bluuebunny/crossref_metadata_2025 huggingface dataset:
P6254Care cascade of hypertension in people living with HIV
Authors: Nascimento Costa A , Bairronuevo M B , Val F , Macedo A R E , Vegas N C , Terro P , Marques M , Ribeiro F , Rabelo A L , Paixao S , Comte De Alencar Filho A , Lacerda M V G
Published: October 2019

Background

Life expectancy of people living with HIV (PLHIV) has been increasing since the advent of antiretroviral therapy. However, prevalence of non-communicable diseases (NCD) and associated deaths has followed the same trend. From these NCDs, those of cardiovascular origin have become the most prevalent among PLHIV.

Purpose

In this study we delineate a cascade of care for hypertension screening, diagnosis, treatment, drug adherence and control in PLHIV.

Methods

Male and female patients diagnosed with HIV above 40 years of age attending to an outpatient clinic of a reference tertiary care centre for infectious diseases were cross-sectionally screened for hypertension through blood pressure (BP) measurement during outpatient consultation.

Results

A total of 298 subject were enrolled. Of these, 107 (35.9%) presented elevated BP consistent with hypertension according to national guidelines. Of these, only 36 (33.6%) were aware of the diagnosis, 19 (17.7%) were on regular cardiological follow-up, 17 (15.8%) were under treatment and 11 (10.2%) responded to be adherent to BP lowering medication.

Care Cascade HIV_HTN

Conclusions

Steep decline was revealed in several steps of the cascade of care, especially regarding the awareness level. Integrative methods for NCD and HIV care are urgently needed. Early screening of hypertension, diagnosis, treatment, adherence and ongoing BP control should be equal targets in HIV care. Finally, there is an urgent need to encourage HIV primary care and infectious disease health professionals to early screen for cardiovascular outcomes.

Acknowledgement/Funding

Fundação de Amparo à Pesquisa do Estado do Amazonas – FAPEAM
P6256Revascularisation for acute coronary syndrome: are we offering elderly patients the correct treatment?
Authors: Al-Othman S , Zheng Y , Malik N
Published: October 2019

Purpose

Acute coronary syndrome (ACS) is treated with revascularisation procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). Whilst reasonable clinical exclusion criteria exist, age is not one of them and patients of advanced years have been shown to have better outcomes with both treatments than with medical management. We set out to investigate the management and outcomes of patients age seventy five and over, with ACS.

Methods

A retrospective data analysis of all patients age seventy five and above, prescribed dual antiplatelet therapy (DAPT - aspirin plus clopidogrel or aspirin plus ticagrelor), admitted to our institution over a one year period (April 2015 to April 2016). We analysed electronic records and discharge documents and excluded patients without a diagnosis of ACS.

Results

207 patients over 75 years old were treated for ACS; 83.6% (173) were diagnosed with non ST elevation myocardial infarction (NSTEMI), 9.6% (20) diagnosed with ST elevation myocardial infarction (STEMI) and 6.8% (14) diagnosed with unstable angina. 73.4% (152) of patients were managed medically, 14.5% (30) had an angiogram, 11.1% (23) had PCI and 1.0% (2) had CABG. 74.0% (153) of patients were treated with aspirin plus clopidogrel, 26.0% (54) with aspirin plus ticagrelor. Major bleeds were reported in 21 patients (10.1%), 18 of the medically managed patients (8.7%) and 3 in the intervention group (5.5%) (P value 0.30). There were 17 major bleeds in the aspirin and clopidogrel group (11.1%) and 4 in the aspirin and ticagrelor group (7.4%) (P value 0.60). 93 (61.2%) of the medically treated group were alive at one year compared to 47 (85.5%) of the intervention group (P value 0.0008).

Conclusion

Our data show a clear survival benefit in the intervention group, although comparisons between the groups are challenging given confounding factors, such as co-morbidities and patient preference. However, the high proportion (73.4%) of over 75-years old treated medically warrants further evaluation, given the evidence of benefit for patients in this age group, treated with PCI. We feel there is a need for further research in to the ideas and practice surrounding the management of ACS in the over 75's, and their relation to the available evidence.
P6260ACS-group 75+: real clinical practice
Authors: Kruchinova S , Raff S A
Published: October 2019

Purpose

to evaluate the features of treatment and outcomes in elderly patients with acute coronary syndrome.

Methods

The elderly group comprised 2385 (28.9%) patients ≥75 years of the 8249 patients enrolled in the KRACS registry.

Results

When comparing patients of different ages, it was shown that among the elderly, dyspnoea was the most common manifestation of ACS, 9% vs 4% (p=0.015), they were less often hospitalized in “invasive” hospitals - 36% vs 49% (p=0.003), At admission, they often had the class Killip ≥ II - 36% vs 17% (p<0.001), a high risk for the GRASE-68% vs 30% (p<0.001). In addition, in elderly patients significantly lowered levels of Hb and increased creatinine were detected more often.

Drug treatment of elderly patients was characterized by less frequent use of ticagrelor - 3% vs 21% (p<0.001), LMWH or fondaparinux - 4% vs 12% (p=0.004). Thrombolytic therapy in STEMI in the elderly was more often streptokinase - 30% vs 18% (p=0.04), less often - tissue activator plasminogen - 2% vs 10% (p=0.03).

