bluuebunny/crossref_metadata_2025 huggingface dataset:
P6272First plus recurrent CV and hospitalization events in the CArdiovascular and Renal Microvascular outcomE study with LINAgliptin (CARMELINA) in patients with type 2 diabetes and cardiorenal disease
Authors: Marx N , McGuire D K , Johansen O , Rosenstock J , Kahn S E , Cooper M E , Toto R , Wanner C , Pfarr E , Schnaidt S Y , George J T , Von Eynatten M , Perkovic V , Zinman B , Alexander J A
Published: October 2019

Background/Introduction

CARMELINA was a randomized placebo-controlled clinical trial designed to demonstrate the cardiovascular (CV) safety of linagliptin in patients with type 2 diabetes (T2D) and concomitant cardiorenal disease. Despite a particularly elevated CV risk, only limited long-term evidence from randomized controlled trials for safety and efficacy of glucose lowering medications is available for this population.

Purpose

To characterize the effects of linagliptin on net CV disease and hospitalization burden in this population.

Methods

People with T2D and either i) urine albumin creatinine ratio (UACR) >30 mg/g with concomitant CV disease, or ii) estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 regardless of UACR, or eGFR ≥45–75 mL/min/1.73m2 and UACR >200 mg/g, were randomized to linagliptin 5 mg or placebo q.d. in a double-blind fashion in addition to standard of care. We assessed the effects of linagliptin versus placebo on all first plus recurrent CV events and all-cause hospitalizations using a using a negative binomial model to account for within-subject correlation.

Results

A total of 6979 participants were enrolled (mean age 66 years, 63% male, eGFR 54.6 ml/min/1.73m2, median UACR 162 mg/g, 59% with history of ischemic heart disease, 27% with history of heart failure (HF)) and followed for a median of 2.2 years. Adding recurrent events increased the number of events for analysis from 5.3–57.5% across CV/HF outcomes and 112.4% for hospitalizations. In analyses of first plus recurrent events, the event rate ratio (95% CI) with linagliptin versus placebo was 0.98 (0.82, 1.16; p=0.78) for 3-point MACE, 1.03 (0.79, 1.35; p=0.83) for myocardial infarction 1.03 (0.83, 1.29; p=0.77) for myocardial infarction plus revascularization, 0.89 (0.65, 1.22; p=0.48) for stroke, 0.94 (0.70, 1.27; p=0.69) for stroke plus TIA, 0.94 (0.75, 1.20; p=0.63) for hospitalized HF, 0.92 (0.77, 1.11; p=0.40) for the composite of CV death or hospitalized HF, and 0.96 (0.87, 1.06; p=0.40) for all-cause hospitalization (Figure).

Conclusion

Linagliptin showed similar risk of either first or recurrent CV or hospitalization events compared with placebo in patients with T2D and cardiorenal disease. These data support the CV safety of linagliptin and, considering the high volume of recurrent events, underscores the significant CV disease burden experienced by patients with T2D and cardiorenal disease

Acknowledgement/Funding

Boehringer Ingelheim and Eli Lilly
P6301Pro-inflammatory intermediate monocytes relate to right ventricular pressure in heart failure of adult congenital heart disease
Authors: Wienecke L M , Fraccarollo D , Galuppo P , Treptau J , Kockelmann F , Bauersachs J , Westhoff-Bleck M
Published: October 2019

Background

Heart failure (HF) is a leading cause of mortality in adults with congenital heart disease (ACHD). ACHD is characterized by predominant right heart disease. In non-congenital heart disease inflammation and its mediators such as monocytes/macrophages play an important pathophysiological role in HF. We aimed to evaluate the role of circulating monocyte subsets in ACHD-HF.

Methods

This cross-sectional study includes 209 ACHD outpatients (mean age: 35.3±11.0 years; NYHA class I/II/III-IV 58.3%/19.6%/13%; male: 59.8%) and 21 healthy controls (age: 29.8±12.6 years; male: 47.6%). Patients with clinical signs of infection, inflammatory diseases or malignancies were excluded. Multivariate analysis was used to relate blood monocyte subsets to NYHA class and echocardiographically derived parameters of right and left ventricular function.

Results

Compared to control, ACHD had significantly higher circulating levels of pro-inflammatory HLA-DR+CD14++CD16+ intermediate monocytes (24.0±3.3 vs. 43.6±1.7 cells/μL; p<0.001).

NT-proBNP was independently associated with reduced left (p<0.0001) and right (p<0.001) ventricular function, diastolic dysfunction (p=0.04) and vena cava diameter (p=0.02).

Independent predictors of NYHA class were intermediate monocytes (p=0.022), plasma noradrenaline (p=0.002), albumin (p=0.001) and NT-proBNP (p<0.001). Elevated right ventricular systolic pressure (>35 mmHg) was independently associated with both, higher intermediate monocyte counts (OR 1.36; 95% CI: 1.13–1.62; p=0.001) and low oxygen saturation (OR 0.8; 95% CI: 0.7–0.92; p=0.001), even after multivariable adjustment for age, sex and NYHA class.

Conclusions

Right ventricular pressure and oxygen saturation are linked to elevated intermediate monocytes, suggesting an important link between inflammation and HF in ACHD. Circulating blood intermediate monocytes represent a promising biomarker in ACHD.

Acknowledgement/Funding

German Heart Foundation (Deutsche Herzstiftung e.V.)
P6312Pregnancy outcomes in women with cardiothoracic transplants: a systematic review and meta-analysis
Authors: Dong S , D'Souza R , Acuna S , Zaffar N , Bhagra C , Silversides C , Ross H
Published: October 2019

Background

Increasing numbers of women with heart-lung transplants (HLT) are now planning and continuing with pregnancies. The risks of pregnancies in these women have not been systematically assessed.

