bluuebunny/crossref_metadata_2025 huggingface dataset:
P2550The influence of tonic-clonic seizures on heart rate variability in patients with refractory epilepsy
Authors: Faria M T , Rodrigues S , Dias D , Rego R , Rocha H , Sa F , Oliveira A , Campelo M , Pereira J , Rocha-Goncalves F , Cunha J P S , Martins E
Published: October 2019

Background

Heart Rate Variability (HRV) is an increasing area of interest in patients with epilepsy. The effects of epilepsy on the autonomic control of the heart are not completely understood and that autonomic dysfunction has been implicated in some cases of Sudden Unexpected Death in Epilepsy (SUDEP).

Objective

To study the influence of generalized tonic-clonic seizures (GTCS) on HRV of patients with focal refractory epilepsy.

Method

We prospectively evaluated (January 2015 to July 2018) 121 patients admitted to our institution's Epilepsy Monitoring Unit. All patients performed a 48-hour Holter recording. Patients who had GTCS during the recording were included and we selected the first GTCS as the index seizure. HRV (AVNN, SDNN, RMSSD, pNN50, and LF/HF) was evaluated by analyzing 5-min-ECG epochs during inter-ictal and post-ictal periods: baseline, pre-ictal (5 min before the GTCS seizure), post-ictal (5 min after the seizure), and late post-ictal (>5 hours after the seizure). We compared HRV data from these patients with normative values for a healthy population (controlling age and gender). The study was approved by our Institution Ethics Committee and all patients gave informed consent.

Results

Twenty three patients were included (mean age: 38.61±11.58; 70% Female). Thirty percent presented cardiovascular risk factors without known cardiac disease. We found significant differences between the analyzed periods for all but one (LF/HF) HRV metrics (using Friedman test, p<0.05, two-tailed). Specifically during the post-ictal period, we found a significant reduction for AVNN, SDNN, RMSSD and pNN50 (Wilcoxon test, p<0.05; two-tailed). LF/HF was increased during this period, but changes were not statistically significant. There was also a tendency for a reduction of AVNN, SDNN, RMSSD and pNN50 and an increase of LF/HF in our patients during all the analyzed periods when compared to normative healthy population values.

Conclusion

Our work shows reduced HRV after a GTCS in patients with focal resistant epilepsy, both in inter-ictal and post-ictal periods, when compared to normative healthy population values. These results might reflect long term structural changes in autonomic centers. The HRV changes were significant particularly during the post-ictal period, and should prompt further investigation, giving this period is critical for SUDEP.
P2553Combined with ticagrelor, 50 mg aspirin daily can reduce bleeding events without increasing ischaemic risk compared with 75–100 mg aspirin daily in coronary artery disease patients
Authors: Li J
Published: October 2019

Aim

To investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin than that recommended by guidelines.

Methods

Hospitalized patients received ticagrelor (90 mg twice daily) plus aspirin (50–100 mg/day) for up to 12 months. The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared among the groups treated with 50 mg and 75–100 mg aspirin.

Results

MACE risk was not significantly different between the two groups (OR=0.829, 95% CI: 0.279–2.461, P=0.736). However, 75–100 mg aspirin was associated with a greater risk of bleeding events (OR=1.524, 95% CI: 1.082–2.146, P=0.016), particularly mild and moderate bleeding events (OR=1.480, 95% CI: 1.047–2.092, P=0.026). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR=1.850, 95% CI: 1.025–3.339, P=0.041), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR=4.565, 95% CI: 1.081–19.270, P=0.039).

MACEs and bleeding events within 1 year Endpoint 75–100 mg (n=744) 50 mg (n=188) Unadjusted (95% CI) P value Adjusted# (95% CI) P value MACEs 18 (2.4) 4 (2.1) 0.876 (0.296–2.588) * 0.876 0.829 (0.279–2.461)* 0.736 Bleeding 311 (41.8) 60 (31.9) 1.532 (1.091–2.152)** 0.014 1.524 (1.082–2.146)** 0.016 Severe bleeding 14 (1.9) 2 (1.1) 1.784 (0.402–7.916)** 0.447 1.807 (0.405–8.069)** 0.438 Mild bleeding 297 (39.9) 58 (30.8) 1.489 (1.057–2.098)** 0.023 1.480 (1.047–2.092)** 0.026 #Adjusted for age, sex, LDL-C, hs-CRP, diabetes mellitus, hypertension, hyperlipidaemia and MI history. *Hazard ratio (high vs low); **Odds ratio (high vs low).

Conclusion

Among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75–100 mg aspirin daily.

Acknowledgement/Funding

The study was supported by AstraZeneca's fund for the TIFU study (ESR-15-11199).
P2555Efficacy and safety of oral anticoagulant versus antiplatelet therapy for secondary prevention of cardiovascular disease in patients without atrial fibrillation
Authors: Ricci F , Ianni U , Forcucci F , Fedorowski A , Zimarino M , Gallina S , Renda G
Published: October 2019

Background

Anticoagulation is the mainstay of prevention of arterial thromboembolism in patients with atrial fibrillation, but it could be effective also in secondary prevention of patients who are in sinus rhythm.

Purpose

We performed this meta-analysis to determine relative efficacy and safety of oral anticoagulant therapy (OAC) as compared with antiplatelet therapy (APT) in patients with prevalent cerebro-cardiovascular disease without atrial fibrillation.

Methods

Our systematic review of the literature published through January 31st, 2019 sought all phase III randomized controlled trials which compare OAC with APT in patients with sinus rhythm and report at least one of the following outcomes: ischemic stroke, death, myocardial infarction, and major bleeding, assessed at the longest available follow-up. We used random-effects models to estimate summary relative risk reduction (RRR) and 95% confidence intervals (95% CI).