The frequency of performing any invasive interventions for any type of ACS in elderly patients was significantly lower - 16.7% vs 46.3% (p<0.0001), and the incidence of fatal outcomes during hospitalization for any type of ACS was significantly higher - 16, 0% vs 6.1% (p<0.0001). When assessing the incidence of fatalities in different facilities, it was found that STEMI, patients ≥75 years old hospitalized in “invasive” hospitals died significantly less frequently than when they got into “non-invasive” hospitals - 15.6% vs 50.0% (p=0.013). At the same time, among patients <75 years hospital mortality in “invasive” and “non-invasive” hospitals was not significantly different - 14.7% vs 9.9% (p=0.50).

There was also a clear trend towards a higher incidence of deaths among elderly patients who were left without PCI, compared with those who had been intervened. In patients <75 years, this trend was absent.

Conclusion

thus, the results obtained indicate that elderly patients, with a higher risk and worse outcomes, receive treatment that is less consistent with the requirements of modern guidelines for the treatment of ACS. Important factors associated with better outcomes in elderly patients is their hospitalization in “invasive” hospitals and the implementation of PCI.
P6261Aortic stiffness and carotid intima thickness in hypercholesterolemic males with erectile dysfunction: relation to smoking status and statin therapy
Authors: Ioakeimidis N , Vlachopoulos C , Terentes-Printzios D , Koutagiar I , Pantou S , Abdelrasoul M , Sigala E , Angelis A , Skoumas I , Rokkas K , Tousoulis D
Published: October 2019

Purpose

Aim of the study was to examine possible differentiation of aortic stiffness and carotid atherosclerosis among hypercholesterolemic patients with erectile dysfunction (ED) according to smoking status and statin therapy.

Methods

We measured carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) in three age-matched groups of ED patients with a moderate cardiovascular risk (SCORE) and low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL: Smokers not receiving statin therapy (n=106), Smokers actively under statin treatment for at least three months with no dose adjustment for a minimum of six weeks (n=59) and Non-smokers not receiving statin therapy (n=97). The severity of ED was evaluated with measurements of penile peak velocity (PSV) 20 min after the intracavernous injection of prostaglandin E1 (20 μg).

Results

The groups of untreated smokers and non-smokers had similar mean LDL-C level. The mean LDL-C of patients under statin therapy was lower, however the differences with the level of the untreated patients was not statistically significant. Overall 33 (56%) of the patients under statin therapy reached their LDL-C goal. Body mass index and the prevalence of hypertension were not different between the three groups. The PSV was significantly lower in smokers with or without therapy compared to that of non-smokers, denoting significant influence of smoking status on the smaller in size penile arteries and consequently, a unfavorable effect on erectile function. Figure illustrates the differences in cfPWV (left plot) and cIMT (right plot) mean (±SE) values between the three groups. Smokers not receiving statin therapy had significantly higher cfPWV compared to the other groups while smokers under statin therapy had no different cfPWV than that of non-smokers not receiving therapy. The cIMT values were not different between the three groups.

Smoking, statins and vascular changes

Conclusions

Smokers ED patients receiving statin therapy exhibited similar atherosclerotic burden compared to untreated hypercholesterolemic individuals, however, the cfPWV was significantly lower, possibly because of the known pleiotropic effects of these drugs on the aortic elastic properties. Although the cross-sectional design precludes drawing conclusions of causal relationships, the findings of this study have important clinical implications given the harmful effect of both hypercholesterolemia and smoking in men suffering from ED and the higher risk for future cardiovascular events that ED confers.
P6267Novel direct effects of SGLT2 inhibitor, Canagliflozin, on myocardial redox state in humans
Authors: Kondo H , Akoumianakis I , Akawi N , Cristina M , Herdman L , Badi I , Kotanidis C , Akbar N , Antonopoulos A , Oikonomou E , Chuaiphichai S , Channon K , Antoniades C
Published: October 2019

Background

Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that control plasma glucose levels by inhibiting reabsorption of glucose in kidney. Recent clinical trials have suggested a class effect of SGLT2 inhibitors in preventing hospitalization due to heart failure. However, the underlying mechanism has not been fully elucidated.

Purpose

We investigated the direct effect of the SGLT2 inhibitor, Canagliflozin (Cana), on myocardial redox state in humans.

Methods

The study included 48 patients undergoing cardiac surgery. Fresh myocardial tissues were incubated ex vivo with or without Cana and then used for superoxide quantification and Western immunoblotting. NADPH-oxidases activity was evaluated with NADPH 100μM stimulation, while nitric oxide synthase (NOS) coupling was assessed by using N(ω)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). A human cardiomyocyte (HCM) cell line was also used for in vitro validation of the effects of Cana on myocardium.

Results

Ex vivo incubation of myocardium with Cana significantly reduced baseline (A) and NADPH-oxidase-derived O2·− (B) and improved NOS coupling reflected by positive L-NAME delta O2·− values (C). Regulation of NADPH-oxidases activity by Cana was found to result from reduced GTP-activation (D) and consequent membrane translocation (E) of Rac1, a key subunit of NADPH-oxidases. Cana also reduced tetrahydrobiopterin (BH4) oxidation, increasing its bioavailability (F), which is a key mechanism to improve NOS coupling. Incubation with Cana enhanced phosphorylation of AMPK, and the downstream signalling, ACC (not shown). Additional Compound C, which is inhibitor of AMPK, significantly reversed these effects of Cana (A, B, C, D, E, F). These findings were replicated in HCM (not shown). In line with these, Cana increased the ADP/ATP ratio of cytoplasm in HCM, which could provide an upstream mechanism for AMPK activation.

