bluuebunny/crossref_metadata_2025 huggingface dataset:
P2499Effects of aerobic and resistance exercise on skeletal muscle of infarcted rats
Authors: Gomes M J , Lima A R R , Pagan L U , Damatto F C , Oliveira L R S , Souza L M , Rodrigues E A , Pontes T H D , Sodre F S S , Murata G M , Fernandes A A H , Zornoff L A M , Okoshi K , Okoshi M P
Published: October 2019

Background

Skeletal muscle changes contribute to reduced physical performance after myocardial infarction (MI). Exercise has been recommended to stable patients. However, the effects of resistance exercise after MI are not clear. We compared the effects of aerobic and resistance exercise initiated during compensated cardiac remodeling in infarcted rat gastrocnemius muscle.

Methods

Three months after MI induction, Wistar rats were divided into four groups: Sham (n=20); sedentary MI (MI-S, n=9); aerobic exercised MI (MI-A, n=9); and resistance exercised MI (MI-R, n=13). Exercised rats trained three times a week for 12 weeks on a treadmill or ladder. Energy metabolism, oxidative stress markers, and antioxidant enzyme activities were assessed by spectrophotometry. Satellite cells activation markers (MyoD, NCAM, and myosin heavy chain neonatal isoform) were assessed by immunofluorescence or Western blot (Pax-7). Statistical analysis: ANOVA or Mann Whitney.

Results

Physical aerobic capacity was greater in MI-A and strength gain higher in MI-R. Cardiac structures and left ventricular function evaluated by echocardiogram did not differ between infarcted groups. Histological analysis showed that MI size and gastrocnemius cross sectional area did not differ between infarcted groups. Oxygen reactive species production was higher in MI-S than Sham and lipid hydroperoxide concentration was lower in MI-A than the other groups. Catalase activity was higher and glutathione peroxidase lower in infarcted groups than Sham. Superoxide dismutase activity was higher in Sham and MI-R than MI-S. Skeletal muscle metabolism enzyme activity did not differ between groups, except for increase pyruvate kinase in MI-S against the other groups, and β-hydroxyacyl CoA dehydrogenase in MI-S against Sham. Satellite cell activation and protein expression of MAPK and NF-kB did not differ between groups.

Conclusion

Aerobic and resistance exercise respectively improves physical capacity and muscle strength without changing echocardiographic parameters of infarcted rats. Myocardial infarction increases oxygen reactive species production and changes antioxidant enzyme activity and glucose and fatty acid metabolism. Aerobic exercise is superior to resistance exercise against oxidative stress reducing muscle lipid hydroperoxide concentration and attenuating change in glutathione peroxidase activity.

Acknowledgement/Funding

Financial support: Fapesp, CNPq, Capes, and UNESP
P2500The high-sensitivity cardiac troponin I and T response following strenuous activity is attenuated by smokeless tobacco:The North Sea Race Endurance Exercise Study (NEEDED) 2014
Authors: Skranes J , Kleiven O , Aakre K M , Skadberg O , Melberg T H , Omland T , Orn S
Published: October 2019

Background

Use of snus, a smokeless oral tobacco product, is increasing among athletes and recreational exercisers in Scandinavia. Strenuous physical activity is associated with an acute increase in high-sensitivity cardiac troponins (hs-cTn) in healthy individuals. Current smoking is associated with lower baseline hs-cTn concentrations in current smokers in the general population, but whether tobacco affects the hs-cTn response to exercise remains unknown.

Methods

We measured serial cTnI and cTnT concentrations in 1002 healthy recreational athletes before, 3 and 24 h after a 91 km bicycle race. Self-reported snus habits were reported as: non-current (n=794) and current (n=118). The association between snus use and change in log hs-cTnI and hs-cTnT (differences between concentrations at baseline and 3 h (Δ3 h) and 24 h (Δ24 h)) were assessed by multivariable linear regression analysis.

Results

Current snus use was associated with lower cTnI (current users of snus vs non-current: median, 1.7 ng/l; interquartile range (IQR), 1.6–2.3 vs 2.0 ng/L; IQR 1.6–3.2; p=0.020) and cTnT (current users of snus vs non-current: median, 3.0 ng/L, IQR, 3.0–3.5 vs 3.0 ng/L, IQR 3.0–4.3; p=0.021) concentrations at baseline. Both in unadjusted and fully adjusted linear regression models, users of snus had significantly lower Δ3 h and Δ24 h cTnI and cTnT concentrations (Table).

Association between snus use and change in concentrations of hs-cTnI and hs-cTnT (95% CI) Model 1 Model 2 Model 3 Model 4 ΔcTnI 3 h   Current snus −28% (−46% to −10%), p=0.003 −33% (−51% to −14%), p=0.001 −31% (−49% to −13%), p=0.001 −29% (−47% to −11%), p=0.002 ΔcTnI 24 h   Current snus −38% (−62% to −15%), p=0.002 −36% (−59% to −12%), p=0.003 −32% (−56% to −9%), p=0.007 −30% (−54% to −7%), p=0.010 ΔcTnT 3 h   Current snus −28% (−10% to −46%), p=0.003 −33% (−51% to −14%), p=0.001 −31% (−49% to −13%), p=0.001 −29% (−47% to −11%), p=0.002 ΔcTnT 24 h   Current snus −20% (−4% to −36%), p=0.015 −23% (−39% to −8%), p=0.004 −21% (−36% to −5%), p=0.009 −19% (−34% to −14%), p=0.013 Model 1 unadjusted; Model 2 adjusted for sex and age; Model 3 adjusted for Model 2 and systolic blood pressure, body mass index, low-density lipoprotein and estimated glomerular filtration rate; Model 4 adjusted for the same variables as in Model 3 but also race duration and resting heart rate.

Conclusion

The exercise-induced cTn response in healthy recreational cyclist is attenuated in users of smokeless tobacco compared to never users. These findings extend observations of lower hs-cTn concentrations in tobacco smokers in the general population.

