bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4552The prognostic impact of worsening and improved renal function in acute decompensated heart failure with and without plasma volume expansion
Authors: Kawai T , Yamada T , Morita T , Furukawa Y , Tamaki S , Iwasaki Y , Kawasaki M , Kikuchi A , Seo M , Fukunami M 
Published: October 2019

Abstract

Background
Recent studies showed that both worsening renal function (WRF) and improved renal function (IRF) during hospitalization are associated with poor prognosis in patients with acute decompensate heart failure (ADHF). On the other hand, plasma volume (PV) expansion plays an essential role in ADHF. However, there is little information about the difference of prognostic impact of WRF and IRF in ADHF patients, relating to PV status (PVS).

Methods
We prospectively studied 348 patients admitted for ADHF. PVS was defined as follows: actual PV = (1 - hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females); and PVS = [(actual PV - ideal PV)/ideal PV] × 100 (%). WRF and IRF were defined as an increase and a decrease in serum creatinine of ≥0.3 mg/dl from admission to discharge, respectively. The endpoint was readmission for worsening heart failure (WHF) within 1 year.

Result
Median PVS was 6.7% (IQR: −4.1%–16.7%). 43 and 21 patients had WHF in groups with high PVS (PVS ≥ median) and low PVS (PVS > median), respectively. In high PVS group, multivariate Cox analysis showed that IRF was independently and significantly associated with WHF (p=0.016, HR: 2.4 [1.2–4.8]), but WRF was not (p=0.55, HR: 0.7 [0.3–2.1]). On the other hand, in low PVS group, WRF was independently associated with WHF (p=0.035, HR: 3.0 [1.1–8.1]), but IRF was not (p=0.27, HR: 2.1 [0.6–8.0]). Kaplan-Meier analysis revealed that only patients with IRF had a significantly higher risk of WHF than those with stable renal function (SRF) in high PVS group, while patients with WRF had a significantly higher risk of WHF than those with SRF in low PVS group.
Worsening heart failure-free rate curves

Conclusion
In ADHF patients with PV expansion, IRF during hospitalization could predict poor outcomes, but WRF could not. On the other hand, in ADHF patients without PV expansion, not IRF but WRF could predict poor outcomes. PVS guided-therapy may be considered in secondary prevention for WHF.
P4554Central-acting aminopeptidase a inhibitors for new treatment of hypertension: from discovery to clinical trial
Authors: Llorens-Cortes C , Marc Y , Hmazzou R , Keck M , Flahault A , Roques B P , Balavoine F , Azizi M 
Published: October 2019

Abstract

The hyperactivity of the brain renin–angiotensin system (RAS) has been implicated in the development and maintenance of arterial hypertension (HTA).
Our aim was to demonstrate that normalizing brain RAS hyperactivity could constitute a new therapeutic approach for HTA treatment
We first demonstrated in the brain that aminopeptidase A (APA) is the enzyme generating angiotensin III (AngIII) from AngII. Then, using the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), we showed that AngIII is one of the main effector peptides of the brain RAS, exerting a tonic stimulatory control over blood pressure (BP) in hypertensive rats. This suggests that brain APA may be a potential therapeutic target for HTA treatment. We then designed RB150 {4,4-dithio[bis(3-aminobutyl sulfonic acid)]}, an orally active prodrug of EC33. RB150, given orally in conscious deoxycorticosterone acetate-salt (DOCA-salt) rats or spontaneously hypertensive rats, crosses the intestinal, hepatic and blood-brain barriers, enters the brain, where it is cleaved by brain reductases, generating two active molecules of EC33 which inhibit brain APA activity, block the formation of brain AngIII and induce a marked and sustained decrease in BP. The RB150-induced BP decrease is due to a reduced vasopressin release, which increases diuresis, reducing extracellular volume, a decrease in sympathetic tone, leading to a reduction of vascular resistances and the improvement of the baroreflex function (Figure below). RB150 was renamed firibastat by OMS. Phase Ia/Ib clinical trials showed that firibastat is clinically and biologically well-tolerated in healthy volunteers.

Firibastat could constitute the first drug candidate of a new class of antihypertensive agents targeting the brain RAS, the clinical efficacy of which (Phase IIa and Phase IIb) in hypertensive patients was achieved.