Conclusions

We demonstrate for the first time in humans, that Cana suppresses myocardial NADPH-oxidases activity and improves NOS coupling through an AMPK-mediated pathway. This could be an underlying mechanism for the cardioprotective effects of SGLT2 inhibitors.
P6275Role of autophagy in imatinib-induced cardiotoxicity
Authors: Kobara M , Naseratun N , Watanabe Y , Toba H , Nakata T
Published: October 2019

Background

Cardiotoxicity is one of the severe adverse effects of chemotherapeutic agents. Imatinib, a therapeutic agent for chronic myelogenous leukemia, has been reported to induce cardiotoxicity. Autophagy is an intracellular bulk protein and organelle degradation process, but it is unclear whether autophagy functions as pro-death or pro-survival program during disease conditions. We examined whether imatinib induces myocyte autophagy and the role of autophagy in imatinib-induced cardiotoxicity in in vitro and in vivo experiments.

Methods

In in vitro experiments, neonatal rat cardiac myocytes were treated with imatinib (1, 5, 10 μM; 1–6 hrs). Inhibition of autophagy was performed using 3-methyl-adenine (3MA), an autophagic inhibitor, and transfection with Atg5-targeted siRNA. Myocyte apoptosis was detected by morphological change in nuclei and caspase 3 activity. Mitochondria-derived reactive oxygen species production was detected using MitoSOX and mitochondrial membrane potential was assessed by TMRM staining. Expressions of cytochrome c in mitochondria and cytosole were examined by Werstern blotting. Myocyte autophagy was assessed by monodansylcadaverine staining and microtubule-associated protein light chain (LC) 3-II expression. In in vivo experiments, C57BL6 mice were treated with imatinib (50 and 200 mg/kg/day) for 5 weeks in the presence or absence of 3MA. Cardiac function was examined by echocardiography. In cardiac tissue, apoptotic myocytes were examined by TUNEL assay and autophagy was examined by LC3-II expression.

Results

In in vitro experiments, imatinib increased apoptotic nuclei and caspase 3 activity, in a dose-dependent manner. Consequently, imatinib augmented production of mitochondria-derived reactive oxygen species, loss of mitochondrial membrane potential, and the release of cytochrome c from mitochondria to cytosole, suggesting that imatinib induced mitochondrial-apoptotic pathway. On the other hand, imatinib significantly increased monodansylcadaverine stained dots and LC3-II expression, suggesting that imatinib increased autophagy. 3MA and Atg5 siRNA augmented imatinib-induced apoptosis by 60% and 30%, respectively. In in vivo experiments, imatinib (200 mg) exhibited the dilatation of left ventricle by 15% and the depression of left ventricular fractional shortening by 23%. Ratio of apoptotic myocytes was significantly increased and LC3-II expression in cardiac tissue was enhanced by imatinib in a dose-dependent fashion. Co-treatment with 3MA and imatinib further impaired imatinib-induced myocyte apoptosis by 3 fold and LV dysfunction by 20%.

Conclusion

These results indicate that imatinib induced myocyte apoptosis, leading to cardiac dysfunction. Imatinib enhanced myocyte autophagy as a consequence of apoptosis and autophagy was a beneficial phenomenon in this condition.
P6282Myocardial redox state predicts 3-year mortality in patients undergoing cardiac surgery: the ox-HVF study
Authors: Kotanidis C , Antonopoulos A , Psarros C , Akoumianakis I , Herdman L , Oikonomou E K , Badi I , Krasopoulos G , Sayeed R , Petrou M , Srivastava V , Farid S , Channon K , Antoniades C
Published: October 2019

Background

NADPH oxidase activity is a major source of superoxide anions (O2·−) in the human myocardium, linked with adverse short-term clinical outcomes after cardiac surgery, but its prognostic value for the long-term clinical outcome of these patients is unknown.

Purpose

To explore the association between NADPH oxidase activity in the human myocardium and the clinical outcome of patients undergoing cardiac surgery.

Methods

A total of 216 patients from the Oxford Heart Vessels and Fat (OxHVF) cohort were enrolled. Myocardial tissue samples were collected during cardiac surgery and used for RNA isolation and myocardial O2·− quantification using lucigenin-enhanced chemiluminescence (5μmol/L). The specific contribution of NADPH oxidase activity to myocardial O2·− production was quantified as the Vas287021 (40 μmol/L)-inhibitable signal following NADPH (100μmol/L) stimulation (Vas2870 is a NADPH oxidases inhibitor). Malonyldialdehyde and hsCRP levels were measured in plasma isolated from peripheral blood collected pre-operatively. Patients were followed-up for a mean of 2.9±1.4 years for the primary endpoint of cardiovascular mortality.

Results

Myocardial NADPH oxidase activity was not correlated with systemic oxidative stress (evidenced by malonyldialdehyde, panel A) or systemic inflammation (reflected by hsCRP levels, panel B). NADPH oxidase activity was significantly higher in the cardiovascular death group (panel C) and was associated with cardiovascular (HR [95% CI]: 1.53 [1.10–2.13], p=0.01 per SD increase) but not all-cause mortality (HR [95% CI]: 1.32 [0.96–1.80], p=0.08 per SD increase). This association remained significant after adjustment for EuroscoreII (HR [95% CI]: 1.80 [1.14–2.82], p=0.01 per SD increase). For an optimal cut-off value of 7,920 RLU/sec/mg tissue, patient survival was significantly poorer in the high vs. low NADPH oxidase activity subgroup (panel D). Adding NADPH oxidase activity to the baseline clinical model significantly improved model's performance (panel E). Interestingly, myocardial NOX gene expression levels didn't show any significance in mortality prediction, highlighting the fact that NADPH oxidase activity, rather than enzyme levels, is the key outcomes regulator.

Conclusion

Increased NADPH oxidase activity in the human myocardium independently predicts high cardiovascular mortality in patients with advanced coronary atherosclerosis. Targeting NADPH oxidase in the human heart may be a rational therapeutic approach.