Acknowledgement/Funding

Operating grant from North Sea Race, Abbot Diagnostics, Lærdal Foundation. PhD fellowship from South-Eastern Norway Regional Health Authority.
P2518Failure of completion of post-myocardial infarction rehabilitation programme - Who and why? Single center experience with novel Coordinated Comprehensive Care program in Poland
Authors: Telec W , Kalmucki P , Krysztofiak H , Szyszka A , Baszko A
Published: October 2019

Background

Rehabilitation after acute myocardial infarction is a well-proven strategy to improve outcomes and reduce complications rate. Poland recently introduced a novel, fully-reimbursed Coordinated Comprehensive Care (CCC) program after myocardial infarction, a significant portion of which comprises access to free-of-charge cardiac rehabilitation.

Purpose

The purpose of the study was to analyze all patients qualified for the Coordinated Comprehensive Care Program and evaluate reasons for not completing rehabilitation. We compared two groups of patients - those who completed the rehabilitation and those that did not - in terms of clinical, demographic and laboratory characteristics.

Methods

All patients (n=169) referred from the cardiology department for the CCC program were included in the study. They were divided into two groups, depending on single, strict criterium of completion or non-completion of the rehabilitation program. Demographic, clinical and laboratory data were collected and analyzed.

Results

The majority of the patients (n=100, 59.2%) did not undergo cardiac rehabilitation. 61 of them were not qualified for rehabilitation programme by the consortium of doctors: 33 of them due to the need for further invasive treatment, the remainder 28 were disqualified due to severe comorbidities. 32 patients did not commence the program despite referral and encouragement, mostly (n=25) due to personal reasons, 7 patients did not specify reasons for not participating in the rehabilitation. 7 patients were lost to follow-up.

Patients who completed rehabilitation (n=69, 40.8%) were younger that those who did not (64.4±9.8 vs. 67.1±9.5 years, respectively; p=0.076), had significantly higher baseline LVEF (49.1±9.4 vs. 44.7±11.9%, p<0.03), and had lower serum creatinine level (0.99±0.28 vs. 1.15±0.59 mg/dl; p<0.03). There were more patients with LVEF<35% (n=23; 23%) in the no-rehabilitation, than in the other group (n=5; 7.25%; p<0.01).

Rehabilitation completed (n=69) Rehabilitation NOT completed (n=100) p Gender – male 40 (35.4%) 73 (64.6%) <0.05 LVEF- % 49.12 (±9.43) 44.69 (±11.97) <0.03 No. of patients with EF <35% 5 (7.25%) 23 (23%) <0.01

Conclusion

Although fully-reimbursed cardiac rehabilitation is provided for all patients following acute myocardial infarction, there is a significant number of patients who fail to complete the programme. This group comprises more male patients with worse clinical and laboratory test results, especially LVEF and renal function. Efforts should be made to address the problem and modify the programme accordingly.
P2545Long-term use of anabolic-androgenic steroids in male weightlifters is associated with left ventricular systolic dysfunction
Authors: Abdullah R , Bjornebekk A , Dejgaard L , Hauger L , Edvardsen T , Haugaa K , Almaas V
Published: October 2019

Background

Illicit use of anabolic-androgenic steroids (AAS) is widespread and has adverse psychological and cardiovascular effects. Few well-powered studies have explored the effect of long-term AAS-use on left ventricular systolic function.

Purpose

To explore the relationship between long-term use of AAS and left ventricular mass and systolic function.

Methods

We included male weightlifters with a history of >1 year of cumulative AAS-use and male weightlifters unexposed to AAS. We performed echocardiography in all and assessed left ventricular mass using 2D echocardiographic linear measurements and Cube formula, left ventricular ejection fraction (EF) ad modum Simpson, and left ventricular global longitudinal strain (GLS) by speckle-tracking echocardiography.

Results

We recruited 100 male weightlifters, 58 of whom were previous or current AAS-users with mean±SD AAS-use of 10.4±7.0 years, and 42 unexposed weightlifters. There were no difference in age (35.5±9.2 vs. 35.3±7.5 years, p=0.8) nor body mass index (BMI) (BMI 31.4±5.0 vs. 30.1±3.5, p=0.6) between AAS-exposed and unexposed weightlifters. Compared with unexposed weightlifters, AAS-exposed weightlifters demonstrated thicker interventricular septum (11.2±2.4 vs. 9.2±1.3 mm, p<0.001), thicker left ventricular posterior wall dimension (10.1±2.1 vs. 8.9±1.3 mm, p<0.001), and higher left ventricular mass index (99.7±25.4 vs. 78.4±12.1 g/m2, p<0.001). Both left ventricular EF and left ventricular GLS were decreased in AAS-exposed weightlifters compared with unexposed weightlifters (49±9 vs. 53±6%, p=0.02, and −15.6±2.6 vs. −18.3±2.1%, p<0.001) (Figure).

Conclusion

AAS use in male weightlifters was associated with increased left ventricular mass and impaired left ventricular systolic function. Our results suggest considerable adverse cardiac effects of AAS use, but the results need confirmation in prospective observational trials.
P2556TXNDC5 is a novel therapeutic target of atrial fibrosis and fibrillation
Authors: Wu P C , Lin B C , Yeh Y H , Chen W J , Yang K C
Published: October 2019

Background

Atrial fibrillation (AF), one of the most common cardiac arrhythmias, increases the risk of stroke, systemic embolization and cardiovascular mortality. Atrial fibrosis, a hallmark of chronic AF, provides substrates to initiate/propagate fibrillation waves in the atria. There, however, lacks effective and specific therapeutics targeting atrial fibrosis. We have recently identified an endoplasmic reticulum (ER) protein thioredoxin domain containing 5 (TXNDC5) as a critical mediator of cardiac ventricular fibrosis. We hypothesized that TXNDC5 could also play an important role in the pathogenesis of atrial fibrosis and fibrillation.