Methods

A search strategy was designed for MEDLINE, EMBASE, and Cochrane Central from inception to January 2018 to identify studies reporting outcomes in three or more pregnancies following HLT. Pooled incidence of maternal outcomes and fetal and neonatal outcomes were calculated using random-effects meta-analysis and reported per 100 pregnancies with 95% confidence intervals (CI). Risk-of-bias was determined using the Joanna Briggs Checklist for Case Series. Subgroup analysis was conducted based on transplanted organ.

Results

A total of 3658 records were identified, 172 full texts reviewed, and 12 studies included. The included studies reported on 385 pregnancies in 272 transplant recipients. Maternal complications included mortality during pregnancy [0.5% (0, 1.1%)], mortality during the specified follow-up period [15.4% (10,4, 20.3%)], graft rejection during pregnancy [7.4% (4.2, 10.5%)], preeclampsia [12.3% (7.2%, 17.5%)], gestational diabetes [6.4% (2.6, 10.1%)], and caesarean deliveries [41.4% (33.4, 48.7%)]. As many as 78.4% (69.8, 86.9%) pregnancies resulted in live births. Of the remainder, 13.6% (6.3, 20.9%) resulted in miscarriages (fetal loss under 20 weeks of gestation), 2% (0.3, 3.7%) resulted in stillbirths (fetal loss after 20 weeks of gestation), and 6.8% (4.3, 9.3%) in pregnancy terminations for various reasons. Of those born live, 3.4% (1.3, 5.6%) succumbed in the neonatal period. Over half the pregnancies [51.2% (31, 71.3%)] resulted in preterm deliveries (<37 weeks of gestation). There were subgroup-specific variations in the prevalence of complications. For example, lung transplant recipients were less likely than heart transplant recipients to have pregnancies complicated by preeclampsia [8.3% (3.0, 13.6%) vs. 17.8% (10.8, 24.8%)] suffer maternal mortality during the follow up period [41.4% (23.4, 59.3%) vs. 10.8% (5.9, 15.8%)]. Studies had a moderate risk-of-bias.

Conclusions

Although large proportions of pregnancies in women with HLT result in live births and few maternal deaths occur during pregnancy, these women are at increased risk for preeclampsia, preterm birth, perinatal mortality and maternal mortality following childbirth. Subgroup-specific variations should be taken into account while counselling HLT recipients contemplating pregnancies.

Acknowledgement/Funding

None
P6318Survival rate in patients with the identification of predictors for antibody mediated rejection
Authors: Tkhal L , Kosmacheva E , Pashkova I
Published: October 2019

Introduction

Antibody mediated rejection (AMR) is still an important issue in heart transplantation (HT). The standard methods of diagnosis and treatment remain controversial, whereas immunosuppressive therapy is mainly used to prevent cellular rejection.

Purpose

To determine predictors of AMR using the routine investigations in clinical practice.

Methods

During 7 years we conducted a single center study of 181 HT recipients. Patients were divided into 5 groups based on AMR and detected anti-HLA, such as DSA and non-DSA antibodies. Recipients underwent immunology screening and HLA antibodies tests, DSA; 2D-speckle-tracking echocardiography using the Kruskal-Wallis and Wilcoxon signed-rank tests; Spearman correlation, the table of critical values for the Pearson correlation. Kaplan-Meier curves were used to estimate the survival rate. Roc-analysis was used to measure the diagnostic accuracy. Statistical analysis was performed with the STATISTICA 10 (Tibco, USA).

Results

The study demonstrated the lowest survival in patients with anti-HLA antibodies, such as anti-HLA and non-DSA antibodies versus recipients without anti-HLA de novo. Survival in patients with DSA is 40%, and in patients without DSA is 68%. It should be noted that comparing of survival in patients with HLA identified in different post-transplant period showed that patients with HLA-antibodies identified in late post-transplant period had worse survival (50%) than recipients who developed antibodies in the early post-transplant period (75%). On the second stage of the study we conducted 2D-speckle-tracking echocardiography. At first we estimated 2D-STE parameters for the selected groups of patients in the first period of our study, and then during AMR and the late period of the study. AMR effectively reduces the parameters of deformation and mechanics, GLPS LV,%i = −9,94±1,37, RadS LV,% 19,36±3,66, Cir SLV,% −17,83±4,89, ROT APEX°,4,51±1,46, ROT BASE°, −4,75±2,12, ROT MID° 1,94±1,41, TWIST,% 8,90±1,85, RV-FWS,% −15,89±0,89. The possible criteria for diagnosis of AMR include global peak systolic strain, sensitivity (S) 86,2%, specificity (Sp) 90,4%, radial systolic strain, S 75,8%, Sp 84,5% circular systolic strain, S 78,6%, Sp 84,4%; left ventricular twist S 66,7%, Sp 94,2% (p<0,001).

Conclusions

There is a correlation between changes and parameters of 2D-speckle-tracking echocardiography. DSA limits the survival and increases the risk for AMR.
P6319CT derived fractional flow reserve (FFRct) for functional coronary artery evaluation in the follow-up of patients after heart transplantation
Authors: Budde R P J , Nous F M A , Constantinescu A A , Nieman K , Koweek L M , Leipsic J , Manintveld O C
Published: October 2019

Background

Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after heart transplantation. Annual screening is recommended to improve risk stratification and early treatment of CAV and is often performed with invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) with CCTA-derived fractional flow reserve (FFRct) might be a non-invasive alternative to ICA for the surveillance of CAV providing both anatomical and functional information.

Purpose

To describe our initial results with CCTA and FFRct for detection of CAV in a cohort of heart transplant patients.