Acknowledgement/Funding

BHF, EPSRC
P6294NLRP3 inflammasome is activated in the atrium of an ovine model of sustained obesity
Authors: Saljic A , Hohl M , Li N , Agbaedeng T , Twomey D , Lau D H , Mahajan R , Linz D , Jespersen T , Sanders P
Published: October 2019

Introduction

Obesity and enhanced inflammatory response are two independent risk factors involved in the pathogenesis of atrial fibrillation (AF). Components of the NLRP3 inflammasome have been found to be expressed in cardiomyocytes and cardiac fibroblasts and that increased inflammasome activation contributes to the pathogenesis of AF. The NLRP3 inflammasome is a multi-protein signaling complex that is activated in two steps: 1st) a priming event that includes a NFκB-activating stimuli which increases the expression of pro-inflammatory cytokines, and 2nd) a triggering event that includes the assembly of the inflammasome complex and activation of caspase-1 which promotes the production of pro-inflammatory cytokines like interleukin 1 beta (IL-1b).

Purpose

We used a sheep model of sustained obesity to characterize the association between atrial myocardial fat infiltration, atrial activation of the NLRP3 inflammasome and the development of an atrial arrhythmogenic substrate for AF.

Methods

Eight sheep were fed ad libitum calorie-dense diet over 40 weeks to gain weight and were maintained in this state of sustained obesity for another 40 weeks. Eight lean, weight-controlled and aged-matched sheep served as control. Atrial fat infiltration was determined by oil-red staining and NLRP3 inflammasome activation was assessed by immunoblot in atrial whole-tissue lysate. Atrial effective refractory periods (aERPs) were evaluated (twice diastolic threshold, cycle length (CL) of 400 ms, S1S2 -protocol).

Results

Sustained obesity was associated with increased atrial fat infiltration (lean: 0.8±0.3% vs. obese: 2.3±1.2%, p=0.1) and shorter aERP (lean: 169±22ms vs. obese: 138±26ms, p=0.03). Protein levels of caspase-1 and mature IL-1β were significantly enhanced (p=0.04 and p=0.01, respectively). Further shortening of aERP correlated with increasing atrial protein levels of caspase-1 (r=0.59, p=0.02). In contrast, levels of TNFα and NFκB were not significantly changed in atria of sheep with sustained obesity.

Conclusions

Sustained obesity is associated with increased expression of NLRP3 inflammasome-related proteins and the development of an arrhythmogenic substrate for AF. Our study suggest that the increased activity is due to increased triggering, rather than increased gene transcription. Whether NLRP3 inflammasome activation represents a modifiable target to prevent AF in obesity warrants further study.
P6313RAAS inhibition improves event-free survival in cardiac transplant recipients: results of the prospective cohort study
Authors: Shevchenko A , Gautier S , Shevchenko O , Kachanova J , Kwan V
Published: October 2019

Background

Despite known achievements, long-term survival of heart transplant (HT) recipients still needs to be improved. The Renin-Angiotensin-Aldosterone System (RAAS) hyper-activation could be the result of heart denervation and immune suppressive therapy in these patients. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have been shown to be beneficial in patients with hypertension, heart failure (HF) and diabetic nephropathy.

Purpose

The study was aimed to assess the effects of ACEI and ARB on the prognosis and cardiac transplant remodelling in HT recipients.

Methods

Four hundred ninety-six critical HF patients had cardiac transplant surgery between January 2012 and December 2016 in Shumakov National Research Centre of Transplantology, and Artificial Organs (Moscow, Russian Federation) which accounted to 57.9% of all heart transplantations (HTx) performed in the country during that period. All patients >18 years old who survived 30 days after the operation without known contraindications for ACEI or ARB were sequentially included in the study. A non-randomised controlled trial study design was used. Study endpoints included death from any cause and re-transplantation due to the irreversible cardiac transplant failure.

Results

385 HT recipients (mean age 46.3±2.3 years, 51 females and 334 males) enrolled in the study. Thirty days after the HTx, a RAAS inhibitor was assigned to 141 recipients. Patients receiving ACEI or ARB had significantly better event-free survival than the control group (log-rank p=0.045) during the follow-up for 1856.5±68.3 days. Unadjusted analysis revealed other factors related to the risk of death or irreversible HT failure: recipient age <37 years old, donor age>44 years old, aortic cross-clamping time >117 min, peri-operational ECMO>3 days of duration, acute renal failure requiring dialysis during first 30 days after the operation, right atrium size, mitral regurgitation 2+, tricuspid regurgitation 1+, donor's heart posterior wall thickness (PWT) >12mm, and left ventricle (LV) end-diastolic dimension (EDD). When adjusted to the RAAS inhibitors use, only the donor's age and early renal failure remained significant. LV EDD did not change over time in both groups, whereas LV PWT in the control group significantly increased from 12.3±0.3 to 13.5±0.5 mm (p<0.05).

Conclusions

Heart transplant recipients who received RAAS inhibitors had better survival and less LV hypertrophy progression that could reflect the beneficial effects of ACEI and ARB after heart transplantation.
P6317Recipient or donor age in heart transplantation:which one fits more?
Authors: Di Nora C , Lechiancole A , Ferrara V , Sponga S , Tursi V , Guzzi G , Nalli C , Livi U
Published: October 2019

Increasing recipient (RA) and donor age (DA) are independently associated with mortality after Heart Transplantation (HT). The aim of this study was to analyse the impact of age-matching on HT survival. 485 recipients who underwent HT between 1990 and 2018 in our Institution were divided into four groups: RA<60-DA<50 (Group 1), RA<60-DA>50 (Group 2), RA>60-DA<50 (Group 3), RA>60-DA>50 (Group 4), and their outcomes were compared. Emergency HT, bridge with MCS and re-HT were excluded. Mean follow-up was 109±84 months.