Purpose

To determine the role of TXNDC5 in atrial fibrosis and fibrillation.

Methods and results

TXNDC5 transcript and protein levels were both significantly upregulated in the atrial tissue from patients with AF. In addition, TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor β1 (TGFβ1) and extracellular matrix (ECM) proteins in human atrial tissue. Knockdown of TXNDC5 in human atrial fibroblasts (hAF) attenuated TGFβ1–induced hAF activation, proliferation and ECM protein upregulation, whereas overexpression of TXNDC5 was sufficient to trigger hAF activation, proliferation and ECM protein production. Further experiments revealed that the fibrogenic effects of TXNDC5 were dependent on c-Jun N-terminal kinase (JNK) signaling. Furthermore, using α-MHC-TGFβcys33ser mice, a transgenic mouse model with cardiac-specific overexpression of constitutively active TGFβ, which develop extensive atrial fibrosis and inducible AF, we showed that TXNDC5 was strongly upregulated in the fibrotic atria of α-MHC-TGFβcys33ser mice and specifically enriched in collagen-secreting atrial fibroblasts. Targeted deletion of TXNDC5 (Txndc5−/−) in α-MHC-TGFβcys33ser mice considerably mitigated the extent of atrial fibrosis. In addition, transesophageal atrial burst pacing induced AF in 75% (3 out of 4) α-MHC-TGFβcys33ser mice, whereas knockout of Txndc5 markedly reduced the inducibility of AF (25%, 3 out of 12) in α-MHC-TGFβcys33ser mice (Figure).

TXNDC5 KO Reduces AF Inducibility

Conclusion

The present study revealed that ER protein TXNDC5 augments atrial fibrosis by promoting cardiac fibroblast proliferation and ECM protein production via JNK signaling activation. Targeted deletion of Txndc5 protects against TGFβ induced atrial fibrosis and AF. Targeting TXNDC5, therefore, could be a promising new therapeutic approach to treat or prevent atrial fibrosis and AF.
P2574Sexual activity and dysfunction in adult patients with congenital heart disease
Authors: Diller G P , Helm P , Gundlach C , Baumgartner H , Bauer U M M
Published: October 2019

Background

Although the number of adults with congenital heart disease (CHD) is increasing, there is little research into the impact of CHD on sexual activity and -dysfunction. Whether and to what extent sexual function is discussed with patients in clinical practice is also unknown.

Purpose

To study the current knowledge level, problems, wishes and fears of adult CHD patients regarding sexual activity.

Methods

Patients recruited via the German National Register for Congenital Heart Defects were invited to an online survey about sexual function. Overall, 4,484 patients (2,264 female) were invited to the survey and 873 patients (502 female) participated (19.5%). Patients were divided into four groups based on the underlying CHD severity classification: simple CHD (136 patients), moderate CHD (354 patients), complex CHD (340 patients).

Results

301 (35.6%) patients reported that they had very rarely or no sex at all in the six months preceding the survey (simple CHD: 25.7%, moderate CHD: 33.6%, complex CHD: 38.2%, other CHD: 39.5%). Based on the last six months, 71.2% of the surveyed male patients estimated the probability of having and maintaining an erection as high or very high (simple CHD: 85%, moderate CHD: 71.4%, complex CHD: 69.7%). In addition, 60.6% of the interviewed male patients reported to be almost always or always able to get a full erection sufficient for sexual intercourse. In contrast, 14.6% of the male patients already had erectile dysfunction, but did not discuss this issue with their physician. Overall, only 3.5% of the male patients stated that they were offered a consultation regarding erectile dysfunction by their treating physician. In contrast, 29.6% of the male patients would like to receive such counseling during routine medical examinations. In the last six months, 56.4% of the interviewed female patients, reported no difficulties with lubrication. 44% of the female patients already received advice from their physician on sexuality, contraception and pregnancy and 64.5% of the female patients would like to receive additional medical advice and information on sexuality, contraception and pregnancy in the context of routine medical check-ups.

Conclusions

This study reveals important issues regarding sexual function in male and female adult patients with CHD. The study reveals important gaps in counselling patients regarding sexual issues beyond contraception and pregnancy.
P2586Cardiac progenitor cell exosome-associated periostin triggers reentry of cardiomyocytes into cell cycle
Authors: Balbi C , Bolis S , Barile L , Vassalli G
Published: October 2019

Introduction

Nanovesicles known as exosomes (Exo) from cardiac-derived progenitor cells (CPCs) are cardioprotective and improve cardiac function after myocardial infarction; however the mechanisms of benefit are incompletely understood, especially with respect to endogenous cardiomyocytes (CM) renewal. Periostin (POSTN), a secreted extracellular matrix protein, is emerging as a matricellular factor that can trigger CM proliferation. We have identified POSTN as a protein secreted by CPC and enriched in their exosomal fraction.

Purpose

We sought to determine whether Exo-CPC can induce proliferation of CM and to explore the role of exosomal POSTN in inducing reentry of CM into the cell cycle.

Methods

Exo were isolated from CPC condioned medium by density gradient ultracentrifugation. Fractions were analyzed by Western blotting for the presence of POSTN as well as specific Exo markers (TSG101, CD9). POSTN-depleted Exo (ExoCPC_SiPOSTN) were obtained by transfecting CPC with specific siRNA. Active DNA synthesis was assessed on primary cell culture of rat neonatal CM by EdU incorporation. H9C2 cardiomyocytic cells were used to assess by real-time RT-PCR the expression of downstream genes Hippo/Yes-associated protein (YAP) signaling pathway.