Acknowledgement/Funding
INSERM, College de France, ANR LabCom, Quantum Genomics
P4558Hemodynamic management of resistant hypertension
Authors: Chacon-Lozsan F J , Rojas R , Rodriguez M 
Published: October 2019

Abstract

Background
Hypertension is the most prevalent chronic disease worldwide and is is related with high probability of cardiac disease, kidney disease and cerebrovascular events. Blood pressure measurement was used in the last decades to diagnose and guide antihypertensive therapy; however blood pressure is the result of interaction of more complex hemodynamic parameters previously reserved to experimental studies or critical care patients management using invasive methods. Since 1996 few studies has proposed the use of hemodynamic parameters to classify and guide hypertension therapy with good results.

Purpose
The present study purpose was to measure hemodynamic parameters in patients with non-controlled resistant hypertension and use it to guide pharmacologic treatment in order to archive control blood pressure values according to the European Society of Cardiology guidelines.

Methods
A total of 84 patients between 32 and 95 years old diagnosed with non-controlled primary resistant hypertension were recruited and after previous therapy washout hemodynamic parameters were measured using noninvasive methods: preload by central venous pressure (CVP) using inferior vena cava diameter, cardiac index and systemic vascular resistance using Lyljestrand & Zander modified formula. Patients were classified in 3 basic groups depending on which parameter was above normal value: hyperdynamic (HD) for high cardiac index >3.5 L/min/m2, fluid overload (FO) for CVP >8cmH2O and high systemic vascular resistance index (HSVRi) >2500 dynes/sec/m2/cm–5, also 3 combined groups were a patient had 2 simultaneous hemodynamic alterations (HD+FO, HD+HSVRi and FO+HSRVi), according to this classification pharmacotherapy was guided indicating Bisoprolol in HD group, Amlodipine to HSVR patients and Hydrochlorothiazide to FO patients, in combined groups, combined therapy was given. Patients were observed for 6 months period taking as primary endpoint blood pressure control, acute cardiovascular events and hypotension.

Results
A significant reduction of hemodynamic parameters and blood pressure was observed since the first month of treatment obtaining a 100% hemodynamic and blood pressure goals in all patients at the third month of therapy without hypotension or acute cardiovascular event during this period, the HD+FO group reach goals at the 6th month of treatment without reported complications.

Conclusions
In this preliminary studied we observed that hemodynamic guided high blood pressure control may be a useful tool to a better understanding, classifications and treatment in patients with resistant hypertension; however a larger outcome studies to confirm this hypothesis.
P4562Bilateral sphenopalatine ganglion block reduces blood pressure in never treated hypertensive patients. A randomized controlled study
Authors: Triantafyllidi H , Arvaniti C , Schoinas A , Benas D , Voutsinos D , Ikonomidis I 
Published: October 2019

Abstract

Background
Sphenopalatine ganglion (SPG) area is connected through sympathetic fibers with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension.

Methods
We performed bilateral SPG block with lidocaine 2% in 53 newly diagnosed and never treated hypertensive patients (study group, mean age 49+12 years, 38 men) and a sham operation with water for injection in 11 patients (control group, mean age 51+12 years, 8 men). All patients have been subjected to 24 hour ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters derived from ABPM (blood pressure, heart rate, blood pressure load and variability). We defined as responders to SBG block those patients with a 24h average SBP decrease >5 mmHg.

Results
In the study group, a month after SPG block: a. 24h average SBP and DBP were reduced by 1.3+7mmHg and 1.8+5 mmHg, respectively, and b. 24h average DBP (p=0.03), daytime DBP (p=0.01) and daytime DBP load (p=0.01) were significantly decreased. Interestingly, in the responders group (14/42, 33%) a month after SPG block: a. 24h average SBP and DBP were reduced by 9+4mmHg and 6.5+3 mmHg, respectively, b. SBP and DBP were decreased during overall 24h and daytime (p<0.001) and night-time periods (p=0.002 and p=0.02, respectively) and c. SBP load was decreased during daytime and night-time while DBP load was decreased during daytime (p<0.001). As it was expected, no differences regarding BP were found in the sham operation group.
BP decrease after SPG block