Methods

Heart transplant patients who underwent CCTA with FFRct as part of routine annual assessment for CAV were enrolled in a prospective registry from February 2018 to February 2019 in a single center. The most recently known CAV score (0–3) based on invasive angio and single photon emission computed tomography (SPECT) before CCTA was recorded. CCTA image quality was scored as non-diagnostic, moderate, good or excellent. FFRct analysis was performed off-site by a commercial company. For each coronary stenosis >30%, an FFRCTvalue distal to the stenosis was measured. For the RCA, LAD and CX without a stenosis, the FFRct value in the most distal location in the vessel was recorded. CAV classification was rescored based on CCTA. Demographics, additional diagnostic tests, and treatment plans were evaluated including major adverse events (MACE) during 90-day follow-up.

Results

65 patients (56 (39–65) years (median/ 25th–75thpercentile), 40% women) that were 11 (7–16) years after transplantation were included. The most recent CAV score was 0 in 52 patients (80%) and 1 or 2 in 13 patients. CCTA image quality was good or excellent in 59 (91%) patients. CCTA reclassified CAV scores in 32 (49%) patients to 33 patients with CAV 0, 18 patients with CAV 1, 9 patients with CAV 2 and 5 patients with CAV 3. In 17 patients (26%) at least one stenosis with FFRct ≤0.80 was detected including 11 patients with single vessel disease, 5 with two-vessel disease and one with three-vessel disease. In the 48 patients without a focal stenosis, mean distal FFRct values were 0.88 (0.86–0.91), 0.87 (0.85–0.90) and 0.90 (0.86–0.91) at less than 10, 10–15 or more than 15 years after transplantation, respectively (p=0.457). Additional tests were performed in 10 (15%) patients (1 SPECT and 10 invasive coronary angiographies), which resulted in revascularization by PCI in 6 (9%) patients. No MACE occurred during 90-day follow-up.

Conclusion

CCTA with FFRct can be successfully performed in heart transplant patients, detects patients with significant coronary stenosis and CCTA leads to substantial reclassification of CAV grades.

Acknowledgement/Funding

FFRct analysis was performed as part of the ADVANCE registry which is supported by Heartflow Inc.
P6320Unilateral phrenic nerve stimulation improves functional capabilities in heart failure patients
Authors: Potratz M , Gutleben K J , Rudolph V , Fox H
Published: October 2019

Introduction

Central sleep apnea is highly common in heart failure (HF) patients and often appears as Cheyne-Stokes-respiration (CSR). Presence of CSR in HF has been clearly shown to connote worse prognosis and HF patients with CSR experience increased mortality. Since widely used adaptive servoventilation is now contraindicated in HF with reduced ejection fraction alternative approaches for CSR treatment are needed. Unilateral phrenic nerve stimulation (PNS) is a novel technique to treat CSR and has recently been demonstrated to be safe and effective in HF patients, resulting in its market approval. While PNS has been shown to sufficiently treat CSR nothing is known in regard to functional characteristics in PNS treated HF patients. Therefore, this study investigated standardized six-minute walk test (6MWT) before and during PNS treatment in HF patients assessing functional impact of PNS on HF.

Methods

We prospectively enrolled 25 HF patients that have been implanted with novel PNS, mean age 67.05±11.22 years, 88% male, showing effective PNS CSR treatment. Adjacent to determine PNS effectiveness on CSR treatment standardized 6MWT was conducted before, at 6 months and at 12 months after PNS implantation.

Results

25 (100%) patients had CSR, introduced PNS significantly suppressed respiratory events from 118.33±96.35 before to 34.65±51.41 after PNS therapy onset (p=0.001). Regarding functional improvements 6MWT improved from initial 369.5±163.56 meters before PNS implantation to 410±169.71 meters after 12 months. Hereby, total walking distance increased by 49.5% ± 100.8% (p=0.035).

Conclusion

PNS treatment is not only a novel technique to allow CSR treatment in HF, but for the first time, we provide comprehensible data illustrating functional improvements in HF in 6MWT, implying significant enhancements in daily physical capability of HF CSR patients treated with PN.
P6324Contribution of muscle efficiency in heart failure patients post phase 2 cardiac rehabilitation
Authors: Sa Mendes G , Durazzo A , Moreno L , Santos S , Neto M , Mendes M
Published: October 2019

Background

Muscle efficiency (ME), can help explain the observed improvement in patients without increase in oxygen uptake (VO2) after cardiac rehabilitation programme (CRP). The better use of energy, independent to the oxygen delivery to muscle, may improve the functional capacity in Heart failure (HF) patients. Our aim was to evaluate the contribution of muscle efficiency improvement after CR on functional capacity.

Methods

We analyse consecutive patients data that had their phase 2 CR concluded, with HF as admission indication with no medical therapy changes and CRT implantation during this period. The aetiology of HF and biometric data, functional class, BNP, Minnesotta and EuroQol questionnaires and cardiorespiratory test pre and post 4 months of CRP were collected. The average of the exercise load in the first two and last two training sessions were recorded. ME was calculated at peak exercise during cardiopulmonary exercise test in pre and post CRP (see formula above).

