bluuebunny/crossref_metadata_2025 huggingface dataset:
P4166Efficacy and safety of novel biodegradable device for closure of atrial septal defect: from preclinical study to first-in-man experience
Authors: Li Y F , Xie Y M , Xie Z F , Wang S S , Li B N , Zhang Z W
Published: October 2019

Background

closure of atrial septal defect (ASD) has emerged as the treatment of choice for the majority of defect. The biodegradable ASD closure device is a novel, absorbable device made of poly-L_latic acid (PLLA). This study evaluates the feasibility, safety and effectiveness of PLLA biodegradable ASD closure device in a swine model and for the first time in human.

Objective

The study reports on the 24- and 36- month follow-up results of PLLA device implanted in a swine model and the first-in- man experience with 6-month follow-up.

Method

Preclinical study was done in a swine ASD model. In a clinical setting, 5 pediatric patients with a secundum ASD who a clinically left-to-right shunt were enrolled in our center. Percutaneous ASD closure procedure with PLLA device was performed with fluoroscopic and transcatheter echocardiography (TTE) guidance. Procedure results and clinical outcomes at 1 day, 30 days, 3 months and 6 months after closure procedure were analyzed.

Results

24- and 36-month follow-up results of preclinical study demonstrated that the PLLA device exhibited good endothelialization and degradability in a swine model. In clinical study, device implantation was successfully achieved in all of 5 patients (median age, 3.6 years; range, 3.1–6.5 years). The mean ASD size was (13.4±2.4)mm (range, 10–16mm). The mean pulmonary-to-systemic blood flow ratio (Qp:Qs) was (1.7±0.2):1 with a range of 1.5:1 to 2.0:1. The mean procedure time and the mean fluoroscopy time were (36.2±11.3) and (6.4±1.0)minutes, respectively. There was no evidence of short-term complications related to the device or the delivery system. No device dislodgement, significant aortic valve or mitral valve regurgitation, new onset cardiac arrhythmia, or other adverse events were reported.

Characteristics and procedure data of the 5 patients who underwent ASD closure procedure with PLLA device Patient No. Age Weight Gender Defect size Qp:Qs Mean Pulmonary Pressure Device size (mm) Sheath (Fr) Procedure time Fluoroscopy time Immediate residual shunt (years) (kg) (mm) (mmHg) (mm) (Fr) (min) (min) 1 4.9 23.5 Male 17 1.7:1 22 24 12 52 7.6 None 2 3.1 10.0 Male 14 2.0:1 19 20 12 26 5.4 None 3 6.5 21.0 Male 15 1.8:1 22 20 12 31 6.0 None 4 3.2 14.5 Female 12 1.5:1 13 18 10 44 7.3 None 5 3.6 12.5 Male 10 1.5:1 17 14 10 28 5.5 None

Conclusion

This study is the first to demonstrate the feasibility, safety and effectiveness of PLLA biodegradable device in human, with no evidence of short-term complications and a high rate of early shunt closure.

Acknowledgement/Funding

National Key R&D Program of China (Grant Number: 2016 YFC1100305)
P4346Religious education and midlife observance are associated with lower coronary heart disease (CHD) mortality 23 years later
Authors: Eilat-Adar S , Goldbourt U
Published: October 2019

Objective

To determine whether self-reported religiosity is associated with decreased coronary mortality risk in middle-aged men when rates are adjusted for known confounders.

Design

The Israeli Ischemic Heart Disease (IIHD) Project (n=10,232) was chosen by stratified sampling of civil servants and municipal male employees, men aged 40–65 in 1963. Subjects were seen upon enrollment (1963) and at two follow-up visits (1965 and 1968). Extent of religiosity according to belief and practice collected in 1965 on a scale from 1 to 5. Religiosity was defined as follow: (1) The most-strict observance of religious rules “Haredim”. (2) “Religious” (3) “Traditional” (4) “Secular” (5) The part of the latter who declared themselves to be “nonbelievers” were categorized as “agnostic”.

Main outcome measure

Coronary heart disease (CHD) death, determined from death certificates in 23 years of follow-up

Results

Among 9245 participants, 1098 died from CHD during 23 years follow up. Ever smoking, Body mass index (BMI) and socioeconomic status were significantly lower while age and diabetes were higher according to increasing religiosity. Religiosity was inversely related to CHD mortality. Demographic, anthropometric characteristics according to religion, and odds ratio (OR), 95% confidence interval (95% CI), for CHD mortality, (using agnostic as a reference group) are presented in table 1.

