bluuebunny/crossref_metadata_2025 huggingface dataset:
P2244Anomalies in women of the aortic arch in Turner syndrome as an important risk factor for premature morbidity and mortality
Authors: Klaskova E , Kapralova S , Zapletalova J , Tudos Z , Adamova K
Published: October 2019

Introduction

Turner syndrome (TS) represents the most common chromosomal disorder in women being, caused by the absence or structural abnormality of X chromosome. Congenital heart defects affect up to 50% of females with TS.Prevalence of coarctation of the aorta in TS has been estimated 7–18% depending on imaging method. Introduction of cardiac magnetic resonance imaging (MRI) into the routine practice markedly increased the detection rate of anomalies of the aortic arch such as elongated transverse aortic arch with abnormal curvature, i.e.kinking, pseudocoarctation or aberrant right subclavian artery. Aims of study was to estimate prevalence of anomalies of the aortic arch in our study group according to the karyotype.

Methods and patients

Study group consisted of 67 patients with TS at the age 7.3 yrs (range 0.1 - 16.5 yrs.). Complete cardiovascular examination (echocardiography, MRI of the heart and great vessels) and cytogenetic examination were performed in each of our study patient.

Results

The prevalence of anomalies of the aortic arch was 15% (10 patients). Four of them had elongated transverse aortic, coarctation of the aorta was found in three cases, aberrant right subclavian artery in two patients and one girl had right aortic arch. 45,X cell line was presented in every patient with anomaly of the aortic arch, none of them had structural abnormality of X chromosome.

Conclusions

Compared with the general population, the prevalence of CoA and the others anomalies of the aortic arch is significantly higher in women with TS, especially with 45,X cell line. As far as CoA is considered to be one of the major risk factor for aortic dissection detailed cardiovascular screening focused on thoracic aorta anomalies seems to be crucial in order to prevent it.

Acknowledgement/Funding

Supported by Ministry of Health, Czech Republic - MZ VES 2017 (Reg. No. NV17-29111A).
P2254Impaired autophagic off-rate causes cardiac aging in progeria mouse model
Authors: Kamihara T , Kureishi Bando Y , Nishimura K , Yasheng R , Ozaki R , Murohara T
Published: October 2019

Background/Introduction

Aging is known to be one of the primary causes of heart failure. Werner syndrome is one of the aging disorder that caused by dysfunction of DNA helicase-regulatory protein (WRN). However, there is little information whether WRN may cause any specific myocardial remodeling and vulnability for heart failure. More interestingly, ample evidences demonstrated DNA damage occurred in progeria causes autophagic disorder, contributing to aging phenotype, in short, autophagy may be a guardian of the genome. Although autophagic disorder has been implicated to cause cardiac remodeling in heart failure; however, it remains uncertain whether autophagic disorder may link to the mechanism of aging-induced cardiac remodeling.

Purpose

To elucidate whether autophagic disorder may be mechanistically responsible for cardiac aging we hypothesized whether aging-related DNA injury may affect autophagy that may lead to myocardial remodeling.

Methods

We employed progeria mouse model harboring amino acid (AA) substitution of WRN at position 577 (WRN-K577M), which were evaluated in terms of cardiac function and remodeling at the phase of adult (18 week-old).

Results

WRN-K577M exhibited diffuse left-ventricular (LV) hypertrophy, enhanced fibrosis, and diastolic LV dysfunction with preserved systolic ejection fraction. DNA microarray analysis of WRN-K577M heart revealed that the 253 genes were upregulated compared to age- and gender-matched wild-type counterpart. Sixteen genes were increased >4 fold higher than wild-type as follows: hypertrophy (Myh7, Klkb11), fibrosis (Fgf21, CTGF), inflammatory molecules (Ap1s3, Pla2g2e, Has1, MMP9), and oxidative stress (catalase). Cardiac aging markers (PARP-1, p53 and γH2AX) increased in heart of WRN-K577M with concomitant increase in oxidative stress (DHE staining) and apoptosis (TUNEL). Notably, autophagic turnover markers (i.e., increased on-rate of autophagy; p62 and LC3-II/I) were increased in myocardium of WRN-K577M, which was refractory to fasting-induced autophagic activation, indicating the on-rate step of autophagy is pathologically augmented under cardiac aging observed in WRN-K577M. In contrast, one of the key regulators of autophagy is the target of rapamycin, TOR kinase, which is the major inhibitory signal that shuts off autophagy with concomitant activation of Akt signaling. In contrast, blockade of the lysosomal fusion into autophagosome by systemic treatment with chloroquine (50 microg/g body weight) reduced LC3-II/I ratio, indicating the retarded off-rate of autophagy mediated by impaired lysosome fusion is presumably responsible for cardiac aging.

Conclusion(s)

DNA damage impairs autophagy in heart, leading to myocardial oxidative stress. In WRN-mutant progeria model, off-rate disorder of cardiac autophagy is, at least in part, the cause of increase in oxidative stress and inflammation in heart leading to HFpEF.
P2255Senescence associated secretory phenotype exacerbates overload pressure-cardiac hypertrophy
Authors: Nugroho D B , Ikeda K , Haryono A , Rinastiti P , Barinda A J , Emoto N
Published: October 2019

Background

Advanced age is a significant risk factor for cardiovascular diseases such as hypertension and cardiac hypertrophy. The vascular system forms an essential component of cardiac tissue, to provide routes for circulation and transportation of nutrients and oxygen throughout the cardiac muscle. In addition to its function in vascular biology such as vasodilation and neovessel formation, endothelial cell (EC) also provides many secreted angiocrine factors that are crucially involved in maintaining tissue homeostasis. Ageing induces cellular senescence in various cells including EC. Senescent cells produce senescence-messaging secretomes that have deleterious effects on the tissue microenvironment, referred to as the senescence-associated secretory phenotype (SASP). Because of the crucial roles of EC in tissue homeostasis, EC senescence is presumed to play significant roles in age-related cardiac dysfunction, however, whether and the mechanism by which EC senescence affects age-related cardiac dysfunction remains to be elucidated.

