bluuebunny/crossref_metadata_2025 huggingface dataset:
P3496Empagliflozin improves cardiac function through the increased production of acetylcarnitine in a murine non-diabetic heart failure model
Authors: Nakao M , Shimizu I , Yoshida Y , Katsuumi G , Hayashi Y , Ikegami R , Suda M , Wakasugi T , Minamino T
Published: October 2019

Background

Empagliflozin is a renal sodium glucose transporter 2 (SGLT2) inhibitor, thereby mediates its anti-diabetic effect via excretion of glucose into urine. EMPA-REG OUTCOME study, the first big randomized control trial of empagliflozin have shown significant reduction of mortality and hospitalization due to heart failure in diabetic patients. This trial hasn't only had a huge impact to cardiovascular field, but also raised a number of questions about underlying mechanisms. It is also uncertain about the efficacy of empagliflozin in non-diabetic heart failure. In this study, we aimed to elucidate the biological effects and its underling mechanism of empagliflozin in a murine non-diabetic heart failure model.

Methods

We generated a heart failure murine model due to left ventricular (LV) pressure overload by performing transverse aortic constriction (TAC) operation to C57BL/6NCr mice. Two weeks after TAC operation we started empagliflozin administration mixed with diet at the ratio of 0.03% w/w. LV function was measured with echocardiography after administration of empagliflozin for two weeks (four weeks after TAC operation) and compared to a littermate control (no treatment) group. Then, heart samples were collected and subjected to further studies including metabolomic analysis. In-vitro studies including Seahorse Extracellular Flux Analyzer were also conducted with differentiated C2C12 cells and neonatal rat ventricular myocytes (NRVM).

Results

We found that empagliflozin treatment (Empa) significantly ameliorated LV systolic dysfunction induced by TAC compared to control group (Con) (figure.A) while heart weight/body weight ratio wasn't reduced. To explore key metabolites that can contribute to improvement of LV function, we conducted metabolomic analysis and found that empagliflozin significantly increased plasma acetylcarnitine level both in sham and TAC groups (figure.B). Previous studies have shown that acetylcarnitine acts as a substrate of acetyl CoA to fuel tricarboxylic acid cycle, and we tested the efficacy of acetylcarnitine for mitochondrial respiration capacity in differentiated C2C12 cells with Seahorse Extracellular Flux Analyzer. This analysis revealed that administration of acetylcarnitine resulted in a significant increase of oxygen consumption reflected by enhancing mitochondrial respiration. Similary, acetylcarnitine also markedly ameliorated impairment of mitochondrial respiration induced by isoproterenol in NRVM.

Conclusion

Our results indicated that empagliflozin has cardioprotective effect in murine heart failure model by enhancing mitochondrial respiration through the increased production of acetylcarnitine. We provide new evidence that empagliflozin would become a promising therapeutic agent to heart failure without diabetes.
P3500The primary cilium, a sensory apparatus of cells regulates the profibrotic capacity of fibroblasts in atrial fibrillation
Authors: Kawasaki M , Nariswari N A , Van Den Berg N W E , Neefs J , Meulendijks E R , Wesselink R , Baalman S W E , Van Boven W J P , Driessen A H G , De Groot J R
Published: October 2019

Background

Atrial fibrosis is a hallmark of atrial fibrillation (AF) and serves as an important arrhythmogenic substrate. It is formed by fibroblasts in response to tissue dyshomeostasis induced by multiple factors such as ageing, hypertension and inflammation. How fibroblasts phenotypically transform into an active form with enhanced profibrotic capacity in AF pathophysiology remains elusive. The primary cilium is an antenna-like small organelle, that function as a sensor to transduce external stimuli to intracellular signaling thereby potentially mediating the fibroblast's profibrotic capacity. Their involvement in AF pathophysiology is not known.

Objective

To explore the role of fibroblasts' primary cilium in the formation of the atrial fibrosis in AF.

Methods

Left atrial appendages (LAA) were obtained from persistent AF patients (AF: n=10) and patients without AF undergoing cardiac surgery (control: n=10). Primary cilia were immunostained with anti-acetylated a-tubulin in cryosections of the LAA. The loss of cilia in fibroblasts isolated from fresh LAA (AF: n=3, control: n=3) was induced by RNAi targeting IFT88, an essential factor for cilia formation. Gene expression and protein levels in LAA were quantified by qPCR and western blot, respectively (AF: n=20, control: n=20).

Results

The ratio of fibroblasts with primary cilium was significantly decreased in LAA of AF cohort (AF: 14.7%±4.6 vs control: 25.9%±3.6, p<0.01). Correspondingly, the protein levels of acetylated a-tubulin, an exclusive component of cilia, were significantly decreased both in whole LAA and fibroblast fraction of AF cohort compared to control (p<0.05). The loss of primary cilia induced by RNAi in fibroblasts resulted in increased differentiation of fibroblasts into myofibroblasts and the expression of extracellular matrix genes in response to TGF -b1.

Primary cilium is disassembled along with degradation of acetylated a-tubulin by HDAC6. Indeed, a negative correlation between the protein levels of acetylated a-tubulin and HDAC6 were observed in the LAA of AF cohort (p<0.05) but not in control. Furthermore, the gene expression of AURKA and HEF1, upstream activators of HDAC6, was increased by 1.5-fold (p=0.09) and 3-fold (p<0.001), respectively, in the LAA of AF cohort compared to control.