Results

We identified a total of 9 randomized controlled trials including a total of 34,912 patients (ASA, n=17,726; adjusted-dose warfarin, n=4,460; rivaroxaban, n=12726), with a mean follow-up of 2.2 years. When compared with antiplatelet therapy, OAC was associated with reduced risk of ischemic stroke (RRR 38%, 95% CI: 1; 47; P=0.04; I2=72%) and myocardial infarction (RRR 13%, 95% CI: 0,23; P=0.05, I2=0%), but increased risk of major bleeding (RRR −52%, 95% CI: −129; −1; P=0.04; I2=76%). Compared to antiplatelet treatment, OAC did not significantly affect the risk of all-cause death (RRR 1%, 95% CI: −9; 10; P=0.86; I2=12%).

Conclusions

In sinus rhythm patients with prevalent cardiovascular disease, OAC reduces risk of ischemic stroke and myocardial infarction, but significantly increases risk of major bleeding. The choice of antithrombotic treatment does not appear to influence all-cause mortality.
P2564Levosimendan shortens action potential duration, decreases alternans threshold and prevents ventricular arrhythmia during therapeutic hypothermia in isolated rabbit hearts
Authors: Hsieh Y C , Li C H , Liao Y C , Lin J C , Weng C J , Lin S F , Huang J L , Wu T J
Published: October 2019

Background

Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias (VA) by prolonging action potential duration (APD) and facilitating arrhythmogenic spatially discordant alternans (SDA). The calcium sensitizer levosimendan has been reported to shorten APD by enhancing ATP-sensitive K current. We hypothesize that levosimendan might shorten the already prolonged APD during TH, decreasing SDA threshold, and prevent the occurrence of VA.

Methods

Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, epicardial APD was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle length (PCL) that induced SDA phenomenon. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s using the shortest PCL that achieved 1:1 ventricular capture.

Results

Levosimendan shortened the ventricular APD (at PCL 300 ms, from 229±9 ms to 211±18 ms, p=0.02) and decrease the SDA threshold (from 327±88 ms to 311±68 ms, p=0.001) during TH. The VF inducibility was decreased by levosimendan from 39±30% at 30°C to 14±12% after levosimendan infusion. In control hearts, the APD (p=0.75), SDA threshold (p=ns) and VF inducibility (p=0.12) were not changed by vehicle during TH.

Conclusions

Levosimendan protects the hearts against VA during TH by shortening APD and decreasing SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel approach to prevent VA during TH.
P2567First experience of non-invasive and invasive activation maps merge in carto system for topical diagnosis of focal arrhythmias
Authors: Budanova M , Chmelevsky M , Zubarev S , Potyagaylo D , Parreira L , Adragao P
Published: October 2019

Background

Correct preoperative topical diagnostics of atrial and ventricular arrhythmias allows for operation time reduction by facilitating the ablation target localization, especially in case of several ectopic sources.

Purpose

To implement a non-invasive electrocardiographic imaging (ECGI) technique in CARTO system for aiming at topical diagnostics of focal arrhythmias improving.

Methods

Twelve patients (m/f – 10/2, age (min–max) – 50,5 (32–71)) with focal arrhythmias underwent ECGI in combination with CT or MR imaging. Two subjects had atrial premature contractions (PAC), while ten patients suffered from ventricular premature contractions (PVC) with indications for ablation. Before the ablation procedure Carto LAT mapping was performed in all patients. Using ECGI epi-/endocardial polygonal models of the heart were created, isopotential and activation maps were calculated, uploaded into the Carto system and merged with the CARTO FAM models (Figure 1).

Results

For six patients with PVC and two patients with PAC, earliest activation zones (EAZs) anatomical locations obtained by invasive and non-invasive methods were the same (RVOT septum, RVOT lateral-anterior and RV lateral-basal walls, right aortic cusp, LVOT, coronary sinus (CS), CS ostium, RA posterior wall), and arrhythmias ablation was successful. Two patients featured coherent EAZs (RV lateral-basal wall and RVOT septum) but a negative ablation outcome. In one patient, EAZs were situated in different anatomical regions: CARTO showed the PVC EAZ in RV septum, whereas Amycard system identified endocardial surface of lateral-basal RV wall. In this patient, PVC was ablated partially. For another patient with MRI late enhancement area in LV lateral wall the EAZs were in the same LV segment but with mismatch in epi/endocardial surface.

Conclusion

Non-invasive and invasive activation maps merge can improve localization of ablation targets in focal arrhythmias, potentially increasing effectiveness of the EP procedure and reducing operation time.
P2568Larger vectorcardiographic QRS area is associated with increased risk of heart failure development among left bundle branch block patients: a register-based cohort study
Authors: Andersen D , Petersen L , Kragholm K , Graff C , Soerensen P , Nielsen J , Pietersen A , Soegaard P , Atwater B , Torp-Pedersen C , Polcwiartek C
Published: October 2019

Background

QRS morphology including left bundle branch block (LBBB) and duration remain the most widely used surrogate markers in the 12-lead electrocardiogram (ECG) for assessing ventricular dyssynchrony and predicting future burden of heart failure (HF) and cardiovascular mortality. However, the vectorcardiographic QRS area has recently been proposed and evidence suggest that this marker may more accurately predict HF development.

Purpose

The aim of this study was to investigate the association between vectorcardiographic QRS area and risk of HF development in LBBB patients.

