8 7.1±8.7 14.5±17.5 15.0±17.7 0.14 8.0±9.9 14.7±17.4 0.03 Well-apposed and uncovered struts (%) 7.9±9.9 5.9±7.7 11.7±13.1 12.3±14.0 0.15 7.0±8.9 11.9±13.4 0.04 Malapposed struts (%) 0.8±1.6 1.3±2.2 2.7±5.8 2.7±4.7 0.33 1.0±1.9 2.7±5.3 0.07 Mean NIH thickness (μm) 102±57 121±48 78±28 88±33 <0.01 111±53 82±31 <0.01

Conclusion

The present OCT study demonstrated that delayed neointimal healing characterized by the presence of uncovered struts and lower mean NIH thickness was less common in BP group than DP gruop. Biodegradable-polymer may be more favorable than durable-polymer from the point of view of vascular healing.
P3396Identification of patients at extremely-high cardiovascular risk within a very-high risk population from the TERCET Registry
Authors: Dyrbus K , Gasior M , Skrzypek M , Osadnik T , Desperak P , Banach M
Published: October 2019

Background

The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) introduced a new “ultra-high risk” category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dL (1.4 mmol/L) is advised.

Purpose

Based on the above, we aimed to identify the proportion of patients, who are at ultra-high/extremely-high cardiovascular (CV) risk.

Method

Finally, we analyzed the data of 19,781 consecutive patients included in theHyperlipidaemia Therapy in the tERtiary Cardiological cEnTer (TERCET) Registry admitted to the Polish tertiary cardiovascular centre between 2006 and 2018. Among them, there were 7,319 patients admitted with ACS: 3,085 due to ST-segment elevation myocardial infarction (STEMI), 2,256 due to non-ST-segment elevation myocardial infarction (NSTEMI), and 1,978 due to unstable angina (UA), as well as 12,462 due to stable angina (SA). According to the European Society of Cardiology (ESC), all patients included in the Registry are at very high CV risk. All of the patients included in the registry underwent coronary angiography during the hospital stay. On the basis of the multivariate analysis, we aimed at determining the subgroup of the patients with the most unfavourable 12-month outcomes and therefore to indicate the risk factors responsible for extremely-high CV risk.

Results

According to the results of the multivariate analysis performed with stepwise backward regression, we identified the following risk factors: LVEF<40% (odds ratio [OR]=3.51, 95% CI: 2.87–4.29), prior stroke (OR=2.28, 95% CI: 1.65–3.01), diabetic nephropathy (OR=2.16, 95% CI: 1.68–2.77), age>75 years (OR=1.84, 95% CI: 1.33–2.55), atrial fibrillation (OR=1.81, 95% CI: 1.45–2.25), acute MI at admission (OR=1.56, 95% CI: 1.26–1.95), multivessel CAD (OR=1.40, 95% CI: 1.15–1.72), prior MI (OR=1.31, 95% CI: 1.07–1.60) and lower body-mass index (OR=1.02 per 1 kg/m2+ less, 95% CI: 1.00–1.04) that might help to define the group of very high risk patients, who should be considered as of extremely-high cardiovascular risk (all p<0.05). The aggregate summary of risk factors associated with “ultra-high” risk is presented in the attached Figure.

Multivariate analysis results

Conclusions

To our best knowledge, the presented study is the first such an analysis conducted on such a large population of very-high cardiovascular risk patients gathered in the registry of secondary cardiovascular prevention. In very-high cardiovascular risk patients, potential risk factors were identified that might help to establish the group of individuals at extremely high CV risk what contributes to higher 12-month mortality.

Acknowledgement/Funding

None
P3405Association between heart rate thresholds for cardiovascular risk defined by new ESC/ESH Guidelines and neuroadrenergic markers
Authors: Seravalle G , Dell'oro R , Gardini M , Quarti Trevano F , Marro G , Mancia G , Grassi G
Published: October 2019

Background

The ESC/ESH Guidelines for hypertension issued in 2018 identify resting heart rate (HR) values greater than 80 beats/minute as predictors of cardiovascular risk, with the undocumented evidence that this detection might represent the occurrence of a sympathetic cardiovascular overdrive.

Purpose

In the present study we tested this hypothesis throughout the use of direct and indirect markers of sympathetic neural function.

Methods

In 167 untreated and uncomplicated mild-to moderate essential hypertensives recruited for different investigations and aged 51.8±3.2 years (mean±SEM) without other cardiovascular or non-cardiovascular disease, we measured clinic and ambulatory blood pressure (BP), HR (EKG), venous plasma norepinephrine (NE, HPLC assay) and efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography). We then subdivided the study population in 2 groups according to HR values ≤ or >80 beats/minute.