Conclusion

The formation of primary cilia in fibroblasts is actively suppressed in AF via HEF1/AURKA/HDAC6 cascade, which in turn enhances the profibrotic response of fibroblasts. This study provides an innovative paradigm for fibrosis formation in AF, and implicates that the primary cilium of fibroblasts potentially become a novel therapeutic target to treat the AF substrate.
P3510Cardiac function and Ca2+-cycling are different according to the level of cardiac-specific FKBP12.6 overexpression
Authors: Gandon-Renard M , Lefebvre F , Courilleau D , Gomez S , Gomez A M , Mercadier J J
Published: October 2019

Cardiac ryanodine receptors (RyR2) have a key role in excitation-contraction coupling by releasing Ca2+ from sarcoplasmic reticulum (SR). In cardiomyocytes, two FK506 binding protein (FKBP) isoforms have been shown to bind and to stabilize RyR2 opening: FKBP12 and FKBP12.6, the later having a stronger affinity for RyR2 despite its lower abundance. Cardiac-specific FKBP12.6 overexpressing mice have fewer arrhythmias induced by β-adrenergic stimulation than wild type (WT) mice, suggesting an implication of FKBP12.6 in an antiarrhythmic mechanism. Heart failure (HF) syndrome has a high incidence of arrhythmias, which may be explained by a decrease of FKBP isoform expression.

The precise mechanism of the antiarrhythmic effect of FKBP12.6 overexpression remains unknown.

To gain insight into this mechanism, we developed 2 transgenic mouse lines with cardiac-specific moderate- (TG1) and high- (TG2) FKBP12.6 overexpression levels. We characterized cardiac function, [Ca2+]i cycling and its response to β-adrenergic stimulation in both mouse lines.

TG1 and TG2 mice developed mild and marked cardiac hypertrophy, respectively, associated with basal cardiac function increase in TG1 mice only. In stimulated cardiomyocytes, [Ca2+]i transient amplitude, measured by confocal microscopy, was higher in TG1 than in WT mice, without a significant difference in their SR Ca2+ content. The effect of β-adrenergic stimulation (50 nM isoproterenol) was attenuated in TG1 mice compared to WT mice, in association with the prevention of pro-arrhythmogenic Ca2+ release events, such as Ca2+ waves. In contrast, TG2 mice showed [Ca2+]i handling characteristics similar to HF, with slower [Ca2+]i transient relaxation. Interestingly, and contrary to HF, pro-arrhythmogenic Ca2+ release events were also reduced in TG2.

These results indicate that the level of FKBP12.6 overexpression has distinct effects on cardiac function and on Ca2+-cycling and its response to β-adrenergic stimulation.
P3514Gender differences in prognosis for total mortality among patients with ADHF: results of four-year follow-up
Authors: Polyakov D , Fomin I
Published: October 2019

Aim

To obtain information on the effect of various predictors on the prognosis of a patient with acute decompensated heart failure (ADHF).

Methods

We investigated a sample of patients (n=719) hospitalized due to ADHF for 4 years (average observation duration was 2.3 years). 27 predictors were included in the model (clinical conditions and clinical signs of ADHF). We used regression tree method with CHAID algorithm with 10-fold cross-validation to determine the most important predictors of the prognosis.

Results

The most significant predictor for total mortality at the first branching was the gender of the patient. Mortality rate was 65.0% among males vs 47.9% among females (p<0.001). In the subgroup of males, the next most significant predictor for the prognosis was the level of systolic blood pressure (SBP): mortality rates was 79.6% with SBP ≤125 mm Hg vs. 57.2% with SBP >125 mm Hg (p=0.001). In the subgroup of males with SBP >125 mm Hg mortality rates differed depending on the presence of X-ray signs of congestion; when present, the total mortality was 65.7% vs. 47.8 in the absence (p=0.01). In the subgroup of females, the first most significant predictor of prognosis was diabetes mellitus (DM): mortality rates was 60.1% with DM vs. 41.2% without DM (p<0.001). The worst prognosis was found among those who are over 78 years old (55.8%) compared with younger (32.4%, p=0.001) for females with DM.

The model has high sensitivity (74.9%) but low specificity (50.3%). In the ROC analysis, AUC was 0.673 (95% CI: 0.634–0.712).

Regression tree for total mortality rate

Conclusion

The 4-year survival rate for patients with ADHF varies by gender. Among men, the most important predictors of prognosis were the level of SBP and the presence of congestion in the lungs at the hospital admission. Among women, DM and age had the greatest influence on the prognosis.
P3531Continual measurement of arterial dP/dtmax enables mini-invasive monitoring of left ventricular contractility in acute heart failure
Authors: Vondrakova D , Vondrakova D V , Kruger A K , Janotka M J , Neuzil P N , Ostadal P O
Published: October 2019

Introduction

Continuous reliable evaluating of left ventricular (LV) contractile function in patients with advanced heart failure requiring intensive care remains challenging. Recently, continual monitoring of dP/dtmax from arterial line became available for hemodynamic monitoring. However, the relation between arterial dP/dtmax and LV dP/dtmax measurement is not fully understood.

Purpose

The aim of our study was to determine the relation of arterial dP/dtmax and LV dP/dtmax assessed by echocardiography in patients with acute heart failure.

Methods

Forty-eight patients with acute heart failure requiring intensive care and hemodynamic monitoring were recruited into the study (mean age 70.4 years, 65% were males). Hemodynamic variables including arterial dP/dtmax were continually monitored using arterial line pressure waveform analysis. LV dP/dtmax was assessed using continuous-wave Doppler analysis of mitral regurgitation flow.

Results

The values from continual arterial dP/dtmax monitoring significantly correlated with the LV dP/dtmax assessed by echocardiography (r=0.72, 95% confidence interval [CI] 0.54–0.83, P<0.0001). Linear regression revealed that (LV dP/dtmax) = 0.87×(arterial dP/dtmax) + 291, P<0.0001. Arterial dP/dtmax significantly correlated also with the stroke volume (r=0.55, P<0.0001), cardiac output (r=0.32, P=0.0289), mean arterial blood pressure (r=0.43, P=0.0155) and systolic blood pressure (r=0.79, P<0001). On the other hand arterial dP/dtmax did not correlate with the systemic vascular resistance (SVR), heart rate, dynamic arterial elastance, diastolic blood pressure or central venous pressure.