Results

Western blotting analysis allowed to specifically determining the presence of Exo markers and POSTN in the different fractions of secreted vesicles. Smaller fractions (f1-f3) have the highest amount of TSG101 and CD9 as well as POSTN, thus suggesting that CPC secrete POSTN associated with Exo. The silencing of POSTN in cells resulted in a 60% reduction of Exo-associated POSTN compared to naïve ExoCPC. ExoCPC but not ExoCPC_SiPOSTN, were able to increase phosporylation of AKT and ERK in H9C2 cells. YAP phosporylation and its degradation was decreased resulting in the activation of the downstream gene AurBKinase. By real-time PCR, AurBKinase expression was increased by 2.6 folds with ExoCPC and 1.5 folds with ExoCPC_SiPOSTN compared to cells not exposed to Exo. ExoCPC were able to increase 1.5 fold EdU incorporation in cardiac troponin-positive primary rat CM. ExoCPC_SiPSTN did not affect proliferation.

Schematic figure

Conclusion

These results suggest that POSTN may promote cardiomyocyte proliferation through the direct activation of the AKT/ERK/Hippo-Yap pathway. Exosomes released by CPC are an important source of POSTN and may have a potential for promoting cardiac regeneration.

Acknowledgement/Funding

This work has been supported by The Swiss National Science Foundation under grant n° 310030_169194
P2587Cardiosomal microRNAs are essential in post-infarction myofibroblast phenoconversion
Authors: Sardu C , Shu J , Matarese A , Santulli G
Published: October 2019

Background

Circulating microRNAs (miRNAs) are actively transported, via inclusion in extracellular microvesicles/exosomes (herein named cardiosomes since they are deriving from cardiomyocytes), allowing protection from degradation and underlying cell-cell communications.

After myocardial infarction (MI), quiescent cardiac fibroblasts can acquire an activated phenotype, and a recognized marker of such activation is the expression of α-smooth muscle actin (α-SMA); such cells are commonly known as myofibroblasts.

Hypothesis

We hypothesize that cardiosomal miRNAs play a pivotal role in the activation of myofibroblasts following ischemic injury.

Methods

Using an established murine model of MI, obtained via permanent ligation of the left anterior descending coronary artery, we tested our hypothesis by measuring in primary isolated fibroblasts and cardiosomes the expression levels of a set of miRNAs, which we found to be upregulated in cardiomyocytes post-MI and to be involved in myofibroblast phenoconversion.

Results

Bioinformatic studies validated by biological assays identified three cardiomyocyte-specific miRNAs (namely miR-92a, miR-195, and miR-494) that are upregulated following cardiac ischemia and are also known to regulate α-SMA expression. We demonstrated that these miRNAs are upregulated in fibroblasts post-ischemia and are also contained in cardiosomes; to ensure that these miRNAs were confined inside cardiosomes, the samples were treated with RNase, showing that the level of miRNAs was not affected by RNase treatment, unless in presence of the detergent Triton X-100. The activation of myofibroblasts was confirmed by the increased expression of α-SMA. Using a luciferase assay, we also validated that miR-92a, miR-195, and mir-494 target the 3'UTR of α-SMA and regulate its transcription. Moreover, we observed that primary isolated cardiac fibroblasts were activated both when incubated with cardiosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post-MI cardiomyocytes, whereas no significant effects were detected following incubation with cardiosomes or medium from sham cardiomyocytes. Strikingly, myofibroblast phenoconversion was markedly attenuated when GW4869, an inhibitor of neutral sphingomyelinase 2 responsible for cardiosomes secretion, was added to cultured post-MI cardiomyocytes.

Conclusion

Taken together, our findings indicate that three cardiomyocyte-specific miRNAs (miR-92a, miR-195, and miR-494) are crucial in the activation of myofibroblasts.
P2593Evaluation of an ambulatory heart failure service - a 2 years' experience
Authors: Doleman F , Santon M , Clewes J , Laithwaite C , McIntosh R , Ahmed H , Ahmed N
Published: October 2019

Background

Heart failure accounts for 1–2% of health care expenditure in the National Health Service in the United Kingdom. Approximately 60–70% of that cost is in hospitalization for treatment. Various methods have been employed to reduce hospitalization in chronic heart failure; however effectiveness and safety of these methods have yet to be evaluated. Our ambulatory heart failure unit, run by specialist heart failure nurses, seeks to reduce admissions to hospital for heart failure by administering intravenous (I.V) diuretics in a day unit setting for ambulatory patients.

Purpose

We have reviewed data from December 2016 to December 2018 of patients using the ambulatory heart failure services in our hospital and evaluated its safety and effectiveness.

Methods

Retrospective evaluation of data collected from the ambulatory heart failure unit over a 24-month period as well as hospital data on admissions and length of stay of heart failure patients. Qualitative data was also collected from patients using the ambulatory heart failure unit.

Results

Since the opening of the ambulatory heart failure unit in December 2016, we have had 393 patient episodes. Referrals were largely from the community (265, 67%) however 128 (33%) patients were referred from an inpatient setting. Patients were treated for a mean of 12 days with intravenous furosemide infusion. The minimum dose of furosemide used was 120mg over 1 hour whereas maximum dose was 360mg over 2 hours. This translated into 4351 hospital bed days saved in a 24-month period. 144 (37%) of patients had heart failure with preserved ejection fraction (EF >40%), and 239 (61%) had heart failure with reduced ejection fraction (EF <40%).

28 patients (7%) referred to the unit were deemed inappropriate for unit and required admission. A further 35 patients (9%) were admitted to hospital for other illnesses whilst being treated on the unit due to various reasons. 3 patients (0.8%) died in the community during the period they were receiving care on the unit. Of the 63 patients (16%) admitted to hospital 23 (6%) died during that hospital admission. The number of all cause mortality of our patients was 26 (7%) during the time they were treated on the unit.

Whilst the number of heart failure hospital admissions remained similar, the average length of stay in hospital for heart failure dropped by 0.99 days. Patient feedback on the unit was excellent, with patients feeling more independent and in control of their health.