Results

From 55 HF patients sequentially admitted in our CRP, during the last 24 months, 45 were included, since 2 were transplanted, 1 died and the 7 didn't concluded the program or not had all the data mentioned in the methods. The mean age was 60,5±10,3 years and 78% were male. Ischemic aetiology with depressed ejection fraction (64%) was the main admission indication, followed by cardiomyopathies (18%). Betablockers, ACEi or ARBs or ARNi and MRA were taken in 91%, 93%, 46%, respectively. ICD and CRT were previously implanted in 44% of the patients. Comparing pre and post CRP VO2 at peak exercise and aerobic threshold levels no statically differences were found. In this cohort 27 (60%) patients increased ME. At the end of the CRP, this group had a higher improvement in METs (p=0,021), higher gain in lean mass (p=0,041), in EuroQoL (p=0,002) and in physical dimension of Minnesotta questionnaire (p=0,032), when compared with patients that didn't improve the ME in at least 5%. In 22 patients that increased ME, the VO2 at aerobic threshold level didn't improve by at least 5% and in this group the same benefits were confirmed.

Formula of Muscle Efficiency

Conclusions

The improvement in exercise load reached in the post CRP cardiopulmonary test, independently of possible cardiac output changes (VO2 peak), seems to be explained in part by the increase in ME improvement.
P6328Relationship between exercise capacity and muscle function in adult patients with heart failure
Authors: Chiala O , Klompstra L , Vellone E , Stromberg A , Jaarsma T
Published: October 2019

Introduction

Physical fitness is a multidimensional concept and is of great importance to assess in heart failure (HF) patients, due to that HF is associated with exercise intolerance, dyspnea and fatigue. Some measures of physical fitness have been associated to HF severity, rehospitalization and mortality risk.

Purpose

The aim of this study was to explore the relationship between two different measures of physical fitness in patients with HF: exercise capacity and muscle function.

Methods

This is a secondary analysis performed on the baseline data of a multi-centre RCT study aimed at exploring the effect of exergame access to improving exercise capacity in HF patients. Physical fitness was assessed by two different measures: exercise capacity assessed by the 6-minute walk test (6MWT), and muscle function assessed by 3 different isometric tests of upper and lower limbs. Descriptive statistics, Spearman correlation and principal component analysis were used to analyse the data.

Results

In total, 605 HF patients were included in this analysis (mean age 67±12, 29% women, 90% NYHA II/III). Exercise capacity (6MWT) was correlated with all of the muscle function tests, with correlation-coefficients ranging from r=0.23 to r=0.50 (p<0.001). Principal component analysis showed a bi-dimensional nature of physical fitness, with the first dimension including the lower body strength and the second dimension including the upper body strength and exercise capacity. These two dimensions explained 71% of the total variance of the measured variables.

Correlation matrix (n=605) 6MWT Right Heel-Lift Left Heel-Lift Shoulder abduction Right Shoulder Flexion Left Shoulder Flexion 6MWT 1 Right Heel-Lift 0.23** 1 Left Heel-Lift 0.26** 0.86** 1 Shoulder abduction 0.40** 0.30** 0.34** 1 Right Shoulder Flexion 0.47** 0.51** 0.48** 0.52** 1 Left Shoulder Flexion 0.50** 0.49** 0.48** 0.52** 0.83** 1 **p<0.001.

Principal Component Analysis

Conclusions

Although strong correlations between exercise capacity and muscle function tests, the measures loaded on two different factors. The results suggest that upper body strength and exercise capacity had a stronger relationship than with lower body strength. This may imply that muscle function tests for upper and lower limbs and exercise capacity represent different aspects of physical fitness and to attain a more complete assessment of physical fitness all three tests are important.

Acknowledgement/Funding

Swedish National Science Council, The Swedish Heart and Lung Association, The Swedish Heart and Lung Association, Swedish Heart-Lung Foundation
P6332Prevalence and prognostic impact of sarcopenia identified according to Asia Working Group for Sarcopenia definition in non-dependent elderly patients with heart failure
Authors: Iwatsu K , Ikeda T , Matsumura K , Ashikawa H , Sakamoto M , Sakata T , Haratani K , Fujita R , Takabayashi K , Kitaguchi S , Nohara R
Published: October 2019

Background

Sarcopenia is a geriatric syndrome characterized by loss of muscle mass and muscle function. As the population ages, there is a growing worldwide interest in the intersection of sarcopenia and heart failure (HF). However, estimates of the prevalence of sarcopenia in HF vary widely because of difference in diagnostic criteria. Although the Asian Working Group of Sarcopenia (AWGS) has announced a consensus on the diagnostic criteria of sarcopenia in Asian people, the prevalence and prognostic impact of sarcopenia based on AWGS criteria in patients with HF remains unclear.

Purpose

The aim of this study was to investigate the prevalence and predictive value of sarcopenia identified according to AWGS definition in non-dependent elderly patients with HF.

Methods

This study was a prospective, single-center cohort study in Japan. We consecutively enrolled 274 patients, aged 65 years or older, hospitalized due to acute HF or acute exacerbation of chronic HF and who were able to walk at least 20 m at discharge. Patients with severe cognitive or psychiatric disorders were excluded. Patients with implantable cardiac pacemaker or cardioverter defibrillator were also excluded because skeletal muscle mass was estimated by using bioimpedance analysis. At hospital discharge, we collected data on age, gender, left ventricular ejection fraction, brain natriuretic peptide, estimate glomerular filtration rate, body mass index and sarcopenia. Sarcopenia was diagnosed according to the AWGS criteria: low skeletal muscle index (<7.0 kg/m2 in men, <5.7 kg/m2 in women) and either slow usual walking speed (<0.8 m/s) or low handgrip strength (<26 kg in men, <17 kg in women). Study outcome was rehospitalization for worsening HF within 180 days after discharge. We assessed the independent association between sarcopenia and HF rehospitalization by using multivariate Cox proportional hazards regression analysis.

Results

In this study, a total of 199 patents (43.4%) fulfilled sarcopenia criteria at discharge. During follow-up, 57 patients (20.8%) readmitted for HF. Kaplan-Meier survival curves showed that patients with sarcopenia had significantly lower event-free survival than those without sarcopenia (Figure). After adjusting for other prognostic factors, sarcopenia was independently associated with HF rehospitalization (hazard ratio: 2.31, 95% confidence interval: 1.20–4.53).