Conclusion

Our results revealed that arterial dP/dtmax values tightly and highly significantly correlate with LV dP/dtmax. Arterial dP/dtmax could be, therefore, used for continual monitoring of LV contractility.

Acknowledgement/Funding

Institutional grant MH CZ - DRO (Na Homolce Hospital- NNH, 00023884), IG150501
P3536Prevalence and clinical impact of social frailty in elderly patients hospitalized for acute decompensated heart failure: a multicenter prospective cohort study
Authors: Hamada T , Kubo T , Nakaoka Y , Kawai K , Yabe T , Furuno T , Kondo F , Yamada E , Yamasaki N , Kitaoka H
Published: October 2019

Purpose

The aim of this study was to investigate clinical characteristics of socially frail patients and an association with social frailty and short-term rehospitalization for worsening heart failure.

Methods

We analyzed 169 elderly patients (≥65 years old) hospitalized for acute decompensated heart failure (ADHF) between June 2017 and August 2018 in our prospective HF registry in Japan. The patients with activities of daily living dependence and without data of social frailty and outcome were excluded. Social frailty was determined based on their responses to the 5 questions (living alone, eating alone, going out less frequently, rarely visiting friends, not helpful to friends or family). Patients with none of these components were considered social non-frailty; those with one component were considered social prefrailty; those with two or more components were considered social frailty. The outcome was rehospitalization for worsening HF within 6 months after discharge.

Results

The mean age was 79±8 years old. Social frailty in 86 patients (50.8%), social prefrailty in 41 patients (24.3%), and social non-frailty in 42 patients (24.9%) were observed. Age, body mass index, geriatrics nutritional risk index, Hasegawa dementia rating scale-revised score, gait speed, and handgrip strength values were significantly different among the these three groups (all Ps for trend <0.01). Left ventricular ejection fraction, brain natriuretic peptide values, and the proportion of the patients with the symptom of New York Heart Association class III/IV did not vary significantly between the groups. Kaplan-Meier analysis revealed that higher prevalence of rehospitalization for worsening HF within 6 months in the social frailty group compared to that in the social non-frailty group (Log-rank p<0.05). In a Cox proportional hazard model after adjusting covariates, patients with social frailty (hazard ratio 4.77; 95% CI 1.61–14.12, p<0.005) and social prefrailty (hazard ratio 3.73; 95% CI 1.12–12.41, p<0.05) had an increased risk of rehospitalization for worsening HF within 6 months compared with those with social non-frailty.

Conclusion

This study revealed that social frailty was common in elderly patients hospitalized for ADHF, and social frailty was an independent predictor of rehospitalization for worsening HF within 6 months after discharge.
P3546EPIT-HF survey of chronic heart failure with preserved, mid-range and reduced ejection fraction. Focus on therapy
Authors: Dubrava J , Sidlo R
Published: October 2019

Background

There is only a limited range of data on comparison of therapy for all three phenotypes of chronic heart failure (HF).

Purpose

In a prospective survey, to determine and compare pharmacological and non-pharmacological treatment for three phenotypes of chronic HF– HF with reduced, mid-range and preserved ejection fraction (HFrEF, HFmrEF and HFpEF).

Methods

The survey was performed by 115 cardiologists and 46 internists. Consecutive outpatients diagnosed with chronic HF aged at least 18 years were enrolled. There were no exclusion criteria. The HF phenotypes were defined according to LVEF: HFrEF – LVEF <40%, HFmrEF – LVEF 40–49%, HFpEF – LVEF ≥50%. A total of 2 677 patients were enrolled. The subgroups of HFrEF, HFmrEF and HFpEF comprised of 1 169 (43.7%), 720 (26.9%) and 788 (29.4%) of patients, respectively.

Results

The pharmacotherapy and electroimpulse therapy was significantly different between the HF phenotypes. The most striking differences were found between HFrEF and HFpEF. Among these phenotypes, there were significant differences in the treatment prevalence across all drug classes, CRT-D, CRT-P and ICD. HFmrEF resembled HFrEF more than HFpEF in terms of pharmacotherapy. The prevalence of therapy for HFmrEF by any drug class, CRT-D, CRT-P and ICD, was always intermediate between HFrEF and HFpEF.

Comparison of therapy HFrEF (1) HFmrEF (2) HFpEF (3) p (n=1169) (n=720) (n=788) Overall 1 vs 2 1 vs 3 2 vs 3 BB 91.9% 90.4% 83.4% <0.001 0.275 <0.001 <0.001 ACEI 77.4% 71.1% 62.9% <0.001 0.003 <0.001 <0.001 ARB 18.7% 23.3% 29.1% <0.001 0.016 <0.001 0.012 ACEI/ARB 92.8% 92.9% 87.7% <0.001 1.0 <0.001 <0.001 MRA 80.1% 55.4% 28.9% <0.001 <0.001 <0.001 <0.001 Ivabradine 39.7% 34.7% 28.1% <0.001 0.032 <0.001 0.005 Furosemide 89.9% 75.0% 54.7% <0.001 <0.001 <0.001 <0.001 CRT-D 8.2% 0.8% 0.4% <0.001 <0.001 <0.001 0.324 ICD 16.2% 2.2% 0.8% <0.001 <0.001 <0.001 0.029 HTx 0.3% 0% 0.6% 0.104 0.304 0.498 0.063 Assist devices 0.3% 0% 0.1% 0.367 0.292 0.653 1.0

Conclusion

We presented the real-world data on pharmacological and non-pharmacological treatment of all three phenotypes of HF. The therapy for HFrEF, HFmrEF and HFpEF differed significantly. Pharmacotherapy for HFmrEF has been more closely related to HFrEF treatment than to HFpEF treatment.