Purpose

We aimed to investigate the role of senescent ECs in cardiac hypertrophy and heart function.

Methods

To investigate a contribution of senescent EC in age-related cardiac tissue dysfunction in vivo, we generated EC-specific progeroid mice that overexpress the dominant negative form of telomeric repeat-binding factor 2 (TRF2), which play a central role in the protection of chromosome ends, under the control of the vascular endothelial cadherin promoter (VEcad-TRF2DN-Tg). To induce pathological cardiac remodeling, Transverse Aortic Constriction (TAC) was performed in mice at the age of 10–12 weeks old. Cardiac function was assessed using fractional shortening percentage and ejection fraction measured with echocardiography every week until sacrifice day. Mice were sacrificed 4 weeks after TAC, heart tissue was collected for histological analysis, cardiac morphometry analysis, gene expression and protein expression analysis. In vitro, H9C2 rat cardiomyoblast cells were incubated with conditioned medium derived from control or senescent EC in the presence or absence of angiotensin II to induce cardiac hypertrophy.

Results

The serial echocardiographic analysis after TAC revealed the exacerbated LV dysfunction in VEcad-TRF2DN-Tg compared to that in wild-type mice. Morphometric and histological analysis 4 weeks after TAC showed increased heart weight and aggravated cardiac fibrosis in VEcad-TRF2DN-Tg mice. In vitro studies demonstrated that conditioned medium derived from senescent ECs enhanced cardiomyocyte hypertrophy in H9C2 cells. Of note, we found that treatment with Y2762, a Rho Kinase inhibitor, canceled the exacerbated cardiac hypertrophy caused by endothelial SASP.

Conclusion

These findings demonstrate for the first time that senescent ECs play causative roles in age-related cardiac disorders through the SASP, potentially by activating Rho-ROCK pathway in cardiomyocytes.
P2273Predictors of short- and mid-term outcomes after TAVR in low-flow, low-gradient aortic stenosis
Authors: Emer Egypto Rosa V , Echeverri D , Sztejfman M , Jaikel L A G , Dager A , Abud M , Charry P , Chauvet A A , Tarasoutchi F , Cura F , Ribeiro H B
Published: October 2019

Background

There is a lack of data on outcomes in classical (C-LFLG) and paradoxical low-flow, low-gradient aortic stenosis (P-LFLG) patients undergoing TAVR.

Purpose

We aim to compare baseline characteristic and procedural outcomes between C-LFLG, P-LFLG and high-gradient aortic stenosis (HG-AS) patients undergoing TAVR.

Methods

Patients included in the Transcatheter RegistrY of aorTic valve biOprosthesis in Latin-AMerica (TRYTOM Registry) were divided in 3 groups: 1) HG-AS: mean transaortic gradient (MG) ≥40 mmHg; 2) P-LFLG: MG <40 mmHg and left ventricular ejection fraction (LVEF) ≥50%; 3) C-LFLG: MG <40 mmHg and LVEF <50%. The outcomes were evaluated at 30-days and 1-year and were classified according to definitions of the VARC-2.

Results

1040 patients were included, 677 (65%) classified as HG-AS, 223 (21%) as P-LFLG and 140 (14%) as C-LFLG. Median follow-up was 16 months (range 0–109). There were baseline differences between HG-AS, P-LFLG and C-LFLG regarding age (80±7 vs 80±5 vs 78±8 years, respectively; p=0.017), NYHA FC III and IV (61.0 vs 72.6 vs 83.6%, respectively; p<0.001), coronary artery disease (44.1 vs 47.1 vs 57.9%, respectively; p=0.012), EuroSCORE II (7.2±6.3 vs 7.5±5.0 vs 12.9±10.4%, respectively; p<0.001), LVEF (56±11 vs 61±7 vs 32±9%, respectively; p<0.001), MG (53±13 vs 30±6 vs 27±7 mmHg, respectively; p<0.001), aortic valve area (0.65±0.16 vs 0.74±0.15 vs 0.70±0.16 cm2, respectively; p<0.001) and creatinine (1.2±0.7 vs 1.1±0.5 vs 1.5±1.3 mg/dl, respectively; p<0.001). Despite these significant baseline differences, we found similar outcomes after TAVR between HG-AS, P-LFLG and C-LFLG regarding device success (89.8 vs 95.1 vs 90.7%, respectively; p=0.057), in-hospital mortality (6.1 vs 5.9 vs 11.8%, respectively; p=0.144) and all other VARC-2 major outcomes, including major bleeding, major vascular complication and disabling stroke. In addition, female sex (OR 2.13, 95% CI 1.16–3.92, p=0.014), LVEF (OR 1.02, 95% CI 1.00–1.04, p=0.039) and MG (OR 0.97, 95% CI 0.95–0.99, p=0.004) were the only predictor of device success by multivariate analysis. Furthermore, 1-year mortality was similar among the groups (9.5 vs 8.3 vs 14.3%, respectively; p=0.358; Figure 1), and by multivariate analysis, diabetes (HR 2.44, 95% CI 1.10–5.41, p=0.028), creatinine (HR 1.65, 95% CI 1.17–2.33, p=0.004), conversion to general anesthesia (HR 7.93, 95% CI 2.08–30.20, p=0.002) and post-procedure disabling stroke (HR 12.84, 95% CI 3.09–53.40, p<0.001) predicted increased 1-year mortality, irrespective on the LVEF and MG.