Conclusion

Based on AWGS criteria, sarcopenia is highly prevalent even among non-dependent elderly HF patients, and is an independent strong predictor of rehospitalization for worsening HF. AWGS criteria for sarcopenia may be useful for risk prediction in HF.
P6350Impact of diabetes on serum biomarkers in heart failure with preserved ejection fraction: insights from the spironolactone for heart failure with preserved ejection fraction (TOPCAT) trial
Authors: De Marco C , Claggett B , De Denus S , Huynh T , Desai A S , Sirois M G , Jarolim P , Solomon S D , Pitt B , Rouleau J L , Pfeffer M A , O'meara E
Published: October 2019

Background and purpose

Diabetes mellitus (DM) is common in heart failure with preserved ejection fraction (HFpEF). Patients with DM and HF with reduced ejection fraction have higher levels of prognostic biomarkers relative to non-diabetics. We sought to examine differences in biomarkers at baseline and over time in patients with HFpEF with and without DM (non-DM).

Methods

The Americas cohort of the TOPCAT trial included 248 subjects with baseline measurements of serum biomarkers and follow-up measures 12 months later. Subjects were identified as non-DM or DM at baseline. Baseline values were compared using non-parametric tests and 12-month changes were compared via linear regression after log-transformation and adjustment for baseline biomarker value, age, gender, randomization strata, and randomized treatment.

Results

At baseline, DM patients had significantly lower eGFR and higher hsCRP, PIIINP, TIMP1, and Gal-3 levels versus non-DM patients (Table). In addition, there was a significantly larger increase over time in levels of hs-TnT, a marker of myocyte death, in DM vs. non-DM patients (p=0.016).

Baseline and 12-Month Biomarkers Baseline % Change at 12 Months Non-DM (n=132) DM (n=116) p Non-DM (n=110) DM (n=94) p eGFR (mL/min/1.73m2) 67 [57, 77] 57 [46, 73] 0.003 −14% (−17, −10) −14% (−18, −10) 0.34 hsCRP (mg/L) 2.4 [1.1, 5.6] 3.1 [1.6, 7.5] 0.046 1% (−5, 3) −11% (−27, 7) 0.54 NT-proBNP (pg/mL) 624 [338, 1235] 629 [278, 1429] 0.80 −2% (−12, 10) −5% (−21, 13) 0.48 hs-TNT (ng/mL) 5.7 [3.1, 12.4] 7.1 [3.7, 14.2] 0.17 −1% (−14, 13) 11% (−3, 27) 0.016 Soluble ST2 (ng/mL) 28 [22, 32] 28 [21, 35] 0.36 −1% (−7, 5) −4% (−9, 2) 0.60 Aldosterone (ng/L) 149 [120, 202] 142 [113, 174] 0.09 17% (9, 26) 23% (14, 33) 0.76 PICP (ng/mL) 137 [101, 169] 127 [102, 155] 0.29 5% (−5, 17) 1% (−9, 12) 0.07 CITP (ng/mL) 1.6 [1.0, 2.8] 1.6 [0.9, 3.0] 0.93 −25% (−37, 10) −23% (−36, −8) 0.87 PIIINP (ng/mL) 23 [16, 30] 28 [21, 36] <0.001 5% (−4, 15) 5% (−3, 14) 0.12 TIMP-1 (ng/mL) 188 [170, 212] 212 [183, 245] <0.001 −1% (−4, 2) −2% (−5, 2) 0.59 Galectin-3 (ng/mL) 20 [16, 23] 22 [18, 28] <0.001 6% (3, 10) 9% (4, 14) 0.52 eGFR, estimated glomerular filtration rate; hsCRP, high-sensitivity CRP; NT-proBNP, N-terminal pro-B-type natriuretic peptide; hs-TnT, high-sensitivity troponin T; PICP, pro-collagen type I carboxy-terminal peptide; CITP, collage type I; PIIINP=pro-collagen type III amino-terminal peptide; TIMP-1=tissue inhibitor of MMP-1.

Conclusions

In comparison to patients without DM, those with DM had poorer renal function and higher baseline levels of markers of myocardial stretch, myocyte death, and pro-fibrotic biomarkers. Further, hs-TnT increased over 12 months only in patients with DM.
P6354Decreased beneficial effects of oral heart failure medications in patients with acute decompensated heart failure and hyperglycemia: results from an international observational cohort
Authors: Akiyama E , Cinotti R , Arrigo M , Lassus J , Miro O , Celutkiene J , Cohen-Solal A , Maggioni A P , Mueller C , Parenica J , Spinar J , Sato N , Tamura K , Kimura K , Mebazaa A
Published: October 2019

Background

Hyperglycemia is common, regardless of diabetes mellitus (DM), and is associated with increased mortality in patients with acute heart failure (AHF). Current oral heart failure (HF) medications improve the outcome in patients with AHF. However, the relationships between HF medications, admission glucose levels, and prognosis in AHF patients remained unknown.

Purpose

This study sought to investigate the effect of oral HF medications on relationships between hyperglycemia at admission and 1-year all-cause mortality in patients with AHF.

Methods

From the GREAT (Global Research on Acute Conditions Team) registry, 13840 patients presenting with AHF whose admission glucose levels were available were included and followed up for 1-year all-cause mortality. Hyperglycemia was defined as a glucose levels of ≥7 mmol/L for patients without history of DM and ≥10 mmol/L for those with history of DM. Patients with hypoglycemia (defined as a glucose levels of ≤4 mmol/L, n=193, 1.4%) were excluded in this analysis.