Acknowledgement/Funding

EPIT-HF survey was supported by the educational grant of Servier.
P3549Impact of mitral regurgitation on alveolo-capillar membrane diffusion: an hemodynamic and functional study
Authors: Bandera F , Ghizzardi G , Agnifili M , Pizzocri S , Giammarresi A , Boveri S , Losito M , Labate V , Alfonzetti E , Guazzi M
Published: October 2019

Background

In HFrEF patients, high pulmonary vascular resistances (PVR) reflect a combined increase of pre- and post-capillary pressures, associated with worse outcome. Mitral regurgitation (MR) may play a role in this complex physiopathology. We sought to investigate MR impact on lung DLCO and pulmonary vascular hemodynamic in HFrEF patient.

Methods

22 HFrEF patients (age 67±11; LV EF) underwent right heart catheterization, rest and exercise echocardiography, right ventricle 3D assessment and lung alveolo-capillary membrane DLCO. We identified 2 subgroups according to normal (<3 WU, n=17) or abnormal (>3 WU, n=5) PVR.

Results

Abnormal PVR patients showed increased pulmonary artery pressures and TPG, reduced CO and pulmonary artery compliance. Total DLCO was not significantly different between groups. The membrane component (Dm) and the alveolar volume (Va) were significantly reduced in abnormal PVR group, while the capillary volume (VC) showed a strong trend toward higher values. Abnormal PVR group had a very high percentage of moderate-to-severe MR. The TASPE/SPAP ratio and the circumferential component of RV systolic function were significantly reduced in abnormal PVR group.

Normal PVR (n=17) Abnormal PVR (n=5) p NTproBNP, ng/L 3021±2527 7023±8785 0.55 MR moderate-to-severe, n (%) 3 (19%) 4 (80%) 0.025 TAPSE/SPAP, mm/mmHg 0.4761±0.1695 0.2956±0.0739 0.019 3D RV global EF, % 40.616±9.350 29.486±14.062 0.119 3D RV longitudinal EF, % 15.611±7.773 12.086±9.694 0.497 3D RV circumferential EF, % 31.0567±6.5744 21.1746±11.5823 0.019 Lung diffusion of CO (DLCO), ml/min/mmHg 19.021±4.643 15.233±1.761 0.197 Dm ml/min/mmHg 26.8±8.2 17.8±4.1 0.047 VC, ml 110±77 247±152 0.121

Graphics

Conclusion

The presence of severe MR, in this cohort of HFrEF patients, is associated with alveolar-capillary membrane remodeling (lower Dm), worse hemodynamic profile (higher PA pressures, lower PA compliance and higher PA resistance) and worse right ventricle to pulmonary circulation coupling (lower TAPSE/SPAP and lower 3D RV circumferential EF), confirming the use of therapeutic strategies aimed at correction of valvular disease.
P3555Lower native T1, extracellular volume and T2 on cardiac magnetic resonance imaging is related to more left ventricular reverse remodeling in nonischemic dilated cardiomyopathy
Authors: Oh J , Hong Y J , Ha J , Chun K H , Kim H , Lee C J , Kim Y J , Choi B W , Kang S M
Published: October 2019

Introduction

Guideline-directed medical therapy can induce left ventricular reverse remodeling (LVRR) in nonischemic dilated cardiomyopathy (NIDCM). Some predictors for LVRR have been reported but, there were few studies about the relationship between cardiac magnetic resonance imaging (CMR) parameters and LVRR in NIDCM on optimal GDMT.

Methods

We retrospectively analyzed echocardiogram and CMR data of newly diagnosed 142 NIDCM patients (age: 57±16 years old, 71.8% male) in a single center from Jan 2012 to Dec 2017. NIDCM was defined as left ventricular ejection fraction (LVEF) <45% and the ischemic etiology was excluded by CMR, coronary angiography or coronary CT or SPECT scan. LVRR was defined as improvement in LVEF ≥10% during follow-up period (median 403 days).

Results

Baseline LVEF and LV end diastolic dimension (LVEDD) were 27±8% and 64±8 mm. There were 87 patients (61.3%) of LVRR in our cohort. In LVRR group, native T1 value was significantly lower (1326±66 for LVRR vs 1369±72ms, p<0.001), extracellular volume (ECV) was significantly lower (28.3±3.6 for LVRR vs 32.4±4.4%, p<0.001), and T2 value was significantly lower (49.6±4.6 for LVRR vs 52.1±5.4ms, p=0.004) compared with non-LVRR group. ECV was an independent predictor for LVRR after adjusting current LVRR predictors such as age, sex, LVEF, LVEDD, systolic blood pressure, heart rate and QRS duration (Odd ratio 0.706, 95% confidence interval 0.616–0.809, p<0.001).

Conclusion

Lower native T1, ECV and T2 on CMR is related to higher incidence of LVRR in NIDCM. Further larger prospective study should be warranted to confirm the relationship between CMR parameters and LVRR in NIDCM.
P3557Heart failure patients show increase of white matter lesions in MRI-imaging: LIFE-Adult-Study
Authors: Stegmann T , Chu M L , Villringer A , Laufs U , Loeffler M , Zeynalova S , Wachter R
Published: October 2019

Background

Heart Failure (HF) is a risk factor for stroke and dementia and is associated with cognitive impairment. However, whether or not HF is directly linked to structural brain changes is unknown. White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischemia and cognitive dysfunction. However, there are only a few reports on HF and WML.

Purpose

We hypothesized that the presence and duration of heart failure are associated with WML.

Methods

LIFE Adult is a population-based study whose participants are a representative sample of the city of Leipzig, Germany (approximately 580,000 inhabitants). All study participants (18–80 years of age) underwent an extensive core assessment program (5–6 h) including structured medical interviews, medical and psychological questionnaires, physical examination and bio specimen collection. A subgroup of 2490 participants additionally underwent cerebral MRI (cMRI). The Fazekas Score was used for the classification of the WML (none or mild WML versus moderate or severe WML). Raters were blinded to other medical information of study participants. History of HF and other diseases were ascertained as part of the self-reported medical history questionnaire.