Conclusions

Apart from baseline differences, TAVR in P-LFLG and C-LFLG was feasible and with similar clinical outcomes when compared to HG-AS. Mid-term mortality rates was associated with diabetes, creatinine and procedure complications.
P2274Single-center experience with different regimes of antiplatelet therapy and oral anticoagulation in transcatheter aortic valve replacement
Authors: Veulemans V , Hellhammer K , Afzal S , Maier O , Westenfeld R , Jung C , Kelm M , Zeus T , Polzin A
Published: October 2019

Background

Antithrombotic therapy in transcatheter aortic valve replacement (TAVR) is highly controversial. Dual antiplatelet therapy (DAPT) for 3–6 months with aspirin and clopidogrel is the current recommendation. Whereas in patients with indication for OAC several regimes were described, ranging from OAC monotherapy to dual and even triple therapy. Besides vitamin K antagonists (VKA), non-Vitamin K oral anticoagulants (NOAC) are frequently used in TAVR patients with indication for permanent OAC.

Purpose

We therefore aimed to evaluated different antithrombotic regimes and their impact on outcome.

Methods

We performed a single center retrospective analysis in 1160 patients treated by transfemoral approach (TF TAVR). Primary endpoints were 30-day mortality, stroke and bleeding according to VARC-2 criteria. Secondary endpoint was all-cause mortality at 1 year.

Results

In 1160 patients with TF TAVR, a broad range of regimes occurred in clinical practice. The majority of patients were on DAPT (637 patients, 55.0%), followed by VKA + clopidogrel (186 patients, 16%). Other patients received OAC mono (98 patients; 9%), triple therapy (93 patients; 8%), NOAC mono (31 patients; 3%), single antiplatelet therapy (SAPT, 40 patients; 4%) or NOAC + clopidogrel (31 patients, 3%).

All-cause mortality 30 days after TF TAVR differed between the regimens. (SAPT/OAC+SAPT/N-OAC+DAPT 0.0% vs DAPT 3.6% vs OAC 10.2% vs. NOAC 1.3% vs NOAC+SAPT 0.3%; pANOVA<0.0001). Severe bleeding events were comparable (SAPT 5.0% vs DAPT 2.4% vs OAC 7.1% vs NOAC 1.3% vs OAC+SAPT 3.2% vs NOAC+SAPT 0.0% vs. N-OAC+SDPT 4.3%; pANOVA=0.15). Stroke rates were comparable in all subcohorts as well (SAPT 5.0% vs DAPT 3.0% vs OAC 7.1% vs NOAC 2.7% vs OAC+SAPT 1.6% vs NOAC+SAPT 0.0% vs. N-OAC+DAPT 1.1%; pANOVA=0.13). Only 2 hemorrhagic strokes (5.6%) appeared under DAPT and OAC mono respectively, whereas all others were of thromboembolic origin (94.4%). Surprisingly, all-cause mortality at one-year after TF TAVR was higher in OAC patients compared to all other used regimes (logrankoverallp=0.0012).

Conclusion

Data from our retrospective analysis indicate that a variety of different antithrombotic regimes occur even in a single centre analysis. All-cause mortality was enhanced in patients with oral anticoagulation. Therefore, clinical trials need to investigate if this is only explained by additional atrial fibrillation.
P2446Defining values of volumes and longitudinal strain for the different types of left ventricular remodeling patterns in subjects with normal ejection fraction - a single center study
Authors: Jadav R , Nhola L , Thaden J , Pellikka P , Pislaru P , Villarraga H
Published: October 2019

Background

The left ventricle (LV) undergoes different types of remodeling to normalize its wall stress. There has been an increase in the trend in research regarding the process of remodeling but little is known about how LV volumes and global longitudinal strain (GLS) may vary depending upon the type of remodeling.

Purpose

To define the values of LV volumes and GLS in patients with different types of LV remodeling with normal ejection fraction (EF).

Methods

Single center retrospective study conducted from 2008 to 2018. We selected 10,356 subjects >18 years (5808 females, 4548 males) with normal EF and who underwent 2D echocardiography (2DE) at Mayo clinic, Rochester. They were categorized into 4 groups (Figure) i.e., group 1 = normal geometry, group 2 = concentric remodeling, group 3 = concentric hypertrophy, group 4 = eccentric hypertrophy based on their LV mass index (102 g/m2 in males, 88 g/m2 in females) and relative wall thickness (0.42) values measured by 2DE (figure). The patterns of LV GLS, end diastolic and end systolic volumes (EDV, ESV) indexed to body surface area were analyzed in these four groups by gender and body mass index (BMI). Mean±SD, One-way Anova, two sample t-test and Tukey- Kramer HSD were applied.

Results

The mean age of the selected population is 57.9 years ±14.9 (females=57.7±14.7, males=58.2±15.1) and the body surface area of 1.9 m2±0.2 (females=1.8±2 and males=2.1±0.2). The LV GLS values (Figure) of groups 1, 2, 3 and 4 were −20.7, −18.9, −17.5 and −19.9 and their EDV cc/m2 values were 63.6, 58.5, 61.2 and 68.2 respectively. LV GLS and Biplane EF values were higher in females while Biplane EDV and ESV were higher in males. When each gender is sub-divided based on their BMI (<25 and ≥25), the LV GLS, EDV and ESV values were higher in all groups with BMI<25 except in males with concentric remodeling and females with concentric hypertrophy where they were low.

Remodeling distribution

Conclusion

To our knowledge, this is the biggest single center study to evaluate LV GLS and volumes based on type of remodeling by gender and BMI. When compared with normal geometry, LV volumes and GLS values were statistically different among each type of remodeling as well as for gender and BMI. These results can be used as reference values in patient population studies where remodeling is being analyzed in subjects with normal LV EF.