Characteristics according to religion Religiosity Haredim (n=2103) Religious (n=1528) Traditional (n=1782) Secular (n=2085) Agnostic (n=1747) P for trend Age years (SD) 50.2 (6.9) 48.8 (6.6) 48.4 (6.7) 48.8 (6.6) 45.9 (6.8) <0.001 Ever smoking% 58.7 67.6 70.7 71.9 72.6 0.001 Systolic blood pressure (mmHg) 136 (21) 135 (20) 135 (21) 134 (20) 135 (20) 0.115 Diabetes (%) 9.8 11.1 8.3 8.8 6.5 <0.001 Socioeconomic status 2.2 (1.3) 2.3 (1.1) 2.7 (1.1) 2.7 (1.2) 3.1 (1.4) <0.001 BMI kg/m2 (SD) 22.5 (3.6) 25.9 (3.5) 25.9 (3.2) 25.6 (3.2) 25.4 (2.9) 0.028 Cholesterol (mg%) 201 (38) 207 (41) 208 (39) 214 (40) 218 (40) 0.001 Number of death (% category) 187 (8.9) 161 (10.5) 185 (10.4) 228 (10.9) 225 (12.9) <0.001 OR (95% CI)* 0.67 (0.53–0.85) 0.85 (0.67–1.08) 0.84 (0.67–1.05) 0.87 (0.71–1.08) 1 *Adjusted for age, cigarette smoking, systolic blood pressure, diabetes, socioeconomic status, body mass index and cholesterol.

Conclusion

Religiosity was associated with lower CHD death in employed middle aged Israeli men followed up prospectively for 23 years.
P4347Automated echocardiographic quantification of left ventricular ejection fraction without volume measurements using a machine learning algorithm mimicking a human expert
Authors: Asch F M , Poilvert N , Abraham T , Jankowski M , Cleve J , Adams M , Romano N , Hong H , Mor-Avi V , Lang R M
Published: October 2019

Background

Echocardiographic quantification of left ventricular (LV) ejection fraction (EF) relies on either manual or automated identification of endocardial boundaries followed by standard calculation of model-based end-systolic and end-diastolic LV volumes. Recent developments in artificial intelligence resulted in computer algorithms that allow near automated detection of endocardial boundaries and measurement of LV volumes and function. However, boundary identification is still prone to errors limiting accuracy in certain patients. We hypothesized that a fully automated machine learning algorithm could be developed, which circumvents border detection and instead estimates the degree of ventricular contraction, similar to a human expert trained on tens of thousands of images.

Purpose

This study was designed to test the feasibility and accuracy of this approach.

Methods

Machine learning algorithm was developed and trained on a database of >50,000 echocardiographic studies, including multiple apical 2- and 4-chamber views, to automatically estimate LVEF (AutoEF, BayLabs). Testing was performed on an independent group of 99 unselected patients, whose automated EF values were compared to reference values obtained by averaging measurements by 3 experts using conventional volume-based technique. Inter-technique agreement was assessed using linear regression and Bland-Altman analysis of bias and limits of agreement (LOA). Consistency was assessed by mean absolute deviation (MAD) among automated estimates based on different combinations of apical views. Finally, sensitivity and specificity of detecting of EF≤35% was calculated. These metrics were compared side-by-side against the same reference standard to those obtained from conventional EF measurements by clinical readers.

Results

Automated estimation of LVEF was feasible in all 99 patients. AutoEF values showed high consistency (MAD=2.9%) and excellent agreement with the reference values: r=0.95, bias=1.0%, LOA=±11.8%, with sensitivity 0.90 and specificity 0.92 for detection of EF≤35%. This was similar to clinicians' measurements: r=0.94, bias=1.4%, LOA=±13.4%,sensitivity 0.93, specificity 0.87.

Conclusions

Machine learning algorithm for volume-independent LVEF estimation is highly feasible and similar in accuracy to conventional volume-based measurements, when compared to reference values provided by an expert panel.

Acknowledgement/Funding

Bay Labs, Inc.
P4371Right ventricular remodeling during the first weeks of life in healthy neonates
Authors: Sandoe A , Silesen A S , Raja A A , Pihl C , Vejlstrup N , Iversen K , Bundgaard H
Published: October 2019

Background

The right ventricle (RV) serves as the dominant ventricle in utero. The transition from fetal to post-natal circulation at birth involves marked structural and functional cardiac changes including a large increase in pulmonary blood flow and closure of fetal shunts. Little is known about how the transitional circulation influences RV structure and function in healthy neonates during the first weeks of life. The purpose of this study was to systematically assess RV remodeling in a large, unselected cohort of healthy neonates.

Methods

Transthoracic echocardiograms of unselected neonates <26 days old without any signs of structural cardiac abnormalities performed between April 1st, 2016 and August 12th, 2017, were consecutively included from the Copenhagen Baby Heart study until at least 90 neonates per day were included. Left parasternal long-axis RV anterior end-diastolic wall thickness and short-axis RV outflow tract end-diastolic diameter were measured offline by one sonographer according to recommendations by the American Society of Echocardiography. RV parameters were corrected for body surface area (BSA). Comparisons were made by T-tests and correlations were computed using univariate linear regression.

Results

A total of 3,412 echocardiograms were assessed, of which 414 were excluded due to age ≥26 days (n=159), presence of cardiac abnormality (n=179), or suboptimal parasternal views (n=76). Thus, a total of 2,998 (48% male) were included for analysis. Age, weight, and length at examination were (mean±SD) 11.1±7.5 days, 3.6±0.6 kg, and 52±2.6 cm, respectively. BSA-corrected mean (95% CI) end-diastolic outflow tract diameter and end-diastolic anterior wall thickness according to age are presented (Figure). There was a small age-related reduction in end-diastolic RV outflow tract diameter (r2=0.018, p<0.001), whereas the BSA-corrected end-diastolic anterior wall thickness decreased by 35% (from 14.2 to 9.2 mm/m2, p<0.001) from birth to day 25.