Results

Mean age was 64 years and 46% were female. On univariate analysis age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF and diabetes were positively associated with WML. On multivariate analysis, only age, hypertension, stroke and HF were associated with WML. Interestingly, the Odd's ratio (OR) for HF was 2.5 (95% confidence interval (CI) 1.1; 5.6) and numerically higher than the OR for stroke (OR 2.0 (95% CI 1.0; 3.8)). Additionally, the OR increased with longer duration of HF (OR 1.3 for HF-duration <3 years, OR 1.7 for HF 4–6 years duration and OR 2.9 for HF-diagnosis >6 years).

Conclusion

HF is independently associated with structural brain damage, i. e. WML. Future research is needed to elaborate whether WML could be a therapeutic target for treatment targeting cognitive decline in HF.
P3568The relationship between plasma renin and aldosterone levels and the reduction of blood pressure with spironolactone in patients with resistant hypertension
Authors: Obertynska O
Published: October 2019

The group of patients with resistant hypertension (RH) is not homogeneous on concentration of renin and aldosterone (AS). A lot of studies have shown that spironolactone (SP) was by far the most effective blood pressure-lowering treatment for patients with RH. However, it has been unknown whether SP would be the most effective in patients with different plasma renin profile.

The aim was to determine whether plasma renin and AS predict the most effective treatment of SP.

Methods

79 patients with RH were included in the study (a mean of 3.4±1.4 drugs per patient including diuretic, ACE-I or an ARB). The plasma AS and active renin concentration (ARC), the plasma aldosterone-to-renin ratio (ARR) were estimated at baseline. After chemical evaluation patients started on SP treatment with a mid-dose 25 mg daily (range 12.5–50 mg). At baseline and after 12 weeks of therapy patients underwent clinic and 24-hour BP measurement, also hematocrit, potassium (K), serum creatinine (C), eGFR were checked.

Results

In patients with RH the ARC varied widely and they were divided into low 46%, normal 29% and high renin 25% subgroups. All groups of patients had similar AS levels. Patients with high renin hypertension (HRH) had significantly worse renal function than patients with low renin (LRH) or normal renin hypertension (NRH), also hematocrit were significantly higher in HRH patients than in patients with LRH and NRH. At baseline in patients with RH was an excellent correlation between ARC and eGFR (P<0.001). After SP in whole group, the change from baseline in the clinic BP was −13.4/−6.8 mm Hg (P<0.0001 for both) and in 24-hour BP was −10.6/−6.1 mm Hg (P<0.001 for both), but patients with HRH showed less efficacy than patients with LRH and NRH (−5.4/−3.1 mm Hg; P<0.05 for both) and in 24-hour BP was −4.8/−2.9 mm Hg (P<0.05 for both). Moreover, in HRH patients the hematocrit and C levels increased significantly after the start of SP (P<0.001; P<0.0001 respectively). By regression analysis in whole group patients RH ARC and AS levels were not associated with the changes in BP, only eGFR was significantly associated with BP change for DBP (0.391, P<0.05); in patients with LRH and NRH was a mild relation between the change for SBP and ARR (P<0.05 for both), but not for HRH patients.

Conclusion

SP showed additional antihypertensive effect in the whole group of patients with RH, but in patients with HRH was less effective than in patients with LRH and NRH and lead to the worsening of renal function. In the whole group of patients with RH plasma renin and aldosterone levels were not associated with BP response to SP, but the change in DBP was correlated with baseline eGFR. Only in patients with LRH and NRH was a mild association between BP response to SP and ARR. So, we can't treat all RH patients with the help of one universal algorytm and treatment should be tailored to each patient according to neurohumoral profile and renal function.
P3569The effect of percutaneous renal revascularization upon cardiac structure and function in patients with significant atherosclerotic renal artery stenosis
Authors: Geavlete D O , Beladan C , Deleanu D , Zaharia M R , Tautu O , Popescu B A , Ginghina C , Chioncel O
Published: October 2019

Introduction

Different consequences concerning the cardiac function and structure in patients with renal artery stenosis (RAS) and completely different patterns of activation of the renin-angiotensin-aldosteron system were reported, depending on RAS severity. These changes might have an impact upon the outcomes after renal revascularization.

Purpose

The study was aimed to analyze the effect of renal stenting upon echocardiographic parameters of cardiac structure and function in the studied population and by comparison between 3 different RAS-profile patients.

Methods

A total of 78 hypertensive patients diagnosed by renal angiography with significant RAS (>70%) were prospectively enrolled, thus subsequently resulting in 3 groups (34-unilateral RAS, 28-bilateral RAS, 14-RAS in a solitary kidney). Clinical, laboratory and echocardiographic parameters (left ventricular (LV) dimensions, LV mass index (LVMI), relative wall thickness (RWT), type of cardiac geometry, systolic and diastolic function, LV filling pressures) were assessed before renal stenting and 12 months after the procedure. The evolution of renal function was based on the glomerular filtration rate (eGFRCKD-EPI). Blood pressure evolution after revascularization was defined as cured, controlled, improved or stationary.

Results

Similar baseline characteristics were found for the 3 study groups regarding demographics, cardiovascular risk factors, baseline LV diameters, RWT and LVMI (p>0.05), although higher values of echocardiographic parameters were observed in solitary kidney RAS patients. Only 9.6% of all cases had normal geometry, the majority of the patients presenting concentric hypertrophy (58.9%) of similar proportions in the defined groups. Analyzing variations of echocardiographic parameters before and 12 months after stenting confirmed significant changes in all structural parameters (LV walls dimensions, LVMI, RWT, p<0.05), with significant differences between the 3 study groups. The most favorable evolution after revascularization was observed in bilateral-RAS patients (significant decreased cardiac mass, p=0.018), while RAS in a solitary kidney was associated with non-significant changes of the analyzed parameters. The evaluation of cardiac geometry evolution 12 month after renal stenting showed a stationary cardiac remodeling profile (p>0.05).