Conclusions

The ambulatory heart failure unit reduces the burden on the hospital by reducing the length of stay of heart failure patients and may be preferred by patients. Intravenous diuretics on a day case basis are safe, as evident by unchanged overall mortality of heart failure patients.
P2596Right ventricular function after anthracycline therapy: specificities of myocardial necrosis markers
Authors: Quinaglia T Q , Ferreira De Souza T , Bianchini Cardoso F , Silva L M , Toledo C , Neilan T , Antunes-Correa L , Herold M J , Coelho-Filho O R
Published: October 2019

Background

Anthracycline therapy may induce left ventricle (LV) dysfunction. However, few studies investigated how it may affect the right ventricle (RV).

Purpose

The goal of this study was to assess RV systolic function and biomarkers that may predict early dysfunction in breast cancer patients treated with anthracyclines.

Methods

Twenty-seven women with breast cancer (51.8±8.9 years), underwent CMR prior, and up to 3-times after doxorubicin with matching measurements of biomarkers: high-sensitive troponin T (TnT), creatinine-kinase MB isoenzyme (CK-MB) and C reactive protein (CRP).

Results

Before anthracyclines, all subjects had normal LVEF (69.4±3.6%) and RVEF (55.1±9%) and LV and RV EF correlated significantly (ρ=0.42; p=0.031). At 351–700 days after anthracycline, LVEF and LV mass index declined to 58±6% (P<0.001) and 36±6 g/m2 (P<0.001) (table). RVEF also decreased, reaching 46±8% at 231,4 days after (P<0.001), but lost the correlation with LVEF seen at baseline (r=0.22; P=0.068). RVEF showed strong negative association with serum CK-MB (r=−0.4, p=0.004) and no significant correlation with TnT (r=−0.18, p=0.28) or CRP (r=0.03, p=0.932) (figure). In patients with a peak TnT of >10 pg/ml the change of RVEF overtime was significant (Regression Splines coefficients for RVEF: 1.0, p=0.731–peak TnT ≤10pg/ml; 2.51, p<0.001–peak TnT >10 pg/ml). LVEF was not associated with CK-MB (p=ns).

Baseline and Follow-Up CMR Findings Median days after anthracycline Pre-DOX (79,146] (146,231] (231,350] (350,700] N 27 16 19 14 16 LVEF, % 69.4±3.6 61.1±7.6† 55.99±5.0† 53.8±8.4† 57.5±6.1† LVEDV index, ml/m2 60.2±9.9 64.3±9.6 66.7±17.7 * 56.9±18.5 59.2±12.6 LVESV index, ml/m2 18.3±4.0 24.7±7.3# 29.0±7.3† 26.2±9.7† 25.3±8.2† LV mass index, g/m2 51.4±8.0 45.3±3.8† 43.2±4.9† 39.9±5.4† 36.0±6.1† RVEF, % 55.1±9.4 51±8.1 48±8.5 46±8.5 50±7.4 RVEDV index, ml/m2 45.07±6.6 46.5±11.31 47.35±9.16 41.14±9.7 46.16±7.3 RVESV index, ml/m2 20.45±5.4 22.31±5.8 24.77±6.6 21.96±6.4 22.24±4.7 Data are presented as mean ± SD. LV: left ventricle; RV: right ventricle; EF: ejection fraction; EDV: end diastolic volume; ESV: end systolic volume (average±SD). *Significantly different from Pre-DOX level (p<0.05 from linear mixed effects model). #Significantly different from Pre-DOX level (p<0.01 from linear mixed effects model). †Significantly different from Pre-DOX level (p<0.001 from linear mixed effects model).

RVEF and correlate variables

Conclusions

RVEF reduction does not follow LVEF changes after anthracyclines and CK-MB may be a more specific biomarker to assess RV dysfunction. A higher peak cTnT could predict a greater change in RVEF during follow-up.
P2599Echo color doppler evaluation of renal hemodynamic during acute heart failure
Authors: Sacchi A , Galassi M , Brugioni F , Ricco' B , Lami F , Messora R , Bortolotti M , Pinelli G , Turrini F
Published: October 2019

Background

Acute heart failure (AHF) is often accompanied by impairment in renal function. A profound derangement of normal abdominal haemodynamic is always present during this clinical phase.

Methods

14 patients (6 F – mean age 80 – mean EF 0.39) admitted for acute heart failure underwent cardiac and renal Echo Doppler examination at day 1-3-5 of Hospital stay. Parameters of arterial and venous flow within cortical right kidney were recorded. Venous Doppler Profile (VDP) was classified as: continuous (C), pulsatile (P), biphasic (B) or monophasic (M) according to the growing degree of derangement. Arterial resistive index (RI) >0.8 was considered elevated. Correlation between renal hemodynamic (and its changes) with biohumoral and echo parameters was sought.

Outcome

At day 1 VDP was M or B in 8 patients (57%) and in four (50%) of them dropped to C or P at day 5. RI was elevated in 8 patients at day 1 while only in 4 at day 5. VDP and RI were not related to EF or BNP values. One patient died before day 5, no other worsening heart failure episodes occurred. Two patients (14%) developed acute kidney injury but their VDP and RI were normal and did not change. Three patients (21%) did not improve their BNP (decrease >30%) but this was not associated with VDP or RI changes. Elevated derived pulmonary artery systolic pressure (>40 mmHg) was present in 6 out of 8 patients (75%) with M or B VDP and in all 4 patients with both elevated RI and M or B VDP.

Venous Pattern Day 1 Day 3 Day 5 Continous 2 8 5 Pulsatile 4 2 4 Biphasic 2 1 2 Monophasic 6 3 2 Arterial RI >0.8 8 6 4 BNP, pg/ml 1060±1180* 372±281* 424±213* Creatinine, mg/dl 1.4±0.6 1.5±0.6 1.3±0.6 Hb, g/dl 12.1±2.3 12.3±3.6 13.2±2.3 *p>0.05.