Figure 1. Mean (95% CI) BSA-corrected end-diastolic RV anterior wall thickness and end-diastolic RV outflow tract diameter. P-value for correlation.

Conclusion

RV remodeling during the first 25 days of life in unselected neonates included a small decrease in RV outflow tract diameter and a 35% decrease in anterior wall thickness.
P4426Prolonged troponin t elevation in male and female master athletes after long-distance running
Authors: Eliasson S A , Sarajlic P , Wandell P , Wallen H , Back M , Braunschweig F
Published: October 2019

Background

Troponin levels may be elevated after long-distance running, probably due to increased membrane permeability of cardiomyocytes. It is believed that elevated troponin post exercise, in contrast to acute coronary syndromes, normalize within 24 (−48) hours. This phenomenon has been mainly studied in young and elite athletes. However, participation in endurance exercise is increasingly popular among elderly and recreational sportsmen.

Purpose

To assess troponin levels in master athletes before and up to 7 days after long-distance running.

Method

We studied 97 participants (56 males and 41 females, matched for age) in the world's largest cross-country race (30 km, Lidingöloppet). They were ≥45 years (53±5 years). Baseline evaluation included a physical exam, blood pressure, BMI, NT-proBNP and an ECG. Blood tests were taken at baseline, immediately after as well as 1d, 4d and 7d after the race, including high sensitive troponin T (TnT), creatinine and high sensitive CRP. Elevated TnT was defined as ≥15 ng/l.

Results

After the race TnT had increased from 5±3 ng/l at baseline to 46±32 ng/l (range 11–180; p<0.0001). TnT was still significantly elevated at day 1 (16±16ng/l, range 4–106; p<0.0001) and day 4 (8±8 ng/l, range 4–63; p<0.01) with a borderline increase at day 7 (6±3; range 4–22; p=0.062). Both men and women showed a significant TnT increases at day 1 and day 4. Elevated TnT above the diagnostic threshold for myocardial infarction was observed in 96% (post race), 34% (day 1), 9% (day 4) and 3% (day 7). Males had generally higher TnT levels. At day 1, elevated TnT levels were present in 39% of males and 17% of females while all subjects with elevated TnT at day 4 and day 7 were male.

Conclusion

TnT is elevated in the vast majority of male and female master athletes after participation in a 30 km cross country race. To our knowledge, this is the first report showing that TnT levels can be still significantly elevated four days after endurance running. Prolonged TnT values above the diagnostic threshold for myocardial infarction were predominantly seen in males. Our findings are relevant to the clinical management of patients with increased troponin values after endurance exercise.

Acknowledgement/Funding

Hjärt och lungfonden (Swedish heart- and lung fund). Governmental grants.
P4462Atorvastatin and fenofibrate exert opposite effects on the vascularization and characteristics of visceral adipose tissue
Authors: Perez-Mendez O , Luna-Luna M , Mondragon-Garcia A , Aranda-Fraustro A
Published: October 2019

Background

Statins may precipitate the onset of type 2 diabetes (T2D) in high-risk patients. In contrast, only the subset of individuals with insulin resistance (IR) and/or diabetes receives cardiovascular benefits with fibrates. The mechanism responsible of such effects may be related with visceral adipose tissue (VAT). In this context, previous observations have suggested that atorvastatin induced an increase of VAT whereas fenofibrate had the opposite effects in rabbits.

Purpose

To determine the mass, morphology and vascularization of VAT in New Zealand white rabbits that received of atorvastatin or fenofibrate during two months.

Methods

New Zealand white rabbits (n=6 per group) received by oral gavage during 2 months, 0.33 mg/kg of atorvastatin or 2.6 mg/kg fenofibrate. The control group received 0.5 mL of vehicle. Plasma lipids were monitored. The visceral adipose tissue (VAT) was dissected and quantified. The expression of genes related with vascularization, VEGF-A and TGF-β, FGF2 as well as TNF-α were determined by qPCR in VAT. Histological slices were stained by hematoxilin and eosin to determine the size of adipocytes. The marker of angiogenesis, PECAM-1, was determined by immunohistochemistry.

Results

As expected, the cholesterol from atorvastatin was lower after treatment while triglycerides decreased in fenofibrate group. The mass of VAT from fenofibrate group was 46% lower compared with the controls meanwhile atorvastatin was associated with a larger diameter of adipocytes (+65%) than that of the control and fenofibrate groups. FGF2 gene expression was lower in fenofibrate than in control group (−54%). By contrast, VEGF-A gene expression in fenofibrate-treated rabbits was 110% higher than in control group. TGF-β and TNF-α remained comparable among groups. In agreement with the gene expression, the marker of angiogenesis PECAM-1 was slightly but significantly higher (+10%) in rabbits treated with fenofibrate than in controls, as determined by immunohistochemistry.

Conclusion

Fenofibrate enhanced the VEGF-A gene expression, PCAM-1 in VAT whereas decreased its total mass. In contrast, atorvastatin increased the adipocyte size without any effect on vascularization markers. These results suggest that fenofibrate is associated with a favorable remodeling of VAT, in contrast with atorvastatin, which induced a non-favorable remodeling of VAT. These results may be related with the cardiovascular benefits of fenofibrate and the increased risk of T2D in high-risk subjects induced by atorvastatin.
P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension
Authors: Keck M , De Almeida H , Compere D , Inguimbert N , Flahault A , Balavoine F , Roques B P , Llorens-Cortes C
Published: October 2019

Background

Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration.