Conclusions

The current analysis showed favorable outcomes after renal angioplasty with stent in RAS patients with regard to structural changes of the LV (regression of LVMI, RWT). However, the impact of these beneficial changes did not have the magnitude for producing a significant effect upon cardiac geometry one year after renal revascularization.
P3570Bilateral renal artery stenting is effective method for the treatment of uncontrolled hypertension and renal function
Authors: Uzokov J , Alyavi A L , Alyavi B A , Iskhakov S A , Payziev D D
Published: October 2019

Background

Renal artery (RA) stenosis is one of the main causes of severe uncontrolled primary hypertension among population. Aim of the study was to investigate effectiveness of stent replacement in renal arteries and influence it on renal function in uncontrolled hypertensive patients (UHP) with pharmacotherapies.

Methods

86 consecutive UHP with renal etiology confirmed by angiography were enrolled in this study. Mean age of the patients was 43.2±12.5 years (aged 31–59 years, male=46%). Blood pressure, serum creatinine, microalbuminuria were assessed at baseline and after the intervention and during the follow-up for statistics. Mean follow-up was 2.0±1.0 years.

Results

Total of 128 hemodynamically significant renal artery stenosis were treated by implanting stents in all 86 patients. Among them in 42 patients were performed bilateral stenting (Group I) and 44 patients unilateral stenting (Group II). Systolic and diastolic blood pressure (SBP, DBP) decreased in both groups during the follow-up, however it was noted that only SBP were decreased significantly in Group I (unilateral stenting) whilst reduction in DBP not significantly when compared to Group II. Mean reduction in SBP was from 165.0±20.5 mmHg to 130.4±14.0 mmHg in Group I vs. from 158.0±22.0 to 135.0±15.0 mmHg in Group II (P=0.003 when compared two groups) and in DBP was from 95.0±11.2 mmHg to 83.4±8.0 mmHg in Group I vs. from 93.0±10.0 to 82.0±7.5 mmHg in Group II (P>0.05 when compared two groups). Serum creatinine levels were reduced from 123.0±49.0 μmol/l to 85.4±30.6 μmol/l in Group I vs 116.8±51.2 μmol/l to 86.9±35.5 μmol/l (P<0.05 when compared two groups). Significantly reduction in MAU were noted in both groups (P<0.05) but when compared two groups there were no significant changes in reduction.

Conclusion

Renal artery stenting is effective method for the treatment of UHP and may improve outcomes of the patients. Bilateral stenting seems to be more effective in blood pressure and serum creatinine control in UHP.
P3585Prognostic value of the assessment of coronary sinus flow by phase contrast cine-magnetic resonance imaging in patients with acute coronary syndrome
Authors: Kanaji Y , Sugiyama T , Hoshino M , Hirano H , Horie T , Yuki H , Kanno Y , Ohya H , Sumino Y , Hada M , Yamaguchi M , Yonetsu T , Kakuta T
Published: October 2019

Background

Phase contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying global coronary sinus flow (CSF) and global coronary flow reserve (G-CFR) without the need for ionizing radiation, radioactive tracers, or intravascular catheterization.

Purpose

We evaluated the prognostic value of G-CFR by quantifying CSF using PC-CMR in patients with ACS treated with primary or emergent percutaneous coronary intervention (PCI).

Methods

The study prospectively enrolled 387 ACS patients who underwent uncomplicated primary or emergent PCI within 48 hours of symptom onset. Breath-hold PC-CMR images of CS were acquired to assess absolute CSF at rest and during maximum hyperemia within 30 days after primary PCI and revascularization of functionally significant non-culprit lesions of ACS. The association of G-CFR and baseline clinical characteristics with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for congestive heart failure) was investigated.

Results

In the final analysis of 366 patients (Male 294 (80.3%), mean age 65) including 233 patients (63.7%) with ST-segment elevation myocardial infarction (STEMI) and 133 patients (36.3%) with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), rest and maximal hyperemic CSF and corrected G-CFR were 1.24 [0.83, 1.71] ml/min/g, 2.56 [1.87, 3.66] ml/min/g, and 2.20 [1.53, 3.17], respectively. During a median follow-up of 16 months, MACE occurred in 84 patients (cardiac death: 9, nonfatal myocardial infarction: 11, late revascularization: 59, hospitalization for congestive heart failure: 5). Cardiac event-free survival was significantly worse in patients with a corrected G-CFR <2.00 (log-rank χ2=20.2, P<0.001). Cox proportional hazards analysis showed that corrected G-CFR were independent predictors of adverse cardiac events during follow-up in patients with STEMI (hazard ratio, 0.66, 95% confidence interval, 0.51–0.85, p=0.001) and NSTE-ACS (hazard ratio, 0.64, 95% confidence interval, 0.43–0.95, p=0.026), respectively.

Conclusions

In ACS patients successfully revascularized within 48 hours of onset, G-CFR obtained by noninvasive PC-CMR provided significant prognostic information independent of infarction size and conventional risk scores.
P3587Tip detection method using the new short-tip IVUS with pull-back system which facilitates the 3D wiring technique in percutaneous coronary intervention for chronic total occlusion
Authors: Tanaka K , Okamura A , Iwakura M , Nagai H , Sumiyoshi A , Okada M , Inoue H , Takayasu K , Inoue K , Koyama Y , Iwakura K , Fujii K
Published: October 2019

Background

The strategy of intravascular ultrasound (IVUS)-guided wiring for CTO PCI, that is, leading the second guidewire into the true lumen under observing by IVUS from subintimal space, is the last resort. We developed the angiography-based 3D wiring method. During establishment of the angiography-based 3D wiring method, we deduced that observation of the guidewire tip as well as the shaft named “The tip detection method” simplifies and facilitates 3D wiring under IVUS-guided wiring. Therefore, we produced New CTO IVUS which is the upgraded version of Navifocus WR IVUS by adding the pull-back transducer system. This pull-back system enables us to detect the tip as well as the shaft of the second guidewire in real time (tip detection method), which facilitates the 3D wiring technique under IVUS-guided wiring.