Acknowledgement/Funding

None
P2459Do left atrial strain measurements provide information independent from left ventricular function parameters?
Authors: Malaescu G G , Petrescu A , Duchenne J , Capota R , Voigt J U
Published: October 2019

Introduction

LA strain has been proposed to be a reliable and independent prognostic marker, as well as a useful surrogate of LA function.

Purpose

To assess if LA deformation measurements add independent information to standard echocardiographic measurements.

Methods

We included 66 normals and patients with a wide range of pathology and diastolic dysfunction grade from the echo data base of our hospital if image quality was sufficient for both LA and LV strain analysis. Patients with a mobile interatrial septum, arrhythmias and more than mild valvular regurgitation were not considered. Standard echocardiographic measurements including LA and LV volumes were performed according to current guidelines. LA and LV longitudinal strains were assessed by 2D speckle tracking in the same cardiac cycle in apical 4 and 2 chambers views using peak R as time reference. Peak LA and LV strain as well as LA and LV strain at onset of LA contraction were measured to calculate the strain components of all three phases of the cardiac cycle (systolic, early diastolic and late diastolic).

Results

In our cohort, the ratio of LA and LV systolic strain was directly and strongly related to the volume ratio of the two chambers (R2=0,894, slope=-1.001, p<0.0001, see Figure 1). This was confirmed by a multivariate regression analysis, where systolic LA strain proved to be strongly dependent on systolic LV strain, LA volume and LV volume (R2=0.872, p<0.0001 for the final model).

For early diastolic strain, confounders were LV early diastolic strain, LA volume, LV volume and lateral wall E' tissue velocity (R2=0.784, p<0.0001); while LA late diastolic strain was dependent on LV late diastolic strain, LA volume, LV volume and lateral wall A' tissue velocity (R2=0.823, p<0.0001).

Strain ratio vs volume ratio

Conclusions

Our data suggest that systolic LA strain (reservoir strain) is strictly dependent on systolic LV strain and the volume ratio of both chambers and, therefore, its measurement cannot provide additional information beyond classical measurements. Diastolic LA strain components show a less strict dependence on LV function and may therefore provide additional information.
P2482Sex-based differences in cardioprotective role of SGLT-2 inhibitors in patients with type 2 diabetes mellitus
Authors: Madan N , Sohal S , Parapid B , Sperling L , Januzzi J L , Lalic K , Lundberg G , Butler J , Kosiborod M , Santos Volgman A
Published: October 2019

Background

Randomized studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce major cardiovascular events in patients with type 2 diabetes mellitus. However, it is not known whether there are significant sex-based differences in the cardioprotective role of SGLT-2 inhibitors.

Purpose

To investigate whether sex differences exist in reduction of major cardiovascular events (MACE)in patients with type 2 diabetes mellitus when treated with SGLT2i.

Methods

A comprehensive PubMed search was conducted using keywords, (“Diabetes” AND (“Dapagliflozin” OR “Empagliflozin” OR “Canagliflozin” OR “Ertugliflozin”) AND “Outcomes”) that resulted in a total of 221 studies. Studies were included in our meta-analysis if they were randomized controlled trials, placebo-controlled, reported MACE as the primary outcome and reported sex-based subgroup analyses of these outcomes. Only 2 RCTs (EMPA-REG and DECLARE-TIMI 58) met our inclusion criteria.The sex-based event data for both trials was pooled to calculate risk ratios (RR) with 95% confidence intervals (CI). Analyses was performed using Comprehensive Meta-analysis (CMA) software. Fixed effect models, random effect models and mixed effect models were used.

Results

Pooled datafrom the 2 RCTs (EMPA-REG and DECLARE-TIMI 58) resulted in a total of 24,180 patients who were included in our primary analysis. Of these, 2331 patients were reported to have MACE. In our pooled data, SGLT2i reduced MACE in patients with diabetes with an overall risk ratio of 0.92 (0.85–0.99), p=0.03 (I2=0, p=0.31)using fixed effect model (Table 1). We also performed subgroup analysis of the pooled data categorizing by sex and using mixed effect model. Our subgroup analysis by sex showed a Q statistic of 1.88 with p-value of 0.17 suggesting that there is no significant difference in MACE reduction between men and women with diabetes when treated with SGLT2i. However, on further analyzing the sex differences in the individual trials, we found that women may have greater reduction in MACE compared with their male counterparts (RR in females: 0.66 (0.42–1.04); RR in males: 0.92 (0.84–1.00)), however this finding did not meet statistical significance (Table 2).

Conclusion

Our meta-analysis included the pooled data from 2 major RCTs (EMPA-REG and DECLARE-TIMI 58) assessing the cardioprotective role of SGLT2i in diabetic patients and shows that SGLT2i significantly reduce the risk of major adverse CV events in patients with type 2 diabetes mellitus. However, we did not find any significant sex-based differences in reduction of MACE between men and women with diabetes when treated with SGLT2i.
P2497Exercise training could reduce inflammatory activity of visceral adipose tissue in overweight women
Authors: Pahk K , Kwon H W , Eo J S , Seo H S , Kim W , Kim S
Published: October 2019

Objectives

Visceral adipose tissue (VAT) plays pivotal roles for an increased risk of cardiometabolic disease through triggering inflammatory process. This prospective study aimed to evaluate whether the exercise training could reduce inflammatory activity of VAT assessed by 18F-fluorodeoxyglucoase (FDG) positron emission tomography-computerized tomography (PET/CT).