Purpose

However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity.

Methods

We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements.

Results

We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations.

Conclusions

This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment.

Acknowledgement/Funding

ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.
P4482Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers
Authors: Soares Sturzeneker M C , Noronha L , Olandoski M , Wendling L U , Precoma D B
Published: October 2019

Background/Introduction

Hypertension is highly prevalent in NAFLD patients (39%). NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies and emerge as the most frequent cause of chronic hepatic disease in adults. Therefore, we can deduce that treating hypertension in NAFLD carriers will be often necessary. However, there are no established criteria for choosing the most appropriate drug therapy for hypertension in patients with NAFLD, and the basic research may be the first step to the development of these criteria.

Purpose

We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, used preventively, in NAFLD induced in rabbits fed hypercholesterolemic diet. Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers.

Methods

Olmesartan study: Thirty-four rabbits were divided into three groups (control, untreated and olmesartan). The untreated and olmesartan group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day.

Ramipril study: Twenty-nine rabbits were divided into three groups (normal, placebo, and ramipril). The placebo and ramipril groups were fed a hypercholesterolemic diet. The groups were orally administered 0.35 mg/kg/day of ramipril, and an equivalent volume of vehicle was administered to the placebo group. In both studies, at the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD.

Results

The comparison between two groups (olmesartan with untreated group and ramipril with placebo) showed that ramipril and olmesartan significantly diminished the development of steatosis (p<0.013, p=0.032), lobular inflammation (p<0.001, p=0.006), and fibrosis (p=0.015, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p<0.001, p=0.003).

Conclusion(s)

The preventive use of olmesartan and ramipril attenuates the development of hepatic steatosis, lobular inflammation and fibrosis in hypercholesterolemic rabbits. These results can serve as the basis to the establishment of criteria for choosing the most appropriate drug therapy for hypertension in NAFLD carriers.
P4496Copeptin and coronary artery calcium score in elderly adults without a cardiovascular history. A report from the ICELAND MI cohort
Authors: Smaradottir M I , Andersen K , Eiriksdottir G , Gudnason V , Nasman P , Ryden L , Mellbin L G
Published: October 2019

Background

Copeptin, a marker for vasopressin, is related to advanced cardiovascular disease such as myocardial infarction.

Purpose

The aim of the present investigation was to assess whether copeptin is associated with the different atherosclerotic plaque stages expressed by coronary artery calcium scores (CAC score).

Methods

Copeptin and CAC score were studied in 677 participants in the ICELANDIC MI cohort without a history of a myocardial infarction at baseline. The Agatston method was used to measure coronary artery calcification visualized by means of computed tomographic scans. The CAC score was categorized into four classes: 0, 1–99, 100–399, and ≥400. Correlations between the CAC score and copeptin were assessed using Spearman's Rank Correlation while the predictive value of copeptin and CAC score were evaluated with Cox proportional Hazard regression analysis (unadjusted and adjusted for age groups, serum creatinine, gender, hypertension and type 2 diabetes mellitus). The primary outcome was cardiovascular events (CVE) while total mortality served as secondary outcome.

Results

The median copeptin level was 6.4 pmol/L and the median CAC score 227.0 (IQR: 48.3–692.4) for the total cohort. The highest copeptin level was seen in people with a CAC score ≥400. Copeptin predicted total mortality in the unadjusted analysis and the CAC score predicted both outcomes. Only the CAC score that predicted outcome following adjustments (CVE: HR 1.35, 95% CI 1.23–1.48; p<0.001; and total mortality: HR 1.29, 95% CI 1.16–1.43; p<0.001). The cardiovascular prognosis was similar in those with CAC score less than 400 and above 400 regardless of the copeptin level (Figure).

Figure 1

Conclusion

In this cohort of elderly individuals without a previous MI a high CAC score was as a significant predictor of future cardiovascular events. People with high a CAC score had elevated copeptin levels but copeptin did not serve as a prognostic indicator. This suggests that copeptin elevation in people with CAD is an expression for the general state of disease rather than an indicator of a pathophysiological role of vasopressin in this context.
P4504Pulmonary circulatory-right ventricular uncoupling in acute decompensated heart failure: a key mediator of congestion
Authors: Losito M , Barki M , Labate V , Giammarresi A , Caracciolo M , Bandera F , Rovida M , Alfonzetti E , Guazzi M
Published: October 2019

Background

The degree of congestion in patients hospitalized for acute decompensated heart failure (ADHF) is estimated using traditional non-invasive markers such as echo-derived inferior vena cava diameter (IVCD) and NT-proBNP levels. The deterioration of right ventricular (RV) function and its uncoupling to pulmonary circulation (Pc) represents a turning point in terms of prognosis and clinical outcome in patients affected by heart failure. However, how RV-to-Pc uncoupling correlates with markers of decompensation and congestion in ADHF patients has never been explored.