Results

Sixty-eight patients displayed resting HR >80 beats/minute while the remaining 99 below this threshold value, the 2 groups showing superimposable age values and gender distribution. Body mass index, clinic and ambulatory BP were similar in the 2 groups this being the case also for LVMI and metabolic variables. In contrast MSNA values were significantly greater (P<0.02) in the former than in the latter group both when expressed as bursts incidence over time (49.2±1.8 vs 39.5±1.4 bs/min) and when corrected for HR (60.7±3.0 vs 51.4±2.5 bs/100 hb). NE showed a tendency to be greater in the former group without achieving, however, statistical significance. In the whole population there was a significant direct relationship between MSNA and HR values (r=0.61, P<0.01)

Conclusions

Thus hypertensive patients displaying HR >80 beats/minute are characterized by a marked sympathetic overdrive, particularly when direct adrenergic markers are employed. This finding suggests that cardiac and peripheral sympathetic activation may participate at the increased cardiovascular risk detected in this group of patients.
P3408The signal peptide of CNP is a novel predictor of MI, MACE and bleeding risk in chest pain patients
Authors: Pemberton C J , Lee J A , Aldous S , Appleby S , Chew-Harris J , Than M , Troughton R W , Richards A M
Published: October 2019

Aim

CNP is an important vascular and cardiac derived member of the natriuretic peptide family. We have previously provided the first reports that the signal peptide of CNP (CNPsp) is present in the human circulation and is elevated in those with chest pain suspicious of ACS. Here, show that CNPsp levels are highly predictive of new MI, MACE and post-index bleeding in patients presenting with potential ACS.

Methods

We prospectively recruited 493 patients presenting with the primary complaint of acute chest pain to our hospital ED. Patients were adjudicated as ACS by 2 independent cardiologists in accordance with ESC guidelines with hsTnI as biomarker. Plasma EDTA samples taken at presentation and 2 hours after were interrogated for CNPsp measurements using our validated, specific assay. Clinical data/variables, standard biochemistry analytes, hsTnT and NT-proBNP (both Roche Cobas e411) were also measured. Statistical assessments were made using SPSS v23. Data for all biomarkers were treated as continuous variables and are presented as median (interquartile range, (IQR)). Statistical assessment of the comparative abilities of CNPsp, hsTnT, NT-proBNP and hsTnI (log values) to predict new MACE, MI, bleeding and mortality within 2 yrs of index presentation was undertaken using a logistic regression base model (95% CI) that included all clinical variables and hsTnI and hsTnT and NT-proBNP, with CNPsp added to into the multivariate analyses.

Results

Of the 493 recruited patients (median age 63 (IQR: 54–73, 35% female), 148 were adjudicated to have ACS (30%, 109 MI, 39 UAP). Presentation CNPsp levels were not higher in those with adjudicated ACS versus non-ACS (51, (45–65) vs. 50, (42–63) pmol/L, P=0.412), did not correlate with hsTnI, hsTnT or NT-proBNP, but were significantly lower in those with a history of MI (49, (42–59) vs. 51, (43–64) pmol/L, P=0.044). In contrast, they were significantly higher in those with ECG ST-depression (56, (47–85) vs. 50 (42–62) pmol/L, P=0.038). In the multivariate regression model of all 493 patients, lower values of CNPsp were a significant multivariate predictor of new MI (n=37, 95% CI: 0.06–0.89, P=0.038), MACE (n=64, 95% CI: 0.08–0.81, P=0.020) and new bleeding (n=40, 95% CI: 0.05–0.63, P=0.005) within 2 years of presentation. This predictive ability was additive and independent from NT-proBNP and troponin.

Conclusion

This is the first report that CNPsp measurement provides meaningful and independent risk assessment of important outcomes in ACS patients. In particular, the fact that lower levels of CNPsp are predictive of negative MI, MACE and bleeding outcomes suggests that CNPsp may have an unappreciated protective role in the cardiovascular system.

Acknowledgement/Funding

Health Research Council of New Zealand; Heart Foundation of New Zealand
P3418The relationship between circulating vitamin d3 and subclinical atherosclerosis in elderly asian: contributor or bystander?
Authors: Lu Y , Chou R , Tsai Y , Huang P
Published: October 2019

Background

Vitamin D deficiency had been suggested to be the risk factor of cardiovascular diseases and metabolic disorders. However, current evidence about the association between vitamin D deficiency and atherosclerosis are conflicted and inconclusive.

Purpose

We tried to investigate the relationship between serum vitamin D concentrations and subclinical atherosclerosis in the elderly Asian population.

Methods

The I-Lan longitudinal study (ILAS), 1798 community-dwelling adults older than 50 years old were enrolled and divided into two groups according to serum vitamin D level (sufficient, ≥20 ng/mL, and deficient <20 ng/mL). The concentrations of serum vitamin D3 was measured by chemiluminescence immunoassay and demographic data recorded from chart review. The carotid intima-media thickness (cIMT) was measured at bilateral common carotid arteries. Subclinical atherosclerosis was defined as mean cIMT more than 0.81mm, which had been proved to be associated with an increased risk of stroke and coronary events.

Results

Subjects with vitamin D deficiency (n=604, 33.6%) were younger, composed of more woman, smoker, with a higher incidence of hypertension, dyslipidemia, and metabolic syndrome. Compared with subjects without vitamin D sufficiency, patients with vitamin D deficiency were associated with lower risk of subclinical atherosclerosis (crude OR: 0.63, 95% CI: 0.50–0.81, p<0.001) in the univariate analysis. However, after adjusting gender and age, vitamin D deficiency was no more associated with risk of subclinical atherosclerosis.