Methods

Twenty-three overweight women who participated in exercise training program were included. Exercise training program was composed of aerobic exercise (45 min/session, 300 Kcal/day) and muscle strength training (20 min/session, 100 Kcal/day) 5 times per week for 3 months. They underwent F-18 FDG PET/CT before starting exercise program (baseline) and after completion of 3 months exercise program. Anthropometric data, clinical laboratory data, VAT area, and maximum standardized uptake value (SUVmax) of VAT were compared between baseline and after completion of the total exercise program.

Results

Baseline VAT SUVmax showed significant correlation with body weight, body mass index (BMI), waist circumference, and hip circumference. VAT SUVmax was significantly reduced by exercise training program. Exercise training program also reduced body weight, BMI, waist circumference, hip circumference, VAT area, subcutaneous adipose tissue area and blood pressure. The change of VAT SUVmax was significantly higher than the change of VAT area.

Conclusions

Exercise training could reduce the inflammatory activity of VAT assessed by F-18 FDG PET/CT. Thus, exercise would be a promising non-pharmacological strategy to reduce inflammatory activity of VAT. Furthermore, F-18 FDG PET/CT could be useful to evaluate the effect of therapeutic intervention targeted to inflammatory VAT activity.
P2502Intensity and duration of lifestyle interventions for long term weight loss and association with mortality: a meta-analysis of randomised trials
Authors: Benatar J R , Singh N , Stewart R A H
Published: October 2019

Background

Lifestyle interventions are widely recommended for weight management, particularly in patients with diabetes and cardiovascular disease. The intensity and duration of interventions needed to achieve sustained weight reduction are uncertain.

Objectives

To investigate the importance of the frequency and duration of lifestyle interventions for achieving weight loss over ≥ one year, and to evaluate associations between weight loss and all-cause mortality.

Method

Meta-analysis of randomised trials published in English-language journals from 1980 to June 2018 that assessed lifestyle compared to control interventions on weight loss in ≥100 subjects, and which reported weight change and mortality for ≥ one year.

Results

31 randomised trials with a total of 20 816 overweight or obese participants, 70% of whom had cardiometabolic risk factors, were included. The weighted mean difference in body weight between diet and lifestyle intervention and control arms at 1 year was −3.65, 95% confidence interval (CI) −4.66, −2.65 kg, and at 3 years was −2.45, 95% CI: −3.73, −1.17kg. Weight loss at one year was greater in studies with more compared to fewer interventions (>vs ≤28/year (−4.53 [IQR −5.93, −3.12] kg vs −2.38 [−3.98, −0.78] kg, p=0.001). There were 593 deaths (rate ∼0.3%/year), and the odds ratio for mortality for weight loss interventions compared to the controls was 0.86 (95% CI 0.74, 1.01), p=0.09.

Table 1. Association with intervention intensity with weight loss achieved and mortality Number of interventions in first year N studies# Number of patients Mean difference p Total deaths Odds ratio p Random effect model (kg) (95% CI) Fixed effect model (95% CI) ≤6 3 510 −0.84 [−1.40, −0.28] <0.0001 5 1.45 [0.22, 9.40] 0.7 7–12 6 2022 −2.04 [−3.24, −0.84] <0.0001 10 1.34 [0.35, 5.16] 0.67 13–24 6* 3490 −2.46 [−5.59, 0.67] <0.0001 23 1.20 [0.49, 2.96] 0.69 ≥25 18 13717 −3.53 [−4.13, −2.92] <0.0001 555 0.84 [0.71, 1.00] 0.05 Total 31 100 −2.98 Total 31 *2 studies reported mortality but not weight loss.

Conclusion

Lifestyle programs with frequent patient interactions sustained over a year or more achieve modest weight loss. The level of intervention needed for clinically meaningful weight reduction may be unrealistic for most medical practices. There is a modest non-significant reduction in mortality with lifestyle programs, but limited data on whether lifestyle interventions for obesity decrease mortality in persons at higher risk because of cancer, heart failure or ischaemic heart disease.

Acknowledgement/Funding

None
P2503Clinical outcomes of discordant exercise electrocardiographic and echocardiographic findings in patients with chest pain and no history of coronary artery disease
Authors: Im E.-S , Sohn I.-S
Published: October 2019

Purposes

The aim of this study was to evaluate comparative clinical outcomes of discordant electrocardiographic (ECG) and echocardiographic (Echo) findings compared to concordant findings during treadmill exercise echocardiography in patients with chest pain and no history of coronary artery disease (CAD).

Methods

A total of 1725 consecutive patients who underwent treadmill echocardiography with chest pain and no history of CAD were screened. The patients were classified into four groups: ECG−/Echo− (negative ECG and Echo), ECG+/Echo− (positive ECG and negative Echo), ECG−/Echo+, and ECG+/Echo+. Concomitant CAD was determined using coronary angiography or coronary computed tomography. Major adverse cardiac events (MACEs) were defined as a composite of coronary revascularization, acute myocardial infarction, and death.

Results

MACEs were similar between ECG−/Echo− and ECG+/Echo− groups. Compared to ECG+/Echo− group, ECG−/Echo+ group had more MACEs [adjusted hazard ratio (HR) adjusted by clinical risk factors (95% confidence interval), 3.57 (1.75–7.29), p<0.001]. Compared with ECG+/Echo+ group, ECG−/Echo+ group had lower prevalence of concomitant CAD and fewer MACEs [HR, 0.49 (0.29–0.81), p=0.006].