Objective

We evaluated the efficacy of the tip detection method during 3D wiring for CTO PCI with New CTO IVUS.

Method

We created a target pinpoint penetration model and performed the procedures using an experimental heartbeat model. The target (a tube with a lumen 0.6 mm in diameter) was placed in the distal part of a CTO 20 mm in length made of 2.5% agar. After the second guidewire (Conquest-12g) was advanced into the CTO lesion to within 5mm of the target using the angiography-based wiring, IVUS-guided wiring was performed by using Navifocus WR or New CTO IVUS each five times.

Result

The frequency of the puncture time was reduced using the new CTO IVUS compared to the Navifocus WR (1.7±0.8 vs. 28.8±23.2, p=0.17). The procedure time was significantly shorter using the new CTO IVUS compared to the Navifocus WR (103±61 vs. 459±373 seconds, p=0.04).

Conclusion

The tip detection method during 3D wiring with the new short tip IVUS with the pull-back system enables us to easily perform 3D wiring and will change the CTO PCI strategy.
P3598Cardiac Cycle - The effect of exercise on cardiac troponin release
Authors: Marshall L , Lee K , Strachan F E , Fujisawa T , Stewart S , Dhaun N , Ferry A , Ross M , Mills N L
Published: October 2019

Introduction

International guidelines recommend the use of low concentrations of high-sensitivity cardiac troponin to risk stratify patients with suspected acute coronary syndrome, however, troponin concentration may also rise due to physical exercise. Interpreting cardiac troponin concentration in this context is challenging because the magnitude and duration of troponin elevation following physical exercise is uncertain.

Purpose

To determine the effect of intensity and duration of physical exercise on cardiac troponin concentration.

Methods

We invited 10 physically active healthy volunteers (7 male and 3 female; mean age: 34±7) to attend 3 study visits, during which they underwent exercise on a stationary bicycle at prespecified intensities and durations. The first visit involved low intensity cycling (50–60% of the participant's lactate threshold [LT]) for 60 minutes. During the second visit, participants cycled at high intensity (80–90% LT) for 60 minutes and during the third study visit, participants cycled at moderate intensity (60–70% LT) for 4 hours. High-sensitivity cardiac troponin I (hs-cTnI) concentration was measured at the start of exercise and every hour up to 6 hours during each study visit and subsequently at 1, 2 and 7 days after each exercise visit.

Results

Study participants had a median hs-cTnI concentration of 1.8 ng/L (interquartile range [IQR] 0.8–5.7 ng/L) at baseline. Cardiac troponin concentration was elevated following moderate- and high-intensity exercise (P=0.006 and P<0.001, respectively) but not following low-intensity exercise (P=0.137). Troponin concentrations were significantly higher following the shorter duration of high-intensity exercise (peak hs-cTnI concentration = 13 ng/L [IQR 6.5–27.1 ng/L]) compared to the longer duration moderate-intensity exercise (peak hs-cTnI concentration = 6.9 ng/L [2.9–7.9 ng/L]; P-value <0.001). Following both moderate- and high-intensity exercise, cardiac troponin concentration returned to baseline within 48 hours (Figure 1).

Troponin concentrations ng/L / time

Conclusions

Our study suggests that elevation in cardiac troponin concentration is associated with the intensity rather than duration of physical exercise, and that exercise-induced troponin elevations resolve within 48 hours. These findings have important implications for the interpretation of cardiac troponin in the risk stratification and diagnosis of patients who present with symptoms suggestive of acute coronary syndrome following physical exercise.

Acknowledgement/Funding

British Heart Foundation
P3599Minicare high sensitivity troponin: a novel point-of-care tool to improve ACS workflows
Authors: De Theije F , Van Reenen A , Peeters E , Meijering B , Van Damme H , Van Der Lugt A , Jacobs M , Nieuwenhuis J
Published: October 2019

Background

Cardiac troponin (cTn) has been broadly accepted as the biomarker of choice in the diagnosis of patients presenting with Acute Coronary Syndrome (ACS). Point-of-care (POC) cTn testing, defined as testing near the patient with rapid availability of results, has attracted a strong interest in the emergency department (ED) setting. It offers the potential to improve workflows, expedite clinical decisions and to reduce the length of stay. Workflows could be further optimized when a first measurement can already be performed by the emergency medical services prior to admission to the hospital.

Advances in assay technology have led to high sensitive (HS) cTn assays that have a profound impact on clinical practice, providing early results at presentation and 1 hour after admission which speed up clinical decision-making. Here we evaluate the Minicare HS cTnI POC test under development, which has the potential to combine the benefits of HS-cTnI protocols with a POC workflow.

Objective

Evaluate the analytical and clinical capability of the Minicare HS-cTnI test under development to meet the criteria‡ for HS cTn of having a 10% CV <99th percentile and a percentage measurable (>LoD) of >50%.

Methods

The evaluation is based on the Clinical Laboratory Standards Institute (CLSI) guidelines. Li-heparin whole blood and Li-heparin plasma samples were used to establish LoB, LoD, and LoQ, sample matrix comparison and linearity in the low range. The clinical performance for Minicare HS-cTnI was assessed and compared to Abbott Architect high-sensitivity troponin using banked samples from patients with ACS and collected at t=2–4h after admission. The percentage measurable was assessed and compared to Abbott Architect high-sensitivity troponin in a healthy population of 165 individuals.