The survival of Group 1 patients was significantly higher than that of patients in other groups (p=0.001). The outcome of young recipients who received older donor grafts did not significantly differ from that of older recipients. At multivariate analysis, donor age, recipient age, Diabetes Mellitus and hypercholesterolemia correlated with long-term mortality.

Demographic variables 1 (d/r) 2 (r/D) 3 (R/d) 4 (D/R) P Value Recipients data   No. of patients 241 61 107 76 –   Female, n (%) 50 (21) 16 (26) 17 (16) 11 (14) 0.25   Age (years), mean ± sd 49±10 54±7 64±3 65±3 <0.001*   Creatinine (mg/dl), mean ± sd 1.3±0.8 1.5±0.5 1.4±0.4 1.5±0.5 0.49   Diabetes Mellitus, n (%) 33 (14) 17 (28) 38 (36) 30 (39) <0.001*   Hb (g/dl), mean ± sd 12.9±2.4 11.5±2 13±1.7 12±2 0.08   Tot. Bilirubin (mg/dl), mean ± sd 1.3±1 1±0.6 1.2±0.8 1.1±0.7 0.63   sPAP (mmHg), mean ± sd 42.4±14.2 47.5±15.9 44.6±14.8 49.6±16.2 0.07 Etiology 0.003*   Ischemic, n (%) 74 (30) 25 (41) 55 (51) 40 (53)   Dilative, n (%) 110 (46) 24 (39) 40 (37) 29 (38)   Valvular, n (%) 19 (8) 5 (8) 5 (5) 5 (6) Donors and Surgical data   Age, (years) mean ± sd 31±10.5 56.5±4 36±10.5 57.5±4.5 <0.001*   Female sex, n (%) 73 (30) 30 (49) 38 (35) 33 (43) 0.02*   LVEF, mean ± sd 58±4 56±5 60±9 63±9 0.73   Graft ischemia time (min), mean ± sd 198±63 205±62 209±64 193±69 0.75   ECC time (min), mean ± sd 218±72 213±64 214±70 192±53 0.45

In this study, the use of hearts from older donors did not affect survival of older recipients; conversely, in young recipients it increased the risk of mortality.
P6322Trajectories of functional limitations during 14 months after discharge among patients with heart failure: a multicenter cohort study
Authors: Adachi T , Iwatsu K , Kamisaka K , Iida Y , Yamada S
Published: October 2019

Background

Severity of functional limitations (FLs) has been considered as a prognostic factor in patients with heart failure (HF). However, trajectory patterns of FLs after discharge and their associated factors have remained unclear.

Purpose

This study aimed to explore trajectories of FLs after discharge and to examine clinical characteristics based on the identified trajectories.

Methods

This study was performed as a part of a multicenter cohort study. The cohort study enrolled hospitalized patients due to acute HF or exacerbation of chronic HF and who were able to walk at discharge. Patients with severe cognitive or psychological disorders or less than 6-month life expectancy were excluded. FLs were assessed using Performance Measure for Activities of Daily Living-8 (PMADL-8; higher scores indicate worse FLs) at discharge and 1-, 6-, 10- and 14-month after discharge. To identify FLs trajectories getting worse after discharge, we excluded patients already having severe FLs at discharge (PMADL-8 ≥21, a cut off value for predicting poor prognosis). Group-based trajectory modeling (GBTM) was conducted to identify distinct PMADL-8 trajectories. Then, associated factors of trajectory group that showed increasing FLs after discharge were examined using logistic regression analysis adjusted for potential confounders.

Results

A total of 953 patients were included in the analysis (age: 70.6±11.8 years, men: 70.9%, left ventricular ejection fraction <40%: 41.3%). GBTM identified four PMADL-8 trajectories: two separate trajectories where PMADL-8 remained low (T1: 14.1%, T2: 31.3%), mildly increasing PMADL-8 trajectory (T3: 41.0%) and rapidly increasing PMADL-8 trajectory (T4: 13.6%) (Figure). Logistic regression analysis showed that age (odds ratio 1.05, per 1 year; 95% confidence interval 1.02–1.07), women (2.12; 1.31–3.45), brain natriuretic peptide ≥200 pg/mL (1.88; 1.10–3.21), estimated glomerular filtration rate <30 mL/min/1.73m2 (2.50; 1.41–4.41), depression (2.34; 1.44–3.80), and re-hospitalization due to HF during 1-year follow-up (2.85; 1.56–5.21) were independent associated factors of T4 group.

Figure 1. Trajectories of PMADL-8

Conclusions

The high-risk population for increasing FLs after discharge was identified by GBTM. The findings of this study suggest the importance of long-term HF management for preventing FLs after discharge especially among those with older age, female gender and depression.

Acknowledgement/Funding

This work was supported by a Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science [16H01862].
P6325Gas exchange improvements during exercise correlate with hemodynamic changes in heart failure patients with a left ventricular assist device
Authors: Seuthe K , Morosin M , Smail H , Gerhardt F , Simon A , Dumitrescu D
Published: October 2019

Background

The implantation of left ventricular assist devices (LVAD) has established its role in therapy for patients with end stage heart failure.

Benefits in survival as well as an improved quality of life, compared to optimized medical therapy (OMT) alone, has been proven.