Purpose

To investigate, in a cohort of ADHF patients, the association between the degree of RV-to-Pc uncoupling, assessed by the ratio between tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), IVCD and right atrial pressure (RAP) estimated at echocardiography.

Methods

Fourty-six ADHF patients both with reduced and preserved EF (mean age 73.15±10.85 years, 60.8% males) admitted to the Cardiology Department were prospectively enrolled within 24–48 hours from admission. In the acute phase all patients underwent transthoracic echocardiography and laboratory blood tests. Patients were then stratified in tertiles according to TAPSE/PASP ratio (group I: <0.4 mm/mmHg; group II: 0.4 to 0.6 mm/mmHg and group III: >0.6 mm/mmHg) correlating the degree of RV-to-Pc with non-invasive markers of congestion such as NT-proBNP, IVC maximum diameter and RAP. Other echocardiographic parameters including left ventricular (LV) systolic function and LV filling pressures were considered.

Results

An exponential inverse relationship was found between NT-pro-BNP levels at admission with levels decreasing progressively with the increment of the ratio (Group I: 12828±10600 ng/l; Group II 5549±5383 ng/l; Group III 3695±3870 ng/l; p=0.004) (Figure 1a). An analogous correlation was observed when considering the IVC maximum diameter (Group I: 20.87±5.37 mm; Group II 18.08±4.35 mm; Group III 10.9±3.36 mm; p<0.001) (Figure 1b) and the RAP estimated at echocardiography (Group I: 12.875±5.25 mmHg; Group II 9.157±4.82 mmHg; Group III 4±1.61 mmHg; p<0.001) (Figure 1c).

In addition, progressively increasing values of LVEF (Group I: 28±11.3%; Group II 42±17.3%; Group III 49±11.8%; p=0.001) were detected from the lowest to the highest TAPSE/PASP tertiles. No correlation was observed in the three groups for E/E' values at admission (Group I: 17.17±6.7; Group II 19.42±8.36; Group III 15.92±5.7; p=0.5).

Figure 1

Conclusions

In ADHF, the association between RV to Pc uncoupling, echo-derived measures of congestion and natriuretic peptide levels is here described for the first time. The extent of RV dysfunction in ADHF deserves attention and seems to represent a critical and quite underestimated key mechanism between congestion resolution and in-hospital worsening HF.
P4529Atrioventricular optimization in cardiac resynchronization therapy with quadripolarleads, improves energy handling and quality of life in heart failure patients: HUMVEE Trial
Authors: Antoniou C K , Konstantinou K , Chrysohoou C , Dilaveris P , Magkas N , Skiadas J , Antonakos V , Kakioris K , Gatzoulis K , Tousoulis D
Published: October 2019

Background

Cardiac resynchronization therapy (CRT) is a well-established technique for symptomatic heart failure (HF) patients, producing significant clinical benefits. Recent studies have revealed the potential role of multipoint pacing (MPP) in improving response and clinical outcomes. The aim of Heart failUre study of Multisite pacing effects on VEntriculoartErial coupling (HUMVEE) trial was to evaluate the association between MPP of the left ventricle vs those of standard biventricular pacing (BVP) on: a) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, b) diastolic function, c) quality of life, and d) NT-proBNP levels.

Methods

HUMVEE is a single-center, prospective (13 months) trial (clinicaltrials.gov identifier NCT03189368), of 54 NYHA III patients (69±9 years; 79% men; 50% dilated cardiomyopathy), under optimal tolerated medical therapy, with standard BVP indication, having being implanted with a CRT system able to deliver both modes of pacing. Creatinine and NT-proBNP levels and echocardiographic measurements (VAC calculation, strain rate, diastolic function assessment), as well as 6-min-walking-test and quality of life (MLHF questionnaire) were measured at baseline, 6 months post BVP optimization (right before MPP activation) and at the end of follow-up (6 months post MPP optimization). Cardiac power (CP) was calculated according the equation: CP=Cardiac Output x Mean Aortic Pressure/451.

Results

Both CRT and MPP improved 6-min-walk (differences at baseline/6 mo/end of FU: 277±27 vs. 345±27 vs 363±27 m, p=0.07); left ventricular ejection fraction (24,2% vs 30,6%vs, 32%, p=0.05); end -diastolic diameters of left ventricle (65±1,4 vs. 63±1.7 vs. 61±1.1, p=0.03); end-systolic volume (150±15 vs. 140±10 vs. 131±13, p=0.08); stroke volume (41.6±9 vs. 53.6±14 vs. 62±9, p=0.0001 for MPP); left atrial volume (76±5 vs. 74±10 vs 61±6, p=0.001 for MPP), E/Emv (14±5 vs. 12±4 vs. 11±3, p=0.05 for MPP); NtproBNP (2782±1000 vs. 2080±2500 vs. 2000±1000, p=0.05 for MPP). VAC was reduced from 1.14±0.27 to 1.1±0.17 (p=0.1) while CP increased from 564.2±142 to 768±103 (p=0.009). Quality of life score (the lower the better) improved from 23.75±17 at baseline to 17.25±10 at end of FU (p=0.05).