Methods

From 2001–2015, the Copenhagen General Practitioners' Laboratory was used to identify patients with a first-time LBBB ECG (QRS>120 ms; LBBB morphology), from which QRS area was derived using the Kors transformation method and grouped into quartiles. Outcome was a composite of HF diagnosis, redeemed prescriptions of loop diuretics, or death from HF. Death from other causes was accounted for as a competing risk.

Results

We included a total of 2843 LBBB patients who were free of heart failure (median age, 70 years; female, 58%; ischemic heart disease, 9%). QRS area quartiles comprised Q1, 67–158 μVs; Q2, 159–189 μVs; Q3, 190–228 μVs; and Q4, 229–739 μVs. During 6-month, 1-year, and 5-year follow-up, 9%, 12%, and 28% of patients reached the combined HF endpoint, and 1%, 2%, and 8% of patients died from other causes, respectively (Figure 1). After multivariable adjustment, the highest QRS area quartile, Q4, was associated with increased HF risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.35–2.00) compared with the lowest quartile, Q1. We did not observe any significant increase in HF risk for remaining quartiles (Q2 or Q3 vs. Q1).

Figure 1

Conclusions

Among primary care patients with newly discovered LBBB, a large vectorcardiographic QRS area (229–739 μVs) is associated with increased risk of developing the incident, combined HF endpoint. This indicates that the QRS area derived using the Kors method may serve as a valuable prognostic marker when assessing risk of HF in patients with LBBB.
P2571Differentiation of iPS-derived cardiac mesoderm cells into cardiomyocytes using inducible shRNA technology
Authors: Garcia Duran A , Nazari-Shafti T , Kurtz A , Falk V , Gossen M , Stamm C
Published: October 2019

Introduction

The development of robust and scalable cardiomyocyte differentiation protocols from human pluripotent stem cells (hPSCs) offers the opportunity to derive large number of autologous cardiomyocytes for cell therapy. However, human induced pluripotent stem cells-derived cardiomyocytes (hiPSCs-CM) do not proliferate, are susceptible to ischemia and poorly retained in the recipient myocardium. In addition, arrhythmias are a severe side effect of cell therapy with hiPSC-CM, probably due to their immature phenotype. Based on previous observations in our lab, we speculate that the heart environment might be an important factor to enable full maturation and in situ coupling of the implanted cells in vivo. We therefore speculate that transplantation of robust, proliferative, partially committed, non-tumorigenic cardiac mesoderm cells and subsequent differentiation in situ may overcome these limitations.

Purpose

We seek to engineer hiPSC-derived cardiac mesoderm cells for implantation in the failing myocardium that, once they have settled, consolidated, and proliferated in situ, can be selectively induced to mature into cardiomyocytes.

Methods

Wnt signalling induces mesoderm lineage differentiation of hiPSCs and inhibits further maturation towards CM. To induce Wnt signalling inhibition, we designed a customized biomimetic shRNA targeting the Wnt agonist β-catenin fused to a fluorescent reported protein controlled by a Tet-ON promoter. This transgene was transferred to the safe harbour locus AAVS1 of the OPTI-OX hiPS cell line constitutively expressing the reverse tetracycline transactivator protein (rtTA) in the ROSA26 locus. In this configuration, gene expression can be activated in trans upon doxycycline administration.

Results

We studied the kinetics of gene expression activation on the engineered undifferentiated hiPSCs and observed that a maximal reduction of 80–90% β-catenin correlating with reporter expression was achieved upon a 4-day treatment with doxycycline. Importantly, this activation could be fully reverted 6 days upon withdrawal. Furthermore, in vitro differentiation of cardiac mesoderm cells into cardiomyocytes was enhanced upon doxycycline administration as compared to the untreated cells as assessed by the upregulation of cardiomyocyte specific genes and the increased percentage of cTNT+ cells.

Conclusion

An inducible system for targeted β-catenin downregulation by shRNA allows for significant, sustained, and reversible Wnt signalling modulation, which is sufficient to induce cardiomyocyte differentiation of cardiac mesoderm cells in vitro. This technology may be implemented to differentiate the transplanted cells in the failing myocardium, opening new prospects to overcome the current limitations of hiPSC-based cardiac cell therapy.

Acknowledgement/Funding

BMBF funding (FKZ 13GW0098, FKZ 13GW0099) DFG funding through the BSRT GSC 203
P2573Modelling the duchenne muscular dystrophy-induced dilated cardiomyopathy using patient-specific induced pluripotent stem cells-derived cardiomyocytes
Authors: Souidi M , Sleiman Y , Moreau A , Amedro P , Meyer P , Rivier F , Lacampagne A , Meli A
Published: October 2019

Introduction

Duchenne Muscular Dystrophy (DMD) is a X-linked degenerative pathology with a prevalence of 1/3500 boys due to absence of functional dystrophin in muscles. In a late stage of DMD, patients developed a dilated cardiomyopathy (DCM) which can lead to heart failure and premature death.

In the past, we showed that DMD (mdx) mice exhibit a perturbation of the intracellular calcium homeostasis correlated to a pathological remodelling of the calcium ryanodine receptor channel (RyR2) leading to DCM with aging. However, mouse model does not represent a pertinent prototype to study DMD. Human pluripotent stem-cell derived-cardiomyocytes (hiPSC-CMs) are a pertinent tool to model patient-specific inherited cardiac diseases and screen pharmacological drugs in a Petri dish.

Objective

Based on the clinical history of DMD patients in the local Hospital, our main objective is to model DMD-induced DCM using hiPSC-CMs and compare the functional and molecular features with the clinical echocardiography. To that, we hypothesize that hiPSC-CMs are a powerful technology to model in vitro DCM and to better understand the pathophysiological mechanisms underlying DCM.