Conclusions

This is the first study exploring changes in renal hemodynamic by echo Doppler during AHF. With respect to previous studies among stable patients, our preliminary data shows a higher proportion of deranged renal venous and/or arterial pattern. After diuretic therapy a trend towards improvement in VDP was recorded. No clear association with other clinical and hemodynamic parameters seems evident.
P2605Liver stiffness assessed by fibrosis-4 index; noninvasive marker using serum biomarkers is associated with right ventricular function and cardiovascular prognosis in HFpEF
Authors: Nakashima M , Sakuragi S
Published: October 2019

Background

Liver stiffness is reported to be associated with right atrial pressure and worse prognosis of heart failure. Fibrosis-4 (FIB4) index (age (years) × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)) is known as a useful and simple marker for evaluating liver stiffness. However, the association between FIB4 index and prognosis in heart failure with preserved ejection fraction (HFpEF) was not elucidated.

Purpose

This study aimed to clarity the association between FIB4 index and right ventricular (RV) function and major adverse cardiac events (MACE) of HFpEF.

Method

From February 2012 to December 2015, 132 subjects diagnosed as HFpEF after hospitalization of acute decompensation were enrolled (79 years, 59 male). Subjects performed thoracic surgery or percutaneous coronary intervention within half a year and died before discharge were excluded. All subjects were measured FIB4 index and tricuspid annular plane systolic excursion (TAPSE) to assess RV function before discharge. In addition, patients were classified into two groups: high-(≥3.01, n=52) and low-FIB4 index groups (<3.01, n=80). MACE incidence during the follow-up period were compared between these groups.

Results

Patient with high-FIB4 index were older and higher level of blood pressure. There was no difference in prevalence rates of history of liver disease. In multivariate Linear regression analysis, FIB4 index was significantly association with TAPSE independently confounding factors. Kaplan-Meier analysis showed that patients with high-FIB4 index experienced more CV events during the 1734 days of follow-up (42.3% vs 26.2%, p=0.028) (figure).

Kaplan-Meier curve freedom from MACE

Conclusions

FIB4 index is associated with RV dysfunction and a high risk of future CV event of HFpEF.
P2622Use of intravenous vasodilators in patients hospitalized with acute heart failure: insights from Tokyo cardiovascular care unit network database
Authors: Shiraishi Y , Kohsaka S , Katsuki T , Harada K , Miyamoto T , Matsushita K , Iida K , Takei M , Fukuda K , Yamamoto T , Nagao K , Takayama M
Published: October 2019

Background

Despite recommendations from clinical practice guidelines, there is scant evidence confirming the effects of vasodilators on clinical outcomes in patients with acute heart failure (AHF).

Purpose

We sought to investigate the effects of intravenous vasodilators on clinical outcomes and to identify the potential patient populations that would benefit from its use.

Methods

Data of 26 212 consecutive patients urgently hospitalized for AHF between 2009 and 2015 were extracted from a multicenter data registration system (Tokyo Cardiovascular Care Unit Network Database, including 72 institutions within the Tokyo metropolitan area in Japan). Patients who did not present with typical AHF episodes, including those without pulmonary congestion on physical and/or chest X-ray and serum B-type natriuretic peptide level <500 pg/ml, as well as those who had hypotension and/or hypoperfusion (systolic blood pressure [SBP] <100 mmHg) as dominant presentation, were excluded. Propensity scores were calculated with multiple imputation and 1:1 matching performed between patients with and without vasodilators. The primary endpoint was in-hospital mortality and the secondary endpoints were length of intensive/cardiovascular care unit (ICU/CCU) stay and hospital stay.

Results

Overall, 8 863 patients were included in the present analysis; they were predominantly male (57%) with a median age of 79 (interquartile range: 70–86) years. Compared with the group without vasodilator use, the vasodilator group had higher SBPs and heart rates and higher frequency of assisted ventilation use, but lower frequency of intravenous diuretics use. After propensity score matching, there were no significant differences in in-hospital mortality rates (7.8% vs. 8.9% in patients without vasodilators, p=0.16) or in length of ICU/CCU stay (5.8 days vs. 5.4 days, p=0.44) and hospital stay (22.7 days vs. 23.8 days, p=0.22) between the groups. However, in subgroup analyses, favorable impacts of vasodilator use on in-hospital mortality were observed among patients who had higher SBPs and among those who had no atrial fibrillation upon admission (Figure). In addition, vasodilators were likely to be more effective in AHF patients with SBP increasing; while levels below 140 mmHg of SBP appeared to be associated with an increased risk for mortality among patients treated with vasodilators compared with those without vasodilators.

Figure 1

Conclusions

In patients with AHF, vasodilator use was not universally associated with improved in-hospital outcomes; however, its effect was dependent of individual clinical presentation. Detailed phenotyping might aid tailoring of treatment strategies for patients with AHF.

Acknowledgement/Funding

the Tokyo Metropolitan Government
P2629Early benefits of empagliflozin in patients with type 2 diabetes with heart failure are not offset by increased adverse events: results from the EMPA-REG OUTCOME trial
Authors: Pellicori P , Pernille Ofstad A , Fitchett D , Zeller C , Wanner C , George J , Zinman B , Brueckmann M , Lindenfeld J
Published: October 2019

Background

The cardiovascular (CV) benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have been demonstrated in long-term clinical trials. In the EMPA-REG OUTCOME trial, the SGLT2 inhibitor empagliflozin (EMPA), compared with placebo (PBO), significantly reduced the risk of CV death and hospitalisation for heart failure (HHF) in patients with T2D and established CV disease, with a median follow-up time of 3.1 years.

Purpose

To investigate the early benefits and safety associated with use of EMPA in patients enrolled in the EMPA-REG OUTCOME trial according to heart failure (HF) status at baseline.