Risk of vitD3 and cIMT Subclinical Atherosclerosis (cIMT >0.8mm) Odds Ratio 95% Confidence Interval p-value Model 1   Vit D3 normal (≥20) Reference – –   Vit D3 deficiency (<20) 0.63 0.50–0.81 <0.001 Model 2   Vit D3 normal (≥20) Reference – –   Vit D3 deficiency (<20) 0.81 0.62–1.06 0.127 Model 3   Vit D3 normal (≥20) Reference – –   Vit D3 deficiency (<20) 0.93 0.69–1.24 0.599 Model 1: adjust for vit D3 (univariate); Model 2: adjusted for age, vit D3, Gender; Model 3: adjusted multivariate significantly in univariate analysis.

Conclusion

Vitamin D deficiency was not an independent risk factor for subclinical atherosclerosis in the elderly Asian population. The association observed in the univariate analysis may be confounded by gender difference or comorbidities.
P3428Algorythm for estimation of long-term prognosis for patients with AMI complicated with acute cardiorenal syndrome
Authors: Siverina A , Skorodumova E A , Kostenko V A , Skorodumova E G , Pivovarova L P , Ariskina O B , Fedorov A N , Rysev A V , Malishev M
Published: October 2019

Objective

To develop medical and statistical model to assess the long-term prognosis (1,5 years) in patients with myocardial infarction (MI) and acute kidney injury (AKI).

Materials and methods

227 patients treated in our Institute of emergency care were examined. in 2016 about MI. Sex distribution included 60,2% males and 39,8% females. Average age: 67,1±4,2 years. 1st group included 105 patients with MI had AKI, 2nd one – 122 patients without AKI. Cohorts were comparable by sex and age. Patients were followed-up for 18 months: 15 patients died (12 with in the 1st group, 3 in the 2-nd).At the hospital biochemical and haematological tests (glucose, serum creatinine and WBC levels) were performed, as well as polymorphisms of the NOS3 gene T786C were detected. Results were statistically processed.

Results and discussion

Medico-statistical model was created for the total sample of deaths in the long term period using the method of the classification trees (see Fig. 1). Data obtained showed that the first order node was the distribution of genotypes of polymorphism T786C of NOS3 gene. Patients with the homozygous genotype CC died 10 times more often - 27,8%, people's with the genotypes TT and TC mortality was 2,6%. In patients with the genotype CC elevated levels of WBC in the blood was found, and their levels in frames of 9,9–12,0×109/l were correlated with mortality increased by 97,8%, and further WBC elevation up to 12 ×109/l led to 100% mortality. A third-order node can be considered as the level of serum creatinine at the time of discharge. It's elevation >127 μmol/l correlated with increased mortality in patients with TT and TC genotype by 21,4%, and with associated hyperglycemia >9,3 mmol/l reached 100%. Leukocytosis in patients with TT and TC genotype and serum creatinine >127 μmol/l increased mortality up to 15,5%. The obtained model was tested with the use of ROC-analysis. The area under the curve was – 0,97, which corresponds to the expert assessment as “excellent”. The sensitivity of the model was 93,9%, specificity 83,5%.

Figure 1. Model of long-term prognosis assessment

Conclusion

The proposed medical-statistical model, which includes biochemical (serum creatinine), haematological (WBC) and genetic (polymorphism T786C of NOS3 gene) markers, allows to predict unfavorable outcomes in patients with MI and AKI for a long-term period up to 1,5 years.
P3437Impact of epicardial adipose tissue on global longitudinal strain: a study in patients with normal left ventricular ejection fraction
Authors: Maimaituxun G , Kusunose K.E.N.Y.A , Fukuda D.A.I.J.U , Yagi S , Torii Y , Hirata Y.U.K.I.N.A , Nishio S , Yamada N A O , Yamada H , Soeki T , Wakatsuki T , Sata M , Shimabukuro M
Published: October 2019

Background

Epicardial adipose tissue (EAT) locates anatomically and functionally contiguous to the myocardium and coronary arteries. It has been suggested that EAT accumulation is associated with cardiac remodeling and impaired cardiac performance. However, its role in left ventricular (LV) wall strain remains unclear.

Purpose

In this study, we aimed to clarify: whether EAT accumulation is related to global longitudinal (GLS), circumferential (CS) and radial strain (RS); and if so, in which extent or by which amount of EAT are required to deteriorate these strain.

Methods

Total 180 patients who had no obstructive coronary artery disease (CAD) on multi-detector computed tomography (MDCT) coronary angiography and normal left ventricular ejection fraction (LVEF) on conventional echocardiography were recruited. Cardiac CT was used to quantify EAT volume (EATV) and echocardiographic speckle tracking was used to measure the GLS, CS and RS. EATV index (EATV/Body surface area) was determined as: EAT volume, the sum of the EAT area from the base to the apex of the heart (cm3)/body surface area (m2). Adipose tissue was determined as the density range between −190 and −30 Hounsfield unit. According to the median value (68 cm3/m2), patients were divided into lower and higher EATV index two groups.