Methods

3 blood samples from DMD patients with different DCM degrees of severity and 3 from healthy control (HC) were collected, reprogrammed in hiPSC and differentiated into cardiomyocytes.

Results

Our preliminary data indicate that DMD hiPSC-CMs present an abnormal intracellular calcium homeostasis characterized by the presence of leaky diastolic calcium events compared to HC hiPSC-CMs suggesting a RyR2 dysfunction. In DMD hiPSC-CMs, we also observe alterations in the contractile properties and a perturbation of the mitochondrial respiration.

Conclusion

Our results support the fact that DMD-inducing DCM can be modelled in the dish using patient-specific hiPSC-CMs. Such modelling may provide a better understanding of the pathophysiological mechanisms and the pharmacological treatment of the DMD-induced DCM.
P2606Analysis of myocardial work: a potential new tool for a better assessment of left ventricular function
Authors: Rimbas R C , Chitroceanu A M , Luchian M L , Visoiu S I , Mihaila-Baldea S , Magda L S , Memis H , Lungeanu-Juravle L , Velcea A , Balinisteanu A , Andronic A A , Vinereanu D
Published: October 2019

Background

Left ventricular (LV) deformation is dependent on mechanical load and does not reflect directly the myocardial energy consumption. Thus, measurement of global and regional myocardial work might be alternative and complementary methods for the assessment of myocardial function. However, there is no data regarding myocardial work changes during the heart failure continuum, from normal to diastolic dysfunction (DD), and to heart failure with preserved ejection fraction (HFpEF).

Methods

We assessed 80 subjects by 2D conventional and speckle tracking echocardiography (2DSTE): 25 patients with DD, 30 with HFpEF, and 25 normal, control subjects. We measured NTproBNP, LV ejection fraction (EF), and E/E' ratio. We used a new approach to calculate myocardial work, during mechanical systole and isovolumetric relaxation, by 2DSTE: global constructive work (GCW), as the “positive” work of the heart; global wasted work (GWW), as the “negative” work of the heart; global work efficiency (GWE), as the GCW/(GCW + GWW) in %; and global work index (GWI), as the GCW added to GWW. Similarly, a regional, segmental analysis was performed (18 segments model) (Figure 1).

Results

GCW increases in patients with DD, probably as a compensatory mechanism to preserve LV function against an increased after load, and decreases back to the normal values in HFpEF, while GWE significantly decreases from normal subjects to patients with DD, and then further in patients with HFpEF (table). Meanwhile, GWW increases from normal subjects to patients with DD, and then further in patients with HFpEF. As expected, GWI does not change significantly. By segmental analysis, first segment affected in terms of myocardial work is basal antero-septal segment, with low WE and higher WW (figure), probably due to the flat shape (based on the Laplace law), with a compensatory increased CW in the apical segments. NTproBNP level and E/E' ratio correlated only with GWW (r=0.4, p=0.013).

Comparative global myocardial work Group LVEF (%) E/E' NTproBNP (pg/ml) GWI (mmHg%) GWE (%) GCW (mmHg%) GWW (mmHg%) Controls 58±6 7.3±2.4 – 2102±303 95.5±1.8 2295±279 87.9±39.6 DD 57±8 7.7±2.4 36±25 2296±431 94.8±2.3 2550±463 108±50 HFpEF 63±7 10.3±3.1 349±418 2074±485 93.5±2.5 2300±535 125±51 P (Anova) 0.004 <0.001 <0.001 0.12 0.008 0.05 0.019

Figure 1. Myocardial Work

Conclusion

Myocardial work efficiency decreases and wasted work increases in parallel with the severity of LV dysfunction. The first myocardial segment affected is basal antero-septal. Therefore, new parameters of myocardial work, derived from 2DSTE, might provide a better assessment of LV function in patients with DD or HFpEF.

Acknowledgement/Funding

This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III
P2611The prognostic value of serum magnesium levels in patients with heart failure with preserved left ventricular ejection fraction
Authors: Nishihara T , Sueta D , Yamamoto E , Fujisue K , Usuku H , Oike F , Takae M , Takashio S , Sakamoto K , Kaikita K , Tsujita K
Published: October 2019

Background

In heart failure (HF) patients, various factors, such as hyperactivity of the renin-angiotensin system, influence of drug therapy such as loop and thiazide diuretics, undernutrition and others, can causes hypokalemia and hypomagnesemia. Although serum magnesium (Mg) levels are closely associated with the prognosis of HF patients, the clinical significance of serum Mg levels in cardiovascular outcomes of HF with preserved ejection fraction (HFpEF) patients is not fully understood.

Purpose

We examined the relationship between serum Mg and future HF-related events in patients with HFpEF.

Methods

This study was a retrospective, single-center, observational study. We enrolled 452 consecutive HFpEF patients admitted to our university hospital between January 2007 and September 2013 and followed them for 4 years or until occurrence of HF-related events. We defined lower serum Mg as <2.0 mg/dL (=0.8 mmol/L) and higher serum Mg as ≥2.0 mg/dL based on recent clinical evidences and compared their clinical characteristics and prognosis.