Methods

We evaluated the effects of treatments on glycated haemoglobin (HbA1c) levels and on the clinical endpoints of HHF, HHF or CV death, and HHF or all-cause mortality (ACM), as well as the occurrence of adverse events (AEs), at 12 weeks, 6 months, and 1 year after randomisation. Outcomes data were explored descriptively at 12 weeks, and assessed by Cox regression models adjusting for baseline risk factors at 6 months, and 1 year, whereas safety data were explored descriptively. Effects on HbA1c were evaluated using a Mixed Model Repeated Measures (MMRM) model.

Results

A total of 7020 participants, 706 (10%) with investigator-reported HF at baseline, were randomised to PBO, or two different doses of EMPA (10 mg or 25 mg once daily). In patients with HF at baseline, the adjusted mean differences in HbA1c between pooled EMPA and PBO at 12 weeks, 6 months, and 1 year after randomisation were −0.55, −0.54 and −0.53%-point, respectively, p<0.001 vs PBO for all, with similar results in those without HF (p for interactions 0.822, 0.939 and 0.539 at 12 weeks, 6 months and 1 year, respectively). Already at 12 weeks, patients assigned to EMPA had a lower frequency of all evaluated clinical outcome events (HHF, HHF or CV death, HHF or ACM) compared with PBO, regardless of HF status. This effect was sustained and significant at 6 months and 1 year in those with and without HF (see Figure). During the same time frame, the rates of AEs were generally higher in those with HF than without HF, but were not increased by the use of EMPA. At 1 year, any AE occurred in 206 (84.4%) and 1694 (81.1%) patients with and without HF, respectively, on PBO vs 363 (78.6%) and 3246 (76.8%) patients with and without HF on EMPA; any serious AE at 1 year occurred in 79 (32.4%) and 447 (21.4%) patients with and without HF on PBO vs 105 (22.7%) and 764 (18.1%) of those with and without HF on EMPA.

Conclusions

In the EMPA-REG OUTCOME trial, EMPA led to early beneficial effects on morbidity and mortality outcomes in patients with T2D with or without HF, which were not offset by an increased risk of AEs.
P2659Difference of prognostic impact of Killip classification in ACS patients with or without hemodialysis
Authors: Takasaki A , Kurita T , Masuda J , Dohi K , Hoshino K , Tanigawa T , Saito Y , Kitamura T , Kakimoto H , Setsuda M , Makino K , Ichikawa T , Ito M
Published: October 2019

Background

Cardiovascular deaths are more frequently in hemodialysis (HD) patients compared to general population. However, difference of prognosis of acute coronary syndrome (ACS) patients with or without HD were not well evaluated.

Purpose

The purpose of this study was to evaluate the clinical and prognostic characteristics of ACS patients with HD compared to that of ACS patients without HD.

Methods

We investigated 3427 ACS patients including 63 HD and 3364 non-HD patients between 2013 and 2017 using date from Mie ACS registry, a retrospective and multicenter registry. The primary outcome was defined as all-cause mortality.

Results

HD patients showed significantly higher prevalence of diabetes mellitus, past treatment of coronary artery disease, history of myocardial infarction and Killip ≥2 compared to non-HD patients (p<0.05, respectively). During the follow-up periods (median 719 days), 425 (12.4%) patients experienced all-cause death. HD patients demonstrated the higher all-cause mortality rate compared to that of non-HD patients during the follow-up (11.9% versus 38.1%, p<0.001, chi square). Kaplan Meier survival curves demonstrated that HD and non-HD patients with Killip 1 showed similar 30-day mortality, and Killip ≥2 patients also showed similar prognosis (Left side of figure). On the other hand, all cause mortality at 2 years were higher in Killip 1 HD patients compared to Killip 1 non-HD patients and similar between Killip 1 HD patients and Killip ≥2 non-HD patients in the 30 days landmark analysis (Right side of figure). In addition, cox regression analyses for all cause mortality demonstrated that HD was a strongest independent prognostic factor not of 30-day mortality but of after 30-day mortality with hazard ratio of 4.09 (95% confidential interval: 2.32–7.21, p<0.001).

Figure 1

Conclusion

Careful management are required in chronic phase for ACS patients with HD even in Killip 1 classification.
P2689Irregular protrusion area is associated with incidence of cardiac events after implantation of new generation drug-eluting stents - optical coherence tomography study
Authors: Yanagawa K , Nishino M , Nishino M , Nakamura H , Nakamura H , Matsuhiro Y , Matsuhiro Y , Yasumoto K , Yasumoto K , Tanaka A , Tanaka A , Matsunaga Y , Matsunaga Y , Nakamura D , Nakamura D , Yano M , Yano M , Yamato M , Yamato M , Egami Y , Egami Y , Shutta R , Shutta R , Tanouchi J , Tanouchi J
Published: October 2019

Background

Several studies using optical coherence tomography (OCT) have shown that the prevalence of irregular protrusion was associated with the incidence of adverse cardiac events. However, the correlation between cardiac events and protrusion area is not well investigated.

Method

One hundred twenty-nine consecutive patients with 138 clesions with 2nd and 3rd generation drug-eluting stents (DES) which had pre-stenting and post-stenting OCT imaging between April 2016 and April 2018 were evaluated. We compared baseline characteristics, procedure findings and OCT findings including minimum stent area, protrusion type and maximum protrusion area between target lesion revascularization (TLR) group and non-TLR group.

Results

TLR occurred in 12 (9.3%) in 129 patients. The baseline characteristics and procedure findings were similar between TLR group and non-TLR group. Univariate analysis revealed that maximum irregular protrusion area was significantly larger (0.51 [0.00–0.63] vs 0.00 [0.00–0.27], p=0.036) in TLR group than non-TLR group. Receiver operating characteristic curve analysis revealed that the suitable cutoff value of maximum irregular protrusion area were 0.43mm2 for TLR. In multivariate analysis using the parameters with p value<0.10 determined by univariate analysis, maximum irregular protrusion (≥0.43mm2) and minimum stent area (MSA) were independently correlated with TLR (table).