Results

In higher EATV index group (95±19 cm3/m2), mean age, body mass index (BMI), prevalence of hyperlipidemia and prevalence of CAD were larger than in lower EATV index group (48±14 cm3/m2). Male gender, hypertension, diabetes, smoking and LV mass index were comparable between two groups. Patients in higher EATV index had lower GLS than those in lower EATV index (−19.4±1.2% vs. −18.8±1.3%, p=0.002). However, there were no significant difference between two groups regarding to the CS and RS. Linear regression analysis showed that there was strong correlation between EATV index and GLS (R=0.216, p=0.004); whereas, both RS and CS were strongly associated with the interventricular septum thickness (RS: R=0.248, p=0.003; CS: R= −0.192, p=0.023) and relative wall thickness (RS: R=0.178, p=0.036; CS: R= −0.184, p=0.030) but not with EATV; on multiple regression analysis, EATV was a predictor of GLS independent of age, male gender, BMI, diabetes, hyperlipidemia, hypertension and CAD (Adjusted R2=0.238, p<0.001).

Conclusion

EATV is independently associated with GLS despite the preserved LVEF and lacking of obstructive CAD, and may play a significant role in estimating impaired longitudinal LV performance.
P3444Overweight and obesity in a Mediterranean pediatric population: impact in cardiac chambers morphology and systolic function
Authors: Fernandez Cabeza J , Aristizabal Duque C U , Blancas Sanchez I M , Ruiz Ortiz M , Delgado Ortega M , Rodriguez Almodovar A , Romero Saldana M , Fonseca Del Pozo F J , Pan Alvarez Ossorio M , Mesa Rubio D
Published: October 2019

Background

Obesity is a major medical and public health problem. A high body mass index has been associated with increased mortality and cardiovascular disease morbidity. Obesity in adults is related to hypertrophy and left ventricular dilatation. Previous studies have shown that, in Spain, the prevalence of overweight and obesity in childhood is 26% and 12.6% respectively. The association between obesity and left ventricular morphology has been poorly studied in the pediatric population.

Aim

To investigate the relationship between childhood obesity and the dimensions of cardiac structures and systolic function in a Mediterranean pediatric population.

Methods

A random sample of children and adolescents in primary and secondary education was selected, stratified by age, gender and educational centers in a rural town of 2864 inhabitants in southern Spain. Children between 6 and 17 years old were included. A transthoracic echocardiogram was performed for the evaluation of cardiac chambers morphology and systolic function.

Results

A total of 212 children were studied (10.9±3.0 years old and 51.9% males): 106 (50%) were normal weight, 57 (26.9%) were overweight and 49 (23.1%) were obese. Results are shown in the table. Age and sex were similar in the three groups. Overweight and obesity were related to larger values of left ventricle end-diastolic diameter and volume, left atrial volume and right ventricle basal diameter, and lower values of left ventricle ejection fraction.

Normal weight Overweight Obese p Age 10.9±3.2 10.7±2.7 11.0±2.8 0.79 Male (%) 50.9% 49.1% 57.1% 0.69 End-diastolic left ventricle diameter (mm) 41.1±5.5 42.8±5.4 44.2±5.5 0.003 End-diastolic left ventricle volume (mm) 57.9±18.6 64.3±18.3 78.1±22.4 <0.0005 Interventricular septum (mm) 6.3±1.4 6.7±1.3 7.0±1.7 0.01 Left ventricle mass (g) 69.3±30.1 80.9±30.2 94.8±36.5 <0.0005 Left atrium volume (mm) 19.7±6.8 22.6±6.5 27.9±7.4 0.004 Basal right ventricle diameter (mm) 27.6±4.5 28.0±3.9 30.2±4.2 0.001 Left ventricle ejection fraction (%) 65.7±3.6 63.6±4.7 61.5±4.6 <0.0005

Conclusions

Overweight and obese children have larger cardiac chambers, higher left ventricular mass, and worse systolic function compared with normal weight children of similar age and sex.
P3453Gender difference in impact of ischemic heart disease on long-term outcome in patients with heart failure reduced ejection fraction
Authors: Kim H J , Kim M A , Lee D I , Kim H L , Choi D J , Han S , Cho M C , Jeon E S , Kim J J , Yoo B S , Shin M S , Chae S C , Ryu K H , Kang S M
Published: October 2019

Background

Ischemic heart disease (IHD) is a major underlying etiology in patients with heart failure (HF). Although the impact of IHD on HF is evolving, there is a lack of understanding of how IHD affects long-term clinical outcomes and uncertainty about the role of IHD in determining the risk of clinical outcomes by gender.

Purpose

This study aims to evaluate the gender difference in impact of IHD on long-term clinical outcomes in patients with heart failure reduced ejection fraction (HFrEF).

Methods

Study data were obtained from the nationwide registry which is a prospective multicenter cohort and included patients who were hospitalized for HF composed of 3,200 patients. A total of 1,638 patients with HFrEF were classified into gender (women 704 and men 934). The primary outcome was all-cause death during follow-up and the composite clinical events of all-cause death and HF readmission during follow-up were also obtained. HF readmission was defined as re-hospitalization because of HF exacerbation.