Results

There were 6418 (%) patients with hyperglycemia and 7229 (%) patients with normoglycemia. One-year mortality was higher in patients with hyperglycemia than those with normoglycemia (1911 [30%] and 1821 [25%], respectively). Even after adjustment, the risk for 1-year mortality was significantly higher in hyperglycemia (HR 1.14, 95%-CI 1.04–1.26, P=0.008) compared with normoglycemia. Detrimental effects of hyperglycemia on 1-year mortality were more severe in de novo AHF patients than in patients with history of HF (p for interaction 0.004). Oral HF medications (beta blockers and/or angiotensin converting enzyme inhibitors/angiotensin receptor blockers) at discharge were effective in AHF patients with normoglycemia regardless of history of HF. Oral HF medications at discharge are very effective in de novo AHF patients with hyperglycemia and less effective in acute decompensated HF patients with hyperglycemia (Figure).

HF medications and 1-year mortality

Conclusions

Hyperglycemia at admission is associated with increased risk for 1-year mortality. Current oral HF medications are effective in most of subgroups, though they were less effective in patients with acute decompensated HF and hyperglycemia. These patients might need more aggressive therapies to improve outcomes.

Acknowledgement/Funding

This work was supported by a research fellowship from Japan Heart Foundation (E.A.)
P6376The role of circulating lymphocytes on hypertensive heart disease
Authors: Schluter K.-D , Schreckenberg R , Wolf A , Kutsche H , Troidl C , Simsekyilmaz S , Niemann B
Published: October 2019

Aims and background

Hypertension is a disease accompanied by moderate inflammation. Physical activity and pharmacological intervention protect the organisms against hypertension-dependent end-organ damage. They should therefore interfere with the mobilization of lymphocytes. Different subsets of lymphocytes should specifically interfere with vascular and cardiac remodeling. In this study we correlated the amount of circulating lymphocytes with the expression of vascular and cardiac specific genes in the aorta and left ventricle to identify the tissue-specific effects of these cells.

Methods

50 female spontaneously hypertensive rats (SHR) and 6 female normotensive Wistar rats (Wis) were analyzed. They were grouped in 7 subgroups exposed to different treatment regimes (modification of activity, type of activity, aldosterone blockade, and a combination thereof. Indicator genes of mal-adaptive vascular and cardiac remodeling were quantified by qRT-PCR.

Results

SHRs had an increased number of circulating NK cells and monocytes, but lower numbers of T cells. T cells inversely correlated with the vascular expression of p22phox, a member of the NADPH oxidase complex. Thus, lower number of T-cells favors the vascular expression of p22phox and thereby oxidative stress. In the left ventricle, T cells are inversely correlated with the expression of arginase-1 and UCP-2 but positively correlated with Glut-4 expression. The lower number of T cells in SHR therefore favors the expression of proteins often associated with oxidative stress and glucose metabolism. Monocytes are positively correlated with key markers of left ventricular hypertrophy (such as ANP, collagen-1, and β-MHC). Thus, the increased number of monocytes in SHRs supports cardiac hypertrophy. NK cells are inversely correlated with the expression of anti-inflammatory cytokines in the aorta (IL-10, IL-15). Thus, high number of circulating NK cells seems to favor a pro-inflammatory phenotype in the vasculature.

Conclusion

In a standard model of essential hypertension the profile of circulating lymphocytes differs from that in normotensive rats. The different subsets of lymphocytes specifically interfere with specific processes in the ventricle and vessel. Collectively, the difference between hypertensive and normotensive rats (less T cells, more NK cells and monocytes) supports a mal-adaptive role under hypertensive conditions.
P6377Cardiopulmonary effects of nitric oxide supplementation in a model of chronic hypoxia pulmonary hypertension
Authors: Reinero M , Beghetti M , Samaja M , Milano G
Published: October 2019

Objective

We previously demonstrated that the inhibition of phosphodiesterase type-5, an enzyme that degrades cGMP into inactive 5'-GMP, attenuates pulmonary remodeling and right ventricular (RV) hypertrophy (RVH) during exposure to chronic hypoxia (CH). The nitric oxide (NO) pathway is thought to play a major role in these changes. In this study, we investigate whether L-Arginine (L-ARG), a substrate of endothelial NO synthase (eNOS) and molsidomine (MOL), a NO donor, might alleviate the cardiovascular and pulmonary dysfunction led by CH.

Methods

Male rats (n=80; 10/group) were maintained in normoxic (21% O2) or hypoxic chambers (10% O2) for 14 days. Hypoxic rats were subdivided in four groups: untreated control, treated with L-ARG (45 mg/kg), eNOS inhibitor N-nitro-L-arginine methyl ester (L-NAME, 45 mg/kg) or MOL (15 mg/kg). Drugs were given daily in the drinking water. After sacrifice, we measured RV systolic pressure (RVSP), RV contractility (dP/dt), RVH, the lung/body weight ratio, the pulmonary vessels medial wall thickness, and the cardiac and pulmonary eNOS phosphorylation.

Results

Although CH increased RVSP, RV contractility and RVH, these increases were attenuated by L-ARG and MOL. Whereas L-ARG attenuated the RVH increase, MOL and L-NAME were ineffective. No treatment prevented the increase in lung/body weight ratio. Under all conditions, the lung tissue water content was unchanged, indicating no edema development. By contrast, CH rats developed a marked increase in medial wall thickness of small (0–100 mm) pulmonary arteries, while larger arteries were not affected. This increase was attenuated by L-ARG or MOL. Although CH decreased cardiac and pulmonary phosphorylated eNOS, L-ARG and MOL restored the normoxic level.