Results

The mean serum Mg level was 2.12 mg/dL (median, 2.1 mg/dL; interquartile range, 2.0–2.28 mg/dL). The follow-up period was 0–50 months (median, 47.3 months) and 48 HF-related events (10.6%) were recorded. The frequency of HF-related events was significantly higher in the lower serum Mg group compared with the higher serum Mg group (n=16, 17.4% vs. n=32, 8.9%; P=0.018). There were no significant differences between groups in the use of all drugs (loop diuretics, mineralcorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, β-blockers, statins and Mg preparations). The lower serum Mg group (n=92) showed significantly higher prevalence of diabetes mellitus (DM), uric acid levels and B-type natriuretic peptide (BNP)levels compared with the higher serum Mg group (n=360). Kaplan-Meier curve revealed a significantly higher probability of HF-related events in the lower serum Mg group compared with the higher serum Mg group (log-rank test, P=0.012, Figure). Multivariate Cox proportional hazard analysis revealed that the lower serum Mg group had significantly and independently higher probabilities of HF-related events compared with those in the higher serum Mg group (hazard ratio: 2.37, 95% confidence intervals: 1.27–4.41, P=0.007). We reclassified the risk of a HF-related events after adding the lower serum Mg to the prognostic factors (age, previous hospitalization for HF, DM, ln-BNP); the continuous net reclassification improvement was 29.0% (p=0.041).

Conclusion

We first demonstrated that serum Mg was significantly correlated with the occurrence of future HF-related events in HFpEF patients. Lower serum Mg is able to successfully predict future HF-related events, and management of serum Mg in HFpEF patients is thus important.

Acknowledgement/Funding

None
P2635Prevalence of appropriate treatment in elderly heart failure patients and impact on clinical outcomes: a subgroup analysis from REPOSI registry
Authors: Proietti M , Marra A M , Salzano A , Romiti G F , Mannucci P M , Nobili A , Cittadini A
Published: October 2019

Introduction

Therapeutic appropriateness in chronic diseases is a key factor in obtaining better clinical outcomes over clinical follow-up, in particular in elderly patients. Data about therapeutic appropriateness in elderly patients with heart failure (HF) are scarce.

Purpose

To describe the prevalence of appropriate treatment in elderly HF patients and its impact on clinical outcomes.

Methods

REgistro POliterapie SIMI (REPOSI) cohort was used to assess study aims. REPOSI is an Italian Nationwide Registry of elderly (≥65 years) hospitalized patients in Internal Medicine and Geriatric wards. HF diagnosis was assessed at hospital admission according to ICD-9 code 428.XX. Therapeutic appropriateness was defined according to International Guidelines.

Results

Among the 7003 patients originally enrolled, a total of 1095 (15.6%) patients reported a diagnosis of HF at hospital admission. At admission, 230 (21.0%) patients were considered as treated appropriately, with 245 (22.4%) treated appropriately during hospitalization and 249 (22.7%) at discharge (p=0.0.248). Focusing on patients aged ≥80 years, prevalence of appropriate treatment was respectively: 18.9% at admission, 20.3% during hospitalization and 21.0% at discharge (p=0.266). Among the 1095 patients with HF, 815 (74.4%) had available follow-up data. Patients appropriately treated at discharge, compared to those not treated appropriately, had a lower rate of CV death (5.1% vs. 11.9%, p=0.006) and all-cause death (7.2% vs. 26.1%, p<0.001) during follow-up, with no difference in rates of rehospitalization and CV rehospitalization. A logistic regression analysis adjusted for age, sex, risk factors, comorbidities and polypharmacy, showed that appropriate therapy at discharge was inversely associated with the risk of CV death and all-cause death (Table). In patients ≥80 years, appropriate HF treatment was inversely associated with risk of all-cause death (Table).

Logistic Regression Analysis All Patients ≥80 years OR (95% CI) OR (95% CI) CV Death 0.46 (0.23–0.94) 0.59 (0.26–1.36) All-Cause Death 0.26 (0.14–0.46) 0.27 (0.14–0.53) CI = Confidence Interval; CV = Cardiovascular; OR = Odds Ratio.

Conclusions

In elderly hospitalized HF patients, prevalence of therapeutic appropriateness was consistently low at admission, during hospitalization and at discharge, particularly in patients ≥80 years. Appropriate HF therapy was inversely associated with the risk of CV death and all-cause death in all patients and with the risk of all-cause death in patients ≥80 years.

Acknowledgement/Funding

None
P2646Determinants of aortic root dilatation over time in hypertensive treated patients: the Campania Salute Network
Authors: Canciello G , Mancusi C , Izzo R , De Luca N , Trimarco B , Barbato E , De Simone G , Losi M A
Published: October 2019

Background

We demonstrated that aortic root (AR) dilatation assessed by standardized difference between observed and predicted values is present at baseline in about 30% of treated hypertensive patients and predicts cardiovascular (CV) events independently of left ventricular (LV) hypertrophy (LVH).

Purpose

We investigate whether a CV phenotype exists predicting AR dilatation during follow-up of treated hypertensive patients.

Methods

5301 hypertensive treated patients (age 53±11 years, 42% women) without prevalent CV disease and with normal ejection fraction (≥50%) were studied. AR dimension was measured in the parasternal long-axis view at the level of sinus of Valsalva in end-diastole, using the leading-edge to leading-edge method at first and last available echocardiograms. The z-score of AR dimension (AOz) was generated based on the difference between observed AR and predicted AR dimension, divided by sex-specific observed SD.

Results

Initial AOz exhibited a normal distribution and was correlated positively with age, male sex, systolic and diastolic blood pressure (BP), BMI, fasting glucose, and glomerular filtration rate (GFR, by EPI-CKD) and negatively with pulse pressure (PP) and cholesterol (all 0.0375th percentile of the AOz distribution). Similar to baseline, initial SVi and BMI remained the most potent covariates of the final AOz (both p<0.0001), independently of significant effect of male sex, high diastolic BP, BMI, SVi, low PP, and low HDL-cholesterol. Variance inflation factor was <2 in both regression models. Figure shows initial SVi in relation with AR at follow up.