Conclusions

MPP is a new, promising pacing modality with the potential to improve HF patients' outcome, offering additive effects on myocardial energy balance, cardiac power, systolic and diastolic ventricular function and aortoventricular coupling, especially in ischemic patients. HUMVEE trial illustrates those clinical, imaging and biochemical divergences of MPP from standard BVP that reflect significant improvement in quality of life in patients with advanced HF and cardiac dysychronization.
P4557Factors associated with treatment and control of hypertension in a healthy elderly population free of cardiovascular disease: a cross-sectional study
Authors: Chowdhury E , Nelson M R , Ernst M E , Margolis K L , Beilin L J , Johnston C I , Murray A M , Woods R L , Wolfe R , Tonkin A M , Williamson J D , Stocks N P , McNeil J , Reid C
Published: October 2019

Introduction

Despite readily available treatments, control of high blood pressure (BP) in the ageing population remains suboptimal. Gaps in understanding the management of high BP amongst the elderly exist, as most studies have been in predominantly middle-aged populations.

Purpose

We explored pharmacological BP lowering treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both “untreated” and “treated but uncontrolled” high BP.

Methods

We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and the US in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mmHg and/or use of any BP-lowering medication. `Controlled hypertensives” were those receiving BP-lowering medication and with BP <140/90 mmHg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control.

Results

Overall, 74% (14,213/19,114) of participants were hypertensive, and of these 29% (4,151/14,213) were untreated. Among those treated, 47% (4,732/10,062) had BP <140/90 mmHg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to “treated but uncontrolled” hypertension included older age, being men, Black race (versus White), using BP lowering monotherapy and residing in Australia (versus US) (Figure 1).

Conclusion(s)

There were high levels of “untreated” and “treated but uncontrolled” BP, in an otherwise healthy elderly population, suggesting that opportunities for better BP control exist through targeting intervention to high-risk individuals.

Acknowledgement/Funding

National Institute on Aging and the National Cancer Institute at NIH; NHMRC Australia, Monash University, Victorian Cancer Agency (Australia)
P4647Next generation sequencing in 83 fetal left-sided CHDs reveals the entire genetic architecture of left-sided CHDs in fetal population
Authors: Sun H R , Hao X Y , Yi T , Gu X Y , He Y H
Published: October 2019

Background

No data is available for the contribution of single gene disorders (SGDs) to left-sided congenital heart defects (LSCHDs) in the fetal population.

Purpose

The aim of this study was to explore the entire genetic architecture of LSCHDs, especially the contribution of SGDs in a cohort of fetal LSCHDs.

Methods

Low-pass whole genome sequencing (WGS) and whole exome sequencing (WES) were performed on specimens from 83 deceased fetuses with lSCHDs, including 48 HLHS, 22 CoA, 5 AS, 3 AAH, 2 AS+CoA and 1 case of AA, AS+MS, MA. Sequencing was predominantly performed in fetus-parent trios (n=63, 75.9%), or in fetus only (n=20, 24.1%).

Results

34.9% (n=29) of the 83 fetal left-sided CHDs were identified with related genetic abnormalities. WGS analysis identified 14 (16.9%) with chromosomal abnormalities, including 6 (7.2%) aneuploidies and 8 (9.6%) pathogenic copy number variants (CNVs). WES analysis of the remaining 69 cases without chromosomal abnormalities identified 15 (15/69, 21.7%) with pathogenic/likely pathogenic variants. Of these 15 cases, KMT2D was the most frequently mutated gene (7/69, 10.1%), followed by NOTCH1 (4/69, 2.5%). Compound heterozygosity was identified in 3 genes (DNAH11, POFUT1, CRB2) that are not yet well established as CHD genes. Finally, we also observed a LOF variant in NONO (X-linked) that was maternally transmitted to an affected male case.

The genetic results of this cohort Aneuploidies Trisomy 18 4 Turner syndrome 2 CNVs 11q terminal deletion 3 1p36 deletion 1 15q terminal deletion 1 7q11.23 deletion 1 4p terminal deletion 1 12q complex internal duplication 1 SGDs AD (KMT2D = 7; NOTCH1 = 4) 11 AR (DNAH11, POFUT1, CRB2) 3 X-recessive (NONO) 1 AD: autosomal dominant; AR: autosomal recessive.

Conclusions

Our experience supports that SGDs contribute a significant part to the pathogenesis of fetal CHDs, WES has the potential to provide molecular diagnoses in fetal left-sided CHDs without chromosomal abnormalities. KMT2D mutations accounted for a large fraction of left-sided CHDs in fetal population. If the KMT2D mutation is detected, further diagnosis of Kabuki syndrome should be considered.
P4730Underweight is associated with unfavourable short- and long-term outcomes after MitraClip therapy: a body mass index derived subgroup analysis of the German Transcatheter Mitral Valve Interventions (
Authors: Kalbacher D , Tigges E P , Boekstegers P , Puls M , Plicht B , Eggebrecht H , Nickenig G , Von Bardeleben R S , Zuern C S , Franke J , Sievert H , Ouarrak T , Senges J , Lubos E
Published: October 2019

Background

Underweight and obesity represent classical risk factors for patients undergoing cardiac surgery or interventional treatment. The multicentre German Transcatheter Mitral Valve Interventions (TRAMI) registry comprises a large and prospectively enrolled real-world cohort of patients treated by MitraClip implantation.