Results

133 women (18.9%) were died and 168 men (18.0%) were died during follow-up (median 489 days; inter-quartile range, 162–947 days). As underlying cause of HF, IHD did not show significant difference between genders. Women with HFrEF combined with IHD had significantly lower cumulative survival rate than women without IHD at long-term follow-up (74.8% vs. 84.9%, Log Rank p=0.001, Figure 1). However, men with HFrEF combined with IHD had no significant difference in survival rate compared with men without IHD (79.3% vs. 83.8%, Log Rank p=0.067). After adjustment for confounding factors, Cox regression analysis showed that IHD had a 1.43-fold increased risk for all-cause mortality independently only in women. (odds ratio 1.43, 95% confidence interval 1.058–1.929, p=0.020). On the contrary to the death-free survival rates, there were significant differences in composite clinical events-free survival rates between patients with HFrEF combined with IHD and HFrEF without IHD in both genders.

Figure 1

Conclusions

IHD as predisposing cause of HF was an important risk factor for long-term mortality in women with HFrEF. Clinician need to aware of gender-based characteristics in patients with HF and should manage and monitor them appropriately and gender-specifically. Women with HF caused by IHD also should be treated more meticulously to avoid a poor prognosis.

Acknowledgement/Funding

None
P3462IDO activity forecasts obesity in premenopausal females in 10-year follow-up study: the Cardiovascular Risk in Young Finns Study
Authors: Niinisalo P , Raitakari O T , Kahonen M , Viikari J , Juonala M , Kaaja R
Published: October 2019

Background

Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that has an important immunomodulator function. Human inflammatory response promotes upregulation of IDO level in blood. This may lead to suppression of inflammation in atherosclerotic vessel wall and consequently may slow the progression of the disease. Previous studies have shown that IDO activity correlates with early signs of atherosclerosis especially in females but is not an atherosclerosis-specific marker.

Materials and methods

IDO levels were measured from females (n=544; age 24–39; weight 40.5–134.4 kg) in 2001 along with several risk factors for atherosclerosis. Follow-up risk factor measurements were performed in 2007 and 2011. Here we aimed to elucidate the relationship between IDO measurements from 2001 and several atherosclerotic risk factors from 2007 and 2011 by analyzing correlations and risk ratios from the Cardiovascular Risk in Young Finns Study patient cohort.

Results

After age standardization, IDO correlated significantly with BMI (p=0.0008), waist (p=0.0009) and logarithmically modified triglycerides (p=0.0488) and CRP (p=0.0014) in female samples (n=434) from 2007. When female samples (n=384) from 2011 were examined, statistically significant correlations were discovered in BMI and Waist in both unadjusted (p<0.0001 and 0.0003, respectively) and age-adjusted analysis (p=0.0007 and 0.006, respectively). In contrast, only weak correlations were found in male samples. In risk ratio analysis IDO promoted obesity (RR=1.027, p=0.01) in females (n=431) in 10-year follow-up study even after the data was adjusted for age, CRP and BMI.

Conclusions

It is concluded that IDO activity forecasts obesity – a well-characterized risk factor for diabetes and atherosclerosis – in premenopausal females.
P3503Transcriptome changes in atrial myocytes during the transition from a proliferative into a contractile phenotype and vice versa
Authors: Liu J , Tsonaka R , Mei H , Akerboom B , Schalij M , Pijnappels D , De Vries A
Published: October 2019

Background

iAM-1 cells are conditionally immortalized neonatal rat atrial myocytes allowing toggling between proliferative and contractile phenotypes by a single-component change in culture medium composition. In the absence of proliferation stimuli, the cells synchronously differentiate into functional cardiomyocytes. Following re-expression of the immortalization factor, the fully differentiated iAM-1 cells dedifferentiate and start to proliferate again.

Purpose

The aim of our study was to investigate the changes in gene expression profile in iAM-1 cells during one round of cardiac differentiation and dedifferentiation in order to identify potential (new) regulators of atrial myocyte differentiation and proliferation.

Methods

RNA sequencing was performed on iAM-1 cells at 9 time points during one cycle of cardiomyogenic differentiation and dedifferentiation (20 million 150-bp paired-end reads per sample, 4 samples per time point). The resulting sequence data were analysed by EdgeR. Hierarchical clustering and principle component analysis were performed in R. GO category enrichment was determined using DAVID.