Conclusions

We demonstrate that both volume (SVi) and pressure loads (diastolic BP) influence AR enlargement over time, AR dilatation is predictable in male obese patients with diastolic hypertension and other metabolic disturbances.
P2650Antihypertensive treatment with calcium channel blockers in patients with moderate or severe aortic stenosis: relationship with all-cause mortality
Authors: Saeed S , Mancia G , Rajani R , Parkin D , Chambers J B
Published: October 2019

Background

Hypertension is prevalent in patients with aortic stenosis (AS) and optimal blood pressure (BP) control is advised to reduce arterial load and avoid cardiovascular events. Whether calcium channel blockers (CCB) are safe is not known.

Methods

A total of 314 patients (age 65±12 y, 68% men) with moderate or severe asymptomatic AS were included.

Results

The prevalence of hypertension was 73.6%, and 65% took antihypertensive treatment. Patients who used a CCB (25%) (CCB+) were older, had higher clinic systolic BP, were more likely to have hypercholesterolemia and coronary artery disease (CAD), and to use a diuretic or alpha blocker compared to CCB- patients (all p<0.05) (Table). During the baseline ETT, patients who used a CCB achieved a lower peak heart rate, a shorter exercise time and were more likely to have a blunted BP response compared to those who did not use a CCB (all p<0.05) (Table). Event-free survival was significantly lower in CCB+ than CCB- patients (Fig) (all-cause mortality 16 [20.3%] versus 13 (5.6%); p<0.001). In a multivariable Cox regression model, CCB+ was associated with a 6.8-fold increased hazard ratio (HR) for all-cause mortality (HR 6.77 95% CI 1.66–27.54, p=0.008), independent of age, gender, systolic BP, hypertension, diabetes, CAD, hypercholesterolemia and aortic valve area.

Table 1. Baseline characteristics of patients CCB− (n=234) CCB+ (n=80) p Age, y 64±12 70±10 <0.001 CAD, % 45 66 0.006 Hypercholesterolemia, % 62 78 0.015 Clinic systolic BP, mmHg 139±19 150±17 <0.001 Left atrial diameter, cm 3.7±0.7 3.9±0.6 0.007 LV end-diastolic diameter, cm 4.5±0.7 4.8±0.6 0.002 LV mass index, g/m2.7 50±17 57±17 0.007 Aortic valve area, cm2 0.94±0.22 0.93±0.22 0.716 LV stroke work, g-m/bmp 155±46 175±69 0.046 Peak HR at baseline ETT, bmp 138±24 120±25 <0.001 Blunted BP response, % 33 49 0.013 Exercise duration, min 10.1±4.5 8.3±3.7 0.001 Double Product, mmHg·bmp 1.85±0.43 2.08±0.54 <0.001

Figure 1

Conclusion

The use of calcium channel blockers was associated with an adverse effect on treadmill exercise and reduced survival in apparently asymptomatic patients with moderate or severe AS.

Acknowledgement/Funding

None
P2651Seasonal variations in the pathogenesis of acute coronary syndromes
Authors: Kurihara O , Takano M , Yamamoto E , Yonetsu T , Kakuta T , Soeda T , Yan B P , Crea F , Higuma T , Minami Y , Adriaenssens T , Nef H M , Lee H , Mizuno K , Jang I K
Published: October 2019

Background

Seasonal variations in acute coronary syndrome (ACS) has been known with the winter being the peak in incidence and mortality. However, underlying pathophysiology for this variation has not been studied.

Purpose

We sought to compare pathobiology of the culprit lesions assessed by optical coherence tomography (OCT) among the four seasons.

Methods

Patients with ACS who underwent OCT were recruited from 6 countries in the Northern Hemisphere. The prevalence of 3 most common pathologies, plaque rupture, plaque erosion and calcified plaque, and other features of coronary plaques were compared among the four seasons.

Results

In 1113 patients with ACS, 284 (25%) patients were admitted in spring, 243 (22%) patients in summer, 290 (26%) patients in autumn and 296 (27%) patients in winter. The proportion of underlying 3 pathologies was significantly different in each season (prevalence of plaque rupture, plaque erosion, calcified plaque was 50%, 39%, and 11%, respectively in the spring; 44%, 43%, and 13% in the summer; autumn: 49%, 39%, and 12% in the autumn; 57%, 30%, and 13% in the winter; P=0.039). The proportion of plaque rupture was higher in winter but lower in summer, and that of plaque erosion was higher in summer, but lower in winter. Maximum and minimum temperatures on the day of OCT procedure were significantly lower in the plaque rupture group than in the plaque erosion group (P=0.02 and P=0.012, respectively). In the rupture group, the prevalence of hypertension was significantly higher in winter, but in the erosion group, it was not different among the four seasons.

Figure 1. The proportion of culprit lesion characteristics were significantly different among the 4 season groups. (P=0.039) The proportion of plaque rupture was significantly higher in winter but lower in summer. In contrast, the proportion of plaque erosion was higher in summer, but lower in winter.

Conclusions

Seasonal variation of the underlying mechanisms of ACS reflects different pathobiology. The proportion of plaque rupture is highest in winter and the proportion of plaque erosion is highest in summer. A different approach may be needed for the prevention and treatment of ACS depending on the season of its occurrence.
P2669Prognostication in out-of-hospital cardiac arrest
Authors: Pimenta D , Barakat M F , Obika B D , Mitchell A C , Lockie T P E
Published: October 2019

Background

Out-of-hospital cardiac arrest (OOHCA) remains an area where little progress has been made in outcomes despite significant advances in cardiac care. The OOHCA cohort requires a large amount of resources, including primary coronary intervention and intensive care, often with poor eventual outcomes. A clinical prognostic scoring system would allow resources to be focused on OOHCA patients who are likely to survive; rather than expensive and futile treatments in those who are not. Several different scoring systems have been published but have not been compared in a real world cohort of OOHCA patients.