Conclusions

Positive exercise Echo alone during treadmill exercise echocardiography had worse clinical outcomes than positive ECG alone, and the latter had similar outcomes to both negative ECG and Echo. Positive exercise Echo alone also had better clinical outcomes than both positive ECG and Echo. Therefore, exercise Echo findings might be superior for predicting clinical outcomes compared to exercise ECG findings. Additional consideration of ECG findings on positive exercise Echo will also facilitate better prediction of clinical outcomes
P2509Less effect of cardiac rehabilitation for elderly cardiac patients with lower educational attainment
Authors: Kjesbu I , Mikkelsen N , Sibilitz K , Wilhelm M , Gil C P , Iliou M C , Zeymer U , Meindersma E P , Ardissino D , Van Der Velde A E , Van't Hof A W J , De Kluiver E P , Prescott E
Published: October 2019

Background

Previous analyses from EU-CaRE study have shown that elderly cardiac patients with basic education have a greater burden of cardiovascular risk factors and a lower exercise capacity at baseline of cardiac rehabilitation (CR). We hypothesize that participation in CR will diminish this socioeconomic gap.

Purpose

To describe if educational level predicts the benefits of CR in an elderly population in Europe.

Methods

The observational EU-CaRE study is a prospective study with eight participating CR centers in seven countries (Denmark, France, Germany, the Netherlands, Italy, Spain and Switzerland). Consecutive patients age 65 or older with coronary heart disease or valve surgery participating in CR were included. Data were obtained at baseline (T0) and at the end of CR (T1) and include risk factors for cardiovascular disease, clinical and psychological assessment, medical treatment and exercise capacity. Patients were divided into basic, intermediate and higher educational levels. We compared changes from T0-T1 by multiple regression models.

Results

A total of 1621 (99% of included) patients were eligible for follow-up analyses. At baseline patients with basic education had more diabetes, higher BMI, lower exercise capacity (VO2 peak) and higher scores for depression (GAD) and anxiety (PHQ-9). At T1 they had improved significantly less on these parameters. The results were not affected by adjustment for gender, age, country and baseline value of the variable. Use of evidence-based medication did not differ by level of education.

Difference between T0 and T1 Factor High Intermediate Basic p-value* N total 1621 N=386 N=775 N=460 BMI, mean (SD) −0.16 (0.71) −0.08 (0.82) −0.26 (0.95) 0.794 LDL (mmol/L), mean (SD) −0.07 (0.63) −0.11 (0.62) −0.04 (0.58) 0.978 HbA1c (mmol/mol), mean (SD) 0.23 (3.70) 0.52 (4.39) 0.04 (5.79) 0.021 GAD score, mean (SD) −0.92 (2.72) −0.76 (3.07) −0.13 (3.47) 0.003 PHQ-9 score, mean (SD) −1.45 (3.21) −1.16 (3.36) −0.93 (4.49) <0.001 Diet score, mean (SD) 0.57 (1.72) 0.63 (1.90) 0.23 (1.81) 0.003 VO2 peak (ml/kg/min), mean (SD) 2.47 (2.90) 1.95 (2.78) 1.75 (2.56) 0.016 *Adjusted for gender, age, country and baseline value.

Difference in VO2peak, GAD and PHQ score

Conclusions

In this large European study with high-quality data from 7 CR centers we found an increased gap disfavoring the lower educated elderly patients participating in CR. These results indicate that “one-size cardiac rehabilitation” does not fit all and indicate that a more personalized CR with attention to the different needs of some patient groups is appropriate.

Acknowledgement/Funding

Horizon2020
P2511Effects of two different preventive counselling programs with remote support on salt and sodium-reach foods intake patterns in coronary patients with abdominal obesity
Authors: Pogosova N , Salbieva A O , Sokolova O Y , Yufereva Y M , Ausheva A K , Karpova A V , Yusubova A I
Published: October 2019

Background

Salt restriction is essential for a healthy diet, especially for patients (pts) with cardiovascular diseases. Pts education has a potential to promote healthier dietary patterns.

Purpose

To assess the impact of 2 preventive counselling programs with subsequent remote support resulted after hospitalization on salt intake in pts with coronary artery disease (CHD).

Methods

A prospective randomized parallel-group study in hospitalized nonsurgical pts with confirmed stable CHD and concomitant abdominal obesity. Most hospitalizations were due to elective percutaneous coronary intervention. Pts were randomized (1:1:1) into 3 groups. Before discharge, Groups 1 and 2 received comprehensive counselling with focus on diet followed by remote counselling by phone (Group 1) or via text messages (Group 2). Remote counselling was delivered weekly (Months 1–3) and then monthly (Months 4–6). Group 3 received standard advice only. Self-reported salt intake was assessed by consumption of sodium-reach foods such as sausages, pickles and by adding salt to cooked foods.

Results

A total of 120 pts (mean age±SD, 57,75±6,25 years, men, 83.4%) were enrolled. The Table presents self-reported dietary habits at baseline and at 12 months. At 1 year, significant improvements of relevant dietary habits vs control were seen in both intervention groups.

Group 1 Group 2 Group 3 (Control) Group 1 vs 3, Group 2 vs 3, (n=40) (n=40) (n=40) P for change from baseline P for change from baseline Pts adding salt to cooked foods at least sometimes   Baseline 87.5% 90.0% 85.0%   At 12 months 25.0%** 10.0%** 89.5% <0.01 <0.01 Pts avoiding pickled vegetables   Baseline 17.5% 20.0% 15.4%   At 12 months 62.5%* 77.5%** 7.9% <0.05 <0.01 Pts avoiding wurst, sausages, smoked meats   Baseline 0.0% 10.0% 7.5%   At 12 months 77.5%** 87.5%** 2.6% <0.01 <0.01 *p<0.05, **p<0.01 vs baseline within group.