Conclusions

NO supplementation during CH attenuates RVSP, RVH and pulmonary remodeling, probably due to increased phosphorylation of eNOS. Despite normalizing RVSP, MOL does not influence RVH development.
P6379The impact of coronary artery evaluation and intervention to predict mortality and neurological outcome in out-of-hospital cardiac arrest patients with extra corporeal cardiopulmonary resuscitation
Authors: Kato S , Matsuda J
Published: October 2019

Background

Refractory cardiac arrest (CA), as defined by the absence of a return of spontaneous circulation (ROSC) is associated with poor prognosis. Current guidelines advocate the use of extracorporeal cardiopulmonary resuscitation (ECPR) for selected patients with CA. Although previous studies have reported the association of survival with some prognostic factors such as age, bystander CPR attempt, low-flow duration or lactate serum level, the impact of the evaluation of coronary artery by coronary angiography (CAG) and the revascularization of coronary artery stenosis have not been sufficiently elucidated.

Purpose

We sought to investigate impact of the CAG and the revascularization of coronary artery stenosis to predict mortality and neurological outcome at 30 days in out-of-hospital CA (OHCA) patients resuscitated by ECPR.

Methods

1382 out-of-hospital cardiac arrest patients were transferred to our critical care center, of which 899 patients with refractory CA at the emergency department were extracted from the institutional consecutive database between January 2015 and December 2018. Among those patients, we performed ECPR for 85 patients, who were successfully resuscitated. To predict mortality in hospital and neurological outcome at 30 days, we investigated basic patients' characteristics, pre-hospital information, and post-hospital care including CAG and coronary revascularization.

Results

Among those who had first resuscitated by ECPR, 20 patients (23.5%) survived and 10 patients (11.8%) achieved good neurological outcome (cerebral-performance-category (CPC) =1 or 2) at 30 days. We performed CAG for 40 patients (47.1%) and revascularization by percutaneous coronary intervention for 25 patients (29.4%). Younger age (P=0.037), CAG (P=0.001), PCI (P=0.001), and hypothermia therapy (P<0.001) were associated with low mortality. In the multivariate analysis, age (Odds ratio (OR) 0.95; 95% confidence interval (CI) 0.91–0.99; P=0.0025), PCI (OR 4.5; 95% CI 1.15–17.6; P=0.031), and hypothermia therapy (OR 13.7; 95% CI 1.52–124; P=0.020) were independent predictors of 30-days survival. Without diabetes mellitus (P=0.024), CAG (P<0.001), PCI (P=0.006), and hypothermia therapy (P=0.038) were associated with good neurological outcome. PCI (OR 7.39; 95% CI 1.73–31.6; P<0.001) was independently predictive for good neurological outcome.

Conclusions

Successful PCI was an independent predictor of 30-days survival and good neurological outcome in OHCA patients who were resuscitated by ECPR.
P6382The use of a mobile GPS-tracking system to activate volunteer first responders increases survival among patients with out-of-hospital cardiac arrest in residential areas
Authors: Jangaard L , Mickley H , Joergensen G , Schakow H , Gerke O , Henriksen F L
Published: October 2019

Background

In residential areas, survival in patients with out-of-hospital cardiac arrest (OHCA) is less than one third compared with the survival in patients with OHCA in public areas. New strategies are needed to improve outcomes in residential areas.

Purpose

To evaluate the effect on survival in OHCA patients in residential vs. public areas, when using a mobile GPS-tracking system to activate volunteer first responders (VFRs).

Methods

In 2012 a mobile GPS-tracking system was brought into use by a first aid volunteer corps on a rural island with a population of about 12,000 inhabitants. In all cases of emergency calls where an emergency medical service (EMS) was requested, the system was activated. Three VFRs were recruited and successively provided with distinct VFR roles. One of the VFRs was guided to the nearest automatic external defibrillator before approaching the patient.

We retrospectively screened all emergency ambulance journals in the years 2012–2017 to identify patients with OHCA. Additional information was collected from hospital records. Location was categorized as residential or public place. OHCAs witnessed by EMS, occurring at nursing homes or at uncertain locations were excluded. Clinical outcome was 30-day survival.

Results

During the 6-year period, there was a total of 114 OHCAs. Of these, 66 (57.9%) took place in residential areas, 16 (14.0%) in public areas and 32 (28.1%) were excluded. The 30-day survival in OHCA patients in residential vs. public areas was 15.2% and 12.5%, respectively (p=0.79).

Demographic and survival results Residential area (n=66) Public area (n=16) P value Age, mean (SD) 71 (13) 69 (13) 0.14 Male sex, no. (%) 47 (71) 13 (87) 0.22 Volunteer first responder activated, no. (%) 55 (83) 15 (94) 0.30 AED arrives before EMS, no. (%) 36 (55) 9 (56) 0.34 Shock given before EMS, no. (%) 8/63 (13) 3/15 (20) 0.88 First rhythm shockable by EMS, no. (%) 11/64 (17) 3 (19) 0.63 30-day survival, no. (%) 10 (15) 2 (13) 0.79 The table shows the differences in OHCA located at residential areas versus public areas. AED: Automated external defibrillator; EMS: Emergency medical service; OHCA: Out-of-hospital cardiac arrest; SD: Standard deviation.

Conclusion

The use of a mobile GPS-tracking system to activate VFRs increases the 30-day survival among patients with OHCA in residential areas to a level comparable with the survival observed in public areas.