Method

The Cardiac Arrest Hospital Prognosis (CAHP) score that utilises 7 variables and a simpler three-factor prognostic score derived by Hirt et al were applied retrospectively to a cohort of 157 consecutive OOHCA patients presenting to a regional Centre in our city, UK between 2016 and 2018. For each patient the CAHP score was calculated where a score of >200 predicts a Cerebral Performance Category (CPC) outcome of 3–5 (severe disability, vegetative coma or death). They were also categorised using the Hirt algorithm into “Futile”, “Approaching Futility” and “Non-Futile” groups. CPC outcomes were then compared using both scores and diagnostic accuracy assessed.

Results

A CAHP score of >200 predicted a CPC outcome of 3–5 with 97% specificity and a positive predictive value of 92%. A CAHP score >200 predicted 30-day mortality with 96% specificity, and a positive predictive value of 89% (Fig. 1A). The same cohort categorised by the Hirt algorithm was less accurate; in those patients sorted into the “futile” category 15% of patients survived, and in the “approaching futility” group survival was 100% (Fig. 1B). The specificity and PPV of predicting futility was 94% and 85% respectively.

Conclusion

Although a simple three-factor prognostic score as suggested by Hirt et al is attractive in this cohort of OOHCA patients it did not discriminate those patients who were likely to survive and, the CAHP score was more accurate in predicting outcome. Further validation is required in prospective, multi-centre studies to ensure that application of these scores are reproducible in real-world OOHCA populations in decision making for emergency coronary angiography.

Acknowledgement/Funding

None
P2670Predictors of survival to discharge in the acute myocardial infarction patients presenting with out-of-hospital cardiac arrest after return of spontaneous circulation
Authors: Wu Y.-C , Lin J.-L , Liu Y.-H
Published: October 2019

Approximately 70% of survivals of out-of-hospital cardiac arrest (OHCA) have coronary artery disease, with acute vessel occlusion observed in 50%. Predictors of mortality in acute myocardial infarction (AMI) patients successfully resuscitated for OHCA were not well-determined.

Between May, 2016 and July, 2018, 1428 consecutive patients with OHCA visited the emergency department of Far Eastern Memorial Hospital, New Taipei City, Taiwan. A total number of 117 patients with return-of-spontaneous-circulation (ROSC) were diagnosed of AMI, mostly confirmed by coronary angiography. The mean age was 60.0±13.6 (mean SD) with male gender 105/117. Endpoint was survival to discharge. The survival rate was 55.6%.

Shockable rhythm (Ventricular tachycardia or fibrillation) during CPR (correlation coefficient, CC: 0.635; p<0.001), ST elevation myocardial infarction (CC: 0.550; p=0.003), sinus rhythm on first ECG (CC: 0.474; p=0.012) and higher HDL (CC: 0.471; p=0.0027) were associated better outcome (survival and neurological recovery). However, older age (CC: −0.564; p=0.002), ST depression on first ECG post resuscitation (CC: −0.481; p=0.011), hyperglycemia (CC: −0.419; p=0.030), higher HbA1C level (CC: −0.569; p=0.007), and hyperkalemia (CC: −0.612; p=0.001) were associated with worse outcome (Mortality).

In conclusion, in the AMI patients presenting with OHCA after ROSC, unshockable rhythm during CPR, older age, non-sinus rhythm and ST segment depression on first ECG post resuscitation, hyperglycemia, higher HbA1C level, lower HDL level, and hyperkalemia were associated with higher hospital mortality.
P2674Rapid rule-out of myocardial infarction with a novel high precision point-of-care troponin assay appears safe and effective
Authors: Aldous S , Pickering J , Young J , George P , Watson A , Troughton R , Pemberton C , Richards M , Cullen L , Than M
Published: October 2019

Background

High sensitivity troponin assays were developed to improve analytical sensitivity and precision at the decision cut-points for the diagnosis and rule out of acute myocardial infarction (AMI). Central laboratory assays have achieved this but point of care assays, which have the ability to accelerate decision making due to much shorter turnaround times, have remained lacking.

Purpose

To ascertain the threshold for decision making and subsequent clinical utility for ruling out AMI on presentation in patients attending the emergency department acutely with chest pain, using a high precision point of care troponin assay (TnI Nx), (i-STAT, Abbott).

Methods

We measured arrival TnI-Nx concentrations in stored plasma samples in adults presenting acutely to the emergency department with chest pain. The primary outcome was an AMI or cardiac death on index admission or within 30 days. We used 2000 bootstrapped data sets to derive and validate a suitable threshold for TnI-Nx before calculating diagnostic test performance. We pre-specified this threshold must have a <1% false negative rate for the primary outcome. We compared this with a core laboratory high sensitivity troponin I (hs-TnI) (Abbott Architect) using the early rule-out cut-point (European Society of Cardiology) at the limit of detection (2 ng/L).

Results

We recruited 1320 patients of whom 192 (14.1%) had the primary outcome. The TnI-Nx threshold was determined to be 8 ng/L with subsequent sensitivity of 99.0% (95% confidence interval: 97.3% to 100%), negative predictive value of 99.7% (99.2% to 100%) and specificity of 59.0% (56.0% to 62.0%). The hs-TnI had a sensitivity of 99.5% (98.2% to 100%), negative predictive value of 99.7% (99.0% to 100%), and specificity of 28.4% (25.8% to 31.2%) at 2ng/L.