Conclusions
We have proved that the minimally invasive option of the SPG block leads to blood pressure decrease, probably through SNS modulation. Moreover, due to its short-term anesthetic effect, SPG block might act as a method of selection of those hypertensives with an activated SNS before any other invasive procedure.
P4580The effect of anesthetic techniques on cardiac troponin-T after non-cardiac surgery
Authors: Oh E , Kwon J , Park J , Min J , Lee J 
Published: October 2019

Abstract

Background
The effects of anesthetics on cardiac protection and clinical outcomes have shown conflicting results in patients undergoing non-cardiac surgery. Unlike cardiac surgeries in which cardio-protective effects of anesthetic techniques have been reported, it lacks evidence and reproducibility in non-cardiac surgery. A current generation high-sensitivity cardiac troponin (hs-cTnI) is known to detect perioperative myocardial injury in non-cardiac surgery which is closely related to clinical outcomes. In this study, we hypothesized that balanced anesthesia using both remifentanil and volatile agents is the most effective in reducing postoperative myocardial injury, and compared the incidence of postoperative myocardial injury among different types of general anesthesia.

Methods
We analyzed the data of 3555 patients who underwent general anesthesia for non-cardiac surgery in our hospital between February 2010 and December 2016. In all patients, hs-cTnI was detected in preoperative period and postoperative period within 48 hours. Major exclusion criteria was troponin elevation before surgery. Patients were stratified into three groups; 661 patients who were received propofol-remifentanil total intravenous anesthesia (TIVA group), 1279 patients who were received volatile anesthesia without remifentanil (Volatile group) and 1622 patients who were received volatile anesthesia with remifentanil (Balanced group). The Primary outcome was troponin elevation [hs-cTnI≥0.04 ng/mL] within post-operative within 48 hours, and the incidence of postoperative complications such as postoperative acute kidney injury, new-onset atrial fibrillation and in-hospital mortality were also compared.

Results
The occurrence of myocaridial injury were significant difference between three groups. The occurrence of myocardial injury was significantly lower in the Balanced group than in Volatile group after adjustment (Odds ratio (OR) = 0.727; 95% confidence interval (CI) = 0.59–0.89; P-value = 0.002). Balanced group and TIVA group showed comparable results in risk of postoperative troponin elevation after adjustment (OR 1.131; 95% CI 0.96–1.33; P-value = 0.133). The incidence of troponin elevation was significantly higher in Volatile group than TIVA group after adjustment (OR 1.6; 95% CI 0.52–0.96; P-value = 0.005). The incidence of AKI was significantly lower in Balanced group than Volatile group after adjustment (OR 0.637; 95% CI 0.49–0.81; P-value <0.001).

Conclusion
The remifentanil combination during general anesthesia may be associated with myocardial protection effect in patients undergoing non-cardiac surgery. Whether this impact leads to adverse long-term outcome remains unclear, and requires further investigation.
P45945-years clinical outcomes of patients underwent percutaneous coronary intervention for calcified lesions with rotational atherectomy and second-generation drug eluting stent
Authors: Ogata K , Koiwaya H , Shinzato K , Goriki Y , Yoshioka G , Shibata Y 
Published: October 2019

Abstract

Background
Percutaneous coronary Intervention (PCI) with rotational atherectomy (RA) was useful for severe calcified lesions. However, the long-term clinical outcomes of PCI with second-generation drug eluting stent (DES) following RA has been still unclear.

Purpose
The purpose of this study was to investigate the long-term clinical outcomes of RA followed by second-generation DES.

Methods
We retrospectively enrolled 254 consecutive patients treated with second-generation DES following RA. The primary outcome was the cumulative 5-year incidence of MACE, defined as cardiac death, myocardial infarction, clinically-driven target lesion revascularization and definite stent thrombosis.