Acknowledgement/Funding

One year grant from Odense University Hospital's PhD Fund. One year grant from University of Southern Denmark. A 500,000 DKKR grant from TV2 Funen and OUH
P6385Association of prehospital acetylsalicylic acid and heparin administration with favourable neurological outcome after out-of-hospital cardiac arrest: a matched-pair analysis
Authors: Grabmaier U , Von Der Helm M , Massberg S , Weckbach L T , Fischer M
Published: October 2019

Background/Introduction

To date, no prehospital administered drug has shown to influence favourable neurological outcome in patients with out-of-hospital cardiac arrest (OHCA). Early administration of antiplatelet and anticoagulant medication might affect organ microcirculation and therefore favourable neurological outcome in the setting of OHCA.

Purpose

To evaluate the effect of prehospital acetylsalicylic acid and heparin (AH) administration on favourable neurological outcome and overall survival after OHCA in a large multicentre registry.

Methods

We examined patients with cardiac causes of OHCA that were prospectively included in the German Resuscitation Registry. Patients that were administered AH in the prehospital setting were matched in a 1:4 ratio with patients that were not administered AH. Pairs were matched for age >80 years, public place of collapse, initial ECG rhythm, witnessed by lay people and by emergency medical services (EMS), bystander CPR, usage of vasopressors, ECG signs of ACS or diagnosed ACS, coronary angiography conducted and hypothermia conducted. Analyses in the patients were stratified by treatment arm. Data was collected from 2011 to 2017 and analysed from January 2019 to March 2019. The primary endpoint was favourable neurological outcome at hospital discharge defined as cerebral performance category (CPC) 1 or 2. Secondary endpoints were return of spontaneous circulation (ROSC) as well as survival to hospital discharge. Logistic regression analysis and chi square analysis were used to evaluate the primary and secondary endpoints, respectively.

Results

Within the German Resuscitation Registry, 17,139 patients included between 2011 and 2017 had a presumably cardiac cause of OHCA with completed follow-up data. 205 patients were administered AH in the prehospital setting, whereas 16,934 were not. After matching in a 1:4 ratio, 174 patients in the AH group and 696 in the noAH group were suitable for analysis of the primary and the secondary endpoints. Prehospital AH administration was associated with favourable neurological outcome (OR for CPC 1 or 2 at hospital discharge 1.489 [1.026–2.162], p=0.036). Patients with AH were more likely to have ROSC (73.6% vs. 65.7% in the noAH group, p=0.047). Survival to hospital discharge was not statistically different between groups (32.8% vs. 28.5% in the noAH group).

Consort flow-diagram

Conclusion(s)

In this matched-pair analysis, prehospital administration of AH was associated with an enhanced ROSC rate and with favorable neurological outcome. Randomized controlled trials are needed to confirm these results.
P6402Ischemic and bleeding events during dual antiplatelet therapy after second-generation drug-eluting stent implantation in hemodialysis patients: a propensity score-matched analysis
Authors: Shimizu A , Sonoda S , Setoyama K , Inoue K , Miura T , Anai R , Tsuda Y , Araki M , Otsuji Y
Published: October 2019

Background

Dual-antiplatelet therapy (DAPT) after second-generation drug eluting stent (2-DES) implantation reduced the risk of stent thrombosis and subsequent ischemic events, with an increase in bleeding risk. Although chronic kidney disease patients have high ischemic and bleeding risk, little is known about both risks in hemodialysis patients after 2-DES implantation during DAPT.

Method

From July 2009 to March 2017, we retrospectively analyzed post-discharge major adverse cardiac and cerebrovascular events [MACCE: cardiac death, myocardial infarction, target vessel revascularization (TVR) and cerebral infarction] and bleeding events in 644 consecutive patients during DAPT after 2-DES implantation. We divided them into 2 groups [102 hemodialysis (HD) and 518 non-hemodialysis (Non-HD) patients, mean age, 71±10 years] after excluding 24 patients (lost to follow up and peritoneal dialysis). Follow-up period was 49±24 months. Median DAPT duration was 12 months. The primary endpoint was MACCE. The secondary endpoint was bleeding events according to the Bleeding Academic Research Consortium (BARC) type 2, 3, or 5. MACCE and bleeding events were compared between HD and Non-HD by using the propensity score-matching (PSM) method.

Results

Among the 620 eligible patients, the primary and secondary events occurred in 207 (33.3%) and 76 (12.3%) patients, respectively. The rates of unadjusted MACCE [HD vs Non-HD: 53.9% vs 29.3%; Hazard ratio (HR) 2.39, p<0.01] and bleeding events (HD vs Non-HD: 21.6% vs 10.4%; HR 2.50, p<0.01) were significantly higher in HD than Non-HD.

After 1-to-1 propensity score adjustment for baseline differences (hypertension, diabetes mellitus, low ejection fraction, low albumin, anemia, and high C-reactive protein), a total of 160 patients (80 HD vs 80 Non-HD) was created. The rate of MACCE [HD vs Non-HD: 52.5% vs 31.3%; adjusted HR 2.04, p<0.01] was significantly higher in HD than Non-HD. Regarding MACCE, cardiac death (HD vs Non-HD: 18.8% vs 8.8%; adjusted HR 2.65, p=0.03) and TVR (HD vs Non-HD: 15.0% vs 6.3%; adjusted HR 2.74, p=0.046) occurred significantly higher in HD. On the other hand, bleeding events did not exhibit significant differences though HD had a numerically higher event rate (HD vs Non-HD: 25.0% vs 16.3%; adjusted HR 1.68, p=0.15), indicating that the bleeding risk in HD would be strongly dependent on the patient's background.

Conclusions

As a result of PSM, HD was shown to contribute to ischemic risk rather than bleeding risk. Even in the 2-DES era, HD was an independent risk factor of cardiac death and TVR. Therefore, further study on the current regimen of DAPT would be necessary while balancing both ischemic and bleeding risk.