There are limited data in the literature on the metabolic changes during exercise in LVAD patients, and in most studies no increase in peak oxygen consumption on cardiopulmonary exercise test (CPET) could be shown early after surgery. However, recent data suggests an improvement in peak oxygen uptake (VO2) as a late effect after rehabilitation.

To further investigate these findings we sought to analyse CPET data from patients before LVAD implantation as well as in the early and late follow up in correlation with hemodynamic changes at these times.

Methods

We collected and retrospectively analysed data of heart failure patients who had undergone LVAD implantation, and in whom a right heart catheterization, a cardiopulmonary exercise test and an echocardiography had been performed at time before, as well as 6 Months and 12 months after LVAD implantation, respectively.

Results

Data of 43 patients implanted with an LVAD between 2011 and 2017 were analysed. There was significant improvement in cardiac output (3,2 vs 4,3 L/min, p<0,001) and VE/VCO2 slope (46 vs 38, p=0,001) 6 months after LVAD implant as well as a significant reduction in PCWP (26 vs 11 mmHg, p<0,001), PAP mean (40 vs 22 mmHg, p<0,001), RA mean (12 vs 8 mmHg, p=0,002) and PVR (4,2 vs 2,5 WU, p<0,001). However, there was no significant increase in peak VO2 after 6 months.

12 months after LVAD implantation there were no further significant changes in cardiac output, intracardiac pressures or VE/VCO2 slope, which all remained similar to the 6 months follow up. However, at that point, a significant increase in peak VO2 was seen, compared to baseline (1060 vs 1410ml/min, p=0,001) and to 6 months after surgery (Figure 1).

Conclusion

Cardiac output increases in heart failure patients early after LVAD implantation. Consequently, permanent ventricular off loading results in the reduction of intracardiac pressures and improvement in the VE/VCO2 slope 6 months after surgery. However, a significant rise in peak oxygen consumption could only be noted 12 months after surgery, suggesting either a delayed long-term effect of improved hemodynamics or other causes such as enhanced mobility or training due to improved quality of life.
P6326Which results of the cardiopulmonary exercise test deserve greatest attention to establish the prognosis in heart failure?
Authors: Gama F , Freitas P , Ferreira A , Durazzo A , Aguiar C , Tralhao A , Ventosa A , Ferreira J , Mendes M
Published: October 2019

Background and aim

Limitation of exercise tolerance is one of the cardinal manifestations of heart failure (HF). Cardiopulmonary exercise testing (CPET) provides a thorough assessment of exercise integrative physiology involving the pulmonary, muscular, and oxidative cellular systems. We aimed to identify which data collected during a CPET shows the best prognostic performance with respect to predicting mortality or the need for heart transplantation (HT).

Methods

Single-centre retrospective cohort study of consecutive HF patients performing a CPET for functional and prognostic HF evaluation from October 1996 till May 2018. Left ventricular ejection fraction was not an exclusion criterion. A Cox model was fit with time to death or heart transplantation (whichever recorded first within 5 years) as the dependent variable and CPET parameters as the independent variables. Both unadjusted and adjusted covariate Cox regressions were performed. ROC curve analysis was used to determine whether the significant variables, as a model, could reliably predict the study endpoint.

Results

The study population consisted of 513 patients, median age 58 (IQ 16) years, and 74.9% male. The majority had reduced ejection fraction (75.4%), and the most common HF aetiology was ischemic heart disease (55.8%). During the 5-years follow up, 126 patients died and 60 underwent heart transplantation. In unadjusted Cox regression, nearly all CPET variables were significantly associated with the study endpoint. After covariate adjustment, with prior exclusion of redundant variables, three measures remained associated with the study endpoint: peak VO2 consumption (hazard ratio [HR] 0.85; 95% confidence interval [CI], 0.81–0.90); VE/VCO2 slope (HR 1.02; 95% CI, 1.00–1.02); presence of oscillatory ventilatory pattern (HR 3.73; 95% CI, 2.43–5.72). As a model, these 3 variables showed a strong discriminatory ability (c-statistic 0.87; 95% CI, 0.83–0.90) (see figure) for the study endpoint.

Figure 1

Conclusion

When using the CPET for prognostic stratification of HF patients, the presence of an oscillatory ventilatory pattern, the peak VO2 and the VE/VCO2 slope are the most important tools on which clinicians should focus.
P6330Obesity paradox in heart failure with mid-range ejection fraction
Authors: Zamora E , Lupon J , De Antonio M , Domingo M , Moliner P , Santiago-Vacas E , Santesmases J , Boldo M , Diez-Quevedo C , Troya M I , Rivas C , Gonzalez B , Diaz V , Velayos P , Bayes-Genis A
Published: October 2019

Background

Obesity is identified as an independent risk factor for developing congestive heart failure (HF). Paradoxically it has been reported that obesity is associated with improved survival in different cohorts of HF patients. Nevertheless, the presence of obesity paradox in HF with mid-range ejection fraction (HFmrEF) is not completely elucidated.

Objective

To analyse the relationship between body mass index (BMI) and mortality in a HFmrEF ambulatory cohort of different aetiologies followed in a HF unit, with especial focus on the role of obesity in prognosis.

Methods

Baseline BMI was analysed as continuous variable and categorized in 4 groups based on 2009 WHO classification: low weight (BMI <20.5 kg/m2), normal weight (BMI 20.5 to <25.5 kg/m2), overweight (BMI 25.5 to <30 kg/m2) and obesity (BMI ≥30 kg/m2). All-cause mortality was the primary end-point of the study. Cox regression analyses adjusted by age, sex and NYHA functional class were performed and survival curves plotted.