Aims

The current analysis examines the impact of underweight, overweight and obesity on intra-hospital, short and long-term outcomes in patients treated by MitraClip therapy.

Methods and results

From 08/2010 until 07/2013, 799 patients (age 75.3±8.6 years, male gender 60.7%, median logistic EuroSCORE 20% [12; 31], functional mitral regurgitation (MR): 69.3%) were prospectively enrolled into the multicentre, industry-independent German Transcatheter Mitral Valve Interventions registry. Patients were stratified according to body mass index (BMI) into four groups: BMI<20 kg/m2 (underweight, n=49), BMI 20.0 to <25.0 kg/m2 (normal weight, n=293), BMI 25.0 to <30.0 kg/m2 (overweight, n=296) and BMI≥30 kg/m2 (obese, n=132). Procedure and radiation time were comparable among all groups. Significant increased rates of procedural failure (12.2% vs. 2.1 [normal weight], p<0.001), transfusion/bleeding (20.8% vs. normal weight: 5.6%, obesity: 7.0%, p<0.01), sepsis or multiorgan failure and low cardiac output failure were found for underweight patients only. Kaplan-Meier survival curves demonstrated inferior survival for underweight patients, but comparable outcomes for all other patients (global log rank test, p<0.01). Multivariable Cox-regression analysis (adjusted for age, gender, creatinine≥1.5mg/dl, diabetes, left ventricular ejection fraction<30% and chronic obstructive pulmonary disease) confirmed underweight (as compared to normal weight) as an independent risk factor of death (hazard ratio [HR]: 1.58, 95%-confidence interval (CI): 1.01–2.46, p=0.044) and overweight as protective against death (HR: 0.71; 95%-CI: 0.55–0.93; p=0.011).

Conclusion

Underweight patients are exposed to increased rates of procedural failure, bleeding and low cardiac output as well as increased short- and long-term mortality rates when undergoing MitraClip implantation and should therefore be carefully discussed within the heart team.

Acknowledgement/Funding

The TRAMI registry has been supported by proprietary means of IHF. Additional funding is provided by “Deutsche Herzstiftung” and a grant from Abbott.
P4735Preoperative frailty is a predictor of worse in-hospital outcomes after coronary artery bypass graft surgery and improves the predictive accuracy of EUROSCORE I and II
Authors: Rosler A , Constantin G , Nectoux P R , Borges D , Fraportti J , Pontes M R N , Dal Lago P , Lucchese F A
Published: October 2019

Introduction

Although coronary artery bypass grafting (CABG) is the most widely performed cardiovascular procedure in the world and is the standard treatment for complex coronary artery disease, the risk prediction for the procedure has major gaps. In this context, preoperative frailty may have a relevant role in the prediction of surgical risk.

Purpose

Our goal was to evaluate the impact of frailty on in-hospital outcomes after CABG and verify if any other comorbidity enhances the effects of fragility.

Methods

Prospective cohort of patients submitted consecutively to isolated CABG between Jan/2013 and Dec/2017. Frailty was defined as any deficiency in the Katz Index. Of the 1508 patients, 126 (8.4%) were classified as frail. Baseline characteristics and outcomes were compared by univariate analysis. Multivariate regression models were applied for the adjusted analysis of outcomes. The predictive accuracy of the regression models were analyzed using ROC curves. The additional predictive accuracy of the frailty and other risk variables were evaluated by comparing the ROC curves with the DeLong test.

Results

The frail patients presented more advanced age, more comorbidities and the majority were female. Frailty was an independent predictor for in-hospital mortality (OR 5.55, p=0.002) and MACCE (OR 5.60, p=0.001). In addition, by means of an adjusted analysis, we identified that the frailty was associated with a longer time of hospitalization (B 4.61, 95% CI 2.12–7.10, p<0.001). We also identified that preoperative anemia was classified as an independent predictor for hospital mortality and MACCE and improved the effect of frailty on outcomes. In this way, we could verify that when associated with surgical risk scores, frailty and anemia significantly improved the predictive accuracy of EuroScore 1 and EuroScore 2 for in-hospital mortality.

Predictive accuracies

Conclusions

Frailty and preoperative anemia are independent predictors of hospital mortality and MACCE after CABG. Frailty was also a predictor of longer hospitalization time. The association of frailty and anemia with surgical risk scores resulted in a significant improvement in the predictive accuracy of the scores. Frailty screening by Katz Index improved the risk assessment for isolated CABG and, when associated with anemia, demonstrated that frail and anemic patients had worse surgical outcomes.

Acknowledgement/Funding

The development of the present study was funded entirely by the Institution itself.
P4739Novel tissue-engineered heart valve without any foreign materials
Authors: Takewa Y , Nakayama Y , Shimamura J , Katagiri N , Tatsumi E
Published: October 2019

Background

We are developing a novel autologous tissue-engineered heart valve with a unique in-body tissue engineering. This is expected to be a viable bioprosthesis keeping better biocompatibility.

Purpose

We developed a conduit-type valve without any foreign materials and tested the feasibility and long-term availability in large animal experiments.