Results

Approximately 13,000 genes were extracted from the RNA sequencing analysis. In general, dynamic changes in mRNA levels during the transition from a proliferative into a contractile phenotype opposed those that occurred when differentiated iAM-1 were re-exposed to proliferation stimuli. These inverse trends were most evident for genes involved in cell cycle progression, DNA replication, sarcomere formation and cardiac contraction. Moreover, the RNA-SEQ data allowed us to make a distinction between genes contributing to the early and late phases of cardiomyogenic differentiation and dedifferentiation and to identify similarities and differences in the transcriptional programs underlying the cardiomyogenic differentiation of iAM-1 cells versus those of embryonic stem cells and induced pluripotent stem cells. The transcriptome analysis also unveiled several genes with potentially important and previously unrecognized roles in cardiomyocyte differentiation and proliferation.

iAM-1 differentiation and dedifferention

Conclusions

Due to their ability to homogenously and synchronously differentiate and dedifferentiate, iAM-1 cells offer unique new insights into the transcriptional regulation of cardiomyocyte differentiation and proliferation.
P3506A novel urinary biomarker predicts 1 year mortality after discharge from Intensive Care
Authors: Zhang Z Y , Nkuipou-Kenfack E , Yang W Y , Mujaj B , Thijs L , Latosinska A , Acloque E , Mischak H , Mebazaa A
Published: October 2019

Rationale

Tools reflecting molecular processes predicting death after discharge from intensive care unit (ICU) are currently unavailable.

Objectives

To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.

Methods

In 1081 patients, enrolled in the French and European Outcome Registry in Intensive Care Unit (NCT01367093), the urinary proteome was measured at ICU discharge using capillary electrophoresis couple with mass spectrometry along with clinical variables; circulating biomarkers (NT-proBNP, hsTnT, biologically active adrenomedullin, soluble ST2, and NGAL) and urinary albumin were available in 886 patients.

Measurements and main results

In the discovery sample (60/256 deaths/survivors), support vector machine modelling identified ACM150, mainly consisting of collagen fragments, yielding an AUC of 0.676 (95% CI, 0.615–0.737). In the replication sample (151/608 deaths/survivors), AUC was 0.704 (0.659–0.750). While accounting for center and clinical risk factors, the hazard ratios in all available patients were 1.27 (1.18–1.37) for ACM150 (+1 SD), 1.20 (1.16–1.33) for the Charlson score (+1 point), and ≥1.30 (P≤0.0071) for the other biomarkers (+ 1 SD). Model performance assessed by adding ACM150 to a basic model including the aforementioned covariables, the Charlson score or any other biomarker confirmed the prognostic accuracy of ACM15 with significant increases (P≤0.0038) in integrated discrimination (≥ +0.50) and net reclassification improvement (≥ +53.7) and AUC (≥ +0.037). Interactome mapping (STRING) based on 72 sequenced peptides and 25 parental proteins gravitated around collagen nodes.

Conclusions

ACM150 is a urinary proteomic classifier predicting 1-year post-ICU mortality over and beyond other biomarkers and reflects dysregulation of collagen turnover as underlying pathophysiological process.
P3509Leukocyte derived tumour necrosis factor modulates cardiac function in health and disease
Authors: Walker S , Gutierrez Del Arroyo A , Sanchez J , Ackland G L
Published: October 2019

Purpose

Tumour necrosis factor alpha (TNFα) regulates both normal and pathophysiological cardiac function. The regulatory role of TNFα derived from different sources (leukocyte versus cardiac cells) in cardiac physiology is unclear. Deficiency of iRhom2 protein prevents circulating immune cells from shedding TNFα (and CD62L, an adhesion molecule essential for effective immune function). Here we investigated the role of leukocyte derived TNFα in constitutive cardiac function and after cardiac injury.

Methods

Adult iRhom2-deficient mice (KO) and wildtype (Wt) littermates, of both genders, underwent echocardiography to assess cardiac physiologic function at least 1 week before receiving a single dose of isoproterenol (300mg/kg IP) to induce cellular death in 10% of the cardiomyoctes [1]. Cardiac echocardiography was repeated 36 hours after isoproterenol. Peripheral and cardiac-resident leukocytes were phenotyped by flow cytometry and molecular markers of cardiac stress (atrial and brain natriuretic protein, ANP, BNP) and inflammation (NFkB) were quantified using RT-PCR.

Results

Peripheral leukocytes from iRhom2 KO mice failed to shed CD62L in response to isoproterenol induced cardiac injury (e.g. neutrophils CD62L Mean Fluorescence Intensity KO: 9149±4616, Wt: 972±558, p<0.0001, n=9). iRhom2-deficient mice had higher cardiac output at baseline (KO 23±2 mL/min, n=11) compared to their wildtype littermates (Wt 18±3 mL/min, n=9). Wild type mice increased contractility after isoproterenol (Wt ejection fraction: baseline 60±6%, isoproterenol 68±6%, n=8) whilst iRhom2-deficient mice were unable to (KO ejection fraction: baseline 66±9%, isoproterenol 61±5%, n=8). ANP and BNP mRNA were elevated in ventricular tissue of iRhom2-knockout mice after isoproterenol, when compared to naïve tissue (ANP 2ΔCT: 3x increase, BNP 2ΔCT: 1.6x increase) whereas only ANP was elevated in wildtypes (ANP 2ΔCT: 2.7x increase, BNP 2ΔCT: 0.9x increase). No difference in immune cell infiltration of ventricular cardiac tissue was observed (number of CD45+ cells KO: 3014±3482, Wt: 2555±1411, p=0.7, n=9) NFkB mRNA was upregulated at baseline (2ΔCT KO: 0.2±0.08, Wt: 0.1±0.09) suggesting constitutive cardiac inflammation in iRhom2-deficient mice.