Results

With a time to result within 10 minutes, the LoB is determined at 1.0 ng/L and the LoD at 2.1 ng/L. Plasma and whole blood results correlated well and showed comparable results. The 10% and 20% CV LoQ are established at 7.9 ng/L and 3.1 ng/L, well below the anticipated 99th percentile of 26 ng/L. With a percentage measurable of 77%, the criteria for a HS-cTnI assay are met in a POC device. A sensitivity of 93% and an NPV of 99% are found for Minicare HS-cTnI for a t=2–4h protocol vs 90% and 98% for Abbott Architect high-sensitivity troponin. In this study the area under the curve is 0.98 for Minicare HS-cTnI and 0.97 for Architect HS-cTnI.

ROC curve t=2-4 h

Conclusions

With HS-cTnI capability on the Minicare platform, we show the potential to support a 0/1 h sampling protocol, combined with the speed of a POC workflow. This may enable even more rapid and safe rule-out of patients with ACS.
P3632Prognostic impact of aortic valve stenosis in patients with acute myocardial infarction
Authors: Mizutani H , Kurita T , Kasuya S , Mori T , Ito H , Tanimura M , Ichikawa K , Goto I , Masuda J , Sawai T , Ito M , Dohi K
Published: October 2019

Background

Aortic valve stenosis (AS) is associated with the presence and severity of coronary artery disease independently of clinical risk factors, which leads to increased cardiovascular mortality. However, the prevalence of AS and its prognostic value among patients with acute myocardial infarction (AMI) remain unknown.

Purpose

The purpose of this study was to investigate the prevalence and prognostic impact of AS in AMI patients.

Methods

We studied 2,803 AMI patients using data from Mie ACS registry, a prospective and multicenter registry. Patients were divided into subgroups according to the presence and severity of AS based on maximal aortic flow rate by Doppler echocardiography before hospital discharge: non-AS <2.0 m/s, 2.0 m/s≤mild AS <3.0 m/s, 3.0 m/s≤moderate AS <4.0m/s and severe AS≥4.0 m/s. The primary outcome was defined as 2-year all-cause mortality.

Results

AS was detected in 79 patients (2.8%) including 49 mild AS, 23 moderate AS and 6 severe AS. AS patients were significantly older (79.9±9.8 versus 68.3±12.6 years), and higher killip classification than non-AS patients (P<0.01, respectively). However, left ventricular ejection fraction, and prevalence of primary PCI was similar between the 2 groups. During the follow-up periods (median 725 days), 333 (11.9%) patients experienced all-cause death. AS patients demonstrated the higher all-cause mortality rate compared to that of non-AS patients during follow up (47.3% versus 11.3%, P<0.0001, chi square). Kaplan-Meier curves showed that the probability of all-cause mortality was significantly higher among AS patients than non-AS patients, and was highest among moderate and severe AS (See figure A and B). Cox regression analyses for all-cause mortality demonstrated that the severity of AS was the strongest and independent poor prognostic factor (HR 1.71, 95% CI 1.30–2.24, P<0.001, See table).

Cox hazard regression analysis Hazard ratio 95% Confidential interval P-value Severity of aortic valve stenosis 1.71 1.30–2.24 <0.001 Killip classification 1.63 1.46–1.82 <0.001 Age 1.07 1.06–1.09 <0.001 Serum creatinine level 1.05 1.03–1.08 <0.001 Max CPK level 1.00 1.00–1.01 <0.001 Left ventricular ejection fraction 0.96 0.95–0.97 <0.001 Primary percutaneous coronary intervention 0.67 0.47–0.96 0.03 CPK suggests creatinine phosphokinase.

All cause mortality

Conclusions

The presence of AS of any severity contributes to worsening of patients' prognosis following AMI independently of other known risk factors.

Acknowledgement/Funding

None
P3634Cancer patients have a higher long-term risk of death and myocardial infarction after percutaneous coronary intervention - A matched cohort analysis of 3,560 patients
Authors: Guo W , Lewis B , Johnson M , Lerman A , Herrmann J
Published: October 2019

Background

Cancer patients have a higher risk of thromboembolic events but it is not well known if these patients also have a higher risk of death, myocardial infarction (MI) or repeat revascularization after percutaneous coronary intervention (PCI) is unknown.

Methods

Cancer patients who underwent first-time single vessel PCI from January 1, 2003, through December 31, 2013 were identified by cross-matching of institutional cancer and PCI registries. These cancer patients were matched 4:1 to non-cancer patients, likewise undergoing first-time single vessel PCI in the time period. The combined primary endpoint was death, MI and revascularization at 5 year follow-up. Secondary endpoints were death and MI combined and the individual components of the primary endpoint. Both time dependent and non-time-dependent analyses were conducted.

Results

A total of 712 cancer patients were identified and matched to 2,848 non-cancer patients (one third women in either group). Bare-metal stents were used in one third of patients in both groups. The combined primary study endpoint was significantly more frequently encountered in the cancer than in the non-cancer group in both time-dependent (Figure 1) and non-time dependent analyses (5-year event rate 48.6% vs. 31.2%, p<0.001). This was driven by a higher 5-year event rate of death (39.0% vs. 20.1%) and MI (14.8% vs 4.86%) in the cancer group. The 5-year rate of revascularization did not differ significantly between the two groups (10.5% vs 10.3%).

Figure 1. MI + revascularization-survival

Conclusion

Cancer patients have a two times higher rate of death and a three times higher rate of MI over the first 5 years after PCI. Future studies will need to define the etiology and factors accounting for this higher event rate in cancer patients, especially of these patients are predisposed to stent thrombosis and need longer term dual antiplatelet therapy.