Conclusion

Pre-discharge preventive counselling with subsequent remote support in coronary patients with abdominal obesity resulted in significant improvement of dietary habits in terms of salt and high-sodium foods intake.
P2523Hand grip strength as a predictor of exercise capacity in coronary heart disease
Authors: Choi C U , Choi J I , Kim W , Jang W Y , Kang D O , Park Y , Na J O , Kim E J , Rha S W , Park C G , Seo H S , Kim J W
Published: October 2019

A recent study has shown that quadriceps strength can be used to predict the level of exercise capacity in patients with coronary heart disease (CHD). We investigated whether the relationship between muscular strength and exercise capacity is also observed with hand grip strength (HGS). We studied 443 participants (age, 61.8±11.2 y; 77.7% male) who underwent coronary intervention and participated in cardiac rehabilitation between 2015 and 2018. Participants were assessed for grip strength, measured using a Jamar dynamometer. Logistic regression was used to assess the relationship between various clinical measures (HGS, age, sex, etc) with the distance walked on a 6-minute walk test (6MWT) and maximal oxygen uptake (VO2max). HGS was significantly related to distance walked on the 6MWT (r=0.435, p<0.001). It was the only predictor of all exercise capacity categories, and one of the strongest predictors of each exercise capacity category. A HGS of 25.5% of body weight predicted an achievement of a 200 m walk on the 6MWT (positive predictive value = 0.95). However, HGS less than 35.5% of body weight predicted that 500m could not be done in 6 minutes (negative predictive value = 0.97). This trend was also observed in the subgroups in which VO2max was measured. This study demonstrates that HGS is associated with exercise capacity in CHD and can be used to predict the level of exercise capacity. These findings may contribute to setting the recommended level of daily activity as well as the level of cardiac rehabilitation in CHD.

Logistic regression models for different levels of exercise capacity Level of exercise capacity B±S.E p-value Odd ratio 95% CI Distance of 6MWT   200 m Grip strength 0.054±0.014 <0.001 1.056 1.027–1.086   300 m Grip strength 0.042±0.009 <0.001 1.042 1.024–1.062   400 m Grip strength 0.047±0.011 <0.001 1.048 1.026–1.070   500 m Grip strength 0.051±0.016 0.001 1.053 1.021–1.086 VO2max level   4 METs Grip strength 0.054±0.010 <0.001 1.056 1.036–1.076   6 METs Grip strength 0.059±0.011 <0.001 1.061 1.039–1.083   8 METs Grip strength 0.081±0.015 <0.001 1.085 1.053–1.117   10 METs Grip strength 0.113±0.049 0.019 1.12 1.019–3.232 Data are presented as mean ± standard deviation (SD). 6MWT, 6-minute walk test; STEMI, ST-Elevation Myocardial Infarction; SE, standard error; CI, confidence interval; VO2max, Maximal Oxygen uptake; METs, Metabolic equivalents.
P2526Association between preoperative nutritional status and clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention
Authors: Chen S , Leu H B
Published: October 2019

Background

Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. Different nutritional assessment tools have been developed to provide a better screening tool for malnutrition status evaluation. The prognostic significance of the Controlling Nutritional Status (CONUT) score has been widely used but has limited information for the predictive value in coronary artery disease (CAD) patients.

Methods

We conducted a cohort which enrolled 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score which comprises of serum albumin and total cholesterol levels, and total lymphocyte count. Higher scores reflect worse nutritional status. The patients were classified as normal (0–1), mildly (2–4), moderately (5–8), or severely malnourished (9–12) based on the CONUT score. The association between nutritional status and future events including acute myocardial infarction (AMI), ischemic stroke, revascularization, congestive heart failure, major adverse cardiovascular events (CV death, stroke and AMI) and total cardiovascular events were evaluated.

Results

81.5% of our patients were male, and the mean age was 71.5±12.1 years. The mean CONUT score was 2.6. Patients with higher COUNT score were older, have lower body weight, BMI, lower LDL-C values and worse renal function. The Kaplan-Meier analysis revealed patients with high CONUT score was significantly associated with higher rates of the major event including MACE (log-rank P<0.001), acute myocardial infarction (P<0.001), cardiovascular death (P<0.001), congestive heart failure (P<0.001) and total CV events (log-rank P<0.001). After adjusting for comorbidities and medication, increasing CONUT score was independently associated with higher risk of developing AMI (HR: 1.13; 95% CI 1.03–1.24, P=0.008); CV death (HR: 1.18, 95% CI: 1.07–1.30, P=0.001); CHF (HR: 1.11, 95% CI: 1.04–1.18, P=0.002); MACE: (HR: 1.14, 95% CI: 1.07–1.22, P<0.001) and total CV events (HR: 1.11, 95% CI: 1.07–1.15, P<0.001). The subgroup analyses demonstrated that the association of CONUT score existed independently with other established cardiovascular risk factors.

Nutritional status and MACE

Conclusion

CONUT score is a promising marker for long-term outcome prediction and risk stratifications in patients with CAD undergoing PCI.

Acknowledgement/Funding

None
P2527Accumulative impact of poor nutrition and frailty on 1-year mortality among acute decompensated heart failure patients
Authors: Sumi T , Oguri M , Takahara K , Umemoto N , Shimizu K , Tanaka A , Ishii H , Murohara T
Published: October 2019

Background

Several studies have proved that both poor nutrition (PN) and Frail are associated with poor prognosis among heart failure patients. However, it has not been fully revealed whether PN and frail could have impact on prognosis accumulatively.

Purpose

The purpose of the present study was to evaluate the impact of nutritional and Frailty status on 1-year mortality among hospitalized patients with acute decompensated heart failure (ADHF).

Methods

Study subjects comprised of 315 hospitalized patients with ADHF. To evaluate the nutritional and Frailty status, we calculated the controlling nutritional status (CONUT) score and the Study of Osteoporotic Fractures (SOF) index at hospital admission. PN and Frailty were defined as the CONUT score ≥5 and SOF index ≥2, respectively.