Results

Three-hundred thirty patients were included in the study (age 65.9±13.2 years, 68% men). The main aetiology was ischemic heart disease (52%, followed by dilated cardiomyopathy (11%) and hypertensive cardiomyopathy (11%). The majority of patients were in NYHA class II (65%) and III (26%). Mean ejection fraction was 43.2% ± 2.7. During a mean follow-up of 5.3±4.6 years 142 patients (42%) died. BMI showed a protective effect on survival in Cox regression analysis (HR 0.96 [95% CI 0.92–0.99], p=0.01). When categorized groups of BMI were analysed, obese patients showed a trend towards lower mortality than normal weight patients (reference): adjusted HR 0.65 [95% CI 0.40–1.03], p=0.07. Survival curves adjusted by age, sex and NYHA functional class according to BMI category are depicted in the figure. As a significant interaction (p=0.02) was found between BMI and ischemic aetiology of HF, separate analyses were performed for BMI categories for ischemic and non-ischemic patients, with remarkably different results: ischemic aetiology: HR 0.97 [95% CI 0.52–1.79], p=0.91; non-ischemic aetiology HR 0.28 [95% CI 0.13–0.64], p=0.003.

Conclusions

A greater BMI was associated with lower mortality rates in patients with HFmrEF during a mean follow-up of five years. Obesity showed a protective effect in HFmrEF patients, which remarkable in patients from non-ischemic aetiology and was absent in patients from ischemic aetiology.
P6351A point-of-care risk score predicts 30-day readmission in patients hospitalized with heart failure (HF): derivation and validation of the LENT index
Authors: Van Spall H G C , Lee S F , Averbuch T , Erbas Oz U , Perez R , Ko D T , Connolly S J
Published: October 2019

Background

Risk prediction models in heart failure (HF) are typically complex, derived retrospectively from administrative databases, and modest in their ability to discriminate between high, medium, and low risk categories. The complexity of these models makes them difficult to use at the point of care.

Purpose

To determine if a simple risk index using Length of hospital stay (L), number of Emergency department visits in the preceding 6 months (E), and either admission or discharge N-Terminal (NT) prohormone of Brain Natriuretic Peptide (pro-BNP) at the point of care can predict 30-day readmissions in patients hospitalized for HF.

Methods

This is a sub-study of the Patient-Centered Care Transitions in HF (PACT-HF) stepped-wedge cluster randomized trial. We included 772 patients hospitalized for HF at 10 Canadian hospitals. We used log-binomial regression models with Length of stay, Emergency department visits in the preceding 6 months, and either admission or discharge N-Terminal prohormone of Brain Natriuretic Peptide (NT-pro-BNP) as the predictor variables and 30-day all-cause readmission as the outcome. We derived the LENT risk score from the β-coefficients of the regression model (Fig. 1). All the models were adjusted for post-discharge services. We assessed model discrimination with C-statistics and model calibration with the net reclassification index (NRI). We used the bootstrapping approach with 100 runs for internal validation.

Results

The LENT index had a possible score ranging from 1 to 13 (Fig 1). Increments in the LENT risk score were associated with an increased risk of 30-day readmission; a 1-point increase in the LENT index using the admission and discharge NT-pro-BNP predicted a 23% and 19% increase in 30-day readmission risk, respectively. The internal validation produced similar results. Compared to a null model, the LE index had an NRI of 0.35 [95% CI 0.18, 0.53], and admission and discharge NT-pro-BNP further improved calibration of the LE index (NRI 0.15 [95% CI 0, 0.32] and 0.20 [95% CI 0.03, 0.37], respectively). The LENT index offered modest discrimination for 30-day readmission (C-statistic 0.64 [95% CI 0.59, 0.69]), similar to more complex risk models.

Figure 1. The LENT index scoring system

Conclusion

A simple risk index based on Length of stay, Emergent visits, and NT-pro-BNP at the point of care can reliably predict 30-day readmissions. The LENT index offers ease of use over traditional risk prediction models.

Acknowledgement/Funding

Canadian Institutes of Health Research, Ontario MOHLTC, Roche Diagnostics
P6358Novel biomarkers for prediction of acute cardiorenal syndrome
Authors: Dankova M , Minarikova Z , Danko J , Gergel J , Pontuch P , Goncalvesova E
Published: October 2019

Objectives

Acute kidney injury (AKI) is frequent event in patients with acute heart failure (AHF) and is associated with poor short and longterm outcome. Aim of the study was to decribe diagnostic yield of selected novel biomarkers in prediction of AKI in patients addmitted for AHF.

Methods

We performed a prospective cohort study of 72 consecutive patients (46/26 M/F) aged 69±10,3 years admitted for AHF. Renal damage was defined according to KDIGO guidelines. Patients were divided into two groups: AKI- (without renal injury, n=52) and AKI+ (with renal injury, n=20). Urine samples for AKI biomarkers measurements (NGAL, TIMP2, IGFBP7) were collected at admission. The ROC and linear logistic regression of new biomarkers and selected clinical variables was performed for evaluation of the AKI prediction.

Results

Patients with AKI + were older (median age: 75 vs. 64 years, p=0,01), had lower BMI (median: 28 vs. 29,5 kg/m2, p=0,04), were with higher proportion of patients with HF with reduced ejection fraction (55% vs 23,1%, p=0,01) and higher level of serum NTproBNP. Urinary NGAL at admission was significantly higher in the AKI+ compared to AKI – group (152 vs. 19,5 ng/ml, p <.0001); also median of u-TIMP-2 and u-IGFBP-7 in the AKI+ patients were significantly higher: 194,1 versus 42,5 ng/ml (p<0.0001) and 379 versus 92,4 pg/ml (p<0.0001) resp. Age, u-NGAL, u-TIMP2, u-IGFBP7, s-hemoglobin, NTproBNP and LVEF were associated with the development of AKI. Urine concentration IGFBP-7 performs the best for the prediction AKI (AUC 0,94).