Conclusions

Inability to shed CD62L and TNFα is associated with constitutive and acquired cardiac dysfunction in iRhom2-deficient mice. These data support the hypothesis that leukocyte-derived TNFα is required for maintaining cardiac function in health and disease.

Acknowledgement/Funding

National Institute of Academic Anaesthesia/Royal College of Anaesthetists/British Journal of Anaesthesia; National Institute for Health Research
P3519Sex-based disparities in end of life care among patients with heart failure
Authors: Van Spall H G C , Hill A , Fu L , Ross H , Wunsch H , You J , Fowler R
Published: October 2019

Background

There are sex-based disparities in care and outcomes among patients with heart failure (HF), but the association between sex and health care services received at the end-of-life health is unknown.

Purpose

To assess for sex-based differences in location of death and the type and intensity of health care services received at the end of life among patients with HF.

Methods

We conducted a retrospective cohort study of adults (≥18 years) who died between April 1, 2004 and March 31, 2017 in Ontario, Canada. We included decedents who had a diagnosis of HF and a hospitalization for HF in the year preceding their death. We obtained demographic, clinical, health care utilization, and healthcare system cost data from population-based administrative databases, using unique encrypted identifiers to link records. We used descriptive statistics and a 2-level multivariable logistic regression model with patients (1st level) nested in regions (2nd level) to assess whether sex was independently associated with death in hospital.

Results

We identified 396,024 adults (51.5% women) who died of HF between April 1, 2004 and March 31, 2017. Mean (SD) age at death was 81.8 (10.7) years and a majority of deaths (53.4%) occurred in the hospital. During the last 6 months of life, a significantly lower proportion of women than men experienced emergency department visits (81.7% vs 86.5%; p<0.001); hospitalizations (75.6% vs 80.8%; p<0.001); intensive care unit (ICU) admissions (22.8% vs 30.1%; p<0.001); mechanical ventilation (15.5% vs 20.8%; p<0.001); cardiac catheterization (2.8% vs 4.6%; p<0.001); coronary revascularization (1.5% vs 2.6%; p<0.001); hemodialysis (4.8% vs 7.7%; p<0.001); or care from 10 or more different physicians (57.6% vs 67.1%; p<0.001). In the last 6 months of life, women spent fewer days than men in the hospital (mean 16.4 vs 18.3; mean difference [MD] 1.9 [95% confidence interval 1.7–2.0]; p<0.001), in an ICU (mean 2.1 vs 3.0; MD 0.9 [95% CI 0.8–0.9]; p<0.001), and on a ventilator (mean 1.4 vs 1.9; MD 0.5 [95% CI 0.5–0.5]; p<0.001). These differences persisted and remained significant in the last month of life. There was no difference in the proportion of women vs men receiving palliative care services (45.1% vs 45.0%; p=0.53) in the last 6 months of life. After adjusting for age, socioeconomic status, comorbidities, place of residence, and year of death, women had lower odds of dying in a hospital than men (adjusted odds ratio 0.88 [95% CI 0.87–0.89]).

Conclusion

In this large cohort study in Ontario, Canada, women with HF received disproportionately lower in-hospital and invasive care services than men in their last 6 months of life and were more likely than men to die at home.

Acknowledgement/Funding

Canadian Institutes of Health Research
P3525Buspirone effect on chemoreflex and central apneas in heart failure
Authors: Borrelli C , Giannoni A , Mirizzi G , Emdin M , Passino C
Published: October 2019

Background

Increased chemosensitivity to carbon dioxide (CO2) is an important trigger of central apneas in heart failure (HF), contributing to HF progression and mortality. We hypothesized that buspirone, a 5HT1A receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO2 chemosensitivity, thus preventing CA in patients with HF.

Methods

Sixteen patients with systolic HF (age 71.3±5.8 years, left ventricular ejection fraction 29.8±7.8%) and moderate-severe central apneas (nighttime apnea/hypopnea index AHI≥15 events/hour) underwent a double-blind, placebo-controlled, cross over, randomized study of oral buspirone administration (45 mg/day for 1 week).

Results

Buspirone reduced CO2 chemosensitivity compared to placebo (1.2 IR [1.1–1.5] vs. 2.0 [1.6–2.2] L/min/mmHg, p=0.008). Furthermore, buspirone improved: the AHI at nighttime (16.5 [8.5–24.7] vs. 27.5 [23.0–37.3] events/hour, p=0.002), and daytime (8.0 [2.3–11.5] vs. 11.5 [6.3–18.8] events/hour, p=0.006); the central apnea index at nighttime (4.0 [1.0–19.0] vs. 12.5 [8.3–27.3] events/hour, p=0.01) and daytime (1.0 [0.0–3.0] vs. 4.0 [1.3–6.0] events/hour, p=0.009); and the oxygen desaturation index at nighttime (4.7 [1.0–11.0] vs. 20.0 [8.7–26.5] events/hour, p=0.004) and daytime (0.2 [0.1–0.7] vs. 1.2 [0.3–4.8] events/hour, p=0.005). Buspirone showed a good safety profile and had no effect on neurohormones, arrhythmias, exercise capacity and mood/daytime sleepiness.