Results
The incidence of MACE was 22.8% at 5-years. Multivariate analysis showed 3 predictors of MACE, hemodialysis, diabetic mellitus and extremely angulated lesions (>90°).Significantly higher MACE was observed in the high-risk (≥2 risk factors) group, compared with the low-risk (2< risk factors) group (68.7% vs. 18.7%, P<0.001, Figure).
Multivariate analysis for MACE at 5 year Hazard ratio (95% Confidence Interval) P-value Diabetic Mellitus 2.58 (1.35–4.91) 0.004 Hemodialysis 4.57 (1.64–12.76) 0.004 extremely angulated (>90°) 3.08 (1.06–8.93) 0.04
Kaplan-Meier curves for 5-years MACE

Conclusions
The long-term clinical outcomes of PCI for severely calcified lesions was acceptable. However, the clinical outcomes of patients classified high risk cohort was unsatisfactory.
P4599Strict versus no fasting prior to cardiac catheterization: a prospective evaluation of safety and clinical outcomes
Authors: Mishra A , Singh M , Kane M , Acker W , Kaluski E , Sattur S , Sethi A , Arora S , Sporn D 
Published: October 2019

Abstract

Background/Methods
No studies have examined safety of a no fasting (NF) strategy as compared to current nil per os (NPO) practice in patients undergoing non emergent cardiac catheterization (CC). We compared these two strategies in this single center, prospective, randomized study. Fasting group was NPO for solids after midnight but could have clear liquids up to 2 hours prior to procedure. NF group had no restriction or oral intake.

Results
A total of 520 patients enrolled till December 2018 were included in this interim analysis. Both groups had similar baseline characteristics (figure 1). As compared to the fasting group (n=274), NF group (n=246) had similar rates of primary outcomes: CIN (0.02% in both groups), peri-procedural hypotension (0.02% vs 0.03%), aspiration pneumonitis (none vs 0.009%), nausea/vomiting (0.05 vs 0.07%), hypoglycemia (0.007% vs 0.008%) respectively [p=not significant for all].Secondary outcomes including patient's satisfaction and 30-day mortality were also similar in both groups. Cost of index hospitalization was significantly lower in NF group (table 1).
Outcome table Outcomes Fasting group (n=274) Non- Fasting group (n=246) p value Length of Stay (days)† 2.13±0.2 1.96±0.19 0.524 SBP post catheterization† 133.31±1.44 133.15±1.39 0.936 Hypotension peri procedurally 6 (2%) 7 (3%) 0.617 Fluid resuscitation required for hypotension 2 (0.7%) 3 (1%) 0.669 Pressor required for hypotension 1 (0.4%) 2 (0.8%) 0.603 Acute Kidney Injury 10 (4%) 9 (4%) 0.981 Contrast induced nephropathy 5 (2%) 6 (2%) 0.612 Hypoglycemia 2 (0.7%) 2 (0.8%) 1 Hyperglycemia 12 (4%) 4 (2%) 0.080 Symptomatic hypotension 1 (0.4%) 2 (0.8%) 0.603 Nausea/vomiting 12 (5%) 15 (7%) 0.344 Aspiration pneumonitis 0 (0%) 2 (0.9%) 0.219 Patient satisfaction score† 4.39±0.06 4.45±0.06 0.438 Alive on discharge 271 (98.9%) 240 (98%) 0.622 30-day mortality 4 (1.5%) 6 (2.4%) 0.417 30-day Cardiac readmission 32 (13%) 26 (11%) 0.557 Total Cost (US Dollars)† 10148.97±985.71 7710.914±648.33 0.040 Results are shown as number (%). †Expressed as mean ± standard error.

Conclusion
NF strategy is safe and cost effective as compared to traditional NPO practice in patients undergoing CC.

Acknowledgement/Funding
A financial grant of USD15,000 from Guthrie Research Foundation
P4601Reduced exercise capacity and clinical outcomes following acute myocardial infarction
Authors: Tashiro H , Tanaka A , Ishii H , Motomura N , Arai K , Adachi T , Okajima T , Hitora Y , Hayashi M , Furusawa K , Imai H , Ogawa Y , Kawaguchi K , Murohara T 
Published: October 2019

Abstract

Background
Reduced exercise capacity is known to be an important predictor of poor prognosis and disability in patients with cardiovascular diseases and chronic heart failure, and even members of the general population. However, data about exercise capacity assessed by cardiopulmonary exercise testing (CPX) in acute myocardial infarction (AMI) patients who underwent primary percutaneous coronary intervention (PCI) is scarce. The purpose of this study is to assess the associated factors and clinical influence of exercise capacity measured by CPX in AMI patients.