Odd's ratio (95% CI) P value Major irregular protrusion (≥0.43mm2) 17.3 (3.63–82.6) <0.001 MSA 2.13 (1.15–3.93) 0.002

Conclusion

Major irregular protrusion (>0.43mm2) in post-stenting OCT findings may be a powerful predictor of TLR in the patients with new generation DES.
P2694Early and late restenosis after excimer laser coronary angioplasty and paclitaxel-coated balloon combination therapy for drug-eluting stent restenosis
Authors: Higaki T , Nishioka K , Suruga K , Takemoto H , Nakano T , Hashimoto Y , Tomomori S , Oi K , Dai K , Kawase T , Nakama Y , Suenari K , Otsuka M , Masaoka Y , Shiode N
Published: October 2019

Background

Drug-eluting stent restenosis (DES-ISR) is associated with poorer outcomes than those of bare-metal stent restenosis after treatment with paclitaxel-coated balloon (PCB), and late restenosis after PCB angioplasty for DES-ISR is a residual problem. Excimer laser coronary angioplasty (ELCA) is thought to be advantageous for ISR treatment by removing neointima. However, whether the combination of ELCA and PCB angioplasty is more effective than the use of PCB only angioplasty in DES-ISR has not been studied so far.

Purpose

We evaluated the efficacy of ELCA and PCB combination therapy for DES-ISR at mid-and late-term after revascularization.

Methods

From January 2014 to March 2016, 166 DES-ISR lesions were treated with ELCA and no-ELCA prior to PCB. Two serial angiographic follow-ups were planned for the patients (at 6–12 and 18–24 months after procedure). Acute procedural and follow-up angiographic results were assessed by quantitative coronary angiography. ELCA and no-ELCA group included 74 lesions and 92 lesions, respectively.

Results

There was no significant difference between the two groups in the clinical characteristics except the prevalence of hemodialysis, the rate of first-generation DES (37.9% vs 36.8%, p=0.897), previous stent size (2.90±0.39 mm vs 2.77±0.39 mm, p=0.063), and reference vessel diameter (2.65±0.46 mm vs 2.60±0.65 mm, p=0.593). Early follow-up angiography was performed in 66 lesions (89.1%) of ELCA group, and was done in 76 lesions (82.6%) of no-ELCA group. In the ELCA group, percentage diameter stenosis (%DS) just after procedure and at 6–12 months later were significantly smaller than those of no-ELCA group. Besides, target lesion revascularization (TLR) rate at 6–12 months after procedure was tended to be lower in the ELCA group. Late follow-up angiography was performed for 93 lesions (81.6%) of the remaining 114 lesions (excluding TLR lesion), late restenosis was found 9 lesions (18.6%) in the ELCA group and 11 lesions (24.4%) in the no-ELCA group (p=0.504). Late luminal loss was similar in both groups (0.37±0.71 mm vs 0.24±0.82 mm, p=0.438), and %DS at 12–18 months after revascularization was not different between the two groups.

Changes of %DS and TLR rate

Conclusions

%DS in the ELCA group was smaller at just after procedure and the advantage was kept even after 1-year. However, late restenosis and TLR at 2-year after revascularization for DES-ISR could not be reduced by ELCA and PCB combination therapy.
P2700Impact of instantaneous wave-free ratio on graft failure after coronary artery bypass graft surgery
Authors: Wada T , Shiono Y , Higashioka D , Kashiwagi M , Shimamura K , Kuroi A , Honda K , Matsuo Y , Kitabata H , Ino Y , Kubo T , Tanaka A , Hozumi T , Nishimura Y , Akasaka T
Published: October 2019

Background

It has been reported that preoperative fractional flow reserve (FFR) is associated with graft patency after coronary artery bypass graft (CABG) and the patency is excellent when a bypass graft is anastomosed on a vessel with positive FFR. However, the association with graft patency has not yet been investigated in its novel counterpart, instantaneous wave-free ratio (iFR), and iFR sometimes contradicts FFR results.

Purpose

The purpose of this study is to assess an impact of preoperative iFR on a graft failure after CABG in patients with coronary arteries showing positive FFR (≤0.80).

Methods

We retrospectively identified patients who had undergone preoperative coronary angiography in conjunction with resting and hyperemic intra-coronary pressure measurements, CABG, and graft evaluation by coronary computed tomography angiography. After excluding vessels with negative FFR (>0.80), vessels were divided into two groups: negative iFR group (iFR >0.89) and positive iFR group (iFR ≤0.89). The rate of graft failure within 1 year after CABG was compared between the two groups.

Results

We analyzed 131 vessels in 89 patients (35 vessels in the negative iFR group and 96 vessels in the positive iFR group). The negative iFR group showed significantly higher iFR (0.92±0.02 vs. 0.74±0.13, P<0.0001) and FFR (0.72±0.06 vs. 0.63±0.09, P<0.0001) than the positive iFR group, although percent diameter stenosis (%DS) was comparable (57±10 vs. 56±9, P=0.47). The graft failure significantly often occurred in the negative iFR group than in the positive iFR group (28.6% vs. 8.3%, P=0.0029). In order to reduce the imbalance in the baseline characteristics except for iFR, 70 vessels were selected by using propensity score matching (n=35 in each group). The propensity score matched vessels also demonstrated significantly higher rate of graft failure in the negative iFR group than in the positive iFR group (28.6% vs. 5.7%, p=0.026) despite much more balanced FFR (0.72±0.06 vs. 0.69±0.07, p=0.02) and %DS (57±10 vs. 57±9, p=1.000).

Conclusions

Even when FFR is positive, the graft failure is likely to occur when a bypass graft is anastomosed on a vessel with negative iFR compared to a vessel with positive iFR.

Acknowledgement/Funding

None