Results

z Sixty-nine subjects (21.9%) were died within 1-year. PN and Frailty were observed in 33.3% and 55.6% of study subjects, respectively. Both PN and Frailty were similarly related to the 1-year mortality by univariate cox regression analysis (Hazard Ratio (HR) 2.43, 95% confidence interval (CI) 1.51–3.91, p=0.0003: HR 3.13, 95% CI 1.83–5.66, p<0.0001, respectively).

Study subjects were classified into 4 groups according to the nutritional and frailty status: control (normal nutrition without Frailty, n=110), PN alone (PN without Frailty, n=30), Frailty alone (Frailty without PN, n=100), and PN + Frailty (PN with Frailty, n=75). The Kaplan-Meier event curves for 1-year all-cause mortality illustrated that subjects with PN + Frailty had a significantly higher mortality than in subjects with control, PN alone and Frailty alone (log rank p=0.0001, 0.0180, 0.0070, respectively).

As well as, cox regression analysis revealed that PN + Frailty showed significantly higher mortality than control, PN alone and Frailty alone. (HR 5.33, 95% CI 2.75–11.1, p<0.0001: HR 2.99, 95% CI 1.26–8.78, p=0.011: HR 2.07, 95% CI 1.21–3.61, p=0.008, respectively). Moreover, multivariate cox regression analysis also revealed that PN with Frailty was independently associated with 1-year mortality even after adjustment for age, body mass index, systolic blood pressure, and chronic kidney disease. (HR 3.40, 95% CI 1.69–7.32, adjusted p<0.001)

Kaplan-Meier curve for 1year mortality

Conclusions

The combination assessment consisted with nutrition and frailty could identify poor prognosis patients with ADHF.
P2528Responsiveness to nutritional intervention would impact on future cardiovascular prognosis in poor fitness patients
Authors: Ehara M , Shibata K , Kameshima M , Fujiyama H , Terai M , Shimizu K , Matsui Y , Higashida Y , Watanabe M , Shimada A , Ohkawa Y , Yamada S
Published: October 2019

Purpose

Nutritional improvement has been proposed for long-term cardiovascular prognosis as well as fitness recovery. We aimed to examine whether “responsiveness” to nutritional and exercise interventions would impact patients' cardiovascular prognosis even patients in low baseline fitness level.

Methods

We included 254 consecutive patients who participated in the phase II comprehensive cardiovascular rehabilitation (CCR) for at least three months. All patients underwent cardiopulmonary exercise test (CPX) at the initial and completion phases of CCR. Nutritional guidance was periodically performed individually during CCR. Peak oxygen uptake (PVO2) was measured through CPX to evaluate the fitness level, whereas nutritional status was evaluated using the geriatric nutritional risk index (GNRI). Patients were divided into “low fitness” and “normal fitness” groups based on the median of baseline PVO2. Each group was further classified into four categories according to the changes in VO2 and GNRI during CCR: “Both NOT improved”, “Only GNRI improved”, “Only PVO2 improved”, and “Both improved”.

Results

Cox proportional regression analysis showed that the category of “both NOT improved” was an independent predictor for cardiovascular risk among the baseline low fitness group (Hazard ratio: 4.5, p=0.007); whereas no significant difference among the normal fitness group. Kaplan-Meier analysis revealed that the event-free survival rate was significantly lower in the “both NOT improved” category (log rank p=0.002) among the baseline low fitness group (figure); whereas no significant difference among the normal fitness group.

GNRI/PVO2 improvement vs. prognosis

Conclusion

Responsiveness to nutritional and exercise intervention could be a predictive factor of cardiovascular prognosis even in low fitness patients.
P2560Metalloprotease nardilysin controls heart rate through the transcriptional regulation of ion channels critical for sinus automaticity
Authors: Ohno M , Matsuura H , Makiyama T , Nishi K , Iwasaki H , Matsuda S , Kimura T , Nishi E
Published: October 2019

Nardilysin (NRDC; N-arginine dibasic convertase) is a metalloprotease of the M16 family. We have demonstrated that NRDC in the extracellular space enhances ectodomain cleavage of multiple membrane proteins. We also reported that nuclear NRDC regulates transcription of several target genes as a transcriptional coregulator. These results indicated that NRDC is a protease having localization-dependent multiple functions. NRDC-deficient mice (Nrdc−/−) showed wide range of phenotypes such as hypomyelination, hypothermia, and bradycardia. In this study, we have explored a role of NRDC in the regulation of heart rate. (1) Pharmacological blocking of autonomic nervous system revealed that an intrinsic heart rate of Nrdc−/− was significantly reduced compared with that of wild-type mice. (2) In Nrdc−/− hearts, mRNA levels of Cav3.1 and HCN1/4, ion channels responsible for sinus automaticity, were significantly reduced. (3) Funny (If) current and T-type Ca current measured in the sinus node cells were markedly reduced in Nrdc−/− cells, indicating that the functions of Cav3.1 and HCN4 are impaired. (4) Gene knockdown of NRDC in primary rat ventricular myocyte led to the reduction of mRNA level of HCN4. (5) Chromatin immunoprecipitation-PCR analysis showed that NRDC binds to the promoter region of Cav3.1 and HCN4, suggesting the direct involvement of NRDC in transcriptional regulation of these ion channels. (6) Atrium-specific Nrdc−/− (Sarcolipin-Cre) showed mild bradycardia and reduced Cav3.1 mRNA expression. Together, our results indicated that NRDC in cardiomyocyte controls heart rate through the transcriptional regulation of ion channels critical for sinus automaticity.

Acknowledgement/Funding

KAKENHI (17K09575)