Methods

We created plastic molds for Biovalves with 3D printer easily and quickly considering the recipient character. We embedded them in the subcutaneous spaces of adult goats about 2 months. After extracting the molds with the tissue en-block and removing the plastic molds only, Biovalve with tri-leaflets similar to those of the native valves were constituted from completely autologous connective tissues and fibroblasts. Total 21 conduit-type Biovalves were implanted in the apico-aortic bypass or the pulmonary artery of goats, (8 and 13, respectively). No anticoagurants were used after implantation.

Results

The valves were successfully implanted and showed smooth movement of the leaflets with a little regurgitation in angiogram, and the maximum duration reached to 3 years 7 months. Histological examination of the Biovalves showed the autologous cells covering the laminar surface of the valve leaflets as the endothelium and also getting inside to construct characteristic tissues like native leaflets.

Conclusion

The valves have a potential to be used for viable bioprosthetic valves and to keep better function and biocompatibility longer than current ones.
P4740Clinical predictors of graft occlusion after coronary artery bypass grafting: a case-control study
Authors: Cheng Y J , Ma X T , Zhou Y J , Zhao Y X , Liu X L , Ma Y , Liu F , Sun Y , Zhang D
Published: October 2019

Objective

Coronary artery bypass grafting (CABG) is still one of the most common surgical procedures aimed at improving blood circulation in atherosclerotic coronary arteries.Graft occlusion influences outcome CABG. The risk factors of long-term graft occlusion remain uncertain.The aim of the present study was to investigate the clinical predictors of graft occlusion after CABG.

Methods

All patients with prior CABG in our center who underwent coronary computed tomography angiography (CTA) and/or percutaneous coronary angiography for follow-up between Aug 2013 and Dec 2017 were included in the present study. We excluded patients who underwent multiple CABG surgeries or percutaneous coronary intervention after index CABG. With regard to one patient with two or more different angiography results, we selected the angiography result which showed graft occlusion for the first time or the last angiography result. The baseline clinical data at index CABG was analyzed for their independent impact on graft occlusion in a case-control study using multivariate logistic regression.

Results

1178 (27.5%) of 4289 patients experienced at least one graft occlusion. The mean age was 63.23±9.02 years, 1004 (23.4%) patients were female. From all the occlusion cases, artery occlusion occurred in 337 (28.6%) patients and saphenous vein graft occlusion occurred in 875 (74.3%) patients.Complete baseline data was available for evaluation from 1178 of them (case group). We matched these patients through gender, age and time interval between the index CABG and angiography/CTA to another 1178 patients who did not have graft occlusion (control group). After multivariate logistic regression, chronic renal dysfunction (OR=1.008; 95% CI, 1.001–1.021; P=0.038) hyperuricemia (OR=1.89; 95% CI, 1.101–3.876; P=0.040) and hyperlipemia (with low density lipoprotein increased) (OR=1.377; 95% CI, 1.021–1.926; P=0.042) significantly increased the risk of long-term graft occlusion.

Conclusions

Chronic renal dysfunction hyperurcemia and hyperlipemia were independent risk factors of long-term graft occlusion.

Acknowledgement/Funding

National Key Research and Development Program of China (2017YFC0908800)
P4765Men who live alone have poor anticoagulation control: results from Danish registries
Authors: Bonde A N , Bjerre J , Proietti M , Gislason G , Lip G Y H , Hlatky M
Published: October 2019

Background

Efficacy and safety of vitamin K antagonists (VKAs) depend on quality of anticoagulation control, usually measured as time in therapeutic range (TTR). Factors that predict low TTR on VKAs could be used to identify patients who might benefit from interventions, or who would be better treated with a non-VKA oral anticoagulant (NOAC). Patients living alone may have difficulties in taking their medications, managing their diets, or coming to clinic for monitoring.

Purpose

To assess influence of cohabitation status on TTR with VKA among men and women.

Methods

We identified all Danish patients with atrial fibrillation (AF) who initiated VKA between 1997 and 2012, and studied patients who had 6 months of continuous VKA use and international normalized ratio (INR) monitoring. Patients were divided according to sex and whether they lived alone or with others. We calculated TTR using the Rosendaal method, and INR variability using Fihns method. We used a linear regression model to test for associations between TTR and covariates, and adjusted for age, income, medications and comorbidities.

Results

We identified 4,772 AF patients with 6 months of continuous VKA use and INR monitoring. 713 (15%) were men living alone, 1,073 (23%) were women living alone, 2,164 (45%) were men not living alone and 822 (17%) were women not living alone. INR was measured a median of 11 (interquartile range 8–15) times during the 180 days of VKA use, but men who lived alone had 0.6 (95% confidence interval (CI): 0.2 to 1.2) fewer INR measurements during the period. Median TTR was lowest among men living alone (57.2%), followed by women living alone (58.8%), women not living alone (61.0%) and men not living alone (62.5%). After multivariable adjustment, men who lived alone had a 3.6% (CI −5.6 to −1.6) lower TTR compared with men not living alone, but women who lived alone did not have significantly lower TTR (P=0.80) compared with women not living alone. Living alone had significantly greater effect on TTR among men than among women (interaction P=0.02). Men living alone also had higher adjusted INR variability (0.2, CI 0.0 to 0.4) compared with men not living alone.

Conclusion

Living alone was significantly related to low quality of anticoagulation control among men, but not among women.

Acknowledgement/Funding

this study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research