Methods
Among 594 consecutive AMI patients who underwent primary PCI, we examined 136 patients (85.3% men, 64.9±11.9 years) who underwent CPX during hospitalization for AMI. CPX was usually performed five days after the onset of AMI. Reduced exercise capacity was defined as peak oxygen consumption (peak VO2) ≤12. Clinical outcomes including all-cause death, myocardial infarction, and hospitalization due to heart failure were followed.

Results
Among 136 patients, reduced exercise capacity (peak VO2 ≤12) was seen in 38 patients (28%). Patients with reduced exercise capacity were older, more likely to have hypertension, and had lower renal function. In echocardiography, patients with reduced exercise capacity had higher E/e' and larger left atria. Median follow-up term was 12 months (interquartile range: 9–22). The occurrence of composite endpoints of all-cause death, myocardial infarction, and hospitalization due to heart failure was significantly higher in patients with peak VO2≤12 than those with peak VO2>12 (p<0.001). Multivariate logistic analysis showed that E/e' (Odds ratio, 1.19, 95%, confidence interval 1.09 to 1.31, p<0.001) was an independent predictor of reduced exercise capacity (peak VO2≤12).
Cumulative incidence of clinical events

Conclusion
Diastolic dysfunction is associated with reduced exercise capacity following successful primary PCI in AMI patients and may lead to poorer clinical outcomes.
P4605Landiolol, a beta-blocker, optimizes cardiac energetics and peripheral microhemodynamics better than ivabradine while reducing heart rate at hemodynamic resuscitation of experimental septic shock
Authors: Uemura K , Kawada T , Nishikawa T , Zheng C , Meihua L , Sigimachi M 
Published: October 2019

Abstract

Background
Septic shock is associated with sympathetic over-activation characterized by tachycardia, which is associated with poor survival. Though several kinds of drugs are available to reduce heart rate (HR), it is not clear which drug should be used to reduce HR effectively in initial hemodynamic resuscitation in septic shock.

Purpose
The aim of this study was to experimentally investigate comparative effects of landiolol (a β-blocker) and ivabradine (an If-channel inhibitor) on initial hemodynamic resuscitation in a canine model of endotoxin shock.

Methods
We used 19 anesthetized dogs. Seven dogs were allocated to control (CT) group, six dogs to landiolol (BB) group, and six dogs to ivabradine (IVA) group. In all the groups, endotoxin shock was induced by intravenous infusion of Escherichia coli lipopolysaccharide (4 mg/kg) over 1 h. After induction of endotoxin shock, we started hemodynamic resuscitation to restore mean arterial pressure (AP) and cardiac output (CO) by infusing noradrenaline (NA) and Ringer acetate solution (RiA). Dose of NA and RiA were automatically titrated with use of a computer-controlled drug infusion system that we developed previously. Hemodynamic resuscitation was continued for 4 h. During resuscitation, the BB group was given landiolol infusion at a low-dose range (1–10 μg/kg/min, manually titrated), while the IVA group was given ivabradine at 0.25 mg/kg bolus-injected every 2 h.

Results
The drug infusion system automatically restored AP to 70 mmHg and CO to greater than 90% of baseline level in all the groups. The restored AP and CO were not significantly different among the three groups (Figure A, B). There were no significant differences in the computer-controlled infusion rate of NA and cumulated volume of RiA infused among the three groups (Figure C). During the first 2 h of resuscitation, HR was significantly reduced in the BB and IVA groups in comparison to the CT group (Figure D). However, only in the BB group, cardiac oxygen consumption was significantly lower than that in the CT group (Figure E). Blood lactate level decreased significantly after hemodynamic resuscitation only within the BB group (Figure F).
Figure 1

Conclusions
In the initial hemodynamic resuscitation of septic shock, both low-dose landiolol infusion and ivabradine injection may be used to reduce HR. However, to optimize cardiac energetics and peripheral microhemodynamics, low-dose landiolol infusion may be preferable to ivabradine injection.

Acknowledgement/Funding
This work was supported by JSPS KAKENHI Grant Number 15K01307, 18K12126.