Conclusion

Buspirone reduces CO2 chemosensitivity and inhibits central apneas both during the day and the night in patients with systolic HF.
P3542Natriuretic peptides added to clinical parameters predict two-year prognosis of patients with chronic heart with mid-range and reduced ejection fraction
Authors: Spinar J , Spinarova L , Spinarova M , Labr K , Jarkovsky J , Ludka O , Krejci J , Malek F , Ostadal P , Parenica J
Published: October 2019

Background

The guidelines recommend to determine natriuretic peptides, clinical status (NYHA classification) and comorbidities in order to predict the prognosis in patients with heart failure. The aim ofthis registry was to develop a prognostic score in chronic heart failure patients, using clinical status, comorbidities and natriuretic peptides.

Methods

Consecutive 1088 patients with stable chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40–49%) were enrolled. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (MACE).

Results

The occurrence of MACE was 14.9% and increased with higher NYHA, 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III-IV) (p<0.001). The occurrence of MACE was 3%, 10% and 15–37% in patients with NT-proBNP levels ≤125pg/ml, 126–1000pg/ml and >1000pg/ml respectively. Discrimination abilities of NYHA and NT-proBNP were (AUC 0.670; p<0.001 and AUC 0.722; p<0.001). The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and taking a higher dose of loop diuretics (>40 mg furosemide daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790).

Conclusion

Natriuretic peptides, clinical status and comorbiditis predict two year prognosis and they can help to a better identification of a high-risk groups of patients with heart failure with reduced and mid range ejection fraction in which more intense treatment should be considered, mainly LVAD implantation or listing to heart transplantation waiting list.

Acknowledgement/Funding

None
P3559Renal sympathetic nerve activity, assessed by renal 123-iodine metaiodobenzylguanidine scintigraphy, reflects disease severity in heart failure with reduced ejection fraction
Authors: Yoshitaka Y , Murai H , Tokuhisa H , Takamura M
Published: October 2019

Background

Sympathetic nerve activity is related to cardio-renal syndrome, which plays a crucial role in deterioration in heart failure with reduced ejection fraction (HFrEF). Previous studies reported that renal denervation was effective in HFrEF patients. Recently, we have demonstrated that renal 123-iodine metaiodobenzylguanidine (MIBG) scintigraphy is useful for assessment of renal sympathetic function in hypertension. However, it is unclear whether renal MIBG would reflect disease severity in HFrEF patients.

Methods

Twenty-four HFrEF patients and eleven control without heart failure were included in this study. HFrEF patients were performed MIBG and MSNA and hemodynamics inspection using Swan-Ganz's catheter (SGC). HFrEF was defined as echocardiography with EF of 50% or less. MSNA was recorded from the right peroneal nerve to evaluate direct sympathetic nerve activity to the peripheral vascular bed. MSNA was expressed as the number per minute (burst frequency = BF) and the number per 100 heartbeats (burst incidence = BI). Renal MIBG scintigraphy was simultaneously performed with cardiac MIBG scintigraphy. The 20 minutes (early) and 180 minutes (delayed) kidney-to-mediastinum ratio (K/M), early and delayed heart-to-mediastinum ratio (H/M), and washout rate (WR) were measured.

Results

In the HFrEF group, the EF was significantly lower than control group (EF 34.8±9.51% vs. 63.0±7.43, p<0.01), and MSNA parameters were significantly increased (burst incidence (BI), 57.7±18.7 vs. 37.0±11.3, p<0.01; BF 42.7±14.4 vs. 24.1±8.50, p<0.01). WR of cardiac MIBG was not related to MSNA parameters but negatively related to cardiac output (r=−0.46, p<0.05) and stroke volume (r=−0.61, p<0.01) and delayed H/M negatively correlated with mean pulmonary capillary wedge pressure (r=−0.57, P<0.05). WR of both left and right renal MIBG showed a strong correlation with MSNA (BI; left, r=0.69, p<0.01, right 0.60, p<0.01, BF; left, r=0.64, p<0.01, right, r=0.58, p<0.01) and no significant correlation between renal MIBG and hemodynamics parameters. HFrEF patients were divided into stage B and stage C based on American College of Cardiology/American Heart Association (ACC/AHA) classification (stage B, n=13; stage C, n=11). There was no significant difference between the two groups in cardiac MIBG parameters. Renal WRs in stage C was increased than stage B (Lt renal WR,51.6±10.6 vs. 40.6±6.53, p<0.05; Rt renal WR, 43.9±9.97 vs. 35.1±11.3, p<0.05).

Conclusions

Cardiac WR negatively correlated with cardiac output and renal WR correlated with MSNA. Renal WRs had a significant difference in the heart failure stage of ACC/AHA classification, but cardiac MIBG parameters did not. These results indicate that renal MIBG might be useful to assess renal sympathetic nerve activity in patients with HFrEF and suggesting that renal SNA might be promising therapeutic target in HFrEF.