Conclusion

Urine concentrations of NGAL, TIMP2, IGFBP7 at the time of admission for AHF predict developement of AKI. Age, NTproBNP, LVEF and s-hemoglobin are also associated with AKI in AHF patients.

Acknowledgement/Funding

Project was supported by Slovak Society of Cardiology research grant 2015-2018.
P6364Challenges of implementation of new European Guidelines 2018 on hypertension in a real clinical practice
Authors: Alieva A S , Konradi A O , Kurapeev D I
Published: October 2019

Objective

Novel European guidelines 2018 on Hypertension raised the question about the implementation of new target blood pressure (BP) levels into real practice. The aim of the present study was to compare achieved target BP levels in clinical practice according to European guidelines 2013 and 2018.

Design and methods

Data of 25428 hypertensive patients form the electronic data base of ambulatory of the Research Centre during 2016–2018 years were analyzed. 8484 hypertensive patients were examined in 2016, 8490 patients – in 2017 and 8454 patients – in 2018 year. Only patients with hypertension as the major disease and on current medication were and under the age of 80 years included.

Results

Applying the Guidelines 2013, 5978 patients (23,5%) were on target and have had BP control under 140/90 mm Hg, while according to new Guidelines 2018 only 1749 patients (6,9%) have achieved recommended BP level under 130/80 mm Hg.

BP control according to both Guidelines Year Sex Age group Number of hypertensive patients BP <140/90 mm Hg BP <130/80 mm Hg 2016 Women Under 50 716 208 (29%) 72 (10,1%) Women 50 and older 4894 1197 (24,5%) 344 (7,0%) Men Under 50 997 252 (25,3%) 57 (5,7%) Men 50 and older 1877 402 (21,4%) 104 (5,5%) 2017 Women Under 50 716 201 (28,1%) 66 (9,2%) Women 50 and older 4734 1049 (22,2%) 325 (6,9%) Men Under 50 1156 266 (23%) 59 (5,1%) Men 50 and older 1884 339 (18%) 84 (4,5%) 2018 Women Under 50 744 224 (30,1%) 87 (11,7%) Women 50 and older 4544 1126 (24,8%) 360 (7,9%) Men Under 50 1364 312 (22,8%) 80 (5,9%) Men 50 and older 1802 402 (22,3%) 111 (6,2%)

Conclusion

According to the previous criteria approximately quarter of all hypertensive patients in real clinical practice in St.Petersburg are on target, while recommended in 2018 Guidelines new target levels are achieved less that in 12%t. Women under 50 have a better BP control. It seems that implementation of new targets for BP will be extremely hard and needs huge investment in education, motivation, compliance and new strategies.
P6366High blood pressure cut-off by 130/80 mmHg in middle-ages may be valid for predicting heart failure in ages of seventies
Authors: Sasaki N , Ozono R , Maeda R , Kihara Y
Published: October 2019

Background

ESC/ESH Guidelines (2018) recommended that treated BP values should be targeted to 130/80 mmHg or lower in most patients. However, it remains unclear whether this target in middle-aged population is associated with future development of heart failure.

Purpose

We conducted a retrospective analysis to determine whether high blood pressure cut-off by 130/80 mmHg in the middle-age predicts the risk of heart failure, detected by high N-terminal pro-brain natriuretic peptide (NT-proBNP) level, in the elderly in a cohort in which longitudinal blood pressure records exist.

Methods

The cohort consists of health check examinee who consulted the examination institute between 2015 and 2018 (n=8513), aged 70 years or older, and had previous institution-visit record at least once from 50 to 69 years old. We measured serum NT-proBNP level in the all examinee and defined the group of high NT-proBNP as ≥144 pg/ml [defined as the highest quartile, n=2135 (25%)]. The number of participants whose previous blood pressure records exists was 8123 (95%) for 65–69 years old, 6980 (82%) for 60–64 years old, 5233 (61%) for 55–59 years old, and 3018 (35%) for 50–54 years old, respectively. The each generation subgroups were divided into the three gradual categories according to the blood pressure records: SBP ≥140 and/or DBP ≥90, SBP130–139 and/or DBP80–89, and SBP <130 and DBP <80 mmHg.

Results

Categorization to high NT-proBNP group in ages of 70 or more was significantly associated with the categorization to high blood pressure, which was not only the SBP ≥140 and/or DBP ≥90 mmHg but also the SBP130–139 and/or DBP80–89 mmHg at any time points of previous blood pressure measurements. The multivariable adjusted odds ratios for having high NT-proBNP level in the elderly against the two high blood pressure categories based on the previous blood pressure measurements were shown in the Table.

Table 1. Multivariable adjusted OR for high NT-proBNP level in elderly Age N SBP 130–139 and/or DBP 80–89 SBP ≥140 and/or DBP ≥90 OR P OR P 65–69 8123 1.30 <0.001 1.68 <0.001 60–64 6980 1.26 0.002 1.55 <0.001 55–59 5233 1.25 0.013 1.41 <0.001 50–54 3018 1.32 0.023 1.58 <0.001 Model included age, gender, BMI, serum creatinine, hemoglobin, and presence of antihypertensive medications, and cardiac disease.

Conclusion

High blood pressure cut-off by 130/80 mmHg in the middle-age may be valid to predict the risk of heart failure in the elderly.