Conclusion

A high precision point of care assay, TnI-Nx, with a decision threshold of 8ng/L, has comparable rule out performance compared with a core laboratory high sensitivity assay and therefore could potentially be used for early decision making in the assessment of acute chest pain.

Acknowledgement/Funding

Research grant from Abbott Point of Care. Senior Research Fellowship from ECF, CMRF and CDHB. Clinical Research Fellowship from NZ HRC
P2675Validation of a 0/1h diagnostic algorithm using a point of care high-sensitivity troponin I assay
Authors: Soerensen N , Neumann J T , Ojeda F , Giannitsis E , Spanuth E , Blankenberg S , Westermann D , Zeller T
Published: October 2019

Background

The numbers of patients presenting to emergency departments with suspected acute myocardial infarction (AMI) are increasing worldwide. The use of point of care (POC) troponin assays with an increased sensitivity – equal to laboratory-based high-sensitivity immunoassays – might enable faster decision making in this high-risk population.

Objective

To validate a rapid diagnostic algorithm using a novel point of care (POC) high-sensitivity troponin I (hs-TnI) assay in comparison to a laboratory-based hs-TnI assay.

Methods

A diagnostic 0/1h algorithm for the POC hs-TnI assay (PATHFAST hs-cTnI, LSI Medience) was derived in a dataset of 669 patients with suspected AMI, aiming for a negative predictive value (NPV) ≥99.5% for rule-out and a positive predictive value (PPV) ≥75% for rule-in of non-ST-elevation myocardial infarction (NSTEMI). The performance of the developed algorithm was tested in a validation cohort of 610 patients. Diagnostic accuracy of the POC hs-TnI assay was compared to an established hs-TnI assay (Abbott ARCHITECT) using an ESC guideline-recommended 0/1h diagnostic algorithm.

Results

The derived 0/1h algorithm consisted of an admission POC hs-TnI <4 ng/L and a delta from 0h to 1h <3 ng/L for rule-out and an admission POC hs-TnI ≥90 ng/L or a delta from 0h to 1h ≥20 ng/L for rule-in of NSTEMI. Application of the algorithm in the validation cohort showed a NPV of 99.7% (Confidence Interval (CI) 98.1%-100.0%) and 48.0% of patients ruled out, while 14.6% were ruled in with a PPV of 86.5% (CI 77.6%-92.8%). The diagnostic performance of the POC hs-TnI assay was comparable to guideline-recommended use of a laboratory-based hs-TnI assay (Figure 1).

Conclusion

The clinical application of a 0/1h diagnostic algorithm based on a novel POC hs-TnI assay showed good diagnostic performance and was comparable to a laboratory-based hs-TnI assay.

Acknowledgement/Funding

German Center of Cardiovascular Research, Abbott Diagnostics, DIAneering GmbH, German Heart Foundation/ German Foundation of Heart Research
P2701Comparison of myocardial ischemia assessed by contrast-flow quantitative flow ratio (cQFR) and by stress MRI in patients with stable coronary artery disease
Authors: Lenk K , Schwarzbach V , Antoniadis M , Blum M , Hagendorff A , Lavall D , Laufs U
Published: October 2019

Background

Contrast-flow quantitative flow ratio (cQFR) is a new technology for evaluation of coronary stenosis. cQFR allows to derive the fractional flow reserve (FFR) from coronary angiograms. Based on a three dimensional coronary model, FFR is calculated from computational fluid dynamics. Head to head comparisons with FFR showed an overall diagnostic accuracy of 85%. cQFR does not require coronary wires or hyperemia. However, the ability of cQFR to detect myocardial ischemia is unknown. Therefore, the aim of this study was to evaluate the relationship between cQFR and myocardial ischemia assessed by stress magnetic resonance imaging (stress MRI).

Methods

cQFR analysis was performed in patients selected from the hospital database who received stress MRI and coronary angiography. A relevant ischemia on stressMRI was defined as a perfusion deficit in ≥2 of 16 segments. The cQFR was based on 3-dimensional quantitative coronary angiography (3D-QCA) using the QAngio XA 3D 1.1, Medis Medical Imaging System, Leiden, The Netherlands. Two blinded investigators analysed all 3 main coronary vessels of each patient measuring diameter stenosis (DS), area stenosis (AS) and cQFR. A cQFR of ≤0.8 was considered abnormal. The primary endpoint was sensitivity and specificity of cQFR using stress MRI as a reference standard.

Results

125 vessels of 53 patients could be fully analysed by cQFR (78.6%). The sensitivity of cQFR in detecting significant epicardial stenoses of coronary vessels with documented ischemia in stress MRI was 75%, the specificity was 87%. The 3D-QCA-derived diameter stenoses and area stenoses in vessels with positive stress MRI were significantly higher than in vessels without ischemia (see Table 1).

Table 1. Means of diameter stenosis (DS) und area stenosis (AS) with interquartile range (IQR) Total (n=125) Ischemia (n=32) No Ischemia (n=93) p-value DS [%] 42.3 (28.3–53.1) 57.1 (47–68.5) 37.7 (27.6–45.1) <0.0001 AS [%] 51.8 (32.4–69.7) 68.9 (56.8–85.9) 46.5 (29.7–62.7) <0.0001

Conclusion

The analysis reveals a high correlation between relevant coronary stenosis measured by cQFR and ischemic areas detected by stress MRI. Differences between the two methods are plausible because stress MRI detects ischemia due to other reasons than epicardial stenosis. Further randomized studies are mandatory to verify the prognostic significance of the cQFR measurements.